Birth Outcomes in Women Who Have Taken Vedolizumab in Pregnancy: Results From the Vedolizumab Pregnancy Exposure Registry

Abstract

OBJECTIVES:

There are limited data on the safety of vedolizumab in pregnancy for the treatment of Crohn's disease or ulcerative colitis. Between 2015 and 2022, the Organization of Teratology Information Specialists conducted a prospective, observational pregnancy registry study with 275 pregnant women residing in the United States or Canada.

METHODS:

Women were enrolled in 1 of 3 cohorts: vedolizumab-exposed (N = 99); disease-matched unexposed to vedolizumab, but treated with another biologic in pregnancy (N = 76); or unexposed with no chronic health conditions (N = 100). Women and their infants were followed up to 1 year postpartum with maternal interviews, questionnaires, medical records abstraction, and a subset of infants who received a physical examination. Study outcomes were major structural birth defects, minor birth defects, pregnancy loss, preterm delivery, prenatal and postnatal growth deficiency, serious or opportunistic infections, malignancies, and developmental milestones.

RESULTS:

In the overall registry, 17 of 275 pregnancies (6.2%) were lost to follow-up. Among pregnancies ending in at least 1 live born infant, 7 of 94 (7.4%) in the vedolizumab-exposed cohort compared with 4 of 71 (5.6%) in the disease-matched cohort had a major birth defect (adjusted risk ratio 1.07, 95% confidence interval [CI] 0.33, 3.52). Compared with the disease-matched cohort, women in the vedolizumab-exposed group were not statistically significantly more likely to experience spontaneous abortion (adjusted hazard ratio 1.01, 95% CI 0.17, 5.89). Women in the vedolizumab-exposed group were slightly but not significantly more likely to deliver preterm (adjusted hazard ratio 1.58, 95% CI 0.65, 3.82).

CONCLUSIONS:

No significant increased risks were noted with vedolizumab exposure for any of the other study outcomes. These data add reassuring evidence in support of the safety of vedolizumab in pregnancy.

INTRODUCTION

Vedolizumab is a humanized immunoglobulin G1 monoclonal antibody directed against the human lymphocyte integrin α₄β₇. The α₄β₇ integrin mediates lymphocyte trafficking to gastrointestinal (GI) mucosa and gut-associated lymphoid tissue through adhesive interactions with mucosal addressin cell adhesion molecule-1, which is expressed on the endothelium of mesenteric lymph nodes and GI mucosa. Vedolizumab exclusively targets the α₄β₇ integrin, antagonizing its adherence to mucosal addressin cell adhesion molecule-1 and thus impairing the migration of leukocytes into GI mucosa. By virtue of its gut-selective mechanism of action, vedolizumab is expected to have immunomodulatory activity without the generalized immunosuppression found with current treatments of Crohn's Disease (CD) or ulcerative colitis (UC) (1).

Preclinical reproduction studies with vedolizumab were performed by the manufacturer in pregnant rabbits at single intravenous doses up to 100 mg/kg administered on Gestation Day 7 (about 20 times the recommended human dosage) and revealed no evidence of impaired fertility or harm to the fetus due to vedolizumab. A prenatal and postnatal development study in monkeys showed no evidence of any adverse effect on prenatal and postnatal development at intravenous doses up to 100 mg/kg (about 20 times the recommended human dosage) (2).

However, data on the safety of vedolizumab in human pregnancy are limited. Mitrova et al (3) (2022) reported on 39 women exposed to vedolizumab and found the rate of pregnancy complications did not differ significantly from a comparison group of women exposed to antitumor necrosis alpha (TNF) inhibitors. Moens et al (4) (2020) presented data from a retrospective multicenter observational study on 79 pregnancies treated with vedolizumab compared with 2 disease-matched groups and found the overall risk of adverse pregnancy outcomes was similar between the groups. More recently, Chugh et al (5) (2024) reported on data from the prospective US Pregnancy Inflamatory bowel disease And Neonatal Outcome study (PIANO) registry in which 66 vedolizumab-exposed pregnancies were compared with pregnancies in women both receiving other treatments or untreated and found no differences for any adverse pregnancy or infant outcomes.

With the completion of the Vedolizumab Pregnancy Exposure Registry, we sought to add prospective observational data regarding the safety of vedolizumab when used in pregnancy for CD or UC.

METHODS

Design and setting

MotherToBaby/Organization of Teratology Information Specialists (OTIS) conducts prospective pregnancy cohort studies (registries) involving pregnant participants across the United States and Canada. The methods of MotherToBaby/OTIS cohort studies have been described previously (6–8).

In brief, MotherToBaby services, located in academic institutions, hospitals, or health departments throughout the United States and Canada, provide counseling to women and their healthcare providers who contact the services with questions about the risks of exposures in pregnancy. Pregnant women who meet the criteria for a study are referred to the OTIS Research Center at the University of California San Diego where they are screened, consented to participate and where all subsequent data collection takes place. Additional methods of recruitment are also used, including physician referrals and direct-to-consumer awareness activities through social media and the MotherToBaby website. In all cases, the pregnant woman is the individual who provides consent to participate in the study and she is the primary source of medication exposure data.

Participants

A Pregnancy Exposure Registry for vedolizumab was initiated in 2015, and study data on enrolled pregnant women and their infants were collected through 2022. Women with a diagnosis of CD or UC and prenatal exposure to vedolizumab were prospectively recruited into an exposed cohort. Women with CD or UC but no treatment with vedolizumab were recruited into a disease-matched comparison cohort. An additional cohort of unexposed comparison women without chronic diseases was also recruited and followed in the same manner.

Women met the inclusion criteria for all 3 cohorts if they enrolled in the study before 20 weeks of gestation, did not have prenatal diagnosis before enrollment with this pregnancy of a fetus with a major structural birth defect, and had not enrolled in the registry study with a previous pregnancy, i.e., only 1 pregnancy per woman was eligible. Inclusion criteria for the vedolizumab-exposed group required receipt of any dose of vedolizumab at any time in pregnancy from the 1st day of the last menstrual period (LMP) to the end of the first trimester with or without continued use of the medication through the remainder of gestation. Women met the inclusion criteria for the disease-matched comparison group if they had a diagnosis of CD or UC, were not treated with vedolizumab at any time in pregnancy, but were treated with another biologic such as an anti-TNF agent. Women in the nondiseased cohort met the inclusion criteria if they did not have any chronic diseases and no exposure to a known human teratogen at the time of enrollment. A list of exposures considered to be known human teratogens is provided in Supplemental Table 1, http://links.lww.com/AJG/D684.

Maternal interviews

Women in all cohorts completed up to 3 telephone interviews during pregnancy and 1 at the completion of pregnancy. These were conducted by trained study staff in English or Spanish. The enrollment interview obtained information on demographic; pregnancy and family medical history; tobacco, alcohol, and caffeine consumption; recreational drug use; infections; fever; and prenatal tests. Data regarding products, dosages, dates, and indications for treatment were collected on all medications (prescription, over-the-counter), vitamins/minerals, herbal products, and vaccines used/administered from the 1st day of the LMP through the date of the interview. Subsequent maternal interviews elicited information on additional exposures or events since the last interview. The Slone Epidemiology Center's Drug Dictionary was used to code exposures (9). In the exposed and disease-matched comparison cohorts, women also responded at each interview to the Short Quality of Life in Inflammatory Bowel Disease Questionnaire (SIBDQ) (10).

Outcomes

Outcomes were collected by maternal interview and by medical records obtained from the obstetrician, gastroenterologist, pediatrician, and delivery hospital as well as pathology reports if relevant. Data were collected on outcome status of each pregnancy (live birth, stillbirth, spontaneous abortion, and elective termination), gestational age at outcome, mode of delivery, sex and number of infants, birth weight, length, and head circumference and the presence or absence of major birth defects detected up through the first year of life. Maternal report of major birth defects was confirmed by medical record review.

Major structural defects were reviewed by a birth defects specialist who was a coinvestigator for this study (K.L.J.), and final classification was made using the US Centers for Disease Control and Prevention Metropolitan Atlanta Congenital Defects Program coding system (11). Spontaneous abortion was defined as spontaneous pregnancy loss at <20.0 gestational weeks. Preterm delivery was defined as delivery at <37.0 gestational weeks. Ultrasound dating was used to correct gestational weeks, as necessary for discrepant dates or if the LMP date was unknown using a standard algorithm. Small for gestational age (SGA) infants on weight, length, and head circumference was defined as ≤10th centile for sex and gestational age in live born infants using standard US growth charts for full-term and preterm infants (12–14).

Minor structural defects were evaluated through a study-specific physical examination of live born infants offered to participating parents and conducted by 1 of a team of pediatric specialists in dysmorphology/genetics. Examinations were performed in the participant's home or by telemedicine. The examiners were blinded to the mother's/infant's exposure status at the time of the evaluation. A study-specific checklist of minor structural defects (Supplemental Table 2, http://links.lww.com/AJG/D684) was used to document the presence or absence of approximately 132 minor features. In addition, infant length and head circumference were measured and infant photographs were taken if the parent provided specific consent.

Live born children were routinely followed for 1 year postpartum. Medical records from the pediatrician were requested and abstracted for additional evidence of any major structural birth defects, postnatal growth, serious or opportunistic infections, and malignancies. Postnatal growth deficiency was defined as ≤10th centile for weight, length, and head circumference for sex and chronological age at about 1 year using standard US growth charts. Serious or opportunistic infections were defined as infections requiring hospitalization or those from a specific checklist (Supplemental Table 3, http://links.lww.com/AJG/D684). Mothers of live born infants were also asked to complete the Ages and Stages Questionnaire, Third Edition when the child was about at the age of 1 year to assess developmental milestones (15).

All participants provided informed consent. Institutional review board approval for the study was obtained through the University of California San Diego, La Jolla, California. Annual interim, final results, and conclusions of the study investigators were reviewed by an independent Scientific Advisory Board with expertise in epidemiology, congenital malformations, and maternal autoimmune diseases.

Statistical methods

The primary study outcome was major structural birth defects among pregnancies ending in at least 1 live born infant. The unit of analysis for major birth defects was the pregnancy, i.e., a singleton or multiple pregnancies that ended in 1 or more malformed infants was considered 1 major birth defect outcome.

A point estimate of the crude (i.e., unweighted) risk ratio (RR) of the exposed group versus each unexposed group, as well as its 95% confidence interval (CI) was computed using the normal approximation method. When the expected frequency of any of the cells of the contingency table was less than 5, the CI was obtained by an exact method using the software StatXact (16).

Potential confounders appropriate for each study end point were considered from the list of the baseline characteristics. Three criteria were applied to define confounders (17,18): (i) by assessing each considered variable in a logistic regression model containing the exposure and the outcome variable to determine if inclusion of that single covariate changed the estimate of the odds ratio for exposure by 10% or more, (ii) standardized mean differences greater than 0.1, and (iii) association with the outcome with P value < 0.2 in the unexposed cohort (using χ² test, Fisher exact test, or 2 sample t test). The confounders identified above were used to build the propensity score for exposure (19). Standardized mean differences were used to check the balance of the covariates between the cohorts.

For the primary analysis of major structural birth defects, the adjusted RR (aRR) was estimated using inverse probability of treatment weighting (20). The 95% CIs were obtained using the bootstrap-estimated variance and asymptotic normality, with 200 bootstrap samples. The propensity score was recomputed for each bootstrap sample to account for variability in the estimation of the weights.

For the analysis of spontaneous abortion, survival methods were used to handle left truncation as women entered the study at varying gestational ages, as well as right-censoring when a participant was lost to follow-up. This approach avoids bias for events such as spontaneous abortion where the risk of the event declines with advancing gestational age, and women are only eligible for the study who have not yet experienced the event (21,22). The left-truncated Fleming-Harrington estimator was used to calculate the spontaneous abortion rate at 20 weeks of gestation (23,24). Marginal structural Cox models incorporating left truncation were used to estimate the adjusted hazard ratio (aHR) and to obtain the 95% CIs. Preterm delivery was analyzed similarly using survival methods to handle possible right-censoring. This analysis excluded pregnancies with twins or higher order multiples.

SGA at birth and postnatal growth deficiency at about 1 year of age on weight, length, and head circumference were binary end points. The analyses of these were similar to the primary end point of major birth defects. However, in the analyses of growth, twins or higher order multiples were excluded.

Multiple births were included in the analyses of minor structural defects, serious or opportunistic infections, malignancies, and assessment of developmental milestones within the first year of life. These outcome variables were thus likely to contain correlated data such as twins, and the generalized estimating equations approach was used (25–27). More specifically, the crude RR with 95% CI was estimated using log-binomial link and independent working correlation (R package “geepack”). The weighted HR was estimated based on infants as the unit of analysis, and confidence intervals were obtained using bootstrap.

For minor structural birth defects, the analysis was restricted to infants for whom the study-related physical examination was completed. The prevalence of any 3 or more minor structural birth defects was compared between cohorts. In addition, among the vedolizumab-exposed, clusters of any 2 or more infants with the exact same 3 or more minor structural defects were identified and the prevalence of those patterns was compared with the prevalence of the same specific clusters in the unexposed groups.

Missing values for each potential confounder were assumed to be missing at random. When there were missing values for any of the selected confounders, multiple imputation was conducted, using the R package multivariate imputation by chained equations (MICE) (28).

Sensitivity analyses were conducted only for the primary end point. In these analyses, the comparisons between cohorts were performed with the inclusion of pregnancy losses along with live births in the numerator and denominator. A second sensitivity analysis examined the primary outcome within each of 2 strata, according to whether the participant had prenatal diagnostic testing before enrollment in the study or not. The purpose of this was to address potential bias introduced by prior knowledge of normal prenatal diagnostic testing results in advance of enrollment. A third sensitivity analysis excluded coexposure to known human teratogens. A fourth analysis was stratified by the underlying primary indication for maternal treatment to address potential differential findings by disease group. All analyses were conducted using R open-source statistical software or StatXact (2011).

RESULTS

A total of 275 pregnant women enrolled in the study: 99 were exposed to vedolizumab in pregnancy, 76 were disease-matched unexposed to vedolizumab, and 100 were nondiseased comparison pregnancies. A total of 17/ of 275 enrolled women (6.2%) were lost to follow-up.

In comparison with the disease-matched cohort, those in the vedolizumab-exposed group were on average younger, more likely to be Hispanic, lower socioeconomic status, have fewer years of education, and have high body mass index, pregestational hypertension, and unintended pregnancies. By contrast, years since first diagnosis of the underlying disease, treatment with systemic steroids in pregnancy, and scores on the SIBDQ did not differ significantly between these 2 groups (Table 1).

Table 1.

Characteristics of women enrolled in the Vedolizumab Pregnancy Exposure Registry 2015–2022

In comparison with the nondiseased cohort, those in the vedolizumab-exposed group, on average, were more likely to be of White race, enroll earlier in gestation, to have comorbid asthma, reside in the United States, and were less likely to have had a previous spontaneous abortion (Table 1).

Descriptive outcomes are presented in Table 2. In the vedolizumab-exposed cohort, the diseased comparison cohort, and the nondiseased comparison cohort, the proportion of pregnancies ending in at least 1 live birth was 94.9%, 93.4%, and 85.0%, respectively. There were no stillbirths in the exposed cohort, 1 stillbirth in the diseased comparison cohort, and 0 in the nondiseased comparison cohort. There were no elective abortions in any cohort.

Table 2.

Pregnancy outcomes in the Vedolizumab Pregnancy Exposure Registry 2015–2022

Among pregnancies ending in at least 1 live born infant, 7 of 94 (7.4%) in the vedolizumab-exposed cohort compared with 4 of 71 (5.6%) in the disease-matched cohort had a major birth defect (aRR 1.07, 95% CI 0.33, 3.52). In the nondiseased cohort, 4 of 85 (4.7%) had a major birth defect (aRR 2.64, 95% CI 0.85, 8.23) (Table 3). In each of the sensitivity analyses, the results did not materially differ; however, the point estimates within the CD stratum were higher than that in the UC stratum (Supplemental Table 4, http://links.lww.com/AJG/D684). The specific major birth defects identified in each cohort are described in Supplemental Table 5 (http://links.lww.com/AJG/D684). Although there were 3 ventricular septal heart defects in the vedolizumab-exposed cohort, 2 of the 3 resolved spontaneously after birth. There was no pattern of minor anomalies identified in the vedolizumab-exposed group among the subset of infants who received the specialized physical examination (Table 3).

Table 3.

Birth prevalence of major structural birth defects and minor structural defects in the Vedolizumab Pregnancy Exposure Registry 2015–2022

Women in the vedolizumab-exposed group had comparable risk of spontaneous abortion in comparison with the disease-matched cohort (aHR 1.01, 95% CI 0.17, 5.89) or the nondiseased cohort (HR 1.16, 95% CI 0.12, 11.48). Similarly, the hazard of preterm delivery was not significantly elevated in the vedolizumab-exposed cohort compared with the disease-matched group (aHR 1.58, 95% CI 0.65, 3.82) or the nondiseased group (aHR 1.20, 95% CI 0.58, 2.47) (Table 4).

Table 4.

Spontaneous abortion^a,b and preterm delivery^c in the Vedolizumab Pregnancy Exposure Registry 2015–2022

Prenatal and postnatal growth deficiency did not differ between groups in any comparison, except that the vedolizumab-exposed group was less likely to have small head circumference at birth than the nondiseased comparison group (Table 5).

Table 5.

Small for gestational age^a and postnatal growth deficiency^b in the Vedolizumab Pregnancy Exposure Registry 2015–2022^c

Point estimates for serious or opportunistic infections in the first year of life were increased when comparing the vedolizumab-exposed group with either comparator cohort, but not significantly so, with very wide CIs that included 1 (Table 6). The specific infections are provided in Supplemental Table 6 (http://links.lww.com/AJG/D684). There were no malignancies reported in any infants in the study. Of those who completed the Ages and Stages Questionnaire, Third Edition on developmental milestones, 10 of 70 (14.3%) had at least 1 concern in the vedolizumab group, compared with 14 of 62 (22.6%) in the disease-matched group (aRR 0.38 95% CI 0.20, 0.72) and 11 of 60 (18.3%) in the nondiseased cohort (aRR 0.91 95% CI 0.41, 2.03).

Table 6.

Serious or opportunistic infections and malignancies up to 1 yr of age in the Vedolizumab Pregnancy Exposure Registry 2015–2022

DISCUSSION

In this study, for the outcome of major birth defects, there was no significant increased risk in the vedolizumab-exposed group compared with the disease-matched group among pregnancies ending in at least 1 live birth (aRR 1.07, 95% CI 0.33, 3.52). In addition, we found no significant increased risks for spontaneous abortion, stillbirth, preterm delivery, prenatal or postnatal growth deficiency, malignancies, serious or opportunistic infections, or developmental concerns in pregnancies/infants prenatally exposed to vedolizumab compared with either disease-matched or nondiseased, unexposed pregnancies/infants. These findings are consistent with several previous small studies.

Mitrova et al (3) (2022) reported on 39 vedolizumab-exposed pregnancies compared with 90 pregnancies treated with anti-TNF therapy from a prospective multicenter observational study. Rates of congenital malformations, spontaneous abortion, preterm delivery, and low birth weight did not differ between groups.

Moens et al (2020) presented data gathered retrospectively from 29 centers in 9 European countries. Pregnancies treated with vedolizumab (N = 79) were compared with pregnancies treated with TNF inhibitors (N = 186) and to pregnancies with inflammatory bowel disease but no treatment with immunomodulators or biologics (N = 184). Even though women in the vedolizumab-treated group were more likely to have active disease early in pregnancy than the comparison groups, there were no differences between groups on rates of congenital malformations, spontaneous abortion, stillbirth, preterm delivery, reduced birth weight, infections, or malignancies (4).

Chugh et al (2024) analyzed data from the multicenter prospective US-based PIANO study on 66 vedolizumab-exposed pregnancies compared with pregnancies treated with biologics and immunomodulators or pregnancies with inflammatory bowel disease but untreated. No differences between groups were found for congenital malformations, spontaneous abortion, preterm birth, SGA, placental complications, developmental milestones, or serious infections up to the age of 1 year (5).

By contrast, in a meta-analysis conducted by Nielsen et al (2022), including some of the data cited in the 3 studies above, the authors found that vedolizumab treatment in 4 studies was associated with higher risk of spontaneous abortion and preterm delivery compared with treatment with other TNF inhibitors pooled. No other adverse outcomes were associated with vedolizumab in that meta-analysis (29). In our study, we found no evidence of an increased risk of spontaneous abortion; however, the estimates were based on only 7 events across the 3 cohorts. We did note a higher rate of preterm delivery in the vedolizumab-exposed group (14.5%) than the disease-matched comparison group (8.4%) and the nondiseased group (7.2%). This translated to an elevated point estimate of the aHR of 1.58 for the comparison of the vedolizumab-exposed group with the disease-matched group, but the CI were wide and included the null (0.65, 3.82). In addition, while the study included the SIBDQ, use of systemic steroids, and years since diagnosis as measures of disease activity or severity, these measures may not have been adequate to fully address the contribution of the maternal underlying disease activity to risk for preterm delivery.

Our study had several limitations. The study approach was prospective but not randomized. Although we used appropriate methods for statistical adjustment for confounders, as discussed, there were likely unmeasured or inadequately measured confounders such as underlying disease severity, which could have biased results in either direction. The sample size, similar to most other pregnancy registries, was small, leading to, in some cases, imprecise estimates and limited statistical power to detect more modest differences. However, the differences that were detectable would be considered clinically meaningful. The study relied on volunteers, which could have led to selection bias. Selection bias could affect generalizability, i.e., participants might not represent the entire population of exposed and unexposed women. However, the inclusion of internal comparator groups and prospective enrollment before the known outcome of pregnancy supports internal validity. Furthermore, the primary objective of this study was to evaluate teratogenicity. Human teratogens are not known to differentially affect certain subgroups of the population, so these findings are relevant to the general population of exposed pregnancies.

The study had several strengths, including prospective enrollment before the known outcome of pregnancy, low lost to follow-up, and overall <5% missing values for covariates, thereby minimizing bias because of incomplete data and evaluation of a range of outcomes including developmental screening at about the age of 1 year. Two internal comparator groups were followed using the same methods as the vedolizumab-exposed group, supporting internal validity. Outcomes reported by the study participant were confirmed with medical record review and augmented by the specialized study examination. However, not all live born infants received the physical examination.

In conclusion, we found no meaningful evidence of increased risks for major structural birth defects or any of the other adverse outcomes under study. While the sample size was limited, and the study relied on volunteer participants, the findings of this study were consistent with 3 other previously published controlled studies. Taken together, the available evidence does not suggest an increased risk for any of the adverse pregnancy or infant outcomes studied.

CONFLICTS OF INTEREST

Guarantor of the article: Christina D. Chambers, PhD, MPH.

Specific author contributions: C.D.C.: contributed to the planning and conducting of the study, collecting and interpreting data and drafting the manuscript. D.L.J.: contributed to the planning and conducting of the study, collecting and interpreting data and drafting the manuscript. Y.L.: contributed to the planning and conducting of the study, collecting and interpreting data and drafting the manuscript. R.X.: contributed to the planning and conducting of the study, collecting and interpreting data and drafting the manuscript. M.P.A.: contributed to the planning and conducting of the study, collecting and interpreting data and drafting the manuscript. S.R.B.: contributed to the planning and conducting of the study, collecting and interpreting data and drafting the manuscript. K.L.J.: contributed to the planning and conducting of the study, collecting and interpreting data and drafting the manuscript. The OTIS Collaborative Research Group authors contributed to recruitment of participants into the study and to the interpretation of data. All authors have approved the final draft submitted.

Financial support: Funding support for this study was provided by Takeda Pharmaceutical Company. The content is solely the responsibility of the authors and does not necessarily represent the official view of the funder. As this study was conducted to meet a postmarketing regulatory responsibility, the funder provided input on the study design and the plan for analysis, and had the opportunity to provide comments on the manuscript.

Potential competing interests: Drs. Chambers, Jones and Xu receive research funding support from the following industry sponsors and a foundation: Amgen, AstraZeneca; Bristol Myers Squibb, GlaxoSmithKline; Janssen Pharmaceuticals; Pfizer, Inc.; Regeneron; Hoffman La-Roche-Genentech; Genzyme Sanofi-Aventis; Takeda Pharmaceutical Company Limited; Sanofi; UCB Pharma, USA; Leo Pharma, Sun Pharma Global FZE; Gilead; Novartis; and the Gerber Foundation.

EUPAS register: 11681.

Clinical trial registration: NCT02878052.

Study Highlights.

WHAT IS KNOWN

• ✓ There are limited data on safety of vedolizumab in pregnancy.

WHAT IS NEW HERE

• ✓ The vedolizumab pregnancy registry evaluated a range of safety outcomes in 99 exposed and 176 comparison pregnancies.

• ✓ No specific safety signals were identified.

• ✓ These data are reassuring for pregnant persons who require treatment with vedolizumab.

ABBREVIATIONS:

AI

Auto Immune

CD

Crohn’s Disease

CDC

Centers for Disease Control

CI

Confidence Interval

GALT

Gut-associated lymphoid tissue

GEE

Generalized estimating equations

IBD

inflammatory bowel disease

IPTW

Inverse probability of treatment weighting

LMP

Last menstrual period

MAdCAM1

Mucosal addressin cell adhesion molecule1

MI

Multiple imputation

MICE

Multivariate Imputation by Chained Equations

NCHS

National Center for Health Statistics

OTIS

Organization of Teratology Information Specialists

PIANO

Pregnancy Inflammatory bowel disease And Neonatal Outcome study

RR

Risk Ratio

SAB

Spontaneous Abortion

SES

Socioeconomic status

SIBDQ

Short Quality of Life in Inflammatory Bowel Disease Questionnaire

UC

Ulcerative colitis