Systematic review and meta-analysis on the effects of thiopurines on birth outcomes from female and male patients with inflammatory bowel disease

Inflamm Bowel Dis. 2013 Jan;19(1):15-22. doi: 10.1002/ibd.22948.

Abstract

Background: Inflammatory bowel disease (IBD) affects people during their prime reproductive years. The thiopurines (6-mercaptopurine and azathioprine), commonly used for induction and maintenance of remission, are U.S. Food and Drug Administration (FDA) pregnancy category D, raising concern for fetal risk. We performed a systematic review and meta-analysis to evaluate the effects of thiopurine exposure during pregnancy or at the time of conception on three measures of fetal risk in women and men with IBD.

Methods: A systematic search of PubMed and Web of Science using a combination of Mesh and text terms was performed to identify studies reporting birth outcomes from IBD women and men exposed to thiopurines within 3 months of conception and/or during pregnancy. A meta-analysis was performed using the random effects model to pool estimates and report odds ratio (OR) for three outcomes in women: low birth weight (LBW), preterm birth, and congenital abnormalities and one in men: congenital abnormalities.

Results: In women with IBD exposed to thiopurines, the pooled ORs for LBW, preterm birth, and congenital abnormalities were 1.01 (95% confidence interval [CI] 0.96, 1.06), 1.67 (95% CI 1.26, 2.20), and 1.45 (95% CI 0.99, 2.13), respectively. In men, the pooled OR for congenital abnormality was 1.87 (95% CI 0.67, 5.25).

Conclusions: Thiopurine exposure in women with IBD was not associated with LBW or congenital abnormalities, but was associated with preterm birth. Exposure in men at the time of conception was not associated with congenital abnormalities.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Azathioprine / adverse effects*
  • Congenital Abnormalities / etiology*
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Infant, Low Birth Weight
  • Infant, Newborn
  • Inflammatory Bowel Diseases / complications
  • Inflammatory Bowel Diseases / drug therapy*
  • Male
  • Mercaptopurine / adverse effects*
  • Meta-Analysis as Topic
  • Odds Ratio
  • Pregnancy
  • Pregnancy Complications / chemically induced*
  • Premature Birth / chemically induced
  • Prognosis

Substances

  • Immunosuppressive Agents
  • Mercaptopurine
  • Azathioprine