No excess risks in offspring with paternal preconception exposure to disease-modifying antirheumatic drugs

To examine pregnancy outcomes in the partners of male patients with inflammatory joint disease who were or were not exposed to disease-modifying antirheumatic drugs (DMARDs) before conception compared with the outcomes in reference subjects from the general population.

Linkage of data from a longitudinal observational study of patients with inflammatory joint disease (the Norwegian Disease-Modifying Antirheumatic Drug [NOR-DMARD] registry study) and the Medical Birth Registry of Norway (MBRN) enabled a comparison of pregnancy outcomes in the partners of men with inflammatory joint disease. Outcomes of pregnancies in which the father was exposed to DMARDs within 12 weeks of conception and those in which the father was never exposed to DMARDs were analyzed separately and compared with the outcomes in reference subjects. Potential associations between DMARD exposure and adverse pregnancy outcomes were assessed by logistic regression analysis.

A total of 1,796 men with inflammatory joint disease were associated with 2,777 births in the MBRN. In 110 of these births, the father had been exposed to DMARDs within 12 weeks before conception, and in 230 births the father had never been exposed to DMARDs before conception. The DMARDs (monotherapy or combination treatment) to which the fathers were exposed most frequently within 12 weeks of conception were methotrexate (n = 49), sulfasalazine (n = 17), and tumor necrosis factor inhibitors (n = 57). Neither adverse pregnancy outcomes nor occurrence of congenital malformations differed between patients and reference subjects in either group.

Preconception paternal exposure to DMARDs was not associated with an increase in adverse pregnancy outcomes. Importantly, no increased risk of congenital malformations was observed.