JAMA Psychiatry

Z-drug exposure in first trimester not linked to congenital malformation risk

January 8, 2026

First trimester exposure to Z-drugs (eszopiclone, zaleplon, zolpidem) wasn’t linked to an overall rise in congenital malformation risk, and there wasn’t a consistent signal for organ-specific or other particular malformations examined, according to this cohort study.

This U.S. population-based cohort study (4.28 M pregnancies) used two databases to examine risks of malformations with first-trimester exposure to 1 or more dispensings of a Z-drug vs. no dispensing of these drugs. Researchers used propensity-score fine stratification weights to control for confounding factors.

First-trimester exposure was seen in 0.5% of pregnancies in one database and 0.6% of the other database; zolpidem was the Z-drug in 92% of exposed pregnancies. Adjusted pooled relative risk for malformations was 1.01 (95% confidence interval, 0.95-1.08). While certain rare, specific congenital malformations were elevated with exposure in one database, this wasn’t replicated in the other database, and researchers cited issues with imprecise estimations. Authors concluded that these data provide reassurance on Z-drug use for sleep dysregulation in pregnancy.

Source:

Fung K, et al. (2025, December 23). JAMA Psychiatry. Z-Drug Use in the First Trimester of Pregnancy and Risk of Congenital Malformations. https://pubmed.ncbi.nlm.nih.gov/41432941/