(263) Antiseizure medication use during pregnancy and the Risk of adverse neonatal birth outcomes in two Canadian provinces

Background: Antiseizure medication (ASM) exposure in-utero has been associated with an increased risk of adverse birth outcomes.

Objectives: We aimed to study the association between ASM use during pregnancy and the risk of adverse neonatal outcomes among all pregnant people, pregnant people with epilepsy (PPWE) and pregnant people without epilepsy (PPWOE)

Methods: We conducted a multisite population-based retrospective cohort study of pregnant people in Manitoba (1998-2021) and Saskatchewan (1995-2023). We examined the association between ASM exposure anytime during pregnancy and the following outcomes: risk of small for gestational age (SGA), low birth weight (LBW), preterm birth, NICU admissions, infants’ length of hospital stays (LOS) (>3days), infant mortality (≤27days), neonatal mortality (≤365days), persistent pulmonary hypertension (PPHTN), neonatal respiratory distress syndrome (NRDS), severe neonatal morbidity (SNM) and neonatal readmissions. This analysis was done among all pregnant people, PPWE and PPWOE. Multivariate regression models were adjusted for maternal age, pain, maternal comorbidities, urban/rural, socioeconomic status, multiple births, and teratogenic drugs exposure in the first trimester. Random effects models were used to meta-analyze the aggregated data from the two sites.

Results: We included a total of 545,121 pregnancies in our analysis, with 6,874 (1.26%) ASM exposed pregnancies. We observed a significant increase in the risk of SGA (adjusted odds ratio [aOR] 1.13, 95%CI 1.08-1.19), LBW (aOR 1.19, 95%CI 0.61-2.30), preterm birth (aOR 1.36, 95%CI 1.06-1.76), NICU admissions (aOR 1.30, 95%CI 1.08-1.57), LOS infant (aOR 1.18, 95%CI 1.05-1.31), infant mortality (aOR 1.21, 95%CI 1.02-1.44), neonatal mortality (aOR 1.23, 95%CI 1.07-1.43), and PPHTN (aOR 1.38, 95%CI 1.20-1.57). No significant association was observed with neonatal readmissions (aOR 1.10, 95%CI 0.94-1.29), SNM (aOR 1.08, 95%CI 0.81-1.44) and NRDS (aOR 1.06, 95%CI 0.79-1.43) when compared with unexposed pregnant people. Similar significant increased risks were observed among PPWOE. PPWE analysis was underpowered. The findings were consistent between the two sites.

Conclusions: ASM exposure in all pregnant people and PPWOE is associated with a significant increase in specific adverse birth outcomes. ASMs for non-epilepsy indications should be rationalized, especially when alternate treatments may be safer during pregnancy. Larger studies among PPWE are recommended to identify and separate the effect of ASMs from underlying epilepsy.