Pregnancy in IBD Brian Bressler MD, MS, FRCPC CDDW 2014

Pregnancy in IBD
CDDW 2014
Brian Bressler MD, MS, FRCPC
Director, Advanced IBD Training Program
Clinical Assistant Professor of Medicine
Division of Gastroenterology
University of British Columbia
Bressler Financial Interest Disclosure
(over the past 24 months)
Commercial Interest
Relationship
Abbvie
Advisory Board, Speaker
Janssen
Advisory Board, Speaker
Ferring
Speaker
Shire
Advisory Board, Speaker
Warner Chilcott
Advisory Board
Takeda
Advisory Board
CanMEDS Roles Covered in this Session:
ü
Medical Expert (as Medical Experts, physicians integrate all of the CanMEDS Roles,
applying medical knowledge, clinical skills, and professional attitudes in their provision of
patient-centered care. Medical Expert is the central physician Role in the CanMEDS
framework.)
ü
Communicator (as Communicators, physicians effectively facilitate the doctor-patient
relationship and the dynamic exchanges that occur before, during, and after the medical
encounter.)
ü
Collaborator (as Collaborators, physicians effectively work within a healthcare team to
achieve optimal patient care.)
ü
Manager (as Managers, physicians are integral participants in healthcare organizations,
organizing sustainable practices, making decisions about allocating resources, and
contributing to the effectiveness of the healthcare system.)
Health Advocate (as Health Advocates, physicians responsibly use their expertise and
influence to advance the health and well-being of individual patients, communities, and
populations.)
Scholar (as Scholars, physicians demonstrate a lifelong commitment to reflective learning,
as well as the creation, dissemination, application and translation of medical knowledge.)
Professional (as Professionals, physicians are committed to the health and well-being of
individuals and society through ethical practice, profession-led regulation, and high personal
standards of behaviour.)
Objectives
1. Know what to tell IBD patients wanting to get
pregnant
a.  discussion of fecundity/infertility
b.  explain the risks of flaring, risk of
complications
2. Understand the safety of medical therapy in
pregnant IBD patients
IBD Patients Fear Infertility
n 
n 
n 
n 
43% IBD patients fear infertility
• 
CD more than UC (47% v. 26%)
• 
Females more than males (54% v. 33%)
14% were childless
24% with children had fewer kids than
desired or planned
Reasons for voluntary infertility included:
• 
Fear of IBD-related congenitial abn, genetic
risk of IBD, medication toxicity, medical advice
IBD 2009; 15:720.
RISK OF IBD IN OFFSPRING
n 
First degree relatives
• 
n 
Both parents with IBD
• 
n 
10-15 fold increase
33% risk
Concordance of Type of Disease
Gastroenterology 2001 Laharie D.
Are Patients with Crohn’s Infertile?
n 
Involuntary
• 
• 
n 
Rates similar to controls (4-14%)
Higher in surgically managed patients (20% v.
8%)
Voluntary
• 
• 
Rates higher than controls (14-30%)
Higher in medically managed patients (36% v.
23%)
Int J. Gynec & Obs 1997;58:229. Gastro 1990; 99:987.
Are Patients with UC Infertile?
n 
Involuntary
• 
• 
n 
Overall similar rates to controls (2-15%)
Higher in surgically managed patients (30% v.
13%)
Voluntary
• 
• 
Rates higher than controls (21-25%)
Higher in surgically managed patients (45% v.
21%)
Int J. Gynec & Obs 1997;58:229. Gastro 1990; 99:987.
Female Infertility After IPAA
Before After
IPAA pts
Diseases of Colon & Rectum 2004:47:1119
Ann Surgery 2012
Open vs. Laparoscopic IPAA
One year pregnancy rate 30% (open) and 56%
(laparoscopic)
6 mo and 1 yr rate for 29 yo – 64% and 85%
Pregnancy & Risk of an IBD Flare
n 
If in remission at conception:
• 
similar to 1-year risk in non-pregnant patients
• 25% CD (highest in 1st trimester)
• 33% UC
n 
If have active disease at conception
• 
UC – 45% get worse, 25% better, 25% same
• 
CD – 1/3 worse, 1/3 better; 1/3 same
AJG 2007; 102:1414. Gut 1984; 25:52.
Outcome of IBD on Pregnancy
n 
n 
Meta-analysis (3907 IBD pts v. 320,521 controls)
Results reported as OR (odds ratios)
IBD
CD
UC
1.87
1.97
1.34
Low Birth Weight (<2500 g)
2.1
2.82
NS
Caesarean Section
1.5
1.65
NS
Small for Gestational Age
NS
NS
NS
Still Births
NS
NS
NS
Prematurity (<37 wks)
Gut 2007; 56:830
Impact of disease activity on pregnancy outcomes
Danish population study comparing 71 pregnant patients with disease
Activity to 86 patients without disease activity
Norgard B, et al. Am J Gastro 2007
FERTILITY
SULFASALAZINE
• 
• 
• 
• 
Oligospermia
Reduced Motility
Abnormal Morphology
Not dose-dependent
METHOTREXATE
•  Reversible oligospermia
• 
• 
AZATHIOPRINE
No effect on semen quality
1.5-2 mg/kg
INFLIXIMAB
•  Counter negative effects of TNFα
Gastroenterology 2001 Vol 121(5)
Inflamm Bowel Dis 2005 11(4)
Journal of Crohn’s and Colitis 2012 Vol 6 (8)
SAFETY OF IBD MEDICATIONS
FDA
Category
Description
A
Adequate and well controlled studies
showing no risk
B
No risk demonstrated in human studies
C
Animal studies; benefits may be acceptable
despite potential risks
D
Human studies; benefit from the drug may be
acceptable despite potential risks
X
Human studies show risk; RISK >>>
BENEFIT
FDA classification
5-ASA
FDA Class B
FDA Class C
•  Dipentum®
•  Asacol®
Asacol® coating contains DBP
(debutyl phthalate)
SULFASALAZINE
•  Needs folate
supplementation
•  Animal studies at doses >190
times the human dose
•  Skeletal malformations and male
reproductive system
200 x
Reproductive Toxicology 2013
Thiopurine/Pregnancy Outcomes Meta analysis
Birth Weight
Preterm Birth
Akbari et al. Inflamm Bowel Dis 2013
Thiopurine exposure and Congential Abnormalities
Maternal
Paternal
Akbari et al. Inflamm Bowel Dis 2013
Thiopurines and Breast Feeding
n 
n 
Major excretion in breast milk within 4 hours
of taking medication
Worst case scenario: max concentration
0.0075mg/kg
Christensen S et al. APT 2008
Infliximab Exposure
* Flare
Mahadevan et al. Clin Gastro Hep 2013
ADA Exposure
Does this matter?
Proportion of Patients (%)
Infliximab in Pregnancy:
Outcomes of Women Exposed to
Infliximab During Pregnancy
80
70
67
67
66
67
60
Live births
50
Miscarriages
40
Therapeutic
termination
30
20
17 16
11
10
0
17
General
Population
Crohn’s
Disease
15
20
19
13
All Infliximab Infliximab
Patients
Patients with
(N=96)
CD (N=82)
Adapted from Katz JA, et al. Am J Gastroenterol 2004;99:2385-92; Ventura et al. National Center for Health Statistics
Vital Health Stat 2000;21:1-59; Hudson et al. Int J Gynaecol Obstet 1997;58:229-37.
Infections
n 
Fatal case of disseminated BCG infection in an
infant born to mother on infliximab for CD
Infant died at 4.5 months of age
Cheet K. JCC 2010
Don’t give infants live vaccines
Immune Response to Vaccines
n 
Influenza vaccine
• 
• 
n 
Pediatric IBD patients on infliximab and
immunomodulators had higher rates of inadequate
response compared to healthy controls1
Among adults on infliximab, proportion with
protective titer not different from controls;
however, mean antibody titer was significantly
lower2
Pneumococcal vaccine
• 
Infliximab +/- methotrexate had lower response
to pneumococcal vaccine3
1. Mamula P, et al. Clin Gastroenterol Hepatol 2007;5:851-6; 2. Gelnick A. Ann Rheum Dis
2005;64:181; 3. Visvanathan S, et al. J Rheumatol 2007;34:952-7.
BREASTFEEDING
MEDICATION
? SAFE
Sulfasalazine
5-ASA
Sulfapyridine secreted into breast milk
< 10% of therapeutic dose - Compatible
Methotrexate
Contraindicated
AZA or 6-MP
<1% of maternal dose - Compatible
Majority excreted in first 4 hours
Corticosteroids
<0.1% of maternal dose of prednisolone Compatible
Infliximab
Adalimumab
Not detected in breast milk – Compatible
No data
Cyclosporine
Secreted at high concentrations – Not recommended
Diarrhea
Summary/Conclusions
n 
n 
n 
n 
Fertility and pregnancy are common concerns
to patients with IBD – Talk to your patients!
Involuntary infertility is more common in IBD
patients managed surgically
Voluntary infertility is higher in surgically
managed UC patients and medically managed
CD patients
Female infertility is significantly decreased
after IPAA
Summary/Conclusions (2)
n 
n 
n 
n 
IBD outcomes are better if pt is in remission
at the time of conception
IBD pregnancies (mostly CD) have increased
odds of prematurity, low birth weight, Csection, and congenital abnormalities
Safety signals suggests Adalimumab and
Infliximab are reasonable medications to use
in pregnancy
Fetal exposure may occur if given anti-TNF
agents in 3rd Trimester
Canadian National Working Group for IBD
and Pregnancy: 2nd meeting‫‏‬
Salon 3 on the 19th floor