Gastroenterology

Gastroenterology

Volume 146, Issue 1, January 2014, Pages 76-84
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Limited Risks of Major Congenital Anomalies in Children of Mothers With IBD and Effects of Medications

https://doi.org/10.1053/j.gastro.2013.09.061Get rights and content

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.

Section snippets

Defining the Study Population

We studied all live singleton children born to women aged 15–45 years between 1990 and 2010 using an anonymized mother-child–linked data set from The Health Improvement Network, a nationally representative UK database of primary care records containing medical diagnoses, events, and drug prescriptions.22 For each mother-child pair, we defined women as having IBD in pregnancy if they had a diagnosis of IBD ever before childbirth or if they had a diagnosis after childbirth but prescriptions of

Results

Of 386,514 children, 0.4% were born to mothers who had IBD before childbirth (n = 1703) and 0.2% were born to mothers with CD (n = 893). Table 1 shows the maternal characteristics for children born to women with and without IBD. Compared with children in the control group, children in the IBD group were less likely to be from socioeconomically deprived areas, were more likely to be born later in the study period, and their mothers were slightly older (Table 1). However, children born to women

Principal Findings

This study is among the largest in terms of the number of women with IBD included, number of births, and number of major congenital anomalies that has yet been conducted to assess the risks of congenital anomalies among children of women with IBD. It showed no overall excess risk of a major congenital anomaly in children born to mothers with IBD and none associated with azathioprine/6-mercaptopurine, corticosteroids, or 5-aminosalicylate use within the maternal IBD population. The study also

Conclusions

We conclude that neither IBD, nor its common medical treatments, are likely to be major risk factors for congenital anomalies, but that this message may not have reached all pregnant women. About one quarter of women stop their medication in pregnancy. Although this may increase the risk of flares later in pregnancy, we were unable to show such increase.

Acknowledgments

All authors contributed to the conception and design of the study, and analysis and interpretation of the study results; Timothy Card, Laila Jal Tata, and Lu Ban drafted the manuscript; all authors revised the manuscript; and Timothy Card supervised the study and is the guarantor of the article.

References (40)

  • J.A. Dominitz et al.

    Outcomes of infants born to mothers with inflammatory bowel disease: a population-based cohort study

    Am J Gastroenterol

    (2002)
  • J.D. Lewis et al.

    Seasonal variation in flares of inflammatory bowel disease

    Gastroenterology

    (2004)
  • F. Zorzi et al.

    Efficacy and safety of infliximab and adalimumab in Crohn's disease: a single centre study

    Aliment Pharmacol Ther

    (2012)
  • J.L. Weaver

    Establishing the carcinogenic risk of immunomodulatory drugs

    Toxicol Pathol

    (2012)
  • A. Bortoli et al.

    Pregnancy outcome in inflammatory bowel disease: prospective European case-control ECCO-EpiCom study, 2003–2006

    Aliment Pharmacol Ther

    (2011)
  • M. Bush et al.

    Perinatal outcomes in inflammatory bowel disease

    J Maternal Fetal Neonatal Med

    (2004)
  • J. Cornish et al.

    A meta-analysis on the influence of inflammatory bowel disease on pregnancy

    Gut

    (2007)
  • O. Stephansson et al.

    Congenital abnormalities and other birth outcomes in children born to women with ulcerative colitis in Denmark and Sweden

    Inflamm Bowel Dis

    (2011)
  • B. Nørgård et al.

    Azathioprine, mercaptopurine and birth outcome: a population-based cohort study

    Aliment Pharmacol Ther

    (2003)
  • L. Park-Wyllie et al.

    Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies

    Teratology

    (2000)
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    Conflicts of interest The authors disclose no conflicts.

    Funding This study was funded by the National Association for Colitis and Crohn's Disease. The funders had no role in the conception, conduct, interpretation, or write-up of the study.

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