Neonatal outcomes after gamma-aminobutyric acid analog use during pregnancy: a meta-analysis of cohort studies

Eur J Clin Pharmacol. 2022 Nov;78(11):1739-1747. doi: 10.1007/s00228-022-03384-1. Epub 2022 Sep 10.

Abstract

Background: Gamma-aminobutyric acid (GABA) analogs are being used by an increasing number of reproductive-age women. However, there is concern regarding the teratogenic potential of GABA analogs.

Methods: We performed this systematic review and meta-analysis to assess the relationship between GABA analog exposure and risk of adverse neonatal outcomes.

Results: Eight cohort studies were included in the meta-analysis. Exposure to a GABA analog during pregnancy was not associated with an increased risk of congenital malformation (odds ratio [OR] 1.19, 95% confidence interval [CI] 0.96-1.46, P = 0.106) or a small for gestational age (SGA) infant (OR 1.99, 95% CI 0.78-5.1, P = 0.152) compared to no exposure. However, exposure to a GABA analog was associated with an increased risk of preterm birth (PB) (OR 1.56, 95% CI 1.04-2.35, P = 0.033), spontaneous abortion (SA) (OR 1.64, 95% CI 1.14-2.38, P = 0.008), or termination of pregnancy (TOP) (OR 3.02, 95% CI 2-4.56, P < 0.001).

Conclusion: Exposure to GABA analogs during pregnancy does not appear to be associated with congenital malformation, although there was some evidence of a higher risk of several other negative neonatal outcomes. Given the few studies included, larger prospective studies controlling for important confounders are needed to verify our findings.

Keywords: Antiepileptic; Maternal; Meta-analysis; Prenatal.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Cohort Studies
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Pregnancy
  • Pregnancy Outcome
  • Premature Birth* / chemically induced
  • Premature Birth* / epidemiology
  • Prospective Studies
  • gamma-Aminobutyric Acid / adverse effects

Substances

  • gamma-Aminobutyric Acid