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

Clin Gastroenterol Hepatol. 2022 Jan;20(1):74-87.e3. doi: 10.1016/j.cgh.2020.09.021. Epub 2020 Sep 12.

Abstract

Background & aims: Biologics are used routinely 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-tumor necrosis factor [TNF], anti-integrins, and anticytokines). 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%) for preterm birth, 0% (95% CI, 0%-0%; I2 = 0%) for stillbirth, 8% (95% CI, 5%-10%; I2 = 87.0%) for low birth weight, and 1% (95% CI, 1%-2%; I2 = 78.3%) for congenital malformations. These rates are comparable with 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 vs anti-TNF users. Meta-regression did not show 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% CI, 0.47-3.49; I2 = 0%).

Conclusions: Adverse pregnancy outcomes among pregnant IBD women using biologics are comparable with that of the general population. PROSPERO protocol #CRD42019135721.

Keywords: Biological Agents; Crohn’s Disease; Pregnancy Outcome; Ulcerative Colitis.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Biological Products* / adverse effects
  • Female
  • Humans
  • Infant, Newborn
  • Inflammatory Bowel Diseases* / chemically induced
  • Inflammatory Bowel Diseases* / complications
  • Inflammatory Bowel Diseases* / drug therapy
  • Pregnancy
  • Pregnancy Outcome
  • Premature Birth* / chemically induced
  • Premature Birth* / epidemiology
  • Tumor Necrosis Factor Inhibitors

Substances

  • Biological Products
  • Tumor Necrosis Factor Inhibitors