Immunosuppressive and Biologic Therapy in Expectant Fathers With IMIDs Not Linked to Adverse Birth Outcomes

Researchers examined the safety of exposure to immunosuppressive or biologic agents around the time of conception in expectant fathers with IMIDs.

Exposure to immunosuppressive or biologic agents shortly before conception is not associated with an increased risk for adverse birth outcomes among expectant fathers with immune-mediated inflammatory diseases (IMIDs), according to a study in Gastroenterology.

The retrospective cohort study evaluated birth outcomes in children fathered by men with IMIDs who were exposed to conventional immunosuppressive or biologic agents within 3 months before conception. Researchers identified the expectant fathers from a large administrative claims database (OptumLabs Data Warehouse), which includes data on more than 100 million commercially insured and Medicare Advantage enrollees throughout the United States.

A total of 7453 expectant fathers (mean age [SD], 35.8 [5.6] years; 68.8% white) with IMIDs (inflammatory bowel diseases, rheumatoid arthritis, psoriasis/psoriatic arthritis, ankylosing spondylitis) who were linked to at least 1 newborn were identified between January 1, 2005, and December 31, 2018. Neonatal follow-up was 3 months after the delivery date.

Among the cohort, 1846 (24.8%) participants were exposed to immunosuppressive or biologic medication in the periconception period, and 5607 were unexposed. In the exposure group, 461 (25.0%) participants were exposed to thiopurines, 171 (9.3%) to methotrexate, 1082 (58.6%) to tumor necrosis factor (TNF)-α antagonists, and 132 (7.1%) to non–TNF-α–targeting biologics (ustekinumab in 114 patients, vedolizumab in 18 patients).

The primary outcome was the risk of major congenital malformations, and secondary outcomes included the risk of preterm birth (<37 weeks of gestation) and low birth weight (<2500 g at birth).

About 3.5% of newborns were born with major congenital malformations, with cardiovascular system and urinary system anomalies the most frequently occurring. No significant association was found between paternal exposure to any immunosuppressive or biologic medication and the risk for major congenital malformations.

Regarding the specific drugs, the investigators found no association between exposure to thiopurines (relative risk [RR], 1.12; 95% CI, 0.66-1.76), methotrexate (RR, 0.67; 95% CI, 0.21-1.55), TNF-α antagonists (RR, 1.14; 95% CI, 0.81-1.57), and non–TNF-α–targeting biologic agents (RR, 1.75; 95% CI, 0.80-3.24) and the risk for major congenital malformations.

Among the secondary outcomes, 7.3% of total newborns were born pre-term, with a similar rate observed in those born to fathers not exposed to immunosuppressive or biologic medications in the periconception period (7.3%) compared with those who were exposed to medications (7.4%). In addition, 4.3% of total newborns had low birth weight, and the prevalence was similar in those born to fathers not exposed to immunosuppressive or biologic medications in the periconception period (4.2%) vs those exposed to medications (4.4%).

Among several study limitations, the researchers noted that they were unable to determine the impact of paternal exposure on fertility, abortion, and stillbirth. Furthermore, they did not account for exposure to smoking or alcohol in fathers and mothers. Finally, the cohort had limited ethnic diversity, and dispensed medication may not have been equal to medication intake at the time of conception.

“Overall, these findings are very reassuring to expectant fathers and mothers with IMIDs, that exposure of IMID-directed pharmacotherapy does not appear to increase the risk of major adverse birth outcomes,” the investigators concluded. “These findings fill an important evidence gap and support continuing pharmacotherapy without interruption in fathers planning conception.”

Disclosures: Some of the authors reported affiliations with pharmaceutical companies. Please see the original reference for a full list of disclosures.


Meserve J, Luo J, Zhu W, et al. Paternal exposure to immunosuppressive and/or biologic agents and birth outcomes in patients with immune-mediated inflammatory diseases. Gastroenterol. Published online March 17, 2021. doi: 10.1053/j.gastro.2021.03.020