PAKISTAN PAEDIATRIC JOURNAL

Vol. 34(2) June, 2010
ISSN 0304 4904
PAKISTAN
PAEDIATRIC
JOURNAL
A JOURNAL OF PAKISTAN PAEDIATRIC ASSOCIATION
Indexed in EMBASE/Excerpta Medica & Index medicus WHO – IMEMR
[email protected]
www.ppa.org.pk
http://www.pakmedinet.com/PPJ
ISSN 0304-4904
Founder
Prof. SMK Wasti (Late)
PAKISTAN PAEDIATRIC
JOURNAL
Patron
Prof. SM Haneef
Chief Editor
Prof. Said ul Haque
Managing Editor
--------------------------------------------------------
Pak Paed J 2009, 34(2)
CONTENTS
Prof. M Ashraf Sultan
Editors
Prof. AG Nagi
Prof. A Hameed
Prof. Akmal Laeeq
Prof. Ayesha Arif
Prof. DS Akram
Prof. Iqbal Memon
Prof. Shakila Zaman
Prof. Tahir Msood
Prof. Nadeem Khawar
Prof. ZA Bhutta
Dr. Asad Hafeez
Editorial Executive
Committee
Prof. Agha Shabbir Ali
Prof. Abdul Waheed
Prof. Javaria Mannan
Prof. Muhammad Ali Khan
Prof. Sajid Maqbool
Editorial Board
International
David Southall (UK)
Mobeen Rathore (USA)
Prof. Peter Raine (UK)
Prof. Charlotte M Wright (UK)
Statistical Adviser
Prof. Amanullah
63-64
Editorial
Original articles
1.
2.
3.
4.
5.
National
Prof. Afroz Ramzan
Prof. A H Haquani
Prof. Asma Fouzia Qureshi
Prof. Atta Ullah Mazhar
Prof. Ayesha Mehnaz
Prof. Pervaz Akbar
Prof. Qamar ud din Nizami
Prof. Salman Ali (Brig)
Prof. Tariq Bhutta
Dr. Abdul Rehman
Dr. Humyaun Iqbal Khan
Dr. Liaquat Ali
Dr. Tayyaba Khawar Butt
Page
Article
6.
Kerosene
Oil
Ingestion
among
Children
Presenting to the Emergency Department of a
Tertiary Care Paediatric Hospital
BADER-UN-NISA, MUHAMMAD ASHFAQ, YASMIN CHANNA
Perinatal Mortality and contributing factors at
Teaching Hospital
SHAKIRA PERVEEN, SUBHANA TAYYAB
Interictal electroencephalography
diagnosis of childhood epilepsy
(EEG)
65-69
70-74
and
75-79
Neonatal Hypoglycemia: Frequency And Clinical
Manifestations In A Tertiary Care Centre
80-84
MUHAMMAD SAEED, MALLIKARJUNA MEGHAJI,
MUHAMMAD AL-MALKY, Saad Al-Tubaity
AMIR RASHID, ARIF ZAHEER, HUMAYUN IQBAL KHAN
Does Electroencephlography Help in Early
Diagnosis
of
Subacute
Sclerosing
Panencephalitis?
TIPU SULTAN, AHSAN WAHEED RATHORE,
MALIK MUHAMMAD NAZIR KHAN
Optimal DNA Isolation Method for Detection of
Bacteria in Clinical Specimens by Using the
Technique of PCR
85-89
90-93
GUL-E-RAANA, RUKHSHAN KHURSHID,
MUHAMMAD MUSTANSAR, Mammoona Naz,
Mahjabben Saleem, Shaista Bashir
Pakistan Paediatric Forum
1.
2.
Management of Hepatitis B and C in Children
ABDUL REHMANM, ATTAULLAH MAZHAR
Immunization Coverage of BCG among Children
Reporting to Tertiary Care Hospital by Gender
and Nutritional Status
94-106
107-11
EMAD UD DIN SIDDIQUI, SHAHEENA HANIF, UZMA SIDDIQUI,
Syed Jamal Raza
Case report
Langer
Giedion
Syndrome
(Trichorhinophalangeal Syndrome Type II)
112-15
MUHAMMAD SAEED, MATAR AL-ALMALKI, AHMAD ABABNEH
Abstract service
116-19
News and views
120
II
PAEDIATRICIANS AND MEDICAL PRACTITIONERS
All paediatricians can become member of
Pakistan Paediatric Association. And, also, all
those who take care of children in their practice
may become associate member of the Pakistan
Paediatric Association.
Please enroll as a Member of the Pakistan
Paediatric Association by contacting any one of
the followings in your region.
1. Prof. Abdul Hameed, President Centre,
St. # 1, H # 228, Jinnah Abad, Peshawar.
2. Prof. M. A. Arif, General Secretary Centre,
D-138, Avenue 6, Block-5, Kehkashan Clifton,
Karachi 75600.
3. Prof. Khurshid Ahmed Abbasi, President Sindh
Branch, 3-Khaliq Colony, Airport Road,
Larkana.
4. Dr. Khalid Zubari, Secretary Sindh Branch,
E002 Rufi Lake Drive, Gulstan-e-Jauhar,
Block-18, Karachi.
5. Dr. Aamir Daud, President Balochistan Branch,
17-A, Chaman Housing Scheme, Quetta.
6. Dr. Bashir Ahmed Abro, Secretary Balochistan
Branch, Al-Hameed Super Store, Main
Brewery Road, Quetta.
7. Prof. Nadeem Khawar, President N.W.F.P
Branch, H # 73-G2, St. # 6, Phase 2,
Hayatabad, Peshawar.
8. Dr. Irshad Ahmed, Secretary N.W.F.P
Brach, H # 991, St. # 38, D-4, Phase 1,
Hayatabad, Peshawar.
9. Prof. Parveen Tariq, President Federal
Branch, A-1, St. # 1, RMC Staff Colony
Chaklala, Rawalpindi.
10. Dr. Rubina Zulfiqar, Secretary Federal
Branch, H # 79-A-V/2, Sattellite Town,
Rawalpindi.
11. Prof. Muhammad Asghar Butt, President
Punjab Branch, Punjab Medical College,
Faisalabad.
12. Dr. Munir Akhtar Saleemi, Secretary
Punjab Branch, B-5, Married Flats Sheikh
Zayed Hospital, Lahore.
13. Prof. Saidul Haque Chaudhry, Chief Editor,
Pakistan Paediatric Journal (PPJ), 180-H
Block, Phase-II, Johar Town, Lahore.
14. Prof.
Muhammad
Ashraf
Sultan,
Managing Editor, Pakistan Paediatric
Journal (PPJ), 124-SD House, Askari
Housing Complex, Walton, Gulberg-III,
Lahore.
Please inform the editorial office about
your membership so that your name is placed on
mailing list of the Pakistan Paediatric Journal.
EDITOR
------------------------------------------------------------------------------------------------------------------------------------------------------Pakistan Paediatric Journal is published quarterly in March, June, September and
December. Inland annual subscription for 2010 is Rs.600. The price of single copy is Rs.150.
Special rates are applicable for postgraduates and for subscribers from Mid Eastern,
SAARC and developing countries. Separate rates for institutions in Pakistan and abroad.
Annual subscription for United Kingdom: ₤ 40, USA, rest of the world and for those having
sub-office in Pakistan US $ 50.
Pakistan Paediatric Journal: No part of this journal may be reproduced in any form or by
any means mechanical or electronic including information storage and retrieval system
without the written permission of the publisher.
Recognized by PM&DC, Indexed in index Medicus WHO – IMEMR & EMBASE/Excerpta
Medica & Global Health/CAB Abstracts.
Declaration No.PC.PB/25573/17951 dated 07-09-1977
www.ppa.org.pk
III
PAKISTAN PAEDIATRIC JOURNAL
INSTRUCTIONS FOR AUTHORS
INFORMATION FOR CONTRIBUTORS
Pakistan Paediatric Journal is the official
publication
of
The
Pakistan
Paediatric
Association. The first issue was published in 1977
as Pakistan Paediatric Journal, ISSN No.0304-4904.
Since then, the journal has been published without
interruption
and
has
contributed
tremendously to several advances in paediatrics
in Pakistan. Our journal covers clinical and
research works on all aspects of the healthcare
of children. The journal aims to contribute to cure
of the paediatric diseases and improvement of
the health of children. The manuscripts are
categorized as review articles, original articles
and case reports. The journal is published
quarterly and official language of Pakistan
Paediatric Journal is English. The journal is
distributed to all members of The Pakistan
Paediatric Association, medical colleges, libraries
and related institutes. The journal is also
expedited to libraries of several major universities
in the world.
Manuscripts for publication are accepted from
authors both within the country and abroad.
These should be prepared in accordance with
the fifth edition of Uniform Requirements for
Manuscripts Submitted to Biomedical Journals
established by Vancouver group (International
Committee of Medical Journal Editors, ICMJE)
originally published in New England Journal of
Medicine 1997; 336:309-15. The complete
document, updated October 2008, appears at
http:/www.icmje.org/index.html and should not
have been offered for publication elsewhere or
published previously. If so permission for republication must be enclosed from the
editors/copy holders. Authors should disclose at
the time of submission, information on financial
conflicts of interest that may influence the
manuscript.
Manuscript should be submitted by the
corresponding authors, who should indicate the
address, phone number, fax number, and e-mail
address for correspondence in the title page of
manuscript.
EDITORIAL AND PEER REVIEW PROCESS
Editorial and Review Board of Pakistan Paediatric
Journal reviews all the received materials. The
manuscripts are sent to three most relevant
investigators for review of the contents including
statistical analysis. The editor selects peer referees
from the specialist database owned by the
Editorial and Review Board. For review, names
and their affiliations of the authors are blinded.
Acceptance of the manuscript is decided, based
on the critiques and recommended decision of
the referees. A referee’s decision is made as
“acceptance without revision”, “acceptance
after revisions”, “review again after revisions”,
“rejection” and “additional review by outside
reviewers”. If there is marked discrepancy in the
decisions between the three referees or in
opinions between the author and referees(s), the
Editor may send the manuscript to another
referee
for
additional
comments
and
recommended decision. Names and decisions of
the referees are masked. A final decision on
acceptance or rejection for publication is
forwarded to the corresponding author from the
Editorial Office.
The usual reasons of rejection are insufficient
originality, serious scientific flaws, poor quality of
illustrations. Rarity itself of a disease condition is
not an acceptable condition of case reports. The
peer review process takes usually six weeks after
the manuscript submission. Revisions are usually
requested to take account of criticism and
comments made by referees. Three copies of
revised manuscript should be submitted,
including one set of original illustration. Failure to
resubmit the revised manuscript within two
months is regarded as a withdrawal. The
corresponding author must indicate clearly what
alterations have been made in response to the
referee’s comments point by point. Acceptable
reasons should be given for noncompliance with
any recommendation of the referees. Once
accepted, original articles will be published within
three months.
www.ppa.org.pk
IV
General
Two complete copies of the manuscript should
be sent to the Editors, Pakistan Paediatric Journal.
101, H-Block, Gulberg-III/GPO Box:308, Lahore,
Pakistan. These will not be returned unless
requested at the time of submission. Authors
should keep one set of the entire manuscript with
them.
Manuscripts and references should be typed in
double line spacing with a 4 cm margin on the
left side. Pages must be numbered and each
page carries a running title. Submission of articles
online would be preferred. If this facility is not
available to the author then he/she may send
article on re-writeable CD.
Articles are submitted for peer review and the
editors may make such alterations as considered
necessary. The views expressed are those of the
authors and may not reflect the policies of the
Journal or the Association. Concise Oxford English
dictionary is used as a reference for spellings and
hyphenation.
All measurements must be in SI units except blood
pressure (mm Hg) and drugs (metric units).
Generic names of drugs must be used.
In statistical analysis of data, 95% confidence
intervals must be employed.
Use terms from the medical subject headings
(MeSH). Uncommon abbreviations should be
avoided and should be preceded by the full
word before their next appearance in the text.
Abbreviations for some of the commoner units
are Gram (gm); Kilogram (kg); Milligram (mg);
Microgram (ug); Nanogram (ng); Picogram (pg);
Hour (hr); Second (sec); Cubic Millimeter (mm3);
Millimeter (mm); Centimeter (cm); Milliliter (ml);
Pound (lb); Milliequivalent (mEq); Micron (u);
Percent (%). Plural words have the same
abbreviation.
Tables should be typed in double line spacing
without ruled lines and should include essential
data. Avoid crowding. Main heading should be
in capital letter. Below this a caption in small
letters must be included.
Illustrations and figures should preferably be
professionally drawn. These should be given
capital letters and numbers eg Figure-2 and
www.ppa.org.pk
table-4. Tables and figures must bear a number
corresponding to a similar number in the text.
Except for especially complicated drawings,
which show large amounts of data, all figures are
published at one single page width, the smallest
parts of the figure must be legible.
All the legends for figures should be typewritten in
double space. Do not use a separate sheet for
each legend. Figure legend should describe
briefly the data shown, explain any abbreviations
or reference point in the photographs, and
identify all units, mathematical expressions
abscissas, ordinates and symbols.
Photographs should be uncounted, black & white
on glossy paper, and submitted in a separate
envelope backed by a stiff card board. The
name of author, title of paper and top or bottom
must be marked on the back of illustrations and
photographs. Pictures, scans etc should be
arrowed ( ↑ ) an overlay to show specific areas or
attach explanatory drawings, sketches etc.
Color photographs will be published if the Editor
decide them absolute necessary. The entire
expense of reproducing colour photographs will
be charged to the author. The author is
responsible for submitting prints that are of
sufficient
quality
to
permit
accurate
reproduction, and of approving the final colour
galley proof. All photographs should be correctly
exposed, sharply focused, and submitted on
glossy white paper
Pakistan
Paediatric
Journal
assumes
no
responsibility for the quality of the photography
as they appear in the Journal. Current estimates
for color reproduction can be obtained from the
Editors Office.
A legend for each light microscopic photograph
should include name of stain and magnification.
Electron microscopic photographs should have
an internal scale marker. All kinds of figures may
be reduced enlarged or trimmed for publication
by the Editor.
GENERAL CATEGORIES
Include invited review articles, Original
articles, Short reports, Annotations/Editorials,
V
Letters to the editors, Book reviews and Notes and
Notices.
Preferably in one format only i.e. script, tables
or figures without repetition as far as possible.
1. Invited review articles describe concise
review on important subjects of paediatrics.
The review articles are accepted after
editorial evaluation.
Discussion and Conclusions: comment on the
observations, conclusions drawn, implications
of the study, its limitations and how the study
compares with other similar or relevant
studies. Recommendations for further study
may be recorded when indicated.
2. Original Articles: should normally include a
title, Abstract, Introduction, Materials &
Methods, Results, Discussion and Conclusions,
Acknowledgements, References.
Title: use a separate page. Give the title of
the article, names(s) and academic degrees
of author(s) place(s) where the work was
done, address for correspondence and a
running title (that is carried on subsequent
pages). Title should have not more than 10
words.
Abstract: (separate page) should comprise of
not more than 150 words and should include
what was done, the main findings and their
implications. Details should be avoided.
Introduction: should briefly state the purpose
of study, pertinent but not extensive review of
the subject with 5-6 references.
Materials and Methods: should describe the
criteria for selection of material and identify
clearly the methods, materials and apparatus
used. Avoid using names of patients or other
clues that can lead to disclosure of their
identity.
We endorse the principles embodies in the
Declaration of Helsinki and expect that all
investigations involing human materials have
been performed in accordance with these
principles. For animal experiment, “the
Guiding Principles in the Care and Use of
Animals” approved by the American
Physiological Society have to be observed.
Method of statistical analyses and criteria of
significance level should be described. In
case reports, case history or case description
replace the Materials and Methods section as
well as Results section.
Results: should be presented systematically
Acknowledgements: should be recorded on
a separate paper.
References: These must be numbered in the
order according to which they appear in the
text and should include all information
(Vancouver style). Abstracts and personal
communications may be cited in text but
should not be included in the references.
Authors are responsible for the accuracy of all
references. These cannot be checked by the
editors.
3. Short Reports
These must not exceed 1000 words, including
an abstract of no more than 50 words, 1 or 2
tables or illustrations and 5-6 references. The
table title should be less than 8 words.
4. Annotation/Editorial
Suggestions for topics and for authors are
welcome. Usually these are written by the
editors.
5. Letter to Editor
Should contain not more than 300 words with
few references and should be signed by all
the authors. Readers are invited to freely
contribute to this column as regard their
experience,
importance
of
paediatric
research.
6. Book reviews
Are welcome from readers.
7. Notes & Notices
Association
news,
forthcoming
events,
conferences and other academic and
literary pursuits etc are included.
www.ppa.org.pk
VI
LETTER OF UNDERTAKING
This is to confirm that the manuscript entitled ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------submitted for publication in Quarterly “Pakistan Paediatric Journal” has not been offered for
publication to, or published in, any other journal and if accepted for publication it will not
be published in any other medical periodical in Pakistan or overseas.
Name of the authors*
Signature
1. ------------------------------------------
------------------------------------------------
2. ------------------------------------------
------------------------------------------------
3. ------------------------------------------
------------------------------------------------
* Please mention role of co-authors.
(This letter must be signed by all the authors)
ELECTRONIC SUBMISSION OF ARTICLES
“PAKISTAN PAEDIATRIC JOURNAL” now accepts electronic submission of articles via email, attachment in MS Word format at following address
[email protected]
Note: The figures should be sent in the format of JPEG or GIF to
ensure good quality images
Electronic submission saves time, postage costs and allows the
manuscript to be handled in electronic form throughout the publication process.
www.ppa.org.pk
VII
THE FINAL CHECKLIST
The authors must ensure that before submitting the manuscript for publication, they have taken
care of the following:-
o
Double spaced typing in A4 size white paper with 12-point font
o
Sequence of title page, abstract and keywords, introduction, materials and methods,
results, discussion, acknowledgments, reference, tables and figure legends. All pages
should be numbered consecutively starting from the title page
o
Title page with article title, authors’ full name(s) and affiliation, address for
correspondence (including telephone, fax number and e-mail address), running title
(less than 10 words) and footnotes if any.
o
Check the total/percentage in the table carefully
o
Abstract in structured format for original article and in unstructured format for case
report within 250 words, and key words as in MeSH.
o
Two copies and one original text, tables and figures.
o
All take and figure numbers found in the text.
o
Reference listed in proper format. Check that all references listed in the references
section and cited in the text and vice versa.
o
A covering letter
o
An undertaking signed by all the authors stating the material is not published
previously, and will not be submitted for publication elsewhere, and stating conflicts of
interest of all listed authors, if any.
CD disk with manuscript in Microsoft Word format
www.ppa.org.pk
VI
www.ppa.org.pk
EDITORIAL
Pakistan Paediatric Journal
-----------------------------------------------------------------Pak Paed J 2010; 34(2): 63-64
Poisoning in Children
Poisoning and foreign body inhalation/ingestion is
a common emergency in paediatric emergency
room. Oral intake is a common route of poisoning
but topical, dermal, ophthalmic and inhalational
may also be seen quite often. Infants and
children younger than 5 years of age are the
common victims of poisoning. Important issue in
this regard is that in 50% of cases, these poisoning
results from non pharmacological substances like
cosmetics, kerosene oil, cleansing solutions,
hydrocarbons and foreign bodies. One should
also keep in mind that in >90% cases, poisoning in
young children is accidental. It results from
unique tendency of younger children to put
everything in their mouth.
Active sensations in mouth is not the only factor
responsible for this high incidence of poisoning in
young children but poor parental education, lack
of awareness and counselling in making the
children environment “poison proof”, keeping
kerosene oil and similar hydrocarbons in
attractive cool drink bottles, and making baby
bounties and sweets available in same size and
packing as adult pharmacological preparations
are common predisposing factors in childhood
poisoning. In older children especially adolescent
and preadolescent age, intentional intake of
poisonous substances is common and E.R.
paediatrician should always keep suicidal
ideation at top of the suspected underlying
causes in this age group.
Poisoning in younger children is usually not very
serious or fatal and many a times managed at
home or nearby medical centre. This is because
of the fact that substance ingested is not very
toxic and secondly amount taken is usually too
little to produce clinically significant effects. It
does not mean that it minimises the
responsibilities of paediatricians to make
endeavours to prevent poisoning in children.
One cannot describe the exact number of
childhood poisoning in our country as national
data base of this important paediatric
emergency is not available, but studies from
different tertiary care hospitals of Karachi,
Bahawalpur, Lahore, Peshawar depicts that
nature of poisoning and common age of its
young victims is similar at every centre.
These studies are from three provinces but results
are similar i.e. Preschool children are the
commonest victims of poisoning and kerosene oil,
cleansing solutions, caustics are the common
poisonous substances. Opiates, antidepressant
and antihypertensive drugs used by adults in that
family has also been reported in these studies.
Recommendations and suggestions of study
groups have never been taken seriously as no
practical steps has so far been taken at
government or institutional level in our country to
reduce the incidence of poisoning or combat its
clinical effects.
No paediatric emergency centre in any tertiary
care hospital of this country can claim to be fully
equipped to take appropriate care of child with
poisoning. Antidotes of common poisoning or anti
snake venom are not available all the time at the
hospital
pharmacies
and
even
private
pharmacies in the cities cannot regularly provide
these life saving drugs. Foreign body inhalation in
children has increased in last decade with the
widespread use of “chalia” and “sonf spari” in
children. Facility of appropriate bronchoscopy
and endoscopy for children is available at 2-3
centres only in whole country. Lack of these
facilities further augment the miseries of parents
at the time of emergency and sometime have
fatal outcome of a simple clinical problem.
Management of poisoning emergency in
children requires multidisciplinary approach.
Improving medical care in emergency room
(E.R.) will not resolve this issue. It needs a joint
www.ppa.org.pk
64
Editorial
effort
of
health
department,
paediatricians and their associations.
legislators,
Paediatricians and their associations have a
pivotal role in the prevention and optimum
management of childhood poisoning. Easy to
understand but comprehensive material on
prevention and control of childhood poisoning
should be written and provided to parents and all
care givers of children. These preventive
measures should be discussed with parents at
every well baby visit especially at the time of
vaccination and thereafter. It should include all
the ways and means to make baby environment
“poison proof”. Centres for immediate and
subsequent management of common poisoning
should be established in every city where antidots
and anti venoms should be readily available.
Working staff should be trained in the diagnosis
and management of poisoning. There must be a
toll free number for these centres which should
be functional 24hours and 7days/week. Every
parents and doctors should be aware of this
number and encouraged to use it where ever
they need so. Media should play its role by
motivating people on this common public issue
and pressing health authorities to provide funds
and logistic support for these measures.
Hospital / Quaid-I-Azam Medical College,
Bahawalpur, BV Hospital / Qamc Bahawalpur. Pak Paed J, Jun 2000; 24(2): 65-67.
3.
Nabeel M, Syed MA, Bushra M, Syeda F. The
Study of Etiological and Demographic
Characteristics
of
Acute
Household
Accidental Poisoning in Children, at Dow
University, Karachi, Pakistan, BMC Pediatrics
2010, 10:28 DOI:10.1186/1471-2431-10-28.
4.
Suliman MI, Jibran R, Rai M. The Analysis Of
Organophosphorpus
Poisoning
Cases
Treated At Bahawal Victoria Hospital,
Bahawalpur In 2000-2003. Pak J Med Sci
2006; 22: 244-49.
5.
Afzal S, Ahmad M, Mubarik A, Saeed F, Rafi
S, Saleem N et al. Acute Organophosphorous Poisoning - An Experience. Pak
Armed Forces Med J 2006; 56: 150-56.
6.
Assar S, Hatami S, Lak E, Pipelzadeh M,
Joorabian M. Acute Poisoning In Children.
Pak J Med Sci 2009; 25(1): 51-54.
7.
Aqeel M, Munir A, Khan A. Pattern and
Frequency of Acute Poisoning In Children.
Pak J Med Sci 2009; 25(3): 479-83.
8.
Barry JD. Diagnosis and management of
the poisoned child,Pediatr Ann 2005; 34:
937-46.
9.
Centers For Disease Control And Prevention:
Nonfatal,
unintentional
medication
exposures among young children, united
states,2001-03.MMWR 2006; 55: 1-5.
10.
Riordan M, Rylance G, Berry K. poisoning in
children 4: Household products, plants, and
mushrooms. Arch Dis Child 2002; 87: 403-6.
11.
Woolf A, Litovitz T. Progress in the Prevention
of Childhood Iron Poisoning. Arch Pediatr
Adolesc Med, 2005; 159: 593-95.
Agha Shabbir Ali
Professor of Paediatrics,
Postgraduate Medical Institute/LGH,
Lahore.
E-mail: [email protected]
REFERENCES
1.
2.
Hashim EK, Areeba YK, Hanafi IA.
Accidental Poisoning In Children In Karachi,
Pak Paed J Dec 1997;21(4):159-62.
M Aijaz A, Khichi QK, Naveed S. Acute
Poisoning In Children Reported at BV
www.ppa.org.pk
ORIGINAL ARTICLE
Kerosene Oil Ingestion among Children Presenting to the
Emergency Department of a Tertiary Care Paediatric
Hospital
BADER-UN-NISA, MUHAMMAD ASHFAQ, YASMIN CHANNA
-----------------------------------------------------------------ABSTRACT
See end of article for author’s
affiliations
--------------------------------------------Correspondence to:Yasmin Channa
3-D/3, Doctors Colony JPMC
Karachi
E-mail:
[email protected]
Pak Paed J 2010; 34(2): 65-69
Objectives: The objectives of our study were to identify common factors
responsible for exposure to kerosene oil poisoning, its presenting features
and outcomes.
This was a descriptive study conducted in the Emergency department,
at the National Institute of Child Health Karachi Pakistan from February
2006 to August 2006.
Patients and Methods: Sixty children between the ages of 6 months 12 years with a history of kerosene oil ingestion were enrolled in the study.
Information was obtained from parents or guardians. Patients with history
of poisoning other than kerosene oil poisoning were excluded.
Results: Sixty patients with history of kerosene oil poisoning were seen,
ages ranged from 6 months to 12 years. Most patients were between the
ages of 1 and 3 years and 75% were boys. Most cases were from poor
socioeconomic condition seen during the summer season. The common
sites of storage were in the kitchen and under the stairs. Common
containers were soft drink bottles and plastic bottles. Clinical
presentations were vomiting, cough and tachypnea. One patient in our
study died after 48 hours secondary to central nervous system
involvement
Conclusion: There is a need to create public awareness on child rearing
and home safety. Further studies should be conducted to assess the
success of the educational programs.
Key Words: kerosene oil poisoning, children, preventive measures
INTRODUCTION
Kerosene, also known as paraffin, is refined oil
obtained by distillation and purification of crude
petroleum or rock oil. It is a hydrocarbon, used for
cooking, heating and lighting- a cheap fuel
which, due to cultural practices, unfortunately is
stored in containers and places, which are
accessible to children.
Ingestion of kerosene, herbal remedies and
caustic agents are important causes of serious
accidental poisonings in the developing world1,2
Kerosene has been identified as the most
common cause of accidental poisoning in
studies on children in South Africa3, West Bengal4,
India5 and Pakistan6.
Inadequate legislation on the sale of kerosene
allows it to be sold in unlabelled containers7.
Although cases of poisoning have been largely
controlled in the developed world, they continue
to be an important cause of morbidity and
mortality in the developing world1. The cost of
providing health care to these patients is
www.ppa.org.pk
66
Nisa BU, Ashfaq M, Channa Y
considerable. In a certain fiscal year poison
related admissions cost about one million dollars8.
A study from South Africa estimated that the cost
of treating 436 children per year was equivalent
to providing 95% of the houses with child resistant
paraffin containers9.
The pattern of poisoning varies in different areas
and also with changing times. Aspiration usually
occurs at the time of ingestion when coughing
and gagging are common, but can result from
vomiting after ingestion. Ingestion of even 1 ml of
kerosene oil is significantly related to pulmonary
complications10 and more than 10 ml may be
fatal.
Low viscosity of kerosene enhances penetration
into more distal airways and low surface tension
facilitates spread over a large area of lung tissue.
Most accidents usually occur due to negligence,
on the part of the parent or the guardian to
prevent exposure of the child to harmful
substances11.The importance of accidental
poisoning among children makes it imperative
that poison information services should be aware
of the morbidity and mortality pattern of
poisoning12.
The objectives of the study were:
•
To assess the factors associated with exposure
and clinical features of kerosene oil poisoning
•
Parents’ knowledge about kerosene oil safety
MATERIAL AND METHODS
Our study was conducted over a period of six
months between February and August 2006 in the
Emergency department of The National Institute
of Child Health in Karachi. This is a large multi story
Children’s Hospital, located in the heart of
Karachi. It is government run organization,
catering to the health needs of children in the
entire country. Sixty children were registered with
a history of kerosene oil ingestion. Parents or
guardians were interviewed and a questionnaire
was filled out for the following parameters: age,
sex, type of container, place of storage, time of
ingestion, vomiting induced or not, past history of
kerosene oil poisoning in patient or sibling.
Clinical observation included assessment of level
of consciousness, vitals and signs of respiratory
distress. Responses were then compiled and data
www.ppa.org.pk
obtained was analyzed statistically using SPSS
version 10
Inclusion Criteria:
•
All children between 6 months to 12 years
who were suspected to be cases of kerosene
oil poisoning, based on patient history.
Exclusion Criteria:
•
Children who were identified as not having
kerosene oil poisoning
•
Under 6 months and over 12 year of age
Out of 60 cases, 35 were asymptomatic or
showed minor respiratory symptoms for a brief
period. They were kept under observation for 6 to
8 hours. Chest x-ray was not routinely done in
these cases. They were advised to return to the
hospital
if
any
symptoms
developed.
Symptomatic patients were hospitalized and
laboratory investigation i.e. CBC, ABGs and chest
X rays were done. Antibiotics were administered
to 11 patients with lung infiltrates and fever for
more than 48 hours with or without leucocytosis.
Oxygen inhalation by mask and intravenous fluids
were given as needed. A child was deemed fit
for discharge when CNS status normalized and
respiratory distressed resolved.
RESULTS
During the study period, a total of 60 previously
healthy children with a history of kerosene oil
ingestion were seen. These constituted 0.35% of
the total admissions to the emergency
department of the National Institute of Child
Health during that time period. Among the
group, there were 45 boys (75%) and 15 girls
(25%)
(Table 1). Their ages ranged from 1 to 3 years.
This is a public owned hospital, and majority of
the patients who come here are from poor
socioeconomic background.
Most common site of kerosene storage was the
kitchen (Table 2). In over half the cases, kerosene
had been kept in soft drink bottles, which would
be very likely to attract children in the summers
(Table 3). Out of 60 children, 35 required 6- 8
hours of observation only and no further
treatment. 25 children were symptomatic and
were hospitalized. The most common clinical
presentation was vomiting 41.6%, cough,
tachypnea 25%, grunting 16.6% (Table 4).
67
Kerosene oil poisoning, children, preventive measures
Radiological findings were variable ranging from
perihilar densities, areas of infiltration and dense
consolidation. All radiological abnormalities had
completely resolved by three months. The total
leucocyte count ranged from 4,800-15,000
cumm. Polymorph neutrophil count ranged from
50 – 81% with an average of 60%. ABGs done in 5
severely affected patients showed hypercarbia.
A 2 year old boy of average built died about 90
minutes after kerosene ingestion. The amount
ingested could not be determined. He was
brought to the emergency department with
altered
sensorium
and
deranged
vitals:
respiratory rate 48/min, axillary temperature
38.5ºC, heart rate 153/min. CBC showed
leucocytosis and Chest X-ray showed bilateral
infiltrates.
TABLE 1: Incidence, Age and Sex Distribution of
Kerosene Oil Poisoning
Age
(years)
<1 year
1-3 years
3-5 years
>5 years
Male
(n=45)
05
22
11
07
Female
(n=15)
2
6
4
3
Total
(n=60)
07
28
15
10
Percentage
11.6
46.6
25.0
16.6
TABLE 2: Common Containers from Which Kerosene
Was Ingested
Soft drink bottles
Used plastic bottles (various)
Glass/ cup
Toilet can
No. of
patients
35
15
07
03
Percentage
58.3
25.0
11.6
5.0
TABLE 3: Common Sites of Kerosene Storage
Site
Kitchen
Under the stairs
In the bathroom
In the living room
No. of
patients
30
15
10
05
Percentage
50.0
25.0
16.6
8.3
TABLE 4: Clinical Manifestation of Kerosene Ingestion
among 60 Children
Symptoms
Vomiting
Cough, tachypnea
Grunting/ Wheezing
Recession
Drowsiness
No. of
patients
26
15
10
06
03
Percentage
43.3
25.0
16.6
10.0
6.6
DISCUSSION
The accidental ingestion of kerosene oil, in our
study, was most common among boys between
the ages of 1-3 years. Other studies from Pakistan
and around the world show similar age and
gender predominanc12-15. In our study as well as
others most cases of poisonings occurred during
the summer months16. In more than half of the
cases, kerosene oil was stored in the kitchen in
containers which are normally used to hold
beverages. Other studies from different parts of
the world report a similar practice among
people15,17.
Most cases were asymptomatic at the time of
presentation. The majority of symptomatic cases
presented with vomiting, cough and tachypnea.
Morbidity and mortality of kerosene poisoning is
usually related to the subsequent pulmonary
complications. Respiratory distress is due to
aspiration,
rather
than
toxicity
due
to
Therefore,
gastrointestinal
absorption10,18-20.
emetic agents and absorbents such as activated
charcoal are not used as they do not have any
beneficial effect19-20.
In asyptomatic cases, parents suspected
ingestion of kerosene upon observing the
container either in the hands of the child or lying
close by, staining of clothes, or if contents spilled
out on the floor. Odor of kerosene oil is readily
recognized in the breath and vomitus, but it is
difficult to estimate the amount of ingestion.
Antibiotics are used in very ill patients with
significant pneumonitis.
Majeed et al reported that most patients with
neurological manifestations also had pulmonary
symptoms. They hypothesized that neurological
symptoms were secondary to hypoxia produced
by lung injury rather than through direct toxicity21.
However, Lifshitz et al reported that neurological
symptoms
occurred
without
concurrent
hypoxia22.
The most common neurological manifestations in
our study were restlessness and drowsiness. One
patient in our series died secondary to central
nervous system involvement.
Most studies reveal an absence of residual
effects on lungs with complete resolution of
radiological abnormalities several years’ posthydrocarbon ingestion and there is no increased
www.ppa.org.pk
68
Nisa BU, Ashfaq M, Channa Y
occurrence of respiratory symptoms at several
months of follow-up post ingestion23-24. However,
some authors do report presence of pulmonary
abnormalities after long term follow-up [25, 26].
Kerosene oil from different areas has different
proportions of paraffin and naphthelene. The
differing compositions may be one reason for the
difference in outcomes and different severities of
poisoning in different studies27. Central nervous
system depression and pulmonary complications
are common sequelae of hydrocarbon poisoning
and the emergency care physician must know
how to manage them28.
2.
Tshiamo W, Paraffin (kerosene)* poisoning in
under-five
children:
a
problem
of
developing countries. Int J Nurs Pract, 2009;
15(3): 140-44.
3.
Krug A, et al., The impact of child-resistant
containers on the incidence of paraffin
(kerosene) ingestion in children. S Afr Med J,
1994; 84(11): 730-34.
4.
Sarker AK, Ghosh S, Barik K. A study of
accidental poisoning (in children) in a rural
medical college hospital of West Bengal.
Indian J Public Health, 1990. 34(3): 159-62.
South Africa has a huge burden associated with
kerosene poisoning. They report most cases
occurring in the lower socio-economic group in
the summer months when children mistake the
kerosene for a cool refreshing drink. Similar to our
study, they too report most cases among males
with an average age of 2 years13.
5.
Thomas M, et al., Profile of hospital
admissions following acute poisoning-experiences from a major teaching hospital
in south India. Adverse Drug React Toxicol
Rev, 2000. 19(4): 313-17.
6.
Hamid MH, et al. Acute poisoning in
children. J Coll Physicians Surg Pak, 2005;
15(12): 805-8.
7.
Reed RP, Conradie FM. The epidemiology
and clinical features of paraffin (kerosene)
poisoning in rural African children. Ann Trop
Paediatr, 1997; 17(1): 49-55.
8.
Woolf A, Wieler J, Greenes D. Costs of
poison-related hospitalizations at an urban
teaching hospital for children. Arch Pediatr
Adolesc Med, 1997; 151(7): 719-23.
9.
de Wet B et al. Paraffin (kerosene) poisoning
in childhood--is prevention affordable in
South Africa? S Afr Med J, 1994; 84(11): 73538.
10.
Khan M ed. Textbook of Forensic Medicine.
1992, Azam Sons Karachi: 884-85.
11.
Reddy YRRV. Accidental poisoning and
accidents, in Textbook of pediatrics with
special references and problems of child
health in developing countries, U. PM,
Editor. 1999, Jaypee Brothers: New Delhi:
2657-69.
12.
Fernando R, Fernando DN. Childhood
poisoning in Sri Lanka. Indian J Pediatr, 1997;
64(4): 457-60.
13.
Ellis J.B et al. Paraffin ingestion--the
problem. S Afr Med J, 1994; 84(11): 727-30.
CONCLUSION
Kerosene oil is the commonest hazardous
substance ingested accidentally by toddlers
between 1and 3 years of age. There was an
apparent general lack of knowledge on homesafety in most cases that presented to us. There is
a need to create public awareness on child
rearing and home-safety by conducting regular
awareness
programmes.
Information
from
pamphlets and posters could be distributed
through clinics, polyclinics, nurseries and child
care centers.
Courses and talks on related topics by trained
personnel or health workers could be conducted
to disseminate knowledge. Future studies can
then be conducted to assess the effectiveness of
the various educational programmes.
-----------------------------------------------------------------------------Author’s affiliations
Bader-Un-Nisa, Muhammad Ashfaq, Yasmin Channa
Department of Paediatrics, Hamdard
Hospital, M.A. Jinnah Road, Karachi
University
REFERENCES
1.
Meyer S, et al., Unintentional household
poisoning in children. Klin Padiatr, 2007;
219(5): 254-70.
www.ppa.org.pk
69
Kerosene oil poisoning, children, preventive measures
14.
Aqeel M., Munir A, Khan A. Pattern and
frequency of acute poisoning in children.
Pak J Med Sci 2009; 25(3): 479-83.
15.
Fagbule DO, Joiner KT. Kerosene poisoning
in childhood: a 6-year prospective study at
the University of Ilorin Teaching Hospital.
West Afr J Med, 1992. 11(2): 116-21.
16.
Nagi NA, Abdulallah ZA. Kerosene poisoning
in children in Iraq. Postgrad Med J, 1995;
71(837): 419-22.
17.
Nouri L, al-Rahim K. Kerosene poisoning in
children. Postgrad Med J, 1970; 46(532): 7175.
18.
19.
22.
Lifshitz M, Sofer S, Gorodischer R.
Hydrocarbon poisoning in children: a 5-year
retrospective study. Wilderness Environ Med,
2003. 14(2): 78-82.
23.
Kumar V. Accidental poisoning in south
west Maharashtra. Indian Pediatr, 1991;
28(7): 731-35.
24.
Simmank K et al. Prediction of illness severity
and outcome of children symptomatic
following kerosene ingestion. Ann Trop
Paediatr, 1998; 18(4): 309-14.
25.
Joubert PH. Poisoning admissions of black
south africans. Clinical Toxicology, 1990;
28(1): 85-94.
Gurwitz D et al. Pulmonary function
abnormalities in asymptomatic children
after hydrocarbon pneumonitis. Pediatrics,
1978; 62(5): 789-94.
26.
Zucker AR, Berger S,
Wood LDH.
Management
of
kerosene-induced
pulmonary injury. Critical care medicine,
1986; 14(4): 303.
Tal A et al. Residual small airways lesions
after kerosene pneumonitis in early
childhood. Eur J Pediatr, 1984; 142(2): 11720.
27.
George B. Kerosene (paraffin) poisoning.
The Lancet, 1960; 276(7145): 318-19.
28.
Seymour FK, Henry JA. Assessment and
management of acute poisoning by
petroleum
products.
Human
and
Experimental Toxicology, 2001; 20(11): 55162.
20.
Dice WH, et al. Pulmonary toxicity following
gastrointestinal ingestion of kerosene. Ann
Emerg Med, 1982; 11(3): 138-42.
21.
Majeed HA et al. Kerosene poisoning in
children: a clinico-radiological study of 205
cases. Ann Trop Paediatr, 1981. 1(2): 123-30.
www.ppa.org.pk
ORIGINAL ARTICLE
Perinatal Mortality and Contributing Factors at Teaching
Hospital
SHAKIRA PERVEEN, SUBHANA TAYYAB
-----------------------------------------------------------------ABSTRACT
Pak Paed J 2010; 34(2): 70-74
Objective: To determine perinatal mortality rate and contributing risk
factors at a teaching hospital.
See end of article for author’s
affiliations
-------------------------------------------Correspondence to:Shakira Perveen
B-7 Ruknuddin Flats
F.B Area, Block 1
Karachi.
E-mail:
[email protected]
Methods: A retrospective hospital based observational study, conducted
at the Department of Obstetrics & Gynecology Unit 1V Lyari General
Hospital, from June 2005-Dec 2008. All cases of normal / malformed, still /
live born from 20 weeks of pregnancy till first week of life were included
in the study. Detailed maternal history & examination was done.
Confirmation & examination of dead fetus & new born done by
paediatrician. Perinatal mortality & perinatal mortality rate was
calculated.
Results: During 3½-year study period total number of births was 2631. Out
of them 112 (67.06%) were stillbirths & 55 (32.9%) had early neonatal
death. Perinatal mortality is 167 and perinatal mortality rate is 63.47/ 1000
births. Majority of mothers were young, of low parity, non booked & from
low socioeconomic group. Mean gestational age was 32.5 weeks. Risk
factors identified for perinatal mortality were medical disorders 22.1% ,
mismanaged labor 17.9%, congenital anomalies 14.9%, antepartum
hemorrhage 13.7% premature rupture of membranes in11.3 % cases &
miscellaneous factors 19.7% ( pretem labor , conjoint twins & cord
around neck). Major causes of perinatal mortality were prematurity,
perinatal anoxia & congenital malformation.
Conclusion: Factors responsible for high perinatal mortality are avoidable
& perinatal mortality rate can be reduced by public awareness, health
education & delivery of high-risk pregnancies at tertiary care hospital.
Key words: Perinatal mortality, perinatal mortality rate, risk factors.
INTRODUCTION
Perinatal mortality (PNM) is significant public
health problem throughout the world. Perinatal
mortality rate (PNMR) is intimately related to
maternal risks & maternal health services
available to the community1. Pakistan has one of
the highest neonatal and perinatal mortality rates
in
the
world2.
According
to
Pakistan
Demographic & Health Survey 2006-2007 PNMR is
159/1000 births. PNMR in Karachi is reported as
54.1/1000 births3 and in Lahore 53/1000 birth4.
www.ppa.org.pk
Pakistan and other 3rd world countries especially
African and Asian countries have been declared
high PNM regions. A child born in these areas, has
on average, a twenty times more chances of
dying than if born in developed countries. Of
every 100 children born 12 die before the age of
one month in Africa, 10 in Asia, 9 in South East
Asia, 6 in Latin America5.
Risk factors identified for PNM are fetal
abnormalities, intrauterine growth restriction,
abruptio placentae, infection, older maternal
71
Perinatal Mortality and contributing factors at Teaching Hospital
age, mismanaged labor and medical problems
like diabetes, pregnancy induced hypertension,
cardiac disease etc6. The causes of almost one
half of stillbirth are unknown7. PNMR is generally
defined as the number of stillbirths & neonatal
deaths / 1000 total births (live birth & still birth). Still
birth has been variably defined as intrauterine
fetal death after 20 weeks of gestation in the
United States8, 24 weeks in the United Kingdom
and Denmark9,10. The WHO recommended that
the definitions of stillbirth should be based on fetal
weight (≥ 500 gm) rather than the gestational
age11. Neonatal death (NND) is defined as the
death of live born before the 28th day of life.
NNDs are subdivided into early NND, occurring
during the first seven days of life (0-6 days) and
late NND, occurring after the 7th day of life but
before the 28th day of life (7-27 days), while some
definitions of PNM are limited to early NNDs9,10.
The purpose of the study was to determine PNMR
and contributing risk factors at teaching hospital.
Rationale: We would like to determine various
causes of PNM and possible ways to reduce it. In
Pakistan
gap
between
resources
and
requirements is wide and optimal utilization of
resources is important.
OBJECTIVE
To determine perinatal mortality rate
contributing risk factors at teaching hospital.
&
PATIENTS AND METHODS
A retrospective hospital based study carried out
at the department of obstetrics & gynecology
unit 1V, Lyari General Hospital, (affiliated with
Dow University of Health Sciences) from June
2005 - Dec 2008. All deliveries of normal/
malformed, still/ live born after 20 weeks of
pregnancy till 1st week of life were included in the
study. All participants were formally asked to sign
a consent form for detailed investigations and
interviews. Records of all these cases were
thoroughly evaluated regarding gestational age,
symptoms, antenatal period, complications,
previous obstetric history, labor, mode of delivery
and fetal outcome. Socioeconomic index was
developed based on maternal education,
number of rooms, per capita income and source
of light, water and fuel. Fetal death diagnosis was
made
through
history, examination
and
ultrasonography. Pediatrician examined fetuses
for weight, gross features; either old or fresh
dead, normal or malformed. Each neonate was
examined and followed till 7th day of life. PNM has
been calculated as sum of still births and NNDs
and PNMR was estimated/1000 total births.
RESULTS
Total number of births during 3½-year study
period was 2631. Out of them 112 (67.06%) were
still births and 55(32.9%) had early neonatal death
(0-3 days). PNM is 167 & PNMR is 63.47/1000 births
(table 1). Maternal age in 94% was 20-35 years
(mean 27.5), parity in 80.7% was 0-5 (mean 2.5),
86.2 % were non-booked and 89% were from
poor socioeconomic class. Gestational age in
65.8% was 28-37 weeks (mean 32.5) (table 2). Risk
factors identified were medical disorders 22.1%,
mismanaged labor 17.9%, congenital anomalies
14.9%,
antepartum
hemorrhage
13.7%,
premature rupture of membranes 11.3% and
miscellaneous (preterm labor, cord around neck,
conjoint twins) 19.7% cases (table 3).
Statistical analysis: Mean ± SD of maternal age
and parity calculated. Risk factors were
described in numbers and percentage was
determined. Statistical analysis was done by SPSS
version 10.
TABLE 1
Total no. of deliveries
Total no. of still birth
Total no. of early NND
PNM
PNMR
2631
112
55
167
63.47/1000
TABLE 2: Relationship of PNM with Maternal Age, Parity, Booking Status & Gestational Age.
Age (Years)
<20
20-30
>30
%
2.9
94.0
2.9
Booking status
%
B
13.7
NB
82.5
R
03.7
Parity
0-2
3-5
>5
%
53.2
27.5
19.2
Gestational age
%
<28
30.5
28-37
65.8
>37
3.7
www.ppa.org.pk
72
Perveen S, Tayyab S
B= booked, NB= non booked, R= referred
TABLE 3: Risk Factors for PNM:
Risk factors
No.
%
Medical disorders
Mismanaged labor
Congenital anomalies
Antepartum hemorrhage
Premature rupture of membranes
Miscellaneous
37
30
25
23
19
33
22.1
17.9
14.9
13.7
11.3
19.7
Miscellaneous = preterm labor, cord around neck,
conjoint twin
DISCUSSION
Lyari General Hospital is located in the periurban
area of Karachi and caters patients from near
vicinity as well as the adjacent areas of
Balouchistan province. This teaching hospital is
affiliated with Dow University of health sciences.
PNMR in our study is 63.4/1000 births, which is
comparable with local studies 3,4,12. PNMR have
significantly declined in advanced countries like
United States since 1950s, primarily because of
improvements in medical care, but they are still
not rare events; with nearly 7 still birth occurring /
1000 deliveries; in the year 200013. This difference
is mainly because of poorer socioeconomic
status, maternal & paternal illiteracy & poor
standards of obstetric & neonatal care
.Comparing PNM in different areas is misleading
due to different standards of obstetric care,
education & social class.
The young & low parity mothers had higher PNM
than their counterpart, also supported by other
studies12,14,15. One local study on teenage
pregnancy found high risk of anemia, preterm
delivery & low birth weight babies in them16. Poor
nutritional state during pregnancy is an important
contributing factor for poor neonatal outcome as
observed in many studies17,18. Unbooked mothers
were the one’s who either did not receive any
form of antenatal care in our health facility or
were referred from other health facilities. A delay
prior to presentation is commoner among
unbooked mother’s which have been found to
result in poor maternal & neonatal outcome.
Antenatal care is therefore an essential part of
safe motherhood and its quality influence
pregnancy outcome.
www.ppa.org.pk
Risk factors identified were medical disorders,
mismanaged labor, congenital anomalies,
antepartum hemorrhage & premature rupture of
membranes. Main medical disorders identified
were hypertension 10.7%, diabetes 4.1% and
anemia 3.5% cases. Hypertension is responsible
for 23% cases of PNM in civil hospital Karachi12. In
Bangladesh PNMR in hypertnsive mothers is
117.4/1000 births as compared to 48.6/1000 births
in non hypertensive mothers14. PNM in diabetic
pregnancies is 2.5-9 times higher than general
population & 30-50% is due to congenital
anomalies especially in diabetes type 219.
According to WHO: 35-75% of pregnant women
in developing countries are anemic. Anemia in
pregnancy is associated with an increased risk for
preterm delivery, low birth weight and maternal
mortality20,21. One study carried out at Aga Khan
University Hospital found risk of still birth is 3.7 times
higher in anemic women22. Preconception care,
folic acid supplementation, strict control of
medical disorders during pregnancy can reduce
PNM similar to those of general population.
Mismanaged labor accounts for 17.9% cases of
PNM in this study as compared to two local
studies (25% & 26%12,15) is high. High risk
pregnancies for uterine rupture with 100% PNM &
with mechanical factors for obstruction should be
managed in tertiary care hospital. Congenital
Malformations is definite and preventable risk
factor. Many studies found large share of this
factor in high PNM. Around 40% cases had history
of consanguineous marriage, similar to study
carried out at Rawalpindi23. This issue can be
resolved by creating awareness and providing
marital and genetic counseling. Neural tube
defects was commonest anomaly observed in
one study carried out on congenital anomalies in
our department18. Periconception folic acid
supplementation and early diagnosis by highresolution ultrasonography, screening at early
gestational age (16-18 weeks) by testing
maternal serum alpha proteins & termination can
lower PNMR. Antepartum hemorrhage is
significant risk factor of PNM in our as well as in
other study14.
Risk factors for antepartum hemorrhage are
hypertension, folate deficiency and anemia
which can be identified in antenatal period.
Prematurity and infection are major causes of
Perinatal Mortality and contributing factors at Teaching Hospital
PNM in Premature rupture of membranes.
Preterm premature rupture of membranes is
responsible for close to 40% of the cases of
preterm births24. These maternal & fetal risk factors
are responsible for preterm delivery, perinatal
anoxia and congenital malformations.
5
Gill ZU. Proceedings of the regional congress
on maternal & child health 9-11 Oct 1989,
Lahore Pakistan.
6.
Fretts RC. Etiology & prevention of still birth.
Am J Obstet Gynecol 2005; 193: 1923-35.
7.
Goldenberg RL, Kirby R, Culhane JF. Still birth;
a review J Matern Fetal Neonatal Med 2004;
16: 79-94.
8.
Dudley DJ. Diabetic-associated stillbirth:
incidence,
pathophysiology,
and
prevention. Obstet Gynecol Clin North Am
2007; 34 (4): 293-307.
9.
Macintosh MC, Fleming KM, Bailey JA, Doyle
P, Modder J, Acolet D, et al. Perinatal
mortality and congenital anomalies in
babies of women with type 1 or type 2
diabetes in England, Wales, and Northern
Ireland: population based study. BMJ 2006;
333 (7560): 177.
10.
Jensen DM, Damm P, Moelsted-Pedersen L,
Ovesen P, Westergaard JG, Moeller M, et al.
Outcomes in type 1 diabetic pregnancies: a
nationwide, population - based study.
Diabetes Care 2004; 27(12): 2819-23.
11.
World Health Organization. Manual of the
international statistical classification of
disease, injuries and causes of death, vol 1.
Geneva: World Health Organization; 1977,
9th Revision.
12.
Ainuddin JA, Memon GU, Ramejo BG.
Factors contributing to high perinatal
mortality in a tertiary referral center civil
hospital Karachi. Medical channel 2007;
13(3): 27-29.
CONCLUSION
Major causes of high PNMR are prematurity,
perinatal anoxia and congenital malformation.
RECOMMENDATION
Considerable proportion of PNM could be
prevented by adequate antenatal care from
early stages of gestation, provision of early
neonatal care system at the community level to
tackle neonatal casualities, maternal health
education, appropriate training to community
health workers, strengthening of obstetric
monitoring system & counseling services.
--------------------------------------------------------------------------Author’s affiliations
Shakira Perveen, Prof. Subhana Tayyab
Gyn Unit 1V, Dow University of Health Sciences,
Karachi.
REFERENCES
73
1.
Jamal M, Khan N. Neonatal morbidity &
mortality in risk pregnancies. JCPSP, 2002; 12
(11): 657-61.
2.
Aziz S, Billoo AG, Samad NJ. Impact of
socioeconomic conditions on perinatal
mortality in Karachi. J Pak Med Assoc 2001;
51: 354-60.
13.
Fikree FF, Gray RH. Demographic survey of
the level and determinants of perinatal
mortality in Karachi. Paediatr Perinat
Epidemiol 1996; 10(1): 86-96.
Barfield W, Martin J, Hayert D. Racial / ethnic
trends in fetal mortality: United States, 19902000. MMWR Morb Mortal Wkly Rep 2004; 53:
529-32.
14.
Abdullah Al Mamun, Sabu S, Padmadas,
Khatun
M.
Maternal
health
during
pregnancy and perinatal in Bangladesh:
evidence from a large- scale communitybased clinical trial. Pediatric and Perinatal
Epidemiology 2006; 20: 482-90.
15.
Khaskheli MUN, Bbaloch S, Khushk IA, Shah
SS. Patterns of fetal deaths at a University
3.
4.
Chisty AL, Iqbal A, Anjum A, Maqbool S.
Spectrum
of
multiorgan
systemic
involvement in birth asphyxia. Pak Pediatr
Assoc J 2001; 25: 81-87.
www.ppa.org.pk
74
Perveen S, Tayyab S
hospital of Sindh. J Ayub
Abbottabad 2007; 19(2): 32-34.
Med
Coll
16.
Naz S, Perveen R, Bhatti A, Balouch R, Hanif
M. Teenage pregnancy (Are teenagers a
high risk group? ). Medical Channel Jan –
March 2010; 16(1): 140-143.
17.
Save the children. Saving newborn live
initiative. State of the world’s Newborns,
Pakistan, Oct 2001.
18.
19.
Perveen F, Tayyab S. Frequency and
patterns of distribution of congenital
anomalies in the newborn and associated
maternal risk factors. JCPSP 2007; 17(6): 34043.
Melamed N, Hod M. Perinatal mortality in
pregestational
diabetes.
International
Journal of Gynecology and Obstetrics 2009;
104: 20-24.
www.ppa.org.pk
20.
Tufail A, Hashmi HA, Naheed F. Risk factors
for preterm labour in a rural cohort Medical
Channel April- June2009; 15(2): 55-57.
21.
World Health Organization, United Nations
Childrens Fund UNU. Iron deficiency anemia;
Assessment Prevention and Control. A guide
for programme managers. WHO, Geneva,
2001.
22.
Lone FW, Qureshi RN and Emanuel F.
Maternal anemia and its impact on
perinatal outcome. Tropical Medicine and
International Health 2004; 9(4): 486-90.
23.
Hashmi MA. Frequency of consanguinity
and its effect on congenital malformation: a
hospital based study. J Pak Med Assoc 1997;
47: 75-78.
24. Parry S, Strauss 3rd JF. Premature rupture of
the fetal membranes. N Engl J Med 1998;
338: 663-70.
ORIGINAL ARTICLE
Role of Nasal CPAP in Management of Neonates with
Respiratory Distress
MUHAMMAD NADEEM HAMEED, SABA ABDUL SATTAR
-----------------------------------------------------------------ABSTRACT
See end of article for author’s
affiliations
---------------------------------------------Correspondence to:
Muhammad Nadeem Hameed
Department of Paediatrics
Shalamar Medical & Dental
College, Shalimar Link Road
Lahore, Pakistan
E-mail:
[email protected]
Pak Paed J 2010; 34(2): 75-79
Objective: To evaluate the role of nasal continuous airway pressure in
management of neonates with respiratory distress.
Setting: Neonatal Intensive care Unit, Shalamar Hospital, Lahore.
Study Period: January 2007 till December 2008.
Patients and Method: During study period 331 (7.2%) neonates delivered
in this hospital presenting with predominant symptom of respiratory
distress were included. 84 infants who failed to maintain SaO2 > 85% on
humidified oxygen alone, were given nasal CPAP of 3-10 cm of water
through Benveniste’s valve and silastic nasal prongs .
Results: Mean duration of administering CPAP was 58 hours. Hyaline
membrane disease was the commonest indication for starting CPAP
and was associated with best survival rate (60.6%). Outcome was better
in infants weighing > 1500 gm.
Conclusion: Nasal CPAP is an effective and easy therapeutic tool in
managing neonates with respiratory distress.
Abbreviations: ETT – Endotracheal Tube, CPAP –Continuous Positive
Airway Pressure, HMD – Hyaline Membrane Disease, SaO2 - Oxygen
Saturation, IPPV – Intermittent Positive Pressure Ventilation, Transient
Tachypnea of Newborn, MAS – Meconium Aspiration Syndrome , CHD –
Congenital Heart Disease
Key Words: CPAP, Respiratory Distress, Neonates, Hyaline Membrane
Disease
INTRODUCTION
Respiratory distress is one of the commonest
presentation in neonatal age group (3-7 % of all
live births)1. Almost one out of every four
admitted neonates requires some form of assisted
ventilation2. Respiratory distress in newborns
presents with tachypnea, inspiratory recessions
and expiratory grunting. Although endotracheal
intubation and intermittent positive pressure
ventilation (IPPV) remain the gold standard in the
management of acute respiratory failure, yet this
is associated with high rate of complications3.
These
complications
range
from
acute
pharyngeal
and
laryngeal
injury,
vagal
stimulation, apnea and bradycardia, laryngeal
edema, pneumothorax, atelectasis, introduction
of nosocomial infection to late complications like
stricture and subglottic stenosis. Moreover
administration of mechanical ventilation through
endotracheal tube (ETT) requires highly trained
medical staff and sophisticated equipment.
Continuous Positive Airway Pressure (CPAP)
provides assistance to newborns with respiratory
difficulties by improving oxygenation, maintaining
lung volume, lowering upper airway resistance
and reducing obstructive apnea4. Based on this
www.ppa.org.pk
76
Hameed MN, Sattar SA
principle CPAP ventilation delivered through an
ETT was first used in 1971 to treat cases of Hyaline
membrane disease (HMD) successfully5. Since
then various systems to deliver nasal CPAP have
been devised including infant flow driver system,
underwater
bubble
CPAP,
conventional
ventilator for nasal CPAP and Benveniste devise;
having their own advantages and hazards6.
Airway pressure is determined by the flow of
humidified mixture of air and oxygen7. Early
administration of nasal CPAP in very low birth
weight infants significantly reduces the need and
duration of endotracheal intubation as well as
the risk of bronchopulmonary dysplasia8, 9.
In our part of world, infant mortality rate is
alarmingly high and respiratory difficulties are one
of the major causes for this high mortality in
newborn period. Facilities for newborn care are
limited and trained staff for mechanical
ventilation is available only at selected centers of
country. In view of these limitations, nasal CPAP
ventilation is a simple and efficient method of
treating neonates with respiratory distress10.
Therefore we analyzed the role of nasal CPAP in
our newborns requiring respiratory support.
incubator. After a detailed record of history and
physical examination, routine investigations to
determine the cause of respiratory distress were
done including a radiograph of the chest in all
cases.
The sensor of a pulse oximeter was placed
around the foot to automatically monitor the
oxygen saturation (SaO2) and heart rate. Babies
with respiratory distress were first treated with
humidified oxygen by hood at a rate of 4-6L /
min. Indications for shifting to nasal CPAP were:
•
•
Failure to maintain SaO2 > 85 %
Recurrent apneic spells
Benveniste’s valve (jet assembly) was used to
deliver nasal CPAP through Argyle short silastic
nasal prongs placed in both anterior nares and
secured tightly with a knitted bonnet (fig 1).
Smaller size nasal prongs were used for smaller
babies. The nasal prongs were checked regularly
for any displacement or blockade every 4 hours.
Study Period: January 2007 till December 2008.
The positive pressure was generated by a narrow
stream of warmed air/oxygen mixture generated
by an air/oxygen mixer and directed against the
breathing hole in the jet device (fig 2). This gas
mixture was inspired through nasal prongs while
expired gas vented to the surrounding
atmosphere. Flows ranging from 4-20 L/min
served to generate pressure in the infant's upper
airway between 0-10 cm of water. The efficacy
of CPAP ventilation was analyzed in different
weight groups and according to etiology. The
CPAP failure was defined as
Setting: Neonatal Intensive Care Unit, Shalamar
Hospital, Lahore
•
•
MATERIAL and METHODS
Type of study: Descriptive, case series
Sample Technique: Non probability consecutive
sampling.
Inclusion Criteria: Neonates admitted in NICU
Shalamar Hospital, Lahore during study period,
suffering from respiratory distress.
Respiratory distress was defined as presence of
any one of the following signs:
•
•
•
Respiratory rate > 60 times per minute
Inspiratory retractions of chest
Xpiratory grunting
All deliveries were attended by senior resident
registrar. In cases of meconium staining
oropharyngeal suction was done on delivery of
the head followed by tracheal suction after birth.
Infants were nursed either in a resuscitare with
overhead radiant warmer or pre warmed
www.ppa.org.pk
Persistent SaO2 < 85%
Recurrent apneic spells or poor respiratory
effort.
The success was defined as persistent SaO2 >85%
and survival. All CPAP failures were shifted to
IPPV.
RESULTS
Out of 4587 live born neonates during the study
period, 331 (7.2%) were admitted to the Neonatal
Intensive care unit (NICU) with predominant
symptom of respiratory distress. Male to female
ratio was 1.3. Transient Tachypnea of Newborn
(TTN) was the most frequently encountered
diagnosis followed closely by Birth Asphyxia and
Hyaline Membrane Disease (HMD) (table 1). All
77
Role of Nasal CPAP in Management of Neonates with Respiratory Distress
331 neonates who were included in the study
received humidified oxygen as first line respiratory
support. Out of these 331, 11 infants were critical
enough to be shifted on IPPV without receiving
nasal CPAP during initial resuscitative effort (fig 3).
Oxygen alone
nasal CPAP
IPPV alone
Fig 3: primary mode of therapy in cases of
Respiratory distress
TABLE I: Etiology of Respiratory Distress in Neonates
admitted in NICU (n = 331)
Etiological Diagnosis
Fig 1: Baby with respiratory distress on nasal
CPAP (Benveniste’s valve) and Argyle silastic
nasal prongs secured with a knitted bonnet
Frequency
TTN
Birth Asphyxia
HMD
Sepsis
MAS
Apnea of Prematurity
Congenital Pneumonia
Hypoglycemia
CHD
Hypothermia
Inborn Metabolic error
Total
Percentage
70
63
58
52
46
16
7
8
5
4
2
21.1
19
17.5
15.7
13.8
4.8
2.1
2.4
1.5
1.2
0.8
331
100
TTN – Transient Tachypnea of Newborn
HMD – Hyaline Membrane Disease
MAS – Meconium Aspiration Syndrome
CHD – Congenital Heart Disease
TABLE 2 : Indications for using nasal CPAP in newborn
and survival in relation to diagnosis (n=84)
Diagnosis
Fig 2: Air flow mixer directing flow of mixed
gases
Frequency
Survivors on CPAP
Number
%
HMD
Sepsis
Asphyxia
MAS
Apnea of Prematurity
TTN
CHD
Hypoglycemia
Congenital
Pneumonia
Hypothermia
33
12
10
10
9
3
2
2
2
20
3
3
3
4
3
1
2
1
60.6
25
30
30
44.4
100
50
100
50
1
1
100
TOTAL
84
41
48.8
www.ppa.org.pk
78
Hameed MN, Sattar SA
Table 3: Survival on CPAP in relation to birth weight
(n=84)
Survivors on CPAP
Birth Weight gm
Frequency
Number
%
< 1000
1000 - 1500
1500 – 2000
2000 – 2500
> 2500
9
28
32
10
5
1
8
20
8
4
11.1
28.6
62.5
80
80
TOTAL
84
41
48.8
Out of the study group, 84 neonates with
respiratory distress who failed to maintain SaO2
>85% on oxygen alone and were put on nasal
CPAP of up to 10 cm (mean 6 cm) of water. SaO2
rose in all 84 cases initially. 41(48.8%) infants on
CPAP maintained SaO2 steadily >85% and were
the survivors on this ventilation mode. Mean
duration of CPAP among survivors was 58 hour
(range 6 – 128 hour).
Majority (38 out of 43) of infants, who failed to
maintain effective respiratory status on CPAP and
required IPPV, did so during first 48 hours of
therapy.
HMD was the commonest etiological indication
(39.2) for starting nasal CPAP and was also
associated with best survival rate (60.6%)
amongst potentially life threatening conditions
(Table 2).
Mean birth weight of babies receiving CPAP was
1790 gm (range 800 -3800 gm). The overall
prognosis of babies weighing >1500gm was good
(Table 3).
Apart from displacement of nasal prongs and
mild ulceration of nasal mucosa which healed
without scarring, no major complication was seen
on nasal CPAP.
DISCUSSION
During the study period, 7.2% of hospital
delivered neonates presented with respiratory
distress. Similar incidence has been reported in
studies conducted in neighboring country of the
region1,3. CPAP ventilation acts by applying
positive end expiratory pressure to spontaneous
breath without increasing inspiratory work. It
improves ventilation perfusion ratio by expanding
www.ppa.org.pk
partially collapsed small airways. It also improves
lung compliance and decrease work of
breathing. Because of these effects, CPAP has
been extensively used in the treatment of HMD
successfully with survival rates of 67-83%3,5,11. In our
study 20 (60.6%) out of 33 neonates with HMD
survived on CPAP. We also tried this remedy for
treatment of septicemia, although survival was
poor but the cause of death was multifactorial in
this multi-organ failure. In 8 cases of apnea of
prematurity, survival (37.5%) was poor than
reported figures of > 50%12.Most of these preterm
babies were <1500 gm and the possibility of
sudden intracranial hemorrhage could be an
explanation for sudden death in few cases.
Most of babies with asphyxia and MAS could not
survive (30% survival rate) on CPAP. As these
babies were in critical state due to extensive
hypoxic insult, even a few survivals are significant
because CPAP resulted in avoidance of end
tracheal intubations and hazards of prolonged
hospital stay. 43 (51.2%) failures on CPAP had
poor outcome even when shifted to IPPV
regardless of their weight.
We can conclude that CPAP ventilation
complemented with pulse oximetry is a simple
and efficient method for treating neonates with
respiratory distress. Further studies should be
conducted to evaluate this easy to administer
mode of respiratory support.
------------------------------------------------------------------------------Author’s affiliations
Muhammad Nadeem Hameed,
Department of Pediatrics, Shalamar Medical & Dental
College, Lahore, Pakistan.
Saba Abdul Sattar,
Department of Paediatrics, Jankidevi Jamiat Singh
Hospital, Lahore, Pakistan.
REFERENCES
1.
Hijalmarson
O.
Epidemiology
and
classification of acute neonatal respiratory
distress.A prospective study. Acta Pedatr
Scand 1981; 70: 733-83.
2.
Nair PMC, Reddy VG and Jaya S. Neonatal
CPAP-Our Experience with Benveniste's
Valve. Indian Pediatrics 2002; 39: 851-55.
Role of Nasal CPAP in Management of Neonates with Respiratory Distress
3.
Singh M, Deoerari AK, Paul VK. Three years
experience with neonatal ventilation from a
tertiary care hospital in Delhi. Indian Pediatr
1993; 30: 783-89.
4.
Morley C. Continuous distending pressure.
Arch Dis Child Fetal Neonatal Ed 1999; 81:
152-56.
5.
6.
7.
Gregory GA, Klitterman JA, Phibbs RH.
Treatment
of
idiopathic
respiratory
syndrome with continuous positive airway
pressure. New Eng J Med 1971; 284: 1333-40.
De Paoli AG, Morley C, Davis PG. Nasal
CPAP for neonates: what do we know in
2003? Arch Dis Child fetal Neonatal Ed 2003;
88: 168-72.
Lampland AL, Plumm B, Meyers PA, Worwa
CT, Mammel MC. Observational study of
humidified high – flow nasal cannula
compared with nasal continuous positive
airway pressure. J Pediatr . 2009; 154: 177-82
79
8.
Miksch RM, Armburst S, Pahnke J, Fusch C.
Outcome of very low birthweight infants
after introducing a new standard regime
with the early use of nasal CPAP. Eur J
Pediatr. 2008; 167: 909-16.
9.
Morley CJ, Davis PG, Doyle LW, Brion LP,
Hascoet JM, Carlin JB. Nasal CPAP or
intubation at birth for very preterm infants.N
Engl J Med. 2008; 358: 700-08.
10.
Malik RK, Gupta RK. A Two Year Experience
in Continuous Positive Airway Pressure
Ventillation Using Nasal Prongs and Pulse
Oximetry. MJAFI 2003; 59: 36-39.
11.
Rangaswamy R, Manuel D, Carlos L. Pulse
oximetry, in very low birth weight infants with
acute and chronic lung disease.Pediatrics
1987; 79: 612-16.
12.
Hannam S. Apnoea and bradycardia,
In:Roberton’s Textbook of Neonatology, 4 th
edition, 2005: 573-81.
www.ppa.org.pk
ORIGINAL ARTICLE
Neonatal Hypoglycemia: Frequency
Manifestations in a Tertiary Care Centre.
and
Clinical
AMIR RASHID, ARIF ZAHEER, HUMAYUN IQBAL KHAN
-----------------------------------------------------------------Pak Paed J 2010; 34(2): 80-84
ABSTRACT:
See end of article for author’s
affiliations
-------------------------------------------Correspondence to:
Amir Rashid,
Department of Paediatrics,
Lahore General Hospital,
Lahore
E-mail:
[email protected]
Objective: The present study was under taken to find out the frequency
and risk factors of hypoglycemia in newborns in given sample and their
clinical manifestations.
Method: The study was conducted in the Neonatal Unit of Paediatric
Ward, Lahore General Hospital, Lahore, during the period of January
2009 to January 2010. Neonates presented to Neonatal Unit were
screened for hypoglycemia with the consent of their parents and
hypoglycemic neonates were evaluated for clinical manifestations and
categorized into different groups according to weight and gestational
age.
Results: Total of 784 neonates were studied. The frequency of
hypoglycemia was 11.5% of neonatal admissions. Highest number was
42% in preterm small for gestational age (SGA) group. Frequency in termSGA was 13% and in post term SGA 15%. The common clinical features in
hypoglycemic babies were refusal to feed (48%), irritability and jitteriness
(38%), tachypnea (29%), cyanosis (19.5%) and seizures in 15% cases.
Conclusion: Hypoglycemia was frequently seen in newborn babies in our
setup, especially in preterm and SGA categories. Early monitoring and
management can prevent the subsequent morbidity and mortality.
Keywords: SGA, Neonatal, Hypoglycemia
INTRODUCTION
Neonates need continuous supply of glucose for
energy. Most of this glucose is used by the brain.
The fetus gets glucose from the mother through
the placenta. After birth, the normal newborn’s
plasma glucose concentration falls quickly to
level below that in fetal life. This is due to the
normal adaptation as a part of transition to extrauterine existence1. When the adaptation fails as
in immature or sick babies, this supply of glucose
is cutoff and this disturbs cerebral functions2.
Hypoglycemia is the most common metabolic
It
occurs
in
problem
in
newborns3,4.
approximately 1-3 out of 1,000 live births3,5.
www.ppa.org.pk
Incidence varies with the definition, timing of
feeding, method and population6. In a Japanese
study 80% of admission in the nursery after birth
was due to apnea or hypoglycemia in neonates
born at 35 to 36 weeks gestation5,7.
Patients
with
hypoglycemia
may
be
asymptomatic or may present with severe central
nervous
system
and
cardiopulmonary
disturbance2. Glucose level can drop if there is
delay in starting the feed, decreased glucose
production from the liver, increase utilization of
glucose and presence of too much insulin after
glucose boluses. Hypoglycemia is called transient
if it persists for less than seven days and persistent
if more than seven days. Neonatal hypoglycemia
Neonatal Hypoglycemia: Frequency and Clinical Manifestations in a Tertiary Care Centre.
occurs when the newborn’s glucose level is <
30m/dl in the first 24 hrs of life or <45mg/dl after
the first 24 hrs of life3,8. Transient hypoglycemia
can be corrected within 03 to 07 days; however
persistent hypoglycemia requires prolonged
treatment. In the newborn serum glucose level
declines after birth at age of 1 to 3 hrs then it
increases spontaneously9. Liver glycogen stores
are rapidly depleted within hours of birth and
gluconeogenisis primarily from amino acid
alanine can account for 10% of glucose turnover
in the newborn infant by several hours of age.
Infants with risk factors for hypoglycemia include
prematurity, intrauterine growth retardation
(IUGR), SGA, infant of diabetic mother (IDM), birth
asphyxia, large for gestational age (LGA),
neonatal sepsis, endocrine disorder, inborn errors
of metabolism, etc.
Symptoms of hypoglycemia are often vague and
non-specific.
Hypoglycemia
may
be
asymptomatic
or
symptomatic.
Common
symptoms are lethargy, poor feeding, jitteriness,
seizures, hypothermia tachycardia and pallor10,11.
This study was done to determine frequency, risk
factors
of
hypoglycemia
and
clinical
manifestations in newborns presenting to
neonatal unit of Lahore General Hospital, Lahore,
using glucometer and confirming this level by
laboratory.
PATIENTS AND METHODS:
The study was conducted in the neonatal unit of
the Department of Paediatrics, Lahore General
Hospital during the period from January 2009 to
January
2010.
This
was
a
descriptive
observational study. Blood glucose of all babies
presented to neonatal unit was monitored by
Smart Check Glucometer (1601)R and confirmed
from the laboratory Brönger Spectrophotometer
4010 (reagent method). All liveborn or sick babies
requiring admission in neonatal section were
included in this study. A total of 784 such babies
were included and consent was obtained from
the parents. All hypoglycemic neonates were
evaluated for clinical signs and symptoms such as
refusal to feed, jitteriness, sweating, cyanosis,
tachypnea, pallor, apneic spells, and seizures.
Capillary blood obtained by heel prick was
tested by glucometer. Glucose value less than
45mg/dl was confirmed from the laboratory. First
81
glucose level was obtained at 0-3 hours of age
and level of ≤ 35mg/dl was considered as
hypoglycemia. A second blood glucose level
was checked between 3-24 hours of age and
then after 24 hours. Blood glucose levels of ≤
40mg/dl and ≤ 45mg/dl were considered
hypoglycemia respectively.
Newborns having hypoglycemia were managed
and kept in neonatal unit, till their blood sugar
random (BSR) remained at constant level of >
45mg/dl for 72 hours. Infants with persistent
hypoglycemic infants were kept and managed
for prolonged period according to the cause.
All asymptomatic neontes were given oral feed
and symptomatic babies with hypoglycemia
were given I/V D10W at a rate of 6-8 mg/kg/min
to maintain a level of 70-120 mg/dl; no I/V bolus
was administered. Blood glucose was rechecked
at 30 min intervals till it reached within normal
limits (70-120 mg/dl). All the symptomatic infants
were given I/V bolus of D10W at a dose of 02
ml/kg at a rate of 01 ml/min and then D10W
infusion at a rate of 6-8 mg/kg/min followed by
monitoring after every 30-60 min. Persistently
hypoglycemic neonates were treated by giving
D/W infusion at a rate of 16-20 mg/kg/min.
Maximum concentration used was up to
D12.5%W. Patient having recurrent hypoglycemia
after this management were managed by
Hydrocortisone 2.5 mg/kg/dose I/V every 06
hourly. Patient not responding to this therapy
were managed by giving Diazoxide 10-25
mg/kg/day orally in two to three divided doses
especially
in
suspected
cases
of
hyperinsulinemia. Neonates having persistent
hypoglycemia were managed according to the
underlying cause. Hypoglycemic infants were
further classified according to birth weight and
gestational age. The results were given as
percentages and means were calculated; no
statistical test was applied.
RESULTS
A total of 784 neonates were studied during 12
months period. Age ranged from birth to 28 days
with a mean age of 6.5 days. Weight of the
babies ranged from 700 to 4500 grams, with the
mean birth weight 2800 grams. Neonatal
hypoglycemia was seen in 90 patients (11.5%) of
the total admissions. Symptomatic hypoglycemia
www.ppa.org.pk
82
Rashid A, Zaheer A, Khan HI
was seen in 6.5% of cases and asymptomatic
hypoglycemia was seen in 5% cases (table1).
48% neonates presented with refusal to feed and
38% with irritability and jitteriness. (Fig 1)
percentage of patients
percentage of patients
60
48
50
38
40
29
30
19.5
20
15
7
10
3
0
Pallor
Seizures
Tachypnea
Refusal to
Feed
Irritability &
Jitteriness
Cyanosis
Apnea
Fig 1: Sign and symptoms of hypoglycemic babies
Of all the groups, maximum cases of
hypoglycemia were seen in SGA patients. This
group includes 73% (n=66) patients, 42% (n=38)
preterm SGA, 13% (n=12) term SGA and 15%
(n=13) post-term SGA (Table 2). Persistent
hypoglycemia was also more commonly seen in
SGA group. All the symptomatic patients were
given D10W and recurrence of symptoms was
seen in 41.5% cases requiring hydrocortisone.
Mean duration of stay was 8 days. 9% neonates
were managed with D10W and hydrocortisone
and then managed with diazoxide. They also
required prolonged hospital stay (11 days).
decompensation and long term neuronal loss. At
birth with sudden discontinuation of the nutrients
supply from the mother, the neonate mounts
adaptive response including mobilization of
glucose and fatty acids from glycogen and
triglycerides depot to meet the energy demands.
Because of post natal hormonal surge and timely
expression of genes for regulatory enzymes
“uncomplicated” transition to the extra-uterine
environment occurs12. This adaptation is seen
after 2-3 hours of initial decline of glucose.
DISCUSSION
Neonates with
hypoglycemia
Symptomatic
hypoglycemia
Asymptomatic
hypoglycemia
Healthy full term infants born after an entirely
normal pregnancy and delivery do not require
monitoring of glucose. Breastfed infants have low
concentration of blood sugar but higher
concentration of ketone bodies than formula fed
babies. These infants may well tolerate low
plasma glucose level without any significant
clinical manifestations. Hypoglycemia in the
newborn may be associated with both acute
www.ppa.org.pk
TABLE 1: Distribution of
according to symptoms
Hypoglycemic
neonates
No. of Patients
%age
51
6.5%
39
5%
The incidence of hypoglycemia in high risk or
general new-born nursery is difficult to evaluate
because of different criteria used to define
hypoglycemia and dissimilar population12. The
83
Neonatal Hypoglycemia: Frequency and Clinical Manifestations in a Tertiary Care Centre.
incidence of hypoglycemia in our study was
11.5%. Symptomatic hypoglycemia was seen in
6.5% and asymptomatic in 5%. Dashti et al has
reported incidence of 15.15% in their study13
however Phildos et al has reported 5.7% 14 and
Hamid et al reported this incidence to be 38.4%11.
Dashti et al has reported an incidence of 8.35%
and asymptomatic hypoglycemia in 6.8%13.
and their mean stay was 11 days where as Dashti
et al has reported this figure to be 26.8%13.
In our study 48% patients presented with refusal to
feed where as Dashti et al has reported this
symptom in 45% of the cases13. However irritability
and jitteriness was evident in 38% in our study,
compared to this 30% patients in the study
conducted by Dashti et al13.
CONCLUSION
Hypoglycemia resulted in apnea in 3% where as
Dashti et al has reported apnea in 9.8%13. Seizures
developed in 15% of the babies and cyanosis in
19.5% of cases where as Dashti et al has reported
this figure to be 16.6% and 28.4% respectively13.
In our study preterm SGA group has been the
leading cause of hypoglycemia in 42% cases.
Similar incidence was reported by O Lula et al in
their study12. The second commonest cause was
preterm LGA 17% and followed by post-term SGA
15%, where as in term SGA it was noted in 13% of
the cases. Almost same figure is reported by O
Lula et al12 where as Barbara et al has reported
incidence of 5-15% in IUGR’s14. Jane and
Mcgowan reported hypoglycemia in 8% LGA
and 15% of preterm and IUGR cases15.
TABLE 2: Distribution of hypoglycemic in different
categories of neonates (n = 90)
Neonates with
hypoglycemia
Preterm SGA
Term SGA
Post term SGA
Preterm AGA
Term AGA
Post term AGA
Preterm LGA
Term LGA
Post term LGA
No. of Patients
%age
38
12
13
07
02
01
15
01
01
42
13
15
8
2
*
17
*
*
*Too small no. of patients
Recurrence of symptoms after D10W was seen in
41.5% of the patients and their mean stay was 08
days where as Dashti et al has reported this figure
to be 44.5%13. Recurrence after D10W and
hydrocortisone was 9% of the symptomatic cases
As hypoglycemia is leading metabolic disorder
seen in the neonates, it has been seen that
babies who are not fed soon after birth, are left
uncovered in a nursery warmer and crying over
there, are at higher risk.
Hypoglycemia was common in critically ill or
extremely low birth infants in our setup. The
frequency was almost similar in our setup as
compared to previously conducted studies. In
most cases it is multifactorial, transient and easily
supported in our setup. Clinical signs and
symptoms were almost the same as mentioned in
other studies.
--------------------------------------------------------Author’s affiliations
Amir Rashid, Arif Zaheer, Prof. Humayun Iqbal Khan
Department of Paediatrics, Lahore General Hospital,
Lahore
REFERENCES
1.
Schwartz RP. Neonatal hypoglycemia: how
low is too low? J Pediatrics 1997; 131: 1713.
2.
Riodran J. Auerbach K.G. Breast feeding
and human lactation. Boston: Jones and
Bartlett publishers, Inc, 1993.
3.
Stanley CA, Baker L. The causes of neonatal
hypoglycemia. NEJM. April 1999; 340(15):
1200-1.
4.
Boluyt N, Van Kempren A, Offringa M.
Neuro
development
after
neonatal
hypoglycemia: A systematic review and
design of an optimal future study; Pediatrics
Jun 2006; 117 (6): 2231-43.
5.
Cranmer H, Shannas M. Paediatrics,
hypoglycemia. Medscape August 2009.
6.
Cornblath M, Hawdon JM, Williams AF,
Aynsley Green A. Controversies regarding
definition of neonatal hypoglycemia:
Suggested
operational
thresholds.
Pediatrics 2000; 105: 1141-45.
www.ppa.org.pk
84
Rashid A, Zaheer A, Khan HI
7.
Straussman, Sharon; Levitsky, Lynne L.
Neonatal hypoglycemia. Current opinion in
Endocrinology, Diabetes and Obesity. Feb
2010; 17(1): 20-24.
8.
Cornblath M, Wybregt SH, Baens GS, Klein
RI. Symptomatic neonatal hypoglycemia.
Studies of carbohydrate metabolism in the
newborn infant. VIII. Pediatrics. 1964: March;
33: 388-402.
9.
Anderson K, Anderson L, Glanze W. Mosbys.
Medical, Nursing & Applied Health
Dictionary. 5th ed. St. Lous: Mosby; 1998.
10.
Howorth CJ, Machae NK. The neurological
& developmental effects of neonatal
hypoglycemia. A follow up of 22 cases. Can
Med Assoc. J April 1965; 92 (16): 86-65.
11.
Hamid MH, Chisti LA, Maqbool S. Clinical
utility & accuracy of a blood glucose meter
www.ppa.org.pk
for
the
detection
of
neonatal
hypoglycemia. J. Coll Physicians Surg Pak.
April 2004; 14(4): 225-28.
12.
Lubehence OL, Harry B. Incidence of
hypoglycemia in newborn infants classified
by birth weight and gestational age.
Pediatrics, May 1971; 47(5).
13.
Dashti N, Eionollahi N, Abbasi S. Neonatal
hypoglcemia:
Prevalence
&
clinical
manifestations in Tehran Children’s Hospital.
Pak J Med. May Jun 2007; 23(3): 340-43.
14.
Barbara JS. Hypoglycemia in newborn. In:
Kliegman, Behram, Jensan, Stanton (eds)
Nelson Textbook of Pediatrics 18th Edition
Philadelphia; Elsevier; Vol I (1): 785-86.
15.
Jane
E,
Mcgowan.
Neonatal
hypoglycemia. Pediatrics in Review 1999;
20: 6-15.
ORIGINAL ARTICLE
Does Electroencephlography Help in Early Diagnosis of
Subacute Sclerosing Panencephalitis?
TIPU SULTAN, AHSAN WAHEED RATHORE, MALIK MUHAMMAD NAZIR KHAN
-----------------------------------------------------------------Pak Paed J 2010; 34(2): 85-89
ABSTRACT
Objective: To find out the role of electroencephlography in the early
diagnosis of subacute sclerosing panencephalitis.
Design: Cross sectional observational study.
See end of article for author’s
affiliations
--------------------------------------------Correspondence to:
Tipu Sultan
598-D, Johar Town, Lahore
Pakistan
E-mail:
[email protected]
Place & duration of study: Department of Neurology Children’s Hospital,
Lahore from April 15, 2004 to September 15, 2005.
Subjects & Methods: Children between the ages of 4 to 18 years (n=29)
with myoclonic jerks were admitted in the Neurology department. History
and clinical examination was carried out and EEG and CSF antimeasles
antibodies were performed. Children may have EEG findings consistent
with SSPE (EEG abnormalities having burst suppression in high amplitude
slow and sharp waves recur at 3-5 second interval on slow background)
or other EEG findings like myoclonic epilepsy with normal background,
normal EEG etc. CSF of the children was sent for antimeasles antibodies
for further confirmation which was considered diagnostic. Brain imaging
was done in the children to exclude other possible diagnosis.
Results: 19 patients with EEG findings of subacute sclerosing
panencephalitis were further confirmed with CSF anti-measles
antibodies. It was positive in 17 children (P value < 0.05). Ten children had
negative EEG findings and all of them had negative results for CSF
antimeasles antibodies. Male to female ratio was 1.4:1 with 11 males and
6 females. Age range was six to fifteen years.
Conclusion: Subacute sclerosing panencephalitis is not an uncommon
entity in our population with quite variable clinical presentation and
electroencephlography has significant value in early, cost effective and
reliable diagnosis.
Keywords: Subacute sclerosing panencephalitis, Electroencephlography,
Neurodegeneration, Measles.
INTRODUCTION
Subacute sclerosing panencephalitis (SSPE) also
known as Dawn’s encephalitis is a chronic
encephalitis caused of by persistent measles virus
infection of the central nervous system1. Its
incidence is very high in developing countries
because of a number of factors like high
incidence of measles particularly before the age
of 18 months, incomplete measles vaccine or
lack of cold chain maintence2. It occurres in ages
6 months to older than 30 years of age. About 40
million cases of measles occur every year around
the world, out of which 70% occur in Africa and
South Asia3,4. One out of 1000 children gets
encephalitis and out of these 15% die, and 2535% are left with permanent neurologic
sequelae1,5,6. Death caused by sub acute
www.ppa.org.pk
86
sclerosing panencephalitis can occur about 12
years after measles5.
The hallmark of SSPE is myoclonic jerks,
progressive loss of acquired milestone, feeding
difficulties and impairment of intellect7. Age at
the time of onset of symptoms and diagnosis, rate
of progression, and neurological deficit varies
from patient to patient and in later stages of SSPE
disease behaviour may not differentiate it from
other neurodegenerative disorders, so it is
important to diagnose precisely to make the
correct diagnosis for parental counseling8.
Diagnosis of SSPE is based on clinical history
(history of measles and clinical features like
myoclonic jerks, personality changes or loss of
acquired mile stones) typical EEG findings and
presence of antimeasles antibodies in CSF. With
the advancement of new neuroimaging and
neurophysiological tests diagnosis is pretty simple
and confirmed nowadays9,10. Electroencephlography (EEG) has been used for the diagnosis of
SSPE for the last many years and its diagnostic
value has been augmented with the addition of
antimeasles antibodies. EEG in SSPE has its
specific character which is pathognomic for the
diagnosis of SSPE in early stages and rarely seen
in other conditions. However during the later
stages this rhythm does not distinguish condition
from others11-13. Keeping in view the huge burden
of measles, poor recognition of the disease and
mimicking conditions, we have planed this study
to find out the cost effective way of early
diagnosis of SSPE. Nowadays EEG is widely
available in most of the hospitals and is an easy
way of early diagnosis.
PATIENTS AND METHODS
It was a cross sectional observational study
conducted at the Department of Paediatric
Neurology Children’s Hospital, Lahore. Study
duration was from April 15, 2004 to September 15,
2005.
All patients admitted with history suggestive of
myoclonic jerks were enrolled in the study.
Variables used in the study were early diagnosis,
EEG findings consistent with SSPE, positive CSF
findings consistent with the diagnosis of SSPE.
Early diagnosis of SSPE will be labelled when
diagnosis was established in stage I and II while
diagnosis during stage III and onwards was
considered late. EEG was considered positive for
www.ppa.org.pk
Sultan T, Rathore AW, Khan MMN
SSPE when abnormalities have burst suppression
in high amplitude slow and sharp waves recur at
3-5 second interval on a slow background. CSF
anti measles antibodies were sent to either
pathology department of children hospital or to
another laboratory and considered positive when
Immunoglobulin G titer was significant according
to laboratory control.
Inclusion criteria were: history of myoclonic jerks
and age between 4 year to 18 years with or
without regression of acquired mile stones.
Exclusion criteria were: children having sequelae
of central nervous system infections, space
occupying
lesion
of
brain,
progressive
hydrocephalus or evidence of any degenerative
brain disease clinically or on brain imaging.
Our aim was to find out the efficacy of EEG is
picking cases up of SSPE during stage I and stage
II. The patients with myoclonic jerks were
admitted, and history along with clinical
examination was carried out. The children were
subjected to EEG and their CSF was sent for
detection of antimeasles antibodies which was
considered diagnostic. Fundoscopy (done by
ophthalmology department) and brain imaging
(either MRI or CT scan) were done in all cases to
exclude other similar conditions. EEG was
performed by neurology department. All findings
were being recorded on a precoded preforma.
We applied Fischer exact test of significance to
find out the P value.
RESULTS
During the said period 29 children were enrolled
in the study. All of them had myoclonic jerks at
the time of presentation and out of them, 19
children had EEG findings consistent with SSPE.
Out of these 19 children, 17 had positive CSF for
antimeasles antibodies (IgG) as well while only
two children had normal CSF findings. Ten
children had EEG findings not suggestive of SSPE
and all children had negative CSF findings. These
results suggest that EEG has significant capacity
to pick cases of SSPE at an early stage. (P value <
0.05)
11 [59%] were males and 8 [41%] were females
with male to female ratio of 1.4:1. The age range
was 5 years to 14 years. Mean age of onset of
symptoms was 6.5 years while mean age at
diagnosis was 7 years. 2 patients [26%] presented
Does Electroencephlography Help in Early Diagnosis of Subacute Sclerosing Panencephalitis
with age less than 5 years, 11 children [47%] with
age between 5 to 10 years while 6 children [27%]
were of age above 10 years. Spastisity was seen
in 14 [48%] patients, while ataxia was seen in 7
[24%] cases. 5 children [17%] presented with
speech difficulties, 11 [38%] with seizures and 9
[31%] patients with dystonia. All 19 children had
EEG abnormalities having burst suppression in
high amplitude slow and sharp waves recur at 3-5
second interval on slow background. We did the
brain imaging an all the cases and it was normal
in 21 children, brain atrophy was seen in five
children and non specific hyper dence signals in
3 children. Fundus examination revealed optic
atrophy in six children and rest all had normal
findings.
DISCUSSION
SSPE is not a rare disease in Pakistan because of
high incidence of measles. No published local
data is available regarding its incidence at
tertiary care level. We conducted this study to
find out the role of EEG in the early diagnosis of
SSPE and to differentiate this from other diseases
mimicking SSPE.
Through the early diagnosis we may be able to
pick more case of SSPE. Most of the cases have
onset between 10-15 years of age but in Pakistan
mostly cases occur at younger age. Onset is
usually insidious but may be acute or subacute1,2.
Clinically we can divide the course into five
different stages. During the early stages of the
disease, subtle neurological findings are generally
overlooked and only when myoclonic jerks have
been dominated, then diagnosis is not difficult. At
times these patients may present with psychiatric
symptoms and rarely with chorioretinitis15.
Diagnosis can easily be made using Dyken
criteria16. Typical EEG pattern is usually seen in
myoclonic phase and consisting periodic
complexes
having
bilateral
symmetrical
synchronous discharges with high voltage (200500 mv) burst of polyphasic stereotyped delta
waves1,2. When they are not accompanied by
myoclonic spasm, they appear only during sleep
only and if diazepam is given to the patient then
they can be brought in awake state as well. With
progression of the disease there interval may
decrease16.
There are two other forms of periodic complexes
of EEG, which includes type II abnormalities
87
characterized by periodic giant delta waves
intermixed with rapid spikes as fast wave activity
with slow background. Type III periodic
complexes pattern is characterized by long spike
wave discharges interrupted by giant delta
waves. These EEG findings have been found as
markers of prognosis as well and type III is
supposed to be associated with worst outcome
and type II have better outcome17.
At the movement long term prognosis is guarded
and specific treatment that is of limited efficacy
in delaying progression of the disease should be
given to patients in stage II or less18,19. Specific
treatment includes alpha interferon, Isoprinosine,
immunoglobulins and combination of isoprionsine
and alpha interferons. Multidisciplinary approach
should be offered to every case.
SSPE is a preventable disease and by improving
the immunization strategies it can be prevented
and incidence can be lowered. Continuance
surveillance of the problem is necessary to know
about the disease burden and pattern20-22. Simple
and non-invasive tests like EEG which is cost
effective and rapid way of diagnosis should be
offered to every child.
Fig 1: EEG Graph demonstrates burst suppression
www.ppa.org.pk
88
Sultan T, Rathore AW, Khan MMN
TABLE 1: Correlation between EEG Findings and CSF
Findings (n = 29)
6.
Khan HI, Ahmad TJ. Risk factors for
increased mortality in children with
complications of measles. J Coll Physicians
Surg Pak 1999; 9: 247-50.
7.
Sultan T, Qureshi A A, Rahman M, Khan M M
N. The spectrum of neurodegeneration in
children. J Coll Physcian Surg Pak 2006,
16(11): 721-24.
8.
Kalra V. CNS infections In: Prctical
paediatric neurology. Arya Delhi 2002.
9.
Azam M, Bhatti N, Krishin J, Hazir T. Subacute
sclerosing panencephalitis. J Pakistan Inst
Med Sci Jul 2002; 13(1): 618-22.
10.
Modi GH, Campbell BP. Subacute sclerosing
panencephalitis. Changes on CT scan
during acute relapse. Neuroradiology 1989;
31: 433-34.
11.
Tuncacy R, Akman-Demir G, Gokygit A, et
al.
MRI
in
subacute
sclerosing
panencephalitis. Neuroradiology 1996; 38:
636-40.
12.
Yakub
BA.
Subacute
sclerosing
panencephalitis (SSPE): early diagnosis,
prognostic factors and natural history. J
Neurol Sci 1996; 139: 227-34.
13.
Hughes JR. Abnormal rhythms In: EEG in
clinical practice. Butterworth London. 1994.
105-88.
14.
RK Garg. SSPE In: Neurology update. Morris
H, Mayberry J (editors) Radcliffle Publishing
Oxfrd UK 2006. 77-96.
15.
Pati R, Verma A, Kumar P, Parhi LD, Joshi D,
Misra S. Unilateral chrioretinitis: an initial
manifestation
subacute
Subacute
sclerosing
panencephalitis.
J
Assoc
Physicians India 2005; 53(10): 912-13.
16.
Dyken
PR.
Subacute
sclerosing
panencephalitis. Neurol Clin 1985; 3: 179-95.
17.
C P Panayiotopoulos A clinical guide to
epileptic syndromes and their treatment
Bladon U K 2002.
18.
Kuroiwa Y, Celesia G. Clinical significance
of periodic EEG patteren. Arch Neurol 1980;
37: 15-20.
19.
Prashanth LK, Taly AB, Ravi V, Sinha S, Rao S.
Long term survival in subacute sclerosing
CSF findings
EEG
findings
+
_
+
17
02
19
_
0
10
10
17
12
29
Total
(P Value < 0.05)
CONCLUSION
Subacute sclerosing panencephalitis is not
uncommon in our community. EEG has significant
capacity in the early diagnosis and differentiation
of SSPE from other similar conditions.
-------------------------------------------------------------------------------Author’s affiliations
Tipu Sultan**, Ahsan Waheed Rathore*,
Malik Muhammad Nazir Khan**
*Department of Paediatric Medicine
**Department of Paediatric Neurosciences
Institute of Child Health and Children Hospital
Lahore, PAKISTAN
REFERENCES
1.
World Health Organization. Guidelines for
epidemic preparedness and response to
measles outbreaks. Geneva. WHO, 1999.
2.
United Nations Children’s Emergency Fund.
State of world children. Geneva: UNICEF;
2005.
3.
Federal Bureau of Statistics. Pakistan
integrated household survey 2001-20 Round
4: Islamabad: Federal Bureau of Statistics.
2002.
4.
Mishra B, Kakkar N, Ratho RK, Singhi P,
Prabhakar S. Changes trends of SSPE over a
period of ten years. Indian J Public
Health2005; 49(4): 235-37.
5.
Tariq P. Assessment of coverage levels of
single dose measles vaccine. J Coll
Physicians Surg Pak 2003; 13: 507-10.
www.ppa.org.pk
Does Electroencephlography Help in Early Diagnosis of Subacute Sclerosing Panencephalitis
panencephalitis: an enigma. Brain Dev 2006
Mar.20.
20.
21.
Campbell C, Levin S, Humphreys P, Walop
W, Brannan R. Subacute sclerosing
panencephalitis: results of the Canadian
Paediatric Surveillance Program and review
of the literature. BMC Pediatr 2005, Dec 15;
5: 47.
Bellini WJ, Rota JS, Lowe LE, Katz LS, Dyken
89
PR, Zaki SR, Shieh WJ, Rota PA. Subacute
sclerosing panencephalitis: more cases of
this fatal disease are prevented by measles
immunization
than
was
previously
recognized. J Infect Dis 2005 15;
192(10):1679-80.
22.
Sultan T, Mcwilliam R, Zuberi S. Paediatric
neurology
training-Developing
country
perspective. J Coll Physcian Surg Pak 2006;
16(7): 282.
www.ppa.org.pk
ORIGINAL ARTICLE
Optimal DNA Isolation Method for Detection of Bacteria in
Clinical Specimens by Using the Technique of PCR
GUL-E-RAANA,
RUKHSHAN
KHURSHID,
MUHAMMAD
MUSTANSAR,
Mammoona
Naz,
Mahjabben Saleem, Shaista Bashir
-----------------------------------------------------------------ABSTRACT
See end of article for author’s
affiliations
---------------------------------------------Correspondence to:
Gul-e-Raana,
Department of Biochemistry
Fatima Jinnah Medical
College, Lahore
E-mail:
[email protected]
Pak Paed J 2010; 34(2): 90-93
BackGround and Objective: Enteropathogenic Escherichia coli is an
important cause of diarrhea in infants, especially in regions of poor
sanitation. Present study tried to detect enteropathogenic E.coli and its
gene bfp in stool samples of diarrheal children by polymerase chain
reaction in order to facilitate the diagnosis.
Patients and Method: Forty diarrheal sample of children age range 1-3
years were collected from different clinical Laboratories in Lahore in a
period of two-three months. Polymerase chain reaction of DNA was
carried out by using Taq DNA polymerase, and template DNA.
Results: Out of 40 patients’ samples, 5 samples were detected as PCR
positive for bfp, when specific primer for bfp gene was used resulting in
amplification of 330 base pair segment. The rest of samples were
negative in bpf amplification. Identification of E.coli and its DNA was
carried out.
Conclusion:It is therefore concluded that broad-range amplification of
bacterial DNA from complicated cases has proved useful for the
diagnosis of E.coli.
Key Words: Enteropathogenic Escherichia coli, diarrhea, DNA
INTRODUCTION
Bacterial diarrheal diseases represent one of the
significant causes of children mortality and
morbidity in developing countries that lack
sufficient public health standard of sanitation1 In
Pakistan, 40% of population lives in squatter
settlements
where
water
and
sanitary
infrastructure is limited. In these communities,
deaths due to diarrhea are 2 to 3 times more
common than deaths due to acute respiratory
infection2.
Enteropathogenic E.coli (EPEC) is one of the
major causes of human infantile diarrhea
predominantly in less developed countries. This
intriguing
pathogen
exerts
numerous
www.ppa.org.pk
physiological effects on its host target tissue, the
intestinal epithelium and all from an extracellular
location3. Due to these effects, bacterial effecter
molecules transport directly into host cells. As a
result of EPEC attachment to and/or translocation
of proteins into intestinal epithelial cells, many
signaling cascades are activated4,5. Ultimately,
host functions are perturbed, including alteration
of ion transport, disrution of the tight junction
barrier, and activation of the inflammatory
response5.
The bundle forming pilli bpf, Enteropathogenic
E.coli is believed to play a role in pathogenesis by
causing the formation of bacterial mirocolonies
that bind epithelial surfaces of small intestine.
Optimal DNA Isolation Method for Detection of Bacteria in Clinical Specimens by Using the Technique of PCR
MATERIAL AND METHODS
Forty diarrheal sample of children age range 1-3
years were collected from different clinical
Laboratories in Lahore in a period of two-three
months. Identification of E.coli was carried out by
MacConkey agar media plated on petri dishes.
DNA identification was carried out by 0.8% of
agarose gel electrophoresis with a dilution of 1:10
with loading dye. Presence of DNA was visualized
under Gel Documentation system. Concentration
of DNA was determined spectrophotometrically
by UV-VIS spectrophotometer. Polymerase chain
reaction of DNA was carried out by using Taq
DNA polymerase, template DNA. A Primer was
used for amplification of target 330 base pair bfp
gene from E.coli17.
www.ppa.org.pk
1500
1000
500
0
Patients samples
25
In children with infection especially diarrhea, it is
necessary to detect various pathogens rapidly
and accurately, because the infections are often
fatal when diagnosis is delayed. Present study
tried to detect enteropathogenic E.coli and its
gene bfp in stool samples of diarrheal children by
polymerase chain reaction in order to facilitate
the diagnosis.
Out of 40 patients’ samples, 5 samples were
detected as PCR positive for bfp, when specific
primer for bfp gene was used resulting in
amplification of 330 base pair segment. The rest
of samples were negative in bpf amplification
(Fig 2)
13
It is now well recognized that serotype does not
correlate well with the presence of pathogenic
faction. Therefore the detection of pathogenic
genes by PCR may be the best way to identify
the category of diarrheagenic E.coli8. A number
of studies carried out to detect the presence of
E.coli in stool of diarrheal patients by using the
technique of PCR9,10,11. They showed that the
identification of EPEC and other stains by the
Multiplex PCR is a fast and robust technique and
specific for their identification and differentiation
Application of PCR in detection of EPEC
comprises 3 main steps i.e. isolation of DNA from
E.coli, identification of target to be amplified and
visulaization of PCR products i.e. 330 bp bpf gene
fragments. All the diarrheal samples showed the
microbial growth. It was observed that E.coli was
detected in 87.5% (35/40) samples of diarrhea on
MacConkey agar plates. Level of DNA of E.coli
strains was carried out by spectrophotometric
analysis using dilution factor. It was observed that
the min conc 180 ug/ml where as max conc was
1385 ug/ml with a mean level of 798.40,
SD= 334.35 & SE= 66.87 (Fig 1).
19
Identification of diarrheagenic strains requires the
differentiation of pathogenic organism from nonpathogenic members of normal flora. Although
serotype has been carried out to define these
pathogenic strains7.
RESULTS
7
During the course of natural EPEC infections in
children, specific antibodies against intimin and
newly described virulance determinants, such as
BPS or Esps are produced. The presence of
antibodies
against
bacterial
antigens
is
commonly considered a marker for the
production of virulance factor against in vivo6.
1
91
Patients
samples
Concentration
(ug/ml)
Fig 1: Concentration of DNA (ug/ml) in
diarrheal patients.
Fig 2: Amplification of bfp gene in
different diarrheal patient’s sample, Lane
1: negative control; Lane 2-6, samples
92
Raana GE, Khurshid R, Mustansar M, Naz M, Saleem M, Bashir S
DISCUSSION
Diarrheal disease is still the most prevalent and
important public health problem in developing
countries, despite advances in knowledge,
understanding, and management that have
occurred over recent years. It is the leading
cause of death in children under 5 years of
age12,13 .
Present study identified E.coli in 87% of stool
samples of infants. Our study is confirmed by the
other group of workers. A study found,
Escherichia coli isolates from 90% children with
diarrhea by colony hybridization and PCR14.
Another study reported that duration of diarrhea
in patients infected with E.coli is significantly
longer than that caused by other pathogens15.
The possible mechanism of causing diarrhea by
EPEC was proposed by different studies. A study
reported that EPEC uses a type III secretion
machinery to attach to epithelial cells,
translocating its own receptor for intimate
attachment into the host cell, which then binds to
intimin on the bacterial surface. EPEC attaches to
host cells via the outer membrane adhesin,
intimin16.
Our study found that out of 40 patients’ samples,
only 5 samples were detected as PCR positive for
bfp, when specific primer for bfp gene were used
resulting in amplification of 330 base pair
segment. According to a study (Vidal et al)17 the
EPEC virulence-involved gene (bfp gene) is a
histological intestinal alteration known as the
attaching and effacing (A/E) lesion. The
bacterium attaches intimately to the enterocyte
and
induces
assembly
of
cytoskeleton
intracellular actin on the cellular surface, leading
to degeneration of brush border microvilli. It is
reported18 Moriera et al (2006) that the
microcolony formation is one of the initial steps in
biofilm development, and it is mediated by
several adhesins, including the bundle-forming
pilus. This may involve bacterial aggregation.
Lately (Saldana et al (2009)19 reported that the
bundle-forming pilus (BFP) of enteropathogenic
Escherichia coli mediates microcolony formation
on epithelial cells.
CONCLUSION
It is therefore concluded that broad-range
amplification of bacterial DNA from complicated
cases has proved useful for the diagnosis of E.coli.
------------------------------------------------------------------------------Author’s affiliations
Gul-e-Raana, Rukhshan Khurshid,
Muhammad Mustansar, Mammoona Naz
Department of Biochemistry FJMC Lahore.
Mahjabben Saleem, Shaista Bashir
Institute of Biochemistry and Biotechnology, University
of Punjab, Lahore.
REFERENCE
1.
Firkee FF, Azam SI and Berendes HW., 2002.
Time to focus Child Survival Programs on the
Newborn: Assessment of Levels and Causes
of Infant Mortality in rural Pakistan. Bull
World Health; 80: 271-76
2.
Bhutta ZA. Pakistan and the millennium
development goals for health: a case of
too little, too late? J Coll Physicians Surg
Pak, 2004; 14(9):515-17.
3.
Trabulsi LR, Keller R, Tardelli Gomes TA., 2002.
Typical and atypical enteropathogenic
Escherichia coli. Emerg Infect Dis 8(5): 50813.
4.
Grion JA, Donnberg MS, Martin WC, Jarvis
KG, Kaper JB. Distribution of bundle forming
pilus structural gene (bpfA) among
enteropathogenic Escherichia coli J Infec.
Dis., 1993; 168: 1037-40.
5.
Hecht G. Microbes and microbial toxins:
paradigms for microbial-mucosal interacttions. VII. Enteropathogenic Escherichia coli:
physiological alterations from an extracellular position. Am. J. Physiol. Gastrointest.
Liver. Physiol, 2001; 281(1): G1-7.
6.
Marina B, Martinez A, Carla R, Taddei A,
Tagle RA and Trabulish RL. Antibody
response of children with enteropathogenic
E.coli infection to the bundle forming pilus
and locus of enterocyte effacementencoded Virulance determinants. J. infec.
Dis, 1999; 179:269-74.
7.
Levine M.
Escherichia coli that cause
diarrhea; enterotoxigenic, enteropatho-
www.ppa.org.pk
93
Optimal DNA Isolation Method for Detection of Bacteria in Clinical Specimens by Using the Technique of PCR
genic, enteroinvasive, enterohemmorrhagic
and enteroadherent. J. infec. Dis, 1987;
155:377-89.
Escherichia coli Pathotypes, a mini review. J
venom Amin Toxin Inc Trop Dis, 2006; 12 (3):
364-70.
8.
You Y, Fu C, Zeng X, Fang D, Yan X, Sun B,
Xiao D, Zhang J. A novel DNA microarray for
rapid diagnosis of enteropathogenic
bacteria in stool specimens of patients with
diarrhea. J. Microbiol. Methods, 2008; 75(3):
566-71.
14.
Takahashi E, Sultan Z, Shimada S, Aung WW,
Nyein MM, Oo KN, Nair GB, Takeda Y,
Okamoto K. Studies on diarrheagenic
Escherichia coli isolated from children with
diarrhea in Myanmar. Microbiol. Immunol,
2008; 52(1): 2-8.
9.
Bortolini MR, Trabulsi LR, Keller R, Frankel G
and Sperandio V. Lack of expression of
bundle forming pili in some clinical isolates
of enteropathogenic Escherichia coli (EPEC)
is due to a conserved large deletion in the
bfp operon. FEMS. Microbiol. Lett, 1999;
179:169-74.
15.
Ochoa TJ, Barletta F, Contreras C, Mercado
E. New insights into the epidemiology of
enteropathogenic
Escherichia
coli
infection. Trans R Soc Trop Med Hyg, 2008;
102(9): 852-6
16.
DeVinney R, Gauthier A, Abe A, Finlay BB.
Enteropathogenic Escherichia coli: a
pathogen that inserts its own receptor into
host cells Cell Mol Life Sci, 1999; 55(6-7): 96176.
17.
Vidal JE, Canizález-Román A, GutiérrezJiménez J, Navarro-García F. [Molecular
pathogenesis, epidemiology and diagnosis
of enteropathogenic Escherichia coli] Salud
Publica Mex, 2007; 49(5): 376-86.
18.
Moreira CG, Palmer K, Whiteley M, Sircili MP,
Trabulsi LR, Castro AF, Sperandio V. Bundleforming pili and EspA are involved in biofilm
formation by enteropathogenic Escherichia
coli J Bacteriol,2006; 188(11): 3952-61.
19.
Saldaña Z, Erdem AL, Schüller S, Okeke IN,
Lucas M, Sivananthan A, Phillips AD, Kaper
JB, Puente JL, Girón JA. The Escherichia coli
common pilus and the bundle-forming pilus
act in concert during the formation of
localized adherence by enteropathogenic
E. coli. J. Bacteriol, 2009, Feb 13. [Epub
ahead of print].
10.
11.
Muller D, Hagedorn P, Brast S, Heusipp G,
Bielaszewska M, Friedrich WA, Karch A and
Schmidt AM. Rapid identification and
differentiation of clinical isolates of
enteropathogenic Escherichia coli, atypical
EPEC and Shiga toxin producing Escherichia
coli by one step multiplex PCR method. J.
Clin. Microbiol, 2006; 44:2626-29.
Bueris V, Sircili MP, Taddei CR, dos Santos
MF, Franzolin MR, Martinez MB, Ferrer SR,
Barreto ML, Trabulsi LR. Detection of
diarrheagenic Escherichia coli from children
with and without diarrhea in Salvador,
Bahia, Brazil. Mem Inst Oswaldo Cruz, 2007;
102(7): 839-44.
12.
Fagundes-Neto U, Scaletsky IC. The gut at
war: the consequences of enteropathogenic Escherichia coli infection as a factor
of diarrhea and malnutrition. Sao Paulo
Med J, 2000; 118(1): 21-29.
13.
Sousa CP. The vesrsatile strategies of
www.ppa.org.pk
REVIEW ARTICLE
Management of Hepatitis B and C in Children
ABDUL REHMANM, ATTAULLAH MAZHAR
-----------------------------------------------------------------Pak Paed J 2010; 34(2): 94-106
ABSTRACT
See end of article for author’s
affiliations
--------------------------------------------Correspondence to:Abdul Rehman,
Department of Pediatrics,
Quaid-e-Azam Medical
College, Bahawalpur
E-mail:
[email protected]
Hepatitis B and C infections are very common in children in Pakistan.
There are very few hepatologists in Pakistan to manage such cases. This
article gives guidelines for the management of such cases by the
primary pediatrician. The antiviral treatment of acute hepatitis B and C is
not commonly recommended. The treatment of chronic hepatitis B
infection (defined as detectable HBsAg for at least 6 months) is mainly
based on the degree of liver damage caused by hepatitis B virus as well
as viral load while treatment of chronic hepatitis C infection (defined as
the persistence of HCV RNA for at least six months) is based on viral load
of hepatitis C virus. Most of the authorities recommend treatment for
chronic hepatitis B and C in children over 2 years of age. Interferon–α is
the therapy of choice for children with chronic hepatits B while the
second line of drug is lamivudine which is used in interferon- α nonresponders / contraindications to interferon- α. Children with chronic
hepatitis C is treated with pegylated interferon alfa-2b in combination
with ribavirin for duration of 48 weeks irrespective of genotype.
Key words: Hepatitis B; Hepatitis C; Coinfection;
Management; Liver biopsy; Interferon; Lamivudine.
Thalassemia;
Abbreviations: Hepatitis B virus = HBV, Hepatitis B = HB, Hepatitis B surface
antigen = HBsAg, Hepatitis B e-antigen = HBeAg,
Anti hepatitis B e
antibodies = anti-HBe, International units = IU, Alanine aminotransferase = ALT,
α-fetoprotein = AFP, Hepatitis C virus = HCV, Anti- hepatitis C virus = Anti-HCV
INTRODUCTION
National Program for Prevention & Control of
Hepatitis has been implemented in Pakistan since
29th August 2007. The aim of this program is to
reduce the prevalence, morbidity and mortality
due to viral hepatitis infections in the general
population and achieve 50% reduction by
financial year 2010. According to this program
the prevalence of Hepatitis B & C in Pakistan is
3-4% and 5-6% respectively1. The exact
prevalence of these infections in Pakistani
children is unknown but one hospital based study
conducted at Lahore2 showed that 3.35%
children were positive for Hepatitis B surface
antigen (HBsAg) while anti- hepatitis C virus (antiHCV) antibodies were detected in 4.09% children.
www.ppa.org,pk
The prevalence of these infections may be even
higher in children requiring repeated blood or
blood product transfusion. The study done on
multiple transfused thalassemia patients in North
West Frontier Province of Pakistan3 showed
seropositivity of 8.4% for HBsAg and 56.4% for anti
HCV antibodies while another such study
conducted at Bahawalpur4 showed seropositivity
of 9% for HBsAg and 28% for anti HCV antibodies.
The disease courses and managements of these
infections may be different in children as
compared to those in adults and the treatment in
children is more cost effective as compared to
that in adults5.
As there are very few pediatric hepatologists in
95
Management of Hepatitis B and C in Children
Pakistan, so the responsibility management of
these infections mainly lies on the shoulders of
primary pediatricians. The purpose of writing
following guidelines is to help the primary
pediatrician in the management of such cases. In
this article, children are defined as persons less
than 18 years of age.
PATHOPHYSIOLOGY
Pathphysiologically the disease has 4 phases.
1.
The immune-tolerant phase: This phase is
characterized by DNA levels that well exceed
20 000 IU/ml, a normal serum alanine
aminotransferase (ALT) level, positive HBsAg
and hepatitis B e-antigen (HBeAg) in serum
and a minimal liver inflammation and fibrosis6.
It is the phase during which immune system
does not react against virus. Most of the
perinatally infected children are in this phase
and may stay for a long period until
adulthood. But some may progress to the
immune-active phase10. Clinically the child is
asymptomatic6.
2.
The immune-active phase: In this phase serum
The following guidelines are based on the articles
published, on these infections in children,
elsewhere. The help was also taken from the
studies done in adults if there was no data in
children.
It is to be noted that upper level normal for serum
ALT in children is the testing laboratory upper
level normal or 40 IU/L, whichever is lower6. The
European Pediatric HCV Network showed that
reference cutoffs representing the 95th centiles
before 18 months of age were 60 U/L for boys
and 55 U/L for girls, decreasing to 40 U/L for boys
and 35 U/L for girls after 18 months of age7.
viral DNA levels decline but yet remains
detectable and usually >20000 IU/ml. HBsAg
and HBeAg are detectable in serum. There is
elevation of the serum ALT and the
inflammation and fibrosis can develop in the
liver. This phase may be symptomatic and
may lead to cirrhosis and hepatocellular
carcinoma6. Some of the patients go into
inactive HBsAg-carrier phase10.
The term “log drop” in viral load is measured by
decreasing the number by one zero. For instance,
a one log drop in a viral load of 1,000,000 IU is
100,000 IU; a two log drop in a viral load of
1,000,000 IU is 10,000.
Hepatitis B: Hepatitis B virus (HBV) is a DNA-
containing, 42-nm-diameter hepadnavirus, a
DNA virus. Important components of the viral
particle include an outer lipoprotein envelope
containing HBsAg and an inner nucleocapsid
consisting of hepatitis B core antigen. Antibody to
HBsAg (anti-HBs) provides protection from HBV
infection. The viral polymerase can be detected
in preparations of plasma containing HBV. Eight
genotypes of HBV have been identified labeled
A through H. The prevalence of HBV genotypes
varies depending on the geographical location.
The genotype may be related with progression of
liver disease and drug response but the data is
still lacking8.
The HBV DNA can be detected in the serum. The
recommended reporting unit for HBV DNA is in
international units (IU). One IU is equivalent to
approximately 5–6 copies. The same test should
be specified each time when monitoring HBV
DNA levels for a given patient in clinical practice
to ensure consistency9.
Chronic Hepatitis B Infection:
It is defined as
detectable HBsAg for at least 6 months10.
3.
Inactive HBsAg-carrier phase: In this phase
HBeAg becomes undetectable and anti
hepatitis B e antibodies (anti-HBe) is present,
the viral DNA level is low (usually <2000 IU/ml)
or undetectable in the blood. The serum ALT
level normalizes. The liver histology is without
inflammation and the hepatic fibrosis may
regress. The risk of cirrhosis declines. No
treatment is needed6. Some of the inactive
carriers may lose even HBsAg in the future. But
a fraction of them regain active replication
and forms reactivation phase10.
4.
The reactivation phase: In this phase, viral DNA
levels increase, whereas HBeAg remains
undetectable in blood. The serum ALT level
may be either normal or elevated. It is usually
caused by infection with a mutant virus. It
may need antiviral therapy to prevent liver
damage6.
NATURAL COURSE
90% of infants infected as a neonate, 25% to 50%
of children between the ages of 1 and 5 years
who are acutely infected with HBV while <5% of
www.ppa.org.pk
96
Rehmanm A, Mazhar TU
symptomatic and only 5% to 10% of
asymptomatic infected adults and teenagers will
develop chronic hepatitis B6.
INVESTIGATIONS IN A CHILD WITH CHRONIC
HEPATITIS B
The initial investigations include Serum
ALT,
HBeAg, anti-HBe, Quantitative hepatitis B (HB)
DNA, white blood cell and platelet counts as a
part of a complete blood count, hepatitis B
serology, and baseline liver ultrasound used for
crude assessment of liver texture and nodularity
as well as spleen size, α-fetoprotein (AFP) levels to
stratify risk of hepatocellular carcinoma6. In
endemic areas of hepatitis D virus (HDV)
infection, HDV screening should be conducted in
children with chronic HBV infection11. AFP is a
marker of risk of hepatocellular carcinoma but
an elevated AFP level alone often does not
indicate whether hepatocellular carcinoma is
present. AFP elevations commonly occur with
active liver inflammation6. Performing both serum
AFP levels and ultrasounds every 6 months in
those with significant fibrosis is recommended.
Much of this screening is, however, done with
medico-legal concerns because there are no
data that suggest that such screening is cost
effective or that it may alter the natural course of
disease11.
The investigations necessary on follow up are
according to the phase of disease and shown
under the section of “Management of Chronic
Infection”.
Liver biopsy cannot be considered essential for the
diagnosis, management and treatment of
chronic HB in children, but it may be helpful in the
following circumstances8, 12:
1.
To evaluate the suspected co-factors of liver
damage that might interfere with the efficacy
of treatment.
2. In the staging of liver disease in the cases HBe
negative hepatitis with lower HBV DNA levels
(2,000-20,000 IU/mL) and borderline normal or
minimally elevated ALT levels. .
3. In cases where cirrhosis of liver cannot be
ruled out clinically before treatment.
4. When a new drug, or a new combination of
drugs, is tested in a therapeutic trial.
www.ppa.org.pk
5. In cases of where ALT is persistently more
than normal but < 2 times of normal, liver
biopsy may be done for inflammatory
changes and fibrosis in the liver before the
start of treatment.
Treatment may be initiated if there is moderate/
severe inflammation or significant fibrosis on
biopsy8. Repeat liver biopsy is not necessary after
treatment13.
MANAGEMENT OF CHRONIC INFECTION
The optimal goal of antiviral treatment is to clear
HBsAg permanently. But even in adults the
current treatment options are insufficient to
achieve this goal. So the current goal is to
prolong survival and improve long term
outcomes by10:
1. Stopping/decreasing viral replication
2. Normalizing aminotransferases
3. Normalizing liver histopathology
4. Preventing cirrhosis
5. Preventing
hepatocellular
carcinoma.
Consensus guidelines for the treatment of
Hepatitis B infection in children have not been
established yet. But reviewers recommend
treatment for children over 2 years of age10.
Response to treatment is evaluated differently in
interferon and nucleoside analog treatments.
Ideal end point of treatment is sustained HBsAg
loss with or without seroconversion of anti HBs. The
other end points include:
1. Durable HbeAg seroconversion in HbeAg
positive patients.
2. In cases where HbeAg seroconversion is not
achieved, sustained undetectable HBV DNA
either under nucleoside analog treatment or
after interferon treatment10.
It is to be noted that all persons with chronic
hepatitis B not immune to hepatitis A should
receive 2 doses of hepatitis A vaccine 6 to 18
months apart8.
The line of management depends on HBe Ag
status; Sr ALT level and HBV DNA level of the child
and may be as follow:
I.
HBe Ag+, Serum ALT Normal, and HBV DNA >20
000 IU/ml: During this phase no treatment is
effective. Follow up investigations include
97
Management of Hepatitis B and C in Children
serum ALT, HBeAg, Anti-HBe, and AFP every
6 to 12 monthly (6). If ALT is raised ≥ 2 times
of normal, consult subheading II while if it is
increased but < 2 times of normal, consult
subheading III for the treatment8.
II.
HBe Ag+, Serum ALT ≥ 2times of normal, HBV DNA
>20 000 IU/ml: Immediate antiviral therapy is
started if there is clinical decompensation
or patient is icteric. Otherwise treatment is
given in cases of persistent ALT ≥ 2 times of
normal lasting more than 3-6 months (8).
Get serum ALT and AFP levels every 6 to 12
monthly and HBeAg/Anti-HBe and HBV DNA
levels every 12 months if the child is on no
treatment6.
The first line of drug for the treatment is interferonalpha 5-10 million units/ sq meter thrice weekly
subcutaneously. The duration of therapy is
predefined (as it has immune modulatory effects)
and is 16-24 weeks8. The end-point of treatment is
seroconversion from HBeAg to anti-HBe (serologic
response) which may not be present at the end
of therapy and may occur 6-12 months after
completion of therapy13. So the other response is
virologic. The virologic response is defined as
decline in HBV DNA levels below 2000 IU/ml at 24
weeks of therapy on interferon10.
In patients treated with interferon alpha, full
blood counts and serum ALT levels should be
monitored monthly. Serum HBV DNA level should
be assessed at weeks 12 and 24 to verify
response. HBeAg and anti-HBe antibodies should
be checked at weeks 12 and 24 and 24 weeks
post-treatment. HBsAg should be checked at 6months intervals after HBe seroconversion if HBV
DNA is undetectable14.
The second line of drug is lamivudine which is
used in IFN α non-responders / contraindications
to IFN α. The dosage is lamivudine 3mg/kg/day
(max 100mg) orally. Treatment may be
discontinued in patients who have confirmed
HBeAg seroconversion (i.e. serologic response
defined as HBeAg loss and anti-HBe detection on
2 occasions 1-3 months apart) and have
completed at least 6 months of consolidation
therapy after the appearance of anti-HBe8. In
HBeAg-positive patients who do not achieve HBe
seroconversion, a maintained undetectable HBV
DNA level on treatment with lamivudine (i.e.
virologic response which is defined as
undetectable HBV DNA with real time PCR assay
within 48 weeks of lamivudine or other antiviral
therapy) is the next most desirable end-point10,14.
Primary none response is defined as less than 1
log IU/ml decrease in HBV DNA level from
baseline after 12 weeks of treatment10, 11. Primary
nonresponse is rarely observed with lamivudine14
while not applicable to interferon therapy11. In
patients with primary non-response, it is important
to check for compliance. In a compliant patient
with a primary non-response, the possibility of HBV
resistant mutations should be considered14.
During follow up on lamivudine therapy serum
serum ALT should be monitored every 3 monthly
and HBV DNA levels every 3-6 monthly, and
HBeAg and anti-HBe should be tested at the end
of 1 year of treatment and every 3-6 monthly
thereafter. Close monitoring for relapse is needed
after withdrawal of treatment8.
The investigation for post-treatment follow up on
lamivudine is close monitoring every 1-3 monthly
for the first 6 months, and every 3-6 monthly
thereafter8. Reinstitution of lamivudine treatment
is usually effective in patients who have relapsed
but not developed resistance.
HBeAg-positive patients who develop HBe
seroconversion with interferon or antiviral drugs
require long follow-up because of the possibility
of HBeAg-negative chronic hepatitis B14 as
discussed under subheading V.
3. HBe Ag+, Serum ALT increased but < 2 times
of normal, HBV DNA >20 000 IU/ml: If ALT is
more than normal but < 2 times of normal, the
patient should not be treated unless liver
biopsy shows moderate/severe inflammation
or significant fibrosis in the absence of other
etiologies13.The follow up with or without
treatment as well as treatment protocol is
same as given in the paragraph II.
4.
HBe Ag-ve, serum ALT Normal, HBV DNA <20 00
IU/ml: The child should be kept on follow up
by measuring serum ALT and AFP levels every
6 to 12 monthly and HBeAg/Anti-HBe and HBV
DNA levels every 12 monthly. No treatment is
needed during this phase. If HBV DNA or ALT
becomes higher, then manage as given in
paragraph V.
5. HBe Ag -ve, serum ALT increased, HBV DNA >20
000 IU/ml: Since this phase is uncommon in
www.ppa.org.pk
98
Rehmanm A, Mazhar TU
children there is no data on treatment of
HBeAg negative children10. The line of
management (according to recommenddations in adults) is as follows:
Treat with IFN- α for one year in a dosage
shown in subheading II. In cases of IFN α nonresponders / contraindications to IFN α
lamivudine is used in a dosage shown in
subheading II.
The end point of therapy is not defined but
treatment should be continued until the
patient has achieved HBsAg clearance. A
maintained undetectable HBV DNA level on
treatment with lamivudine or a sustained
undetectable HBV DNA level after interferon
therapy is the next most desirable end-point14.
Sometimes the response of INF is observed
6-12 months after completion of therapy13.
The vast majority of children relapsed when
lamivudine was stopped while extending the
treatment results in evolution of lamivudine
resistant mutants. Post-treatment relapse may
occur even in patients with persistently
undetectable serum HBV DNA by PCR assay8.
VI
BeAg +/-ve, HBV DNA Detectable and Cirrhosis:
Treatment of patients with cirrhosis is not
based on ALT levels, as these may be normal
in advanced disease. Interferon alpha is
contraindicated as it increases the risk of
sepsis and decompensation in patients with
advanced cirrhosis. Treatment is indicated
even if HBV DNA level is low in order to
prevent
recurrent
reactivation.
Close
monitoring of HBV DNA levels is important.
Hepatic decompensation may occur with
exacerbations of disease that must be
distinguished from non-compliance and
resistance. Thus patients with cirrhosis require
long-term therapy, with careful monitoring for
resistance and flares. Partial regression of
fibrosis has been reported14. In case of
compensated cirrhosis with HBV DNA >2,000
IU/ml the treatment should be with
lamivudine while if HBV DNA <2,000 IU/mL
then consider treatment with lamivudine if ALT
elevated. In cases of decompensated
cirrhosis, coordinate treatment with transplant
center and lamivudine preferred while refer
for liver transplant. These patients should
receive long-term treatment. However,
treatment may be stopped in HBeAg-positive
www.ppa.org.pk
patients if they have confirmed HBeAg
seroconversion and have completed at least
6 months of consolidation therapy and in
HBeAg-negative patients if they have
confirmed HBsAg clearance.
Close
monitoring for viral relapse and hepatitis flare
is mandatory if treatment is stopped8.
VII HBeAg +/-ve, HBV DNA undetectable and
Cirrhosis: In compensated cirrhosis the child is
only observed while in decompensated
cirrhosis the child should be refered for liver
transplant. Post–liver transplantation life-long
treatment is recommended8.
REFERRAL TO PEDIATRIC HEPATOLOGIST
Children with a family history that is suspicious for
hepatitis B–related cirrhosis or liver cancer or
having an AFP level of >10 ng/ml or children with
uncompensated liver disease should be
considered to be at high risk, and a pediatric liver
specialist should be consulted concerning the
frequency of appropriate monitoring6.
INTERFERONS
HEPATITIS B
AND
ANTIVIRAL
DRUGS
IN
The antiviral drugs and interferons approved by
FDA are adefovir for ages 12 and older; entecavir
for ages 16 years and older, interferon alfa-2b in
children as young as 12 months of age and
lamivudine may be used starting at 3 years of
age6.
Lamuvidine is a good antiviral agent but is not as
potent as the other antiviral drugs. It is associated
with a high viral resistance compared to some
other antiviral agents. Entacavir and tenofovir are
potent antiviral drugs with a higher genetic
barrier (lower viral resistance) and are preferred
antivirals10.
INTERFERON
Interferon–α is the therapy of choice for children
with chronic hepatits B13. The peginterferon
which has the advantages of more convenient
administration
and
more
sustained
viral
suppression, is not yet approved in children for
hepatitis B8. Durable complete response with
interferon in children differs between 37-56%. It
accelerates the natural course of hepatitis B.
HBeAg seroconversion may occur during or up to
12 months after the completion of therapy. There
99
Management of Hepatitis B and C in Children
is a small but reproducible rate of HBsAg
seroconversion after successful interferon-α
therapy that is rarely seen in untreated children.
The advantages include low probability of
resistance and fixed treatment duration while the
disadvantages are the need of multiple
injections, cost and side effects10.
Adverse Events: Children tolerate treatment better
than adults11. The adverse side effects are:
1. Fever is the most commonly observed side
effect and occurs at the beginning of
treatment which may lead to febrile
seizures13.
2. 2- The flulike symptoms of fever, myalgia,
headache, arthralgia and anorexia15.
3. 3-Neutropenia may occur in up to 39% of
children
during
treatment,
sometimes
requiring dose adjustments. Discontinuation of
the medication due to this side effect is rare.
Analysis
of
blood
count
is
usually
recommended during the therapy13.
4. Children lose weight as do adults, but may
also have decreased growth velocity during
treatment. These side effects are reversible,
resolving at least 6 months after treatment is
complete15.
5. 5-Mood disturbances may be significant, and
younger children may have personality
changes, irritability and temper tantrums15.
6. ALT flares during treatment do not mandate
cessation of therapy if there are no signs of
decompensation; these flares often herald
impending seroconversion15.
7. Alopecia and mental disturbance including
severe depression are important side effects
but are rare in childhood11.
8. Interferon- α has been reported to induce the
development of a variety of autoantibodies.
In most instances, this is not accompanied by
clinical illness. However,in adults both hyperand hypo-thyroidism that require treatment
have been reported8.
9. 9-Rarely, retinal changes and even impaired
vision have been reported8.
Contraindications: These are similar to those in
adults15 and include:
1. 1-Decompensated cirrhosis e.g. ascitis,
hepatic
encephalopathy,
hemetemesis
prolonged prothrombin, hypoalbuminemia15.
2. 2- The autoimmune disorders especially in the
presence of antibodies to liver and kidney
microsomal antigens type 1 (LKM 1) because
interferon exacerbate liver damage. Low
titers of other autoantibodies (e.g. antinuclear
or anti-smooth muscles) without other
manifestation of autoimmunity are not
contraindications for treatment13.
3. 3-Organ transplant or serious neuropsychiatric
disease13, 15.
4. 4-Cytopenia caused by hypersplenism15.
5. Severe renal or cardiac disorder11, 13.
6. 6-Neurological diseases although few children
with well controlled epilepsy may tolerate
treatment13.
7. Repeated febrile seizures during treatment
require therapy cessation but children with a
history of febrile seizures should be treated
above the age of risk or provided
temperature is carefully monitored13.
LAMIVUDINE
It is well tolerated. Serious side effects are rare
even after 3 years of continuous treatment. It is
effective, safe and well tolerated even following
unsuccessful interferon-alpha therapy16. Durable
complete virologic response rate is observed in
23-65% of children especially in preschool
children. Lamivudine is easier to administer,
cheap and has no serious side effect but its
drawbacks are induction of mutations, does not
improve the seroconversion and cross resistance
with many new antiviral agents10.
Treatment for longer than 1 year has been
associated with increased risk of resistance.
Continuation of lamivudine once resistance is
developed is controversial. It has been
recommended that lamivudine be continued as
long as HBV DNA remains suppressed, but be
discontinued in the child who has virologic
breakthrough and no serious underlying liver
disease15. Viral relapse and exacerbations of
hepatitis may occur after discontinuation of
lamivudine therapy, including patients who have
developed HBeAg seroconversion, and may be
www.ppa.org.pk
100
Rehmanm A, Mazhar TU
delayed up to 1 year after cessation of
treatment. Reinstitution of lamivudine treatment is
usually effective in patients who have not
developed resistance. In patients who have
breakthrough infection, testing for lamivudineresistant mutants should be performed whenever
possible8.
NEONATE OF HBs Ag POSITIVE MOTHER
Every mother should
pregnancy for HBs Ag.
be
screened
during
Administer 1 dose of hepatitis B immunoglobulin
(0.5ml intramuscularly) and the first dose of
vaccine to newborns of HBsAg-positive mothers
within 12 hours of birth. Completion of the 3 dose
hepatitis B vaccination series by 6 months of age
(0, 1, 6 months). Effectiveness of this management in preventing infection is 95%6.
Postvaccination testing of infants born to HBsAgpositive mothers for protective antibody response
anti-HBs and HBsAg is recommended between 9
and 18 months of age to determine if infection
has been prevented. The protective value of
anti-HBs is ≥ 10 IU/L. If the level is
<10 IU/L then get HBs Ag testing done.
If negative →→ non immune →→ needs active
vaccination
If positive →→ infected →→ follow to document
chronic infection as mentioned above
≥10 IU/L and the child is immune and no action is
needed6.
CHILDREN WHO NEED TO BE TESTED FOR
HEPATITIS B INFECTION
Ideally all Pakistani children, even if they have
received hepatitis B vaccine, should be screened
as Pakistan is endemic for hepatitis B infection. If it
is not possible then the following groups should,
at least, be screened6, 8, 17.
-
Infants born to HBsAg-positive mothers.
-
Children living in a household with an HBsAg
positive individual, including those children
who had received hepatitis B vaccine after
birth and were not screened before
vaccination.
-
Sexual contacts of HBsAg-positive persons.
www.ppa.org.pk
-
Children who have ever injected drugs.
-
Children with chronically elevated ALT or AST.
-
Children infected with HCV or HIV.
-
Children undergoing hemodialysis.
-
Children requiring multiple blood transfusions
or surgery.
-
Children
therapy.
needing
immunosuppressive
Serum HBsAg, along with anti-HBs, is the most
effective screening tool for HBV infection17.
Children found to be HBsAg-positive should be
retested six months later to document chronic
infection. If the child is HBs Ag as well as anti-HBs
negative, he must be immunized while if the child
is HBs Ag negative but anti-HBs positive he is fully
immunized and no action is needed.
SYMPTOMATIC ACUTE HEPATITIS
Antiviral therapy is not recommended in patients
with symptomatic acute hepatitis. In adults there
is some opinion to treat severe acute hepatitis B
(as defined by two of the following three criteria:
hepatic
encephalopathy,
serum
bilirubin
>10.0mg/dL or INR >1.6) and deep jaundice
persisting for >4 weeks. Lamivudine may be used.
Treatment should be continued until HBsAg
clearance is confirmed or indefinitely in those
who undergo liver transplantation. Interferon alpha is contraindicated. There are no studies in
children about the treatment8, 14.
COINFECTION WITH HBV and HEPATITIS D
The only approved treatment of chronic hepatitis
D is interferon alpha in high dose (9 Million units 3
times a week).
HEPATITIS C IN CHILDREN
HCV is an enveloped, single-stranded positivesense RNA virus, belonging to the Hepacivirus
genus within the flavivirus family and has 6 major
HCV genotypes designated 1 to 6, with multiple
subtypes within each viral genotype18. HCV
infection is designated hepatitis C when it is
accompanied by biochemical and/or histologic
evidence of inflammation and necrosis19.
101
Management of Hepatitis B and C in Children
LABORATORY TESTS
Serologic Assays: There is two common antibody
tests used to detect HCV antibodies—HCV EIA
(ELISA) and HCV RIBA (Recombinant immunoblot
assay). Both assays detect IgG anti-HCV
antibody; no IgM tests are available20. The
specificity of current EIAs for anti-HCV (third
generation) is greater than 99%. False positive
results are more likely to occur when testing is
performed among populations where the
prevalence of hepatitis C is low. False negative
results may occur in the setting of severe
immunosuppression such as infection with HIV,
solid organ transplant recipients, hypo- or
aggammaglobulinemia or in patients on
hemodialysis. HCV RIBA assay was originally
developed as a more specific, supplemental
assay to confirm the results of EIA testing.
However, due to extremely high specificity for
third generation EIA results the role for RIBA testing
in HCV diagnosis and management has all but
disappeared21.
Molecular Assays: There is list of commercial assays
available for the detection (qualitative assays) or
quantification (quantitative assays) of HCV RNA.
There is recommendation of use of quantitative
assays, instead of qualitative assays, as the
recent available real time polymerase chain
reaction (PCR) based assays and transcriptionmediated amplification (TMA) assays are even
able to detect RNA as low as 10 IU/ml21. The
specificity of HCV RNA PCR is 98% from birth. The
HCV PCR may be intermittently negative. During
therapy,
serial
quantitative
HCV
RNA
determination is mandatory for the monitoring of
treatment efficacy18.
The IU rather than viral copies is now the
preferred unit to report test results21. Changes in
viral load are sometimes expressed in terms of
logs. There is no standard conversion formula for
converting the amount of HCV RNA reported in
copies per milliliter to the amount reported in
International Units. The conversion factor ranges
from about one to about five HCV RNA copies
per IU. Usually the lab report will list the conversion
from IU/ml to copies/ml22. For monitoring
purposes, it is important to use the same
laboratory test before and during therapy21.
Genotyping Assays: Genotyping is useful in
epidemiological
studies
and
in
clinical
management. HCV genotyping should be
performed in all HCV-infected adults prior to
interferon-based treatment in order to plan for
the dose and duration of therapy and to
estimate the likelihood of response21. But these
assays are not essential for the treatment in
children.
Interpretation of HCV Assays21: Anti-HCV +ve
HCV
RNA +ve Acute or chronic HCV depending on
the clinical context
Anti-HCV +ve HCV RNA -ve Resolution of HCV;
Acute HCV during period of low-level viremia.
Anti-HCV -ve HCV RNA +ve Early acute HCV
infection;
chronic
HCV
in
setting
of
immunosuppressed state;
false positive HCV RNA test
Anti-HCV -ve
infection
HCV RNA -ve Absence of HCV
Chronic Hepatitis C: Chronic infection is defined as
the persistence of HCV RNA for at least six
months23.
NATURAL COURSE AND CLINICAL FEATURES
The natural course of HCV infection in children is
not clearly understood, but overall advanced
liver disease is rare during childhood18. Liver
Biopsy studies in children generally have
demonstrated minimal fibrosis and cirrhosis is
rarely seen without underlying disorders12 but
significant disease may occur as well21.
Spontaneous resolution is defined by sustained
disappearance of HCV RNA from the serum,
accompanied by normalization of aminotransferase enzymes, although anti-HCV antibody
may persist. Defining disappearance of HCV RNA
from serum does not means ‘‘cure’’ as low levels
of HCV RNA, of uncertain clinical significance
may persist below the conventional threshold of
detection. Spontaneous resolution in cases of
vertical transmission is 10-55% while in cases of
transmission by blood transfusions is 27-48%. The
cause of this difference is unknown23.
Children, who are acutely infected with HCV, like
adults, are generally asymptomatic, but they are
more likely than infected adults to spontaneously
clear the virus and are more likely to have normal
www.ppa.org.pk
102
ALT levels21. Most children with HCV infection are
asymptomatic, with minor abnormalities such as
hepatomegaly or mild nonspecific symptoms
occasionally reported. Despite this, most
perinatally infected infants will have intermittently
or
persistently
abnormal
liver
enzymes,
particularly in the first two years of life. Serum ALT
elevation does not correlate well with histological
severity23.
HISTOPATHOLOGY
The full spectrum of elementary histological
lesions described in adult patients can be seen in
the liver of children and adolescents but children
more often exhibit a mild disease activity. The
histological assessment and the grading and
staging system are the same as in adults12.
MANAGEMENT
Although controversial but most experts believe in
treatment of hepatitis C in children. Given the
generally indolent course of HCV infection in
children and the efficacy and safety profile of
available therapeutic options, a reasonable
approach is to offer treatment only to children
with evidence
of
liver
disease, as
is
recommended in adults. Eradicating HCV to
avert the potential hepatic complications in later
life, as well as eliminating the social stigma
associated with harboring a contagious infection,
is a justifiable reason to pursue antiviral therapy in
children. It is well known that the shorter the
duration of infection, the better the response to
treatment. Therefore, it may be argued that all
children with chronic hepatitis C (detectable
serum HCV RNA for longer than 6 months),
irrespective of degree of liver injury, should be
considered for treatment18.
The aim of treatment is to achieve a sustained
viral response i.e. HCV RNA becoming
undetectable and remaining so after treatment
has been completed23. The sustained viral
response is the best correlate of beneficial
changes in hepatic fibrosis and improvement in
other clinical outcomes18.
Children with HCV should be immunized against
hepatitis A and B23.
Drug therapy and age: Children aged 2-17 years
with chronic hepatitis C should be considered
appropriate candidates for treatment using the
www.ppa.org.pk
Rehmanm A, Mazhar TU
same criteria as that used for adults21. With the
increased
possibility
of
spontaneous
seroconversion occurring within the first three
years of life, some authorities recommend to
postpone the treatment at least until age 3 years
or older23, unless significant liver dysfunction
occurs earlier18. For patients in whom liver
histology is available, treatment is indicated in
those with bridging fibrosis or compensated
cirrhosis
provided
they
do
not
have
contraindications to therapy21.
Children should be treated with pegylated
interferon alfa-2b 60 ug/m2 weekly given
subcutaneously in combination with ribavirin 15
mg/kg daily for duration of 48 weeks irrespective
of genotype. The other licensed pegylated
interferon in the United States is peginterferon
interferon alfa-2a. The doses of these two forms of
pegylated interferons differ21. But the results are
compareable18.
In children limited data has shown that at least a
2-log reduction from baseline serum HCV RNA
levels after 12 weeks of therapy rather than loss of
detectable HCV RNA or loss of detectable HCV
RNA after 24 weeks of treatment should be taken
as response and treatment can be safely
stopped in those patients having no response18. If
HCV RNA remains detectable between 12 to 24
weeks of therapy, therapy may be extended to
72 weeks18.
ASSESSMENT AND MONITORING
Although there are no pediatric-specific
guidelines, periodic assessment of children with
chronic HCV infection is recommended. Children
with newly diagnosed HCV infection should
undergo medical evaluation to detect the
presence of liver disease or its sequelae and
exclude other potential concomitant causes of
hepatic dysfunction18.
It is recommended that a pediatric hepatologist
is involved at an early stage. Children with HCV
should be reviewed six monthly to include
assessment of liver function and viral status, and
discuss the role of antiviral treatment. An annual
ultrasound and alpha-fetoprotein estimation is
recommended, to facilitate early diagnosis of
progression of liver disease or emergence of
hepatocellular carcinoma23.
103
Management of Hepatitis B and C in Children
Screening for hepatocellular carcinoma in
children with chronic HCV infection is particularly
problematic because this dreaded complication
is rare in this population and not cost effective.
There are no pediatric-specific guidelines. In
some centers, children with chronic HCV
infection will undergo periodic sonographic
screening at defined intervals (every 3–5 years),
whereas in others, only those with advanced liver
disease will undergo regular screening. To screen
for liver cancer in children with HCV infection with
liver fibrosis or cirrhosis should undergo periodic
surveillance with ultrasonography and afetoprotein concentrations, probably yearly. The
recommendation in adults with HCV infection to
screen for is ultrasonography at every 6 to 12
months’ interval18.
Liver biopsy, like in hepatitis B, is not essential for
the diagnosis, management and treatment of
chronic hepatitis C in children as it is an invasive
procedure. A liver biopsy is likely to be required
mainly for participants in therapeutic trials and for
patients with putative co-factors of liver damage
who are ‘‘difficult to treat’’12. The role of liver
biopsy in relation with genotype is also
controversial18, 21. So it must be noted, however,
that while information obtained from a biopsy is
useful, the procedure is not mandatory for
deciding about treatment21.
Less invasive tests (alternative to liver biopsy) ,
such as the use of serologic markers of fibrosis,
fibroscan (used for liver stiffness measurement),
and magnetic resonance elastography, appear
promising in adults , but so far, little is known
about these tools in children18.
Patients should be monitored during therapy to
assess the response to treatment and for the
occurrence of side effects. A reasonable
schedule would be monthly visits during the first
12 weeks of treatment followed by visits at 8 to 12
week intervals thereafter until the end of therapy.
At each visit the patient should be questioned
regarding the presence of side effects and
depression. They should also be asked about
adherence to treatment. Laboratory monitoring
should include measurement of the complete
blood count, serum creatinine and ALT levels.
HCV RNA should be tested by a highly sensitive
quantitative assay at the initiation of or shortly
before treatment and at week 12, 24 of therapy
and then 4 to 12 week intervals thereafter, the
end of treatment, and 24 weeks after stopping
treatment. Thyroid function should be monitored
every 12 weeks while on treatment21.
TREATMENT RELATED TOXICITY
Adverse events are common during treatment
with peg interferon based therapies alone or in
combination with ribavirin.. The following are
selected antiviral-related adverse events18
‘‘Flu-like’’ symptoms
Fatigue
Anorexia
Weight loss
Depression
69-100% cases
61-73
21-77
20-67
0-13
Mood swings and behavioral changes (per
caregivers reported) 15%.
Anxiety and irritability 40%
Anemia (<10 g/dL) 5-8
Neutropenia (<1000x 109 cells/L) 22-56
Thrombocytopenia1 (<<100,000/dl) <1-2
Premature discontinuation <1- 10
Although rare, suicidal attempt may occur in
treated children. Although autoimmune markers
arise during treatment, their pathobiological
importance is uncertain. Detectable antithyroid
antibodies are particularly common and clinical
thyroid disease occurs, which only rarely
becomes permanent. Adverse events led to dose
modification in 23-31% and dose discontinuation
in 7%21.
Based on above mentioned potentially clinically
significant complications, patients need to be
carefully monitored18.
CONTRAINDICATIONS OF THERAPY
Contraindications mentioned under the heading
of interferon in “Hepatitis B”.
Age less than 2 years
Known hypersensitivity to drugs used to treat
HCV21
RETREATMENT
The studies in adults and published reports in
children with previous failed response gave
following recommendations18, 21.
www.ppa.org.pk
104
1. Retreatment with peginterferon plus ribavirin
in patients who did not achieve a sustained
viral response after a prior full course of
peginterferon
plus
ribavirin
is
not
recommended, even if a different type of
peginterferon is administered.
2. Retreatment with peginterferon plus ribavirin
can be considered for non-responders or
relapsers who have previously been treated
with non-pegylated interferon with or without
ribavirin, or with peginterferon monotherapy,
particularly if they have bridging fibrosis or
cirrhosis.
3. Maintenance therapy is not recommended
for patients with bridging fibrosis or cirrhosis
who have failed a prior course of
peginterferon and ribavirin.
TREATMENT OF CHILDREN WITH NORMAL
SERUM AMINOTRANSFERASE VALUES
These recommendations are based on studies in
adults. The decision to initiate therapy with
pegylated interferon and ribavirin is regardless of
the serum alanine aminotransferase level and
based on the severity of liver disease by liver
biopsy. The treatment regimen is the same as that
used
for
persons
with
elevated
serum
aminotransferase levels as discussed above21.
Mother And Hepatitis C Status: Because of universal
testing of blood donors for anti-HCV since 1992,
mother-to-child
(vertical)
transmission
has
replaced transfusion-associated hepatitis C to
become the most common mode of HCV
transmission21. Both intrauterine and perinatal
transmissions are important routes of vertical
infection. Vertical transmission is almost always
confined to women who have detectable HCV
RNA23. There has been no report of HCV
transmission to an infant born to a woman
positive for anti-HCV antibody but negative for
HCV RNA. However, because serum viral levels
may fluctuate during pregnancy, measuring HCV
RNA concentration to detect active viremia late
in pregnancy is recommended. No difference is
also observed in the vertical transmission of
different HCV genotypes18.
The routine screening of all pregnant women for
HCV antibodies is not recommended. Selective
testing based on high risk has been advocated
www.ppa.org.pk
Rehmanm A, Mazhar TU
by some, but does not detect all cases of HCV
infection21.
There is no contraindication of delivery per
vaginum in anti HCV-infected mothers but the
avoidance of use of fetal scalp monitors and the
delivery within 6 hours of rupture of membranes
to avoid transmission is recommended by many
authorities. The cesarean section is not
recommend by most authorities to prevent
transmission21,23.
Although HCV has been identified in breast milk
of infected mothers, there is no data to show that
HCV is transmitted in breast milk; therefore
breastfeeding is not prohibited in HCV-infected
mothers despite HCV RNA being frequently
detectable in colostrums18, 21.
Testing of infants born to HCV infected women
should be preformed because of the risk of
perinatal transmission. Maternal antibodies
passively transferred to the newborn may persist
for up to 18 months of age. Therefore, it is
recommended to postpone anti-HCV testing in
exposed infants until 18 months of age. If earlier
diagnosis is desired, testing for HCV RNA may be
performed at or after 2 months of age. However,
the sensitivity of HCV RNA testing at this time is
low and a negative test should be repeated at a
later date. Therefore it may be more prudent to
defer HCV RNA testing until 6 months when
sensitivity of the test is improved21. Infants are
considered infected if HCV RNA is positive on two
or more occasions23.
ACUTE HEPATITIS C
Acute hepatitis is asymptomatic while acute
fuminant hepatic failure is extremely rare.
Treatment in children is avoided as there is early
spontaneous resolution18.
PERSONS FOR WHOM HCV SCREENING IS
RECOMMENDED
-
Children who have injected illicit drugs
-
Children with conditions associated with a
high prevalence of HCV infection including:
Persons with HIV infection
Persons who
hemodialysis
have
ever
been
on
105
Management of Hepatitis B and C in Children
Persons with unexplained
aminotransferase levels
-
abnormal
Prior recipients of transfusions or organ
transplants prior to July 1992 including:
Persons who were notified that they had
received blood from a donor who later
tested positive for HCV infection
Persons who received a transfusion of
blood or blood products
Persons who received an organ transplant
-
Children born to HCV-infected mothers
-
Sexual partners of HCV-infected person
Routine screening of internationally adopted
children for HCV is generally not recommended
unless the biological mother has a known high-risk
factor, such as injection drug use.
Patients suspected of having acute or chronic
HCV infection should first be tested for anti-HCV
With interferon monotherapy in HCV RNA–positive
patients, sustained virological response is found
to be 58.7% - 87.5%.Ribavirin is not generally used
in combination with interferon for the treatment
of such patients because of fear of hemolysis and
worsening of anemia due to the ribavirin18. There
are reports of successful usage of ribavirin at the
cost of slightly increased blood transfusion rates25.
Treatment of other factors like iron overload
causing
liver
damage
should
also
be
addressed18.
RESTRICTIONS ON CHILD WITH HEPATITIS B
AND C
Horizontal transmission from child to child is rare.
Therefore, the American Academy of Pediatrics
does not recommend restricting children with
chronic HCV infection from school attendance or
participation in routine activities, including
sports21.
--------------------------------------------------------------------------------
HCV RNA testing should be performed in:
Author’s affiliations
a) Patients with a positive anti-HCV test
Abdul Rehman, Prof. Attaullah Mazhar
b) Patients for whom antiviral treatment is being
considered, using a sensitive quantitative
assay
Department of Pediatrics, Quaid-e-Azam Medical
College, Bahawalpur
c) Patients with unexplained liver disease whose
anti-HCV test is negative and who are
immunocompromised or suspected of having
acute HCV infection.
COINFECTION WITH HBV and HCV
The standard recommendations for the treatment
of these coinfections are not even present for
adults. Combination therapy with peginterferon
and ribavirin was equally effective in patients with
HCV monoinfection and in those with HBV/HCV
coinfection8.
CHILDREN WITH THALASSEMIA
Treatment of chronic hepatitis B in patients with
thalassemia does not differ from that of nonthalassemic patients24.
HCV infection and iron overload may act as
synergistic risk factors for the development of liver
cirrhosis and . Clearly, the treatment of chronic
HCV in these patients has become imperative,
along with the management of iron overload.
REFERRENCES
1.
Prime Minister’s Program for Prevention &
Control
of
Hepatitis.
Available
at:
www.pakistan.gov.pk/divisions/healthdivision/media/FAQ_pch.doc. Downloaded
on 23-10-2009.
2.
Khan HI. A study of seroprevalence of
hepatitis B and C in mothers and children in
Lahore. Pak Paed J 1996; 20: 163-66.
3.
Shah MA, Khan MT, Ulla Z, Ashfaq Y.
Prevalence of Hepatitis B and Hepatitis C
virus
infection
in
multi-transfused
thalassemia major patients in North West
Frontier Province. Pak J Med Sci ; 21: 281-83.
4.
Ali Mubarak, Saleem M, Mazhar A. Hepatitis
B and C status of thassemia major patients.
Medical Channel 2005; 11(3): 19-21.
5.
Louis-Jacques O, Olson AD. Cost-benefit
analysis of interferon therapy in children
with chronic active hepatitis B. J Pediatr
Gastroenterol Nutr 1997; 24: 25-32.
www.ppa.org.pk
106
6.
7.
Rehmanm A, Mazhar TU
Haber BA, Block JM, Jonas MM, Karpen SJ,
London
WT,
McMahon
BJ
et
al.
Recommendations
for
Screening,
Monitoring, and Referral of Pediatric
Chronic
Hepatitis
B.
Pediatrics
2009;124:e1007-e1013.
Available
at:
http://pediatrics.aappublications.org/cgi/re
print/124/5/e1007
England K, Thorne C, Pembrey L, Tovo PA,
Newell ML. Age- and sex-related reference
ranges of alanine aminotransferase levels in
children:
European
paediatric
HCV
network. J Pediatr Gastroenterol Nutr. 2009
Jul; 49(1): 71-77.
8.
Lok ASF, McMahon BJ. Chronic hepatitis B:
update 2009. Hepatology. 2009; 50: 661-62.
9.
Keeffe EB, Dieterich DT, Han SHB, Jacobson
IM, Martin P, Schiff ER,et al. A Treatment
Algorithm for the Management of Chronic
Hepatitis B Virus Infection in the United
States: 2008 Update. Clin Gastroenterol
Hepatol 2008; 6:1315–41.
10.
11.
16.
Liberek A, Szaflarska-Popławska A, Łuczak
G, Góra-Gebka M, Jankowska A, ŁośRycharskda E, et al. Therapy of chronic viral
hepatitis type B in children after previous
ineffective
interferon-alpha
treatment.
[Article in Polish] Med Wieku Rozwoj 2007;
11: 373-79.
17.
Shah U, Memon I,
Thobani S, Mirza R.
the Treatment of
infection in children.
204-07.
18.
Mohan N, Gonza´lez-Peralta RP, Fujisawa T,
Chang MH, Heller S, Jara P, et al. Chronic
Hepatitis C Virus Infection in Children. J
Pediatr Gastroenterol Nutr 2010; 50: 123-31.
19.
Richard D Aach, Roslyn A. Yomtovian and
Maureen Hack. Neonatal and Pediatric
Posttransfusion Hepatitis C: A Look Back and
a Look forward. Pediatrics 2000; 105: 836-42.
20.
Committee on Infectious Diseases. Hepatitis
C Virus Infection. Pediatrics 1998; 101:48185.
Cheema HA, Ali S,
Recommendations for
Chronic Hepatitis B
J Pak Med Assoc 2007;
Makbule EREN. Peginterferon Treatment in
Children: A Review of Chronic Hepatitis B
and Chronic Hepatitis C Treatment. JPS
2009;
1;
e4.
Available
at:
http://www.pediatricsciences.com/ojs/inde
x.php/jps/article/view/5. Downloaded on
20-2-2010.
21.
Ghany MG, Strader DB, Thomas DL, Seeff LB.
Diagnosis, Management, and Treatment of
Hepatitis C: An Update. Hepatologyl 2009;
49: 1335-74.
22.
Shah U, Kelly D, Chang M, Fujisawa T, Heller
S, Gonza´lez-Peralta RP, Jara P, MieliVergani G, Mohan N, Murray KF.
Management of Chronic Hepatitis B in
Children. J Pediatr Gastroenterol Nutr 2009;
48: 399–404.
Highleyman L, Franciscus A. HCV Diagnostic
Tools: HCV Viral Load Tests. HCSP • VERSION
2.1 November 2006; 2007 available at
http://www.hcvadvocate.org/hepatitis/fac
tsheets_pdf/Viralload_%202007.pdf
Down
loaded on 10-1-2010.
23.
Davison SM, Mieli-Vergani G, Sira J, Kelly DA.
Perinatal hepatitis C virus infection:
diagnosis and treatment. Arch Dis Child.
2006; 91: 781-85.
24.
Mallat ME, Sharara AI. Treatment and
prevention of hepatitis B and C in
thalassemia. Hemoglobin. 2009; 33 Suppl 1:
S139-44.
25.
Harmatz P, Jonas MM, Kwiatkowski JL,
Wright EC, Fischer R, Vichinsky E, Giardina
PJ, Neufeld EJ, Porter J, Olivieri N.Safety and
efficacy of pegylated interferon alpha-2a
and ribavirin for the treatment of hepatitis C
in
patients
with
thalassemia.
Haematologica. 2008 ; 93:1247-51.
12.
Guido M, Flavia Bortolotti. Chronic viral
hepatitis in children: any role for the
pathologist? Gut 2008; 57: 873-77.
13.
Liberek A, Luczak G, Gora-Gebka M,
Landowski P. Management of chronic
hepatitis B in children. Hep B Annual 2006; 3:
106-27.
14.
EASL
Clinical
Practice
Guidelines:
Management of chronic hepatitis B.
European Association for the Study of the
Liver. J Hepatol 2009; 50: 227–42.
15.
Jonas MM. Treatment of Chronic Hepatitis B
in Children. J Pediatr Gastroenterol Nutr
2006; 43: 56-60.
www.ppa.org.pk
ORIGINAL ARTICLE
Immunization Coverage of BCG among Children
Reporting to Tertiary Care Hospital by Gender and
Nutritional Status
EMAD UD DIN SIDDIQUI, SHAHEENA HANIF, UZMA SIDDIQUI, Syed Jamal Raza
-----------------------------------------------------------------ABSTRACT
Pak Paed J 2010; 34(2): 107-11
Objective: To determine the immunization status for BCG in children
reporting to tertiary care hospital by gender and nutritional status.
See end of article for author’s
affiliations
-------------------------------------------Correspondence to:
Emad uddin Siddiqui,
Department of Paediatric
Emergency Medicine, Agha
Khan University Hospital,
Karachi
E-mail: [email protected]
Methods: Study was conducted at National Institute of Child Health,
Karachi between June 2004 to December 2005. Total of 180 admitted
patients were approached, 165 consented to participate in the study.
Only inpatients were included. Data were collected using a pre-tested
questionnaire. Convenient sampling was adopted.
Results: There were 165 children, most of them 96(58%) were less than 5
year of age. Females 91(55%) were commonly affected, 68(75%) were
unimmunized, while 57(63%) were malnourished. 42(70%) of female
children were both malnourished and unimmunized. The BCG
vaccination ratio among M:F was.1:0.6, while M:F ratio among
unimmunized children was 1:1.7. Overall 107(65%) cases were
unimmunized. 95(58%) children were malnourished, 39(23%) cases were
in PCM III. Pulmonary tuberculosis 70(42%) was the commonest
presentation. The most serious type affecting primarily the unimmunized
children of less than 05 years was tuberculous meningitis found in 23(14%)
cases.
Conclusion: Female children were less often vaccinated with BCG and
were also more often malnourished than the male children.
Malnourished females especially under 5 years of age and those who
were not vaccinated were admitted with the disease. The social rights of
our children especially the females should be addressed in every forum
and platform. The idea identified need to be re addressed.
Key words: Childhood tuberculosis, Immunization, malnutrition.
BACKGROUND
Tuberculosis is a disease since prehistoric time. Still
a major health burden even today, it is more
dreadful in the developing countries; 95% of all
cases are diagnosed every year in third world
countries. The global incidence of tuberculosis is
rising, with 8.8 million new cases and 2 million
deaths each year world wide1. It is estimated
that, between years 2000 to 2020 nearly one
billion people will be infected and 35 million will
die of tuberculosis if control is not further
strengthened2
Pakistan ranks seventh among the 22 hightuberculous
burden
countries
worldwide3.
According to the World Health Organization
(WHO), Pakistan accounts for 43 percent of the
TB (Tuberculosis) disease burden in the WHO
Eastern Mediterranean Region. Every year,
approximately 270,000 people in Pakistan had
new onset TB4. Prevalence of tuberculosis in
www.ppa.org.pk
108
Pakistan is estimated to be as high as 250,000
cases annually5, where as the incidence is 181
per 100,000 in adult population6. It is estimated
that a single adult with open pulmonary
tuberculosis can transmit the disease to 20
people per year in their close vicinity. These
adults are in direct contact with our children and
hence conveying the disease to them. Children
are not exempted from this brutal disease. It is
estimated that 3-13% of all TB cases in Pakistan
are among children7.
In Pakistan TB is on the rise, even in children10. The
literature on tuberculosis in Pakistan regarding the
prevalence in children is still reticent in spite of
extensive researches. We determined the
immunization status for BCG in children reporting
to tertiary care hospital by gender and nutritional
status.
MATERIAL AND METHODS
Study Design: Case series
Setting: This study was conducted at National
Institute of Child Health, Karachi. It is one of the
largest tertiary and teaching hospital with more
than 500 beds. The study populations were
children with tuberculosis who presented
between June 2004 and December 2005. The
diagnosis of tuberculosis was according to
Kenneth Jones Criteria. A convenient sample was
adapted. One hundred and eighty admitted
patients were approached and 165 consented
to participate in the study. Response rate of 92%
was observed.
Data Collection: Data was collected using a pretested questionnaire from all diagnosed patients
irrespective of their immunization status. We
included children between 6 months to 15 years
of age. Congenital TB (under 6 months of age)
was excluded. Kenneth Jones criteria were
applied for the diagnosis of tuberculosis with the
help of clinical presentation, radiological finding
and laboratory tests.8 Children with chronic illness
i.e. Cystic Fibrosis, Celiac Disease, Irritable Bowel
Disease, Chronic Liver Disease, Chronic Lung
Disease, Chronic Renal Fever, Respiratory Tract A,
congenital or acquired immunodeficiency
disease, patients with malignancy or on
steroids/chemotherapy etc were excluded from
the study. Outpatient cases of TB were excluded.
www.ppa.org.pk
Siddiqui EUD, , Hanif S, Siddiqui U, Raza SJ
Information about age, sex, BCG vaccination
status, weight and mode of clinical presentation
were assessed. Age was divided into three
groups, the preschool (<5 years of age), early
school (5-10 years) and early adolescent (10-15
years of age). Weight was assessed on the basis
of Modified Gomez classification as PCM I, II and
III. BCG immunization status was checked through
two variables, i.e. vaccination records and BCG
scar. This prevented any possible recall bias that
parents may induce if they were not sure of the
immunization status. Special emphasis was
focused on the relation of gender to age,
immunization and nutritional status of the
children.
RESULTS
We observed 180 cases. Fifteen refused to
respond. Total of 165 diagnosed cases of
tuberculosis were found. Most [96(58%)] children
were less than 5 year of age, while 37 (22%)
children were between 5-10 years. Regarding the
gender differences, (55%) female while 74(45%)
male children were found. In children <5 year
age group we found 59(36%) female as
compared to 37(22%) male children (Table 1).
Total of 106 (64%) unimmunized children were
identified, only 59 (36%) were immunized. In 91
females, 68(75%) were unimmunized, while only
23(25%) were immunized. If we compare these
unimmunized females (68) with males (38) we
found 36% males unimmunized out of 106
unimmunized children. Majority 62(65%) of these
children were <5 years of age (Table 1).
Similarly for the nutritional status, we observed
95(58%) malnourished children in either category
of PCM. Again females out numbered males as
we found 57(63%) malnourished female in
comparison to just 37% malnourished males. In
PCM III we found 39(23%) cases of either age
group or nutritional status. While 25(89%) of those
PCM III females were unimmunized also (Fig 1).
It was also observed that 42(70%) female children
included in the study were both unimmunized
and malnourished (PCM I-III) as compared to just
18(30%) males. Only 15(16%) girls were found to
be immunized and were normal for weight. This
shows that over all female children were less
immunized and malnourished as compared to
male child (Fig 1).
109
Childhood tuberculosis, Immunization, malnutrition
60%
50%
Immunized
40%
30%
20%
10%
Non Immunized
Percent
60%
50%
40%
30%
20%
10%
0%
Male
Fem ale
Gender Distribution
Fig 1: Comparsion of Gender, Immunization
and Nutrituional Status of Study Participants
Pulmonary tuberculosis was the commonest
presentation. Total of 70(42%) pulmonary
involvement cases were found. 36(22%) were
female and 34(21%) were male. 45(27%) patients
were
unimmunized
while
25(15%)
were
immunized. 15(9%) were in PCM III. 43(26%) were
of < 5 year age. Tuberculous lymphadenopathy
was
the
commonest
extra
pulmonary
tuberculosis. In our study 27(16%) cases were
isolated, 10(6%) were immunized while 17(10%)
were unimmunized. Tuberculous meningitis was
the most serious form of manifestation. We
observed 23(14%) cases. 13(57%) children had
TBM under the age of 5 years. 8(35%) patients
were immunized while 15(65%) patients were
unimmunized. Out of those 15 unimmunized
children, 11(73%) of them were of less than 5
years of age, while 2 children under 5 year of age
had TBM in spite of BCG vaccination. Abdominal
TB was another common presentation in children
and present with failure to thrive, mal absorption
syndrome
and/or
diarrhea/constipation;
abdominal distention etc. Sixteen (10%) patients
were identified in the study. Skeletal involvement
was present in 16(10%) cases. Thirteen (81%)
cases
were
unimmunized,
3(19%)
were
immunized.
TABLE I: Sex and Age Relation
Male (n =74)
Immunized
Unimmunized
Frequency (%)
Frequency (%)
Female (n = 91)
Immunized
Unimmunized
Frequency %)
Frequency (%)
Total (%)
< 5 years
19(20)
18(19)
15(15)
44(46)
96 (58)
5-10 years
11(30)
11(30)
5(13)
10(27)
37 (22)
10-15 years
Total
6(19)
9(28)
3(9)
14(44)
32 (20)
36(22)
38(23)
23(14)
68(41)
165 (100)
DISCUSSION
Children of younger age group are more prone
to have tuberculosis. They are either non
vaccinated for tuberculosis, with immature
immunity and/or malnourished, letting our
children disease prone. This is true in our younger
female population. In this study, most of children
observed were below 5 year of age as in the
study by Butt9, in which 70% of childhood
tuberculosis occurred in this age group. Similar
domino effect was observed in press trust of
India10. Both testified that younger children were
more prone to have tuberculosis.
The results regarding the immunization (BCG)
what we observed is in context with total BCG
immunization
coverage
in
Pakistan11.
Immunization status of our children was upsetting,
though this was case series from a tertiary care
public sector hospital, the results observed may
not be generalized to the society, even then the
www.ppa.org.pk
110
ugly picture might be an icebreaker for us and for
the concerned authority to formulate a mass
scale, community based study for a better view.
Gender discretion is the ugliest observed part as
we found females to be more malnourished as
compare to males; other than malnutrition they
are more non vaccinated too, this shows the
male dominating society and traditions towards
our female children (vaccinated F/M ratio was
1.2:1.0), especially in the less privileged
community. The combined detrimental effect of
malnutrition and un-immunization on our female
children were showed a figure of 70% in the
study. The study results we observed might reflect
the community echo; more females with the
tuberculosis as compared to males with poor
nutritional status and un-immunization. This need
to be reemphasized and urge to develop new
strategic plan to combat the terrifying results
identified so 100% of our children get vaccination
(BCG) especially our future mothers. Regarding
the nutritional status of our children, we found
95(58%) children malnourished and manifested
Protein calorie malnutrition (PCM) category.
39(23%) were severely malnourished according to
modified Gomez classification. Tajamul12 and
Haneef13 had observed the same results. PCM
and un-immunization have a direct correlation
and both leads to other. 72% PCM III and unimmunized children in the study, symbolizes a
strong association between non-vaccination and
malnutrition. The disease extent and strength
have a negative impact on their growth and
development. The poor nutritional status of these
individuals may impair the immune mechanism,
resulting in susceptibility to tuberculosis and other
infections and vice versa14.
Isolated pulmonary involvement is the usual
presentation mostly in unimmunized, younger
than 5 years and severely malnourished female
children. Malik MZ & Press Trust of India testified
the similar findings10,15. The most serious extrapulmonary tuberculosis was TBM especially in
unimmunized children accounting for overall 14%
of cases, most of them were unimmunized and of
younger age group16. 77 % cases were in stage
II17. This represent that immunization with BCG can
prevent/reduce the intensity of these deadly
presentations of tuberculosis as BCG can prevent
Meta-analysis
50-80%
of
these
cases18.
conducted proves the protective value of BCG
vaccine, against all form of tuberculosis all over
www.ppa.org.pk
Siddiqui EUD, , Hanif S, Siddiqui U, Raza SJ
the world is just 50%, but their protection against
serious and fulminat infection is 64% and 78%
against TBM and Miliary Tuberculosis respectively9.
CONCLUSION
We analyzed that our female children had missed
BCG immunization and were more malnourished
as compared to male children of the same age
group. These ignored females were more
targeted by tuberculosis. Their social rights should
be addressed in every forum and platform.
LIMITATION OF STUDY
This is the hospital based studies. The study
population, selected population, number of
cases and thus the results cannot be generalized.
Diagnosis was another dilemma thus we have to
rely on the clinical, and laboratory support.
Outpatients were not included in the study.
Message: The idea identified need to be readdressed.
The
results
can
be
further
strengthened by conducting a wide community
based study. Immunization and nutritional status
in our children is sub standard which must be
improved so that we can prevent and alleviate
dread-full spread of this and other diseases. There
is a need for all health professional to join hands
with the national TB program to control the
menace of tuberculosis.
Future Prospect: Immunization coverage should be
more strengthened, nutritional counseling and
identification of the career and index case with
appropriate DOTS therapy in utmost important in
reducing the TB burden. Despite some
improvements, the NTP still faces challenges. As
TB planning shifts from the National to the district
level, technical and managerial capacity at the
provincial
and
district
levels
require
strengthening.
ACKNOWLEDGEMENT
At the end I am very thankful for all those who
helped me in writing this paper both in clinical
and clerical work. Special thanks to my beloved
111
Childhood tuberculosis, Immunization, malnutrition
wife (Mrs Uzma Siddiqui) without her ambitious
support I am not able to get the objective.
8.
Dunlap NE, Bass J, Fujiwara P, Hopewell P,
Horseburg RL, salfinger M et all: Diagnostic
standards and classification of tuberculosis in
adults and children. Am J Resp Crit care
Med. 2000; 161(4):1376-95. Reproduce from
Table 8: guidelines for determining a positive
tuberculin test reaction. American Thoracic
Society
9.
Butt MA, Siddiqui MA. Pattern of tuberculosis
in immunized and un immunized children.
Annuals of King Edward Med col. July-Sept
1998; 4(3): 224-26.
10.
TB on rise in Pakistan. Press Trust of India.
Headline: Wednesday, 2002 July 17, New
Delhi.
11.
Khan PA, Kundi ZM. Social and preventive
pediatrics. 6th edition. Multan: Basis of
Pediatric; 2002:33-55.
12.
Begum T, Khattack AA. Tuberculosis, A major
threat to child health. PPJ. 1982; I: 38-40.
13.
Haneef SM, Maqbool S, Arif M A. Protein
Calorie Malnutrition. Text book of pediatric
2000: 97-140.
14.
Goceman AN. Is the BCG test of diagnostic
value in tuberculosis? Tubercle and lung
Disease 1994; 75: 54-57.
15.
Malik MZ, Khan PA. Prevalence of
tuberculosis in hospitalized children in PPJ
1982; VI. I: 1-7.
16.
Humpries MJ, Eoch R. Factors of prognostic
significant in Chinese children with TBM.
Lancet 1996; 582-96.
-------------------------------------------------------------------------------Author’s affiliations
Emad ud Din Siddiqui, Uzma Siddiqui,
Department of Emergency Medicine, Agha Khan
University, Karachi
Shaheena Hanif,
Civil Hospital, Karachi.
Syed Jamal Raza
National Institute of Child Health, Karachi
REFERENCES
1.
World report on tuberculous control and
surveillance, panning and financing. WHO
press, Switzerland UNICEF. World Health
Organization. 2004
2.
Shingadia D. Diagnosis and treatment of
tuberculosis in children. Lancet .J Infectious
dis. October 2003; 3: 624-31.
3.
Malik M. T.B control. Daily Times Lahore 2006
November Thursday, 02. Letter to editor.
Sited
on:
http://www.dailytimes.com.pk
/default. 2006: 3-6.
4.
USAID, Office of health. Infectious disease
and nutrition. July 2005.
5.
Ministry of Health, Govt. of Pakistan .PC-I
Form, from National Tuberculosis Control
Program for 1996-2001. Islamabad, Govt of
Pakistan, Ministry of health. 1996: 2-6.
6.
Seema HI, Hassan RQ. Assessment of
resistance in multi drug resistant tuberculosis
patients. JPMA Sept 2006; 56(9): 397-400.
17.
Shamim AQ, Saira K. Epidemiology of Child
hood Tuberculosis in Hospital setting PIMS.
JPMA April 1998; 48 (4): 4, 90-93.
7.
Khan EA, Hassan M. Recognition and
Management of Tuberculosis in children.
Current Pediatric J 2002; 12: 545-50.
18.
Jeffrey RS, Muonz. MF Tuberculosis. Nelson
Text Book of Pediatric; Vol. 1, part 1. Section
07:1240-54.
www.ppa.org.pk
CASE REPORT
Langer
Giedion
Syndrome Type II)
Syndrome
(Trichorhinophalangeal
MUHAMMAD SAEED, MATAR AL-ALMALKI, AHMAD ABABNEH
-----------------------------------------------------------------Pak Paed J 2010; 34(2): 112-15
See end of article for author’s
affiliations
--------------------------------------------Correspondence to:
Muhammad Saeed
Department of Neurology,
The Children Hospital Taif,
Saudi Arabia
E-mail:
[email protected]
ABSTRACT
Langer-Giedion syndrome is a rare genetic disorder, first described by
Giedion in 1966, caused by a deletion of long arm of chromosome 8. This
disorder is also known as trichorhinophalangeal type II.
Key words: Langer Giedion Syndrome ( Trichorhino-phalangeal type II)
INTRODUCTION
Langer-Giedion syndrome is a rare inherited multisystem disorder. LGS is characterized by fine, thin
hair; unusual facial features; progressive growth
retardation resulting in short stature (dwarfism);
abnormally short fingers and toes (clinobrachydactyly); "cone-shaped" formation of the
"growing ends" of certain bones (epiphyseal
coning); and/or development of multiple bony
growths (exostoses) projecting outward from the
surfaces of various bones of the body1,2,3. In
addition, affected individuals may exhibit
unusually flexible (hyperextensible) joints, cleft
palate or high arched palate, simian crease,
broad nasal bridge, colobomata of iris,
diminished muscle tone (hypotonia), wrinkled or
excess folds of skin (redundant skin), and/or
discolored
elevated
spots
on
the
skin
(maculopapular
nevi),
microcephaly
and
prominent ears4,5.
CASE REPORT
A 6 days-old male presented with respiratory
infection and dysmorphic features. He was 1st
issue born to a non-consanguineously married
couple by cesarean section at term, with birth
weight of 2.3 kg (below 5th percentile), length
percentile),
and
head
44cm
(at
5th
www.ppa.org.pk
circumference of 33cm (at 5th percentile). His
vital signs were stable at the time of admission. His
blood pressure was 85/50 mm of Hg.
He had distinctive features with microcephaly,
sparse hair, receding frontal hairline, large
prominent and low set ears with flattened helices,
broad nasal root with bulbous nose, large flat
philtrum and micrognathia Fig1 and Fig 3. There
were broad great toes and angulation was also
noted. He had colobomata of the irises with
deep set eyes, thin upper lip, a high arched
palate, and absent eyebrows with scanty
eyelashes {Fig 1, Fig 3}. Mild entropion of the both
eyes were also present, very rare association
reported once only in previous literature. He was
also noted to have broadening and flexion of the
proximal interphalageal joints of the 2nd to 4th
fingers and deviation of phalangeal axis, with no
limitation of movements. There were no exostoses
noted because the patient is new born, cone
shaped epiphysis and exostoses appear around 4
years of age.
Skin especially over abdomen and limbs was
extremely lax and wrinkled (Fig 2 Fig 4). He had
cryptorchidism. His systemic examination was
unremarkable. These typical features were
suggestive of Langer-Giedion syndrome or
TRPS11.
Langer Giedion Syndrome (Trichorhinophalangeal Syndrome Type II)
113
Fig 4
Fig 1
Fig 5
Fig 2
Radiological
examination
revealed
no
abnormality on X-ray's of hands. Ultrasound of
abdomen was also unremarkable. Whereas renal
parameters like blood urea, serum creatinine and
serum electrolytes were also normal. DNA analysis
reported deletion of chromosome 8 with
karyotype 46, XY; Chromosomal deletions extend
from (8q22.2 to 8q24.2).
DISCUSSION
Fig 3
Trichorhinophalangeal syndrome (TRPS), first
described by Giedion in 19661. These subtypes
with considerable clinical overlap can be
distinguished. Three types of tricho-rhinophalangeal syndrome TRPS I, TRPS II, and TRPS III
have been described in the literature. Features
www.ppa.org.pk
114
Saeed M, Almalki MA, Ababneh A
common to all three types are sparse, slowly
growing scalp hair, laterally sparse eyebrows, a
bulbous tip of the nose, and protruding ears.
Highly characteristic are the long flat philtrum
and the thin upper vermillion border1, 2, 3. The most
typical radiographic findings in TRPS are cone-
shaped epiphyses (CSEs), predominantly at the
middle phalanges. Often, they are not
detectable before 2 years of age. The skeletal
age always lags behind the chronological age
until puberty and then typically accelerates4.
TABLE 1: Features of Trichorhinophalangeal syndromes
Clinical Features
Hair
Facies
Ears
Teeth
Nails
Stature
Axial skeleton
Long bones
Joints
Hands/ Fingers
Radiologic findings
Genetic findings
TRPS-1
Fine, Sparse, brittle
Bulbous, pear shaped
nose,extended philtrum,
groved chin
Frequently lopped, low set
Usually normal
Broad, flat (spatulate)
Mildly shortened
Usually normal
Mildly shortened
Dimpling over MCP joints
premature osteoarthritis
Shortening, stubbiness, and
angulation of fingers
( clinobrachydactly)
Small femoral capital
epiphysis, cone shaped,
occasional subluxation of
femoral heads, patellar
dislocation
Autosomal dominant
deletion of band 8q24.12
TRPS-11
Similar to type 1
Similar to type 1
Similar to type 1
Similar to type 1
Similar to type 1
Similar to type 1
Similar to type 1
Similar to type 1
Spinal, multiple cartilaginous
exostosis or scoliosis, winged scapula
Exostosis
Hyperlaxity
Similar to type 1
Similar to type 1
Similar to type 1
Similar to type 1
Similar to type 1
Pes plannus, foot foot deformities
Similar to type 1
Similar findings with exostoses in
metaphyses of long bones, ribs and
vertebrae
Similar to type 1, no
exostosis severe
shortening of
phalanges,
metacarpels,
metatarsals
Autosomal dominant
Autosomal dominant deletion of
band 8q24.11-q24.13
Most people with LGS also have mental
retardation. LGS is not usually passed through
generations in a family5. However; the condition is
considered a contiguous-gene syndrome. This
means that it is caused by the loss of functional
copies of two genes near each other on
chromosome 8. Research suggests that another
gene may be involved6. Recently identified the
TRPS1 gene, which maps to 8q24.1. The deletion
of both TRPS1 and EXT1 leads to TRPS II7. Patients
have multiple cartilaginous exostoses in addition
to the findings in TRPS I. Mental retardation has
been described in many patients with TRPS II as
well as in two patients with TRPS I and a
cytogenetically visible deletion in 8q248.
There are no reports of prenatal diagnosis of this
condition.
To
provide
accurate
genetic
counseling regarding prognosis and risk of
recurrence, it is important to distinguish this
www.ppa.org.pk
TRPS-111
Similar to type 1
Similar to type 1
condition from others that are similar to it, such as
tricho-rhino-phalangeal syndrome, type 1.
The treatment for LGS is tailored to each person.
Exostoses may need to be surgically removed if
they are causing problems with nerves or blood
vessels. If the two leg lengths are different,
corrective shoes may be helpful. Orthopedic
devices such as braces or, more rarely, surgery
may be indicated in severe cases of skeletal
abnormality9. Plastic surgery to alter specific
features, such as the ears or nose, has been
chosen by some people. The risk of cancer at the
site of the exostoses is not known but may be
higher. Special education for mentally retarded
individuals is in Langer-Giedion syndrome does
not alter life span. Complications from associated
abnormalities such as mental retardation,
however, can cause problems. Asymmetry of the
limbs can interfere with their function and cause
Langer Giedion Syndrome (Trichorhinophalangeal Syndrome Type II)
pain. Psychological effects due to physical
abnormalities may also be experienced10.
As in other situations in clinical medicine, proper
evaluation of the lesions and a specific diagnosis
aid in the management and prognosis of
intellectually disabled patients as well as in family
counseling. This should take as soon as possible.
Therefore, emphasis is laid on provision of genetic
councilling services as soon as possible after the
patients’s birth or after admission to an institution.
4
Giedion A. Phalangeal cone-shaped
epiphyses of the hand: their natural history,
diagnostic sensitivity, and specifity in
cartilage
hair
dyspplasia
and
the
trichorhinophalangeal syndromes I and II.
Pediatr Radiol 1998; 28: 751-56.
5
Vantrappen G, Feenstra L, Frijns JP.
Conductive hearing loss in the tricho-rhinophalangeal syndrome (TRP II) or in the
Langer-Giedion syndrome. Am J Med
Genet 1997; 72: 372-73.
6
Ludecke HJ, Schaper J, Meinecke P,
Momeni P, Gross S, Von Holtum D et al.
Genotypic and phenotypic spectrum in
tricho-rhinopahlangeal syndrome types I
and III. Am J Genet 2001; 68: 81-91.
7
Momeni P, Glöckner G, Schmidt O, von
Holtum D, Albrecht B, Gillessen-Kaesbach
G, ET AL. Mutations in a new gene,
encoding a zinc-finger protein, cause
tricho-rhino-phalangeal syndrome type I.
Nat Genet 2000; 24: 71–74.
8
Yamamoto Y, Oguro N, Miyao M,
Yanagisawa M. Tricho-rhino-phalangeal
syndrome type I with severe mental
retardation due to interstitial deletion of
8q23.3-24.13. Am J Med Genet 1989; 32:
133-35.
9
Bauermeister S, Letts M. The orthopaedic
manifestations of the Langer-Giedion
syndrome. Orthop Rev. 1992; 21: 31-35.
10
Tricho-rhino-phalangeal Syndrome, Type II."
Birth Defects Encyclopedia Mary Louise
Buyse.
Boston:
Blackwell
Scientific
Publications, 1990.
----------------------------------------------------------------------------Author’s affiliations
Muhammad Saeed, Matar Al-Almalki,
Ahmad Ababneh
Department of Neurology, The Children Hospital Taif,
Saudi Arabia
REFERENCES
1
Giedion A. Das. Tricho-rhino-phalangeale
Syndrome. Helv Paediatr Acta. 1966; 21: 420.
2
Langer LO, Krassikoff N, Laxova R, ScheerWillaims M, Lutter LD et al. The trichorhinophalangeal syndrome with exostoses
(or
Langer-Giedion
syndrome):
four
additional
patients
without
mental
retardation and review of the literature. Am
J Med Genet 1994;19: 81-111.
3
Jones KL. Smith's recognizable patterns of
human malformation. Pennsylvania; WB
Saunders Company. 2007: 290-91.
115
www.ppa.org.pk
ABSTRACT
Abstract Service
-----------------------------------------------------------------Pak Paed J 2010; 34(2): 116-19
Hearing
Impairment
in
Childhood
Bacterial Meningitis Is Little Relieved by
Dexamethasone or Glycerol
by
Peltola H, Roine I, Fernández J, González Mata A,
Zavala I, Gonzalez Ayala S, Arbo A, Bologna R, Goyo J,
López E, Miño G, Dourado de Andrade S, Sarna S,
Jauhiainen T. .
Objective: Several studies have evaluated
dexamethasone for prevention of hearing loss in
childhood bacterial meningitis, but results have
varied. We compared dexamethasone and/or
glycerol recipients with placebo recipients, and
measured hearing at 3 threshold levels.
Methods: Children aged 2 months to 16 years
with meningitis were treated with ceftriaxone but
were double-blindly randomly assigned to
receive adjuvant dexamethasone intravenously,
glycerol orally, both agents, or neither agent. We
used the Glasgow coma scale to grade the
presenting status. The end points were the better
ear's ability to detect sounds of >40 dB, 60 dB,
and 80 dB, with these thresholds indicating any,
moderate-to-severe, or severe impairment,
respectively. All tests were interpreted by an
external audiologist. Influence of covariates in
the treatment groups was examined by binary
logistic regression.
Results: Of the 383 children, mostly with meningitis
caused by Haemophilus influenzae type b or
Streptococcus
pneumoniae, 101
received
dexamethasone, 95 received dexamethasone
and glycerol, 92 received glycerol, and 95
received placebo. Only the presenting condition
and
young
age
predicted
impairment
independently through all threshold levels. Each
lowering point in the Glasgow scale increased
the risk by 15% to 21% (odds ratio: 1.20, 1.21, and
1.15 [95% confidence interval: 1.06–1.35, 1.07–
1.37, and 1.01–1.31]; P = .005, .003, and .039) for
any, moderate-to-severe, or severe impairment,
respectively. Each increasing month of age
www.ppa.org.pk
decreased the risk by 2% to 6% (P = .0001, .0007,
and .041, respectively). Neither dexamethasone
nor glycerol prevented hearing loss at these levels
regardless of the causative agent or timing of
antimicrobial agent.
Conclusions: With bacterial meningitis, the child's
presenting status and young age are the most
important predictors of hearing impairment. Little
relief is obtained from current adjuvant
medications.
Pediatrics 2010: 1-8.
Effect
of
Domperidone
on
the
Composition of Preterm Human Breast
Milk
by
Campbell-Yeo ML, Allen AC, Joseph KS, Ledwidge JM,
Caddell K, Allen VM, Dooley KC
Objective:
Domperidone
is
increasingly
prescribed to improve breast milk volume despite
a lack of evidence regarding its effects on breast
milk composition. We examined the effect of
domperidone on the nutrient composition of
breast milk.
Patients and Methods: Forty-six mothers who had
delivered infants at <31 weeks' gestation, who
experienced lactation failure, were randomly
assigned to receive domperidone or placebo for
14 days. Protein, energy, fat, carbohydrate,
sodium, calcium, and phosphate levels in breast
milk were measured on days 0, 4, 7, and 14,
serum prolactin levels were measured on days 0,
4, and 14, and total milk volume was recorded
daily. Mean within-subject changes in nutrients
and milk volumes were examined.
Results: Maternal and infant characteristics,
serum prolactin level, and breast milk volume and
composition were not significantly different
between domperidone and placebo groups on
day 0. By day 14, breast milk volumes increased
117
Abstract Service
by 267% in the domperidone-treated group and
by 18.5% in the placebo group (P = .005). Serum
prolactin increased by 97% in the domperidone
group and by 17% in the placebo group (P = .07).
Mean breast milk protein declined by 9.6% in the
domperidone group and increased by 3.6% in
the placebo group (P = .16). Changes in energy,
fat, carbohydrate, sodium, and phosphate
content were also not significantly different
between groups. Significant increases were
observed in breast milk carbohydrate (2.7% vs –
2.7%; P = .05) and calcium (61.8% vs –4.4%; P =
.001) in the domperidone versus placebo groups.
No significant adverse events were observed
among mothers or infants.
Conclusion: Domperidone increases the volume
of breast milk of preterm mothers experiencing
lactation failure, without substantially altering the
nutrient composition.
Pediatrics 2010; 125: 107-14.
Intravenous Immunoglobulin and Necrotizing
Enterocolitis in Newborns With Hemolytic
Disease.
by
Figueras-Aloy J, Rodríguez-Miguélez JM, Iriondo-Sanz
M, Salvia-Roiges MD, Botet-Mussons F, CarbonellEstrany X
Objective: The objective of this study was to
assess whether the use of high-dose intravenous
immunoglobulin (IVIG) in late-preterm and term
newborns with severe isoimmune hemolytic
jaundice caused by Rh and ABO incompatibility
was a risk factor for necrotizing enterocolitis
(NEC).
Methods: An observational, retrospective study
that encompassed 16 years was conducted. A
total of 492 liveborn infants who were of 34
weeks' gestation and had severe isoimmune
hemolytic jaundice caused by Rh (n = 91) and
ABO (n = 401) incompatibility and were treated
with phototherapy were included in the study.
IVIG (500 mg/kg over 2–4 hours) was indicated
when total serum bilirubin level plus 2 points
reached 85% of the cutoff value for performing
exchange transfusion.
Results: A total of 167 (34%) infants received IVIG.
NEC was diagnosed in 11 (2.2%) patients: 10 (6%)
in the IVIG-treated group and 1 (0.3%) in the non–
IVIG-treated group. Five patients required urgent
operation, and 1 of them died as a result of
massive intestinal necrosis. Another patient died 2
years later as a result of short bowel syndrome. In
the multivariate analysis, cesarean delivery (odds
ratio [OR]: 3.76 [95% confidence interval (CI):
1.10–12.90), Apgar test at 5 minutes (OR: 0.50 [95%
CI: 0.40–0.64), and IVIG (OR: 31.66 [95% CI: 3.25–
308.57]) were independent factors significantly
associated with NEC.
Conclusions: The use of high-dose IVIG for severe
isoimmune hemolytic jaundice in late-preterm
and term infants was associated with a higher
incidence of NEC.
Pediatrics 2010; 125: 139-44.
Use of a Homeopathic Preparation for
"Infantile Colic" and an Apparent LifeThreatening Event
by
Shraga Avinera,b, Matitiahu Berkovitchc,d, Hedva
Dalkian,
Rony
Braunsteine,
Yossef
Lomnickyf,
Menachem Schlesingera,b
a Department of Pediatrics, Barzilai Medical Center,
Ashkelon, Israel;
b Faculty of Health Sciences, Ben-Gurion University of
the Negev, Beer-Sheva, Israel;
c Clinical Pharmacology and Toxicology Unit, Assaf
Harofeh Medical Center, Zerifin, Israel;
d Sackler School of Medicine, Tel-Aviv University, Tel
Aviv, Israel;
e Independent Statistical Consultant, Tel Aviv, Israel;
and
f Maccabi Healthcare Services, Tel-Aviv, Israel
Objective: An apparent life-threatening event
(ALTE) caused by ingestion of drugs or toxins has
been reported rarely among infants. None of
these agents was homeopathic medication. We
report 11 infants who presented with an ALTE after
ingestion of Gali-col Baby, a homeopathic agent
indicated for "infantile colic."
Methods: A retrospective case-control study was
conducted. Charts of all infants who were
younger than 1 year and were admitted with an
ALTE from January 2005 through August 2008 to
the pediatric division at the Barzilai Medical
Center were reviewed. Age-matched infants who
were admitted on the same dates for a reason
other than ALTE served as a control group.
www.ppa.org.pk
118
Information on medications administered before
admission was recorded.
Results: During the study period, 36 635 children
visited the pediatric emergency department of
the Barzilai Medical Center. There were 11 057
admissions to the pediatric division during this
period, 115 of which were because of an ALTE.
Eleven of these infants received Gali-col Baby
before the event as opposed to none in the
control group (P < .005). Three infants received a
significant overdose, compared with the
manufacturer's recommended dosage. After a
thorough investigation, no other presumptive
causes for ALTE were found among the 11 infants.
Conclusions: Gali-col Baby is associated with an
ALTE in some infants. There are no published
controlled trials on the efficacy or safety of its use;
therefore, better control and supervision of Galicol Baby and probably other homeopathic
medications are needed to prevent possible
serious adverse effects.
PEDIATRICS, February 2010 125(2):318-23.
Difficulties in selecting an appropriate
neonatal thyroid stimulating hormone
(TSH) screening threshold
by
Korada SM, Pearce M, Ward Platt MP, Avis E, Turner S,
Wastell H, Cheetham T
Background: The UK Newborn Screening
Programme Centre recommends that a blood
spot thyroid stimulating hormone (TSH) cut-off of
10 mU/l is used to detect congenital
hypothyroidism (CHT). As the value used varies
from 5 to 10 mU/l, we examined the implications
of altering this threshold.
Methods: Our regional blood spot TSH cut-off is 6
mU/l. Positive or suspected cases were defined as
a TSH >6 mU/l throughout the study period (1 April
2005 to 1 March 2007). All term infants (>35
weeks) whose first TSH was 6–20 mU/l had a
second TSH measured. The biochemical details of
infants with a TSH between 6.1 and 10.0 mU/l and
then >6 mU/l on second sampling were sent to
paediatric
endocrinologists
to
determine
approaches to management.
Results: 148 of 65 446 infants (0.23%) had a first
blood spot TSH >6.0 mU/l. 120 were term infants
with 67 of these (0.1% of all infants tested) having
www.ppa.org.pk
Abstract Service
a TSH between 6.1 and 10.0 mU/l and 53 a TSH
>10.0 mU/l. Of the 67 term infants with a TSH
between 6.1 and 10.0 mU/l on initial testing, four
continued to have a TSH >6 mU/l. One with a TSH
>10 mU/l and one infant with a TSH <10 mU/l on
the second blood spot have been diagnosed
with CHT. The survey of endocrinologists
highlighted significant differences in practice.
Conclusions: A reduced threshold of 6 mU/l will
increase the number of false positive term infants
by 126%, but abnormalities of thyroid function
requiring treatment will be detected. We suspect
that the additional expense involved in setting a
lower threshold is justified.
Arch Dis Child 2010;95:169-73
Breastfeeding,
the
use
of
docosahexaenoic acid-fortified formulas
in infancy and neuropsychological
function in childhood
by
Gale CR, Marriott LD, Martyn CN, Limond J,
Inskip HM, Godfrey KM, Law CM, Cooper C,
West C, Robinson SM
Objective: To investigate the relation between
breastfeeding, use of docosahexaenoic acid
(DHA)-fortified formula and neuropsychological
function in children.
Design: Prospective cohort study.
Setting: Southampton, UK.
Subjects: 241 children aged 4 years followed up
from birth. Main outcome measures IQ measured
by the Wechsler Pre-School and Primary Scale of
Intelligence
(3rd
edn),
visual
attention,
visuomotor precision, sentence repetition and
verbal fluency measured by the NEPSY, and
visual form-constancy measured by the Test of
Visual-Perceptual Skills (Non-Motor).
Results: In unadjusted analyses, children for whom
breast milk or DHA-fortified formula was the main
method of feeding throughout the first 6 months
of life had higher mean full-scale and verbal IQ
scores at age 4 years than those fed mainly
unfortified formula. After adjustment for potential
confounding factors, particularly maternal IQ and
educational attainment, the differences in IQ
between children in the breast milk and
unfortified formula groups were severely
119
Abstract Service
attenuated, but children who were fed DHAfortified formula had full-scale and verbal IQ
scores that were respectively 5.62 (0.98 to 10.2)
and 7.02 (1.56 to 12.4) points higher than children
fed unfortified formula. However, estimated total
intake of DHA in milk up to age 6 months was not
associated with subsequent IQ or with score on
any other test.
Conclusions: Differences in children's intelligence
according to type of milk fed in infancy may be
due more to confounding by maternal or family
characteristics than to the amount of long-chain
polyunsaturated fatty acids they receive in milk.
Arch Dis Child 2010; 95:174-179
Automated microscopy, dipsticks and
the diagnosis of urinary tract infection
by
Lunn A, Holden S, Boswell T, Watson AR.
Objective: Automated microscopy is increasingly
used to screen urine samples for suspected
urinary tract infection (UTI). A 98.8% negative
predictive value has been reported in adult
studies. The aim of our study was to validate this
method in a paediatric population.
Methods: Urine samples were collected from
children
with
known
or
suspected
nephrourological disease attending nephrology
and urology clinics over a 6-week period.
Samples were tested with dipstick, the UF-100 flow
cytometer (automated microscopy) and culture.
A gold standard of a positive culture of morethan
105 colony forming units per ml (cfu/ml) with a
pathogenic organism was used and the
sensitivity, specificity and likelihood ratios were
calculated.
Results: 280 urine samples were collected from
263 patients (143 male, median age 10.2 years,
range 0.1–19.75 years). 221 (79%) were midstream
or clean-catch samples. Automated microscopy
identified 42 of 186 samples as requiring culture
and 17 of 19 samples which had a pure growth of
more than 105 cfu/ml. Two patients were not
identified by automated microscopy: one was
treated for vulvovaginitis, and one commenced
prophylactic antibiotics prior to the culture result
being obtained. The sensitivity, specificity, positive
and negative likelihood ratios were 0.89, 0.85,
5.98 and 0.17, respectively. This compared to
0.95, 0.72, 3.34 and 0.29, respectively, with urine
dipstick.
Conclusion: Automated microscopy performed
comparably to urine dipstick in the diagnosis of
UTI with improved specificity and likelihood ratios
with slightly reduced sensitivity. The data support
the use of automated microscopy for screening
urine samples for culture in children, but different
automated microscopy methods and algorithms
require local evaluation.
Arch Dis Child 2010;95:193-197
www.ppa.org.pk
NEWS AND VIEWS
-----------------------------------------------------------------Pak Paed J 2010; 34(2): 120
Infectious Diseases Group’s E-Consultation
Desk @http://www.idgppa.com
Infectious Diseases Group of Pakistan Paediatric
Association is launching an e-consultation service
for our members. Our panel of experts will provide
an online solution (advice and recommendation)
to the problems which the members face in their
day to day practices or otherwise.
Objective of this service is to guide our
colleagues by responding to their queries after
their online submission. The members only have to
long on to our website and submit their query.
Their query will be responded within 3 days of
submission. The details are available on our
website.
Should you have any query regarding this service,
please do not hesitate to contact us at
[email protected], [email protected]
Prof. Muhammad Ashraf Sultan
Chairman
Infectious Diseases Group of
Pakistan Paediatric Association.
7-8th October 2010, Vilnius, Lithuania
Meeting Management company, Olimpieciu str.
1-34, Lt-09200 Vilnius, Lithuania
Tel: 37052000778 fax.37052000782
[email protected] www.vilniuscourse.com
2-4 December,2010
www.excellence-in-paediatrics.org
European Society for Paediatric Research
www.espr.info
Adminstrative office
C/o Kenes International, 1-3, rue de
The
1st
European
Conference
Immunisation Information Systems (IIS)
Stockholm Sweden
7-8 December 2010
Register at: www.smi.se/eciis
Swedish Institute for Infectious Disease Control
[email protected]
www.smi.se/eciis tel.46-(0)704-153496
Pediatric Infectious Diseases Programme
www.conted.ox.ac.uk/cpd/pid
or
email
[email protected]
Paediatric Infectious Diseases Programme Oxford
University Department for Continuing Education
CPD Centre Littlegate House 16/17 St Ebbes
Street Oxford OX1 1PT,UK
Tel:+44 (o) 1865286946 fax.44 (0) 1865286934
17-20 February 2011,
Vienna, Austria
Secretariat – Paragon Conventions
18-Avenue Louis Casai, 1209 Geneva, Switzerland
Tel: 41(0)227477930, E-mail: [email protected]
www.cipediatrics.org
Twelfth Advanced Vaccinology CouseLes
Pensieres. Veyrier du Lac (French Alps
16-27 May 2011
Application deadline: Tuesday 16 Nov. 2010
Contact:
Katia Mielczarek
Tel: 0033(0)472407945 Fax: 00 33 (0) 472407934
[email protected]
ADVERTISEMENT
1.
2.
3.
4.
M/s Hiltan Limited
M/s Procter & Gamble Pakistan (Pvt.) Limited
M/s Unibrand Pakistan Limited (Morinaga)
M/s Sanofi-aventis Pakistan Ltd.
JOURNAL: Printed & Published by Managing Editor,
180-H, Johar Town Lahore,
P.O.Box:308, G.P.O, Lahore, Pakistan
E-mail: [email protected]
Journal Website:i)
www.ppa.org.pk
ii)
http://www.pakmedinet.com/PPJ
www.ppa.org.pk
on
The Ist Global Congress for Consensus in
Child Health & Paediatrics
Update on Paediatric Infectious diseases
Excellence in Pediatrics
Chantepoulet, P.O.Box 1726, Ch-1211, Geneva 1
Switzerland
Tel: 41229069156 fax.41227322607
[email protected]
Enflor
Pamper
Nutri Mama
Creating Vaccines
News and views
55
www.ppa.org.pk