Birth outcomes after preconception paternal exposure to methotrexate: A nationwide cohort study

Background: Methotrexate (MTX), a folic acid antagonist, is often prescribed for moderate to severe inflammatory related diseases. The safety of paternal MTX use prior to conception is unknown. This study, using the National Danish Registries, aimed to examine the association between paternal MTX use three months before conception and adverse birth outcomes. Results: Children fathered by men treated with MTX within three months before conception constituted the exposed cohort (N=193), and children fathered by men not treated with MTX constituted the unexposed cohort (N = 1,013,801). The adjusted odds ratio (OR) for preterm birth was 1.38 (95% CI:0.68-2.81). The adjusted ORs of congenital anomalies (CAs) and small for gestational age (SGA) were 1.10 (95% CI:0.57-2.13) and 0.98 (95% 0:0.39-2.50), respectively. Conclusion: Our results regarding the effect of paternal use of MTX within 3 months before conception on birth outcomes of CAs, preterm birth and SGA are overall reassuring. (C) 2017 Elsevier Inc. All rights reserved.