(273) Gabapentin in Pregnancy and Birth Outcomes: a Population-based Prevalence Study in Nordic Countries (EUPAS38620)

Background: Gabapentin is an antiepileptic drug (AED) indicated for partial seizures in adults and children and for peripheral neuropathic pain. This was a regulator-mandated study to investigate safety of gabapentin in pregnancy.

Objectives: We aimed to describe the use of gabapentin in pregnancy and to estimate the risk of adverse birth and neonatal outcomes compared with no use and with several active comparators.

Methods: This was a population-based prevalence study based on routinely collected data from Denmark, Finland, Norway, and Sweden. The study included pregnancies ending in 2005-2018 as live births, stillbirths or in a termination of pregnancy for fetal anomaly (TOPFA, except Sweden). Gabapentin exposure originated from outpatient dispensings, and diagnoses, from secondary care encounters. We estimated contrasts for gabapentin vs. no AED, vs. pregabalin, vs lamotrigine, and vs either. Primary outcomes were major congenital malformations (MCM), stillbirth, low birth weight (LBW), small for gestational age (SGA), low 5-minute Apgar score, and microcephaly. Prevalence, crude and propensity-score adjusted prevalence ratios (aPRs) and incidence rate ratios, as appropriate, were estimated for each outcome and contrast. For MCMs, first-trimester exposure was considered. We used fixed-effects meta-analysis or Mantel-Haenszel pooling to combine the country-specific estimates.

Results: There were 3,435,599 live births, stillbirths, and TOPFA, including 2008 (0.6%) gabapentin-exposed. The pooled aPR for any MCM was 0.99 (95 % CI: 0.80-1.23) for gabapentin vs no AED. The malformation-specific aPRs were 2.30 (0.83-6.36) (nervous system), 1.12 (0.80-1.58) (congenital heart defects), 3.99 (0.51-31.41) (respiratory), 1.15 (0.47-2.79) (digestive system), 10.52 (2.45-45.17) (abdominal wall). The aPRs were 1.24 (0.66-2.34) for stillbirth, 1.21 (1.02-1.44) for LBW, 1.16 (1.00-1.35) for preterm birth, and 1.10 (0.83-1.46) for SGA, 1.09 (0.80-1.48) for low 5-minute Apgar score, and 0.88 (0.62-1.23) for microcephaly. Several estimates attenuated when using active comparators or MH pooling.

Conclusions: In this post-authorisation safety study based on routinely collected secondary population-based data from four Nordic countries, prenatal exposure to gabapentin was not associated with an increased risk of most adverse birth outcomes. Despite large population size, most outcomes were rare and based on few events even after pooling. The non-null associations may be partially due to residual confounding, although could not be ruled out.