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

Background: Data on the safety of azathioprine and mercaptopurine during pregnancy are very sparse. Aim: To examine the risk of adverse birth outcomes in women who took up prescriptions for azathioprine or mercaptopurine during pregnancy. Methods: This is a Danish cohort study based on data from a population-based prescription registry, the Danish Birth Registry and the Hospital Discharge Registry. To examine the risk of congenital malformations, we included nine pregnancies exposed 30 days before conception or during the first trimester. To examine perinatal mortality, pre-term birth and low birth weight, we included 10 pregnancies exposed during the entire pregnancy. Eleven different exposed women were included in the study. Outcomes were compared with those of 19 418 pregnancies in which no drugs were prescribed to the mothers. Results: Fifty-five per cent of the exposed women had inflammatory bowel disease and 45% other diseases. Adjusted odds ratios for congenital malformations, perinatal mortality, pre-term birth and low birth weight were 6.7 (95% confidence interval, 1.4-32.4), 20.0 (2.5-161.4), 6.6 (1.7-25.9) and 3.8 (0.4-33.3), respectively. Conclusions: Our results suggest that there is an increased risk of congenital malformations, perinatal mortality and pre-term birth in children born to women treated with azathioprine or mercaptopurine during pregnancy. More data are needed to determine whether the associations are causal or occur through confounding.