Biologics for Inflammatory Bowel Disease and their Safety in Pregnancy: A Systematic Review and Meta-analysis

BACKGROUND & AIMS: Biologics are routinely used in pregnant women with inflammatory bowel disease (IBD) but large-scale data reporting adverse pregnancy outcomes among biologic users are lacking. We sought to estimate the prevalence of adverse pregnancy outcomes in women with IBD on biologic therapies.

METHODS: We searched major databases from inception to June 2020 for studies estimating the prevalence of adverse pregnancy outcomes in IBD when using biologics (anti-TNF, anti-integrins, and anti-cytokines). Prevalence and relative risk (RR) were pooled using a random effects model.

RESULTS: Forty-eight studies were included in the meta-analysis comprising 6963 patients. Biologic therapy in IBD pregnancies was associated with a pooled prevalence of 8% (95% CI 6-10%, I2= 87.4%) for early pregnancy loss, 9% (95% CI 7-11%, I2=89.9%) preterm birth, 0% (95% CI 0-0%, I2=0%) still birth, 8% (95% CI 5-10%, I2=87.0%) low birth weight, and 1% (95% CI 1-2%, I2=78.3%) congenital malformations. These rates are comparable to those published in the general population. In subgroup analyses of a small number of studies, the prevalence of early pregnancy loss and preterm birth were higher in vedolizumab versus anti-TNF users. Meta-regression did not reveal an association of disease activity or concomitant thiopurine on adverse outcomes. Continued TNF inhibitor use during the third trimester was not associated with risk of preterm birth (RR 1.41, 95% CI 0.77-2.60, I2=0%), low birth weight (RR 1.32, 95% CI 0.80-2.18, I2=0%), or congenital malformations (RR 1.28, 95% 0.47-3.49, I2=0%).

CONCLUSIONS: Adverse pregnancy outcomes among pregnant IBD women with biologic use are comparable with that of the general population. PROSPERO protocol #CRD42019135721.