Document 6428381

Transcription

Document 6428381

Preconception Care
A review of the literature
First draft
University Medical Centre Rotterdam, Erasmus MC, The Netherlands
Department of Obstetrics and Gynecology, Division of Obstetrics and Prenatal Medicine
Denktaş S, Jong-Potjer LC, Waelput AJM, Temel S, Voorst van SF, Vos AA, Schölmerich VLN,
Bonsel GJ, Kooy van der J, Quispel C, Poeran VJJ, Peters IA, Vujkovic M, Bakker R, Steegers EAP
© 2012, Erasmus MC
Copyright
© 2012, Erasmus MC
First draft
Denktaş S, Jong-Potjer LC, Waelput AJM, Temel S, Voorst van SF, Vos AA,
Schölmerich VLN, Bonsel GJ, Kooy van der J, Quispel C, Poeran VJJ, Peters IA, Vujkovic M,
Bakker R, Steegers EAP
Cite as:
Preconception Care. A review of the literature.
Denktaş S, Jong-Potjer LC, Waelput AJM, Temel S, Voorst van SF, Vos AA,
Schölmerich VLN, Bonsel GJ, Kooy van der J, Quispel C, Poeran VJJ, Peters IA, Vujkovic M,
Bakker R, Steegers EAP
Correspondence:
University Medical Centre Rotterdam, Erasmus MC,
Room Sk-4130, Postbus 2040, 3000 CA Rotterdam, The Netherlands
[email protected].
ALL RIGHTS RESERVED. This study was commissioned by University Medical Centre
Rotterdam, Erasmus MC, The Netherlands, Department of Obstetrics and Gynaecology,
Division of Obstetrics and Prenatal Medicine. Any unauthorized reprint or use of this material
is prohibited. No part of this report may be reproduced or transmitted in any form or by any
means, electronic or mechanical, including photocopying, recording or by any information
storage and retrieval without express written permission form the authors or publisher.
Contents
Page
Chapter I, Preconception care
Preconception care as part of public health programmes provided by health authorities
Preconception care and Millennium Goals
Provision of preconception care
Preconception care initiatives
Guidelines
References
Chapter II, Reaching arget groups
Collective information through local public campaigns
Specific information to groups that are hard to reach
Peer Educators Perinatal Health
Proactive professional approach and promotion of preconception care
Preconception eduction at school
References
Chapter III, The association between preconceptional risk factors and
adverse pregnancy outcomes
Methods
Results
Conclusion
References
Tables
Chapter IV, Effectiveness of the interventions in reducing the risk factors
before pregnancy
Introduction
Methods
Results
Conclusion
References
Tables
Chapter V, Risk assessment in preconception care
Methods
Risk assessment by questionnaires or checklists
Risk assessment by physical examinations, laboratory tests and complementary tests
References
Chapter VI, Overall benefits of preconception care in terms of public health
History
Public Health Perspectives
Beneficial targeting items
Conclusion
References
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2
I. Preconception care
Lieke C. de Jong-Potjer, Adja J.M. Waelput, Rachel Bakker, Semiha Denktaş, Eric A.P. Steegers
Preconception health is widely recognized as a rather new but critical component of maternal
and child health promotion. It is broadly defined as the provision of biomedical and
behavioural interventions prior to conception in order to optimize women’s health and
subsequent pregnancy outcomes. Risk assessment, health promotion, counselling and
intervention are the core components of preconception care.1 Each of them must be
evidence based to generate resources and assure sustainability, and they must be flexible
enough to adapt to accommodate local priorities.
It is important to recognize the key elements of preconception care. In the past 20 years
various definitions have been formulated. In 1992 the following definition of preconception
care was included in Pubmed's MeSH Database:
“An organized and comprehensive program of health care that identifies and
reduces a woman's reproductive risks before conception through risk
assessment, health promotion, and interventions.”2
In 2005 the Centers for Disease Control and Prevention (CDC) and the March of Dimes, in
collaboration with 35 professional and governmental organizations, convened a summit to
discuss an agenda for preconception care programs, research, and policy. They defined
preconception care as a continuum of care designed to meet the needs of a woman
throughout the various stages of her reproductive life. Based on the Select Panel
deliberations and its subsequently published recommendations, preconception care was then
defined as:
“A set of interventions that aim to identify and modify biomedical, behavioral, and
social risks to a woman's health or pregnancy outcome through prevention and
management, emphasizing those factors that must be acted on before conception
or early in pregnancy to have maximal impact.” 3
In 2007 the Health Council of the Netherlands presented the advisory report entitled
Preconception care: a good beginning. The advisory report summarised the knowledge
concerning the various components of preconception health care. On the basis of the
scientific insights obtained, the Committee concluded that the provision of preconception
advice on diet, lifestyle, diseases, use of medication, working conditions, and genetic factors
3
can be seen as an intrinsic part of effective care. Accordingly, it would be appropriate to offer
preconception health care to all prospective parents. The Committee formulated the following
definition for this advisory report:
“Preconception care is the entire range of measures designed to promote the
health of the expectant mother and her child, which, in order to be effective, must
preferably be adopted prior to conception.” 4
Preconception care as part of public health programmes provided by health
authorities
Over the last 30 years several strategies and ideologies were developed to incorporate
preconception care within international maternal and child health programs and policies.
Some of them are well established and analyzed. This has resulted in a growing body of
knowledge. Other policies are more or less hidden within declarations of international
agencies, coalitions and international health movements, such as the promotion of global
primary health care by the declaration of Alma Ata, Safe Motherhood initiatives and women’s
rights and health movements.5
The Inter-Agency group for Safe Motherhood developed a package of services which should
be offered to all women to ensure safe motherhood. This package included various
preconception care services such as family planning, adolescent reproductive health
education services, and community-based education to improve sexual and reproductive
health and safe motherhood.5-6
Preconception care and Millennium Goals
The WHO acknowledges the contribution of preconception care in reaching the Millennium
Development Goals 4 (child mortality) and 5 (maternal health). They are meant to reduce the
under-five mortality rate by two thirds and maternal mortality ratio by three quarters between
1990 and 2015 and to achieve universal access to reproductive health.7 In her strategic
vision on sexual and reproductive health and rights for 2010-2015 the WHO states that
universal access for all women and newborns to appropriate preconception, antenatal,
childbirth and postpartum care should been achieved in 2015.8 Both Millennium goals are
closely related to other key areas including poverty, gender equality, nutrition, education, and
infectious diseases.7
These goals are reinforced in several documents such as the World Health report “make
every mother and child count” (2005), in which the WHO states that a ‘Continuum of Care’ is
needed to ensure maternal, newborn and child health.
4
This continuum consists of an integrated service delivery for mothers and children from prepregnancy to delivery, the immediate postnatal period, and childhood. A variety of specific
interventions, delivered at specific time frames by specific care providers, are to be
integrated. This will lead to multiple benefits, by enforcing each other, reducing costs and
enlarging the efficiency, as has been shown by the introduction of the Integrated
Management of Childhood Illness.6, 9
Such integrated care is to be provided by families and communities, outpatient services,
clinics and other health facilities.6, 9-10
The Pan American Health Organization (PAHO), a regional office of the WHO, has identified
key elements for this continuum of care. Preconception care for all women of childbearing
age should include:
o
Access to good quality health care for all adolescents
o
Vaccination (e.g., rubella and hepatitis B vaccine)
o
Essential nutrition for girls and women and work to combat eating disorders (obesity
prevention), including the administration of folic acid supplements
o
Preventive medical consultations, risk assessment, and psychological counseling (e.g.,
prevention of psychotropic substance abuse, risk behaviors)
o
Family planning, including the promotion of planned, adequately spaced pregnancies
o
Detection and treatment of sexually transmitted infections, especially HIV/AIDS
o
Treatment of chronic diseases (e.g., diabetes, hypothyroidism, malaria, tuberculosis, and
Chagas’ disease).11
The WHO has developed a set of "Essential Interventions, Commodities and Guidelines for
Reproductive, Maternal, Newborn and Child Health". This set should enable policymakers in
low- and middle- income countries to make informed choices on interventions with a
significant impact on maternal, newborn and child survival. The interventions address the
main causes of maternal, newborn and child mortality.10
Preconception care is regarded as one of the essential interventions, with the focus on family
planning, folic acid fortification and/or supplementation for preventing neural tube defects and
the prevention and management of sexually transmitted illnesses (including
Mother-to-Child Transmission of HIV and syphilis).10
Provision of preconception care
The core components of preconception care consists of risk assessment, health promotion
and intervention.5 Preconception care should be part of an interlinked chain from
preconception care through prenatal, neonatal, child, and youth care. Health authorities,
5
Non-Governmental Organizations (NGO’s) and health-care disciplines will be involved, such
as general practitioners, midwives, obstetricians, clinical geneticists, and other maternal and
child health professionals.1,12
Preconception care is meant to improve the health of mother and child by various
complementary forms. Some are aimed at individual parents-to-be, others at all women of
child-bearing age or the general population (Table 1)
Table 1. Schematic overview of provision of preconception care
Paradigm for preconception care: the terms used and how they are related 4
Individual
General individual preconception
For: all couples who want to have a child (e.g.,
preconception care
care
individual advice on stopping smoking, family
history)
Specialist individual
For: a) couples who want to have a child who are
preconception care
already known to be at great risk for adverse
pregnancy outcomes or b) couples who are referred
from general individual preconception care after risk
assessment (e.g., illness in the family, medication,
specific working conditions of prospective mother)
Collective measures with implications for preconception
For: a) everyone (e.g., radiological protection) or b)
care
all couples who want to have a child (e.g.,
nationwide folic acid campaigns)
Depending on the resources available, countries adopt different strategies to promote
preconception health. Wealthier countries tend to provide a broader preconception
programme. Next to addressing both the general population they pay special attention to
reaching (social or medical) high-risk sub-populations within their country. Less-developed
countries mainly provide targeted interventions, such as counselling patients with HIV.5
Collective measures with implications for preconception health include interventions such as
rubella vaccination of children, iodisation of salt, radiological protection of all women in the
childbearing age, cigarette package labelling for preventing low birth weight singletons and
the U.S. food supply folic acid fortification or education campaigns on the use of folic acid.1, 12
Some of them are not primarily undertaken to improve preconception health (e.g., iodisation
of salt), but do benefit the health of mother and child.
6
General individual preconception care is provided by primary care workers (general
practitioner, midwife or community health care worker) to men and women of childbearing
age. Health care workers can reach families and communities with information and resources
to promote behaviours and preventive action. They can mobilize the demand for proper
services. They can form a link between the community or the population at large and the
formal health care services.10
Specialist individual preconception care is provided by medical specialists like
gynaecologists and clinical geneticists. Depending on the medical history consultations by
other specialists might be needed. If so, coordination by a single healthcare professional is
crucially important.4
Professional organisations of nurses, midwives and gynaecologists have developed various
recommendations and guidelines for the provision of preconception care to women in
general and to targeted groups, such as diabetic mothers-to-be.5 Implementation of these
guidelines has to be supported by intervention methods and strategies for:
1. a clear distribution of tasks and responsibilities between the professionals who
provide individual care;
2. standardised risk assessment tools;
3. protocols to ensure care in a uniform manner;
4. training of professionals in the provision of preconception care;
5. standardised communication tools and strategies which can be adapted to the local
situation;
6. involvement of municipal public health institutions, schools, employers, etc.
The directives of the International Federation of Gynaecologists and Obstetricians (FIGO)
and the International Confederation of Midwives (ICM) have incorporated the provision of
preconception care (www.internationalmidwives.org, www.figo.org).
Preconception care initiatives
The goals set by the WHO are ambitious where it comes to universal access to appropriate
preconception, antenatal, childbirth and postpartum care which should be achieved by 2015.
This section tries to grasp the preconceptional programs that have been offered worldwide.
The possibilities for preconception care in primary care vary to the extent in which primary
care is developed in different countries. This entails that in some countries preconception
care programs are only found in hospital settings or in private clinics staffed by
7
gynaecologists. On the other hand, even in countries with firm primary care systems, new
developments tend to start in secondary care. Later on they are partially or totally adopted by
primary care workers (e.g., diabetes or cardiovascular check-ups). It is therefore not
surprising to find that the oldest publications on preconception care programs are found in
secondary care as can be seen in Table 2 Chamberlain et al.13 describes a clinic that was
opened in 1978 in London to serve women with a previous adverse pregnancy outcome. In
18 months 56 women were counselled on the risks and management options for a following
pregnancy. The secondary care setting tends to be easier to target women who are already
at high-risk, as is summarized in Table 2. Studies that target a specific risk factor (e.g.,
diabetes or alcohol consumption) are not included in this overview. The studies described
report on the number of women, sometimes with specification of the type of risk factors that
were found. Cox et al.14 compared the outcome of the pregnancy following preconception
care to the outcome of the previous pregnancy and found the percentage of normal live
births was doubled. De Weerd et al.15 described the increase in folate levels following
preconception consultation.
The largest program described in primary care has been in Hungary. Preconception care
was provided to 8.837 women and 7.600 men that subsequently resulted in 6060
pregnancies. Czeicel et al.16 described that these pregnancies showed 20.6/1,000 major
congenital abnormalities compared to (35.0/1,000) in the whole of Hungary.
Several other studies have been described in primary care using different (teams of)
counsellors and different interventions (Table 3). Also in primary care some of the
interventions focussed on targeting women who were at higher risk of adverse pregnancy.
These studies offered preconception care to women living in socio-financial deprived
communities.17-20 The reported outcome of these studies differ from reporting the number of
risks found,19 to increase in the use of folic acid and less alcohol use in pregnancy21, to no
effect and even one study found an adverse effect in birth weight in the subsequent
pregnancy.20 The quality and effect of the different intervention studies is described in
chapter IV.
Table 4 summarizes other preconception care initiatives. Hillemeier et al.22 describes the
Women’s Health Study in Central Pennsylvania (USA). This study combined active and
passive recruitment activities to reach women for a randomized trial on preconception
counselling in 15 low-income rural communities. In total, 692 women were included in a ratio
2-to-1 to intervention and control groups. The intervention groups were invited to participate
in 6 biweekly small group sessions led by specially trained group facilitators.23 These session
contained information on pregnancy and conception, managing stress, physical activity,
nutrition (including folic acid use), preventing infections, tobacco exposure and alcohol use.
Women in the intervention group reported higher self-efficacy for eating healthy food and to
8
perceive higher preconceptional control of pregnancy outcome; greater intent to eat healthier
foods, be more physical active and reported more daily use of multivitamins containing folic
acid.22 After 12 months follow-up the use of a multivitamin was still significantly higher in the
intervention group. Furthermore, their weight and body mass index was lower compared to
the control group.24 Weisman et al.25 conclude that preconception body mass index
(overweight or obese) and vegetable consumption (at least one serving per day) had
statistically significant independent and positive effects on birth weight and foetal growth.
Maternal weight gain during pregnancy was found to be an independent predictor of birth
weight and foetal growth. Surprisingly, after controlling for preconception and prenatal
maternal characteristics, social demographic variables were not significant predictors of birth
weight or foetal growth.
9
Table 2. Preconception care initiatives in secondary care
Author and year*
Country†
Setting
Target population
Sessions
Counsellor
Results
Previous risks
- One session
Obstetrician/
gynaecologist
Obstetrician/
gynaecologist
Midwife
56 women in 18 months
Chamberlain13
1978
Smith26
1982-1985
Cox14
1982-1990
UK
Hospital
UK
Hospital
UK
University
Hospital
SchranderStumpel27 1994
NL
De Weerd15
1996-2000
Ebrahim28
Since 2004
- Maternal medical problem
- Previous reproductive loss
- Spontaneous miscarriage
- Previous foetal abnormality
- Chronic maternal disease
- One session
- Counselling
Obstetric
gynaecologist
University
Hospital
General population:
advertisement in local paper
No data supplied
NL
University
Hospital
Main reasons for referral:
- Spontaneous miscarriage
- Previous foetal abnormality
- Chronic maternal disease
- Risk assessment
- Counselling
Obstetric
gynaecologist and
clinical geneticist
Obstetric
gynaecologist and
resident
South
Korea
University
Hospital
Women childbearing age; no
further specification
- Risk assessment
- Questionnaire
- Physical examination
- Blood tests
Obstetric
gynaecologist and
fellows in clinical
medicine
200 couples
1,075 couples
81% of women with chronic disease gave birth to live normal
infants compared to 42% in previous pregnancy (95% CI
28.5-54.9%: Chi 2 p<0.001)
106 couples; 45% gynaecological concerns and 55% genetic
concern
484 women data available 459
50% of women had additional testing. Hyperhomocysteinemia
was found in 24%, other form of thrombophilia (coagulopathy)
in 21% and vitamin deficiency in 18%.
N=111 folate level assessment at counselling and at 4 months
follow-up. A significant increase was found among women that
did not use folate supplements prior to the counselling session
N= 132 women
92% had at least one risk factor.
e.g. history of 40% adverse pregnancy outcome, 30%
spontaneous abortion, 15% birth defect, 2% genetic disease in
family
*Year(s) that preconception care was provided
†UK: United Kingdom; NL: The Netherlands; USA: United States of America
10
Table 3. Preconception care initiatives in primary care
Author and year* Country†
Setting
Target population
Sessions
Counsellor
Results
Czeizel 16
1984-1994
Hungary
Primary care
General population addressed
through primary care and
media
Nurse
Counselling of 8,837 women and 7,600 men. 6,060
pregnancies: 20.6/1,000major congenital abnormalities versus
(35/1,000) in Hungary.
Hale 17
1989
USA
Primary care
economically
disadvantaged
Community health care
workers
No data supplied
Moos 19
1989
Jack 29
1993-1995
UK
Primary care
-Risk assessment
USA
Primary care
At delivery of infant, women
received risk assessment for
low weight birth for future
pregnancy
Primarily low-income women in
family planning clinic
General population at time of
negative pregnancy test
- Risk assessment
- Counselling
- 2 x follow-up in
pregnancy
-Risk assessment
-Multiple follow-up
dependant on risk factors
Health-care
professional
No specific program
1,761 risk assessments reviewed; on average, women had 6.8
risk factors
170 women were randomised.
No difference in intervention rates of risk factors
Elsinga21
2000-2003
NL
Primary care
Women 18-40 years in 30
general practices
(control group in 37 practices)
Dunlop18
2003-2004
USA
(Atlanta
Georgia)
Primary care
African-American women with
previous very low birth weight
infant in hospital
24 months primary health
care and social services
Lumley 20
1982-1991
Australia
Primary care/
home visits
Community at higher risk poor
outcome targeted following first
birth
V d Pal 30
2009-2011
NL
Midwives
practice
General population
In intervention group:
-Risk assessment
-Referral if needed
-Information on lifestyle +
time to next pregnancy
- risk assessment
Risk assessment
- GP was sent outcome of
risk assessment and
intervention group was
offered appointment at GP
Risk assessment and
Own general
counselling
practitioner
Team: general
practitioner, nurse
practitioner/ midwife,
periodontist
Midwives
Midwives
Intervention group (sufficient data n=114 control n=1158) Folic
acid use adjusted odds 4.93 (2.81-8.66) reduced alcohol in 1e
trimester 1.79 (1.08-2.97)
20% adverse outcome control group 16% in intervention group
OR 0.77 (0.48-1.22)
1-year: 29 women enrolled retrospective cohort comparison.
Control group had 2.6 more pregnancies <18 months and 3.5
times more adverse pregnancy outcomes
1668 approached, completion study 786
information on second child analysed. In intervention group
the birth weight was lower (-97.4 gr) and 10 births occurred
<32 weeks (1 in control group
N=104 almost all women had one or more risk factors
33% had 3 or more risk facotrs
11
Table 4. Other reports on preconception care
Author and year*
Country†
Setting
Target population
Sessions
Counsellor
Results
6 group sessions of 2hours each on e.g.
lifestyle, pregnancy, stress
and nutrition
Health assessment, health
education and
empowerment and
intensive case
management for highest
risk
- Health assessment
- Educational DVD for
home study
- Nurse and physician
Question whether any
health care worker
addressed preconception
issues
Specifically trained
group facilitators
N=362 Randomised 2-to-1 measured at 14 week follow-up.
Higher self-efficacy and more behavioural changes: reading
food labels, physical activity and use of multivitamin with folic
acid.
N= 2941 Average of 7.9 risk factors
Longitudinal follow-up not provided
Hillemeier 22
Velott23
2008
USA
Community
setting
Low-income rural community
Biermann31
2001-2005
USA
Florida
Community
setting
African-American women 15-44
in socioeconomic high-risk area
Ebrahim28
2005
Hong
Kong
Family planning
association
Interested couples
Williams 32
2004-2008
USA
PRAMS data
Retrospective analysis data
from 4 states
Team: nurse-midwife,
health educator, social
worker
Nurse and physician
problems: obstetric
gynaecologist or
internist
-
Not published. Service is provided to 4000-5000 couples a
year
Cohort n= 30481 of which 32,4% reported receipt PCC.
Adjusted odds (CI)
4.4 (4-4,7) daily pre-pregnancy vitamins,
2.1 (1.8-2.4) 1e trimester prenatal care,
1.3 (1.2-1.5) alcohol drinking cessation
12
Guidelines
The previously described preconception programs in medical literature are still limited.
Programs are often provided in small communities in research settings. Only Hungary has
developed a nationwide program, which was offered to all women preconceptionally by
specifically trained nurses. The heightened attention towards preconception care is also
visible as the number of guidelines on preconception care as a program is growing.
The American Academy of Pediatircs (AAP) and the American College of Obstetrics and
Gynaecologists (ACOG) published the first guidelines for Perinatal care in 1983 in
partnership with the March of dimes Birth Defect Foundation.33 In the appendix it is noted
that “Preparation for parenthood should begin prior to conception”. Ten years later The
March of Dimes published ‘Toward Improving the outcome of Pregnancy; the 90s and
Beyond’ in which the concept of reproductive awareness was introduced.34 It calls for
professional standards, structure and financing to ensure an annual preconceptions risk
reduction visit for every woman from menarche to menopause and integration into the
perinatal care system. In 2005 the ACOG underlined the importance of preconception care in
the continuum of Women’s Health care with a committee opinion paper.35
The Centers for Disease Control and Prevention (CDC) published ‘Recommendations to
improve Preconception Health and Health Care’ in 2006.12 This report presented ten
recommendations for improving preconception health through changes in consumer
knowledge, clinical practice, public health programs, health-care financing, and data and
research activities.
Domus Medica, a Belgium Society for General Practitioners, upgraded their guideline for
neural tube defects to a guideline for preconception care in 200836 and updated it in 2011.37
Five key-elements are noted:

the need for preconceptional risk assessment

advice and were needed a referral

general practitioners should advice all women to stop smoking and deduce alcohol to
a maximum of one unit a day

if there is no evidence of immunity status a blood sample should be drawn to check
rubella and toxoplasmosis anti-bodies
13

the general practitioner should actively discuss the need for folic acid supplement
with all women who are thinking about getting pregnant. Women at increased risk of
neural tube defect (diabetics’ type 1 or 2, family history of neural tube defect, antiepileptic medication or women with thalassemia) should be advised to take 4 mg of
folic acid supplements.
In the Netherlands the Royal Society for Midwives wrote a paper in 200538 to define the role
midwives can play in preconception care.
The Dutch Society of Obstetrics and Gynaecology published an opinion paper in 2008 stating
the essential elements of preconception care and the need to actively offer it to all couples
contemplating pregnancy.39
The Dutch College of General Practitioners (NHG) has published a Preconception care
guideline in June 2011.40 It refers to a web-based risk assessment tool that had previously
been developed by Erfocentrum and Erasmus MC, www.zwangerwijzer.nl. This provides a
summary of risk factors that need attention and also enables the women to send the
summary by email to her caretaker of choice. The key message of this guideline is to create
awareness among general practitioners to:

inform women on preconception issues and the possibility to attend a specific
consultation to address the risk factors

assess which interventions are needed for women with chronic diseases

adjust (chronic) medication for women of childbearing age

family history of both men and women

assess working climate of both men and women

advise folic acid supplements

smoking cessation of men and women

reduce alcohol use in pregnancy

support women in reaching a healthy weight before pregnancy.
The National Institute for Health and Clinical Excellence (NICE) in the UK has no specific
guideline for preconception care. Preconception care is only specified in the guideline for
Diabetes care and the recommendation to use folic acid prior to pregnancy is specified in the
guideline for Antenatal Care. There is a specific guideline concerning weight management
before, during and after pregnancy. Pre-pregnancy body mass index is found to be a greater
determinant of healthy outcome for mothers and babies than any weight gain during
14
pregnancy. Therefore, evidence based recommendations are summarized to help women
achieve a healthy (pre-pregnancy) weight.
The National Health Service does provide information on preconception advice and
management, which can be found as a chapter in the topic Pregnancy in Clinical Knowledge
Summaries online (www.CKS.nhs.uk). It is divided into seven scenarios; advices for all
women, mental health, metabolic disorder, chronic medical conditions, genetic
haemoglobinopathies, advice for older women and advice about genetic screening.
The public health agency of Canada has published national guidelines for Family-centered
maternity and newborn care. A specific chapter is dedicated to preconception care first
stating the importance of preconception care, the expected diversity and the opportunities to
provide it. The Public health agency believes schools and media can play a part in getting
the appropriate message out to the general public. Primary care and community health care
workers should use diverse means to reach men and women. The guideline summarizes the
risk assessment and support on specific issues (social, lifestyle, environmental, physical
activity, nutrition and genetic and health history).
15
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Matern Child Health J 2006;10(5 Suppl):S29-35.
AbouZahr C. Safe motherhood: a brief history of the global movement 1947-2002. Br Med
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UNDG. Indicators for Monitoring the Millennium Development Goals. In. New York: United
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WHO. The World Health Report 2005 - Make Every Mother and Child Count. In. Geneva:
WHO; 2005.
PMNCH. A Global Review of the Key Interven-tions Related to Reproductive, Maternal,
Newborn and Child Health In. Geneva: PMNCH; 2011.
WHO/PAHO. Regional Strategy and Plan of Action for Neonatal Health within the Continuum
of Maternal, Newborn, and Child Care. . In. Washington: WHO/PAHO.; 2008.
Johnson K, Posner SF, Biermann J, et al. Recommendations to improve preconception health
and health care--United States. A report of the CDC/ATSDR Preconception Care Work Group
and the Select Panel on Preconception Care. MMWR Recomm Rep 2006;55(RR-6):1-23.
Chamberlain G. The prepregnancy clinic. Br Med J 1980;281(6232):29-30.
Cox M, Whittle MJ, Byrne A, Kingdom JC, Ryan G. Prepregnancy counselling: experience
from 1,075 cases. Br J Obstet Gynaecol 1992;99(11):873-6.
de Weerd S, Thomas CM, Cikot RJ, Steegers-Theunissen RP, de Boo TM, Steegers EA.
Preconception counseling improves folate status of women planning pregnancy. Obstet
Gynecol 2002;99(1):45-50.
Czeizel AE. Ten years of experience in periconceptional care. Eur J Obstet Gynecol Reprod
Biol 1999;84(1):43-9.
Hale CD, Wilson E, Dimperio D. Preconceptional intervention: a programmatic model to
reduce low birth weight incidence. Health Educ 1989;20(6):32-4.
Dunlop AL, Logue KM, Miranda MC, Narayan DA. Integrating reproductive planning with
primary health care: an exploration among low-income, minority women and men. Sex Reprod
Healthc 2010;1(2):37-43.
Moos MK. Preconceptional health promotion: a health education opportunity for all women.
Women Health 1989;15(3):55-68.
Lumley J, Donohue L. Aiming to increase birth weight: a randomised trial of pre-pregnancy
information, advice and counselling in inner-urban Melbourne. BMC Public Health 2006;6:299.
Elsinga J, de Jong-Potjer LC, van der Pal-de Bruin KM, le Cessie S, Assendelft WJ, Buitendijk
SE. The effect of preconception counselling on lifestyle and other behaviour before and during
pregnancy. Womens Health Issues 2008;18(6 Suppl):S117-25.
Hillemeier MM, Downs DS, Feinberg ME, et al. Improving women's preconceptional health:
findings from a randomized trial of the Strong Healthy Women intervention in the Central
Pennsylvania women's health study. Womens Health Issues 2008;18(6 Suppl):S87-96.
Velott DL, Baker SA, Hillemeier MM, Weisman CS. Participant recruitment to a randomized
trial of a community-based behavioral intervention for pre- and interconceptional women
findings from the Central Pennsylvania Women's Health Study. Womens Health Issues
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Weisman CS, Hillemeier MM, Downs DS, et al. Improving women's preconceptional health:
long-term effects of the Strong Healthy Women behavior change intervention in the central
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Hosp Med 1987;37(4):320, 322-3.
Schrander-Stumpel C, Offermans, J. Preconceptioneel advies door de huisarts: ervaringen
opgedaan met de Preconceptie Polikliniek Maastricht. . Patient care: het tijdschrift voor de
huisarts 1996;23 (6):52-55.
Ebrahim SH, Lo SS, Zhuo J, Han JY, Delvoye P, Zhu L. Models of preconception care
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Samyn E. Opvolgrapport Aanbeveling voor goede medische praktijkvoering
preconceptieadvies. In: Domus Medica Vereniging van Huisartsen; 2011.
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en Gynaecologie; 2008.
De Jong-Potjer L, Beentjes M, Bogchelman M, Jaspar AHJ, Van Asselt KM. NHG-Standaard
Preconceptiezorg. Huisarts en Wetenschap 2011;54(6):310-26.
17
II. Reaching target groups
Vera L.N. Schölmerich, Ingrid A. Peters, Marijana Vujkovic, Eric A.P. Steegers, Semiha Denktaş
Reaching prospective parents before the onset of pregnancy is crucial for effective
preconception care. However, it seems that women do not actively seek preconception care
consultation, nor do they enthusiastically accept the offer to attend a consultation. Research
on why preconception care achieves limited outreach and how this short-coming can be
addressed is scarce. Several studies have indicated that an important problem with reaching
parents on time is that many women do not plan pregnancies, which makes it difficult to raise
their interest in preconception care, let alone provide preconception care to them.1-2 For
instance, 40-50% of pregnancies in the United States of America are unplanned.3,4,5 This
problem is less predominant in some countries such as the Netherlands, where only 20% of
pregnancies are unplanned.6 Other studies suggest that preconception schemes fail to reach
target groups because they are not adapted to the specific situation of the target groups. For
instance, TV spots promoting the use of folic acid will not reach women who do not own a
TV.7, 8
Research on the effectiveness of methods to reach target groups for preconception care is
scarce, and does not paint a clear picture on which methods work.9,10 Given that
preconception care programs have difficulty reaching target groups, several studies
emphasize the necessity to design innovative methods of outreach.11,12,13 The sections below
consider existing or suggested methods on how to reach target groups as well as the efforts
of the programme ‘Ready for a Baby’13 in Rotterdam, the Netherlands.
Collective information through local public campaigns
Public health campaigns attempt to inform and achieve behavioural change in all individuals,
not merely in those seeking help.14 This method spans various strategies, including journal
advertisements, radio ads, newsletters, brochures, flyers, posters, TV spots, information kits,
free product samples, discount vouchers and improved labelling of products.1, 7, 9, 15, 16
Public health campaigns on preconceptional health and behaviour typically focus on one
aspect of preconception health, e.g., folic acid use15 or diabetes awareness for women trying
to conceive.9 Only a few studies have measured the effectiveness of public campaigns in the
domain of preconception (see, for instance17). These studies show varied success of public
campaigns.17 It should be noted here that the assessment of effectiveness of public
campaigns represents a major difficulty as it is difficult to exclude interferences.1
18
Together with the Star-Medical Diagnostic Center and the municipal health authority of
Rotterdam, the Erasmus Medical Center conducted a comprehensive field study at the end
of 2006 to examine the interest among care givers for organized, chain-oriented
preconception care. A small public campaign was conducted in the North of Rotterdam,
where posters were hung up in the streets and in offices of care providers, and house-tohouse information leaflets were distributed.13 These posters and leaflets emphasized the
availability of the website www.ZwangerWijzer.nl. This website contained a questionnaire
that provided information about possible risk factors for adverse pregnancy outcomes
coupled with an invitation for a preconception consult. The short campaign resulted in a
temporary increase of 250 percent in the use of www.ZwangerWijzer.nl. The last two years,
the average number of visitors per day is 400. This result indicates that certain people are, to
a certain extent, interested in preconception health and subsequently look for information on
this topic.
In January 2009, the program Ready for a Baby was launched in Rotterdam.13 The aim of the
10-year programme is to improve perinatal health outcomes in Rotterdam. In this pursuit, a
number of projects have been implemented that are based on standardized care in the
obstetrical chain of care and supplemented by a number of non-medical measures. In close
collaboration with health care and other professionals working in the field, the programme
office formulates and manages selected projects. Professionals involved in a given project
are committed to targets by means of covenants. Within Ready for a Baby, a great deal of
effort was invested in the development and organisation of programme-based preconception
care in primary care (midwifes and general practitioners). A major challenge here is to raise
public awareness for the concept of preconception care among residents.13 Here, a variety of
channels were used, including posters, flyers and banners on trams in the Northern and
Southern parts of Rotterdam.
19
Table 1. Public campaign Ready for a Baby
Product
Aim
Content
Distribution
Posters
(1) Draw attention of the public to the
Short messages in Dutch
General practitioners, midwife
fact that improving perinatal health is
and other languages
and obstetrician practices,
possible and (2) inform the public
(Turkish, Arabic and
health centres, schools,
about the availability of preconception
Papiamentu): e.g., ‘Are you
religious and migrant
care
considering a pregnancy?
organizations, social and
Visit a baby wish
well-being services, and
consultation’
shops
(1,2) and (3) provide the public with
A two-sided A5 format flyer
General practitioners, midwife
information about the content of
explains in simple Dutch (1)
and obstetrician practices,
preconception care and of the do’s
what preconception care is,
health centres, schools,
and don’ts of a healthy pregnancy
(2) why candidate parents
religious and migrant
should visit a consultation,
organizations, social and
and (3) how to enhance
well-being services, and
preconceptional health e.g.,
shops
Flyers
use folic acid
supplementation, stop
smoking, etc.
Website
(1-3) and (4) provide the public with
information of activities of the
programme Ready for a Baby and
preconception related news
Practical information about
(1) the pre-pregnancy
phase: do’s and don’ts of a
healthy pregnancy, the
availability of baby wish
The internet
www.klaarvooreenkind.nl
The web address is listed on
all materials
consultations, (2) during
pregnancy: when and why a
midwife should be visited,
(3) delivery: possible
locations of delivery (home,
hospital, birth clinic),
(4) after delivery: where to
find maternity care services,
maternity care at home or in
the birth clinic, and (5) the
youth health clinic:
vaccinations, growth and
development of the baby
20
Advertisement in
(1,2)
Short messages in Dutch:
Local newspapers are freely
local
e.g., ‘Are you considering
accessible and delivered by
newspapers and
pregnancy? Visit a baby
post; the outside of trams
on public
wish consultation’
were painted with messages
Articles written by a
Local newspapers are freely
journalist about the
accessible and delivered by
programme Ready for a
post, national newspapers
Baby with a focus on the
(not all for freely accessible
preconception projects; e.g.,
but they are mostly freely
interviews with the
accessible on the internet
transportation
Editorials
(1-4)
researchers or participating
midwives and organisations
Specific information to groups that are hard to reach
Public health campaigns attempt to deliver information to the general population. Several
studies have pointed out the difficulty of reaching high-risk target groups via public health
campaigns. A major problem here is that the message of these campaigns is not well
received by these groups. Mullenix et al.18 points out that general public health campaigns
are more apt at reaching the small group of women who actively seek preconception
information and counselling before pregnancy. Moreover, some public health campaigns
leave out specific target groups on purpose, e.g., women with insufficient knowledge of the
host country language.19
High-risk groups are typically socio-economically disadvantaged populations and nonwestern ethnic minorities. In many countries such as the Netherlands, they mostly reside in
deprived neighbourhoods of large cities20, 21, 22 Many studies have demonstrated that highrisk groups are largely underserved by health care, and preconception care is not an
exception here.23,15 Indeed, many studies on preconception care programs indicate
‘incomplete outreach’ as a major barrier for program effectiveness.15,24
In contrast to (local) public health campaigns, peer educator methods attempt to bring
specific information to underserved and mostly high-risk groups. Use of peer education for
preconceptional health promotion is a relatively new phenomenon (for instance, see18). It has
been used within other areas of health, such as diabetes, and is reported to improve access
and health outcomes for high-risk populations by offering care tailored to the socio-economic
and cultural background as well as the social network of the target group.12, 17, 25-26
Peer educators come from a similar socio-economic and cultural background as the target
group, and are therefore expected to have a deeper understanding of the situation of the
21
target group. They are often described as “bridges” between mainstream health care and
high-risk target groups.12, 27 Peer educators in preconception health are often active in
women’s and youth center’s, but other networks have also been found, such as college
campuses.28
The program Ready for a Baby developed several peer educational intervention projects.
The aim of these projects is to expand general knowledge and awareness about
preconceptional healthy behaviour, achieve specific knowledge transfer tailored to subgroups
and the increase of uptake of individual preconception care. This is done via three
educational modules that were developed by the Erasmus MC in cooperation with the
municipal health authority of Rotterdam and executed by six women from different ethnic
origin (Turkish, Moroccan, Hindustani-Surinamese, Antillean, and Cape Verdeans).
All attended a specific training on peer education and preconceptional health. At the same
time, a Turkish male was trained in order to also reach out to men.
The first educational module of the peer educator project is based on a short course
developed by the Dutch National Genetic Resource and Information Center. This peer
educational module consists of four sessions, and the content of these sessions comprises
the importance of a good preparation of a pregnancy, the timely intake of folic acid
supplementation, prenatal screening, genetics and information on the increased prevalence
of genetic disorders among some migrant groups, such as sickle cell disease and
Thalassemia. The method of training is interactive. Several materials are developed e.g., a
healthy pregnancy game with pictures. During the four sessions, women are encouraged to
access appropriate care if they have specific medical questions. Furthermore, myths and
taboos regarding pregnancy are dealt with and women are provided with the tools to achieve
behavioural change if necessary. The sessions take place either at a women’s organization,
in a community centre or in a school, all in the same neighbourhood of the target group
women. In the final session, the group of women visit a midwifery practice accompanied by a
peer educator. The course is still ongoing. In 2010, in one neighbourhood 88 women from
various ethnic origin participated in this course and we performed a qualitative evaluation.
Results are shown in Table 2.
22
Table 2. Qualitative evaluation of the course healthy pregnancy (N=88)
Reasons for participation in the course
1.
Early pregnancy and therefore interested in the topic
2.
A pregnancy wish
3.
Multiple miscarriages
4.
Information need about a healthy pregnancy
Knowledge gaps among participants
1.
The body – fertility – menstrual cycle
2.
Use of contra conceptives
3.
Medication during pregnancy
4.
Genetics
5.
Folic acid use
Specific themes mentioned by participants that need more attention
1.
Pregnancy is mostly a matter of women
2.
Lack of knowledge on causes of multiple miscarriages
3.
Stress as an important reason for adverse pregnancy outcomes
4.
Evil spirits, black magic, and the evil eye as reasons for a adverse pregnancy outcome
5.
Common misunderstandings in communication between care provider and patient
6.
Midwives are unknown professionals in the obstetrical chain of care
The second educational module of the peer educator project is called the ‘Tupperware
method’. Here, a key person in a neighbourhood is recruited by the women’s organization as
a hostess. The hostess sets up a group based on contacts within her own network. She
recruits and motivates the participants to attend the course at her home. The peer educator
then visits the women and gives the four sessions of the first educational module as outlined
above. The same women meet on three occasions, and at the last meeting a midwife is
invited to provide information on midwifery/obstetric care in the Netherlands. The
Tupperware parties are ongoing and in one neighbourhood 211 women (Turkish, Moroccan,
Antillean, Dutch and women from the Cape Verdean Islands) participated in 2011.
The third educational module of the peer educator project is geared towards reaching
women’s partners. This is a shortened version of four sessions of the first educational
module as outlined above. These sessions are geared towards Turkish men and take place
at typical meeting places for men, for example the coffee house or mosque. This module is
unique in the Netherlands. In 2010 and in 2011, in two neighbourhoods in Rotterdam 315
23
Turkish men participated in the course. A qualitative evaluation of this course was performed
and results are shown in table 3. In 2012 the course for men will continue.
Table 3. Evaluation of group education for men (N=88)
Reasons for participation in the course
1.
Interested in topic
2.
Fertility of men – what may influence the fertility
Knowledge gaps among participants
1.
The body – fertility
2.
Influence of smoking, alcohol consumption, medication
3.
Genetics
4.
Folic acid use
Specific themes mentioned by participants that need more attention
1.
Pregnancy is mostly a matter of women
2.
Mother (in law) has more important role in care for pregnant women than men
3.
Understandable written information about a healthy pregnancy
Peer Educators Perinatal Health
In September 2010, in addition to the group courses described above, a Peer Educator
Perinatal Health course was developed. Here, a full-time six month long training was
provided for 16 bilingual women of non-western ethnic minority origin that had obtained a
high school diploma. These trained peer educators are meant to play a bridging function
between caregivers and clients from high-risk groups of deprived neighbourhoods. This
means that they are able to translate the (medical) messages of caregivers into the language
and cultural framework of high-risk target groups. The training of the peer educators was
realised by the programme ‘Ready for a Baby’ in cooperation with educational, municipality,
healthcare and society stakeholders. The content of the educational programme consisted of
seven modules for ‘general health education’ and one for ‘perinatal health specialisation’.
The table below provides an overview of the contents of these modules.
24
Table 4. Training Peer Educators Perinatal Health
Modules
Content
1. Education training
Competencies of a Peer Educator
Professional attitude
Communication skills
Teamwork
2. Communication
Basics of communication
Health education
Health programmes
Self reflection
3. Work in healthcare
Health care and social services
Health care and social services in the Netherlands
Concepts of health care
Insurance
Legislation
4. Know your body
Structure and functions of the body
Respiratory, digestion and circulatory
Skeleton, muscles and nervous system
Fertility and sexuality
5. Basic diseases knowledge
Peer Education about hepatitis and asthma
Stomach, liver, intestinal diseases
Chronic diseases
Women’s diseases
6. Presentation techniques
Personal presentation
Techniques and competences
Content, procedure and relation
Transcultural communication and peer education
Identify, evaluate and report
7. Child raising
Problems with “good” and “bad”
Child raising in practice
Child raising questions and support
8. Perinatal health
Preconception care
Healthy pregnancy
Delivery
The postpartum period and infant and youth centres
Since May 2011 the Peer Educators Perinatal Health are involved in a range of educational
and support activities spanning preconception to the postnatal phase. The table below
provides an overview of the totality of services offered by the peer educators.
25
Table 5. Peer Education Perinatal Health services
Product
Content
1.Group Education Preconception care
A content and organization format for group
preconception care and health education.
2. Group Education Healthy Pregnancy
A content and organization format for group education
about healthy behavior and healthcare use during
pregnancy.
3. Group Education Delivery
about birth care and risk factors.
4. Group Education After Natal Care
about use of ‘After natal care’, specific care tasks and
importance of this kind of care.
5. Individual Perinatal Health Education
Health Education method individual support of women
during preconception care, general practitioner consult
and after natal care.
6. Support for using ‘www.ZwangerWijzer.nl’
Method for patient supervision for using web application
‘ www.ZwangerWijzer.nl’ .
7. Theme meetings
A content and organization format to achieve four theme
meetings: (1) ‘ Child baring in the Netherlands’ , (2) ‘
Baby on the way’ , (3) ‘ Delivery and After Natal Care
and’ (4) ‘ Breastfeeding and bottle-feeding’ .
8. Courses
A content and organization format to achieve three
theme courses: (1) from preconception care to postnatal
care, (2) youth health care and (3) breastfeeding and
bottle-feeding
The module described above has been successful in Rotterdam. In less than seven months,
more than 926 women were reached by the Peer Educators Perinatal Health. For evaluation
purposes, women attending this module were asked to fill in questionnaires prior to and after
having taken part in the sessions. This questionnaire retrieved information about the
women’s background, perinatal health knowledge and how they were reached. A first
analysis was done on 360 questionnaires. The following table indicates the characteristics of
women who participated.
26
Table 6. Background characteristics of women participating in Peer Education
Perinatal Health
Variable
Total N
n
%
Age (years)
222
<20
21
9
20-29
98
45
30-39
60
27
40-59
36
16
<60
7
3
Low
89
28
Intermediate
166
53
High
58
19
Dutch
17
5
Surinamese
16
5
Antillean
27
8
Cape Verdean
16
5
Turkish
38
11
Moroccan
181
50
Other
58
16
First generation immigrant
130
53
Second generation immigrant
82
33
Native
34
14
Deprived area
158
46
Non-deprived area
185
54
Yes
143
63
No
83
37
Yes
143
63
No
83
36
Educational attainment level
Ethnic origin
Generation
Residence
Married
Children
313
353
246
343
226
226
27
The Peer Education Perinatal Health project made use of four methods to reach women. In
order to measure the success of these methods in doing so, we asked participants to provide
information on how they were reached. The flowchart below shows the first results of the four
recruitment methods used based on 360 completed questionnaires. The egg-shaped circles
indicate the method, and how many women in total were reached by this method. The arrows
moving from these circles to the boxes indicate the percentage of women reached by a given
method for a given type of service. The evaluation of these methods is still work-in-progress
and will be expanded upon in the future.
Recruitment
by organizations
(46%)
(1%
)
)
%
(12%)
(4%)
(38%)
(4 2
%)
(2
6%
)
%)
( 7%
)
)
24 x Healthy
Pregnancy
n=120
(1 9
)
9%
(5
%)
5 x Delivery
n=54
(3
%
)
)
( 29 %
6 x Preconception care
n=115
Social network
(16%)
( 4%
(29
Mail
(8
1%
)
(1 8
(66%)
Flyers
13x Postnatal
Care
n=71
Proactive professional approach and promotion of preconception care
Another important method for reaching target groups in the field of preconception health
revolves around the role of care professionals, and their active promotion of preconception
care. Studies have suggested that key care professionals in the area of preconception
(including general practitioners, midwives, nurses, gynaecologists, pharmacists) should take
on a proactive approach to provide and promote preconception care as part of routine care of
women of reproductive age.5, 17, 26 It should be pointed out here that many high-risk groups do
not make adequate use of health care, 23 so the method described here cannot be the sole
strategy employed within a country.
There is only limited research on the effectiveness of a proactive professional approach in
the field of preconception. For example, Elsinga et al.19 found that general practitioners
offering preconception counselling were able to reach 25% of women who became pregnant
a year after the invitation to attend a preconception counselling session was sent out.
28
The program ‘Parents of tomorrow’ (in Dutch: ‘Ouders van Straks’) in Leiden found that
general practitioners who were asked to invite all women of reproductive age to a
preconception consult neglected to invite 45% of these women. However, a large part of
these women became pregnant. The general practitioners had not invited these women out
of fear of insulting them, for instance because they did not have a partner.17
Several projects have been put forth where caregivers are asked to proactively promote
preconception health. For instance, in the study in Leiden mentioned above, general
practitioners were asked to promote preconception health by offering preconception
counselling to women before they get pregnant.19 In Conventry, England, pharmacists were
identified as playing a key role in preconception health promotion, as they are often the first
point of contact for women requesting a pregnancy test or other conception related products
(such as folic acid or ovulation kits).29-31
Preconception education at school
Many public health programs have recognized that the reproductive health trajectory should
also be addressed during adolescence as early health interventions can have great impact
not only on future reproductive outcomes, but also on present and future general health.32
In line with this thought, few projects have been implemented.
In 2010, the state of North Carolina launched a pilot Preconception Health Strategic Plan in
which it developed and tested a Preconception Health Curriculum for high school students.
33
The goal of this pilot was to reach young people with preconception health messages during
(junior) high school. The Healthy Before Pregnancy curriculum consisted of five stand-alone
lesson plans addressing: 1) Pathways to Poor Birth Outcomes, 2) Multivitamins - Take Them
for Life, 3) Healthy Weight Matters, 4) Preventable Factors That Can Lead to Poor Birth
Outcomes, and 5) Reproductive Life Planning. The lesson plans investigated whether
preconception health topics were appealing to high school students in a pilot study of 20
classrooms at 10 high schools. The pilot showed that students were highly receptive to the
preconception health program, had low knowledge that health disparities exist between
population groups, and were surprised that pre-pregnancy health is related to birth
outcomes. From this pilot study it can be concluded that high school teachers and students
are receptive to preconception health lesson plans, and that preconception health topics
should be included in high school curricula.
29
In the state Maine of the United States of America, another study among college students
showed that stage-tailored vs. traditional folic acid education was more effective in improving
the willingness to consume a folic acid-containing multivitamin. The Internet was a successful
medium for targeting college females for preconception health care education.34
30
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essential preventive strategy to improve children's and women's health. J Public Health Policy.
2011;32(3):367-79.
McGovern E MH, Grewal G et al. Factors affecting the use of folic acid supplements in
pregnant women in Glasgow. Br J Gen Pract 1997;47:635–37.
Eicholzer M TO, Zimmermann R. Folic acid: a public-health challenge. Lancet 2006;367:1352–
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women, healthier reproductive outcomes: recommendations for the routine care of all women
of reproductive age. . AJOG. 2009.
Delft M vKE. Anticonceptiegebruik in Nederland. In. Houten: Bohn Stafleu Loghum 2002.
Prue CE FA, Panissidi P et al. But I’ve already had a healthy baby: folic acid formative
research with Latina mothers. J Women Health 2008;17:1257 – 69.
Tedstone A BM, Harrop L, Vernon C, Page V, Swindells J, Hayward W, Croft J, Harris F,
Stockley L. Fortification of selected foodstuffs with folic acid in the UK: consumer research
carried out to inform policy recommendations. J Public Health 2008;20 (1):23-29.
Janz N HW, Becker MP, Charron-Prochownik D, Shayna VL, Lesnick TG, et al. Diabetes and
pregnancy: Factors associated with seeking preconception care. Diabetes Care 1995;18:157–
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Bonsel GJ BE, Denktas S, Poeran J, Steegers EAP. Signalementstudie ‘ Zwangerschap en
geboorte’. Lijnen in de Perinatale Sterfte. Rotterdam: Erasmus MC. ; 2010.
Korenbrot CC SA, Bender C, Newberry S. Preconception care: A systematic review. Matern
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Owens MD KE, Chowdhury FH. Preconception Care and Women with or at Risk for Diabetes:
Implications for Community Intervention. Matern Child Health J 2006.
Denktaş S BG, Van der Weg EJ, Voorham AJ, Torij HW, De Graaf JP, Wildschut HI, Peters
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EA. Individual accumulation of heterogeneous risks explains perinatal inequalities within
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32
III. The association between preconceptional risk factors and
adverse pregnancy outcomes
Sabine F. van Voorst, Sevilay Temel, Amber A. Vos, Rachel Bakker, Semiha Denktaş, Eric A.P. Steegers.
This chapter describes the evidence for each domain – based on their associated risk factors
– that should be addressed in preconception care. In 2008, a supplement in the American
Journal of Obstetrics and Gynaecology (AJOG) focused on the content of preconception care
across different domains of risk factors.1 This supplement was based on a literature review, a
debate among 29 members of a clinical workgroup and interviews with consultants. The
AJOG supplement provided the framework for this chapter. The purpose of this review is to
update the AJOG supplement regarding newly identified risk factors that are potentially
modifiable in preconception care and to add new evidence on the previously described risk
factors. This update contributes to the improvement of the strength of the recommendations
and the quality of evidence in preconception care.
Methods
Search
The study identification and selection process is summarized in Figure 1. We performed an
electronic search in PubMed to identify new evidence on the preconception risk domains
described in the AJOG supplement. The exact search command is given in Appendix 1.
Key words were extracts of ‘preconception care’ or ‘interconception’. Search criteria were:
published from January 1 2008 (the AJOG supplement is based on the evidence until 2008)
until December 22 2011 and no animal studies.
Three reviewers (AV, ST, and SVV) assessed eligibility of identified articles based on title
and abstract. Further selection was performed according to predefined criteria (the study
assesses risk factor(s), present in the preconception phase for an adverse pregnancy
outcome). Articles were retrieved in full text and quality was assessed according to
predefined criteria as described in Appendix 2.
The search resulted in 2214 articles. Based on screening by title and abstract 1779 non
eligible articles were excluded. After screening the remaining articles, 257 full text articles
were excluded for reasons stated. The remaining 178 articles were included.
33
Figure 1. Study identification and selection process
Results
The domains and previously described risk factors used in the AJOG supplement were used
as a framework for this table. We added new evidence from 2008 onwards to these
descriptive tables. Since 2008, for the domains health promotion, chronic medical conditions,
maternal exposure, genetics, nutrition, environmental exposures, psychosocial stressors,
medication, special populations the quality of evidence has improved. In the other domains
(immunization, infection, psychiatric condition, and maternal exposure) the quality of
evidence has not improved. New literature further supporting the risk factors within these
domains strengthening pre-existing evidence is added. Finally, literature regarding new risk
factors associated with adverse foetal and maternal outcome is added. Newly identified
literature is shown in bold.
Health promotion
A short or long interpregnancy interval is identified and added as a new risk factor to the
AJOG table. A short interpregnancy interval, defined as six months or less between delivery
and subsequent pregnancy is associated with an increased risk of preterm delivery, low birth
weight, Small for Gestational Age (SGA), neonatal death and congenital malformations.27
Interpregnancy intervals of 18 months or less (between delivery and subsequent pregnancy)
are associated with low birth weight, preterm delivery and autism in offspring.8-9 Long
interpregnancy intervals, defined as more than 60 months between delivery and subsequent
pregnancies, are associated with preterm birth, SGA, congenital malformations and a higher
risk of premature rupture of membranes.3-4, 6-7
34
Vitamins A, C, B6 and E, folic acid, calcium, iron, zinc and magnesium are important for the
normal development of the embryo and the progress of a healthy pregnancy.10 Excessive
amounts of vitamin E, however, have adverse effects, as has been identified in the nutrition
domain of this chapter.
Chronic medical conditions
There is increase of evidence that pregnancy negatively affects the course of disease in
women with dilated cardiomyopathy during pregnancy.11 Pre-pregnancy characteristics in
women with other cardiac disease, when associated with cyanosis, subaortic or
subpulmonary ventricular dysfunction, pulmonary regurgitation, left heart obstruction or
cardiac events before pregnancy that help to identify women at increased risk for late cardiac
events (for example cardiac arrest, pulmonary oedema, arrhythmia or stroke) were added to
the table.12
Also new to the AJOG table is evidence for women with previous preeclampsia being at
increased risk for presence of a thrombophilic defect and a higher recurrence risk for
preeclampsia compared to women without a history of preeclampsia.13 New evidence is
provided for the association between thrombophilic defect and spontaneous preterm
delivery14 and unexplained still birth.15
Maternal exposure
New evidence suggests that maternal illicit drug exposure is related to cleft palate.16
Genetics
Genetic studies on folic acid metabolism found that some maternal MHTFR polymorphisms
are a risk factor for oral clefts17 or neural tube defects18 in the foetus.
Nutrition
Vitamin B12 and vitamin E were previously not described in the AJOG supplement.19-21 Low
maternal vitamin B12 status is associated with neural tube defects.20 Early detection of
vitamin B12 deficiency provides the opportunity for treatment. High maternal vitamin E by
diet and supplements is associated with an increased risk of congenital heart disease.19
Preconception care can identify women with higher vitamin E levels and supplementation or
excessive dietary intake should be avoided. Furthermore, a maternal Mediterranean diet
(characterised by high intakes of fruit, vegetables, vegetable oil, alcohol, fish, legumes and
cereals, and low intakes of potatoes and sweets) is associated with a reduction in the risk of
spina bifida in the offspring.22
35
A maternal Western dietary pattern (characterised by high intakes of meat, pizza, legumes,
potatoes, and low intakes of fruit) was associated with a higher risk of a cleft lip or cleft palate
in the offspring.23
Environmental exposures
Solvents are added as a risk factor within the environmental exposures group. Both maternal
and paternal occupational exposure to organic solvents can increase the risk of having a
child with anencephaly.24
Psychosocial stressors
Cohort studies that demonstrate an association between maternal low socio-economic status
and intellectual disability in the offspring,25 and between low maternal educational level and
preterm delivery are added.26
New evidence suggests that interpersonal violence is associated with preeclampsia27 and
preconceptional alcohol use.28
Medication
A recent published case-control study found an association between weight loss products in
the preconceptional phase and the occurrence of foetal congenital abnormalities
(dextroposition of the great arteries and anencephaly).29
Special populations
Besides the previously identified risk of low birth weight 30, a more recent cohort study also
found an association with increased premature delivery in these groups.31 Regarding women
who survived cancer, previous radiation of the gonads is also associated with an increased
risk of stillbirth, especially when radiation took place prior to menarche. 32
Conclusion
This chapter provides the up to date evidence regarding the effects of preconceptional risk
factors on foeto-maternal outcome. The update of the literature can be summarized as
follows. Vitamins are important for early embryonic development and excessive amounts of
vitamin E intake (dietary or by suppletion) are associated with adverse outcomes. Short and
long term interpregnancy intervals are associated with adverse pregnancy outcomes.
Women with pre-existing cardiac disease need specific counselling regarding their condition
and future pregnancy. Women with previous preeclampsia should be counselled regarding
recurrence risk, specific attention should go out to underlying thrombophilic disease. Illicit
drug use needs to be identified preconceptionally. As folic acid supplementation is
36
undisputed within preconception care it may be considered to identify women with genetically
altered metabolism of folate (such as in women with MTHFR gene polymorphism). Besides
the importance of assessing the use of prescribed medication, alertness is required for over
the counter drugs. Preconception care should also focus on the risks of the individual in her
physical and psychosocial environment. At a population level subgroups should recognised
as being more likely to have and accumulate risk factors. Routine preconception care should
focus on the risk factors that are associated with adverse foeto-maternal outcome. More
research is needed regarding the impact of interventions addressing proven risk factors.
37
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Lie RT. Folate and one-carbon metabolism gene polymorphisms and their associations with
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SteegersTheunissen RP. Maternal Western dietary patterns and the risk of developing a cleft lip with or
without a cleft palate, Obstet Gynecol, 110 (2007), 378-84.
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39
Appendix 1: Search terms
preconception*[tw] OR pre-conception*[tw] OR prepregnan*[tw] OR pre-pregnan*[tw] OR
pregestation*[tw] OR pre-gestation*[tw] OR periconception*[tw] OR peri-conception*[tw]
OR interconception*[tw] OR inter-conception*[tw] OR interpregnan*[tw] OR interpregnan*[tw] OR intergestation*[tw] OR inter-gestation*[tw] OR internatal*[tw] OR internatal*[tw]) NOT (animals[mesh] NOT humans[mesh]) AND 2008:2011/2012[dp]
Appendix 2: Criteria for Quality Assessment
Quality of evidence
I-a: at least 1 properly conducted randomized controlled trial BEFORE pregnancy
I-b: at least 1 properly conducted randomized controlled trial not necessarily before
pregnancy
II-1: well-designed controlled trials without randomization
II-2: cohort or case-control studies
II-3: multiple time series with or without intervention or dramatic results in uncontrolled
experiments
III: opinions: clinical experience, descriptive statistics, case reports or reports of experts
committees
40
Table 1. Health promotion1*
Domains of
preconceptional
risk factors
Risk factors
Detectability
Treatment
available
Impact of preconception care
Quality
2008
Quality
newly
identified
articles
Family planning and
reproductive life
plan
 Pregnancy intention:
Yes
+/-
The only opportunity to prevent unintended pregnancy is before
conception. Tools are available to facilitate women’s reproductive
life planning; this includes a manual for the caregiver.12 Examples
of reproductive life plans exist, 13 but have not been evaluated for
feasibility and effectiveness in primary care or other related
settings.
III
II-24-11
II-2
II-217-18
- Foetal & maternal: Unintended pregnancy rates differ
around the world.2
- Foetal: Unintended pregnancies are associated with
elective abortions, late entry to prenatal care, low birth
weight, child abuse and neglect, and behavioural
problems in children.3
Assessment of reproductive plans in low-income women
increased subsequent pregnancy planning and intention.14
 Interpregnancy interval:
‐ Short interpregnancy intervals (IPI):
‐ IPI <6 months: associated with preterm
delivery,4-8 low birth weight, 4-6, 8 neonatal death 5
and congenital malformations.5, 9
‐ IPI <12 months: associated with autism in
offspring.10
‐ IPI <18 months: associated with low birth
weight, 11 preterm delivery.11
‐ Long interpregnancy intervals (>60 months):
associated with preterm birth, 5-6 SGA, 5-6 congenital
malformations, 9 higher risk of PROM.8
Physical activity
(PA)
 Physical inactivity:
‐ >50% of adults do not get enough PA to benefit from
health benefits. Activity decreases with age and is less
common among women and among those with lower
income and lower levels of education.15
Yes
Yes
Although there is no evidence of direct benefits of preconception
exercise in terms of pregnancy outcome, indirect benefits may
include achieving a healthy weight and mood stability.
41
‐ Exercise has been associated with reduced allostatic
loads and improved allostasis before pregnancy.16
‐ Physical inactivity has been associated with
perineal lacerations, delivery complications17 and
macrosomia.18
Nutrient intake
 Nutrient intake:
Yes
Yes
The efficacy of achieving the recommended daily amount of
nutrients in terms of disease prevention is unknown. However, all
women of reproductive age should be assessed for nutritional
adequacy and receive the recommendation to take a daily
multivitamin supplement.
III
II-219
Yes
Yes
 Obesity (BMI>30kg/m2):
III
-
‐ A woman’s nutritional status has a profound impact on
her own health and can affect fertility and reproductive
outcomes.
‐ Vitamins A, C, B6 and E; folate; calcium; iron; zinc; and
magnesium are important for normal development of
the embryo and optimal progress of a healthy
pregnancy, but most women are not ingesting sufficient
amount of these nutrients.
‐ Intake of several nutrients contributing to one-carbon
metabolism (folate, riboflavin, vitamins B6 and B12)
and oxidative stress (vitamins C, E, A, b-carotene,
lutein) were associated with reduced neural tube
defects (NTD) and clefts risk.19
‐ A maternal Mediterranean diet (characterised by
high intakes of fruit, vegetables, vegetable oil,
alcohol, fish, legumes and cereals, and low intakes
of potatoes and sweets) is associated with a
reduction in the risk of spina bifida in the
offspring.20
‐ A maternal Western dietary pattern (characterised
by high intakes of meat, pizza, legumes, potatoes,
and low intakes of fruit) was associated with a
higher risk of a cleft lip or cleft palate in the
offspring.21
Weight status
 Obesity (BMI>30kg/m2):
‐ Obesity is identified as the fastest growing health
Preconception care can focus on achieving a healthy weight
status by offering behavioural strategies to decrease caloric intake
42
problem in the Western developed countries.
and increase physical activity.
 Underweight status (BMI<18.5 kg/m2):
‐ Obesity is associated with elevated risks of different
diseases, e.g., diabetes mellitus, hypertension,
infertility, heart disease and several cancers.22
All women with a low BMI should be assessed for eating disorders
and distortions of their body image. Possibly referral for further
evaluation of eating disorders might be needed.
 Underweight status (BMI<18.5 kg/m2):
‐ Foetal risks: increased risks of preterm birth, low birth
weight, and intrauterine growth restriction. Increased
risk for birth defects, such as gastroschisis.23
‐ Maternal risks: nutrient deficiencies, osteoporosis,
amenorrhea, and infertility.
Folate levels
 Inadequate folate intake:
Yes
Yes
Daily supplementation of folic acid has been adopted by <40% of
non-pregnant women of reproductive age.41-42
I-a
-
Yes
Yes
Preconception care can provide protection against preventable
diseases through immunization.
III
-
Yes
Yes
Cessation of smoking during the preconception period and during
pregnancy reduces prenatal exposure to tobacco metabolites.
II-2
-
‐ Women without folate supplementation have an
increased risk of having offspring with NTD and other
birth defects.24-32
‐ Low folate levels have been associated with occurrence
of coronary artery disease, breast and colon cancers,
and the development of some forms of dementia.33-40
Immunizations
 Lack of immunity:
‐ Risk of maternal and perhaps foetal infection during
pregnancy due to a lack of immunity to potentially
harmful infectious diseases.
Substance use
 Tobacco use:
‐ Maternal risks: Tobacco use is the leading preventable
cause of death worldwide. Women who smoke have
higher risk of dysmenorrhoea, secondary amenorrhoea,
and menstrual irregularities. They also enter
menopause at an earlier age and are therefore
exposed to associated risks (such as osteoporosis).
‐ Foetal risks: Smoking during pregnancy is associated
with preterm delivery, spontaneous abortions, stillbirths,
and intrauterine growth retardation. A meta-analysis
43
found a 90% increased risk of placenta abruption
among smokers43; smokers also have an increased risk
of placenta praevia.
 Alcohol consumption:
Yes
Yes
There is no established safe level of alcohol consumption before
or during pregnancy.45 Preconception counselling, addressing the
facts around alcohol exposure (early) in pregnancy to reduce the
number of alcohol exposed pregnancies.
III
-
Yes
Yes
Preconception care, with patient education and counselling about
prevention of STIs and sexual behaviours and pre-exposure
vaccination may reduce risks related to STIs during the
conception phase and during pregnancy.
III
-
‐ Associated with significant maternal and foetal health
risks that include miscarriage, growth restriction, and
foetal alcohol spectrum disorders, which includes foetal
alcohol syndrome.
‐ Prenatal alcohol use is considered a leading
preventable cause of birth defects in the US.44
‐ Many women consuming alcohol are at risk for
unintended conception; the foetus will be exposed to
alcohol in the most detrimental period: in early
pregnancy.
Sexual transmitted
infections (STIs)
 Sexual transmitted diseases:
‐ Approximately 19 million new STIs occur annually in
the US, almost half of which are among young adults
aged 15-24 years.46
* The bold items are the newly identified articles which strengthen evidence or add new risk factors to the AJOG 2008 supplement.
44
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Moos MK, Dunlop AL, Jack BW, et al. Healthier women, healthier reproductive outcomes: recommendations for the routine care of all women of
reproductive age. Am J Obstet Gynecol 2008;199(6 Suppl 2):S280-9.
Henshaw SK. Unintended pregnancy in the United States. Fam Plann Perspect 1998;30(1):24-9, 46.
Brown SS. The best intentions:unintended pregnancies and well-being of children and families. Washington, DC: National Academy Press 1995.
de Weger FJ, Hukkelhoven CW, Serroyen J, te Velde ER, Smits LJ. Advanced maternal age, short interpregnancy interval, and perinatal outcome. Am
J Obstet Gynecol 2011;204(5):421 e1-9.
Grisaru-Granovsky S, Gordon ES, Haklai Z, Samueloff A, Schimmel MM. Effect of interpregnancy interval on adverse perinatal outcomes--a national
study. Contraception 2009;80(6):512-8.
Nabukera SK, Wingate MS, Kirby RS, et al. Interpregnancy interval and subsequent perinatal outcomes among women delaying initiation of
childbearing. J Obstet Gynaecol Res 2008;34(6):941-7.
Rodrigues T, Barros H. Short interpregnancy interval and risk of spontaneous preterm delivery. Eur J Obstet Gynecol Reprod Biol 2008;136(2):184-8.
Cecatti JG, Correa-Silva EP, Milanez H, Morais SS, Souza JP. The associations between inter-pregnancy interval and maternal and neonatal
outcomes in Brazil. Matern Child Health J 2008;12(2):275-81.
Kwon S, Lazo-Escalante M, Villaran MV, Li CI. Relationship between interpregnancy interval and birth defects in Washington State. J Perinatol
2012;32(1):45-50.
Cheslack-Postava K, Liu K, Bearman PS. Closely spaced pregnancies are associated with increased odds of autism in California sibling births.
Pediatrics 2011;127(2):246-53.
Adam I, Ismail MH, Nasr AM, Prins MH, Smits LJ. Low birth weight, preterm birth and short interpregnancy interval in Sudan. J Matern Fetal Neonatal
Med 2009;22(11):1068-71.
Hatcher RA. Contraceptives must fit in reproductive life plan. Contracept Technol Update 1980;1(9):131-2.
Moos MK. Unintended pregnancies: a call for nursing action. MCN Am J Matern Child Nurs 2003;28(1):24-30; quiz 31.
Moos MK, Bangdiwala SI, Meibohm AR, Cefalo RC. The impact of a preconceptional health promotion program on intendedness of pregnancy. Am J
Perinatol 1996;13(2):103-8.
Centers for Disease Control and Prevention. the importance of pyhysical activity. Available at:
http://www.cdc.gov/nccdphp/dnpa/physical/importance/index.htm.
McEwen BS. Stress, adaptation, and disease. Allostasis and allostatic load. Ann N Y Acad Sci 1998;840:33-44.
Voldner N, Froslie KF, Haakstad LA, Bo K, Henriksen T. Birth complications, overweight, and physical inactivity. Acta Obstet Gynecol Scand
2009;88(5):550-5.
Voldner N, Froslie KF, Bo K, et al. Modifiable determinants of fetal macrosomia: role of lifestyle-related factors. Acta Obstet Gynecol Scand
2008;87(4):423-9.
Carmichael SL, Yang W, Feldkamp ML, et al. Reduced Risks of Neural Tube Defects and Orofacial Clefts With Higher Diet Quality. Arch Pediatr
Adolesc Med 2011.
M. Vujkovic, E.A. Steegers, C.W. Looman, M.C. Ocke, P.J. van der Spek and R.P. Steegers-Theunissen, The maternal Mediterranean dietary pattern
is associated with a reduced risk of spina bifida in the offspring, Bjog, 116 (2009), 408-15.
M. Vujkovic, M.C. Ocke, P.J. van der Spek, N. Yazdanpanah, E.A. Steegers and R.P. Steegers-Theunissen, "Maternal Western dietary patterns and
the risk of developing a cleft lip with or without a cleft palate," Obstet Gynecol, 110 (2007), 378-84.
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McTigue KM, Harris R, Hemphill B, et al. Screening and interventions for obesity in adults: summary of the evidence for the U.S. Preventive Services
Task Force. Ann Intern Med 2003;139(11):933-49.
Lam PK, Torfs CP, Brand RJ. A low pregnancy body mass index is a risk factor for an offspring with gastroschisis. Epidemiology 1999;10(6):717-21.
Goh YI, Bollano E, Einarson TR, Koren G. Prenatal multivitamin supplementation and rates of congenital anomalies: a meta-analysis. J Obstet
Gynaecol Can 2006;28(8):680-9.
Bendich A. Micronutrients in women's health and immune function. Nutrition 2001;17(10):858-67.
Oakley GP, Jr. Eat right and take a multivitamin. N Engl J Med 1998;338(15):1060-1.
Botto LD, Mulinare J, Erickson JD. Occurrence of omphalocele in relation to maternal multivitamin use: a population-based study. Pediatrics
2002;109(5):904-8.
Mills JL, Druschel CM, Pangilinan F, et al. Folate-related genes and omphalocele. Am J Med Genet A 2005;136(1):8-11.
Lammer EJ, Shaw GM, Iovannisci DM, Finnell RH. Periconceptional multivitamin intake during early pregnancy, genetic variation of acetyl-Ntransferase 1 (NAT1), and risk for orofacial clefts. Birth Defects Res A Clin Mol Teratol 2004;70(11):846-52.
Khoury MJ, Shaw GM, Moore CA, Lammer EJ, Mulinare J. Does periconceptional multivitamin use reduce the risk of neural tube defects associated
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Itikala PR, Watkins ML, Mulinare J, Moore CA, Liu Y. Maternal multivitamin use and orofacial clefts in offspring. Teratology 2001;63(2):79-86.
Rimm EB, Willett WC, Hu FB, et al. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women.
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Kruman, II, Kumaravel TS, Lohani A, et al. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to
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Duan W, Ladenheim B, Cutler RG, Kruman, II, Cadet JL, Mattson MP. Dietary folate deficiency and elevated homocysteine levels endanger
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Mason JB, Levesque T. Folate: effects on carcinogenesis and the potential for cancer chemoprevention. Oncology (Williston Park) 1996;10(11):172736, 1742-3; discussion 1743-4.
Freudenheim JL, Graham S, Marshall JR, Haughey BP, Cholewinski S, Wilkinson G. Folate intake and carcinogenesis of the colon and rectum. Int J
Epidemiol 1991;20(2):368-74.
Giovannucci E, Stampfer MJ, Colditz GA, et al. Folate, methionine, and alcohol intake and risk of colorectal adenoma. J Natl Cancer Inst
1993;85(11):875-84.
Fuchs CS, Willett WC, Colditz GA, et al. The influence of folate and multivitamin use on the familial risk of colon cancer in women. Cancer Epidemiol
Biomarkers Prev 2002;11(3):227-34.
Bentley TG, Weinstein MC, Willett WC, Kuntz KM. A cost-effectiveness analysis of folic acid fortification policy in the United States. Public Health Nutr
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de Jong-Van den Berg LT, Hernandez-Diaz S, Werler MM, Louik C, Mitchell AA. Trends and predictors of folic acid awareness and periconceptional
use in pregnant women. Am J Obstet Gynecol 2005;192(1):121-8.
Ananth CV, Smulian JC, Vintzileos AM. Incidence of placental abruption in relation to cigarette smoking and hypertensive disorders during pregnancy:
a meta-analysis of observational studies. Obstet Gynecol 1999;93(4):622-8.
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Kesmodel U, Wisborg K, Olsen SF, Henriksen TB, Secher NJ. Moderate alcohol intake during pregnancy and the risk of stillbirth and death in the first
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Hanson JW, Streissguth AP, Smith DW. The effects of moderate alcohol consumption during pregnancy on fetal growth and morphogenesis. J Pediatr
1978;92(3):457-60.
Weinstok H, Berman S, Cates W. Sexually transmitted diseases among American youth: incidence and prevalence estimates, 2000. Perspect Sex
Reprod Health 2004;36:6-10.
47
Table 2. Immunization
Domains of
preconceptional
risk factors
Risk factors
Detectability
Treatment
available
Quality
2008
Quality
newly
identified
articles
Human papillomavirus
 Maternal HPV infection:
Yes
Yes
II-2
-
(HPV)
- Subtypes of the HPV are associated with juvenile
onset recurrent respiratory papillomatosis or
laryngeal papillomatosis, resulting in high morbidity
rates and low mortality rates.1
Preconceptional detection allows treatment before
pregnancy. Treatment of cervical dysplasia with a
vaccine may reduce the risk of precancerous lesions,
avoiding the need of surgical treatments, which may
impact cervical performance during pregnancy.3
Yes
Yes
There are no studies available on the efficacy of a
preconceptional immunization program, but immunization
prior to pregnancy seems more logic than delaying
immunization until pregnancy.13 Treatment achieves
initial response in the majority of patients; however this
effect is only sustained in a small minority.14 In pregnancy
treatment reduces viral load lowering transmission during
parturition and lactation.14 Immunization of the neonate
should start postpartum.14
Also, preconception care can potentially protect or
anticipate on potential infection of the partner.
III
-
Yes
Yes
Vaccination is available and has a 98% efficacy against
infection.7 Immunization is approved for use in women in
childbearing age without a history of chickenpox.
Because immunization, preferably with live vaccine, is
III
-
- HPV infection can be associated with genital warts.
Subtypes of HPV are predisposing to cervical
dysplasia or cancer.
Hepatitis B
 Maternal Hepatitis B seropositivity:
‐ Neonatal transmission:
a) In case of acute hepatitis 10% to 90% risk,
depending on the trimester.4
b) In case of chronic hepatitis B infection 10% risk
in case of maternal HBsAG seropositivity; 90% risk
in case of maternal seropositivity for HBsAG and
Hepatitis B antigen.13
c) Neonatal transmission in utero is associated with
low birth weight and prematurity.5,6
‐ Chronic hepatitis B infection is an etiologic factor to
cirrhosis and hepatocellular carcinoma.13
Varicella
 Lack of immunity to varicella and risk of infection in
pregnancy:
‐ Neonatal transmission 0,4% to 2,0% risk,
depending on the trimester of infection. Risk is
48
Influenza
largest in the twelfth – sixteenth week of
 Non
immunization
status in times of influenza:
13,14
gestation.
‐‐ There
is an
associationinwith
higher
Neonatal
transmission
theafirst
half spontaneous
of pregnancy
13
abortion
rate.
is associated with congenital varicella syndrome
Yes
Yes
III
-
III
-
II-3
-
- Non live vaccines are considered to be safe in
pregnancy, incidence and severity of adverse effects is
low.11 Vaccination of women pregnant during the
influenza season occurs.
(limb atrophy,
skin scarring,
central
nervous
‐ Maternal
morbidity
and mortality
of influenza
system abnormalities
andduring
eye defects)
in 2%
the
infections
are increased
pregnancy,
yetofless
cases.13 compared to the age groups of <2 years
profound
and >65 yearsbefore
or when
associated
with medical
‐ Transmission
delivery
is associated
with a
9,10
conditions.
neonatal varicella of which the mortality rate is
When the decision to vaccinate is brought back to the
preconceptional period, the risk of potential adverse
effects (although rare) is avoided during pregnancy.
30%.14
Diphtheria-TetanusPertussis vaccination
infectiontocan
be fulminant
during
‐ Varicella
Lack of immunity
Diphteria,
Tetanus
or
pregnancy;orthere
is a higher tetanus
mortalityvaccination:
rate in
Pertussis,
a non-updated
pregnancy.13,14
 Diphtheria:
Yes
Yes
Measles, mumps and
rubella (MMR)
of immunity
to MMR
of infectio15n in
‐ Lack
Associated
with foetal
lossand
andrisk
prematurity.
pregnancy:
‐ Maternal: respiratory illness, which is more
 Measles:
fulminant in pregnancy.15
Yes
Yes
‐ Associated
Tetanus: with spontaneous abortion, prematurity,
low birth weight.13 There is no association with
‐ There
is no data
on foetal intrauterine tetanus;
8
birth defects.
tetanus has been found after surgical abortion or
 Mumps:
miscarriage. In the puerperal period tetanus
infection of the umbilical stump is described and
‐ Spontaneous abortion, there is no specific
associated with increased
mortality.12,15
congenital syndrome.8
‐ Maternal: Trismus, rigidity of skeletal muscle.13
‐ Maternal: infection occurs asymptomatic or causes
pulmonary tract symptoms, sometimes complicated
 Pertussis:
by meningitis.8
‐ There is no association with abnormal foetal
 Rubella:
development, foetal morbidity, or other adverse
outcomes of pregnancy. However, higher mortality
‐ Spontaneous abortion, stillbirth,
congenital rubella
rates are known
of infants.13
syndrome.13
‐ Maternal: long-term cough, complications may be
pneumonia, rib fracture. Morbidity during
pregnancy is not different when compared to the
general population.
not safe during pregnancy, the preconceptional period is
Immunization to the most frequent subtypes of influenza
an
opportunity.
viruses
is available.
- Licensed immunization is available. Vaccines are
considered safe in the second and third trimester.13
Passive immunization is probably protective against
neonatal tetanus.13
A licensed vaccine is available (MMR). Preconception
Preconceptional assessment whether or not the patient is
care can be an opportunity to prevent congenital rubella
up to date with tetanus injections seems important.
syndrome. Immunization is not possible during
pregnancy (liveofvaccine),
butcontacts
is possible
Immunization
household
of infants lowers the
preconceptionally.
It is important
that theofpatient
is is
risk
of infection of infants.
Immunization
the mother
counselled
to conceive
within
3 months
after
an
importantnot
step
in avoiding
pertussis
in newborns.
vaccination.
49
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
Silverberg MJ, et al., Condyloma in pregnancy is strongly predictive of juvenile-onset recurrent respiratory papillomatosis. Obstet Gynecol, 2003.
101(4): p. 645-52.
Prevention of genital human papillomavirus infection. Atlanta: Centers for Disease Control and Prevention, 2004.
Crane JM, Delaney T, Hutchens D Transvaginal ultrasonography in the prediction of preterm birth after treatment for cervical intraepithelial neoplasia.
Obstet Gynecol, 2006. 107(1): p. 37-44.
ACOG educational bulletin. Viral hepatitis in pregnancy. Number 248, July 1998 (replaces No. 174, November 1992). American College of
Obstetricians and Gynecologists. Int J Gynaecol Obstet, 1998. 63(2): p. 195-202.
Sheppard T, Catalog of teratogenic agents. Baltimore: John Hopkins University Press, 1998.
Hieber JO, et al., Hepatitis and pregnancy. J Pediatr, 1977. 91(4): p. 545-9.
Marin M, et al., Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep, 2007.
56(RR-4): p. 1-40.
Watson JC, et al., Measles, mumps, and rubella--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and
control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep, 1998. 47(RR-8): p. 1-57.
Fiore S, Haber, et al., Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR
Recomm Rep, 2007. 54: p. 1-49.
Harper SA FK, Uyeki TM, Cox NJ, Bridges CB, Prevention and control of influenza: recommendations of the Advisory Committee on Immunization
Practices (ACIP). MMWR Recomm Rep, 2005. 54: p. 1-40.
Ayoub DM YF, Influenza vaccination during pregnancy: a critical assessment of the recommendations of the advisory committee on Immunization
Practices (ACIP). J. Am Phys Surg, 2006. 11: p. 41.
World Health Organization. Progress towards the global elimination of neonatal tetanus. Weekly Epidemiol Rec, 1999. 74: p. 73-80
Coonrod DV, et al., The clinical content of preconception care: immunizations as part of preconception care. Am J Obstet Gynecol, 2008. 199
(6 Suppl 2): p. S290-5.
Nelson-Piercy, Handbook of Obstetric Medicine. Fourth edition ed. 2010, New York: Informa Health Care.
CDC, Prevention of Pertussis, Tetanus, and Diphtheria Among Pregnant and Postpartum Women and Their Infants. Morbidity and Mortality Weekly
Report (MMWR), 2008. 57(4): p. 1-47.
50
Table 3. Infection*
Domains of
preconceptional risk
factors
Risk factors
Detectability
Treatment
available
Quality
2008
HIV
 Maternal HIV infection and medication:
‐ Mother-to-child transmission can occur during
pregnancy, labour, delivery or breastfeeding.1-2
‐ Perinatal HIV transmission accounts for more than
90% of the cases of paediatric AIDS.2 There are
associations with miscarriage, preterm delivery and
foetal growth restriction. These risks are higher in
non-developed countries.1 HAART is not
associated with congenital malformations, low birth
weight and preterm birth.1, 3
‐ Pregnancy does not increase the risk of
progression of HIV; women with very advanced
disease however may be affected by acceleration
by pregnancy.1
Yes
Yes
Assessing the HIV status of a women before pregnancy
allows reduction in viral load and thereby the risk for foetal
transmission during pregnancy and labour (mother-to-child
transmission). HAART is life prolonging and provides
efficient reduction in viral load, lowering transmission
rates.1
I-b
 Foetal risks:
‐ Neonatal transmission rate: 5% in presence of
maternal viraemia (HCV RNA seropositivity).1
‐ No association with adverse pregnancy outcomes.1
 Maternal risks:
‐ General health: risks of chronic liver disease.
‐ Pregnancy: does not induce acceleration of liver
disease, there is a higher risk of cholestasis.1
Yes
 Maternal tuberculosis (TB) infection during
pregnancy with risk of vertical transmission and
associated medication:
Yes
Hepatitis C
Tuberculosis
Quality
newly
identified
articles
II-23
Perinatal transmission can be reduced to less than 2% in
those women with low viral load and by not
breastfeeding.4-6
Counselling about breastfeeding and postpartum
management is possible.
Yes
Treatment with ribavirin and interferon is available.
However; it is unclear whether treatment prevents longterm sequelae and treatment is not allowed in
pregnancy.1-2 The preconception phase allows treatment
aiming to lower viraemia and neonatal transmission.2
Immunization of the neonate is not recommended.1
III
-
II
-
Furthermore, preconception care facilitates counselling of
the woman about risks and postpartum management.
Yes
Preconceptional diagnosis allows adequate prophylaxis
(completion) or treatment before pregnancy. Treatment of
latent TB with isoniazide is effective.7 More advanced
51
cases or multidrug resistant TB require more toxic and
extensive treatment.1 Treatment for latent TB is safe in
pregnancy.2
‐ Associated with low birth weight.2
‐ Maternal: TB does not adversely affect disease
progression.1
Toxoplasmosis
Cytomegalovirus-virus
(CMV)
Parvovirus
Advantages of preconceptional screening for
toxoplasmosis immunization are:
 Women not immune to toxoplasma gondii or with
congenital toxoplasmosis:
‐ Congenital toxoplasmosis: chorioretinitis, mental
retardation, sensor neural hearing loss, blindness,
epilepsy at birth.
‐ There is a risk for sequelae later in life in
individuals with foetal infection.2
‐ Women who have not contracted toxoplasmosa
gondii do not have antibodies and are at risk for a
primary maternal infection.2
Yes
 Risk of CMV infection during pregnancy in women
without immunity to CMV:
‐ When vertical transmission occurs there is an
association with intrauterine growth restriction,
cerebral palsy, mental retardation,
hepatosplenomegaly, petechiae, jaundice,
chorioretinitis, hearing loss, and thrombocytopenia,
anaemia.2, 8 Severity of the infection declines with
gestational age.2, 9
‐ A recent cohort study shows low transmission
rates and good outcomes of live birth; however
a big proportion of the women underwent
termination of pregnancy.10
‐ Infections are mostly asymptomatic.2
 Risk of Parvo infection during pregnancy in women
without immunity to CMV:
Yes
No
There is no evidence that a screening/ treatment program
prevents infection.11 There is no effective treatment for
primary CMV infection during pregnancy.2 There is no
vaccine.2
Preconception care could aim at primary prevention of
infection.
Yes
No
Screening for immunity during preconception care is not
Uncertain
II-2
-
‐ Reassurance when she is immunised.
‐ Emphasize can be made in women who are not
immune.
‐ Preconceptional measurement of IgG and IgM
provides a baseline measurement; facilitating the
interpretation of testing during pregnancy, if
necessary.
‐ Although preconception testing might lead to a
diagnosis and timely management plan, there is no
evidence of efficacy or cost effectiveness of
screening.2
Treatment of toxoplasmosis during pregnancy reduces
the risk of congenital toxoplasmosis, but does not
eliminate the risk.2
52
Malaria
Gonorrhoea
Chlamydia
Syphilis
‐ Infection in de first half of pregnancy is associated
with anaemia, miscarriage/ foetal loss and foetal
hydrops.2
‐ Neurodevelopmental delay is present in children
who have received intrauterine blood transfusion,
due to anaemia caused by the Parvo infection.12-13
‐ Primary infection in adults can cause arthritis,
arthralgia and anaemia.12-13
 Maternal malaria:
‐ Associated with second trimester miscarriage,
preterm labour, low birth weight.1-2
‐ Congenital malaria occurs in 1-4% due to
tranplacental spread or transmission during
labour.1
‐ Increased risk of maternal anaemia,
hypoglycaemia and severe disease during
pregnancy.
‐ Maternal malaria is one of the leading causes of
maternal death (400000 annually).2
 Maternal gonorrhoea:
‐ Associated with chorioamnionitis, premature
rupture of membranes, and preterm delivery.2
‐ Neonatal transmission: conjunctivitis (which can
result in blindness), meningitis and endocarditis.2
‐ Maternal risk: there is a risk for pelvic inflammatory
disease, which can give rise to future fertility
problems due to pelvic adhesions.
 Maternal chlamydia:
‐ Neonatal transmission during partruition leads to
conjunctivitis (which can result in blindness) and
pneumonia.2
‐ Maternal risk: there is a risk for pelvic inflammatory
disease, which can give rise to future fertility
problems due to pelvic adhesions.2
 Maternal syphilis:
‐ Neonatal transmission is associated with stillbirth,
premature birth, neonatal death, developmental
delay, blindness, deafness, bone and teeth
supported by data.2 The condition generally does not
require treatment, except when anaemia occurs. There is
not treatment in pregnancy reducing foetal risks.2
Primary preventive measures could be addressed during
preconception care.
Yes
Yes
Preconception care offers the opportunity to offer primary
prevention.
Furthermore, adequate treatment of malaria can lower
risks of transmission. Treatment is available in
pregnancy.1-2
Yes
Yes
Preconception care is an opportunity for timely detection
and treatment of gonorrhoea. Treatment is uncomplicated
and effective.2
Yes
Yes
Preconception care is an opportunity for timely detection
and treatment of chlamydia before the health of the foetus
and the reproductive status is jeopardized due to pelvic
inflammatory disease.2 Antibiotic treatment is available.
Yes
Yes
Preconception care is an opportunity to detect and treat
syphilis timely, to prevent neonatal syphilis and comprise
maternal disease burden. Antibiotic treatment is
successful in treating all stages of syphilis; recurrence
53
‐
Herpes simplex virus

‐
‐
‐
Asymptomatic
bacteriuria

‐
‐
abnormalities, and seizures.2
Maternal symptoms vary depending on the stage of
the condition:2
Latent syphilis – asymptomatic;
Primary syphilis – genital ulcers;
Secondary syphilis – widespread rash,
lympheadenopathy, mucocutaneous lesions;
Tertiary syphilis – lesions in the neurologic, visual
and auditory systems.
Primary or reoccurring herpes simplex infection in
pregnancy:
Neonatal transmission leads to neonatal herpes
(the extent varies from a localised skin infection to
encephalitis a multiple organ system failure).2
Herpes simplex infection can be very discomforting
to the patient, and patients can feel systemically ill,
especially in case of primary infection.
Rarely herpes simplex can disseminate and cause
liver problems or even encephalitis or
pneumonitis.2
Asymptomatic bacteriuria or maternal
pyelonephritis in pregnancy:
Maternal pyelonephritis is associated with low birth
weight, prematurity, morbidity and mortality.2
Acute maternal pyelonephritis.2
though is possible.2 When syphilis is treated in early
pregnancy, congenital syphilis can be prevented.2
Yes
Yes
Awareness about the risks of herpes simplex infections
preconceptionally could lead to more timely detection and
then management during pregnancy. Antiviral therapy is
available to reduce the duration of the infection and the
recurrence. The infection cannot be eradicated.2
Yes
Yes
There are no data that screening before pregnancy is
more beneficial than screening and treating during
pregnancy.2, 14 Antibiotic treatments are 90% to 95%
effective in the prevention of progression to
pyelonephritis.2 However, bacteriuria often reoccurs
despite courses of antibiotics.2
Screening and treatment for periodontal disease is of
benefit for maternal health in general; however, there is
no evidence that this reduces adverse pregnancy
outcomes.2 Clinical treatment reduces periodontal
disease, but evidence that adverse pregnancy outcomes
are reduced with treatment is lacking.2
Periodontal disease
 Periodontal infections in pregnancy:
‐ Associated with preterm birth15-16 and
preeclampsia.17
Yes
Yes
Bacterial vaginosis
 Bacterial vaginosis in pregnancy:
‐ Associated with preterm delivery, preterm
premature rupture of membranes, spontaneous
abortion, preterm labour.14
‐ Bacterial vaginosis is a common cause of vaginal
Yes
Uncertain
Screening and treatment of asymptomatic bacterial
vaginosis is not recommended in the general population.19
Preconception care can identify and treat symptomatic
women and women at risk for potential adverse effects of
54
discharge.2
‐ There is support that the organisms resulting in
bacterial vaginosis can contribute to the risk of
pelvic inflammatory disease.18
Group B Strep
Infection (GBS)
 GBS colonisation of the urogenital tract:
‐ GBS is a common cause of neonatal sepsis and
meningitis, associated with high morbidity and
mortality rates.
‐ GBS infection is mostly asymptomatic.
Yes
+/ -
bacterial vaginosis (history of previous preterm delivery or
premature rupture of membrane).2 Antibiotic treatment (in
and outside of pregnancy) corrects microfloral imbalance,
relieving vaginal symptoms. Recurrence often occurs
though.2
Evidence is conflicting regarding the treatment effect on
preterm birth; women treated <20 weeks of gestation
seemed a subgroup with benefit form early treatment in
terms of a lower number of preterm births.20 Treatment
seems to decrease the risk of premature rupture of
membranes in women who have had a preterm delivery
before. Recurrence often occurs.21
Preconceptional screening for genital GBS colonisation is
not valuable:
- There is no evidence that identification of genital GBS
colonisation in non-pregnant women provides clinical
benefit.
- Genital tract colonisation in early pregnancy is not
predictive for neonatal GBS sepsis.22
- Treatment can eradicate GBS successfully, although
reoccurrence mostly occurs.
- Intrapartum antibiotics are 90% effective at the
prevention of early onset neonatal sepsis.
55
References
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3.
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21.
Nelson-Pierson. Handbook of Obstetric Medicine. Fourth edition ed. New York: Informa Healthcare; 2010.
Coonrod DV, Jack BW, Stubblefield PG, et al. The clinical content of preconception care: infectious diseases in preconception care. Am J Obstet
Gynecol 2008;199(6 Suppl 2):S296-309.
Machado ES, Hofer CB, Costa TT, et al. Pregnancy outcome in women infected with HIV-1 receiving combination antiretroviral therapy before versus
after conception. Sex Transm Infect 2009;85(2):82-87.
Ioannidis JP, Abrams EJ, Ammann A, et al. Perinatal transmission of human immunodeficiency virus type 1 by pregnant women with RNA virus loads
<1000 copies/ml. J Infect Dis 2001;183(4):539-45.
US Public Health Service Task Force recommendations for the use of antiretroviral drugs in pregnant women infected with HIV-1 for maternal health
and for reducing perinatal HIV-1 transmission in the United States, 2006. 2006.
ACOG committee opinion number 304, November 2004. Prenatal and perinatal human immunodeficiency virus testing: expanded recommendations.
Obstet Gynecol 2004;104(5 Pt 1):1119-24.
Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. International Union Against
Tuberculosis Committee on Prophylaxis. Bull World Health Organ 1982;60(4):555-64.
Arpino C, Gattinara GC, Rosso M, Pelliccia A, Fariello G, Curatolo P. Cortical maldevelopment in congenital cytomegalovirus infection transmitted by
a woman with preexisting immunity. J Neurovirol 2008;14(2):173-176.
Feldman B, Yinon Y, Tepperberg Oikawa M, Yoeli R, Schiff E, Lipitz S. Pregestational, periconceptional, and gestational primary maternal
cytomegalovirus infection: prenatal diagnosis in 508 pregnancies. Am J Obstet Gynecol 2011;205(4):342 e341-346.
Hadar E, Yogev Y, Melamed N, Chen R, Amir J, Pardo J. Periconceptional cytomegalovirus infection: pregnancy outcome and rate of vertical
transmission. Prenat Diagn 2010;30(12-13):1213-1216.
Duff P. A thoughtful algorithm for the accurate diagnosis of primary CMV infection in pregnancy. Am J Obstet Gynecol
2007;196(3):196-7.
Rodis JF, Rodner C, Hansen AA, Borgida AF, Deoliveira I, Shulman Rosengren S. Long-term outcome of children following maternal human
parvovirus B19 infection. Obstet Gynecol 1998;91(1):125-8.
Nagel HT, de Haan TR, Vandenbussche FP, Oepkes D, Walther FJ. Long-term outcome after fetal transfusion for hydrops associated with parvovirus
B19 infection. Obstet Gynecol 2007;109(1):42-7.
Screening for asymptomatic bacteriuria. US Preventive Services Task Force. Available at: www.ahrq.gov/clinic/uspstf/uspsbact.htm. Accessed 2008.
Offenbacher S, Lieff S, Boggess KA, et al. Maternal periodontitis and prematurity. Part I: Obstetric outcome of prematurity and growth restriction. Ann
Periodontol 2001;6(1):164-74.
Jeffcoat MK, Hauth JC, Geurs NC, et al. Periodontal disease and preterm birth: results of a pilot intervention study. J Periodontol 2003;74(8):1214-8.
Boggess KA, Lieff S, Murtha AP, Moss K, Beck J, Offenbacher S. Maternal periodontal disease is associated with an increased risk for preeclampsia.
Obstet Gynecol 2003;101(2):227-31.
Koumans EH, Markowitz LE, Hogan V. Indications for therapy and treatment recommendations for bacterial vaginosis in nonpregnant and pregnant
women: a synthesis of data. Clin Infect Dis 2002;35(Suppl 2):S152-72.
Bertholet N, Daeppen JB, Wietlisbach V, Fleming M, Burnand B. Reduction of alcohol consumption by brief alcohol intervention in primary care:
systematic review and meta-analysis. Arch Intern Med 2005;165(9):986-95.
McDonald HM, Brocklehurst P, Gordon A. Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev 2007(1):CD000262.
Hay PE, Morgan DJ, Ison CA, et al. A longitudinal study of bacterial vaginosis during pregnancy. Br J Obstet Gynaecol 1994;101(12):1048-53.
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22.
Regan JA, Klebanoff MA, Nugent RP, et al. Colonization with group B streptococci in pregnancy and adverse outcome. VIP Study Group. Am J Obstet
Gynecol 1996;174(4):1354-60.
57
Table 4. Chronic medical conditions*
Domains of
preconceptional
risk factors
Risk factors
Detectability
Treatment
available
Quality
2008
Quality
newly
identified
articles
Diabetes Mellitus
 Maternal diabetes mellitus (type 1 or 2):
Yes
Yes
Preconception diabetes control potentially reduces the risk for
pregnancy loss and congenital malformations in approximately
113000 births each year (National Health Statistics US 2004).
I
I13, 22
Foetal risks:
-
-
Congenital malformations: non-diabetic population: 23%, diabetic: 3-12% (sacral agenesis, complex cardiac
defects, spina bifida, foetal organogenesis (however,
any organ system can be affected).1-4
The rate of congenital malformations in infants born to mothers
with pre-gestational diabetes is significantly reduced when
glucose is controlled during the critical period of organogenesis
(rates nearly similar to non-diabetic population).20-21
Adverse neonatal outcome: premature delivery, low
Apgar, admission neonatal intensive care unit,
perinatal mortality.5-8
Initiation of insulin analogue treatment preconception rather than
during early pregnancy may result in a lower risk of severe
hypoglycaemia in women with type 1 diabetes.22
II-111
II-23-8, 14-19
II-310
- Improved control of maternal glucose and antepartum
foetal surveillance leads to reduction in the perinatal
mortality rate1, 9 and congenital malformation rate 10 in
pregnancies complicated by diabetes. Especially,
pregnancies with poor first trimester glycemic
control are prone to the presence of foetal heart
disease.11
Maternal risks:
- Spontaneous abortion.12 Metformin use has no effect
on abortion risk.13
- Perinatal depression.14
- No association between overweight and obese
women with type 1 or type 2 diabetes and an
increased risk for an asymmetrical large for
gestational age child15, risk for congenital
abnormalities16 or adverse pregnancy outcomes in
type 2 diabetic women.17-18
58
Thyroid disease
-
Maternal smoking, substandard utilization of
antenatal care and hypertension in diabetic women
are associated with stillbirths.19
-
In general, maternal thyroid disease is associated
with congenital anomalies (hydrocephaly, severe
hypospadias, left ventricle outflow tract
obstruction heart defects and anorectal atresia).23
Yes
Yes
Yes
Yes
 Inadequate control of hyperthyroidism24
-
Maternal risks: preeclampsia, congestive heart failure,
thyroid crisis, placental abruption.
-
Foetal risks: foetal growth restriction, low birth weight,
preterm birth, stillbirth.
No well-designed studies have specifically evaluated the
treatment of thyroid disease before pregnancy compared with
during pregnancy. Hyperthyroidism24 However when
hyperthyroidism is treated timely and safely in early pregnancy
prognosis is well for hyperthyroidism.32 When hypothyroidism is
treated safely early in pregnancy prognosis is well for
hyperthyroidism.32 Preconceptional recognition of the risk factor:
maternal thyroid diseases warrants this early treatment.
Furthermore treatment of thyroid disease may improve fertility in
women that have anovulatory menstrual cycles due to thyroid
disease.
II-1
II-223
II-1
-
 Inadequate control of hypothyroidism:25-26
-
Maternal risks: preeclampsia, placental abruption,
anaemia, postpartum haemorrhage, preterm birth, low
birth weight, foetal death, anovulatory menstrual
cycles.
-
Foetal risks: intellectual impairment.
 Subclinical hypothyroidism:25-31
Phenylketonuria
(PKU)
-
Maternal risks: placental abruption, preterm birth, low
birth weight, stillbirth, anovulatory menstrual cycles.
-
Foetal risks: impaired psychomotor development.
 Maternal phenylketonuria:
-
Untreated PKU: mental retardation, microcephaly,
delayed speech, seizures, eczema, and behaviour
abnormalities.
-
Foetal consequences of elevated phenylalanine:
microcephaly, congenital heart disease, facial
dysmorphia, low birth weight, foetal growth restriction,
developmental delay, and learning difficulties.33-36
Adverse outcomes associated with maternal PKU might be
prevented when mothers adhere to a low phenylalanine diet
before conception and continue throughout their pregnancy.33, 37-40
59
Seizure disorders
Hypertension
 Maternal seizure disorders:
-
Both seizures and medication used to treat the
disorder affect pregnancy outcomes.41
-
Maternal risks: increase in frequency of seizures
during pregnancy (in 30%).31
-
Foetal risks: congenital anomalies if mother
experienced seizures during pregnancy (2-3 times
higher compared to women without epilepsy).42
-
Seizures cause spontaneous abortion, low birth
weight, diminished head circumference,
developmental disabilities, neonatal haemorrhagic
disorder, vitamin K deficiency, and perinatal death.42-43
-
Many anticonvulsants are teratogenic: neural tube
defects, cleft lip and palate, cardiac anomalies, and
skeletal abnormalities.44-45.
-
Dependent on dose and polytherapy
(anticonvulsant-related reductions in folic acid and
disturbances in folic acid mediated biochemical
processes).42
 Maternal hypertension:
Maternal:
-
Further increasing blood pressure in pregnancy,
increased risk of preeclampsia and eclampsia, central
nervous system haemorrhage, cardiac
decompensation, renal deterioration.47
Yes
Yes
No literature for specific preconception strategies for management
of seizures.
II-2
-
II-2
II-249
Teratogenic medication: phenytoin, carbamazepine, barbiturates,
valproate; increased risk of teratogenicity at higher doses and with
polytherapy.42, 44-45
Assessment by neurologist: to determine if women are an
appropriate candidate for a withdrawal of anticonvulsant therapy
or adjustment of medication regimen (same principles for pregnant
women as for general population with seizures).46
Yes
Yes
No scientific evidence that antihypertensive therapy will improve
perinatal outcomes in mild hypertension (SDP 140-179 mmHg or
DBP 90-109 mmHg); however treatment decreases progression
to severe hypertension.54-57
Treatment of severe hypertension (SBP>180 mmHg or DPB>110
mmHg) decreases the risk of pregnancy related outcomes.53
Foetal:
-
Associated with preterm birth, intra-uterine growth
restriction, placental abruption, foetal demise.48-49
-
Superimposed preeclampsia in hypertensive women is
associated with severe adverse perinatal outcomes.50
60
Rheumatoid arthritis
(RA)
Pregnancy outcomes are related to the degree of
hypertension and presence of preeclampsia.51-53
Maternal:
Patients should be advised of the natural history of the disease
and likelihood of flaring during pregnancy. No curable treatment;
but control of symptoms.
- The disease remits in approximately 70-80% women
during pregnancy. However, 20-30% have active of
worsening disease during pregnancy.58-59
Methotrexate and Leflunomide are extremely teratogenic; NSAIDs
are safe until 27 weeks of pregnancy; corticosteroids seem save
based on available data.62
 Maternal: Rheumatoid arthritis:
Yes
Yes
III
-
II-2
II-3 65, 71
- RA may prolong time to conception.60
Foetal:
- No increase in morbidity. However, active RA may
increase the risk of intra uterine growth retardation and
prolonged premature rupture of membranes.61
Systemic Lupus
Erythematosus
(SLE)
 Maternal SLE:
Yes
Yes
Maternal:
- Exacerbations during pregnancy are common (57%).63
Active SLE at time of conception is associated with a higher risk of
disease exacerbation during pregnancy and higher rate of adverse
pregnancy related outcomes (7 to 33% vs. 61 to 67%). No curable
treatment; but control of symptoms.
III 64, 72
Better pregnancy outcome can be expected if clinical remission is
achieved before pregnancy and disease activity is adequately
controlled prior to pregnancy.65
- Maternal: gestational hypertension.64
Foetal:
- Foetal: spontaneous abortion, intra-uterine foetal death,
preeclampsia, intra uterine growth retardation, preterm
birth (in 25%), neonatal lupus (10% if anti-Ro
antibodies).63-64
Flares and adverse pregnancy outcomes are particularly elevated
among those with lupus nephritis.66-72
- Prognosis for both mother and child are best when SLE
is quiescent for at least 6 months before pregnancy and
underlying renal function is stable and normal.63
Chronic renal
disease
 Maternal chronic renal disease:
- The potential impact of chronic renal disease is
dependent on the degree of serum creatinine elevation
and the level of hypertension.73
Yes
+/-
Cohort studies report that higher serum creatinine, proteinuria,
and blood pressure prior to conception is associated with a
greater risk of disease progression during pregnancy and adverse
pregnancy outcomes.75-76, 82-83
II-2
II-2 74
61
- Reduced kidney function without hypertension is
not associated with increased risk for small for
gestational age, preeclampsia or preterm birth. 74
- Mild and normal blood pressure: >90% chance of
successful outcome and progression of renal disease is
unlikely.75
- Moderate / severe: worsening of renal function during
pregnancy.76
- Maternal: preeclampsia, anaemia, chronic
hypertension, caesarean delivery.
Foetal:
- Preterm delivery, foetal growth restriction, increased
foetal loss and stillbirth, preterm birth.76-81
- If hypertension is present: 10-fold increase in foetal
loss.82
Cardiovascular
disease
 Maternal cardiovascular disease:
Maternal:
- Physiologic alterations of pregnancy can result in
decomposition of the cardiac condition with increased
symptoms, morbidity and mortality.84-86. Adverse
cardiac events during pregnancy are associated
with increased risk of late cardiac events (cardiac
arrest, pulmonary oedema, arrhythmia or stroke). 87
Yes
Yes
Preconception care can counsel women with cardiac disease
about the risks of pregnancy in their specific condition.
Pre-pregnancy maternal characteristics can help to identify
women at increased risk for a late cardiac event.87
II-3
II-2 85, 87
II-3 86
Foetal:
- Risk of foetal or neonatal death is doubled in pregnant
women with heart disease; the risk of heart disease is
increased in offspring for almost all forms of congenital
heart disease and if the mother is affected.84, 88
- Warfarin: characteristic warfarin associated with
embryopathy and central nervous system and foetal
bleeding after first trimester.89
62
Thrombophilia
 Maternal Thrombophilia:
Yes
Yes
Maternal:
- Maternal: venous thromboembolism (deep vein,
pulmonary, cerebral vein), arterial thrombosis
(peripheral, cerebral), severe preeclampsia.90
No studies have specifically evaluated the effect of treatment;
warfarin is teratogenic so preconception counselling and family
planning are important considerations. Treatment not evidence
based and sometimes controversial.
III (no
warfarin)
II-3
(warfarin)
II-290, 96-97
(no
warfarin)
Preconception counselling for health risks during pregnancy,
medication on pregnancy outcomes; if disorder is heritable:
genetic counselling.
Foetal:
- Foetal: placental infarcts, placental abruption, recurrent
miscarriages, foetal growth restriction, spontaneous
preterm delivery, foetal stroke, unexplained still
birth.91-97
Asthma
 Maternal Thrombophilia:
Maternal:
- In about 30% of women with asthma, the condition
worsens during pregnancy (especially in case of severe
or poorly controlled asthma).98
- Maternal complications (poorly controlled):
preeclampsia, hypertension, hyperemesis.99
Foetal:
Yes
Yes
Subsequent pregnancies tend to follow a course similar to the first
pregnancy.101-102
II-3
II-3102
If asthma is adequately controlled, neonatal outcomes are similar
to those of non-asthmatic women.103-105
Risks of uncontrolled asthma appear to be greater than the risks
of asthma medications.106
Inhaled corticosteroids are recommended as prophylactic
treatment of choice for pregnant women with persistent asthma
(budesonide).107-108
- Foetal complications (poorly controlled): still birth and
infant death, neonatal hypoxia, intra uterine growth
retardation, prematurity, low birth weight.99-100
63
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Rey E, Kahn SR, David M, Shrier I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet 2003;361(9361):901-8.
Hiltunen LM, Laivuori H, Rautanen A, et al. Factor V Leiden as risk factor for unexplained stillbirth--a population-based nested case-control study.
Thromb Res 2010;125(6):505-510.
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Fetal Neonatal Med 2009;22(4):332-336.
Kircher S, Schatz M, Long L. Variables affecting asthma course during pregnancy. Ann Allergy Asthma Immunol 2002;89(5):463-6.
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1998;158(4):1091-5.
Liu S, Wen SW, Demissie K, Marcoux S, Kramer MS. Maternal asthma and pregnancy outcomes: a retrospective cohort study. Am J Obstet Gynecol
2001;184(2):90-6.
Schatz M, Dombrowski MP, Wise R, et al. Asthma morbidity during pregnancy can be predicted by severity classification. J Allergy Clin Immunol
2003;112(2):283-8.
Belanger K, Hellenbrand ME, Holford TR, Bracken M. Effect of pregnancy on maternal asthma symptoms and medication use. Obstet Gynecol
2010;115(3):559-567.
Perlow JH, Montgomery D, Morgan MA, Towers CV, Porto M. Severity of asthma and perinatal outcome.
Am J Obstet Gynecol 1992;167(4 Pt 1):963-7.
Schatz M, Zeiger RS, Hoffman CP, et al. Perinatal outcomes in the pregnancies of asthmatic women: a prospective controlled analysis. Am J Respir
Crit Care Med 1995;151(4):1170-4.
Jana N, Vasishta K, Saha SC, Khunnu B. Effect of bronchial asthma on the course of pregnancy, labour and perinatal outcome. J Obstet Gynaecol
(Tokyo 1995) 1995;21(3):227-32.
The use of newer asthma and allergy medications during pregnancy. The American College of Obstetricians and Gynecologists (ACOG) and The
American College of Allergy, Asthma and Immunology (ACAAI). Ann Allergy Asthma Immunol 2000;84(5):475-80.
National Heart L, Blood I, National Asthma E, Prevention Program A, Pregnancy Working G. NAEPP expert panel report. Managing asthma during
pregnancy: recommendations for pharmacologic treatment-2004 update. J Allergy Clin Immunol 2005;115(1):34-46.
Kallen B, Rydhstroem H, Aberg A. Congenital malformations after the use of inhaled budesonide in early pregnancy.
Obstet Gynecol 1999;93(3):392-5.
68
Table 5. Psychiatric conditions
Domains of
preconceptional
risk factors
Risk factors
Detectability
Treatment
available
Quality
2008
Quality
newly
identified
articles
Depression and
anxiety disorders
- Relapse of pre-existing depression and anxiety is highly
prevalent (10 to 20%).1
Yes
Yes
Allows time to discuss treatment options and change to treatment
regimen.
II-2
II-2 10
 Maternal depression:
- Impact on family life, mother-infant relationship, future
mental health of child.1-7
- Maternal: depression increases the risk of tobacco,
alcohol and illicit drug use, inadequate prenatal care,
increase risk of self-injurious and suicidal behaviour,
postpartum depression.1, 8-9 Reduced interaction and
irritability towards the child.6
There is a high risk of relapse if medication is discontinued (50 to
75%).1, 16
Preconception medication adjustment allows gradual tapering of
antidepressive medication to minimize risk of withdrawal
symptoms (relapse occurs in the initial months following
withdrawal).
- Foetal: preterm delivery, lower birth weight, smaller
head circumference, low Apgar1, 8-10. Short- and long
term developmental, cognitive, and behavioural
effects.1, 11-13
 Anxiety disorders1
- Maternal risks: avoidance of the child by mother,
obstetric complications.
- Foetal risks: Poor neonatal outcome, childhood
behavioural problems.
- Obsessive Compulsive Disorder (OCD)
- Maternal: Worsening of symptoms, obsessions of
infanticide or child harm.14
- Posttraumatic stress syndrome.
69
- Maternal: breastfeeding implications, mother-child
relationship, abuse, frequently comorbidity with
depression and anxiety disorder.5, 14-15
Bipolar disorder
 Maternal depression:
Yes
Yes
Maternal:
- Lower fertility rates, strong genetic loading, recurrence
rate is high if treatment is discontinued abruptly, at risk
for other psychiatric disorders and medical conditions,
unintended pregnancy ((hypo)manic episodes),
postpartum psychosis (suicide and infanticide). 3, 17-19,
high recurrence risk during pregnancy and postpartum
period.2, 20
Preconception care allows time to discuss treatment options and
change to treatment regimen (prior to conception) (medications
used are associated with increased risk of foetal anomalies).
II-2
-
II-2
-
Main goal: euthymic during pregnancy to prevent negative
outcomes.
Women should be informed about high risk of relapse when
discontinuing maintenance medication.
These women often have limited social support.
Foetal:
- Terotogenic risk (medication), strong familial pattern
(10%).21
- Some studies suggest a positive effect on the disorder
during pregnancy.1
Schizophrenia
 Maternal schizophrenia:
Maternal:
- Psychosis during pregnancy gives increased risks for
foetal abuse, neonaticide, inability to recognize signs
and symptoms of labour.1, 22
Yes
Yes
Any necessary changes in medication should be performed prior
to conception to decrease exposure of the foetus to multiple
medications (depending on severity of symptoms).
When possible, antipsychotics should be avoided during first
trimester of pregnancy.3
- Atypical antipsychotics are associated with obesity,
diabetes, and hypertension. Women with schizophrenia
tend to have poor nutrition and high prevalence of
tobacco, alcohol, and illicit drug use.
- Women often have limited social support.
- At risk for unwanted and unplanned pregnancies.
70
Foetal:
- Dearth data about atypical antipsychotics, highpotential typical are less teratogenic than low-potential
antipsychotics.
71
References
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Brockington I, Guedeney A. Motherhood and mental health. Infant Observation 1999;2(2):116-117.
Ross LE, McLean LM. Anxiety disorders during pregnancy and the postpartum period: A systematic review. J Clin Psychiatry 2006;67(8):1285-98.
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interdisciplinary integration. Am J Obstet Gynecol 2005;193(4):1312-22.
Brockington I. Postpartum psychiatric disorders. Lancet 2004;363(9405):303-10.
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Psychiatry 2004;26(4):289-95.
Gavin AR, Chae DH, Mustillo S, Kiefe CI. Prepregnancy depressive mood and preterm birth in black and white women: findings from the CARDIA
Study. J Womens Health (Larchmt) 2009;18(6):803-811.
Talge NM, Neal C, Glover V, et al. Antenatal maternal stress and long-term effects on child neurodevelopment: how and why? J Child Psychol
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Monk C. Stress and mood disorders during pregnancy: implications for child development. Psychiatr Q 2001;72(4):347-57.
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in Infancy. Infancy 2004 (6):319-34.
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Health 2006;9(5):253-63.
Loveland Cook CA, Flick LH, Homan SM, Campbell C, McSweeney M, Gallagher ME. Posttraumatic stress disorder in pregnancy: prevalence, risk
factors, and treatment. Obstet Gynecol 2004;103(4):710-7.
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study. Arch Womens Ment Health 2004;7(4):217-21.
Viguera AC, Cohen LS, Bouffard S, Whitfield TH, Baldessarini RJ. Reproductive decisions by women with bipolar disorder after prepregnancy
psychiatric consultation. Am J Psychiatry 2002;159(12):2102-4.
Yonkers KA, Wisner KL, Stowe Z, et al. Management of bipolar disorder during pregnancy and the postpartum period. Am J Psychiatry
2004;161(4):608-20.
Stewart DE, Klompenhouwer JL, Kendell RE, van Hulst AM. Prophylactic lithium in puerperal psychosis. The experience of three centres.
Br J Psychiatry 1991;158:393-7.
Viguera AC, Whitfield T, Baldessarini RJ, et al. Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood
stabilizer discontinuation. Am J Psychiatry 2007;164(12):1817-24; quiz 1923.
Merikangas KR, Low NC. The epidemiology of mood disorders. Curr Psychiatry Rep 2004;6(6):411-21.
Yaeger D, Smith HG, Altshuler LL. Atypical antipsychotics in the treatment of schizophrenia during pregnancy and the postpartum. Am J Psychiatry
2006;163(12):2064-70.
72
Table 6. Maternal exposure*
Domains of
preconceptional
risk factors
Risk factors
Detectability
Treatment
available
Quality
2008
Quality
newly
identified
articles
Alcohol
 Maternal alcohol consumption:
Yes
Yes
There is no established safe level of alcohol consumption during
pregnancy.6-7
I-a
II-12
Foetal:
Several studies found effectiveness in reducing alcohol prior to
conception by screening, brief advice, behavioural interventions,
effective contraception or a combination in diverse settings.6-9
- Spontaneous abortion,1-3 prenatal and postnatal growth
restriction,2 birth defects, and neurodevelopmental
deficits including mental retardation,4-5 with foetal
alcohol syndrome,1 preterm birth 2 and congenital
defects (craniosynostosis, omphalocele,
gastroschisis,3-4 NTDs.4)
Tobacco
 Maternal tobacco consumption:
II-24
II-34
With reducing alcohol consumption prior to conception adverse
health outcomes will also reduce.
Yes
Yes
I-a
II-25-6 7-10 11
Maternal:
- Regardless of pregnancy status, women who smoke
are at increased risk for a wide range of cancers (i.e.,
lung, cervical, pancreatic, bladder, and kidney),
cardiovascular disease, and pulmonary diseases.
Foetal:
- Foetal effects of exposure to maternal smoking include
intrauterine growth retardation,5 prematurity,6 low birth
weight,7 and sudden infant death syndrome (SIDS),
congenital heart defects,8-9 gastroschisis, 10 and
orofacial clefts.11
- Spontaneous abortion.2-3
73
- Second hand smoke exposure of an infant causes
respiratory illnesses such as asthma and bronchitis, ear
infections, and Sudden infant death.12
- Complication in pregnancy include: premature rupture
of membranes, placenta praevia, and placental
abruption.13
Illicit substances
 Maternal use of illicit substances:
Maternal:
- Women who use illicit drugs often experience higher
rates of STIs, HIV, hepatitis, domestic violence, and
depression.14
Yes
Yes
In one intervention study participants increased participation in
alcohol and drug treatment programs and increased contraception
use from 5% prior to enrolment to 61% at 12 months, reducing
their risk for a drug-exposed pregnancy.18 Contraception services
should be offered and pregnancy should be delayed until
individuals are drug free.
III
II-2 17
Foetal:
- Cocaine use has been linked to increased risks for low
birth weight, prematurity, perinatal death, abruption
placenta, small for gestational age births15-16 and for
the risk of cleft palate.17 Children exposed to cocaine
were associated with only placental abruption and
premature rupture of membranes.6
- Marijuana seems to exert less of a negative impact on
pregnancy outcomes; however, a negative effect on
cognitive development had been reported in young
children.7-8
74
References
1.
2.
3.
4.
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6.
7.
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18.
Mullally A, Cleary BJ, Barry J, Fahey TP, Murphy DJ. Prevalence, predictors and perinatal outcomes of peri-conceptional alcohol exposure-retrospective cohort study in an urban obstetric population in Ireland. BMC Pregnancy Childbirth 2011;11:27.
Patra J, Bakker R, Irving H, Jaddoe VW, Malini S, Rehm J. Dose-response relationship between alcohol consumption before and during pregnancy
and the risks of low birthweight, preterm birth and small for gestational age (SGA)-a systematic review and meta-analyses.
BJOG 2011;118(12):1411-21.
Richardson S, Browne ML, Rasmussen SA, et al. Associations between periconceptional alcohol consumption and craniosynostosis, omphalocele,
and gastroschisis. Birth Defects Res A Clin Mol Teratol 2011;91(7):623-30.
Grewal J, Carmichael SL, Ma C, Lammer EJ, Shaw GM. Maternal periconceptional smoking and alcohol consumption and risk for select congenital
anomalies. Birth Defects Res A Clin Mol Teratol 2008;82(7):519-26.
Ness RB, Zhang J, Bass D, Klebanoff MA. Interactions between smoking and weight in pregnancies complicated by preeclampsia and small-forgestational-age birth. Am J Epidemiol 2008;168(4):427-33.
Haskins A, Mukhopadhyay S, Pekow P, et al. Smoking and risk of preterm birth among predominantly Puerto Rican women. Ann Epidemiol
2008;18(6):440-6.
La Merrill M, Stein CR, Landrigan P, Engel SM, Savitz DA. Prepregnancy body mass index, smoking during pregnancy, and infant birth weight. Ann
Epidemiol 2011;21(6):413-20.
Alverson CJ, Strickland MJ, Gilboa SM, Correa A. Maternal smoking and congenital heart defects in the Baltimore-Washington Infant Study. Pediatrics
2011;127(3):e647-53.
Karatza AA, Giannakopoulos I, Dassios TG, Belavgenis G, Mantagos SP, Varvarigou AA. Periconceptional tobacco smoking and Xisolated congenital
heart defects in the neonatal period. Int J Cardiol 2011;148(3):295-9.
Feldkamp ML, Alder SC, Carey JC. A case control population-based study investigating smoking as a risk factor for gastroschisis in Utah, 1997-2005.
Birth Defects Res A Clin Mol Teratol 2008;82(11):768-75.
Zhang B, Jiao X, Mao L, Xue J. Maternal cigarette smoking and the associated risk of having a child with orofacial clefts in China: a case-control
study. J Craniomaxillofac Surg 2011;39(5):313-8.
Gold DR, Burge HA, Carey V, Milton DK, Platts-Mills T, Weiss ST. Predictors of repeated wheeze in the first year of life: the relative roles of
cockroach, birth weight, acute lower respiratory illness, and maternal smoking. Am J Respir Crit Care Med 1999;160(1):227-36.
Arnold DL, Williams MA, Miller RS, Qiu C, Sorensen TK. Iron deficiency anemia, cigarette smoking and risk of abruptio placentae. J Obstet Gynaecol
Res 2009;35(3):446-52.
Ethics ACo. ACOG Committee Opinion. Number 294, May 2004. At-risk drinking and illicit drug use: ethical issues in obstetric and gynecologic
practice. Obstet Gynecol 2004;103(5 Pt 1):1021-31.
Handler A, Kistin N, Davis F, Ferre C. Coaine use during pregnancy: perinatal outcomes. Am J Epidemiol 1992;135:1425-7.
Hadeed AJ, Siegel SR. Maternal cocaine use during pregnancy: effect on the newborn infant. Pediatrics 1989;84(205-10).
van Gelder MM, Reefhuis J, Caton AR, et al. Maternal periconceptional illicit drug use and the risk of congenital malformations. Epidemiology
2009;20(1):60-6.
Grant TM, Ernst CC, Streissguth AP. An intervention with high-risk mothers who abuse alcohol and drugs: the Seattle Advocacy Model. Am J Public
Health 1996;86(12):1816-7.
75
Table 7. Genetic risks*
Domains of
preconceptional
risk factors
Risk factors
Detectability
Treatment
available
Quality
2008
Quality
newly
identified
articles
General population
 Parental familial genetic defects:
Yes
No
Preconception care can identify individual couples that need
specific genetic counselling. Treatment of genetic diseases is
generally not applicable; there are options to be considered before
conception (adoption, surrogacy, use of donor sperm or eggs, preimplantation diagnosis or avoidance of pregnancy).
III
II-22, 1
II-3
-
- Genetic risks are present across the general
population. Burden of suffering of the descendant
depends on the genetic disease.
- All individuals, regardless of ethnicity are at risk for
Cystic Fibrosis (CF) carriership: CF carriership can be
associated with fertility problems in men (when CF
carriership has resulted in (a) missing ductus deferens;
but is furthermore asymptomatic. The burden of
disease for the descendant with CF: CF is associated
with severe morbidity and shortened life expectancy.
Counselling on Cystic Fibrosis in the general population is a topic
of debate. There is not treatment for Cystic Fibrosis.
- Some MHTFR polymorphisms are a risk factor for
oral facial clefts1 or neural tube defects2.
Ethnicity based
 Genetic diseases associated with ethnicity:
- White – higher prevalence of: Cystic fibrosis.3
- European – higher prevalence of: Cystic fibrosis.3
- Ashkenazi Jewish – higher prevalence of: Canavan
disease, cystic fibrosis, familial dysautonomia, Tay
Sachs disease, Gaucher’s disease, Niemann-Pick
disease Type A, Bloom Syndrome, Mucolipidosis IV,
Fanconi anaemia Group C.3
Yes
No
Preconception care can identify couples with ethnic based genetic
risk factors so genetic risk counselling can be offered. Treatment
of genetic diseases is generally not applicable; there are options
to be considered before conception (adoption, surrogacy, use of
donor sperm or eggs, pre-implantation diagnosis or avoidance of
pregnancy).
- French-Canadian – higher prevalence of Tay Sachs
disease.3
- Cajun – Higher prevalence of: Tay Sachs disease3
76
- African – Higher prevalence of: Sickle cell disease/ trait,
Thalassemia.3
- Mediterranean – Higher prevalence of: Thalassemia.3
- Asian - Higher prevalence of: Thalassemia.3
Family history
 Genetic diseases in the family warrant risks for
Yes
No
Treatment of genetic diseases is generally not applicable. There
are options to be considered before conception (adoption,
surrogacy, use of donor sperm or eggs, pre-implantation diagnosis
or avoidance of pregnancy).
Yes
No
Preconception can be of meaning here in the guidance of the
couple who has experienced miscarriages. There is no treatment
option available for genetic causes of recurrent miscarriage. In
some cases there are management options such as: IVF with
preimplantation genetics.3
descendants:
- Chromosomal disorders.3
II-3
-
III
-
- Clotting disorders.3
- Developmental delay, mental retardation.3
- Early infant death.3
- Heart defects.3
- Cystic fibrosis.3
- Tay Sachs.3
- Neural tube defects.3
- Orofacial clefts.3
- Sickle cell disease or trait.3
- Sudden infant death syndrome.3
- Thalassemia.3
- Thrombophilia.3
- Other known genetic disorders.3
Previous
pregnancies
Recurrent pregnancy loss (≥2 miscarriages) is associated
with genetic risks of both parents including: chromosomal
anomalies, hereditary thrombophilia.4,5,6
77
Preconception care address recurrence risks and if possible,
management options.
Known genetic
conditions
Specific genetic conditions are associated with higher risks
in pregnancy:
- Sickle cell disease: preterm labour and premature
rupture of membranes.7
- Marfan syndrome: risk of aortic dissection during
pregnancy.8
Yes
.
No
Preconception care offers opportunities regarding the control of
the maternal condition [see table chronic diseases, this report]. In
general there are no treatment options, focus on management
options for the maternal condition and the pregnancy.
II-3
-
Preconception care identifies genetic risks for the descendants
and offers the couple chances for genetic consultation.3
- Phenylketonuria: risk of microcephaly, developmental
delay, growth restriction, heart defects.9,10
78
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79
Table 8. Nutrition*
Domains of
preconceptional
risk factors
Risk factors
Detectability
Treatment
available
Quality
2008
Quality
newly
identified
articles
Dietary supplements

Inadequate dietary intake:
Yes
Yes
III
III
‐
Requirements for additional dietary supplementation
increase substantially during the earliest weeks of
pregnancy. Many women use multivitamins, single
vitamins, herbal products, traditional medicines, and
other dietary supplements prior to and during
pregnancy.1-3
Preconception care is an opportunity to assess maternal use of
dietary supplements and advise women in their use.
‐
Intake of dietary supplements is often not assessed by
health care professionals.4-5
‐
Risks of supplements are mostly unknown. (also see
Table 11 Medication).

A maternal Mediterranean diet (characterised by
high intakes of fruit, vegetables, vegetable oil,
alcohol, fish, legumes and cereals, and low
intakes of potatoes and sweets) is associated with
a reduction in the risk of spina bifida in the
offspring.6
Yes
Yes
Preconception care is an opportunity to assess maternal dietary
patterns and advise women if needed.

A maternal Western dietary pattern (characterised
by high intakes of meat, pizza, legumes, potatoes,
and low intakes of fruit) was associated with a
higher risk of a cleft lip or cleft palate in the
offspring.7

Insufficient maternal Vitamin A intake/ suppletion:
Yes
Yes
III
III
‐
Adequate vitamin A is essential for proper visual
functioning, foetal growth, reproduction, immunity, and
Preconception care is an opportunity to detect excessive maternal
vitamin A intake and advise cessation of supplementation and
excessive intake preconceptionally.
Dietary patterns
Vitamin A
80
epithelial tissue integrity.8 Because vitamin A is lipid
soluble, it crosses the placenta easily and has a long
half-life.
Folic acid
Multivitamins
Vitamin D
‐
Although normal foetal development requires sufficient
vitamin A intake, very high levels of preformed vitamin
A (retinoic acid) supplementation has been associated
with miscarriage and birth defects that affect central
nervous system and craniofacial, cardiovascular, and
thymus development.8

Insufficient maternal dietary and supplemental intake
of folate acid:
‐
Important prior to and during pregnancy because of its
proven preventive properties against neural tube
defects.9
‐
Inadequate folate levels have been linked to increased
risks of stroke, cancer, dementia,10-11 and
conotruncal heart defects.12

Insufficient vitamin intake:
‐
Insufficient intake of multivitamins containing folic acid,
vitamin D, and vitamin A can cause neural tube
defects and other birth defects.

Inadequate maternal vitamin D intake or suppletion:
‐
It is essential for the health of pregnant women and
their infants. Vitamin D deficiency is common among
pregnant women in ethnic minorities.20
‐
Deficiency is reflected in lower maternal weight gain;
biochemical evidence of disturbed skeletal
homeostasis in the infant; and in extreme situations,
reduced bone mineralization, radiological evident
rickets, and fractures.21-22
‐
Additionally, deficiency has also been associated with
other health outcomes that affect women, asthma,
Yes
Yes
Women can be advised preconceptionally about adequate dietary
and supplemental folate intake.
I-a
I-a12
Yes
Yes
Taking multivitamins, with at least 400 μg folic acid, daily may also
reduce the incidence of other malformations such as orofacial
cleft, limb deficiencies, cardiac defects, urinary tract defects, and
omphalocele.13-19
II-2
II-2
Yes
Yes
The current recommendations are 10 μg daily. Clinicians should
be aware of the risk factors for vitamin D deficiency.
II-3
II-3
The optimal dose of vitamin D for the conception and during
pregnancy is unknown. More research is needed on the optimal
vitamin D dose and blood concentrations for several health
outcomes.22
81
diabetes, autoimmune diseases, and certain
cancers.23-26
Vitamin B12
Vitamin E
Overweight

Inadequate maternal vitamin D intake or suppletion:
‐
Low maternal B12 status has been associated with
NTDS.27

Excessive maternal vitamin E intake or suppletion:
‐
High maternal vitamin E by diet and supplements
is associated with an increased risk of congenital
heart disease.28

Obesity (BMI>30kg/m2):
‐
Obesity, defined as a body mass index of 30 kg/m2 or
higher, is associated with elevated risks of type 2
diabetes, 29-39 (pregnancy-induced),40-41
hypertension, 30, 32, 34-38, 42-43 preeclampsia,30-33, 35, 44-46
infertility; subfertility,47-48 adverse birth outcomes; heart
disease; gallbladder disease; immobility; osteoarthritis;
sleep apnea; respiratory impairment; social
stigmatization; a variety of cancers ( including breast,
uterine, and colon),49-51 caesarean delivery,30-31, 33, 3637, 44, 46, 52-57 overweight in children,58-65
macrosomia,30-31, 38, 44, 46, 65-76 post term delivery,77
preterm delivery,46-47, 74, 78-86 premature rupture of
the membranes,32, 44, 87-88 abruption placentae,44
postpartum haemorrhage,44 perineal rupture,44
foetal and infant death,31, 89 congenital heart
defects in the offspring,90-92 congenital
anomalies,93 greater placenta weight,55; low Apgar
core,31 different lipid profiles,94 labour induction,33
wound infection,33 postpartum depression,95 cleft
palate,96 elevated plasma cytokine levels,82
stillbirth,97 induction,36 hydramnios,36 neural tube
defects,92, 98 spina bifida,98 cardiovascular
anomalies,98 cleft lip and palate,98 anorectal
atresia,98 hydrocephaly,98 limb reduction
Yes
Yes
Early detection of vitamin B12 gives the opportunity to treat
deficiency of vitamin B12.
-
II-127
Yes
Yes
Preconception care can identify women with higher vitamin E
levels and supplementation should be avoided.
-
II-228
Yes
Yes
The risks associated with high body mass index are best
addressed before conception because weight loss during
pregnancy is not recommended.
I-b
I-b
Losing weight before conception reduces infertility rates, health
risks for the mother and adverse birth outcomes for the infant.
82
anomalies,98 renal agenesia or hypoplasia,99
asthma in children,100 higher level nursery
admissions,38 ADHD symptoms in children,101
infant death.102
Underweight
‐
Women who are obese before conception tend to gain
and retain more weight during pregnancy.103
‐
Interpregnancy BMI changes involving overweight
mothers become more obese, normal weight
mothers become overweight or obese, or obese
mothers maintaining their obesity status across
two pregnancies appeared to play an important
role in subsequent (elevated) stillbirth risk104 and
the risk of gestational diabetes mellitus.105
‐
Interpregnancy weight reduction decreases the
risk of recurrent preeclampsia.106
‐
No association was found between pre-pregnancy
maternal obesity and hypospadias or
cryptorchodism in male infants.107
‐
A weak association was found between prepregnancy maternal obesity and microtia.108
‐
Little consistent evidence of intrauterine effects of
maternal pre-pregnancy overweight on child
cognition and behaviour was found.109-110

Underweight (BMI<18,5kg/m2)
Maternal:
‐
Yes
Yes
Women should be counselled during the preconceptional period
on the potential risks of their weight on fertility and on pregnancy
outcome.
III
II-244
Health risks of being underweight (BMI<18 kg/m2)
include nutrient deficiencies, heart irregularities,
osteoporosis, amenorrhea, and infertility.
83
Foetal:
‐
Low pre-pregnancy weight is associated with
increased risks for preterm birth45, 97, low birth weight,
gastroschisis111, anaemia, placental abruption.30, 44,
71, 73, 81, 112-122
Eating disorders

Maternal:
‐
Associated with postpartum depression.

Foetal:
Yes
Yes
When eating disorders are addressed and treated with a
multidisciplinary approach, adverse health effects on the mother
and on foetal development will be reduced. Also obstetric
complications will be less.
III
III
Miscarriage, low birth weight
‐
Eating disorders are associated with nutritional,
metabolic, endocrine, and psychological changes that
have potential negative effects on foetal development.
84
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Torloni MR, Fortunato SJ, Betran AP, et al. Ethnic disparity in spontaneous preterm birth and maternal pre-pregnancy body mass index. Arch Gynecol
Obstet 2011.
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105.
106.
107.
Zhong Y, Cahill AG, Macones GA, Zhu F, Odibo AO. The association between prepregnancy maternal body mass index and preterm delivery. Am J
Perinatol 2010;27(4):293-8.
Tennant PW, Rankin J, Bell R. Maternal body mass index and the risk of fetal and infant death: a cohort study from the North of England. Hum Reprod
2011;26(6):1501-11.
Gilboa SM, Correa A, Botto LD, et al. Association between prepregnancy body mass index and congenital heart defects. Am J Obstet Gynecol
2010;202(1):51 e1-51 e10.
Arias W, Viner-Brown S. Prepregnancy obesity and birth defects in Rhode Island. Med Health R I 2010;93(10):325-6.
Oddy WH, De Klerk NH, Miller M, Payne J, Bower C. Association of maternal pre-pregnancy weight with birth defects: evidence from a case-control
study in Western Australia. Aust N Z J Obstet Gynaecol 2009;49(1):11-5.
Rankin J, Cans C, Garne E, et al. Congenital anomalies in children with cerebral palsy: a population-based record linkage study. Dev Med Child
Neurol 2010;52(4):345-51.
Vahratian A, Misra VK, Trudeau S, Misra DP. Prepregnancy body mass index and gestational age-dependent changes in lipid levels during
pregnancy. Obstet Gynecol 2010;116(1):107-13.
LaCoursiere DY, Barrett-Connor E, O'Hara MW, Hutton A, Varner MW. The association between prepregnancy obesity and screening positive for
postpartum depression. BJOG 2010;117(8):1011-8.
Villamor E, Sparen P, Cnattingius S. Risk of oral clefts in relation to prepregnancy weight change and interpregnancy interval. Am J Epidemiol
2008;167(11):1305-11.
Hacini Afroukh N, Burguet A, Thiriez G, et al. [Very preterm birth: should we be interested in maternal pre-pregnancy body mass index?]
Grande prematurite : faut-il s'interesser a la corpulence maternelle ? Arch Pediatr 2008;15(6):1068-75.
Stothard KJ, Tennant PW, Bell R, Rankin J. Maternal overweight and obesity and the risk of congenital anomalies: a systematic review and metaanalysis. JAMA 2009;301(6):636-50.
Slickers JE, Olshan AF, Siega-Riz AM, Honein MA, Aylsworth AS, National Birth Defects Prevention S. Maternal body mass index and lifestyle
exposures and the risk of bilateral renal agenesis or hypoplasia: the National Birth Defects Prevention Study. Am J Epidemiol 2008;168(11):1259-67.
Reichman NE, Nepomnyaschy L. Maternal pre-pregnancy obesity and diagnosis of asthma in offspring at age 3 years. Matern Child Health J
2008;12(6):725-33.
Rodriguez A, Miettunen J, Henriksen TB, et al. Maternal adiposity prior to pregnancy is associated with ADHD symptoms in offspring: evidence from
three prospective pregnancy cohorts. Int J Obes (Lond) 2008;32(3):550-7.
Thompson DR, Clark CL, Wood B, Zeni MB. Maternal obesity and risk of infant death based on Florida birth records for 2004. Public Health Rep
2008;123(4):487-93.
Gilberto K, Benicio M, Velasquez-Melendez G. Gestational weight gain and prepregnancy weight influence postpartum weight retention in a cohort of
Brazilian women. J Nutr 2004;134:661-6.
Whiteman VE, McIntosh C, Rao K, Mbah AK, Salihu HM. Interpregnancy BMI change and risk of primary caesarean delivery. J Obstet Gynaecol
2011;31(7):589-93.
Ehrlich SF, Hedderson MM, Feng J, Davenport ER, Gunderson EP, Ferrara A. Change in body mass index between pregnancies and the risk of
gestational diabetes in a second pregnancy. Obstet Gynecol 2011;117(6):1323-30.
Mostello D, Jen Chang J, Allen J, Luehr L, Shyken J, Leet T. Recurrent preeclampsia: the effect of weight change between pregnancies. Obstet
Gynecol 2010;116(3):667-72.
Adams SV, Hastert TA, Huang Y, Starr JR. No association between maternal pre-pregnancy obesity and risk of hypospadias or cryptorchidism in male
newborns. Birth Defects Res A Clin Mol Teratol 2011;91(4):241-8.
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111.
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121.
122.
Ma C, Carmichael SL, Scheuerle AE, Canfield MA, Shaw GM, National Birth Defects Prevention S. Association of microtia with maternal obesity and
periconceptional folic acid use. Am J Med Genet A 2010;152A(11):2756-61.
Brion MJ, Zeegers M, Jaddoe V, et al. Intrauterine effects of maternal prepregnancy overweight on child cognition and behavior in 2 cohorts.
Pediatrics 2011;127(1):e202-11.
Rodriguez A. Maternal pre-pregnancy obesity and risk for inattention and negative emotionality in children. J Child Psychol Psychiatry 2010;51(2):13443.
Lam PK, Torfs CP, Brand RJ. A low pregnancy body mass index is a risk factor for an offspring with gastroschisis. Epidemiology 1999;10(6):717-21.
Belogolovkin V, Alio AP, Mbah AK, Clayton HB, Wathington D, Salihu HM. Patterns and success of fetal programming among women with low and
extremely low pre-pregnancy BMI. Arch Gynecol Obstet 2009;280(4):579-84.
Deutsch AB, Lynch O, Alio AP, Salihu HM, Spellacy WN. Increased risk of placental abruption in underweight women.
Am J Perinatol 2010;27(3):235-40.
Flegal KM, Graubard BI, Williamson DF, Gail MH. Excess deaths associated with underweight, overweight, and obesity. JAMA 2005;293(15):1861-7.
Begum F, Buckshe K, Pande JN. Risk factors associated with preterm labour. Bangladesh Med Res Counc Bull 2003;29(2):59-66.
Borkowski W, Mielniczuk H. [The influence of social and health factors including pregnancy weight gain rate and pre-pregnancy body mass on low
birth weight of the infant]
Wplyw wybranych czynnikow spolecznych i zdrowotnych, w tym tempa przyrostu masy ciala w ciazy i masy przed ciaza, na mala mase urodzeniowa
noworodka. Ginekol Pol 2008;79(6):415-21.
Diouf I, Charles MA, Thiebaugeorges O, et al. Maternal weight change before pregnancy in relation to birthweight and risks of adverse pregnancy
outcomes. Eur J Epidemiol 2011;26(10):789-96.
Liabsuetrakul T, Southern Soil-Transmitted H, Maternal Health Working G. Is international or Asian criteria-based body mass index associated with
maternal anaemia, low birthweight, and preterm births among Thai population? An observational study. J Health Popul Nutr 2011;29(3):218-28.
Watanabe H, Inoue K, Doi M, et al. Risk factors for term small for gestational age infants in women with low prepregnancy body mass index. J Obstet
Gynaecol Res 2010;36(3):506-12.
Velez MP, Santos IS, Matijasevich A, et al. Maternal low birth weight and adverse perinatal outcomes: the 1982 Pelotas Birth Cohort Study, Brazil.
Rev Panam Salud Publica 2009;26(2):112-9.
Salihu HM, Mbah AK, Alio AP, Lynch O, Wathington D, Kornosky JL. Maternal prepregnancy underweight and risk of early and late stillbirth in black
and white gravidas. J Natl Med Assoc 2009;101(6):582-7.
Ricci E, Parazzini F, Chiaffarino F, Cipriani S, Polverino G. Pre-pregnancy body mass index, maternal weight gain during pregnancy and risk of smallfor-gestational age birth: results from a case-control study in Italy. J Matern Fetal Neonatal Med 2010;23(6):501-5.
90
Table 9. Environmental exposures*
Domains of
preconceptional
risk factors
Risk factors
Detectability
Treatment
available
Quality
2008
Quality
newly
identified
articles
Workplace exposure

Maternal workplace exposures:
Yes
Yes
III
II-21-2
‐
Many chemicals with adverse reproductive or
developmental effects are in regular commercial use
and thus pose a risk to women before pregnancy.
During the preconceptional period harmful workplace exposures
can be identified and alternative duty could be recommended.
Consultation with an occupational medicine specialist may assist
in carrying out a more detailed investigation regarding
recommendations for work modification.
Yes
Yes
During the preconception period potential exposures could be
identified. Consultation with an occupational medicine specialist
may assist with a more detailed investigation regarding
recommendations for modifying exposures.
III
III4
Foetal:
Household
exposures
‐
There is an association between parental
exposure to solvents and anencephaly in the
offspring.1 A study in which women where
exposed to solvents at the workplace due to
environmental pollution showed a risk of
childhood cancers, especially leukemia.2

Maternal household exposures:
‐
Hobbies of concern include those involving solvents
such as oil-based paints and heavy metals (lead)
which can be toxic to the foetus.3
‐
Women with a high intake of fatty fish had 50%
higher PCB concentrations than women with low
intake. Maternal high PCB concentrations are
inversely associated with birth weight and
placental weight.4
Potential exposure to PCBs should be carefully considered before
recommending weekly consumption of fatty fish among women of
reproductive age.
The bold items are the newly identified articles which strengthen evidence or add new risk factors to the AJOG 2008 supplement.
91
References
1.
2.
3.
4.
Aguilar-Garduno C, Lacasana M, Blanco-Munoz J, Borja-Aburto VH, Garcia AM. Parental occupational exposure to organic solvents and anencephaly
in Mexico. Occup Environ Med 2010;67(1):32-7.
Sung TI, Wang JD, Chen PC. Increased risk of cancer in the offspring of female electronics workers. Reprod Toxicol 2008;25(1):115-9.
Ellenhorn MJ, Bercelous DG, editors. Medical toxicology, diagnosis and treatment of human poisoning. New York: Elsevier 1988.
Halldorsson TI, Thorsdottir I, Meltzer HM, Nielsen F, Olsen SF. Linking exposure to polychlorinated biphenyls with fatty fish consumption and reduced
fetal growth among Danish pregnant women: a cause for concern? Am J Epidemiol 2008;168(8):958-65.
92
Table 10. Psychosocial stressors*
Domains
of are the Risk
Impact
of preconception care
The
bold items
newlyfactors
identified articles which strengthen evidence or add newDetectrisk factorsTreatment
to the AJOG 2008
supplement.
preconceptional
ability
available
risk factors
Inadequate financial
resources
Intimate partner
violence, sexual
violence, and
childhood
maltreatment

Maternal financial problems:
‐
Poverty or low-income status makes it difficult to
obtain food, shelter and other necessities to a healthy
pregnancy.1-2
‐
Maternal low educational level and low
socioeconomic status are associated with
intellectual disability in offspring (IQ < 70)3 and
low maternal educational level is associated with
preterm delivery.4

Interpersonal violence:
Maternal:
Preeclampsia,5 periconceptional alcohol use,6 physical
harm, inconsistent contraception use, substance use,
unplanned pregnancies, increased risk for sexually
transmitted diseases, depression, at risk for posttraumatic
stress disorder.7-8
‐
Quality
2008
Quality
newly
identified
articles
Yes
Uncertain
It is assumed that increased income can reduce financial stress,
improve food security and improve wellbeing that contributes to a
healthy pregnancy. Benefit programs are seldom able to lift
women out of poverty.
III
II-23-4
Yes
Yes
Main goal is the prevention of violence during pregnancy.
Abuse assessment, providing information about sources of
assistance and about safety plans and a nurse as case
management protocol seem to reduce the level of interpersonal
violence and contribute to adopt safety behaviours in women.12
III
II-25, II-36
There is an increased risk for depression, and
antisocial behaviour.9
Foetal:
‐
Risks of low birth weight and preterm birth
(inconclusive data).10-11
Chronic psychosocial stress may disturb the body’s capacity to maintain stability through a change (called allostatis). Examples of allostasis are: feedback inhibition on the hypothalamic-pituitary-adrenal (HPA)
axis to maintain the body’s stress response and the modulation of inflammatory response by the HPA axis.13-14 In case of chronic and repeated stress, such as the factors stated above, these systems may
deteriorate. If pregnancy occurs when the allostatic system does not function optimally, pregnancy complications could occur, for instance premature delivery. Preconceptional or prenatal stressful events
are also associated with diabetes and overweight15-16 in offspring and congenital anomalies (cleft lip).17 An important objective of preconception care is to restore allostasis by reducing chronic
psychosocial stress before pregnancy.18
93
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
Haas JS, Meneses V, McCormick MC. Outcomes and health status of socially disadvantaged women during pregnancy. J Womens Health Gend
Based Med 1999;8(4):547-53.
Huynh M, Parker JD, Harper S, Pamuk E, Schoendorf KC. Contextual effect of income inequality on birth outcomes.
Int J Epidemiol 2005;34(4):888-95.
Heikura U, Taanila A, Hartikainen AL, et al. Variations in prenatal sociodemographic factors associated with intellectual disability: a study of the 20year interval between two birth cohorts in northern Finland. Am J Epidemiol 2008;167(2):169-177.
Morgen CS, Bjork C, Andersen PK, Mortensen LH, Nybo Andersen AM. Socioeconomic position and the risk of preterm birth--a study within the
Danish National Birth Cohort. Int J Epidemiol 2008;37(5):1109-1120.
Sanchez SE, Qiu C, Perales MT, Lam N, Garcia P, Williams MA. Intimate partner violence (IPV) and preeclampsia among Peruvian women. Eur J
Obstet Gynecol Reprod Biol 2008;137(1):50-55.
Alvanzo AA, Svikis DS. History of physical abuse and periconceptional drinking in pregnant women. Subst Use Misuse
2008;43(8-9):1098-1109.
Coker AL. Does physical intimate partner violence affect sexual health? A systematic review. Trauma Violence Abuse 2007;8(2):149-77.
Kendall-Tackett KA. Violence against women and the perinatal period: the impact of lifetime violence and abuse on pregnancy, postpartum, and
breastfeeding. Trauma Violence Abuse 2007;8(3):344-53.
Roberts TA, Klein JD, Fisher S. Longitudinal effect of intimate partner abuse on high-risk behavior among adolescents. Arch Pediatr Adolesc Med
2003;157(9):875-81.
Sharps PW, Laughon K, Giangrande SK. Intimate partner violence and the childbearing year: maternal and infant health consequences. Trauma
Violence Abuse 2007;8(2):105-16.
Silverman JG, Decker MR, Reed E, Raj A. Intimate partner violence victimization prior to and during pregnancy among women residing in 26 U.S.
states: associations with maternal and neonatal health. Am J Obstet Gynecol 2006;195(1):140-8.
McFarlane JM, Groff JY, O'Brien JA, Watson K. Secondary prevention of intimate partner violence: a randomized controlled trial. Nurs Res
2006;55(1):52-61.
McEwen BS. Protective and damaging effects of stress mediators. N Engl J Med 1998;338(3):171-9.
Chrousos GP. The stress response and immune function: clinical implications. The 1999 Novera H. Spector Lecture.
Ann N Y Acad Sci 2000;917:38-67.
Virk J, Li J, Vestergaard M, Obel C, Lu M, Olsen J. Early life disease programming during the preconception and prenatal period: making the link
between stressful life events and type-1 diabetes. PLoS One 2010;5(7):e11523.
Li J, Olsen J, Vestergaard M, Obel C, Baker JL, Sorensen TI. Prenatal stress exposure related to maternal bereavement and risk of childhood
overweight. PLoS One 2010;5(7):e11896.
Mostowska A, Hozyasz KK, Wojcicka K, Lianeri M, Jagodzinski PP. Polymorphisms of stress-related genes and the risk of nonsyndromic cleft lip with
or without cleft palate. Birth Defects Res A Clin Mol Teratol 2011;91(11):948-955.
Klerman LV, Jack BW, Coonrod DV, Lu MC, Fry-Johnson YW, Johnson K. The clinical content of preconception care: care of psychosocial stressors.
Am J Obstet Gynecol 2008;199(6 Suppl 2):S362-6.
94
Table 11. Medication*
Domains of
preconceptional
risk factors
Risk factors
Detectability
Treatment
available
Quality
2008
Quality
newly
identified
articles
In general medication can be harmful because of the teratogenic characteristics or physiologic effects of the medication; among of which small for gestational age and fertility problems should be named. These
depend on the dosage, route of administration and time in relation to the gestational age of which they are given. Important to emphasize is that under treatment of the disease can lead to higher occurrence of
the perinatal adverse effects of that disease. Medication itself is therefore not the only risk factor; under treatment of the condition the medication aims to treat is an important risk factor when awareness around
medication is addressed itself.
Prescribed
medication

Medications accepted to be contraindicated in the
periconceptional period are:
‐
Angiotensin-converting.
‐
Enzyme inhibitors and angiotensin II receptor
blockers.1,2
‐
Statins.
‐
Androgens and testosterone.
‐
Derivatives.
‐
Carbamazepine.
‐
Folic acid antagonists.3
‐
Leflunomide, thalidomide.
‐
Lithium.
‐
Phenytoin.
‐
Streptomycin and kanamycin.
‐
Tetracycline.
Yes
Yes
Preconception care can identify potentially harmful medication and
propose a management plan in which control of the condition is
not compromised and foetal risks are minimised.
Preconception care can increase awareness that prescribed
medication can be potentially harmful and nonessential prescribed
medication should be avoided.
II-2
II-2 2
II-2 3
II-1 4
II-2 5
III 6
II-2 7
95
Over the counter
drugs
‐
Valproic acid.4-6
‐
Isotretoin.
‐
Some bronchodilators such as albuterol, are
associated with higher risk of cleft lip.7

Medications accepted to be contraindicated in the
periconceptional period are:
‐
Analgesics: Aspirin, Ibuprofen, Ketoprofen, Naproxen.
Yes
Yes
1
Dietary supplements
‐
Cough and cold medication containing
pseudoephedrine, Guaifenisin or Clemastine.1
‐
Gastrointestinal medication containing Nizatidine,
Famotidine.1

Maternal consumption of herbs/ herbal products:
‐
These may be abortifiacient, mimic oxytocin or be
teratogenic at certain doses; studies of effects of
herbal products in pregnancy are lacking to ensure
safety.8
‐
Weight loss products: studies of effects of herbal
products in pregnancy are generally lacking to ensure
safety. On the contrary a new case control trial was
identified in which weight loss products in the
periconceptional phase were associated with
congenital abnormalities (dextroposition of the great
arteries, anencephaly).9
‐
Efficacy of dietary supplements and consequences of
deficiencies in vitamins and minerals are described in
the nutrition table and the efficacy table in this report.
Preconception care can identify potentially harmful over the
counter acquired drugs and propose a management plan in which
control of the underlying symptoms is not compromised and foetal
risks are minimised. Management options and safer alternatives
may be available.1
III
Preconception care can increase awareness amongst the patients
that over the counter drugs are potentially harmful and use of
nonessential over the counter drugs should be avoided.
Yes
Yes
Preconception care can identify potentially harmful dietary
supplements and propose a management plan in foetal risks are
minimised. Management options and safer alternatives may be
available.
II-C
II-29
Preconception care can increase awareness amongst the patients
that dietary supplements are potentially harmful and that use of
nonessential dietary supplements should be avoided.
96
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
Dunlop AL, Gardiner PM, Shellhaas CS, Menard MK, McDiarmid MA. The clinical content of preconception care: the use of medications and
supplements among women of reproductive age. Am J Obstet Gynecol 2008;199(6 Suppl 2):S367-72.
Caton AR, Bell EM, Druschel CM, et al. Maternal hypertension, antihypertensive medication use, and the risk of severe hypospadias. Birth Defects
Res A Clin Mol Teratol 2008;82(1):34-40.
Wen SW, Zhou J, Yang Q, Fraser W, Olatunbosun O, Walker M. Maternal exposure to folic acid antagonists and placenta-mediated adverse
pregnancy outcomes. CMAJ 2008;179(12):1263-8.
Mawer G, Briggs M, Baker GA, et al. Pregnancy with epilepsy: obstetric and neonatal outcome of a controlled study. Seizure 2010;19(2):112-9.
Thomas SV, Ajaykumar B, Sindhu K, et al. Cardiac malformations are increased in infants of mothers with epilepsy. Pediatr Cardiol 2008;29(3):604-8.
Holmes LB, Mittendorf R, Shen A, Smith CR, Hernandez-Diaz S. Fetal effects of anticonvulsant polytherapies: different risks from different drug
combinations. Arch Neurol 2011;68(10):1275-81.
Munsie JW, Lin S, Browne ML, et al. Maternal bronchodilator use and the risk of orofacial clefts. Hum Reprod 2011;26(11):3147-54.
Refuerzo JS, Blackwell SC, Sokol RJ, et al. Use of over-the-counter medications and herbal remedies in pregnancy. Am J Perinatol 2005;22(6):321-4.
Bitsko RH, Reefhuis J, Louik C, et al. Periconceptional use of weight loss products including ephedra and the association with birth defects. Birth
Defects Res A Clin Mol Teratol 2008;82(8):553-62.
97
Table 12. Reproductive history*
Domains of
preconceptional
risk factors
Risk factors
Prior preterm birth
‐
Women with a history of preterm birth have an
increased risk on subsequent preterm birth.1-3 Earlier
preterm birth (in terms of gestation) increases the risk
of recurrence.
‐
1 preterm birth before 35 weeks: 16% reoccurrence
risk, 2 preterm births: is associated wit a recurrence
risk of 41%, 3 preterm births is associated with a
recurrence risk of: 67%.4 5
‐
Risk factors are (besides) previous preterm birth:
Prior foetal growth
restriction
‐
Multiple gestations
‐
African American ethnicity
‐
Chorioamnionitis
‐
Low maternal pre-pregnancy weight
‐
Large interpregnancy weight loss (> 5 kg/m2)
‐
Cigarette smoking
‐
Short pregnancy interval (< 12 months)
‐
History of cervix insufficiency
‐
Maternal periodontal disease
‐
Medication

Foetal risks of growth restriction:
‐
Growth restricted foetuses account for almost half of
all stillbirths. It is also a main cause for foetal
Detectability
Treatment
available
Quality
2008
Quality
newly
identified
articles
Yes
Uncertain
Preconception care provides the opportunity to identify women at
risk for preterm birth due to prior preterm birth and due to risk
factors which can result in preterm birth. Women can be
counselled, about recurrence risks and a management plan can
be formulated, when they are not yet pregnant. The
preconceptional phase is an opportunity to treat some risk actors
and theoretically decrease anxiety regarding reoccurrence of
prematurity.
I-a
-
Yes
+ / -
Preconception care provides the opportunity to identify women at
risk by determining their pregnancy history and planning next
pregnancies
II-2
-
98
asphyxia, meconium aspiration, serious neonatal
morbidity, infant death. It has also consequences in
childhood and adulthood (hypertension, coronary
artery disease, diabetes, obesity, other chronic health
problems).6
Prior caesarean
delivery
Prior miscarriage
Prior stillbirth
Uterine anomalies

Foetal risks of growth restriction:
‐
Elective repeat caesarean: lower risk for dehiscence
or uterine rupture ( gives severe disability of infant
or death,7-8 severe haemorrhage, hysterectomy9-10)
‐
Success of trial of labour depends on type of incision,
type of repair, maternal characteristics, time since last
caesarean, labour initiation, number of prior
caesareans.11
‐
Multiple caesarean sections increase risks for
placenta praevia, placenta increta, placenta
percreta.12-13

Prior miscarriage:
‐
Overall: successful next pregnancy is observed in 50
to 75% of women.
‐
Recurrence rate differs with underlying cause.

Prior stillbirth:
‐
Associations with low socioeconomic status are
found.14
‐
Reoccurrence rate is 2-10 fold increased in women
with prior stillbirth.15-18

Known uterine anomalies:
‐
Prevalence of anomalies in women with history of poor
reproductive outcomes is estimated at 13%.20
Yes
Yes
Counselling for elective caesarean versus trial of labour, which
ideally occurs prior discharge after initial caesarean.
II-2
-
I-a
-
II-2
II-218
Counselling for family planning: the chance on uterine rupture is
reduced 18 months after the initial caesarean section.
Yes
Work up for recurrent spontaneous abortion is done in the
preconception period.
If loss after gestational age of 14 weeks, work-up for ‘prior
stillbirth’ could be considered.
Yes
Depending
on cause
In 50% the cause stays undetermined; Review circumstances and
work-up of previous stillbirth; review autopsy reports.
II-314
Risk on stillbirth is dependent on maternal characteristics and
prior still birth.19
Yes
No
Best results in women with recurrent pregnancy loss with a uterine
septum > 1 cm resection.20-22
II-3
-
Awareness for increased risk for ectopic pregnancy due to uterine
anomaly in early gestation.23
99
Foetomaternal:
‐
Ectopic pregnancy, postpartum haemorrhage, cervical
insufficiency, pregnancy associated hypertension,
uterine rupture, caesarean deliveries, prematurity,
growth restriction, malpresentation, shoulder dystocia.
100
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
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Bloom SL, Yost NP, McIntire DD, Leveno KJ. Recurrence of preterm birth in singleton and twin pregnancies. Obstet Gynecol 2001;98(3):379-85.
Spong CY. Prediction and prevention of recurrent spontaneous preterm birth. Obstet Gynecol 2007;110(2 Pt 1):405-15.
Berghella V. Prevention of recurrent fetal growth restriction. Obstet Gynecol 2007;110(4):904-12.
Bujold E, Gauthier RJ. Neonatal morbidity associated with uterine rupture: what are the risk factors? Am J Obstet Gynecol 2002;186(2):311-4.
Bujold E, Bujold C, Hamilton EF, Harel F, Gauthier RJ. The impact of a single-layer or double-layer closure on uterine rupture. Am J Obstet Gynecol
2002;186(6):1326-30.
Kieser KE, Baskett TF. A 10-year population-based study of uterine rupture. Obstet Gynecol 2002;100(4):749-53.
Hibbard JU, Gilbert S, Landon MB, et al. Trial of labor or repeat cesarean delivery in women with morbid obesity and previous cesarean delivery.
Obstet Gynecol 2006;108(1):125-33.
Shipp TD, Zelop C, Lieberman E. Assessment of the rate of uterine rupture at the first prenatal visit: a preliminary evaluation. J Matern Fetal Neonatal
Med 2008;21(2):129-33.
Getahun D, Oyelese Y, Salihu HM, Ananth CV. Previous cesarean delivery and risks of placenta previa and placental abruption. Obstet Gynecol
2006;107(4):771-8.
Grobman WA, Gersnoviez R, Landon MB, et al. Pregnancy outcomes for women with placenta previa in relation to the number of prior cesarean
deliveries. Obstet Gynecol 2007;110(6):1249-55.
Goy J, Dodds L, Rosenberg MW, King WD. Health-risk behaviours: examining social disparities in the occurrence of stillbirth. Paediatr Perinat
Epidemiol 2008;22(4):314-320.
Greenwood R, Samms-Vaughan M, Golding J, Ashley D. Past obstetric history and risk of perinatal death in Jamaica. Paediatr Perinat Epidemiol
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Samueloff A, Xenakis EM, Berkus MD, Huff RW, Langer O. Recurrent stillbirth. Significance and characteristics. J Reprod Med 1993;38(11):883-6.
Sharma PP, Salihu HM, Oyelese Y, Ananth CV, Kirby RS. Is race a determinant of stillbirth recurrence? Obstet Gynecol
2006;107(2 Pt 1):391-7.
August EM, Salihu HM, Weldeselasse H, Biroscak BJ, Mbah AK, Alio AP. Infant mortality and subsequent risk of stillbirth: a retrospective cohort study.
Bjog 2011;118(13):1636-1645.
Fretts RC. Etiology and prevention of stillbirth. Am J Obstet Gynecol 2005;193(6):1923-35.
Grimbizis GF, Camus M, Tarlatzis BC, Bontis JN, Devroey P. Clinical implications of uterine malformations and hysteroscopic treatment results. Hum
Reprod Update 2001;7(2):161-74.
Homer HA, Li TC, Cooke ID. The septate uterus: a review of management and reproductive outcome. Fertil Steril 2000;73(1):1-14.
Daly DC, Maier D, Soto-Albors C. Hysteroscopic metroplasty: six years' experience. Obstet Gynecol 1989;73(2):201-5.
Lin PC. Reproductive outcomes in women with uterine anomalies. J Womens Health (Larchmt) 2004;13(1):33-9.
101
Table 13. Special groups
Domains of
preconceptional
risk factors
Risk factors
Detectability
Treatment
available
Quality
2008
Quality
newly
identified
articles
Women with
disabilities

Maternal disabilities:
Yes
Uncertain
III
-
‐
Barriers (physical, administrative, attitudinal) to access
care.2-5
‐
Women with functional limitations are more likely to
smoke have hypertension, overweight, mental health
problems or poor health overall, compared to women
without functional limitations.6
Preconceptional planning can aim to maximize social and
environmental support.2 Preconception care can identify relevant
risk factors (associated conditions), as in any group.2 Issue in
efficacy of care is to reach the women due to the barriers.2 3-5
Treatment/ management options for the individual conditions are
available. Evidence that care specifically for disabled women
improve pregnancy outcome is lacking.2
‐
Complications that may develop or worsen during
pregnancy:3-5
‐
Deep venous thrombosis
‐
Urinary tract infections
‐
Respiratory dysfunction
‐
Urinary incontinence
‐
Spasticity
‐
Constipation
‐
Pressure ulcers
‐
Falls

Maternal status of immigrant:
+/-
Uncertain
Preconception care should focus on access of these groups to
primary care, before pregnancy occurs.
III
II-2 149
Immigrant and
refugee populations
Foetal:
‐
Low birth weight;7,8 Among African American
immigrants one cohort study reported higher risk
Furthermore attention to the specific risks the individual has
attained in the country of origin and in the new country should
occur.
102
of premature delivery. 9
Efficiency of care is limited by the barriers of these groups to the
care.2
Maternal:
Cancer survivors
‐
Risks related to the country of origin.2
‐
Risk of infectious diseases endemic to the area of
origin.
‐
Psychosocial stressors exposed to in the country of
origin and the country where the woman immigrated to
(e.g. war, prosecution).2
‐
Under treatment of medical conditions due to the
health care facilities in the country of origin.
‐
Differences in immunisation status (the risk is lack of
immunization to the diseases endemic to the country
that is emigrated to).
‐
Social, language and cultural barriers to health care
access due to arrival in a new country.2,10,11-12

Women who survived cancer who wish to conceive:
Maternal:
‐
Recurrence risk of the disease.2
‐
Comprised fertility.2
‐
Depression chronic fatigue, cognitive changes,
neuropathies may difficult pregnancy and parenting.2
‐
Certain chemotherapies or radiotherapy regimens are
associated damage to the decreased cardiac
condition.13
+/-
No
Preconception care can counsel the woman on possible genetic
risks due to hereditary cancer, fertility issues, specific risks due to
her condition as a cancer survivor (such as the cardiovascular
condition), before pregnancy.
III
II-214
Newly diagnosed cancer patients should be counselled about
fertility preservation.
Foetal:
‐
Low birth weight, when abdominal pelvic radiation has
taken place.2
‐
Risk of stillbirth after radiation of the gonads, this risk
seems higher after radiation prior to menarche.14
103
‐
There does not seem to be a risk for miscarriages,
birth defects.15,16
‐
Here is no documented risk in childhood cancer in the
offspring of the woman who survived cancer16,15. A
longer follow-up time is necessary, because survivors
of hereditary cancers may pass on the genetic
mutations associated with these cancers.
‐
Certain maternal medication taken in case of cancer is
contraindicated in pregnancy due to risk of birth
defects.2
104
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105
IV. Effectiveness of the interventions in reducing the risk
factors before pregnancy
Sevilay Temel, Sabine F. van Voorst, Rachel Bakker, Lieke C. de Jong-Potjer, Chantal Quispel, Amber A. Vos,
Semiha Denktaş, Eric A.P. Steegers
Introduction
This chapter describes the evidence – based on their associated risk factors – of the impact
of the intervention for each domain. In 2009, a Cochrane review focused on the impact of
routine lifestyle interventions in preconception care versus no preconception care or usual
care.1 The scope of this review is not only to identify effective and available interventions
focusing on health promotion but also interventions aiming to identify and modify risk factors.
This is important for a number of potentially modifiable risk factors, which are known to be
associated with poor pregnancy outcomes, such as smoking, drinking (excess) alcohol, and
not taking folic acid supplements during the periconception period. Effective preconception
care interventions could be an opportunity for improving pregnancy outcomes by
encouraging behavioural change and allowing early identification of risk factors
preconceptionally.
Methods
Search
The literature identification and selection process is summarized in Figure 1. We performed
an electronic search in PubMed, Embase and Web of Science to identify evidence on the
effectiveness and availability of interventions for the risk factor concerned including
interventions focusing on (a) health promotion [basic health assessment, advice or both], and
(b) interventions aiming to identify and modify risk factors.
The search (Appendix 1) included preconception interventions ranged from a brief advice to
group education sessions on health and lifestyle over several sessions. Also intensified
treatment in the diabetic group was regarded as preconception intervention. Key words were
extracts of ‘preconception care’ or the ‘time before conception’ or ‘interconception’ and
‘intervention’ or ‘counselling’. Search criteria were: published from 1900 until January 06
2012 and no animal studies. Two reviewers (ST and SVV) independently assessed eligibility
of identified articles based on title and abstract. Further selection was performed according to
predefined criteria (the study assesses interventions, addressed in the preconception phase
for an adverse pregnancy outcome). Articles were retrieved in full text and quality was
assessed according to predefined criteria as described in Appendix 2.
106
The search resulted in 678 articles. As 106 duplicates were found, 572 potential articles were
identified. Based on screening by title and abstract 496 non-eligible articles were excluded.
After screening the remaining 76 articles, 28 full text articles were excluded for reasons
stated. Additionally, based on references extracted from systematic reviews another 56
articles were included resulting in a total of 104 articles.
Figure 1. Study identification and selection process
Results
Since 1946 several preconception interventions to improve either maternal and/or foetal
outcome have been described as preconception care health programs. Studies often
targeted specific risk factors such as diabetes, infectious diseases, folic acid and/or
multivitamin use or targeted specific subgroups. This section summarizes the results.
107
Preconception care health programs (Table 1)
Several preconception counselling and intervention programs aiming to modify health risk
behaviour for adverse pregnancy outcomes have reported some degree of effectiveness. In
the Strong Healthy Women intervention women were more likely to report (a) higher selfefficacy for consuming healthy foods, (b) a higher intention to eat healthy foods and (c)
behavioural changes, e.g. more physical activity and using daily multivitamins with folic acid
as was found 12 weeks after the intervention period2 During a 12-months follow-up the
women of this intervention group were more likely to use multivitamins with folic acid daily,
have lower weight and a lower BMI.3
Other preconception programs have also reported higher internal health locus of control,4
higher knowledge of risk factors5 and a lower mean State Anxiety Inventory score was
reported after preconception counselling,6 indicating lower anxiety when preconceptional risk
factors were identified and addressed during preconception counselling. In contrast to the
study mentioned before, another study observed no change in anxiety levels after
counselling or during the first trimester of pregnancy7. Other effects were a higher use of folic
acid supplementation before pregnancy5, 8-9 with an improvement in cell folate among women
planning to conceive10, reduced alcohol consumption,5, 8, 11 increased daily intake of
vegetables,8 more often read food labels8 and more often women met physical activity
guidelines.8
Chronic diseases: Diabetes (Table 4)
Preconception counselling (e.g. intensive insulin therapy, glycemic control, counselling?) in
women with diabetes type 1 and/or type 2 have resulted in improvement of lifestyle
behaviour with lower intake of alcohol consumption12, less women smoking13 and more
women taking folic acid supplements.14
Lower Hba1C levels were seen following preconception counselling,12, 14-17 women entered
prenatal care at an earlier gestation,14, 17 women had less spontaneous abortions18 and fewer
adverse pregnancy outcome.14 Furthermore women were less hospitalized during
pregnancy, had a shorter mean length of stay after delivery,17 but had a higher rate of
caesarean section.16
Infant outcome also improved after counselling showing lower prevalence of being small for
gestational age16 and less major and minor congenital anomalies.13
Infections and/or Sexually Transmitted Diseases (Table 3)
Prepregnancy pertussis booster vaccination resulted in higher antibody titers against
pertussis antigens as measured in cord blood and in blood of 1-month-old infants.19 This
implies better protection against congenital pertussis infection.
108
Asymptomatic candida colonisation was associated with higher risk of preterm birth and this
risk was reduced with Clotrimazole treatment preconceptionally.20
Preconceptionally given antibiotics are associated with lower acquisition and higher
resolution of Gardnerella.21
Folic acid and/or multivitamins (Table 2)
Preconceptional use of folic acid supplements and/or multivitamins is proven to be
associated with significant reduction in neural tube defects,22-25 less recurrence of neural tube
defects23, 26 and less neural tube defects with associated major congenital anomalies.27
Also the risk on overall congenital heart defects22, 28-30 and particular (outflow tract defects,30
ventricular septal defect30-31 and isolated septal defectt28 heart defects is lower due to
preconceptional use of folic acid supplements and/or multivitamins.
Furthermore, risk reduction is seen in omphalocele,32 cleft lip with/without cleft palate,33-40
orofacial clefts,36 stenosis/atresia of pelvicureteric junction,22, 29, 31, 33, 41 neuroblastoma,42
imperforate anus43 and limb deficiency.44
Besides a risk reduction in structural congenital anomalies, also a risk reduction is reported
in lower birth weight infants (<2500g)45-47 and preterm delivery from 20-32 weeks.48
Higher risk on multiple pregnancies49 50-51 due to preconceptional use of folic acid
supplements and/or multivitamins was also reported.
Eight observational studies examining folic acid food fortification in a meta-analyse gave an
estimate significant risk reduction in neural tube defect incidence of 46%.23
However, adverse effects of preconceptional use of folic acid and/or multivitamins are
reported in two retrospective case-control studies reporting a higher risk of multiple
congenital anomalies52-53 among mothers of infants with previous multiple congenital
anomalies. One RCT from Hungarian reported a significant increase of 16% in rates of
miscarriage between supplemented and trace-element groups.54
Sub-groups (Table 5)
Subfertile women and men attending a preconception counselling clinic reported lower
scores on the median Preconception Dietary Risk (based on six Dutch dietary guidelines)
and on the median Rotterdam Reproduction Risk score (based on lifestyle factors: women 13
items, men 10 items) due to higher physical activity, higher folic acid use, less alcohol use
among men, higher fruit intake among men and women and higher fish consumption among
women.55 Serum cotinine decreased significantly after preconception counselling intervention
on smoking cessation in women (indicating reduced smoking), but none of the women
stopped smoking.56 Women with reported previous spontaneous abortions and treated with a
109
‘single’ therapy on Heparin plus Aspirin preconceptional had higher pregnancy success
rates.57
Conclusion
A list of preconception interventions associated with reduced maternal and/or foetal risk and
reduced adverse outcomes was reviewed. This overview represents the current state of
evidence regarding, merely modifiable, effective preconception interventions to reduce and
modify risk factors in the periconceptional period. Numerous risk factors for maternal and
foetal health have been identified and can be modified. But the numbers of interventions that
are proven effective when started before the conception are still limited. More research is
needed on the effects of preconception interventions to fully understand the additional benefit
of preconception care.
110
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113
Appendix 1: Search terms
PubMed:
(preconception*[tw] OR pre-conception*[tw] OR prepregnan*[tw] OR pre-pregnan*[tw] OR
pregestation*[tw] OR pre-gestation*[tw] OR periconception*[tw] OR peri-conception*[tw] OR
interconception*[tw] OR inter-conception*[tw] OR interpregnan*[tw] OR inter-pregnan*[tw] OR
internatal*[tw] OR inter-natal*[tw] OR intergestation*[tw] OR inter-gestation*[tw]) AND
(education*[tw] OR promotion*[tw] OR care[tw] OR campaign*[tw] OR counsel*[tw] OR
wellness*[tw] OR intervent*[tw]) AND (matern*[tw] OR mother*[tw] OR paternal*[tw] OR father*[tw]
OR parent*[tw]) AND (Humans[Mesh] AND Female[MeSH Terms] AND (Clinical Trial[ptyp] OR
Randomized Controlled Trial[ptyp]) AND English[lang])
Embase:
preconception* OR prepregnan* OR pregestation* OR periconception* OR interconception* OR
interpregnan* OR internatal* OR intergestation* OR pre NEAR/1 (conception* OR pregnan* OR
gestation*) OR peri NEAR/1 conception* OR inter NEAR/1 (conception* OR pregnan* OR
gestation* OR natal*) AND (education* OR promotion* OR care OR campaign* OR counsel* OR
wellness* OR intervent*) AND (matern* OR mother* OR paternal* OR father* OR parent*) AND
([cochrane review]/lim OR [controlled clinical trial]/lim OR [randomized controlled trial]/lim) AND
[female]/lim AND [humans]/lim AND [english]/lim
Web of Science:
Topic=((preconception* OR prepregnan* OR pregestation* OR periconception* OR
interconception* OR interpregnan* OR internatal* OR intergestation* OR (pre NEAR/1
(conception* OR pregnan* OR gestation*)) OR (peri NEAR/1 conception*) OR (inter NEAR/1
(conception* OR pregnan* OR gestation* OR natal*))) AND (education* OR promotion* OR care
OR campaign* OR counsel* OR wellness* OR intervent*) AND (matern* OR mother* OR paternal*
OR father* OR parent*) AND cohort)
Refined by: Document Type=( ARTICLE OR PROCEEDINGS PAPER )
OR father* OR parent*) AND (case control))
Databases=SCI-EXPANDED, SSCI, CPCI-S, CPCI-SSH Timespan=All Years
Lemmatization=On
OR father* OR parent*) AND (observational))
Lemmatization=On
OR father* OR parent*) AND RCT)
Lemmatization=On
114
Appendix 2: Criteria for Quality assessment
Quality of evidence
I-a: at least 1 properly conducted randomized controlled trial BEFORE pregnancy
I-b: at least 1 properly conducted randomized controlled trial not necessarily before pregnancy
II-1: well-designed controlled trials without randomization
II-2: cohort or case-control studies
II-3: multiple time series with or without intervention or dramatic results in uncontrolled experiments
III: opinions: clinical experience, descriptive statistics, case reports or reports of experts committees
115
Table 1. Preconception care health education
Intervention
Author, design and year
study
Outcome
Quality
Strong Healthy Women intervention
Hillemeier et al, 20081
RCT
Two groups:
a) Intervention group (n=252)
b) Control group (n=110)
I-a
 Strong Healthy Women intervention
versus no intervention
Timeframe: unclear
- Significant intervention effects were shown for self-efficacy, behavioural intent and behaviour
change related primarily to nutrition and physical activity.
The Strong Healthy Women intervention
contains six small-group sessions for nonpregnant pre- and interconceptional women,
spread out over a 12-week period in a
community setting.
- Compared to controls, women in the intervention group were more likely to:
1) Report higher self-efficacy for eating healthy food (general linear models (GLM) coefficient
1.109; p-value 0.018) and for perceived preconception control (OR 1.916; p-value 0.031)
compared to controls.
2) Have a greater intent to eat healthier foods (OR 1.757; p-value 0.008) and to be more physically
active (OR 2.185; p-value < 0.001).
3) Have behaviour changes including greater likelihoods of reading food labels for nutritional
values (OR 2.264; p-value 0.001), greater likelihoods of daily multivitamin with folic acid (OR
6.595; p-value < 0.001) and higher rates of meeting recommended physical activity levels (OR
1.867; p-value 0.019).
This intervention aims to modify healthy risk
behaviour for adverse pregnancy outcomes
such as preterm birth and low birth weight.
Healthy risk behaviour include poor nutrition,
low physical activity, tobacco use, alcohol
use and exposure, unhealthy coping with
stress, gynaecologic infections, and
inadequate pregnancy planning or spacing.
- No significant intervention effects were seen in anthropometric and biomarker measures,
including BMI, weight, waist circumference, blood pressure, and blood tests, such as serum
glucose, HDL cholesterol and total cholesterol.
This article reported about the short-term
effects of the intervention.
Strong Healthy Women intervention
 Strong Healthy Women intervention
versus no intervention as described above
- Significant dose effects were found for perceived internal preconceptional control (OR 1.309; pvalue 0.002), reading food labels (OR 1.161; p-value 0.015), engaging in relaxation exercise or
meditation for stress management (OR 1.236; p-value 0.009), and daily use of multivitamin with
folic acid (OR 1.448; p-value < 0.001).
Weisman et al. 20112
RCT
Timeframe: unclear
Patients:
a) Women who participated in the original trial of the Strong Healthy Women intervention (n=362 =
total post-test analyses)
b) Birth records from women who gave birth to singletons during the follow-up period (n=45).
I-a
116
This article reported about the long-term
effects of the intervention (12 months followup).
- Intervention effect on reading food labels for nutritional values dropped off between the 6- and
12-month follow-up (OR, 1.97; 95% CI, 1.07-3.65 and OR, 0.70; 95% CI, 0.40-1.23).
- At 12 months follow-up women of the intervention group were more likely to use multivitamin with
folic acid daily (OR, 2.15; 95% CI, 1.19-3.88), were more likely to have a lower weight (OR -4.33;
95% CI -8.16- -0.49) and were more likely to have a lower BMI (OR -0.75; 95% CI -1.39- -0.11).
- Intervention effect on physical activity, consumption of fruit and vegetables was not maintained
during the follow-up periods (OR 1.00; 95% CI, 0.57-1.76; OR 0.68, 95% CI 0.39-1.21; OR 0.99,
95% CI 0.57-1.71).
- The significant intervention effect on gaining weight during pregnancy among the women in the
intervention group who gave birth to full-term singletons (23.4% vs. 41.4%; p-value 0.023) was no
longer significant when controlling for pre-pregnancy obesity (23.8% vs. 34.2%; p-value 0.138).
- No intervention effects on the odds of exceeding the Institute of Medicine (IOM) recommended
weight gain for women’s each pre-pregnancy BMI category were shown (42.9% vs. 55.6%; p-value
0.645).
Preconception health education workshops
 Single two-hour workshop session for 8 to
12 women at a premarital counselling clinic
for both the intervention and the control
group.
In addition, women in the intervention group
received an individualized healthy lifestyle
training prior to the standard workshop.
Bastani et al, 20103
RCT
2006-2007
I-a
- No significant pre-intervention effects were found for health locus of control (mean score internal
HLOC 15.9 vs. 15.8; p-value 0.918 and mean score external HLOC 23.5 vs. 24.0; p-value 0.409)
and self-efficacy for exercise (mean score in both the intervention and control group 3.5; p-value
0.577).
- Post-intervention effects on external health locus of control (HLOC) maintained not significant
(means scores 23.2 vs. 23.1; p-value 0.890).
The aim of the intervention is empowering
women to understand future risks of
unhealthy lifestyles.
Including education on physical activity,
psychological and emotional health in women
and the relation between (un)healthy
lifestyles and morbidity and mortality, and the
consequences of over- or underweight on
pregnancy and pregnancy outcomes.
Preconception counselling
Two groups of self-reported healthy women planning to conceive in the first year of marriage:
- Post-intervention effects on internal HLOC and exercise self-efficacy became significant different
(mean internal HLOC score of 22.3 vs. 15.9; p-value < 0.001 and self-efficacy scores 18.9 vs.
11.0; p-value < 0.001).
- Pre- and post-intervention mean scores differed significantly for both the intervention and the
control group (internal HLOC p-value < 0.001, external HLOC p-value 0.003, exercise self-efficacy
p-value < 0.001).
Elsinga et al, 20084
Two groups:
I-a
117
 Usual care versus GP-initiated
preconception counselling (PCC) for women
RCT
2000-2003
a) Women participating in PCC (n=211)
b) Women in usual care (n=422)
- Increase in knowledge of women participating in PCC (81.5%; n=211) compared to women in
usual care (76.9%; n=422).
- Significantly more women of PCC group started using folic acid before pregnancy (adjusted odds
ratio [OR], 4.93; 95% confidence interval [CI], 2.81–8.66) and reduced alcohol use during the first
3 months of pregnancy (adjusted OR, 1.79; 95% CI, 1.08–2.97).
- Adverse pregnancy outcomes women PCC: 16% (OR, 0.77; 95% CI, 0.48–1.22). Adverse
pregnancy outcomes women in usual care: 20%
Group education for pre- and
interconceptional women, addressing
pregnancy and conception.
 This article published strategies to recruit
women for group education. Data of the
intervention itself is unpublished, but reported
in a Cochrane review (Whitworth et al, 2009)
which we used as source.
The aim of the intervention was to improve
lifestyle changes, stress management and to
prevent infections
Velott et al, 20085
RCT
Timeframe: unclear
Two groups:
b) Control group received no active intervention (n=110)
I-a
After three months follow-up:
- No significant change in cigarette smoking compared to baseline measurements in both groups.
(Intervention group 67/251 vs. 68/252 and control group 36/109 vs. 33/108 after follow-up).
- Alcohol consumption decreased among women in the intervention group (172/251 before vs.
155/250 after) compared to the control group (64/109 vs. 62/108 after follow-up).
- Folic acid use was higher among women in the intervention group (88/250 before and 180/246
after follow-up in the intervention group vs. 34/109 before and 34/109 and 42/110 after follow-up in
the control group).
- Physical activity guidelines were more often met in the intervention group (82/250 before and
102/250 after) compared to the control group (34/108 before and 33/110 after).
- Daily intake of fruits did not change in both groups (62/252 and 64/251 intervention group vs.
21/110 and 29/110 control group).
- Daily intake of vegetable increased in the intervention group (58/252 vs. 71/252) but decreased
in the control group (27/110 vs. 19/110).
- Food labels were read more often among women in the intervention group (72/252 before and
82/252 after follow-up versus 33/110 before and 29/110 after follow-up).
118
Preconception counselling versus
preconception information only
 To reduce the risk of an alcohol-exposed
Floyd et al, 20076
RCT
2002-2005
pregnancy (AEP) in preconception women
Two groups of non-pregnant women who were ‘risky drinkers’ (8 drinks per week or more than 5
drinks on 1 occasion).
a) Women in the intervention group received preconceptional counselling on reducing alcohol, with
personalised feedback and goal setting (n=416).
b) Women in the control group received written preconceptional information only (n=414).
I-a
Women in the intervention group had higher odds to be at reduced risk for alcohol-exposed
pregnancies (AEP) than the control group at three months follow-up (OR 2.31; 95% CI 1.69-3.20),
at six months follow-up (OR 2.15; 95% CI 1.52-3.06) and at nine months follow-up (OR 2.11; 95%
CI 1.47-3.03).
 Usual care versus GP-initiated
preconception counselling for women
De Jong-Potjer et al, 20067
RCT
2000-2003
Two groups:
a) GP practices providing usual care (control group, n=37 practices)
b) GP practices providing preconception counselling (intervention group, n=30 practices)
I-a
- Mean State Trait Anxiety Inventory I (STAI-I) score before preconception counselling was 36.4
(95% CI 35.4-37.3) (n=466). After preconception counselling the mean STAI-II score was 3.6
points lower (95% CI 2.4-4.8) (n=466).
- Postpartum, when focussing on the first trimester of pregnancy, mean scores of STAI-III were
38.7 (95% CI 37.9-39.5) among women in the intervention group (n=1186) and 38.5 (95% CI 37.739.3) on average in the control group (n=1090).
Pre-pregnancy information, advice and
counselling
 Women who attended local Maternal and
Child Health centres with their first child were
visited by a midwife, who discussed their
previous pregnancy and answered any
questions (control group).
In the intervention group, health assessment,
pre-pregnancy information, advice and
counselling was offered: Pre-Pregnancy
Information and Counselling Service (PPIS).
Lumley et al, 20068
RCT
1982-1994
Two groups, including non-pregnant women with one child in a community setting with high risk of
poor birth outcomes:
I-a
- Infant birth weight was 97.4 gram lower among infants in the intervention group (-97.4 g).
- No significant differences between intervention and control group were found in the proportion of
preterm birth (OR 1.44; 95% CI 0.73-2.91), low birth weight (OR 1.85, 95% CI 0.91-3.91) or birth
weigh < 10th percentile (OR 1.14, 95% CI 0.55-2.38).
- Compared to the controls, the intervention group had more births < 32 weeks (10 vs. 1), more
birth weights < 2000 g (16 vs. 2), and more perinatal deaths due to birth anomalies (5 vs. 2).
119
 to increase the use of folic acid
supplements among preconceptional women
Robbins et al, 20059
RCT
Timeframe: unclear
De Weerd et al, 200210
Cohort study
1997-1999
Women and their partners reported folic acid
supplement intake in a preconceptional
health questionnaire, and the women were
categorized as reported ‘users’ or ‘nonusers’
before counselling
During the subsequent preconception
counselling the use of periconceptional folic
acid was addressed
Psychological impact of preconception
counselling
 Assessment of anxiety levels in women
and men before and after preconception
counselling and during the first trimester of
pregnancy
I-a
- The intervention increased weekly use of folic acid (68% in the intervention group vs. 20% in the
control group; p-value 0.008). No significant differences were found in daily folic acid use (67% in
the intervention group vs. 54% in the control group; p-value 0.549).
The intervention group received a brief folic
acid counselling followed by a reminder
phone call and 30 folic acid tablets.
The control group received a brief
counselling on preventive health behaviours
 To assess whether counselling women
planning pregnancy to start or continue folic
acid supplementation improves folate status
Two groups:
a) Women in the intervention group (n=162, of which 139 were analysed).
b) Women in the control group (n=160, of which 140 were analysed).
A Total of 111 (66%) of 168 eligible women participated.
II-2
Estimated mean red cell folate levels of women who reported no use of folic acid supplements
before counselling increased significanlt after 4 months from 540 nmol/L to 680 nmol/L.
Red cell folate levels of women who reported taking supplements (44%) remained stable up to 1
year after counselling.
Women with low precounselling folate levels showed a highly significant mean increase in red cell
folate from 475nmol/L to 689nmol/L 4 months after counselling.
De Weerd et al, 200111
Cohort study
1997-1999
53 women and 51 men (74%) completed the STAI both before and after counselling.
II-2
Anxiety levels did not change significantly after counselling or during the first trimester of
pregnancy.
Anxiety was assessed using the 40-item
Spielberger State-Trait Anxiety Inventory
(STAI)
120
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Hillemeier MM, Downs DS, Feinberg ME, et al. Improving women's preconceptional health: findings from a randomized trial of the Strong Healthy
Women intervention in the Central Pennsylvania women's health study. Womens Health Issues 2008;18(6 Suppl):S87-96.
Weisman CS, Misra DP, Hillemeier MM, et al. Preconception predictors of birth outcomes: prospective findings from the central Pennsylvania
women's health study. Matern Child Health J 2011;15(7):829-35.
Bastani F, Hashemi S, Bastani N, Haghani H. Impact of preconception health education on health locus of control and self-efficacy in women. East
Mediterr Health J 2010;16(4):396-401.
Elsinga J, de Jong-Potjer LC, van der Pal-de Bruin KM, le Cessie S, Assendelft WJ, Buitendijk SE. The effect of preconception counselling on lifestyle
and other behaviour before and during pregnancy. Womens Health Issues 2008;18(6 Suppl):S117-25.
Velott DL, Baker SA, Hillemeier MM, Weisman CS. Participant recruitment to a randomized trial of a community-based behavioral intervention for preand interconceptional women findings from the Central Pennsylvania Women's Health Study. Womens Health Issues 2008;18(3):217-24.
Floyd RL, Sobell M, Velasquez MM, et al. Preventing alcohol-exposed pregnancies: a randomized controlled trial. Am J Prev Med 2007;32(1):1-10.
de Jong-Potjer LC, Elsinga J, le Cessie S, et al. GP-initiated preconception counselling in a randomised controlled trial does not induce anxiety. BMC
Fam Pract 2006;7:66.
Lumley J, Donohue L. Aiming to increase birth weight: a randomised trial of pre-pregnancy information, advice and counselling in inner-urban
Melbourne. BMC Public Health 2006;6:299.
Robbins JM, Cleves MA, Collins HB, Andrews N, Smith LN, Hobbs CA. Randomized trial of a physician-based intervention to increase the use of folic
acid supplements among women. Am J Obstet Gynecol 2005;192(4):1126-32.
de Weerd S, Thomas CM, Cikot RJ, Steegers-Theunissen RP, de Boo TM, Steegers EA. Preconception counseling improves folate status of women
planning pregnancy. Obstet Gynecol 2002;99(1):45-50.
de Weerd S, van der Bij AK, Braspenning JC, Cikot RJ, Braat DD, Steegers EA. Psychological impact of preconception counseling: assessment of
anxiety before and during pregnancy. Community Genet 2001;4(3):129-33.
121
Table 2. Chronic disease:
diabetes
Intervention
Author, design and year
study
Outcome
Quality
Pre-pregnancy counselling in pregestational diabetes and maternal
health status
Anwar et al, 20101
Retrospective cohort
study
1997-2007
57 pregnant women achieved pregnancy after pre-pregnancy counselling.
II-2
Tripathi et al, 20102
Cohort study
2001-2004
558 women were observed in this study: 448 (77%) had type 1 diabetes
 Glycemic control, review and
consideration of medical conditions,
drug treatment, smoking and alcohol
use, obstetric and general history
and screening of diabetic
complications.
Preconception counselling in women
with diabetes
- HbA1c levels were significantly reduced at prenatal booking compared to pre-pregnancy counselling:
7.5% vs. 8.8%
- Diabetic surveillance (retinopathy and nephropathy screening) was up to date in > 80% of all cases.
- Folic acid was taken by 48 of 54 women at their booking
- No significant reduction in smoking was observed: 23 % vs. 20 % (p = 0.68)
- Alcohol consumption was significantly reduced: 20% vs. 51% vs. 20 %
II-2
Preconception counselling was non-significantly associated with:
- Better glycemic control prior pregnancy (OR 1.91, 95% 1.10-3.04) and first trimester (OR 2.05, 95%CI
1.39-3.03)
- Higher folic acid intake (OR 4.88, 95%CI 3.26-7.30)
- Reduced risk of adverse pregnancy outcomes
Women with type 1 diabetes more often visited preconception counselling compared to women with type 2
diabetes (OR 1.87, 95% CI 1.14-3.07)
Regional prepregnancy care
program in women with type 1 and
type 2 diabetes.
 A preconception leaflet with
advice and telephone contacts for a
prepregnancy care coordinator was
mailed annually to all diabetic
women aged 16-45 years from
diabetes registers
Murphy et al, 20103
Prospective cohort study
2006-2009
680 pregnancies were observed during the study period
- 27% (181 women) attended prepregnancy care
- 54% of women with type 1 and 32% of women with type 2 diabetes attended
II-2
Women with prepregnancy care:
- Presented earlier to antenatal care (6.7 vs 7.7 weeks, p<0.001)
- Were more likely to take 5 mg preconception folic acid (88.2% vs. 26.7%, p < 0.0001)
- Had lower HbA1c levels (6.9 % vs. 7.6%, p < 0.0001)
- Had fewer adverse outcome (OR 0.2, 95% CI 0.05-0.89)
122
 The content of preconception
care was standardized but delivered
by different health care providers
Comparison of different insulin
regimes
 Initiation in the preconceptional
period or in early pregnancy
 Prandial insulin aspart
administrated immediately before
each meal was compared with
human insulin administrated 30
minutes before each meal
Heller et al, 20104
Open-label, randomized,
parallel group trial
2002-2004
Prepregnancy care in women with
type 1 diabetes.
 Women who received
prepregnancy care were seen every
1-3 months by a physician, diabetes
specialist nurse and dietician
 Women were advised to monitor
blood glucose four to seven times
daily and counselled for pregnancy
alterations regarding diabetes
Temple et al, 20065
Cohort study
1991-2002
Influence of preconception care on
the risk of congenital anomalies
Ray et al, 20016
Meta analysis of cohort
studies
1970-2000
322 pregnant women with type 1 diabetes were randomly assigned:
- 99 subjects were preconceptionally assigned: 44 to prandial insulin aspart and 55 to human insulin
- 223 subject were early in pregnancy assigned (< 10 weeks): 113 to prandial insulin aspart and 110 to
human insulin
I-a
The main outcome was severe hypoglycaemia in the preconceptional period, during pregnancy and
postpartum:
- 23% of women experienced severe hypoglycaemia during pregnancy with the peak incidence in early
pregnancy
- The relative risk (RR) of severe hypoglycaemia of therapy initiated in early pregnancy compared with
preconceptional was 1.70 (95%CI 0.91-3.18)
- No significant differences between both insulin regimens were observed
290 pregnancies occurred during the study period: 110 (38%) women received preconception care
II-2
The preconception care group:
- Contained significantly fewer smokers (9.4% vs. 28.7%)
- Registered significantly earlier for antenatal care (6.6 vs. 8.3 weeks)
- Had significantly lower HbA1c levels at booking visit (6.5% vs. 7.6%)
- Adverse pregnancy outcomes and very premature deliveries were also significantly lower in this group
Rates of macrosomia, preeclampsia or maternal severe hypoglycaemic episodes did not differ between
both groups
14 cohort studies in which congenital anomalies were studied were included
II-1
The pooled rate of major and minor congenital anomalies was lower in women who received preconception
care (RR 0.32, 95% CI 0.17-0.59)
Fewer women who received preconception care smoked (19.6% vs. 30.2%)
Mean HbA1c values were reported in 7 studies. In each study the mean levels were lower (2.3%, 95% CI
2.1-2.4), but heterogeneity was present (p<0.20)
123
Preconception care compared to
prenatal care in pregnant women
with type 1 diabetes
Herman et al, 19997
Prospective,
observational study
Time frame: unclear
98 women with type 1 diabetes were studied: 24 women received preconception care; 74 women received
prenatal care
II-3
Diabetic women that received preconceptional care:
- Were earlier seen in gestation (6.7 vs. 9.8 weeks)
- Had significantly lower HbA1c levels
- Were hospitalized significantly less during pregnancy and
- Had shorter inpatient stays (40 days vs. 80 days)
- The mean length of stay after delivery was significantly shorter (3 days vs. 4.8 days)
In addition, preconception care substantially reduced costs
Glycemic control in the preconception period and early
pregnancy
 Preconception counselling was
offered to all women of childbearing
age who visited the clinic for routine
diabetes review to optimize HbA1c
levels
 HbA1c was recorded for time
periods before pregnancy (if
available) and / or during pregnancy
every 2-4 weeks
Gold et al, 19988
Observational study (case
records)
November 1992-May
1996
57 case records of women with type 1 diabetes were reviewed
Pre-pregnancy counselling in type 1
and type 2 diabetic women.
 Normocaloric diet and glycemic
control (intensified insulin therapy
and self-monitoring of blood glucose)
García-Patterson et al,
19979
Observational study
1986-1966
185 pregnancies in diabetic women were studied:
- 152 women with type 1 diabetes
- 33 women with type 2 diabetes
- 36.1% enrolled for pre-conception counselling (n= 54): 41.1% for type 1 diabetes and 9.1% for type 2
diabetes
II-3
The median standardized birth weight was 1.1 SD higher than the non-diabetic mean (reference group not
mentioned)
Glycemic control in the immediate preconception period and early first trimester seems to have a greater
influence on birth weight than glycemic control during later weeks of pregnancy (p < 0.05)
II-3
Significant differences between attenders (A) and non-attenders (NA) were observed for the following
perinatal outcomes:
- Initial HbA1c (Standard deviation around the mean: A: 2.57 vs.. NA: 3.98).
- Caesarean section rate: A: 71% vs.. NA: 54.9 %
- Small for gestational age: 1.8% vs. 8.7%
All other perinatal outcomes were not significant between A and NA
124
Intensive preconceptional insulin
therapy compared with conventional
preconceptional insulin therapy in
type 1 diabetic women.
 Intensive insulin therapy aims to
achieve normal glycemic control
The Diabetes Control and
Complications Trial
Research group, 199610
RCT
1983-1993
180 women in total completed 270 pregnancies:
- 135 women were randomly assigned to the intensive treatment group (94 became pregnant); 135 women
were assigned to the conventional group (86 became pregnant).
- During the study time period, 52 women who became pregnant switched to the conventional group but
received intensive treatment during the preconceptional period
I-a
Preconceptional mean HbA1c levels were significantly lower in women who received intensive insulin
treatment (7.4% vs. 8.1%), but were similar during gestation
There were no significant differences in adverse outcome (abortion, congenital malformations) between
women who initiated intensive therapy preconceptionally and those who began this therapy after
conception. The adverse outcomes were similar to the non-diabetic population
Effectiveness of preconception
counselling in women with pregestational diabetes
 Preconception counselling to
prevent adverse pregnancy
outcomes
Willhoite et al, 199311
Cohort study
1985-1990
A total of 185 pregnancies among 160 women with pre-gestational diabetes were identified:
- 62 (34%) pregnancies occurred in the preconception counselling group with one major congenital defect
(1.6%) and four fetal or neonatal deaths (6.4%)
- 123 pregnancies occurring in women without preconception counselling 8 infants (6.5%) were born with
congenital abnormalities and 26 (21.1%) fetal or neonatal deaths occurred
II-2
Effectiveness of a preconception
program in insulin-dependent
diabetic women
 Glycemic control through
attending a preconception clinic
Rosenn et al, 199112
Case-control study
1984-1989
Study group (28 women) versus control group (71 women enrolled after conception):
- HbA1c 8.5 vs. HbA1c 9.9
- Congenital malformations: none vs. 1.4%
- Spontaneous abortion: 7% vs. 24%
(all non-significant)
II-2
Effectiveness of a preconception
program in insulin-dependent
diabetic women
 Preconception counselling (PCC)
in diabetes type 1 women
Cousins et al, 199113
Multicentre study
1986-1988
Comparing 27 PCC attenders versus 247 controls:
- Malformations: 0% versus 6.3%
II-3
Effectiveness of preconception care
in type 1 diabetes on congenital
anomalies
 Preconception care includes
medical, obstetric, and
gynaecological history, assessment
Steel et al, 199014
Observational study
1976-1990
239 records of women with diabetes were studied
-143 women with type 1 diabetes received preconception care (attenders)
- 96 women with type 1 diabetes did not participate in preconception care program
II-3
Attenders appeared to have lower HbA1c levels (8.4% vs. 10.5%, higher incidence of hypoglycaemia in
early pregnancy and fewer congenital anomalies in offspring (RR 7.4, 95%CI 1.7-33.2)
125
of diabetic complications
(retinopathy, renal function, blood
pressure, ischaemic heart disease,
autonomic neuropathy), optimised
diabetic control, thyroid function
control, rubella immunity
assessment.
Intensive management of diabetes
before versus early pregnancy
 Daily measurement of fasting and
postprandial capillary blood glucose
levels; 40% had DM type 2
Kitzmiller et al, 198815
Single centre study
1982-1988
Cases (84 women treated before conception) versus controls (110 women who were already pregnant
referred at 6-30 weeks of gestation):
- Major congenital anomaly: 1.2% (n=1) versus 10.9% (n=12); p=0.01
II-2
anomalies
 Intensified insulin therapy and
monitoring by blood glucose selfmonitoring in a preconceptional clinic
versus non-attenders
Dicker et al, 198816
Observational study
Timeframe: unclear
Significantly higher (p<0.001) spontaneous abortions among women not seen before pregnancy (n=35)
versus preconceptional glycemic control (n=94)
II-3
anomalies
 Intensified insulin therapy and
monitoring by blood glucose selfmonitoring in a preconceptional clinic
versus non-attenders
Goldman et al, 198617
Single
Timeframe: 1981-1985
Attenders (44 pregnant women with juvenile-onset insulin dependent diabetes) versus non-attenders
(n=31):
- HbA1c 7.4 vs. HbA1c 10.4
- No malformations vs. 9.6% malformations (p=0.07)
II-2
Non-attenders had also more maternal complications (e.g. pre-eclampsia, higher caesarean section rates)
126
References
1.
2.
3.
4.
5.
6.
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Anwar A, Salih A, Masson E, Allen B, Wilkinson L, Lindow SW. The effect of pre-pregnancy counselling for women with pre-gestational diabetes on
maternal health status. Eur J Obstet Gynecol Reprod Biol 2011;155(2):137-9.
Tripathi A, Rankin J, Aarvold J, Chandler C, Bell R. Preconception counseling in women with diabetes: a population-based study in the north of
England. Diabetes Care 2010;33(3):586-8.
Murphy HR, Roland JM, Skinner TC, et al. Effectiveness of a regional prepregnancy care program in women with type 1 and type 2 diabetes: benefits
beyond glycemic control. Diabetes Care 2010;33(12):2514-20.
Heller S, Damm P, Mersebach H, et al. Hypoglycemia in type 1 diabetic pregnancy: role of preconception insulin aspart treatment in a randomized
study. Diabetes Care 2010;33(3):473-7.
Temple RC, Aldridge VJ, Murphy HR. Prepregnancy care and pregnancy outcomes in women with type 1 diabetes. Diabetes Care 2006;29(8):1744-9.
Ray JG, O'Brien TE, Chan WS. Preconception care and the risk of congenital anomalies in the offspring of women with diabetes mellitus: a metaanalysis. QJM 2001;94(8):435-44.
Herman WH, Janz NK, Becker MP, Charron-Prochownik D. Diabetes and pregnancy. Preconception care, pregnancy outcomes, resource utilization
and costs. J Reprod Med 1999;44(1):33-8.
Gold AE, Reilly R, Little J, Walker JD. The effect of glycemic control in the pre-conception period and early pregnancy on birth weight in women with
IDDM. Diabetes Care 1998;21(4):535-8.
Garcia-Patterson A, Corcoy R, Rigla M, et al. Does preconceptional counselling in diabetic women influence perinatal outcome? Ann Ist Super Sanita
1997;33(3):333-6.
Pregnancy outcomes in the Diabetes Control and Complications Trial. Am J Obstet Gynecol 1996;174(4):1343-53.
Willhoite MB, Bennert HW, Jr., Palomaki GE, et al. The impact of preconception counseling on pregnancy outcomes. The experience of the Maine
Diabetes in Pregnancy Program. Diabetes Care 1993;16(2):450-5.
Rosenn B, Miodovnik M, Combs CA, Khoury J, Siddiqi TA. Pre-conception management of insulin-dependent diabetes: improvement of pregnancy
outcome. Obstet Gynecol 1991;77(6):846-9.
Cousins L. The California Diabetes and Pregnancy Programme: a statewide collaborative programme for the pre-conception and prenatal care of
diabetic women. Baillieres Clin Obstet Gynaecol 1991;5(2):443-59.
Steel JM, Johnstone FD, Hepburn DA, Smith AF. Can prepregnancy care of diabetic women reduce the risk of abnormal babies? BMJ
1990;301(6760):1070-4.
Kitzmiller JL, Gavin LA, Gin GD, Jovanovic-Peterson L, Main EK, Zigrang WD. Preconception care of diabetes. Glycemic control prevents congenital
anomalies. JAMA 1991;265(6):731-6.
Dicker D, Feldberg D, Samuel N, Yeshaya A, Karp M, Goldman JA. Spontaneous abortion in patients with insulin-dependent diabetes mellitus: the
effect of preconceptional diabetic control. Am J Obstet Gynecol 1988;158(5):1161-4.
Goldman JA, Dicker D, Feldberg D, Yeshaya A, Samuel N, Karp M. Pregnancy outcome in patients with insulin-dependent diabetes mellitus with
preconceptional diabetic control: a comparative study. Am J Obstet Gynecol 1986;155(2):293-7.
127
Table 3. Infections
Intervention
Author, design and
year study
Outcome
Quality
Prepregnancy pertussis
booster vaccination
Leuridan et al, 20111
Prospective study
Timefream: unclear
24 non-pregnant women were included: blood was drawn from mother and off-spring
II-2
Banhidy et al, 20102
Secondary analyses
of RCT
1984-1992
4,672 pregnant women were evaluated:
- 215 with clinical and 691 with subclinical vaginal candidiasis (asymptomatic candida colonisation)
- 466 with combination of Sexual Transmitted Disease (STD) and vaginal candidiasis
- 795 with STD without vaginal candidiasis
- 2,505 without STD and vaginal candidiasis as references
 Tetanus, diphtheria,
acellular pertussis booster
vaccine (Boostrix®,
GlaxoSimthKline Biologicals,
Rixensart, Belgium) was given
in between the first and
second pregnancy after
breastfeeding was ceased
Preconceptional screening of
sexually transmitted diseases
(STDs)
 Treatment of
preconceptional clinically
diagnosed vaginal candidiasis:
combination of Canesten®
100 mg and Canesten®, 200
mg in 20 g cream, i.e. 1% or
Clomitrazole; vulvar and anal
application and partner
treatment with Clotrimazole
cream; other STD were
treated mainly by clindamycin,
metronidazole and
doxycycline
Efficient transplacental antibody transfer and significantly higher antibody titers against 3 pertussis anitigens were observed
in cord blood and in blood of 1-month-old infants born after a maternal booster vaccination compared with results in their
siblings born before the booster administration
I-a
Association was found with higher risk of preterm birth in:
- Pregnant women with STD (OR 8.5; 95% CI 2.0-34.9)
- Clinically diagnosed vaginal candidiasis (OR 2.5; 95% CI 0.8-7.7)
- Asymptomatic candida colonisation (OR 2.5; 95% CI 1.2-5.2). This risk was reduced with Clotrimazole treatment
- Pregnant women without recognized STD and/or vaginal candidiasis (OR 13.0; 95% CI 5.5-30.7)
128
Interconception antibiotics
 Every 4 months 2 doses of
Azithromycine versus placebo
until conception or until the
study was terminated
Preconceptional Haemophilus
influenza type b conjugate or
pneumococcal polysaccharide
vaccines
 Healthy non-pregnant
women of childbearing age
were randomized to receive a
Haemophilus influenzae type
B conjugate vaccines (either
HbOC or Hib-OMP) or a 23valent pneumococcal
polysaccharide vaccine
(PnPs)
 Infants received Hib-OMP
vaccine at 2, 4 and 12 months
of age
 Vaccine safety and
immunogenicity was evaluated
in the women and their infants
Tita et al, 20073
Secondary analyses
of double-blind
placebo-controlled
RCT
1998-2003
241 women were recruited with singleton pregnancies that ended in a spontaneous preterm birth or pregnancy loss
between 16- 34 weeks of gestation
Santosham et al,
20015
RCT
1991-1994
199 women who gave birth after receiving 1 or more doses of the respective vaccine were evaluated: HbOC n=68, HibOMP n=70 and PnPs n= 61
I-a
Endometrial cultures and histologic types were obtained at randomization among women assigned to the antibiotics group
(n=118) or a placebo group (n=123)
Antibiotics were associated with lower acquisition and higher resolution of microbes:
- 14% of the women who received antibiotics vs. 34% of the placebo group had positive endometrial culture for Gardnerella
after treatment (p<0.05);
- 57% of the women who received antibiotics vs. 33% of the placebo group had a negative follow-up culture ( p<0.05)
I-a
Women immunized with one of the Hib conjugate vaccines compared to PnPs:
- Anti-polyribose ribitol phosphate antibody titers were significantly higher throughout the 37-month observation
Infants born to mothers immunized with Hib vaccines compared with PnPs:
- Significantly higher polyribose ribitol phosphate-specific IgG antibody titers at birth and 2 months of age
- Lower antibody responses to Hib-OMP at 6 months
- Similar titers before and after boosting with Hib-OMP at 1 year of age
129
References
1.
2.
3.
4.
5.
Leuridan E, Hens N, Peeters N, Witte de L, Meeren van der O, Damme van P. Effect of a prepregnancy pertussis booster dose on maternal antibody
titers in young infants,Pediatr Infect Dis J, 30 (2011), 608-10.
Bánhidy F, Dudás I, Czeizel AE, Preconceptional screening of sexually transmitted infections/diseases, Central European Journal of Medicine, 6
(2010), 49-57.
Tita AT, Cliver SP, Goepfert AR, Conner M, Goldenberg RL, Hauth JC, Andrews WW. Impact of interconception antibiotics on the endometrial
microbial flora, Am J Obstet Gynecol, 196 (2007), 226 e1-6.
Fowler KB, Stagno S, Pass RF, Maternal immunity and prevention of congenital cytomegalovirus infection, JAMA, 289 (2003), 1008-11.
Santosham M, Englund JA, McInnes P, Croll J, Thompson CM, Croll L, Glezen WP, Siber GR, Safety and antibody persistence following Haemophilus
influenzae type b conjugate or pneumococcal polysaccharide vaccines given before pregnancy in women of childbearing age and their infants, Pediatr
Infect Dis J, 20 (2001), 931-40.
130
Table 4. (Multi)vitamins and folic acid supplementation
Intervention
Name, design and year
study
Outcome
Quality
Multivitamin supplementation
Burris et al, 20101
Retrospective cohort 19982007
2,374 non-Hispanic white subjects: no association found with birth weight, gestational age,
or weight-for-gestational-age
135 non-Hispanic black subjects: association found with
- 536 gram increased birth weight (p=0.001)
- Longer gestations (not significant)
- Increased foetal growth (+0.86 z score units, 95% CI 0.35-1.36)
II-2
Van Beynum et al, 20102
Case- control study
1996-2005
Cases: mothers with infants with isolated or complex heart defects(CHD), without any related
syndrome or genetic abnormality (n=611)
II-2
 Four or more times/week in the
periconception period (28 days before
conception throughout 28 days after
conception)
Folic acid supplementation
 Daily 0.4 mg alone or as a multivitamin
during at least 4 weeks before pregnancy
until the first two months of pregnancy
Controls: mothers of children with known chromosomal or genetic defect, and with infants
with other non-folate related congenital malformations (n=2401)
18% reduced significant risk of all types of CHD relative to other malformations:
OR 0.82; 95% CI 0.68-0.98
38% reduced risk of isolated septal defects: OR 0.62; 95% CI 0.47-0.82
Folic acid supplementation/ fortification
Blencowe et al, 20103
Meta-analyse of 4 RCT’s and
11 observational studies
The evidence for and the effect of folic acid fortification/supplementation on neonatal
mortality due to neural tube defects (NTD), especially in low income countries was reviewed
in 4 RCT’s and 11 observational studies
Meta-analyse of:
- 3 RCT’s for women with a previous pregnancy with NTD indicates a significant reduction of
70% (95 % CI 0.14-0.65) in recurrence (secondary prevention)
- 1 RCT with 3 cohort studies suggested a significant reduction of 62% (95 % CI 0.49-0.71)
through folic acid supplementation
- 8 observational studies examining folic acid food fortification gave an estimate significant
reduction in NTD incidence of 46% (95% CI 0.37-0.54)
Folate supplementation
 With or without multivitamins
Bukowski et al, 20094
Prospective cohort study
1999-2002
34,480 low –risk singleton pregnancies were enrolled
I-a (RCT’s)
II-1
(observational
studies)
II-2
Comparing no preconceptional folate supplementation to preconceptional folate
supplementation for 1 year or longer was associated with:
- 70% significant decrease in the risk of spontaneous preterm delivery between 20-28 wk (41
131
[0.27%] versus 4 [0.04%]; HR 0.22; 95% CI 0.08-0.61; p=0.004)
- 50% significant decrease in the risk of spontaneous preterm delivery between 28-32 wk (58
[0.38%] versus 12 [0.18%]; HR 0.45; 95% CI 0.24-0.83; p=0.010)
No association was found of preconceptional folate supplementation and the risk of
spontaneous preterm birth:
- Beyond 32 wk
- Shorter duration (<1 year) of preconceptional folate supplementation
- Other complications of pregnancy
The risk of spontaneous preterm birth decreased with the duration of preconceptional folate
supplementation (trend analysis; p=0.01) and was the lowest in women who used folate
supplementation for 1 year or longer
 Containing folic acid or not; intake of
dietary folic acid; analysed in monthly units
from 3 months before pregnancy through
the last month of pregnancy
Mosley et al, 20085
Case-control study
1998-2003
 Daily dosage of 1 mg folic acid or once
weekly dosage of 5 mg; during 12 weeks
 Containing 0.4 mg folic acid versus no
supplementation during periconceptional
period
II-2
Periconceptional supplement use did not reduce the risk of having a pregnancy affected by
NTD
Maternal telephone interviews were
conducted
Cases: women with a pregnancy affected by anencephaly (n=180) or spina bifida (n=385)
with no chromosomal abnormality; controls: random sample of women who delivered a
liveborn infant without a structural birth defect (n=3,963)
Maternal intake of dietary folate was not significantly associated with NTD
Rosenthal et al, 20086
RCT
April-June 2005
140 eligible women aged 18-49 years old were randomised, but 58 remained in the dosage
5mg/week group and 49 in the dosage 1mg/daily
1mg/daily: serum folate levels increased from 6.3 to 14.9 ng/mL (p<0.0001)
5mg/week: serum folate levels increased from 6.9 to 10.1 ng/mL (p<0.0001)
Red blood cell folate concentrations also increased significantly in both groups, although
slower
I-a
Chen et al, 20087
Randomised population based
intervention study
2000-2002
All of the women having pregnancies with birth defects and women without birth defects
were interviewed
I-b
9 NTDs from 25,444 pregnancies in the intervention group versus 48 NTDs among 26,599
pregnancies in the control group  significant protective rate of 80.4% (RR 0.20; 95% CI
0.10-0.40)
132
 Containing folic acid for 3 months before
conception through the first trimester
Bitsko et al, 20078
Case-control study
1993-1995
 During the month before the last
menstrual period and the first two months of
pregnancy
II-2
Controls: random sample of live births
No significant association between taking vitamins containing folic acid during the
periconceptional period and multiple congenital anomalies was found ( OR 1.12; 95% CI
0.75-1.69)
Telephone interviews were conducted to
assess exposure to folic acid through
vitamins, cereal, and food supplements
Multivitamin and folic acid supplementation
Cases: mothers of infants with multiple congenital anomalies
No significant association between vitamin exposure beginning in the first trimester and
multiple congenital anomalies outcomes was found (OR 1.05; 95% CI 0.59-1.87)
Wilcox et al, 20079
Case-control study
1996-2001
Cases: mothers of infants with cleft lip with/without cleft palate (n=377) and cleft palate alone
(n=196); controls: n=763
II-2
Folic acid supplementation (>0.4mg/day) was significantly associated with a reduced risk of
isolated cleft lip with/without cleft palate: aOR 0.61; 95% CI 0.39-0.96
The lowest risk of cleft lip was among women with folate rich diets who also took
multivitamins and folic acid: OR 0.36; 95% CI 0.17-0.77 (significant)
Folic acid provided no significant protection against cleft palate alone: OR 1.07; 95% CI
0.56-2.03
Folate supplementation
 Average consumed folic acid the month
before pregnancy and each of the first three
months of pregnancy
 Periconceptional (-1 month to +2 months
conception) use of multivitamins Elevit
Pronatal
 During 12 weeks before conception
through the date of delivery; dietary intake
and supplementation
Bower et al, 200610
Case- control study
1997-1999
Cases: mothers of infants with orofacial cleft (n=62); congenital heart defects (n=151);
urinary tract defects (n=117); limb reduction defects (n=26); or other major birth defects
(n=119); and 578 control women live-born infants without birth defects
II-2
Neither folic acid supplements nor dietary folate intake in women using supplements was
significantly associated with a reduction in risk in any of the case groups
Czeizel et al, 200611
Case-control study
1980-1996
1,349 cases and 2,405 controls
Shaw et al, 200612
Case-control study
1997-2000
Cases: mothers of infants with cleft palate/lip with/without cleft palate (n=1108): controls:
mothers of infants without malformations (n=2,594)
II-2
No association wad found for a higher risk of multiple congenital anomalies (i.e., two or more
congenital abnormalities in the same person affecting at least two different organ systems)
II-2
No significant reduction in risks with periconceptional use of supplements containing folic
acid was found (aOR cleft palate 1.01; 95% CI 0.82-1.24; aOR cleft lip with/without cleft
palate 1.02; 95% CI 0.77-1.34)
133
 3 or more times/ week during 3 months
before pregnancy and throughout the first
trimester
Yuskiv et al, 200513
Case- control study
1993-1997
Maternal interviews were available for 99 case-infants (multiple congenital anomalies: 2 or
more major birth defects affecting at least two different organ systems, with no recognized
chromosome abnormality or single gene disorder) and 335 control-infants (a random sample
of live births with no major birth defects)
II-2
Periconceptional multivitamin use was associated with a higher risk of multiple congenital
anomalies among all infants: adjusted OR 2.4; 95% CI 0.9-6.7, and especially when limited
to those with no family history or major defects: adjusted OR 4.0; 95% CI 1.3-12.8.
Folate intake
 Intake of folic acid from supplements
was calculated using the amount of folic
acid in every supplement taken. The amount
taken in the month before and in each of the
first three months of pregnancy was
expressed as an average of folic acid in
micrograms (µg) per day per period.
Women consuming an average of 200 µg or
more daily of folic acid from supplement in
each of the four relevant time periods were
considered to be adequately supplemented
 one vitamin tablet/day, or had missed
only one day, for 28 days before conception
and/or until the date of the third missed
menstrual period with the multivitamins
Elevit Pronatal
Bower et al, 200414
Case- control study
1997-2000
Cases: mothers of infants with a previous NTD (n=36); controls: random sample of all
liveborn infants (n=578)
II-2
Supplement use was associated with a non-significant 4% reduction in risk
For women not taking supplements, dietary sources of folate were protective, and most
women obtained at least some folate from fortified food
Controlled- cohort trial
1993-1996
3,069 pregnant women in each cohort
II-1
Supplemented cohort:
- significant reduced congenital cardiovascular malformations (31 vs. 50;OR, 0.60; 95% CI,
0.38-0.96), mainly by ventricular septal defects (5 vs.19; OR, 0.26; 95% CI, 0.04-0.86)
- protective significant effect on NTDs (1 vs. 9; OR, 0.11; 95% CI, 0.01-0.91)
- significant reduction in stenosis/atresia of pelvicureteric junction (2 vs. 13; OR, 0.19; 95%
CI, 0.04-0.86)
Folic acid fortification
 containing folic acid starting from 4
weeks before until 8 weeks after conception;
Kucik et al, 200416
Cohort
1990-2001
510,000 singleton and 7,168 twin pregnancies were evaluated
Van Rooij et al, 200417
Case- control study
1998-2000
Cases: 174 mothers of a child with non-syndromic cleft lip with/without cleft palate and;
controls: 203 mothers of a child without congenital malformations
II-2
There was no upward trend in twinning rates among women younger than 30 years prior to
fortification
II-2
47% significant reduction in the risk of cleft lip with/without cleft palate (OR 0.53; 95% CI
134
93% of women took only folic acid
 each day or only 1 day missing per week
during the periconceptional period (1 month
before to 2 months after conception) with
the multivitamins Elevit Pronatal, Rochem,
Basel, Switzerland
Vitamin C supplementation
 750 mg vitamin C daily alone from the
first day of the third menstrual cycle until
pregnancy test was positive versus no
supplementation or placebo
 Multivitamin with folic acid, iron, zinc and
vitamin A versus no multivitamin with folic
acid, iron, zinc and vitamin A
 Daily 0.4 mg folic acid before and during
early pregnancy
0.33-0.85) and the largest significant risk reductions were found on those mothers who had a
diet of more than 200 μg folate per day in combination with a folic acid supplement (OR 0.26;
95% CI 0.09-0.72)
RCT (1984- 1991) and
controlled-cohort trial (19931996) combined
5,527 supplemented pregnant women with 51 cases of multiple congenital abnormalities
(OR 0.89; 95% CI 0.45-1.68) and 5,447 unsupplemented pregnant women
Hemmi et al, 200319
RCT
1997-2000
122 women were randomised to either vitamin C (n=76) or control (n=46)
Christian et al, 200320
RCT
1998-2001
The final analysis involved 3325 infants allocated to control (n=685), compared to folic acid
(n=628), folic acid-iron (n=635), folic acid-iron-zinc (n=672) or multiple micronutrients
(n=705)
II-1 (controlled
trial)
I-a
No significant difference was seen for:
Maternal outcomes:
- Foetal loss (RR 0.1.28; 95% CI 0.58-2.83)
- Early or late miscarriage (RR 1.17; 95% CI 0.52-2.65)
I-a
Difference was seen for:
Neonatal outcomes:
- More likely to be stunted at six to eight years of age (RR 1.09; 95% CI 1.00-1.19)
- Significantly less likely to have an infant with a birth weight <2500 g (RR 0.94; 95% CI 0.900.99)
Li et al, 200321
Cohort
1993-1996
Folic acid use does not significantly increase the occurrence of multiple births (0.59% in the
supplemented group versus 0.65% not supplemented)
Waller et al, 200322
Cohort
1996-1998
1 003 207 deliveries were examined
The prevalence of twin deliveries conceived before, during and after fortification with folic
acid was compared:
- 1997 versus 1996: 2.4% yearly non-significant increase in twin pregnancies; 1,024 (OR
0.98; 95% CI 0.98-1.07)
Prospectively gathered precise records
information regarding supplementation
No significant evidence was found for preventing or inducing multiple congenital
abnormalities by periconceptional folic-acid containing multivitamin supplementation
I-a (RCT)
II-2
Not confounded by increasing maternal age or the use of ovarian stimulation or assisted
reproductive technologies
II-2
135
- 1998 versus 1997: 4.6% yearly non-significant increase in twin pregnancies; 1,046 (OR
1.00-1.09)
The size and pattern of these increases are consistent with the ongoing increase in twinning
of 1-4% per year which began in the US prior to fortification
 Multivitamin containing 0.8mg folic acid
begun at least one month before conception
Shaw et al, 200323
Cohort
1990-1999
2.5 million births were examined regarding twin pregnancies
Olshan et al, 200224
Case- control study
1992-1996
Vitamin use information was obtained during specific periods before and during pregnancy
from 538 cases (children under age 19 years with new diagnosed neuroblastoma) and 504
control (one control was selected for each case, using random digit dialling based) mothers
through telephone interviews
II-2
After adjusting for maternal age, parity, race/ethnicity, sexes of twin pair, year of birth, and
fortification period no association between fortification and twinning was found
II-2
Daily vitamin and mineral use in the month before pregnancy was associated with a 30-40%
reduction in risk of neuroblastoma
Plasma folate levels
George et al, 200225
Case- control study
1996-1998
Cases (n=468): women who had spontaneously aborted foetuses with gestational age of 612 weeks; controls (n=921): women matched for gestational age of the foetuses
II-2
Women with low plasma folate concentrations (≤4.9 nmol/L) were more likely to have had a
miscarriage than women with plasma folate concentrations between 5.0-8.9 nmol/L
The occurrence of miscarriage was not increased in women with higher plasma folate
concentrations (≥14.0 nmol/L) relative to women with plasma folate concentrations between
5.0-8.9 nmol/L
Supplement use was not associated with an increased occurrence of miscarriage
 Regular periconceptional use
 Regular use in first trimester +/preconceptional use
Botto et al, 200226
Case-control study
1968-1980
72 cases of non-syndromic omphalocele (40 isolated, 32 multiples) and 3,029 controls
Itikala et al, 200127
Case-control study
1968-1980
309 with non-syndromic clefts and 3,029 controls
II-2
Periconceptional multivitamin use was associated with a 60% risk reduction in risk for nonsyndromic omphalocele (OR 0.4; 95% CI 0.2-1.0)
II-2
Periconceptional multivitamin use was significant associated with a risk reduction of:
- 39% in orofacial clefts (overall): OR 0.61; 95% CI 0.43-0.87
- 48% in cleft lip with or without cleft palate: OR 0.52; 95% CI 0.34-0.80
Periconceptional multivitamin use was non-significant associated with a risk reduction of:
- 19% in cleft palate: OR 0.81; 95% CI 0.44-1.52
136
 In early pregnancy
Ericson et al, 200128
Cohort
Timeframe: unclear
Women (n=2,569) who in early pregnancy reported the use of folic acid had an increased
rate of dizygotic twin deliveries (OR 2.13; 95% CI 1.64-2.74) compared the rate of twin births
in the entire Swedish population
II-2
These results were highly confounded by increasing maternal age and the length of
involuntary childlessness, maybe the women were also using assisted reproductive
technologies
Supplementation
 0.4 mg folic acid only (pill) use in any
periconceptional period
Myers et al, 200129
Evaluation of public health
campaign
1993-1995
126,783 women on folic acid supplements and 95,531 women on no supplements
Beaty et al, 200130
Case- control study
1992-1998
135 with non-syndromic clefts and 152 controls
 Regular use in first trimester +/preconceptional use
 0.4 mg folic acid before and during early
pregnancy or not
Folic acid component of multivitamins
Periconceptional daily 0.4 mg folic acid supplementation was significantly associated with a
risk reduction of 50% in imperforate anus of the child (OR 0.50; 95% CI 0.29-0.88)
II-2
No statistically significant association was found for risk reduction of:
- Cleft lip with or without cleft palate: OR 0.59; 95% CI 0.33-1.09
- Cleft palate: OR 0.70; 95% CI 0.31-1.56
Gindler et al, 200131
Cohort
1993-1995
21,935 women had any use of folic acid pills; 1,871 women had no use of folic acid pills
II-2
Prospectively information was gathered; excluding previous miscarriages
Miscarriage rate between folic acid use versus no use: 9.0% versus 9.3% (RR 0.97; 95% CI
0.84-1.12; not significant)
Hernandez-Diaz et al, 200032
Case-control study
1976-1998
Exposure to folic acid antagonists that act as dihydrofolate reductase inhibitors and to certain
antiepileptic drugs was assessed in:
- 3870 infants with cardiovascular defects
- 1962 infants with oral clefts
- 1100 infants with urinary tract defects
- 8387 control infants with malformations
II-2
Increased risk on cardiovascular defects when exposure to dihydrofolate reductase inhibitors
occurred in the second month of pregnancy versus no exposure: OR 3.4; 95% CI 1.8-6.4
Increased risk on oral clefts when exposure to dihydrofolate reductase inhibitors occurred in
the third month of pregnancy versus no exposure: OR 2.6; 95% CI 1.1-6.1
137
 Multivitamin containing folic acid versus
placebo
ICMR 200033
RCT
1988-1991
466 women were enrolled and randomised to either vitamin (n=231) or placebo (n=235)
I-a
Maternal outcomes:
- Foetal loss (RR 1.00; 95% CI 0.75-1.34)
- Early or late miscarriage (RR 1.09;95% CI 0.95-1.25)
Neonatal outcomes:
- Stillbirth (RR 0.86; 95% CI 0.65-1.13)
- Small for gestational age (RR 0.96; 95% CI 0.84-1.08)
- Open NTD: 2.92% in the vitamin group vs. 7.04% in the placebo group (p=0.06)
Maternal outcomes:
- Multiple pregnancies (RR 1.36; 95% CI 1.00-1.85)
Vitamin A supplementation
 Vitamin A and/or beta-carotene versus
placebo
Katz et al, 200034-35
RCT
1994-1997
17,373 pregnancies were allocated to the following groups: vitamin A (n=6070), betacarotene (n=5650) or placebo (n=5653)
I-a
Maternal outcomes:
- Foetal loss (RR 1.04; 95% CI 0.95-1.14)
- Early or late miscarriage (RR 1.09; 95% CI 0.95-1.25)
- Neonatal death (RR 1.11; 95% CI 0.94-1.31)
Maternal outcomes:
Botto et al, 200036
Case-control study
1968-1980
958 with heart defects and 3,029 controls
II-2
Periconceptional vitamin supplementation was significantly associated with:
- Risk reduction of 28% in heart defects (overall): OR 0.76; 95% CI 0.60-0.97
- Risk reduction of 54% in outflow tract defects: OR 0.46; 95% CI 0.24-0.86
-Risk reduction of 39% in ventricular septal defect: OR 0.61; 95% CI 0.38-0.99
 Containing folic acid 3 months before
through 3 months after conception
Shaw et al, 200037
Case- control study
1993-1996
cases: mothers of children with multiple congenital anomalies; controls: randomly selected
from non-malformed liveborn infants.
II-2
Telephone interviews were conducted with 112 case and 195 control mothers
138
Elevated risk for multiple congenital anomalies (OR 2.6; 95% CI 1.1-6.2) was found for
women who used multivitamin supplementation compared to those who did not
 Containing 4 mg folic acid besides
calcium, iron, zinc and vitamins A, B1, B2,
B6 C, D and nicotinamide or placebo
containing calcium and iron only during one
month prior to conception and up to three
months after conception
 3 months before conception and in each
trimester of pregnancy
 1.0 mg versus 2.5 mg preconceptional
 multivitamin plus 0.8 mg folic acid begun
ate least one month before conception
 1.0 mg versus 2.5 mg preconceptional
Thomas et al, 200038
RCT
1988-1991
466 women with previous history of giving birth to a child with NTD were included: 231 in the
vitamin group and 235 in the placebo group
Shaw et al, 199939
Case- control study
1989-1991
Interviews were conducted with 409 NTD cases and 420 non-malformed randomly selected
controls from each area hospital
Rolschau et al, 199940
Double-blind randomized trial
1983-1986
8,184 women took part: 2,310 with supplementation without being randomised and 2,721
women received no folic acid supplementation
Case-control study
1980-1996
473 with clefts and 525 controls
Ulrich et al, 199942
1983-1986
RCT
14,021 pregnancies resulted in child birth:
- 2,721 pregnancies with no supplementation
- 2,310 with folic acid given without randomisation
- 8,184 pregnancies with folic acid with randomisation (1,359 [16.6%] before the last
menstrual period; 6,825 [83.4%] during the first 19 weeks of pregnancy)
I-a
Recurrence of NTD: 2.92% in the vitamin group versus 7.04% in the placebo group (not
significant; p=0.06)
II-2
Most single nutrients studied appeared to be associated with decreased NTD risks in models
that considered intake data in quartiles and did not adjust for other nutrients. Many of these
estimates when adjusted for other nutrients did not reveal reduced NTD risks (potential
confounding effect)
I-b
A supplement of 1.0 mg folic acid had the same effect as 2.5 mg
The effects of supplementing the diet with folic acid preconceptional:
- Slight increase of birth weight
- Decrease in the incidence of preterm labour
- Decrease in infants with low birth weight and SGA
II-2
Periconceptional multivitamin supplementation plus 3.0-9.0 mg folic acid was associated
with:
- Non- significant risk reduction of 13% in cleft lip with or without cleft palate: OR 0.87; 95%
CI 0.73-1.03
- Significant risk reduction of 25% in cleft palate: OR 0.75; 95% CI 0.58-0.96
I-b
139
No dose-dependent differences were found in either total anomalies or in those specific
malformations
 Regular use in first trimester +/preconceptional period
Werler et al, 199943
Case-control study
1993-1996
160 with non-syndromic clefts and 521 controls
II-2
Periconceptional multivitamin supplementation was associated with:
- Non-significant risk reduction of 30% in cleft lip with or without cleft palate: OR 0.7; 95% CI
0.4-1.1
- Significant risk reduction of 60% in cleft palate: OR 0.4; 95% CI 0.2-0.9
157 with outflow tract defects, 186 with ventricle septal defect and 521 controls
Periconceptional multivitamin supplementation was non-significant associated with:
- Outflow tract defects: OR 1.00; 95% CI 0.70-1.50
- Ventricular septal defect: OR 1.20; 95% CI 0.80-1.80
31 with non-syndromic limb deficiencies and 521 controls
- Risk reduction of 50% in limb deficiency: OR 0.50; 95% CI 0.2-1.1
184 with defects of kidney/ureter/bladder/urethra and 385 controls
Periconceptional multivitamin supplementation was significant associated with:
- Risk reduction of 40% in urinary tract defects: OR 0.6; 95% CI 0.4-0.9
 Periconceptional daily intake of 4
mg/day; 0.4 mg/day
 Multivitamin containing 0.8 mg folic acid
begun at least one month before conception
Mathews et al, 199944
RCT; observational study
1983-1991; unclear
The rate of multiple births in both studies was similar for supplemented or unsupplemented;
also when the datasets were combined (p=0.59)
I-a
RCT
1985-1993
2,471 women on multivitamin supplements and 2,391 on trace elements
I-a
II-2
- Risk reduction of 58% in heart defects (overall): OR 0.42; 95% CI 0.19-0.98
- Risk reduction of 79% in urinary tract defects: OR 0.21; 95% CI 0.05-0.99
- Risk reduction of 23% in orofacial clefts (overall): OR 0.77; 95% CI 0.22-2.69
- Risk reduction of 81% in cleft palate: OR 0.19; 95% CI 0.01-4.03
- Risk reduction of 76% in ventricular septal defect: OR 0.24; 95% CI 0.05-1.14
140
 Average multivitamin with folic acid use
in year before conception
Scanlon et al, 199846
Case- control study
1986-1989
126 with outflow tract defect and 679 controls
II-2
Multivitamin and/or folic acid
supplementation
Wald et al, 199747
Secondary analysis of RCT
(MRC study)
1983-1991
Only data from women who became pregnant were analysed: no association was found
between periconceptional folic acid supplementation and an increase in miscarriage rates
(RR 1.06; 95% CI 0.79-1.43; p=0.70)
I-a
Hook et al, 199748
Secondary analysis of RCT
(MRC study)
1983-1991
2787 women in the folic-acid supplemented group; 2653 in the not-folic acid supplemented
group
I-a
Retrospective study
1968-1980
1987-1989
1987-1994
Multiple and singleton births collected from 3 separate birth defect programs; retrospectively
interviews; did not differentiate among types of vitamin supplements used
Yang et al, 199750
Case-control study
1968-1980
117 with non-syndromic limb deficiencies and 3,029 controls
 4 mg folic acid or not
 Periconceptional (before pregnancy and
throughout the first three months after
conception); started early (first month
through at least the third month after
conception); and started later (in the second
or third month after conception)
Non significant increase in spontaneous miscarriages: OR 1.16; 95% CI 1.01-1.3
II-2
A non-significant 30-60% greater prevalence of periconceptional vitamin supplementation
among mothers of multiple births was found
II-2
 Daily single tablet of a multivitamin
containing 0.8 mg of folic acid or traceelement supplement was given during at
least one month before conception and at
least until the date of the second missed
menstrual period
RCT
1985-1993
Multivitamin group: n= 2,471; placebo-like trace element group: n= 2,391 informative
offspring (prenatally diagnosed and terminated malformed foetuses, stillborn foetuses, and
liveborn infants)
I-a
The total rate of major congenital abnormalities was: 20.6/1,000 in the multivitamin and
40.6/1,000 in the trace element group. After the exclusion of six cases of neural-tube defects
in the trace element group the difference was very highly significant (p= 0.0003; RR 0.54;
95% CI 0.39, 0.76).
141
Multivitamin supplementation appeared to result in a significant reduction in:
- The rate of urinary tract abnormalities
- Mainly obstructive defects
- The rate of sporadic cardiovascular malformations, mainly VSDs
 At least three times/ week at any time
during -3 to +3 months conception
Multivitamin or folic acid alone
supplementation
 Containing folic acid from one month
before until two months after conception
Khoury et al, 199652
2 case-control studies
1968-1980; 1989-1991
112 NTD multiple cases and 3568 control babies
Hayes et al, 199653
Case-control study
1988-1991
303 with non-syndromic clefts and 1,167 controls with selected defects
Shaw et al, 199554
Case- control study
1987-1988
Telephone interviews were conducted with mothers of 207 children with cardiac conotruncal
malformations, 178 limb defect cases and of 481 randomly selected liveborn non-malformed
control infants
II-2
Significant risk reduction for multiple NTDs (i.e., NTD cases with associated major defects)
was found: pooled OR 0.36; 95% CI 0.18-0.72
II-2
Periconceptional multivitamin or folic acid alone supplementation was non-significant
associated with:
- Increased risk of orofacial clefts (overall): OR 1.4; 95% CI 0.8-1.7
- Increased risk of cleft lip with or without cleft palate: OR 1.3; 95% CI 0.8-2.1
- Increased risk of cleft palate: OR 0.9; 95% CI 0.5-1.6
II-2
Reduced (non-significant) risks were observed for any compared to no multivitamin use for:
- Conotruncal defects: OR 0.70; 95% CI 0.46-1.1
- Limb defects: OR 0.65; 95% CI 0.41-1.0
Among non-vitamin using women, consumption of cereal containing folic acid was also
associated with reduced risks for both defects
 Multivitamin plus 10 mg folic acid begun
at least one month before conception
Talorava and Harris, 199555
Nonrandomized recurrence
prevention trial
1976-1980
221 women on multivitamin supplements and 1901 not supplemented
II-2
Periconceptional multivitamin plus 10 mg folic acid alone supplementation was significant
associated with:
- Risk reduction of 65% in cleft lip with or without cleft palate: OR 0.35; 95% CI 0.09-0.95
 Use in any periconceptional period
Shaw et al, 199556
Case-control study
1987-1988
489 clefts and 734 controls; 178 with non-syndromic limb deficiencies and 481 controls
II-2
Periconceptional multivitamin use was associated with:
- Significant risk reduction of 50% in cleft lip with or without cleft palate: OR 0.50; 95% CI
0.36-0.68
- Non- significant risk reduction of 27% in cleft palate: OR 0.73; 95% CI 0.46-1.20
142
- Non-significant risk reduction of 36% in limb deficiency: OR 0.64; 95% CI 0.41-1.0
 Any periconceptional use
Li et al, 199557
Case-control study
1990-1991
117 with defects of kidney/ureter/bladder/urethra and 385 controls
II-2
- Significant risk reduction of 83% in urinary tract defects: OR 0.17; 95% CI 0.06-0.48
 Multivitamin with/without folic acid versus
no multivitamin or folic acid from at least 28
days before conception until at least the
second missed menstrual period
Czeizel et al, 199458-59
RCT
1984-1992
7765 women were randomised and 5502 women had a confirmed pregnancy and were
allocated to either multivitamins (n=2819) or control (n=2683).
I-a
Maternal outcomes:
- foetal loss (RR 1.09; 95% CI 0.95-1.25)
- early or late miscarriage (RR 1.09;95% CI 0.95-1.25)
Neonatal outcomes:
- Stillbirth (RR 0.86; 95% CI 0.65-1.13)
- Small for gestational age (RR 0.96; 95% CI 0.84-1.08)
- Congenital malformations (RR 1.47; 95% CI 0.90-2.40)
Birth weight (MD 3.00 g; 95% CI -24.15- 30.15)
Maternal outcomes:
 Daily one tablet of a multivitamin
including 0.8 mg folic acid or trace-element
supplement for at least one month before
conception and at least two months after
conception
RCT
1984-1988
4,156 pregnancies with known outcome and 3,713 infants evaluated in eight month of life
I-a
Vitamins group versus trace-element group:
- Lower rate of all major congenital abnormalities other than NTDs and genetic syndromes:
9.0/1000 versus 16.6/1000 (RR 1.85; 95% CI 1.02-3.38)
- Rate of all major congenital malformations other than NTDs and genetic syndromes was
14.7/1000 versus 28.3/1000 (RR 1.95; 95% CI 1.23-3.09)
143
 Containing 0.4 mg folic acid during 28
days before through 28 days after the last
menstrual period
Case-control study
1988-1991
Cases: mothers of occurrent NTDs (n=436); controls: with other malformations (n=2,615)
II-2
- Significant risk reduction of 60% in the risk of NTDs: RR 0.4; 95% CI 0.2-0.6
For dietary folate, there was a dose-related decline in risk according to the quintile of intake
(p for trend =0.02)
Multivitamin supplementation containing
folic acid
 Single tablet of vitamin supplement (12
vitamins; including 0.8 mg folic acid; 4
minerals; and 3 trace elements) or traceelement supplement (copper, manganese,
zinc, and a very low dose of vitamin C) daily
during one month before conception until
the date of the second missed menstrual
period or later
folic acid
RCT
1984-1988
Vitamin supplement group: n= 2,104; trace-element group: n= 2,052
I-a
Congenital malformations:
- More prevalent in the trace-element group (22.9 per 1000 cases) than in the vitamin
supplement group (13.3 per 1000 cases; p=0.02)
NTDs:
Six cases in the trace-element group versus none in the vitamin group
Cleft lip with/without cleft palate:
Was not reduced by periconceptional vitamin supplementation
Miscarriages:
Significant increase of 16% in rates between supplemented and trace-element group
Kirke et al, 199263
RCT
1981-1988
354 women were randomised to either folic acid alone (n=115), multivitamin with folic acid
(n=119) or multivitamin without folic acid (n=120)
I-a
Maternal outcomes:
- Foetal loss (0.91; 95% CI 0.65-1.27)
no multivitamin or folic acid
MRC 199164
RCT
1983-1991
1,817 women were randomised to either folic acid alone (n=449), multivitamin with folic acid
(n=453), multivitamin without folic acid (n=461) or placebo (n=454)
I-a
Maternal outcomes:
- Foetal loss (RR 1.09; 95% CI 0.95-1.25)
Neonatal outcomes:
- Stillbirth (RR 0.86; 95% CI 0.65-1.13)
- Congenital malformations (RR 1.47; 95% CI 0.90-2.40)
144
Nutritional supplementation
 Interpregnancy Food Program for
Women, Infants, and Children (WIC);
providing food supplementation and
nutritional education to pregnant, lactating,
and postpartum women and children up to 5
years of age who are both low-income and
nutritionally at risk
 Daily 3 tablets multivitamins (‘Spofavit’)
containing 10 mg folic acid for at least 3
months before conception at least until the
end of the first trimester of pregnancy
 Twice daily 4 mg before conception
through early pregnancy versus placebo
 1 tablet three times a day of Pregnavite
Forte F (Bencard) 28 days before
conception until the date of the second
missed period
 Multivitamin versus control without
placebo
Caan et al, 198765
Cohort study
1981-1983
Study group (n=335) received postpartum benefits for 5-7 months versus 0-2 months in the
control group (n=307)
II-2
Infants born to study group women had a higher mean birth weight (131g) and birth length
(0.3 cm) and a lower risk of being ≤2500g
At the onset of the second pregnancy study group women had higher mean Hb levels and
lower risk of maternal obesity
Tolarova et al, 198266
Case- control study
1976-unclear
In the fully supplemented group (n=85) there was one recurrence of cleft lip with/without cleft
palate versus 15 recurrences (7.4%) in the control group (n=212) (p=0.023)
II-2
Laurence et al, 198167
RCT
1954-1969
Supplementation group: 60 women who had a child with NTD (44 complied and 16 not);
placebo group: 51 women
I-a
Smithells et al, 198168
Multicentre non-randomised
study
Timeframe: unclear
Any women who had previously given birth to at least one NTD child, who was not pregnant,
and who planned a further pregnancy at some time in the future were eligible.
People’s league 194669
RCT
1938-1939
5,022 women were allocated to either multivitamins (n=2510) or control (n=2512)
No recurrences of NTDs were observed among the supplementation group versus six
among the placebo group (p=0.04)
II-2
NTD recurrences were:
- 1 (0.5%) in the fully supplemented group (n=200)
- None in the partially supplemented group (n=50)
- 13 (4%) in the unsupplemented group (n=300)
I-a
Maternal outcomes:
- Foetal loss (RR 0.83; 95% CI 0.58-1.17)
- Breastfeeding (RR 0.98; 95% CI 0.96-1.01)
Neonatal outcomes:
- Stillbirth (RR 0.86; 95% CI 0.65-1.13)
145
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the county of Funen in Denmark. Part I. Eur J Obstet Gynecol Reprod Biol 1999;87(2):105-10; discussion 103-4.
Czeizel AE, Timar L, Sarkozi A. Dose-dependent effect of folic acid on the prevention of orofacial clefts. Pediatrics 1999;104(6):e66.
Ulrich M, Kristoffersen K, Rolschau J, Grinsted P, Schaumburg E, Foged N. The influence of folic acid supplement on the outcome of pregnancies in
the county of Funen in Denmark. Part II. Congenital anomalies. A randomised study. Eur J Obstet Gynecol Reprod Biol 1999;87(2):111-3; discussion
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Mathews F, Murphy M, Wald NJ, Hackshaw A. Twinning and folic acid use. Lancet 1999;353(9149):291-2.
Czeizel AE. Periconceptional folic acid containing multivitamin supplementation. Eur J Obstet Gynecol Reprod Biol 1998;78(2):151-61.
Scanlon KS, Ferencz C, Loffredo CA, et al. Preconceptional folate intake and malformations of the cardiac outflow tract. Baltimore-Washington Infant
Study Group. Epidemiology 1998;9(1):95-8.
Wald N, Hackshaw A. Folic acid and prevention of neural-tube defects. Lancet 1997;350(9078):665.
Hook EB, Czeizel AE. Can terathanasia explain the protective effect of folic-acid supplementation on birth defects? Lancet 1997;350(9076):513-5.
Werler MM, Cragan JD, Wasserman CR, Shaw GM, Erickson JD, Mitchell AA. Multivitamin supplementation and multiple births. Am J Med Genet
1997;71(1):93-6.
Yang Q, Khoury MJ, Olney RS, Mulinare J. Does periconceptional multivitamin use reduce the risk for limb deficiency in offspring? Epidemiology
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Czeizel AE. Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. Am J Med Genet 1996;62(2):17983.
Khoury MJ, Shaw GM, Moore CA, Lammer EJ, Mulinare J. Does periconceptional multivitamin use reduce the risk of neural tube defects associated
with other birth defects? data from two population-based case-control studies. Am J Med Genet 1996;61(1):30-6.
Hayes C, Werler MM, Willett WC, Mitchell AA. Case-control study of periconceptional folic acid supplementation and oral clefts. Am J Epidemiol
1996;143(12):1229-34.
Shaw GM, O'Malley CD, Wasserman CR, Tolarova MM, Lammer EJ. Maternal periconceptional use of multivitamins and reduced risk for conotruncal
heart defects and limb deficiencies among offspring. Am J Med Genet 1995;59(4):536-45.
Tolarova M, Harris J. Reduced recurrence of orofacial clefts after periconceptional supplementation with high-dose folic acid and multivitamins.
Teratology 1995;51(2):71-8.
Shaw GM, Lammer EJ, Wasserman CR, O'Malley CD, Tolarova MM. Risks of orofacial clefts in children born to women using multivitamins containing
folic acid periconceptionally. Lancet 1995;346(8972):393-6.
Li DK, Daling JR, Mueller BA, Hickok DE, Fantel AG, Weiss NS. Periconceptional multivitamin use in relation to the risk of congenital urinary tract
anomalies. Epidemiology 1995;6(3):212-8.
Czeizel AE, Dudas I, Metneki J. Pregnancy outcomes in a randomised controlled trial of periconceptional multivitamin supplementation. Final report.
Arch Gynecol Obstet 1994;255(3):131-9.
Czeizel AE, Metneki J, Dudas I. The higher rate of multiple births after periconceptional multivitamin supplementation: an analysis of causes. Acta
Genet Med Gemellol (Roma) 1994;43(3-4):175-84.
Czeizel AE. Prevention of congenital abnormalities by periconceptional multivitamin supplementation. BMJ 1993;306(6893):1645-8.
Werler MM, Shapiro S, Mitchell AA. Periconceptional folic acid exposure and risk of occurrent neural tube defects. JAMA 1993;269(10):1257-61.
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1992;327(26):1832-5.
Kirke PN, Daly LE, Elwood JH. A randomised trial of low dose folic acid to prevent neural tube defects. The Irish Vitamin Study Group. Arch Dis Child
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1991;338(8760):131-7.
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Emp 1946;53(6):498-509.
149
Table 5. Sub-groups
Intervention
Author, design and
year study
Outcome
Quality
Preconception dietary and
lifestyle counselling
 At the first visit, the filled
out questionnaires were
checked by the counsellor
and discussed in detail for
tailored dietary and lifestyle
advice; height and weight
were measured to calculate
BMI; waist-hip circumference
and blood pressure were
measured; venous blood
samples were drawn to
measure red blood cell folate
and plasma total
homocysteine; during the
second visit the same
questionnaire was filled out
to measure differences in
lifestyle compared to the first
visit
Preconceptional smoking
cessation program
 Evaluation of the impact
of smoking cessation advice
given before pregnancy on
smoking behaviour to both
women and their partners; 12
months follow- up
Hammiche et al,
20111
Prospective cohort
2007-2009
Most couples were subfertile (93.8%)
A subgroup of 419 couples was counselled twice (n=110 couples)
II-2
de Weerd et al.
20012
Cohort study
Timeframe: unclear
In a cohort of 111 women followed over a 1-year time period, 16 women reported smoking, whereas 24 were identified as
smokers (serum cotinine >5µg/L, 33% underreporting)
Differences at the second counselling:
- Intake of fruit: increased from 65 to 80% in women vs. 49 to 68% in men
- Recommended intake of fish: increased from 39 to 52% in women
- Median Preconception Dietary Risk (PDR score based on six Dutch dietary guidelines) decreased: Women: 2.6 (95% CI
2.4-2.9) to 2.4 (95% CI 2.1-2.6); Men: 2.5 (95% CI 2.3-2.7) to 2.2 (95% CI 1.9-2.4); both p<0.05)
- Median Rotterdam Reproduction Risk score (R3 score) decreased:
Women: 4.7 (95% CI 4.3-5.0) to 3.1 (95% CI 2.8-3.4); Men: 3.0 (95% CI 2.8-3.3) to 2.0 (95% CI 1.7-2.3); both p<0.01) due to
less alcohol use (-14.6%), more physical exercise and folic acid use in women, and less alcohol use in men (-19.4%) (all
p<0.01)
- Low educated women appeared to show a larger reduction in R3 score than better educated women and men with a
normal BMI showed a larger reduction than overweight men
II-2
20 men admitted smoking habits versus 36 men identified as smokers via serum cotinine assay (44% underreporting)
Women: serum cotinine decreased significantly after intervention (from 214 µg/L to 99 µg/L; p=0.016), but none of the
women stopped smoking. 75% of cotinine-validated smokers and 88% of self-reported smokers reduced smoking after the
preconception counselling intervention
Men: neither reduced nor stopped smoking
150
Smoking was confirmed by
serum cotinine assay and
also paternal smoking
behaviour was assessed
Smoking cessation in infertile
women
 3-5 minute scripted
intervention advice and
booklet vs. standard of care
to assess a ‘stage-of-change’
Hughes et al, 20003
RCT
1996-1999
The effectiveness of Heparin
plus Aspirine as a single
therapy on the pregnancy
success rate in patients with
recurrent spontaneous
abortion.
 Aspirin 100 mg/d from day
1 of the menstrual cycle to 2
wk before the delivery date
 Aspirine injections of
5.000 units/mL; on day +
postovulation, 5.000 units at
12-hr intervals
Cavadid et al. 19994
Prospective clinical
trail
1993-1997
Infertile women at their first visit to a tertiary referral infertility clinic (n=47 intervention; n=47 control) and new patients
seeking pre-natal care (n=56 intervention; n=54 control) who had smoked ≥3 cigarettes in the past six months. Exhaled
carbon-monoxide (CO) monitoring was used to validate exposure in both groups
I-a
Infertile women:
Intervention and control were similarly effective: the rate of maintained cessation rose significantly from 4% to 24% over
twelve months
8 patients associated with allo- and autoimmunity, treated with a complete therapy: pregnancy success was (6/8) 75%
II-2
11 patients associated with allo- and autoimmunity, treated with a single therapy:
pregnancy success was (10/11) 90,9%
151
References
1.
2.
3.
4.
Hammiche F, Laven JS, van Mil N, et al. Tailored preconceptional dietary and lifestyle counselling in a tertiary outpatient clinic in The Netherlands.
Hum Reprod 2011;26(9):2432-41.
de Weerd S, Thomas CM, Cikot RJ, Steegers EA. Maternal smoking cessation intervention: targeting women and their partners before pregnancy. Am
J Public Health 2001;91(11):1733-4.
Hughes EG, Lamont DA, Beecroft ML, Wilson DM, Brennan BG, Rice SC. Randomized trial of a "stage-of-change" oriented smoking cessation
intervention in infertile and pregnant women. Fertil Steril 2000;74(3):498-503.
Cadavid A, Pena B, Garcia G, et al. Heparin plus aspirin as a "single" therapy for recurrent spontaneous abortion associated with both allo- and
autoimmunity. Am J Reprod Immunol 1999;41(4):271-8.
152
V. Risk assessment in preconception care
Jacoba van der Kooy, Rachel Bakker, Sabine F. van Voorst, Chantal Quispel, Jashvant V.V. Poeran,
Semiha Denktaş, Eric A.P. Steegers
The preconceptional period provides opportunity for well-timed risk assessment. In The
Netherlands, one of the main recommendations from the Dutch Health Council regarding
preconception care is to implement evidence based instruments for preconception risk
assessment. Yet, there are only a few evidence-based standardised risk assessment
instruments available.
In this chapter, risk assessment tools for preconception care, identified by an electronic
literature search, are decribed. The instruments are subdivided into the following categories:
questionnaires or checklists, physical examinations, laboratory tests, and complementary
tests.
Methods
The study identification and selection process is summarized in Figure 1. An electronic
search in PubMed was performed to identify new evidence on the preconception risk
assessment instruments. The exact search command is given in Appendix 1. Key words
were extracts of ‘preconception care’ or ‘interconception care’. Search criteria were:
published from January 1, 2008 until December 22, 2011 and no animal studies.
Three reviewers (JK, CQ, and JP) assessed eligibility of identified articles based on title and
abstract. This selection was performed according to predefined criteria; the study assessed
risk factors in the preconception or interconception period, the study examined a
standardized risk assessment instrument, and the article was written in English.
The electronic search resulted in 773 articles. Based on screening by title and abstract 737
non eligible articles were excluded. After screening the remaining articles, 30 full text articles
were excluded for the same reasons as stated above. The remaining 6 articles were included
for analyses.
Risk assessment by questionnaires or checklists
One method to assess preconceptional risks is by self-reported questionnaires or checklists,
filled out at home. An advantage of completing a questionnaire or checklist at home is the
opportunity to attain information from family members in case of a possible complicated
family history.1 The main disadvantage pertains to the sometimes inevitable use of medical
153
terms in checklists, which might lead to incorrect answers due to misunderstandings.1 An
overview of preconception risk assessment instruments is given in Table 1.
An often used preconception care risk assessment instrument used in The Netherlands is the
Preconception Health Assessment form which was originally developed by Cefalo et al.2 De
Weerd and colleagues translated the risk assessment instrument into Dutch and validated
the instrument in a preconceptionally recruited cohort of Dutch women.3 The authors state
that the questions on the form provide an accurate risk assessment tool for preconceptional
risk factors and thus they advocated implementation in various settings to facilitate the
provision of preconception care.3
In the Netherlands one other uniform risk assessment instrument is being repeatedly used,
validated and nationally implemented: ZwangerWijzer.3-4, 5 ZwangerWijzer is based on the
Preconception Health Assessment. It is a risk assessment instrument to identify medical,
genetic, environmental, nutritional, and lifestyle risk factors to be used by couples planning
pregnancy. The identification of risk factors results in recommendations and referral to a
midwife, general practitioner or obstetrician. The Erasmus Medical Center, together with the
Dutch National Genetic Resource and Information Center, developed www.ZwangerWijzer.nl
for the general public (couples having a pregnancy wish). With ZwangerWijzer risk factors
can be easily identified and comprehensive information can be provided. This website is very
successful with 400 to 500 serious visitors per day. Many health care professionals,
obstetricians and midwives, use this site – recommended by the Foundation and Dutch
Working Group on Preconception Care Netherlands - in providing preconception care.
PreconceptieWijzer (www.PreconceptieWijzer.nl) is an instrument developed for health care
providers to be used together with ZwangerWijzer. Individual risks of a couple identified in
ZwangerWijzer can be linked to protocols regarding preconception advice and subsequently
lead to suggestions for referral patterns for specialist individual preconception care in case of
high risks. In this way preconception care can be offered in a structured, protocolized way as
part of chain care.
In 2007, the Department of Obstetrics and Gynaecology of the Erasmus Medical Center in
Rotterdam initiated the preconception outpatient clinic “Achieving a Healthy Pregnancy” (in
Dutch: Gezond Zwanger Worden Spreekuur) for preconception counseling tailored on
nutrition and lifestyle to patient-couples and employees. They showed the feasibility of this
outpatient clinic in a tertiary center in subfertile couples. The Rotterdam Reproduction Risk
score directed on lifestyle behaviors and the Preconception Dietary Risk score (PDR> score)
are used as risk assessment instruments. It revealed that 3 months after counseling an
154
overall 30% decrease in unhealthy lifestyle behaviours and a significant increase of fruit
intake in couples and fish intake in women was established.
Further analyses found that especially women with low education benefit most from
preconception counseling. More than 85% women and men found the counseling useful and
around 70% would recommend it to others.6
Furthermore, a personal coaching program of 26 weeks on the mobile phone tailored on
improvement of nutrition and lifestyle to be used by couples before and during pregnancy
was developed by the Erasmus Medical Center. This program, in Dutch: Slimmer Zwanger,
consists of a website in combination with text messages and email messages, through which
personal support is given at any time, at any place and at very low costs. The screenings
module on nutrition and lifestyle can be used in preconception care by health care providers.7
A promising new instrument which could be used as a preconception care instrument is the
so called GyPsy digital screen-and-advice tool. This instrument screens for psychopathology
and psychosocial problems before conception and has previously been validated among
urban pregnant women.8
Another example of a risk assessment instrument is reported by Livingood et al. The authors
assessed the effect of social determinants, as part of a multiple determinants model of preand interconception care, on birth outcomes. The subsequently developed program showed
promising results related to reducing infant mortality and reducing other high-risk factors of
poor birth outcomes, including low birth weight and the risk of sexually transmitted diseases.
They concluded that social determinant interventions, designed to mitigate the impact of
social class and stress, should be considered with efforts to reduce infant mortality,
particularly the disparities associated with infant mortality.9
Some instruments may be used in practice; however, not been published in scientific
literature. Therefore, we searched on the internet and contacted different organisations
known to work within the preconception care field. We could not find any information on
available instruments used by the following organisations; Los Angeles Mommy and Baby
Project, March of Dimes, and Every Woman California. Furthermore, we could confirm that
no instruments are used by the Centers for Disease Control and Prevention (CDC), and the
Colorado project.
155
Table 1. An overview of preconception risk assessments instruments
Instruments
Valid
Part of
instrument
routine
care
Preconception
Yes
No
ZwangerWijzer4
Partly
Yes
PreconceptieWijzer
Partly
Preconception
Risk domains
Lifestyle
Medical
Psychiatric
conditions
conditions
Nutrition
X
X
X
X
X
Yes
X
X
X
Partly
Yes
X
X
Slimmer Zwanger7
Partly
Noy
X
X
Gypsy8
Yes
No
X
A multiple
Yes
No
Environmental
Social
exposure
environment
X
Medication
Obstetric
Family
history
history
X
X
X
X
X
X
X
X
Health Assessment3
Dietary Risk score
(PDR score)6
X
X
X
X
X
X
determinants model
of pre- and interconception care9
156
Risk assessment by physical examinations, laboratory tests and complementary tests
The aims of clinical testing in preconception care are to identify risk factors and to specify the
magnitude of the risks that require intervention. Part of preconception care overlaps routine
care, therefore diagnostic testing is not specifically different in the preconceptional practice.
A summary of available physical examinations, laboratory tests and complementary tests is
given in Table 2.
Table 2. Summary of existing diagnostic tests (physical, laboratory, and
complementary) per risk factor listed in the risk domains
Risk domain
Risk factor
History
Physical
examinations
Laboratory tests
Complementary
tests
Family planning
and reproductive
life plan
Short or long
interpregnancy
intervals
Self-report,
medical record
-
-
-
Physical activity
Physical
inactivity
Self-report
-
-
-
Weight status
BMI>30 kg/m2
BMI<18.5 kg/m2
-
Body mass
index
-
-
Maternal HPV
infection
History of HPV
infection of
immunisation
Visual
examination
(presence of
genital warts on
the cervix
vagina and
vulva).
Microbiologic
testing in
conjunction to
cytological
screening of the
cervix
-
Hepatitis B
Maternal
Hepatitis B
History of Hepatitis
B infection
-
Serum antibody
and antigen testing
-
Varicella
Maternal lack of
immunity to
varicella
History of previous
infection is
associated with
likely immunity 10
-
Testing of
immunity: varicella
IgG and IgM
antibody tests
-
Measles, mumps
and rubella
(MMR)
Lack of
immunity or
recent
vaccination to
measles,
mumps or
rubella
History of
immunisation
-
Serologic testing of
immunity (specific
antigen based
tests)
-
Influenza
Non
immunisation
status in times
of influenza
History of
immunisation
-
-
-
Diphteria-tetanus-
Lack of
History of
-
Serologic testing of
-
Lifestyle
Immunization
Human
papillomavirus
(HPV)
157
Risk domain
Risk factor
History
Physical
examinations
Laboratory tests
Complementary
tests
pertusis
vaccination
immunity to
Diphteria,
Tetanus or
Pertusis, or a
non updated
tetanus
vaccination
vaccination, last
tetanus
vaccination
HIV
Maternal HIV
infection and
medication
Risks of HIV
infections, known
HIV status.
symptoms
associated with
disease control
Visual
examination
(presence of
rash)
Viral assays (HIV
antibodies, HIV
RNA tests, P24
antigen tests) for
diagnosis and
follow-up (HIV
RNA, CD4 cell
count, complete
blood count (white
and red blood cells,
platelets)11
-
Hepatitis C
Maternal
hepatitis C
infection
Symptoms
associated with
disease control,
risks of Hepatitis C
infection
-
Anti-HCV and HCV
RNA for diagnosis
and follow-up
-
Tuberculosis
Maternal
tuberculosis
Risk assessment
of exposition to
tuberculosis
-
Toxoplasmosis
Lack of
immunity to
toxoplasma
gondii or with
congenital
toxoplas-mosis
Known (possible)
exposures to
toxoplasmosis
gondii
-
Toxoplasmosis IgG
and IgM antibodies
-
Cytomegalovirus
Risk of CMV
infection during
pregnancy in
women without
immunity to
CMV
Risk of exposure
during eventual
pregnancy, known
infection in the
past.
-
CMV IgG and IgM
antibodies
-
Risk of CMV
infection during
pregnancy in
women without
immunity to
CMV
Risk of exposure
during pregnancy,
known infection in
the past
-
Parvo B19 IgG and
IgM antibodies
-
immunization
status (antigen
based tests)
Infections
(CMV)
Parvovirus
Sputum
examination (Ziehl
Neelsen stain),
Mantoux test,
Serologic testing
(interon γ release
essays,
QuantiFeron-TB)
X-ray examination
158
Risk domain
Risk factor
History
Physical
examinations
Laboratory tests
Complementary
tests
Malaria
Maternal malaria
Risk assessment:
visit to an endemic
area
-
-
Gonorrhea
Maternal
gonorrhea
History of sexual
transmitted
infections (STI’s)
or risk factors for
STI’s (symptoms,
sexual behaviour,
promiscuity)
-
Microscopy, blood
tests: malaria
antigen tests
Microbiological
tests: (culture or
PCR) from
cervical swabs/
urine samples
Chlamydia
Maternal
Chlamydia
infection
History of STI’s or
riskfactors for STI’s
(symptoms, sexual
behaviour,
promiscuity)
-
Syphilis
Maternal
Syphilis infection
(latent, primary
or secondary
stage)
Symptoms, risk of
contracting
syphilis. Known
treatment in the
past
Genital
inspection,
inspection of
the skin (rash,
mucocutaneous
lesions,
lympheadenopa
thy) neurologic
examination
serologic testing
(treponemal and
non treponemal
tests)
-
Herpes simplex
virus
Primary or
reoccurring
herpes simplex
infection in
pregnancy
Primary genital
infection with HSV
in the past
Genital
inspection
Culture of the
vesicle, serologic
testing (primary
HSV in the past or
not)
-
Asymptomatic
bacteriuria
Asymptomatic
bacteriruria or
maternal
pyelonephritis in
pregnancy
-
-
Urine culture or
less specific:
dipstick testing,
microscopy
-
Periodontal
disease
Periodontal
infections in
pregnancy
Symptoms
Oral inspection
-
-
Bacterial
vaginosis
Bacterial
vaginosis in
pregnancy
Symptoms
Evaluation of
fluor vaginalis
Amsel criteria
(inspection, KOH
specimen +
microscopy) or
Nugent criteria
(cervical swab)
-
GBS
GBS
colonisation of
the urogenital
tract
Known GBS
colonisation,
especially a history
of neonatal GBS
sepsis after prior
delivery
-
Culture (perianal
and urine sample)
-
-
Microbiological
tests: (culture or
PCR) from
cervical swabs/
urine samples
159
Risk domain
Risk factor
History
Physical
examinations
Laboratory tests
Complementary
tests
Diabetes Mellitus
Diabetes
Mellitus:
inadequate
glycaemic
control
History of
diabetes, use of
medication and
reported
compliance
-
HbA1c, glucose
test
-
Thyroid disease
Maternal thyroid
disease
(hyperthyroidism
and (subclinical)
hypothyroidism
medication use
and inadequate
disease control
Symptoms of
thyroid disease,
compliance with
medication
Blood testing: TSH
and Ft4,TSH
receptor antibodies
-
Phenylketonuria
Maternal PKU
History of PKU
-
Blood
phenylalanine
-
Seizure disorders
Risk of seizures
in pregnancy
due to
inadequate
treatment and
riks of
associated
medication
Evaluation of
medication
regimen,
compliance and
control of seizures
-
Evaluation of
therapeutic levels
of medication on
indication
-
Hypertension
Maternal
hypertension
Medicational
compliance
Blood pressure
-
-
Rheumatoid
arthritis
Maternal
Rheumatoid
arthritis and risk
of associated
medication
Evaluation of
disease control
and medication
use
Evaluation of
flares of arthritis
Markers of disease
activity (on
indication; such as:
erythrocyte
sedimentation rate,
C-reactive protein,
Rheumatic Factor
-
Systemic lupus
erythematosus
(SLE
Maternal
Systemic lupus
erythematosus;
inadequate
disease control
and renal
function
Evaluation of
disease control
-
Erythrocyte
sedimentation rate,
Anti Ro/La, aPLs,
renal status
(creatinine)11
-
Chronic renal
disease
Reduced kidney
function with or
without possible
coexisting renal
hypertension
due to chronic
maternal renal
disease and
medication use
Evaluation of
disease control
Blood pressure
Serum creatinine
-
Cardiovascular
disease
Cardiovascular
disease in
Evaluation of
disease control
Cardiologic
physical
Specific laboratory
testing may be
Echocardiography,
or other diagnostic
Medical conditions
Inspection (dry
skin,
exopthalmus,
enlarged
thyroid),
palpation of the
thyroid
(PKU)
160
Risk domain
Risk factor
History
pregnancy and
possible risks of
associated
medication
Physical
examinations
examination
Laboratory tests
necessary
Complementary
tests
testing may be
necessary
Thrombophilia
Known
thrombophilia or
thrombophilic
events in the
past
Medical history or
family history of
thrombophilia or a
thrombophilic
event (pulmonary
embolisms or deep
venous
thrombosis,
recurrent
pregnancy loss,
preeclampsia,
Intrauterine growth
restriction,
placental
abruption)12
-
Factor V Leiden,
prothrombin
mutation,
antithrombin III
deficiency,
hyperhomocystine
mia, protein C
deficiency, protein
S deficiency, lupus
anticoagulants 12
-
Asthma
Maternal asthma
and disease
control, asthma
medication
Evaluation of
disease control
and medication
use
-
-
Spirometry
Psychiatric conditions
Depression and
anxiety disorders
History of or prepregnancy
depression and
anxiety
disorders; risks
of associated
medication use
Evaluation of
disease state,
psychiatric
assessment and
evaluation of
medication
Psychiatric
assessment
Applicable in some
cases (evaluation
of medication use)
-
Bipolar disorder
Maternal bipolar
disorder and
risks of
associated
medication use.
Evaluation of
disease state,
psychiatric
evaluation,
Evaluation of
medication
Psychiatric
assessment
Applicable in some
cases (evaluation
of medication use)
-
Schizophrenia
Maternal
schizophrenia
and risks of
associated
medication use.
Evaluation of
disease state,
psychiatric
evaluation,
evaluation of
medication
Psychiatric
assessment
Applicable in some
cases (evaluation
of medication use)
-
161
Risk domain
Risk factor
History
Physical
examinations
Laboratory tests
Complementary
tests
Alcohol
Maternal alcohol
consumption
Self-report and
screening tests for
heavy drinkers
(egDSM criteria, TACE, CAGE,
AUDIT, 5 shot)13
Acute signs of
intoxication
Laboratory tests
are available for
heavy drinkers
(γGT, MCV, ASAT,
ALAT, CDT,
%CDT, uric acid,
FAEE, EtG e.g.)
but have limited
value in clinical
practice. 13
-
Tobacco
Maternal
smoking or
secondary
smoking
Self-report of use
-
Laboratory tests
(carbon monoxide,
nicotine, cotinine,
thiocyanate)14 not
used in clinical
practice
-
Illicit substances
Cocaine,
Marijuana,
Heroin, other
illicit substances
Self-report of use
-
Specific
toxicological
screening tests are
available
-
General
population
History of the
couple and both
sides of their
family; including:
medical diseases,
obstetric history,
genetic disorders,
congenital defects,
developmental
delay/ mental
retardation, and
ethnicity.15
-
-
-
Cystic fibrosis
carrier ship
Family history
-
DNA testing of the
CFTR gene16-17
-
MHTFR
polymorphisms
Previous
examinations or
family history
-
MTHFR DNA test
-
Ethnicity or family
history
-
RBC count, iron
indices,
hemoglobin
electrophoresis15
-
White/ European
Ethnicity or family
history
-
-
Ashkenazi
Jewish
Ethnicity or family
history
-
Cystic fibrosis:
CFTR gene test
Canavan disease:
ASPA gene test,
familial
dysautonomia:
Parental exposures
Genetic diseases
All individuals
Ethnicity based
Asian:
thalessemia
-
162
Risk domain
Risk factor
History
Physical
examinations
Laboratory tests
Complementary
tests
IKBAP gene test,
Tay Sachs disease:
hexosaminidase-A
test or of Hexa
gene test,
Gaucher’s disease:
GBA gene,
Niemann-Pick
disease Type A:
SMPD1 gene test,
Bloom Syndrome:
BLM gene test,
Mucolipidosis IV:
MCOLN1 gene
test, Fanconi
anemia Group C:
FANCC gene test
15
French
Canadian
Ethnicity or family
history
-
Tay Sachs disease:
hexosaminidase-A
test or of Hexa
gene test15
-
African
Ethnicity, history,
or family history of
thalessemia
-
RBC count, iron
indices,
hemoglobin
electrophoresis15
-
Mediterranean
Ethnicity, history or
family history
-
RBC count, iron
indices,
hemoglobin
electrophoresis15,
-
18-19
Cajun
Ethnicity or family
history
-
Tay Sachs disease:
hexosaminidase-A
test or of Hexa
gene test15
-
Previous
pregnancies
Recurrent
miscarriage
Obstetric history,
family history
-
Karyotyping,
thrombophilia
tests15
-
Known Genetic
conditions
Maternal or
paternal genetic
condition
Self-report,
medical history
-
Specific test and
availability vary
with the type of
genetic disease15
-
Maternal vitamin
A intake above
daily
recommended
intake
Self-report of
dietary intake and
use of medication
or supplements
containing vitamin
A.
-
Serologic vitamin A
levels can be
evaluated; there is
no place in clinical
practice for this
however.
-
Nutrition
Vitamin A
163
Risk domain
Risk factor
History
Physical
examinations
Laboratory tests
Complementary
tests
Folic acid
Folate intake by
nutrition and
supplements
Nutritional intake
of folate (or if
applicable intake
of fortified food),
use of
supplements
-
Folate can be
measured in serum
(reflection of short
term intake) or in
the erythrocytes
(reflecting long
term intake)
-
Multivitamins
Insufficient
intake of vitamin
supplements
Compliance to
multivitamins
-
Laboratory tests
are available for
each vitamin (see
other vitamins
enlisted)
-
Vitamin D
Maternal vitamin
D deficiency
Symptoms an risk
factors for
deficiency
Skin colour
Blood test: 25-OH
vitamin D3
(Calcidiol)
-
Vitamin B12
Maternal vitamin
B12 deficiency
Symptoms,
evaluation of
nutritional intake,
history of anemia
or vitamin B12
deficiency
-
Cobalamin blood
test
-
Vitamin E
High maternal
vitamin E intake
Evaluation of
nutritional intake
and supplements
and adherence to
daily
recommendations
-
Vitamin E blood
test (although this
is not routine in
clinical practice)
-
Obesity
Maternal BMI
>30 kg/m2
-
Body mass
index
-
-
Underweight
Maternal BMI
<18,5 kg/m2
-
Body mass
index
-
-
Eating disorders
Maternal eating
disorders
(anorexia or
boulimia)
Evaluation of
disease control, or
DSM criteria for
evaluation of not
yet diagnosed
eating disorders
Psychiatric
evaluation
-
-
Environmental exposure
Environmental
exposures
Maternal
exposure to
environmental
hazards
History of
environmental
exposures
-
Tests can provide
information on
certain elements;
although this can
be difficult
-
Workplace
exposures
Maternal
exposure to
hazardous
substances at
the workplace
History of
occupations and
known exposures
-
-
-
164
Risk domain
Risk factor
History
Physical
examinations
Laboratory tests
Complementary
tests
Household
exposures
Maternal
exposure to
hazardous
household
substances
Exposure to
solvents in paints,
pesticides,
herbicides,
soldering of metals
etc. 20
-
-
-
Questions
regarding use or
need of benefits or
economic help
household income,
debts
-
-
-
Financial
resources
Inadequate
financial
resources
165
References
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2.
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4.
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6.
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11.
12.
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17.
18.
19.
20.
American College of Obstetricians, Gynecologists Committee on Genetics. Committee Opinion
No. 478: Family history as a risk assessment tool. Obstet Gynecol. 2011 Mar;117(3):747-50.
Cefalo RC, Bowes WA, Jr., Moos MK. Preconception care: a means of prevention. Baillieres
Clin Obstet Gynaecol. 1995 Sep;9(3):403-16.
de Weerd S, van der Bij AK, Cikot RJ, Braspenning JC, Braat DD, Steegers EA.
Preconception care: a screening tool for health assessment and risk detection. Prev Med.
2002 May;34(5):505-11.
Landkroon AP, de Weerd S, van Vliet-Lachotzki E, Steegers EA. Validation of an internet
questionnaire for risk assessment in preconception care. Public Health Genomics.
2010;13(2):89-94.
de Weerd S, Steegers EA. The past and present practices and continuing controversies of
preconception care. Community Genet. 2002;5(1):50-60.
Hammiche F, Laven JS, van Mil N, de Cock M, de Vries JH, Lindemans J, et al. Tailored
preconceptional dietary and lifestyle counselling in a tertiary outpatient clinic in The
Netherlands. Hum Reprod. 2011 Sep;26(9):2432-41.
Website. www.slimmerzwanger.nl. In Dutch.
Quispel C, Bonsel, G.J., et al. . An innovative screen-and-advice model for psychopathology
and psychosocial problems among urban pregnant women. . J Psychosom Obstet Gynecol.
2012 (in press). .
Livingood WC, Brady C, Pierce K, Atrash H, Hou T, Bryant T, 3rd. Impact of pre-conception
health care: evaluation of a social determinants focused intervention. Matern Child Health J.
2010 May;14(3):382-91.
Coonrod DV, Jack BW, Boggess KA, Long R, Conry JA, Cox SN, et al. The clinical content of
preconception care: immunizations as part of preconception care. Am J Obstet Gynecol. 2008
Dec;199(6 Suppl 2):S290-5.
Nelson-Piercy. Handbook of Obstetric Medicine. . New York: Informa Health Care.; 2010.
Dunlop AL, Jack BW, Bottalico JN, Lu MC, James A, Shellhaas CS, et al. The clinical content
of preconception care: women with chronic medical conditions. Am J Obstet Gynecol. 2008
Dec;199(6 Suppl 2):S310-27.
Aertgeerts B, Buntinx F, Ansoms S, Fevery J. Screening properties of questionnaires and
laboratory tests for the detection of alcohol abuse or dependence in a general practice
population. Br J Gen Pract. 2001 Mar;51(464):206-17.
Jarvis MJ, Tunstall-Pedoe H, Feyerabend C, Vesey C, Saloojee Y. Comparison of tests used
to distinguish smokers from nonsmokers. Am J Public Health. 1987 Nov;77(11):1435-8.
Solomon BD, Jack BW, Feero WG. The clinical content of preconception care: genetics and
genomics. Am J Obstet Gynecol. 2008 Dec;199(6 Suppl 2):S340-4.
Christie LM, Ingrey AJ, Turner GM, Proos AL, Watts GE. Outcomes of a cystic fibrosis carrier
testing clinic for couples. Med J Aust. 2009 Nov 2;191(9):499-501.
Massie J, Petrou V, Forbes R, Curnow L, Ioannou L, Dusart D, et al. Population-based carrier
screening for cystic fibrosis in Victoria: the first three years experience. Aust N Z J Obstet
Gynaecol. 2009 Oct;49(5):484-9.
Lakeman P, Plass AM, Henneman L, Bezemer PD, Cornel MC, ten Kate LP.
Three-month follow-up of Western and non-Western participants in a study on preconceptional
ancestry-based carrier couple screening for cystic fibrosis and hemoglobinopathies in the
Netherlands. Genet Med. 2008 Nov;10(11):820-30.
Lakeman P, Plass AM, Henneman L, Bezemer PD, Cornel MC, ten Kate LP. Preconceptional
ancestry-based carrier couple screening for cystic fibrosis and haemoglobinopathies: what
determines the intention to participate or not and actual participation? Eur J Hum Genet. 2009
Aug;17(8):999-1009.
McDiarmid MA, Gardiner PM, Jack BW. The clinical content of preconception care:
environmental exposures. Am J Obstet Gynecol. 2008 Dec;199(6 Suppl 2):S357-61.
166
APPENDIX 1. Full search command
(preconception*[tw] OR pre-conception*[tw] OR prepregnan*[tw] OR
pre-pregnan*[tw] OR pregestation*[tw] OR pre-gestation*[tw] OR
periconception*[tw] OR peri-conception*[tw] OR interconception*[tw] OR
inter-conception*[tw] OR interpregnan*[tw] OR inter-pregnan*[tw] OR
intergestation*[tw] OR inter-gestation*[tw] OR internatal*[tw] OR
inter-natal*[tw]) NOT (animals NOT humans) AND 2008:2012[dp])
AND Diagnostic Techniques and Procedures"
167
FIGURE 1. Flowchart study identification and selection process
168
VI. Overall benefits of preconception care in terms of public health
Marijana Vujkovic, Semiha Denktaş, Eric A.P. Steegers, Rachel Bakker, Gouke J. Bonsel
As a health theme, reproductive health has an important role on the public health services
agenda. Within the domain of reproductive health the focus has been mainly on prenatal
initiatives; however, recently also the preconception period is acknowledged as an important
phase within the reproductive chain.1-3 Preconception care provided by public health services
is focused on primary prevention at a collective level.4 This chapter describes the benefits of
preconception care on a public health level.
History
Since the 1990s, public campaigns have been carried out in European countries in order to
raise awareness about the use of folic-acid supplementation.5 Despite campaigns to promote
folic acid supplementation, the number of women who take folic acid supplements in the
recommended timeframe - the preconception period until the tenth week of gestation - has
remained relatively low.6-7 In 1995 and in 2004, a public awareness campaign to promote
folic acid use was launched in the Netherlands. Dutch pharmacies started proactively
informing and motivating women to use oral contraceptives to start taking folic acid
supplements before conception. An increase in folic acid uptake was not achieved and
remained low.7-10 It was estimated that approximately 36% of women in the reproductive age
use folic acid supplements, despite the high percentage, about 80%, of planned pregnancies
among the native Dutch population.11
Nowadays, the focus of preconception care has extended to several other domains including
conscious family planning, prevention of sexual transmitted diseases, prevention of tobacco
and drug use, optimising psychosocial health, provision of sexual education, and prevention
of domestic violence and sexual abuse.2 Public health services worldwide increased their
efforts in collective preventive measures, such as cigarette package labelling for preventing
low birth weight singletons12 and food supply folic acid fortification to reduce the risk of neural
tube defects in the offspring.13 Furthermore, their role in surveillance by collecting data on the
prevalence of key indicators has been increased over the last years.14-15
Public health perspectives
Many public health perspectives are relevant in preconception care. First, public health
services are increasingly aware that obesity and nutrition have, besides their effect on the
general population, also clear extensions in the reproductive domain. Initiatives to prevent
169
obesity and poor nutritional status may increase health promotion in couples with a
pregnancy wish.16
A second public health perspective focuses on the long-term effects of better reproductive
health, resulting in subsequent better outcomes of the child. Impaired foetal development
and low birth weight have been associated with increased risks of chronic disease later in
life.17 Conventional outcomes such as perinatal mortality and morbidity are gradually
extended to outcomes in childhood, including psychosocial development and obesity.18-20
Additionally, also more long term outcomes including the development of the metabolic
syndrome, psychopathological disturbances, and cardiovascular consequences are being
recognised.21-24 Long-term consequences for the offspring are in particular importance for
newborns with severe conditions at delivery (prematurity, congenital anomalies, and low birth
weight), since survival of these newborn has improved considerably in the last decade. Given
the non-trivial prevalence of perinatal morbidity, public health epidemiology shows more
interest in the long-term consequences of early preventive efforts, including preconception
care.
The remainder of this chapter will focus in more detail on a third public health perspective,
namely maternal health effects, parallel to the intended reproductive health effects.25-26 The
improvement of reproductive outcome is often a consequence of improved maternal health.
When women in the reproductive age have for example a proper body weight and a
balanced nutritional state, their own health will improve as well. Some distinct beneficial
preconception interventions like folic acid supplementation lack clear-cut benefits for
maternal health.
We have listed nine domains of preconception care in Table 1. For each domain, we
included the most important target items with expected maternal health benefits. We
described the consequences of the diseases mentioned in the table. If preconception care is
successful, such consequences might be avoided to some degree or even completely. The
column 'Overall' provides an indication of possible effectiveness of targeting a particular
preconception care item on the subsequent maternal health conditions. In this manner, Table
1 emphasises the most important maternal benefits for public health initiatives.
If these effects translate into increased mortality and severe morbidity on the individual level,
this is summarized in the columns with the headings 'Mortality' and 'Morbidity'. An ‘A’ refers
to potential presence of mild or moderate benefits, ‘B' refers to potential presence of strong
benefits, and ‘C’ refers to the absence of such benefits.
170
171
Table 1. Preconception care target items of public health and maternal health benefits
PRECONCEPTION CARE
MATERNAL HEALTH BENEFITS
Domains
Target items
Overall* Mortality** Morbidity** Consequences, symptoms and inconviences
1.
2.
3.
4.
5.
6.
7.
Family planning and
reproductive life plan
Substance use
Micronutrient intake
Energy intake
Physical activity
Infectious diseases
- Pregnancy intention
+
C
A
- prevention social abortions, teenage pregnancy
- Inadequate financial resources
- Intimate partner violence, sexual
violence, and childhood
maltreatment27-28
- Tobacco use29-30
+
A
A
++
B
B
- general socio-economic ill-health effect
- physical, mental, sexual disorder
++
B
B
- Cannabis
- Opiate like drugs31
- Alcohol abuse32-34
+
+
+
C
B
A
A
B
B
Hypovitaminosis
- Vitamin D
+
C
A
- Vitamin B1235
- Vitamin E
- Folate levels
Hypervitaminosis
- Vitamin A
+
-
C
C
C
B
A
C
- osteoporosis, bone disease osteomalacia, muscle functioning
- anaemia, neuropsychiatric disorders
- rare disease: blindness, cardiovascular disease, nerve damage,
cognitive dysfunction
--
+
C
A
- liver problems
- Obesity36
++
B
B
- Underweight
- Eating disorders
+
+
C
A
B
B
- Physical inactivity
- HIV37
- Hepatitis B
- Hepatitis C37
- Tuberculosis37
- Toxoplasmosis37
- Cytomegalovirus-virus (CMV)37
- Parvovirus37
+
++
++
++
++
-
C
B
B
B
B
C
C
C
C
B
B
B
B
A
A
A
- diabetes mellitus, hypertension, infertility, cardiovascular disease,
several cancers
- nutrient deficiencies, osteoporosis, dysmenorrhea, infertility
- psychiatric episodes, nutritional, metabolic, endocrine,
psychological problems
- weight stability, mood disorders
- reduction of viral load, disease progression
- prevention of cirrhosis, hepatocellular carcinoma
- chronic liver disease
- lung disease, systemic disease
- mild symptoms
- usually asymptomatic
- arthritis, arthralgia, anaemia
- hypertension, cardiovascular disease, several cancers,
dysmenorrhoea
- mental health problems
- neuropsychiatric disorders, heart failure
- liver disease, neuropsychiatric disorders, cardiovascular disease,
chronic pancreatitis
8.
9.
Sexually transmitted
diseases
Environmental
exposures
- Malaria37
- Asymptomatic bacteriuria37
- Periodontal disease37
- Bacterial vaginosis37
- Varicella
- Measles, mumps and rubella
(MMR)
- Influenza
- Diphtheria-tetanus-pertussis
- Chlamydia37
+
+
+
-
B
C
C
C
C
C
C
C
B
A
A
A
A
A
A
A
- malaria
- acute maternal pyelonephritis
- loss of teeth
- vaginal discharge, pelvic inflammatory disease
- in adults rare complications
- rare symptomatic disease
-- rare in non-immunized adults
+
C
A
- Gonorrhoea37
-
C
A
- subfertility, chronic pelvic pain, pelvic inflammatory disease, eye
disease
- pelvic inflammatory disease, damage to joints and heart valves
- Syphilis37
- Herpes simplex virus37
+
-
A
C
B
A
- Human papillomavirus (HPV)
- Workplace & household exposure
- Noise
- Deprived area
+
+
+
++
A
C
C
C
A
B
A
C
- syphillis local, systemic manifestations
- rare symptomatic disease: hepatitis, encephalitis, pneumonitis,
neurological damage
- genital warts, cervical dysplasia, cancer
- solvents carcinogenic, neurological problems
- loss of hearing
- general ill-health effect
* Indication of possible effectiveness of targeting a particular preconception care item on the subsequent maternal health effects; -: little effect;
+: mild or moderate effect; ++ strong effect.
** Indication of maternal health benefit; A: potential presence of mild or moderate benefit; B: potential presence of strong benefit; C: absence of
such benefit.
Example:
Within the domain 'Family planning and reproductive life plan' we selected the preconception target to strive for positive pregnancy intention
underlying a pregnancy, with avoidance of unplanned unwanted pregnancies. The consequences of an unwanted pregnancy go beyond foetal
disadvantage and are described in the most right column: abortions and teenage pregnancies. The health of teenage pregnant children can be
compromised, and legal and illegal abortion both are causes of health problems and in many cases of risk for the pregnant woman. The
presented rating, only an 'A' at morbidity and a ‘C’ at mortality, obviously represents the state in developed countries where it is possible to
undergo legal abortion for non-medical reasons. However, in some countries there should be a 'B' at morbidity and even an effect indication at
mortality. The resulting rating in the ‘Overall’ column is '+' is reflecting an estimated moderate beneficial effect on the public health level.
173
Beneficial targeting items
In the section below we selected those target items with either '++’ overall effect or a strong
benefit ('B') in terms of mortality or morbidity from Table 1.
Intimate partner violence, sexual violence, and childhood maltreatment
The prevalence of partner violence and sexual violence in developed countries has been
estimated to range between 5-15%, depending on the method of measurement and definition
and thresholds.27 In less develop countries a pevalence as high as 70% has been reported.27
Long-term effects include physical, mental, and sexual disorders.28 Increasing the sensitivity
of health providers in the preconception care to detect these conditions may be an important
strategy to open communication and address gender inequality issues. If appropriate
measures are taken health benefits include better health of the mother.
Tobacco use
Cigarette smoking causes serious health problems, severe diseases, and increases the
mortality risk from many causes.29-30 Smoking also causes an additive risk to the mortality
risk from severe diseases indirectly related to smoking. Quitting smoking reduces the risk for
cancer, cardiovascular disease including hypertension; for some diseases risk lowers
instantaneously.38 Because more benefits are achieved in people who stop smoking at an
earlier age, preconception interventions are an important component of individual and public
health interventions directed at smoking cessation. Many believe, the pregnancy period
offers an excellent window of opportunity.39 In this case, the parental approach (both mother
and father) is essential for effectiveness, adding to health for the father too.
Opiate like drugs
From a theoretical point of view, preconception care offers health benefits to the addicted
woman (and frequently to the addicted father too) as opiate addiction deteriorates health
through direct and indirect mechanisms. With current shift in the pattern of illicit drugs used,
the benefits for the woman change with the risk profile of the particular substance.31 Little is
known on the persisting effect of preconception care in this risk group.
Alcohol abuse
A major difficulty in alcohol abuse is the different risk profile for the mother and the foetus.
From a foetal health point of view, non-use is the single preconception advice which has to
be given.40 From a maternal health point of view, we must acknowledge different subgroups,
including pregnant women, with different health consequences to be anticipated. One glass
of alcohol per day, according to most epidemiological studies does not reflect a specific
174
harm, and may be associated with small health gains at the individual level, yet tangible
health benefits for the population at large.41 For women drinking this amount, the
preconception care advice is to stop drinking. For larger amounts, or in case of an irregular
drinking pattern with occasional excessive consumption, e.g. binge drinking, prevention will
be beneficial to the women's health as alcohol abuse is associated with a wide range of
disadvantages, including liver damage,33 neuropsychiatric disease mediated through
hypovitaminosis,32 mental disorders, and weight problems as alcohol represents high energy
intake.34
Vitamin B12
Vitamin B12 deficiency most commonly occurs in the context of knowledge on risk factors
which are associated with the disorder. It has a heterogeneous background: Helicobacter
pylori infection; however, still inconclusive,42 alcohol abuse,43 vegetarian dietary pattern,44
auto-immune disease45 or gastro-intestinal disease. The symptoms are insidious, but in its
severe form in part irreversible. If discovered by blood testing, the aetiology is a guide to
treatment usually consisting of substitution.46 In diseased persons this represents a
substantial benefit.35
Obesity, underweight and nutritional deficiency
At reproductive age between 30% to 60% of women are obese depending on age and (sub)
population.47 Prevalence strongly depends on socio-economic class and ethnicity; however,
systematic data in pregnant women are unavailable. Being obese increases the risk for type
2 diabetes, cardiovascular disease, musculo-skeletal disorders, and probably some
cancers.36 While being obese in developed countries is priority public health problem, in
underdeveloped countries and in extreme underprivileged groups underweight is also
prevalent. Since overweight is largely preventable, the preconception period is a window of
opportunity as it allows to timely provide an supportive environment for individuals who need
structural guidance towards healthy eating and regular physical activity. In particular, women
from deprived subpopulations may benefit from healthy nutrition, contributing at the same
time to decrease of obesity, and lower prevalence of hypovitaminosis and other symptoms of
undernutrition. Folic acid intake, while being critical for foetal health, is not in the same way
important for maternal health.48
Infectious diseases
The relevance of preconception care for maternal health in infectious diseases is twofold. To
the extent that preconception care includes vaccination or revaccination, in all women or
selected groups, the prevention of the disease represents a benefit for women’s own health.
175
The higher the natural prevalence and the morbidity, the more this is relevant. In some other
diseases, preconception care includes its screening, usually in subpopulations with higher
risks through some known exposure mechanism. In these cases it is secondary rather than
primary prevention which in most cases represents a maternal benefit.
HIV
HIV has a prevalence between 0.1% and 0.7% of the adult population in developed
countries. In 40% of unaware HIV status there is mother-infant transmission37, 49-50 Until the
introduction of an effective HIV vaccine, direct prevention of this immune deficiency disease
is not possible. Still, preconception care offers the possibility to optimize HIV prevention in atrisk women of reproductive age in developed countries, more generally in epidemic regions
like Eastern Europe, and Africa. The gains of therapy (HAART) for the women are obvious:
early treatment has shown to improve long-term outcome. The awareness of being HIVpositive may interfere with pregnancy intentions. Also, in particular in younger couples who
start a family, economic disadvantages may also be present due to job loss as a
consequence of a HIV positive diagnosis. However, stigmatization by HIV positive status and
subsequently losing a job has decreased in most countries during the last years. These
disadvantages are outweighed by the straightforward health benefits of targeted specialist
therapy.
Hepatitis B
While hepatitis B infection in adults leads to recovery in the majority of the cases, 5%
clearing of the virus is incomplete, and some form or chronic disease remains. Liver cirrhosis
is a common serious event after long standing chronic infection.51 Treatment (e.g. with
interferon immune modulation or antiviral drugs) is effective, in particular since the recent
generation of antiviral drugs shows less long term resistance.51 Also, a highly effective
vaccine to reduce the susceptibility of infection is available.52 Migrants from areas where
Hepatitis B infection is endemic should be therefore be vaccinated. This being the case,
maternal health benefits arise from primary prevention, secondary prevention and treatment
of screen-detected cases.
Hepatitis C
Hepatitis C infection in developed countries is a more rare disease compared to hepatitis B.
It is related to - primarily - blood transfusions with donated blood uncontrolled for this
infection before 1992.37 Unlike hepatitis B, clearance is incomplete in the majority of cases,
and although chronic infection may for long remain asymptomatic, many finally develop
chronic liver disease, including cirrhosis.53 As blood donations and its fractions are checked,
176
for the presence of infection, risk for being positive is limited to women older than 30 years.54
Prevalence is still low then, since the probability for blood transfusion is low in young people.
A vaccine does not exist for primary prevention, but treatment of chronic asymptomatic
infection represents a substantial benefit for the mother as treatment options has gradually
extended and successful.55
Tuberculosis
In 2001, the Centers for Disease Control and Prevention (CDC) reported over 15.000 cases
of active tuberculosis, and 10 to 15 million latent infections.37 It is the leading cause of death
among people who are HIV-positive.56 Occasionally women will be detected with chronic or
active tuberculosis, usually in the context of other risks or diseases, including HIV,
intravenous drug use, migrant from specific areas, etc. In these rare cases prompt treatment
will be of benefit.
Malaria
Malaria leads to 400.000 severe maternal anemia per year, mostly in the sub-Sahara
region.37 In terms of preconception care its relevance is negligible in epidemiological terms.
In underdeveloped countries, its prevention and treatment are essential as maternal
pregnancy risks increase with this infection.
Sexually transmitted diseases
Syphilis
Besides the known association of syphilis during pregnancy and stillbirth,57 the burden of
syphilis in the non pregnant population has great impact. The World Health Organization
estimates 12 million new cases of syphilis each year.37 The clinical presentation of syphilis
ranges from asymptomatic to genital ulcers in primary syphilis to more widespread symptoms
(skin rash, lymfadenopathie and mucocuteaneus lesions). The late complications known as
tertiary syphilis are gummatous lesions or involvement of neurological, visual or auditory
systems. Treatment with antibiotics (usually penicillin G) can be used in all stages of syphilis
but are more successful when administered in an earlier stage.37 Many countries screen for
syphilis in the first trimester as a simple blood tests can be used.58 Some states require
syphilis screening to obtain a marriage license. Preconceptional screening in high-risk
populations can reduce the impact of syphilis in women but can also reduce congenital
syphilis.
177
Environmental exposures
A wide range of chemical and physical exposures are known to be relevant in preconception
care.59 Women can be exposed due to their profession, working place, hobby, and place of
living. In particular occupational hazards are frequently underestimated with regard to the
consequences for the worker-employee and the foetus.60 Exposure to e.g. solvents and
noise are obvious examples of environmental exposures with combined effects. The
prevention of exposure or the protection also benefits the women.
A special case is the social environment. Recent research shows the relevance of exposure
to living in deprived areas where a complex of factors decreases maternal and foetal
health.61-62 Preconception care may not easily change this type of exposure, yet by focussing
on other preventable targets both mother and child may benefit.
Conclusion
The focus of public health initiatives should be on maternal effects of preconception care as
well as the foetal effects. Maternal benefits from preconception care affect both the
reproductive outcomes of women in the reproductive age, as well as the general health of
these women during the lifespan. Most evidence thus far is found for prevention of domestic
violence and sexual abuse, smoking cessation and prevention of drug and alcohol use,
prevention of vitamin B12 deficiency, promotion of healthy weight and diet, prevention of
infectious diseases, including HIV, hepatitis B and C, tuberculosis, malaria, syphilis, and limit
workplace and household exposures and noise. These items might to be efficiently
influenced and benefit both foetal and maternal outcomes.
178
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