Children whose fathers were exposed to drugs for the treatment of inflammatory bowel disease (IBD) — primarily azathioprine (AZA) and 6-mercaptopurine (6-MP) — within three months of conception had no significantly increased risk for adverse birth outcomes, according to the results of a large Danish national cohort study.
The study, “Reassuring results on birth outcomes in children fathered by men treated with azathioprine/6-mercaptopurine within 3 months before conception: a nationwide cohort study,” was published in the journal Gut.
“This is the largest and most comprehensive study to date on the effect of preconceptual use of AZA/6-MP in men on birth outcomes, and overall, our results are reassuring,” Dr. Sonia Friedman, MD, and her colleagues from the University of Southern Denmark and Brigham and Women’s Hospital, Harvard Medical School, wrote in a recent news release.
IBD is frequently diagnosed during childbearing years, and both men and women are often concerned about the effects of medications on their potential offspring. The immunomodulators AZA and its active metabolite 6-MP have been used since the 1970s to treat IBDs, especially ulcerative colitis and Crohn’s disease.
Based on nationwide data from the Danish health registries, Friedman and her colleagues tested the potential relationship between paternal use of AZA/6-MP and birth complications.
The “exposed cohort” included 699 children who were fathered by men exposed to AZA/6-MP within three months before conception, and the unexposed cohort included 1,012,624 children whose fathers were not exposed to the medications within three months before they were conceived. The outcomes analyzed were congenital abnormalities (CAs), preterm birth, and small for gestational age (SGA).
The results showed there were no statistically significant increased risks for any of the outcomes analyzed in the exposed cohort compared with the unexposed cohort in both the overall and the IBD subgroup analysis.
However, the risk for small birth weight for gestational age was non-significantly increased in the overall analysis and in the IBD subgroup analysis, and the risk for preterm birth was also non-significantly increased in the IBD subgroup. The numbers were too small to be considered significant.
These results, indicating no significant increased risks of birth complications, are encouraging and support the continuation of paternal AZA/6-MP treatment during conception.
“This nationwide study has the greatest number of exposed patients to date, and since the results are reassuring, [men with inflammatory bowel disease] wishing to conceive should be advised to continue their medications,” the researchers concluded.