Health outcomes of 1000 children born to mothers with inflammatory bowel disease in their first 5 years of life

Gut. 2021 Jul;70(7):1266-1274. doi: 10.1136/gutjnl-2019-319129. Epub 2020 Oct 12.

Abstract

Objective: The aim of this study was to describe the long-term health outcomes of children born to mothers with inflammatory bowel disease (IBD) and to assess the impact of maternal IBD medication use on these outcomes.

Design: We performed a multicentre retrospective study in The Netherlands. Women with IBD who gave birth between 1999 and 2018 were enrolled from 20 participating hospitals. Information regarding disease characteristics, medication use, lifestyle, pregnancy outcomes and long-term health outcomes of children was retrieved from mothers and medical charts. After consent of both parents, outcomes until 5 years were also collected from general practitioners. Our primary aim was to assess infection rate and our secondary aims were to assess adverse reactions to vaccinations, growth, autoimmune diseases and malignancies.

Results: We included 1000 children born to 626 mothers (381 (61%) Crohn's disease, 225 (36%) ulcerative colitis and 20 (3%) IBD unclassified). In total, 196 (20%) had intrauterine exposure to anti-tumour necrosis factor-α (anti-TNF-α) (60 with concomitant thiopurine) and 240 (24%) were exposed to thiopurine monotherapy. The 564 children (56%) not exposed to anti-TNF-α and/or thiopurine served as control group. There was no association between adverse long-term health outcomes and in utero exposure to IBD treatment. We did find an increased rate of intrahepatic cholestasis of pregnancy (ICP) in case thiopurine was used during the pregnancy without affecting birth outcomes and long-term health outcomes of children. All outcomes correspond with the general age-adjusted population.

Conclusion: In our study, we found no association between in utero exposure to anti-TNF-α and/or thiopurine and the long-term outcomes antibiotic-treated infections, severe infections needing hospital admission, adverse reactions to vaccinations, growth failure, autoimmune diseases and malignancies.

Keywords: azathioprine; inflammatory bowel disease; infliximab; non-steroidal anti-inflammatory drugs.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / therapeutic use
  • Adult
  • Anti-Bacterial Agents / therapeutic use
  • Autoimmune Diseases / epidemiology
  • Cesarean Section / statistics & numerical data
  • Child Development / physiology
  • Child, Preschool
  • Congenital Abnormalities / epidemiology
  • Drug Prescriptions / statistics & numerical data
  • Drug Therapy, Combination
  • Female
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Small for Gestational Age
  • Infections / drug therapy
  • Infections / epidemiology*
  • Inflammatory Bowel Diseases / drug therapy*
  • Infliximab / therapeutic use
  • Mercaptopurine / analogs & derivatives
  • Mercaptopurine / therapeutic use
  • Neoplasms / epidemiology*
  • Netherlands / epidemiology
  • Patient Admission / statistics & numerical data
  • Pregnancy
  • Pregnancy Complications / epidemiology*
  • Premature Birth / epidemiology
  • Prenatal Exposure Delayed Effects / epidemiology*
  • Retrospective Studies
  • Tumor Necrosis Factor Inhibitors / therapeutic use
  • Vaccines / adverse effects

Substances

  • Anti-Bacterial Agents
  • Gastrointestinal Agents
  • Tumor Necrosis Factor Inhibitors
  • Vaccines
  • azathiopurine
  • 6-methylthiopurine
  • Infliximab
  • Mercaptopurine
  • Adalimumab