The Safety Assessment of Vedolizumab During Pregnancy in IBD Patient
Conditions: Pregnancy Complications
Sponsor: Ariella Shitrit

 
IBD MOM cohort study 
 
 
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Title 
 
The safety assessment of a variety of stage-4 medications during 
pre-conception and pregnancy in IBD patients. 
 
Background and Rationale 
Little human data is available on the use of a variety of stage-4 IBD medications such as Entivio, 
Stelara and so on during pregnancy. This study has been designed to provide information to 
clinicians and patients on pregnancy outcomes in women exposed to a variety of stage-4 IBD 
medications during pregnancy. Improved understanding of the effects of IBD and the use of these 
medications in pregnant patients on rates of congenital malformations, spontaneous abortions, 
preterm birth, and SGA infants will be of great benefit to prospective mothers with IBD and the 
physicians taking care of this population.  
This cohort study will utilize information available from the institutional prospective pregnancy 
registry from the IBD MOM clinic in the Digestive Disease Institute, Shaare Zedek Medical 
Center, Jerusalem, Israel.   
The IBD MOM clinic was established in June 2011 in response to the vast need of IBD female 
patients in their reproductive years.  This is a unique clinic in which a gastroenterologist and a fetal 
maternal medicine expert consult together.  Since the establishment of this clinic we have a 
prospective cohort data registry of 200 women till June 2015. 
Objective 
The primary objective of this study is: 
 
1. To quantify incidence of major structural birth defects and other birth outcomes in infants 
born to women with UC/CD with exposure to a variety of stage-4 medications compared to 
women with exposure to other biological agents or conventional IBD therapy during 
pregnancy 
 
2.  To assess the health and developmental status of infants up to 4yr of age. 
 
 
 
 

 
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Study Population 
The source population is women attending the IBD MON clinic at Shaare Zedek Medical Center in 
Jerusalem, Israel. The Shaare Zedek Medical Center is located on a vast, 11-acre campus directly 
opposite Mount Herzl, making it Jerusalem’s only major, centrally located hospital. The hospital 
complex, completed in 1979, comprises ten interconnected buildings and an expansive parking 
area. Since occupying the current location, Shaare Zedek has transformed itself from a respected 
regional hospital into a major multi-disciplinary medical center with an international reputation for 
excellence in many areas of expertise. 
  
With a constant commitment to developing increasingly innovative means to provide patient care, 
the 700-bed facility treats hundreds of thousands of patients per year in its thirty inpatient 
departments and 70 departments and units comprising its out-patient clinics.  
  
The cohort will prospectively recruit women attending the IBD MOM clinic who meet the study 
inclusion/exclusion criteria.  In addition, the cohort will be supplemented with women who 
attended the IBD MOM clinic after the commercial launch of stage 4 IBD medications but prior to 
the study. 
 
Inclusion Criteria for the UC/CD Prospective Cohort: 
 The subject is a currently pregnant woman with UC or CD  
 The subject considers pregnancy ( pre-conception stage) 
 The subject agrees to the conditions and requirements of the study including the interview 
Study Design 
The IBD MOM clinic currently follows women with IBD from the preconception stage 
through postpartum period.  In addition, we have now started following the offspring for 1 
year with an option of extending the follow up until 4 years after birth with participation of 
the family health center. Data is collected longitudinally on use of stage-4 IBD medications, 
non-immunomodulator AZA/6MP, biologic therapy infliximab, adalimumab, certolizumab, 
and natalizumab. Corticosteroids,5-ASA  and Methotrexate), disease activity during 
gestation, complications of pregnancy and delivery, and infant birth outcomes during the first 
year of the child’s life because from population-based data, including the Kaiser sample1 and 
studies from Europe2-4 women with IBD clearly have an increased risk of adverse pregnancy 
outcomes such as preterm birth and/or low birth weight infants, even with inactive disease.10.  
Study duration: September 2015- September 2022 
This is a non-interventional observational prospective cohort study to be conducted in an 
actual clinical practice setting.  
This is an exposure-based cohort study in which there will be 3 reference groups. Women on 
conventional therapy only, women on Vedolizumab and women on other biologics. 
 The source database contains information collected from our IBD MOM clinic in Shaare 
Zedek Medical Center in Jerusalem, Israel.  

 
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schedule, release of medical records, and the physical examination of live born infants. 
Exclusion Criteria for the UC/CD Prospective Cohort: 
 The subject has had an exposure to the known or suspected human teratogens: 
– Chlorambucil  
– Cyclophosphamide  
– Mycophenylate mofetil 
 
Any stage 4 IBD drugs exposed mother who does not meet the entry criteria will be entered into 
case series, which will be used to provide support data to cohort study. 
 
Study participants will be categorized into one of the following exposure groups: 
Group 1:   STAGE-4IBD medication  Cohort (Each medication will be analyzed separately) 
 Group 1a Mothers exposed to stage-4 IBD medication at any time during pregnancy and 
pre-conception. 
 Group 1b Infants born to Group 1a patients.   
Group 2:  Anti-TNF Agents Cohort 
 Group 2a Patients with IBD who were exposed to anti-TNFs at any time during pregnancy 
and pre-conception.   
 Group 2b Infants born to Group 2a patients. 
Group 3: Conventional therapy only Cohort 
 Group 3a Patients with IBD who were exposed to conventional therapy only (such as 
Thiopurines) at any time during pregnancy and pre-conception.  
 Group 3b Infants born to Group 3a patients. 
 

 
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Number of Patients:  
The IBD MOM clinic sees approximately 15  pregnant women on Entyvio and 150 pregnant  
women on conventional therapy or other biologic agents each year. 
The sample size is based on anticipated recruitment at the IBD MOM clinic, rather than on the 
sample size needed for a specific minimum detectable relative risk.  Like most similar drug 
exposure pregnancy registries, this study by itself is underpowered to detect specific birth births. 
The intent is for the information generated from this study to be used in conjunction with 
information from several other stage 4 medications pregnancy registries in helping to identify or 
rule out potential risks. 
Based on previous experience of the OTIS Autoimmune Diseases in Pregnancy Project, it is 
estimated that subjects will be an average of 7-10 weeks post-LMP at the time of enrollment. 
Given this mean gestational timing at enrollment, the anticipated spontaneous abortion and 
stillbirth rate is 10%, the estimated elective abortion rate is 10%, the estimated lost-to-follow-up 
rate is 5% (based on previous OTIS experience) resulting in approximately 75 live born infants in 
each group at the end of recruitment. Experience with the current OTIS Autoimmune Diseases in 
Pregnancy Project has demonstrated a yield of approximately 80% live born infants from the total 
proportion enrolled; therefore the estimated yield of 75% in this proposal is conservative.  
Estimates of baseline rates of major structural defects, spontaneous abortion, premature delivery, 
and SGA and the standard deviation for mean birth weight of full-term infants are based on 
previous OTIS studies and on general population data. With this sample size, α of 0.05, 2-tailed 
test of significance (except as noted for pattern of minor anomalies), the minimum effect sizes and 
power shown in Table ‎0.a will be detectable. The primary comparison group for all analyses will 
be “exposed to other biologic drugs” exposure category.  
 
Table ‎0.a 
Sample Size and Power for a Specified Effect Size  
Endpoint 
N of Live Births in 
Each Exposure 
Group 
Baseline Rate 
Minimum 
Detectable 
Relative Risk 
Power (a) 
Major structural defects (b) 
75 
3% 
5.8 
80% 
Specific pattern of 3 or more minor 
structural defects  
75 
1% 
10.0 
71% 
Spontaneous abortion 
85 
10% 
2.8 
80% 
Premature delivery 
75 
6% 
3.8 
80% 
Small size for gestational age 
75 
7% 
3.5 
80% 
(a) Based on Fisher exact test, 2 tailed, and α=0.05, except specific pattern of 3 or more minor structural defects, which 
is based on a 1-sided test. For preterm delivery and SGA, although the population baseline rate is typically 10%, OTIS 
healthy comparison group is typically 6% and 7% incidence of preterm and SGA respectively, thus providing a more 
conservative estimate of power than other registries. 
(b) Primary endpoint.  
 

 
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With respect to the evaluation of minor malformations, the strength of this study 
design is in the ability to examine the data for a pattern of minor and/or major 
structural defects, given that the known human teratogens are typically associated 
with a pattern as opposed to isolated major birth defects. The baseline prevalence of a 
specific pattern of 3 or more minor structural defects is estimated to be essentially 
zero, as the occurrence of the same 3 low baseline frequency minor structural defects 
in any 2 children in a sample of 75 would be an extremely unlikely event. However, 
for purposes of the power calculation, a hypothetical baseline prevalence estimate of 
1% has been used. The minimum detectable relative risk (MDRR) with this sample 
size (10.0) has an approximately 71% power based on an alpha of 0.05 using a 1-
tailed Fisher exact test. A MDRR of 10 with a baseline rate of 1% represents a 10% 
birth prevalence of a specific pattern, which is comparable to the birth prevalence of a 
specific pattern in other known human teratogens of moderate risk such as the 
anticonvulsant medications.  
As the study may be underpowered for some endpoints and individual specific birth 
defects, study results will need to be interpreted with respect to both lower and upper 
bounds of the 95% confidence interval of the relative risk with caution. The following 
guide will be used: 
(a) If the CI lower bound >1 then risk is detected; 
(b) If the CI lower bound <1 and, 
 If the CI upper bound >MDRR, then MDRR is not detected but cannot be 
ruled out. 
 If the CI upper bound <MDRR , then MDRR is ruled out. 
 

 
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Study Procedures: 
Data will be included from patients currently enrolled in the registry and from patients 
who will be enrolled in the registry in the future. Data collection in the first year of 
pre-conception, conception, pregnancy, and delivery will be taken at Shaare Zedek 
and will include: 
Blood samples for CBC, CRP, ESR and others, Urine , stool and saliva samples  
From the infants: Blood tests at birth, 3 months, 6  and 12 months old for both study 
and control group. 
Stool samples will be taken from the infant's first meconium and in the age of one 
month, 3 months, 6 months and 12 months, in order to examine the influence of the 
medications used during pregnancy on the infant's bowel microbiome. These samples 
will be taken from both study and control group. 
 Two ml of mother's milk sample will be taken before the first stage-4 IBD 
medication infusion after birth and every second day during the two weeks later. 
Mother's milk samples will be taken from the control groups as well. 
The data collected during the follow up will include the gestational age, sex, delivery 
date, weight, live or still birth, and birth defects. 
Data collection for infants up until age four will be taken in cooperation with the 
Family Health Center (known as"Tippat Halav"). This will be done with the approval 
of the mom from the infant's vaccine notepad.   
The infants' health status will include: 
 Antibiotic use 
 Hospitalizations 
 Infections, including type of infectious pathogen (viral, bacterial, fungal, 
parasitic) 
 Other important diagnoses, including all congenital malformations 
 
The infants' developmental status will include: 
 
 Turning over from back to stomach or stomach to back at around 6 months 
 Sitting up without adult help between 9 and 12 months 
 Saying a word or significant sound between 9 and 12 months 
 Walking without adult help at 18 months until 2 years of age 
 Running without falling between 2 and 3 years of age 
 Forming sentences of at least 3 words between 2 and 3 years of age 
 Counting at least 3 objects until 4 years of age 
 
The study will assess pregnancy complications and birth outcomes with respect to 
IBD medications taken during pregnancy as well as disease activity. In addition, 
infants will be followed for 1 year to assess hospitalizations, infections, and emerging 

 
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disorders and developmental milestones.  
 
This study is non-interventional.. All decisions on clinical management are 
independent of participation in the study. 
 
The categorization of a patient to an exposure cohort is determined by the medication 
exposure status between 3 month prior to LMP and delivery for the pregnant women, 
using the following rules: 
 
Note that each pregnant woman will be included in only one cohort 
Blood tests for disease activity(CRP,ESR), Fecal calprotectin and lactofferin and 
serum levels for future performing through levels and ab will be taken for each 
patient every trimester and post partum Trough levels and ab will also be taken 
from cord blood and from the newborn at 3 and 6 months and 12 months of age. As 
part of the routine evaluation of IBD pregnant women in our clinic. 
 
 

 
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Outcome Variables: 
Primary Outcome: Major structural defects  
Definition: a major structural defect is defined as a defect that has either cosmetic or 
functional significance to the child (eg, a cleft lip), as defined by the Centers for 
Disease Control and Prevention (CDC; [4]). These defects in aggregate typically 
occur in <4% of the general population. Over 100 specific structural defects are 
considered to be major [4]. 
Secondary Outcome: Minor structural defects 
Definition: a minor structural defect is defined as a defect that has neither cosmetic 
nor functional significance to the child (eg, complete 2,3 syndactyly of the toes) and is 
identified using a study-related checklist incorporated into the study dysmorphology 
examination of live born infants. 
Inclusion Criteria for Structural Defects 
 Time period for identification: major structural defects identified up to 1 year of 
age by the mother, the HCP, or identified in the dysmorphological examination 
will be included in the primary analysis. Defects identified after that time frame 
will be described and considered separately.  
 Confirmation of defects: independent confirmation of certain defects will be 
required. For example, a heart murmur thought to represent a ventricular septal 
defect that is ascertained by the examining dysmorphologist prior to 1 year of age 
will be included if it is confirmed as a heart defect by cardiac ultrasound. 
Similarly, a midline cutaneous marker at L2-L3 noted in the dysmorphological 
examination will be included as occult spinal dysraphism only if confirmed by 
appropriate imaging studies. In addition, minor structural defects that are reported 
only by the mother or medical record but not confirmed by the dysmorphological 
examination will not be included as valid defects. 
 Body measurements: only those growth parameters for which actual 
measurements are available will be considered in the analysis. Measurements of 
head circumference, length, weight, palpebral fissure length, inner canthal 
distance, ear length, and philtrum length will be taken. These will be compared to 
mean values for infants of the same age and sex (where sex-specific normative 
data are available). Less than or greater than 2 standard deviations from the mean 
will be used to define such terms as microcephaly, hypertelorism, etc. 
Exclusion Criteria for Structural Defects 
 Birthmarks: isolated birthmarks will not be included. 
 Variations of normal: features on the physical examination which typically occur 
in greater than 4 percent of the population and have no cosmetic or functional 
significance for the child, eg, 2,3 syndactyly of the toes less than one-third of the 
distance to the tip of the 3rd phalanx, will not be included. 
 Deformational defects: Those deformational defects that do not require casting or 
surgery will not be included.  
 Time period for identification: structural defects ascertained after 12 months of 

 
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age will not be included in the analysis, but will be considered separately in the 
context of a possible pattern. 
 Defects identified in spontaneous abortions or elective terminations: Defects 
identified by prenatal ultrasound or examination of the products of conception 
following elective or spontaneous abortion will be not be included in the primary 
analysis of defects in live born infants due to potential bias involved in non-
uniform use of prenatal diagnosis and pathology evaluation for all abortuses; 
however, these defects will be considered in a separate analysis including all 
defects in the numerator over all pregnancies with known outcome in the 
denominator, and in the context of pattern. 
Additional Secondary Outcomes: 
Spontaneous abortion is defined as non-deliberate embryonic or fetal death that 
occurs prior to 20 weeks’ gestation post-LMP.  
Elective abortion is defined as deliberate termination of pregnancy at any time in 
gestation. Reason for elective abortion will be ascertained. 
Stillbirth is defined as a non-deliberate fetal death that occurs at or after 20 weeks’ 
gestation post-LMP, but prior to delivery.  
Premature delivery is defined as live birth prior to 37 completed weeks’ gestation 
post-LMP. Elective caesarian deliveries or inductions prior to 37 completed weeks are 
not considered premature deliveries, and will be considered separately. 
SGA is defined as birth size (weight, length or head circumference) less than or equal 
to the 10th percentile for sex and gestational age using standard pediatric CDC growth 
curves for full term or preterm infants [5,6]. 
Postnatal growth deficiency is defined as postnatal size (weight, length or head 
circumference) less than or equal to the 10th percentile for sex and age using National 
Center for Health Statistics (NCHS) pediatric growth curves, and adjusted postnatal 
age for premature infants if the postnatal measurement is obtained at less than 1 year 
of age.  
Lost-to-follow-up is defined as an enrolled subject where follow-up information on 
the outcome (live birth, fetal loss) is not obtainable, or for a live birth if the birth 
defect status is designated as “unknown” as of 12 months following the estimated due 
date. The OTIS Autoimmune Diseases in Pregnancy Project has experienced 
extremely low losses to follow-up (<5% of enrolled subjects) by virtue of maintaining 
consistent contact with the pregnant woman. Before a subject is designated as lost to 
follow up, the subject or reporter receives at least 3 reminder telephone calls 
(documented in the database) followed by written correspondence and alternative 
contact information that is requested upon enrollment is utilized. Voluntary subject 
withdrawals will be considered separately.  
Serious or opportunistic infections are defined as commonly accepted, and identified 
in newborn infants up to 1 year of age, or infections that require hospitalization up to 
1 year of age. Pediatric records will be requested with specific requests for 
documentation of hospitalizations and opportunistic infections. 
Malignancies are defined as any malignancy reported in an infant up to 1 year of age. 
Pediatric records will be requested with specific requests for documentation of 

 
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malignancies. 
Pregnancy history variables: maternal age, parity, outcomes of  previous birth 
outcomes; medication used in pregnancy, smoking in pregnancy, alcohol, etc. 
Pregnancy complications 
 
IBD variables 
IBD medications during pregnancy  
IBD sites 
Extraintestinal manifestations 
IBD flares during pregnancy 
IBD severity scores, such as Mayo score) during pregnancy, etc 
 
All variables will be collected by the IBD mom clinic team. 

 
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Management and Reporting of adverse events  
Serious Adverse Events in the Fetus/Infant  
If the investigators becomes aware adverse events occurring in a participant enrolled in the study 
with exposure to any stage-4 medication tested, the event will be reported to the regulatory 
authorities, IRBs and Takeda in accordance with national regulations, regardless of expectedness 
or causality. All SAEs and pregnancy reports will also be reported in English by facsimile to 
Takeda Pharmacovigilance or designee: 
Fatal and life threatening SAEs within 24 hours of the sponsor-investigator`s observation or 
awareness of the event 
All other serious (non-fatal/non-life threatening) events within 4 calendar days of the sponsor-
investigator`s awareness of the event 
SAEs are of the following: 
 Major birth defect. 
 Spontaneous abortion. 
 Still birth. 
 Elective termination of pregnancy. 
 Neonatal death. 
 Serious or opportunistic infection in infant. 
 Malignancy in infant. 
 Reports of adverse drug reactions in a newborn/neonate that are fatal, life-threatening, resulting 
in persistent or significant disability/incapacity or resulting in or prolonging hospitalization, 
except prolongation of hospitalization due to pre-specified study endpoints such as preterm 
delivery and small for gestational age birth weight, or delivery by caesarian section. 
Other Adverse Events in the Infant 
Any other adverse event occurring during the 1st year of life in an infant where the investigator is 
of the opinion that the adverse event is related to vedolizumab exposure, the adverse event will be 
reported to the sponsor within 24 hours of becoming aware of the event, using the Medwatch form. 
Serious Adverse Events in the mother  
If the investigators or research staff becomes aware of any adverse event in the mother that meets 
the following Serious Adverse Event criteria, and the investigator is of the opinion that the adverse 
event is related to vedolizumab exposure, the event will be reported to the sponsor within 24 hours 
of becoming aware of the event, using the Medwatch form: 
 Results in death 
 Is life-threatening. Life-threatening in this context refers to an event in which the subject was at 
risk of death at the time of the event. It does not refer to an event that hypothetically might 
have caused death if more severe 
 Results in persistent or significant disability or incapacity. Disability is defined as a substantial 
disruption of a person’s ability to conduct normal life functions. 
 Requires inpatient hospitalization or prolongation of an existing hospitalization. Hospitalization 
for underlying disease progression will constitute an SAE. Hospitalization for an elective or 

 
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planned procedure to treat a pre-existing condition is not considered an SAE, unless it results in 
one of the other outcomes listed above. 
 Suspected transmission of an infectious agent via a medicinal product 
Any other important medical event that may not result in death, be life-threatening or require 
hospitalization, but based upon appropriate medical judgment, may jeopardize the patient and may 
require medical or surgical intervention to prevent one of the outcomes listed above. 
Reporting to Regulatory Agencies  
Takeda will be responsible for reporting of adverse events to regulatory agencies, according to 
regulatory requirements. 
 
Statistical Analysis 
Groups 3a and 3b will serve as the control groups for the study. 
 Baseline demographics and disease characteristics will be summarized for the 3 disease cohorts 
at the time of enrollment. 
 
Descriptive statistics, such as mean, median, standard deviations, and range for continuous 
variables, and counts and percentages for categorical variables will be used to summarize data. 
All statistical testing will be 2-sided and will use a 0.05 level of significance. Incidence rates by 
exposure cohort will be estimated and compared using Fisher’s exact test. Crude and adjusted 
odds or risk ratios comparing Vedolizumab and reference  will be estimated along with 95% 
confidence intervals. Logistic regression will be used to compare birth outcomes for 
Vedolizumab and control cohort. General linear models will be used to compare infant health 
status between Vedolizumab and control cohorts. The covariates that will be included in models 
to estimate the adjusted risk ratios are provided in the Group Analyses Section. As a main rule 
subjects with missing values of a particular endpoint or covariate will not contribute to the 
analyses. Because missing data are minimal in the data sets, observed data will be used in the 
analysis without imputation. 
 
Data Management 
Data will be obtained and analyzed with the collaboration and assistance of Dr. Ariella Shitrit 
and/or her designees, There will be limited access only to study team. who will be responsible for 
data management and statistical analysis.  
Shaare Zedek Medical Center affiliated with the Hebrew University will serve as the Data 
Management Center and the site for all data management activities. 
 Upon completion of data collection it will be presented in GI conferences noting that this study 
was supported by takeda. 
 

 
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Data to be Extracted 
At 
Registry 
Entry 
3-Month Period 
Prior to Estimated 
LMP  
During Pregnancy and at Delivery 
Infant/Child  
Follow-up Period 
Trimester 
At 
Delivery 
At 4, 9, 12 months  
1st 
 
(LMP to 
Week 13) 
2nd 
 
(>13 weeks until  
Week 26) 
3rd 
 
(>26 weeks until  
Week 40) 
Maternal age at pregnancy 
 
x 
 
 
 
 
 
Maternal smoking  
 
x 
 
 
 
 
 
Maternal substance use (alcohol and/or recreational drugs) 
 
x 
 
 
 
 
 
Maternal diagnosis 
 
x 
 
 
 
 
 
Maternal duration of disease 
 
x 
 
 
 
 
 
Prior surgeries performed on mother 
 
x 
 
 
 
 
 
Maternal disease location 
 
x 
 
 
 
 
 
Maternal disease activity (HBI, SCAI, and modified PDAI)a 
 
x 
x 
x 
x 
x 
x 
Maternal medications  
 
x 
x 
x 
x 
x 
x 
Maternal IBD disease history 
x 
 
 
 
 
 
 
Maternal pre-pregnancy BMI 
x 
 
 
 
 
 
 
Maternal Parity 
x 
 
 
 
 
 
 
Pregnancy type (singleton or multiple) 
 
x 
 
 
 
 
 
Route of delivery  
 
 
 
 
 
 
 
Elective C-section 
 
 
 
 
 
x 
 
Emergency C-section 
 
 
 
 
 
x 
 
Vaginal 
 
 
 
 
 
x 
 
Duration of pregnancy 
 
 
 
 
 
x 
 
Gestational age 
 
 
 
 
 
x 
 
Schedule for Data Extraction 

 
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Spontaneous preterm birth 
 
 
 
 
 
x 
 
Pregnancy outcome 
 
 
 
 
 
 
 
Live birth, normal 
 
 
 
 
 
x 
 
Live birth, abnormal 
 
 
 
 
 
x 
 
Preterm birth 
 
 
 
 
 
x 
 
SGA  
 
 
 
 
 
x 
 
Congenital malformations 
 
 
 
 
 
x 
x 
Perinatal morbidity  
 
 
 
 
 
x 
 
Fetal death 
 
 
 
 
 
x 
 
Induced abortion, including reason for abortion 
 
 
 
 
 
x 
 
Spontaneous abortion 
 
 
 
 
 
x 
 
Stillbirth (intrauterine death) 
 
 
 
 
 
x 
 
Neonatal death 
 
 
 
 
 
x 
 
Infant’s birth weight 
 
 
 
 
 
x 
 
Infant’s sex 
 
 
 
 
 
x 
 
Infant’s APGAR at 5 minutes 
 
 
 
 
 
x 
 
Infant’s hospitalizations up to 4 years 
 
 
 
 
 
 
x 
Indication for hospitalization 
 
 
 
 
 
 
x 
Duration of hospitalization 
 
 
 
 
 
 
x 
Outcome 
 
 
 
 
 
 
x 
Infant’s infections up to 4 years 
 
 
 
 
 
 
x 
Type and location of infection 
 
 
 
 
 
 
x 
Pathogen information, if available 
 
 
 
 
 
 
x 
Antibiotic use 
 
 
 
 
 
 
x 
Parental socioeconomic status b 
 
x 
 
 
 
 
x 
Infant’s/Child’s vaccinations 
 
 
 
 
 
 
x 
New diagnoses that are chronic or severe 
 
 
 
 
 
 
x 
History of breast feeding c 
 
 
 
 
 
 
x 

 
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References 
 
1. 
Mahadevan U, Sandborn WJ, Li DK, et al. Pregnancy outcomes in women with inflammatory 
bowel disease: a large community-based study from Northern California. Gastroenterology. 
2007;133:1106-1112. 
2. 
Fonager K, Sørensen HT, Olsen J, et al. Pregnancy outcome for women with Crohn's disease: A 
follow-up study based on linkage between national registries. Am J Gastroenterol. 1998;93:2426-
30. 
3. 
Kornfeld D, Cnattingius S, Ekbom A. Pregnancy outcomes in women with inflammatory bowel 
disease--a population-based cohort study. Am J Obstet Gynecol. 1997;177:942-946. 
4. 
Nørgard B, Fonager K, Sørensen HT, et al. Birth outcomes of women with ulcerative colitis: A 
nationwide Danish cohort study. Am J Gastroenterol. 2000;95:3165-3170. 
5. 
Dotan I, Alper A, Rachmilewitz D et al. The effect of inflammatory bowel disease during 
pregnancy on long-term helath and illness in children of IBD patients – a multicenter Israeli 
study. Gastroenterology 136(5, Suppl. 1), A-15 (2009). 
6. 
Mahadevan U, Martin CF, Chambers C, Kane SV, Dubinsky,M, Sandborn W, et al. Achievement 
of developmental milestones among offspring of women with inflammatory bowel disease: the 
PIANO Registry. Gastroenterology 2014;146:S–1. 
Medwatch. MedWatch: The FDA Medical Products Reporting & Safety Information Program. 
Accessed 12 March 2013. http://www.fda.gov/medwatch/