Background Despite the theoretic teratogenic effect of methotrexate after paternal exposure, there are only a few and small studies analysing the effect on offspring after paternal methotrexate exposure. It is well known that lack of knowledge on fetal adverse effects can lead to unnecessary fear, abortions and discontinued treatment. The objective of this study is to assess the association between paternal exposure to methotrexate within the 90 days period before conception and congenital malformations in the offspring.
Methods We conducted a study on paternal use of methotrexate in Denmark between 1997 and 2011. Information on fathers and live births were from the Danish Medical Birth Registry, information on malformations from the National Hospital Registry and paternal use of methotrexate within 90 days before conception was from the National Prescription Registry.
Primary outcome was major congenital malformations diagnosed within the first year after birth.
Results We identified a cohort of 849.676 live births with known paternity. Among 127 children with a father exposed to methotrexate before conception, four (3.2 %) were diagnosed with a major congenital malformation compared to 28,814 (3.4 %) children with fathers not exposed to methotrexate before conception. Adjusted odds ratio for major congenital malformations among exposed fathers compared to unexposed fathers was 1.01 (0.37-2.74). Five children (3.9 %) with a methotrexate exposed father were born with either a major or a minor congenital malformation compared to 42,245 (5.0 %) among children to unexposed fathers; revealing an adjusted odds ratio of 0.86 (0.35-2.10). There were no stillborn children to methotrexate exposed fathers.
Conclusion We did not find an association between paternal exposure to methotrexate within 90 days prior to conception and major congenital malformations or stillbirth. Available data does not support that preconception paternal methotrexate exposure should be of major concern.
By Lasse Karlsen Eck, Thomas Bo Jensen, Dimitrios Mastrogiannis, Bjarke Askaa, Torben Kjær Nielsen, Henrik Enghusen Poulsen, Espen Jimenez-Solem and Jon Trærup Andersen.