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Use of Thiopurines During Conception and Pregnancy Is Not Associated With Adverse Pregnancy Outcomes or Health of Infants at One Year in a Prospective Study

Published:March 22, 2017DOI:https://doi.org/10.1016/j.cgh.2017.02.041

      Background & Aims

      Most data on the safety of thiopurine therapy for inflammatory bowel disease (IBD) during pregnancy come from retrospective studies, which makes it difficult to adjust for confounding factors. We performed a prospective cohort study to determine whether thiopurine use affects pregnancy outcomes or health outcomes of children.

      Methods

      We performed a prospective study of all women who visited the IBD preconception outpatient clinic at our tertiary health center in The Netherlands from December 2008 through May 2016. Patients were counseled before pregnancy and seen bimonthly during pregnancy. We collected and analyzed data on medication use, as well as lifestyle and clinical factors, during conception and pregnancy. Pregnancy outcomes (live birth, spontaneous abortion, elective abortion, and stillbirth), birth outcomes (gestational age, birth weight, and congenital abnormalities), and health outcomes of infants 1 year after birth were compared between women who did and did not use a thiopurine during conception and pregnancy. In addition, health outcomes of infants 1 year after birth were compared with infants born to mothers without IBD from the same geographic region.

      Results

      Our study comprised 309 women with confirmed IBD (216 with Crohn’s disease, 85 with ulcerative colitis, and 8 with IBD unclassified). During the study period, 311 pregnancies of 232 women resulted in a live birth; a thiopurine was used during 108 pregnancies (35%). After correction for diagnosis, fertility treatment, and disease activity, there was no association between thiopurine use and spontaneous abortions. Birth outcomes were similar between women who did and did not use a thiopurine. Among infants 1 year of age, there were no differences in median growth, number of infections, allergies, adverse reactions to vaccinations, or chronic diseases between those born to women who did and did not use a thiopurine or between women with and without IBD.

      Conclusions

      In this prospective cohort study, we found no association between maternal thiopurine use during pregnancy and increased spontaneous abortions, adverse birth outcomes, or adverse health outcomes of infants 1 year after birth.

      Keywords

      Abbreviations used in this paper:

      6-MMP (6-methylmercaptopurine), 6-TGN (6-thioguanine nucleotides), aOR (adjusted odds ratio), AZA (azathioprine), BMI (body mass index), CD (Crohn’s disease), CI (confidence interval), cOR (crude odds ratio), HBI (Harvey-Bradshaw Index), HELPP (Hemolysis Elevated Liver enzymes and Low Platelets), IBD (inflammatory bowel disease), IQR (interquartile range), MP (mercaptopurine), OR (odds ratio), PCOS (polycystic ovarian syndrome), RS (respiratory syncytial), SCCAI (Simplified Clinical Colitis Activity Index), SD (standard deviation), SGA (small for gestational age), TG (thioguanine), TNF (tumor necrosis factor), TPMT (thiopurine s-methyltransferase), VSD (ventricular septum defect)
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