Preconceptional paternal antiepileptic drugs use and risk of congenital anomalies in offspring: a nationwide cohort study

Recent studies have shown that certain pharmacological agents used by fathers before conception may increase the risk of adverse neonatal outcomes in offspring. However, little is known about the effect of paternal use of antiepileptic drugs (AEDs) on congenital anomalies in children. Based on Danish national registers, we conducted a cohort study of 733, 282 singletons born from 1997 to 2008, with follow-up throughout 2013. The children whose fathers used AEDs during the 3 months before conception were categorized as the exposed. Logistic regression model was used to examine association between paternal AEDs use before conception and the risk of congenital anomalies in offspring. Compared with unexposed children, the exposed had a 23% increased risk of congenital anomalies (odds ratios (OR) 1.23, 95% confidence interval [CI] 1.10–1.37) after adjusting for potential confounders. When extending the exposure window to 1 year before conception to the end of pregnancy, except for those using AEDs during 3 months before conception (the susceptible period of exposure), the increased risks were also observed in children whose fathers were former users (i.e., those using AEDs only from 1 year to 3 months before conception) (OR 1.29, 95%CI 1.03–1.61) and later users (i.e., those using AEDs only during pregnancy) (OR 1.35, 95%CI 1.12–1.65). This study suggested that the mildly increased risk of congenital anomalies in the offspring associated with paternal AEDs use before conception may be attributable to the underlying indications related to AEDs use.