(301) Prenatal Exposure to Gabapentin and the Risk of Autism Spectrum Disorder in Children

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by challenges in social interaction, communication, and repetitive behaviors. Gabapentin, commonly used off-label for treating neuropathic pain, has seen an increased usage among pregnant people in recent years. The association between gabapentin exposure during pregnancy and ASD is not known.

Objectives: To assess the risk of ASD in children following prenatal exposure to gabapentin.

Methods: We conducted a retrospective population-based cohort study using data from the Manitoba Centre for Health Policy, which included data from pregnancies in Manitoba from January 1, 1998, to March 31, 2021. We included all live singleton births during this period, excluding multiple births and stillbirths. The primary exposure time window of interest for ASD was the second and/or third trimester. A secondary analysis included exposure at any time during pregnancy. The comparison group included pregnancies not exposed to gabapentin. We identified all children with a diagnosis of ASD between birth and the end of follow-up. ASD was defined as having at least one physician visit with ASD code or hospitalization with an ASD code. We assessed the distributions of sociodemographic and clinical characteristics. Using multivariate Cox regression, we reported crude and adjusted hazard ratios (aHRs) and 95% CIs.

Results: The study included 289,794 children, with 51.3% being male. The cohort included 1,029 exposed and 288,765 unexposed children. The mean maternal age was 30 for gabapentin users compared to 28 for non-users. Among the exposed group, 383 (37.2%) were exposed during the second and/or third trimester, and 646 (62.8%) exposed at any time during pregnancy. Out of those exposed, 14 children (2.2%) during the second and/or third trimester and 27 children (2.6%) at any time during pregnancy were diagnosed with ASD. Males with ASD outnumbered females by a ratio of approximately 2:1. The mean age of children at the time of diagnosis was 3.5 years. The aHRs for ASD after gabapentin exposure during the second and/or trimester and at any time were 1.56 (95% CI, 0.92-2.64) and 1.68 (95% CI, 1.14-2.46) respectively.

Conclusions: No significant association was found during the second and/or third trimester. However, exposure to gabapentin at any time during pregnancy was associated with an increased risk of ASD. Further research on gabapentin safety using large longitudinal databases is warranted.