Z-drug exposure during early pregnancy not a risk factor for congenital malformations

The use of nonbenzodiazepine sedative hypnotics (Z-drugs) for sleep dysregulation during the first trimester of pregnancy does not appear to contribute to a meaningful increase in the risk of congenital malformations overall, as shown in a study.

Researchers used evaluated healthcare utilization data in the US from publicly insured beneficiaries in the Medicaid database and commercially insured beneficiaries in the Merative MarketScan database. They identified a total of 4,281,579 pregnancies (mean maternal age at delivery 25.2 years in Medicaid and 31.6 years in MarketScan).

A total of 11,652 (0.5 percent) pregnancies in Medicaid and 10,862 (0.6 percent) pregnancies in MarketScan were exposed to Z-drugs (zaleplon, eszopiclone, or zolpidem) in the first trimester of pregnancy. The vast majority (92.1 percent) of exposed pregnancies had zolpidem exposure.

The primary outcome of major congenital malformations was ascertained using linked maternal and infant claims. Pooled data showed that the risk of malformations overall did not significantly differ between the exposed group and the unexposed group (adjusted relative risk [aRR], 1.01, 95 percent confidence interval [CI], 0.95–1.08).

Notably, the exposed group had a higher risk of abdominal wall defects (aRR, 1.46, 95 percent CI, 0.89–2.38), tetralogy of Fallot (aRR, 1.45, 95 percent CI, 0.86–2.46), and neural tube defects (aRR, 1.62, 95 percent CI, 0.96–2.74) compared with the unexposed group. However, these associations were imprecisely estimated, driven by the Medicaid cohort and not replicated in the MarketScan cohort.

Multiple sensitivity analyses yielded consistent results.