THU0670 PATERNAL USE OF METHOTREXATE AND CONGENITAL MALFORMATIONS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

Background Maternal exposure to methotrexate (MTX) during pregnancy is known to be teratogenic, but less is known about the risk due to paternal MTX exposure. Because of a theoretical teratogenic risk from paternal exposure, treatment recommendations advocate that men should discontinue MTX three months before conception and continue discontinuation during the partners pregnancy. This may lead to suboptimal adherence to treatment, fear among the future parents and pregnancy termination. Objectives The aim was to systematically review and meta-analyze the collective data on paternal MTX exposure and the risk of congenital malformations. Methods We performed a systematic search in the databases PubMed, Embase, Cochrane Central, and Cinahl on March 1, 2018. We included studies with an English abstract that assessed major or all (both major and minor) malformations following any paternal exposure to MTX. Studies that included a control group were included in the meta-analysis. No time restriction was applied. Review Manager Version 5.3 was used for the meta-analysis. Results We identified 36 studies assessing the risk of congenital malformations following paternal exposure to MTX of which 20 contained original data. Five studies met the inclusion criteria for the meta-analysis: Three studies from Denmark had a major overlap in study populations, one study from Norway, and one German study. All studies were cohort studies using national registries except the German that used structured interviews and phone interviews. Because of the overlapping Danish studies, only the largest Danish study for each of the outcomes were included. We included a total of 265 fathers exposed to MTX and 1,004,834 controls in the meta-analysis investigating risk of major congenital malformations. Among the offspring of the MTX-exposed 7 (2.64%) had a major malformation compared to 33,816 (3.37%) among the unexposed. Pooled odds ratios were 1.02 (95% confidence interval [CI] 0.48-2.20) for major malformations and 1.02 (CI 0.62-1.66) for all malformations. Conclusion(s) In this systematic review and meta-analysis, we found no association between preconceptional paternal MTX use and major or all congenital malformations. The current recommendations to avoid paternal MTX use before conception do not appear to be supported by evidence and paternal treatment with MTX could be continued when planning a pregnancy. Disclosure of Interests Thomas Bo Jensen: None declared, Mikkel Bring Christensen: None declared, Nicole Tsao: None declared, Seoyoung Kim Grant/research support from: Pfizer, Bristol-Myers Squibb, Roche/Genentech and AbbVie., Jon Trrup Andersen: None declared