Maternal exposure to lamotrigine and the risk of orofacial clefts in offspring: A systematic review and meta-analysis.

Lamotrigine is used to treat epilepsy, migraine, and psychiatric disorders during pregnancy. However, concerns remain regarding whether lamotrigine exposure increases the risk of orofacial clefts (OFCs) in offspring. A systematic literature search was conducted to identify relevant studies published from inception to February 2025. Random-effects models were used to estimate the overall relative risk. Eight observational studies were included in the analysis. The overall results indicated that maternal lamotrigine exposure during pregnancy was associated with a significantly increased risk of OFCs in offspring (odds ratio [OR] = 1.42, 95 % confidence interval [CI] = 1.05-1.92, P < 0.001, I2 = 39.8 %). However, this association disappeared when data were pooled from cohort studies (OR = 1.4, 95 % CI = 0.67-2.9, P = 0.37) or from studies adjusting for at least five variables (OR = 0.97, 95 % CI = 0.63-1.48, P = 0.871, I2 = 0.0 %). Our findings suggest that in utero exposure to lamotrigine does not increase the risk of OFCs in offspring.