Maternal use of Loratadine during pregnancy and risk of hypospadias in offspring

To examine the risk of hypospadias after exposure to loratadine and other antihistamines during pregnancy, we conducted a population-based case-control study in four Danish counties, which account for 30% of the Danish population (~1.6 M). We obtained data on maternal use of antihistamines from prescription databases, and data on birth outcomes from the Danish Medical Birth Registry (MBR) and the Hospital Discharge Registry (HDR). A total of 65,383 male births with a full prescription history of the mother in the study period from 1989-2002 were available for analysis. Within this cohort, we identified cases with a diagnosis of hypospadias, and 10 selected controls per case without such a diagnosis (matched on birth month, gender and year of birth). We identified 227 cases of hypospadias recorded in the HDR within six months postpartum and 2270 controls. One case (0.4%) and eight (0.4%) controls were exposed to loratadine in the first trimester and up to 30 days before the time of conception. The adjusted odds ratio (OR) for hypospadias among users of loratadine relative to non-users was 1.4 (95% CI: 0.2-11.2) and the corresponding OR for other antihistamines was 1.9 (95% CI: 0.7-5.7). In this study, maternal exposure to loratadine did not appear to be associated with an increased risk of hypospadias when compared with other antihistamines, although it should be noted that the statistical precision of the risk estimates might be limited.