Maternal rheumatoid arthritis and systemic lupus erythematosus and risk of cryptorchidism and hypospadias in boys: a Danish nationwide study

Objectives: RA and SLE are the most prevalent autoimmune rheumatic diseases affecting young women. Both diseases are characterized by systemic inflammation that may affect placental function and fetal development during pregnancy, and both diseases are associated with adverse pregnancy and child outcomes. We investigated the associations between maternal RA or SLE and the two genital malformations, cryptorchidism and hypospadias. Methods: In this nationwide register-based study including all male singleton live births in Denmark from 1995 to 2016, we assessed the occurrence of cryptorchidism and hypospadias according to the prenatal disease-state of the mothers. Using Cox proportional hazards models we calculated adjusted hazard ratios, accounting for varying age at diagnosis. Results: Among 690 240 boys, 1026 had a mother with RA and 352 had a mother with SLE. We found adjusted hazard ratios of 1.72 (95% CI: 1.15; 2.57) for cryptorchidism among boys born to mothers with RA and 1.46 (95% CI: 0.69; 3.06) for boys born to mothers with SLE, compared with the general population. As the number of hypospadias cases was low, multivariate analysis was not feasible. The crude hazard ratios were 0.51 (95% CI: 0.16; 1.58) and 1.00 (95% CI: 0.25; 4.03) for RA and SLE, respectively. Conclusion: Boys born to mothers with RA had higher risk of cryptorchidism, compared with unexposed boys. Boys born to mothers with SLE showed a similar tendency, however with less precision of the estimate. No conclusion could be reached on the risk of hypospadias, due to the low number of events.