Limited risks of major congenital anomalies in children of mothers with IBD and effects of medications

Gastroenterology. 2014 Jan;146(1):76-84. doi: 10.1053/j.gastro.2013.09.061. Epub 2013 Oct 12.

Abstract

Background & aims: Concerns persist about the risk of major congenital anomalies in children of women with inflammatory bowel disease (IBD), and whether medication use affects risk. We assessed these risks, and variations in use of medications by women with IBD before, during, and after pregnancy.

Methods: We accessed data on children born to women 15-45 y old from 1990 through 2010, using a mother-child linked dataset from an electronic database of primary care records containing medical diagnoses, events, and drug prescriptions from across the United Kingdom. We identified pregnant women with IBD, and all prescriptions for 5-aminosalicylates azathioprine/6-mercaptopurine, and corticosteroids were extracted from their primary care records. We calculated risks of major congenital anomaly in children of mothers with and without IBD, and in children exposed or not exposed to 5-aminosalicylates, azathioprine/6-mercaptopurine, or corticosteroids during their first trimester of fetal development. Logistic regression with a generalized estimating equation was used to provide risk estimates adjusted for confounders. We calculated proportions of women taking medications before, during, and after pregnancy and assessed whether cessation was associated with subsequent disease flares.

Results: Risks of a major congenital anomaly in 1703 children of mothers with IBD and 384,811 children of mothers without IBD were 2.7% and 2.8%, respectively. This corresponded to an adjusted odds ratio of 0.98 (95% confidence interval [CI], 0.73-1.31). In children of women with IBD, the adjusted odds ratios of a major congenital anomaly associated with drug use were 0.82 (95% CI, 0.42-1.61) for 5-aminosalicylates 0.48 (95% CI, 0.15-1.50) for corticosteroids, and 1.27 (95% CI, 0.48-3.39) for azathioprine/6-mercaptopurine. No increases in heart, limb, or genital anomalies were found in children of women with IBD; 31.2% of women discontinued 5-aminosalicylates and 24.6% discontinued azathioprine/6-mercaptopurine in early pregnancy. The risk of flares later in pregnancy was not related to cessation of medication.

Conclusions: We found no evidence that IBD during pregnancy or medical therapy for IBD during pregnancy increases the risk of a major congenital anomaly in children. Patients should receive appropriate guidance on use of medication before and during pregnancy.

Keywords: Birth Defects; CD; CI; Crohn's Disease; Crohn's disease; IBD; OR; Treatment; UC; Ulcerative Colitis; confidence interval; inflammatory bowel disease; odds ratio; ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aminosalicylic Acids / therapeutic use
  • Azathioprine / therapeutic use
  • Congenital Abnormalities / epidemiology*
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Inflammatory Bowel Diseases* / drug therapy
  • Inflammatory Bowel Diseases* / epidemiology
  • Logistic Models
  • Mercaptopurine / therapeutic use
  • Mesalamine / therapeutic use
  • Middle Aged
  • Odds Ratio
  • Pregnancy
  • Pregnancy Complications* / drug therapy
  • Pregnancy Complications* / epidemiology
  • Retrospective Studies
  • Risk Factors
  • Severity of Illness Index
  • United Kingdom / epidemiology
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Aminosalicylic Acids
  • Immunosuppressive Agents
  • Mesalamine
  • Mercaptopurine
  • Azathioprine