The use of pregabalin in early pregnancy and major congenital malformations: A systematic review and meta-analysis.

Pregabalin is an antiseizure medication indicated for a wide range of medical conditions other than epilepsy, such as neuropathic pain and generalized anxiety disorder. Preclinical observations have suggested reproductive toxicity for this agent, with skeletal malformations and growth retardation. Human data is sparse and studies lead to contradictory results. Our objective was to conduct a systematic review and meta-analysis on the risk of major congenital malformations (MCMs) associated with pregabalin use in monotherapy during the first trimester of pregnancy. References were identified through a snowballing approach until 2015 and through electronic databases (MEDLINE and Embase) from 2015 to June 30, 2024. All comparative studies including pregnant women exposed to pregabalin monotherapy during the first trimester of pregnancy were included. Two reviewers independently screened citations for eligibility and extracted data using a proprietary collaborative Web-based meta-analysis platform (metaPreg.org). The risk of MCMs between pregabalin exposed and non-exposed pregnancies, and its 95 % confidence interval were estimated using a random effects model. Seven studies, retrospective and prospective cohorts, included data from 3,336,224 pregnant women. Among them, 701 were exposed to pregabalin monotherapy during the first trimester of pregnancy. There was no significant association between the risk of MCMs and first trimester exposure to pregabalin monotherapy (pooled OR 1.79, 95 %CI [0.80; 3.99]). Some between-study heterogeneity was observed (I2 = 51 %;). No significant association between pregabalin monotherapy and the risk of MCMs was found. This result should be interpreted with caution given the small number of studies included and their critical risk of bias.