Rationale and Background:
Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions that
affect the gastrointestinal tract and can be divided into two main types: Crohn's disease
(CD) and ulcerative colitis (UC). Half of the people diagnosed with IBD received their
diagnosis before the age of 35 years, which coincides with the peak reproductive years
for women. Studies have shown that IBD is associated with increased risk of adverse
pregnancy and fetal outcomes, including preterm birth, stillbirth, and low birth weight.
The CorEvitas IBD Pregnancy Registry (IBD-PR) aims to collect real-world evidence on the
safety of IBD pharmacotherapies during pregnancy and the first year of infant life and
provide valuable insights into the risks and safety profiles of IBD medications, enabling
healthcare professionals to make more informed decisions when managing IBD in pregnant
individuals.
Research Question and Objectives: Data collected through the registry may be used to
address a range of research questions and objectives, including but not limited to the
following:
The research question is: Is there an increased risk of adverse maternal, fetal, or
infant outcomes among individuals who are exposed to IBD pharmacotherapies during
pregnancy?
The primary objective of the registry is to estimate the prevalence of major congenital
malformations (MCM) among pregnant individuals with IBD who are exposed to an IBD
pharmacotherapy during pregnancy.
The secondary objectives of the registry are:
To estimate the prevalence of other maternal, fetal, and infant outcomes among pregnant
individuals with IBD who are exposed to an IBD pharmacotherapy during pregnancy
To contextualize the prevalence of outcomes among pregnant individuals who are exposed to
IBD pharmacotherapies during pregnancy and estimate the prevalence of all outcomes of
interest among pregnant individuals with IBD who are not exposed to an IBD
pharmacotherapy during pregnancy
If sample size permits, to estimate the risk ratio for each outcome, comparing the
outcomes of pregnant individuals with IBD who are exposed to an IBD pharmacotherapy with
outcomes of those who are not exposed to an IBD pharmacotherapy
Data collection may be used to determine pharmacotherapy-specific use with or without
unexposed cohorts on an as-needed basis, as sample size allows.
Study Design: This prospective, observational cohort study is designed to estimate the
prevalence of maternal, fetal, and infant outcomes among individuals with IBD who are
exposed to an IBD pharmacotherapy during pregnancy. For this registry, the index date
will be the date of first exposure to the IBD pharmacotherapy for the exposed cohort and
the date of enrollment for the unexposed cohort. The risks of pregnancy-related outcomes,
maternal outcomes, and neonatal/infant outcomes will be estimated for participants with
IBD exposed and unexposed to any IBD pharmacotherapies or an IBD pharmacotherapy of
interest during pregnancy.
Population: The registry population will include two cohorts of pregnant individuals: one
cohort of individuals with a diagnosis of IBD who are exposed to an IBD pharmacotherapy
during pregnancy and one cohort of individuals with a diagnosis of IBD who are not
exposed to IBD pharmacotherapies during pregnancy.
Variables: Individuals will be considered exposed during pregnancy if at least one dose
of an IBD treatment is taken during pregnancy or up to at least five times the product's
half-life before conception. The primary outcome of interest is MCMs. The maternal and
pregnancy secondary outcomes include minor congenital malformations, preeclampsia,
eclampsia, spontaneous abortion, stillbirth, pregnancy termination, preterm birth, small
for gestational age, gestational diabetes, pregnancy-induced hypertension, and placental
abruption. The infant secondary outcomes during the first year of life include postnatal
growth deficiency, infant developmental delay, infant hospitalization, infant infections
(both serious and nonserious), and infant death. Covariates will include demographics,
risk factors for the outcomes, comorbidities, concomitant medications, and predictors of
treatment with an approved IBD pharmacotherapy.
Data Source: This registry will collect data from participants and healthcare providers
involved in their care or the care of their infants via concise data collection forms at
predefined timepoints during pregnancy, at pregnancy outcome, and up to 1 year of infant
age.
Study Size: The registry aims to include as many pregnant individuals as possible, with
no defined upper limit on enrollment in each cohort, to estimate the prevalence of the
primary outcome, MCM, with meaningful confidence and precision. This approach aims to
achieve adequate sample size to address additional research questions of interest, and/or
maintain generalizability and representativeness of the registry population. Assuming a
prevalence of MCM equivalent to 3% in each cohort, 1,143 and 303 live births in the
analysis population of each cohort are needed to estimate the prevalence of MCM with ±1%
and 2% precision, respectively.
Data Analysis: Participant characteristics will be summarized with descriptive statistics
for each cohort. Comparative analyses will be conducted for each outcome if sample size
permits. Supplementary analyses will be conducted that include pregnant individuals who
were excluded from the analysis population. If sample size permits, subgroup and
sensitivity analyses will be performed to examine the extent to which changes in certain
methods or assumptions affect the results.
Milestones: The IBD-PR is expected to launch in March 2025, and the end of data
collection is planned for 30 September 2032.