Pregnancy and Neonatal Outcomes After Fetal Exposure to Biologics and Thiopurines Among Women With Inflammatory Bowel Disease

Gastroenterology. 2021 Mar;160(4):1131-1139. doi: 10.1053/j.gastro.2020.11.038. Epub 2020 Nov 21.

Abstract

Background & aims: Pregnant women with inflammatory bowel disease (IBD) may require biologic or thiopurine therapy to control disease activity. Lack of safety data has led to therapy discontinuation during pregnancy, with health repercussions to mother and child.

Methods: Between 2007 and 2019, pregnant women with IBD were enrolled in a prospective, observational, multicenter study across the United States. The primary analysis was a comparison of 5 outcomes (congenital malformations, spontaneous abortions, preterm birth, low birth weight, and infant infections) among pregnancies exposed vs unexposed in utero to biologics, thiopurines, or a combination. Bivariate analyses followed by logistic regression models adjusted for relevant confounders were used to determine the independent effects of specific drug classes on outcomes of interest.

Results: Among 1490 completed pregnancies, there were 1431 live births. One-year infant outcomes were available in 1010. Exposure was to thiopurines (n = 242), biologics (n = 642), or both (n = 227) vs unexposed (n = 379). Drug exposure did not increase the rate of congenital malformations, spontaneous abortions, preterm birth, low birth weight, and infections during the first year of life. Higher disease activity was associated with risk of spontaneous abortion (hazard ratio, 3.41; 95% confidence interval, 1.51-7.69) and preterm birth with increased infant infection (odds ratio, 1.73; 95% confidence interval, 1.19-2.51).

Conclusions: Biologic, thiopurine, or combination therapy exposure during pregnancy was not associated with increased adverse maternal or fetal outcomes at birth or in the first year of life. Therapy with these agents can be continued throughout pregnancy in women with IBD to maintain disease control and reduce pregnancy-related adverse events. ClinicalTrials.gov, Number: NCT00904878.

Keywords: Crohn’s Disease; Pregnancy; Ulcerative Colitis.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / adverse effects*
  • Azathioprine / adverse effects
  • Biological Products / adverse effects
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / immunology
  • Crohn Disease / drug therapy*
  • Crohn Disease / immunology
  • Drug Therapy, Combination / adverse effects
  • Drug Therapy, Combination / methods
  • Female
  • Humans
  • Infant, Newborn
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology
  • Mercaptopurine / adverse effects
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Pregnancy Complications / immunology
  • Pregnancy Outcome*
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / epidemiology*
  • Prenatal Exposure Delayed Effects / immunology
  • Prospective Studies
  • United States / epidemiology

Substances

  • Anti-Inflammatory Agents
  • Biological Products
  • Mercaptopurine
  • Azathioprine

Associated data

  • ClinicalTrials.gov/NCT00904878