Birth Outcomes in Children Fathered by Men Treated with Anti-TNF-α Agents Before Conception

OBJECTIVES: The safety of paternal use of anti-tumor necrosis factor-alpha (TNF-alpha) agents immediately prior to conception is practically unknown. On the basis of nationwide data from Danish health registries, we examined the association between paternal use of anti-TNF-alpha agents within 3 months before conception and adverse birth outcomes. METHODS: This nationwide cohort study is based on data from all women who had a live born singleton child in Denmark from 1 January 2007 through 2013. Children fathered by men treated with anti-TNF-alpha agents within three months before conception constituted the exposed cohort (N = 372), and children fathered by men not treated before conception constituted the unexposed cohort (N = 399,498). The outcomes were congenital abnormalities (CAs), preterm birth, and small for gestational age (SGA). We adjusted for multiple covariates, and considered paternal underlying disease and concomitant medication. RESULTS: The adjusted risks of CAs and preterm birth were close to unity, and the adjusted odds ratio (OR) for SGA was 1.70 (95% confidence interval (CI): 0.94-3.09). Restricting our analysis to fathers with inflammatory bowel disease, we found no increased risk of CAs or SGA, and the adjusted OR for pretem birth was 1.42 (95% CI: 0.52-3.86). Restricting our analysis to fathers with rheumatologic/dermatological diseases, we found no increased risk of CAs or preterm birth, and the adjusted OR for SGA was 1.70 (95% CI: 0.74-3.89). CONCLUSIONS: Our results are overall reassuring regarding the safety of paternal preconceptional use of anti-TNF-alpha agents. The result regarding SGA should, however, be interpreted with caution as we found an increased risk, although not significantly increased.