TOPLINE:

While overall risks for adverse birth outcomes were not increased in children born to fathers who used disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, for autoimmune diseases in the preconception period, certain agents were linked to increased risks.

METHODOLOGY:

• In this retrospective cohort study, researchers examined birth outcomes in children born to fathers with autoimmune conditions who were exposed to DMARDs before conception.
• They used Taiwanese databases and identified 42,493 live births between January 2004 and December 2020 to fathers diagnosed with an autoimmune disease within 1 year before conception (mean paternal age, 34.45-35.89 years).
• Overall, 14.3% of fathers were exposed to DMARDs 38-60 weeks before delivery (34-58 weeks for preterm births); the remaining were unexposed and served as comparators.
• Exposures included thiopurines, methotrexate, TNF-alpha antagonists, non-TNF-alpha-targeting biologics, and targeted synthetic therapies.
• The primary outcomes were preterm birth (< 37 weeks), small for gestational age, and congenital malformations, including birth defects affecting different body parts.

TAKEAWAY:

• Overall, exposure of fathers to any treatment before conception was not associated with increased odds for birth defects, very small for gestational age, or preterm birth.
• Paternal exposure to methotrexate showed no adverse effects on birth outcomes. Exposure to ciclosporin was linked to higher odds for very small for gestational age (adjusted odds ratio [aOR], 1.45; 95% CI, 1.19-1.76) and preterm birth (aOR, 1.51; 95% CI, 1.35-1.70) than no exposure to any treatment.
• The odds for birth defects were increased in infants whose fathers were exposed to azathioprine (aOR, 1.47; 95% CI, 1.31-1.65), non-TNF inhibitors (aOR, 1.69; 95% CI, 1.48-1.93), or a combination of conventional synthetic DMARDs with biologic or targeted DMARDs (aOR, 1.71; 95% CI, 1.47-2.00).
• Paternal exposure to biologic DMARDs was associated with higher odds for cardiovascular anomalies (aOR, 1.61; 95% CI, 1.37-1.89), oral clefts (OR, 1.62; 95% CI, 1.15-2.29), and musculoskeletal defects (aOR, 2.29; 95% CI, 1.82-2.89) than no exposure to any treatment.

IN PRACTICE:

“Although the number of these events was small, the findings suggest that paternal exposure during preconception could be a potential risk factor for adverse infant outcomes and warranting further confirmation in larger cohorts,” the authors of this study wrote.

SOURCE:

This study was led by Yu-Hsuan Joni Shao, PhD, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. It was published online on November 28, 2025, in Arthritis Research & Therapy.

LIMITATIONS:

This study used claims data and had no measures of disease activity. Very few fathers were exposed to several drug groups, which may have affected the risk estimates. The cohort was not large enough to analyze specific autoimmune diseases and their treatments separately.

DISCLOSURES:

This study received funding from the Ministry of Science and Technology and Taichung Veterans General Hospital, both in Taiwan. The authors declared having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.