Effects of Maternal Epilepsy and Antiepileptic Drug Use during Pregnancy on Perinatal Health in Offspring: Nationwide, Retrospective Cohort Study in Finland

Introduction Perinatal health outcomes other than major congenital anomalies in offspring of women with epilepsy (WWE) have not been widely studied, and results of previous studies are conflicting and are mostly based on small numbers. Antiepileptic drugs (AEDs) pass through the placenta and may affect neonatal outcome. Methods This register-based study is based on information on all pregnancies ending in birth in Finland between 1996 and 2008. The data were obtained from the Finnish national health registers with data linkages based on the unique personal identification numbers. Information on maternal epilepsy diagnosis, AED purchases and other background factors was obtained to evaluate data on perinatal and infant health for all singleton births (n = 751,139). Drug purchases were considered to be an indicator for drug use. The outcomes included mode of delivery (vaginal birth or Caesarean section), preterm birth, low birth weight, weight for gestational age, low Apgar score, need for respiratory treatment, admission to neonatal care unit, perinatal death and infant death. Results In total, 4,867 (0.6 %) infants (including live births and stillbirths) were exposed to maternal epilepsy. More than half of the offspring of WWE were exposed to AED (n = 3,067, 63.0 %) during pregnancy or 1 month prior to and/or during pregnancy, and mostly in monotherapy (n = 2,566, 83.7 %). The most commonly used AED was carbamazepine (n = 1,292, 42.1 %; mostly in monotherapy 83.9 %). WWE were more likely to smoke and to have previous miscarriages, lower socioeconomic status, and more co-morbidity than the reference women with no epilepsy diagnosis and no AED use (WOE). A slightly increased risk for most of the perinatal health outcomes was found in offspring of WWE in relation to offspring of WOE (adjusted odds ratio [aOR] 1.19, 95 % CI 1.04-1.36 for low 5-min Apgar score to aOR 2.10, 95 % CI 1.57-2.81 for needing respiratory care). The risks increased by the number of different maternal AEDs used. In relation to offspring of WWE with no AED exposure (n = 1,800), a slightly increased risk for treatment in a neonatal care unit (aOR 1.48, 95 % CI 1.21-1.82) was observed for offspring of WWE on AED therapy. Conclusions Offspring of WWE have a slightly increased risk for adverse pregnancy-related and perinatal health outcomes when compared with WOE, and AED exposure further increases the risk. The results should be interpreted with caution, as information on type of epilepsy was unavailable.