Benzodiazepines in the first trimester were not linked to more malformations

Design

Population-based cohort study with propensity-score weighting

Population

More than 4.2 million US pregnancies; about 79,000 with first-trimester benzodiazepine fills

Primary outcome

Major congenital malformations

Effect

Pooled adjusted RR 0.99 (95% CI 0.96–1.03)

This US population-based cohort used two large insurance databases covering more than 4.2 million pregnancies. About 79,000 had at least one benzodiazepine prescription filled in the first trimester. Researchers compared major congenital malformations in exposed and unexposed pregnancies, weighting for confounders, and set a relative risk of 1.3 as the threshold for a clinically meaningful effect.

Adjusted malformation risk was 4.0% against 4.1% in the publicly insured group and 4.9% against 4.8% in the commercially insured group. The pooled relative risk was 0.99 (95% CI 0.96–1.03). Specific malformations previously linked to benzodiazepines were not consistently raised, there was no dose-response, and individual benzodiazepines gave similar results. Some analyses of co-exposure with other psychoactive drugs showed raised risks of particular malformations, without a consistent pattern.

For a woman who discovers she is pregnant while taking a benzodiazepine, this is reassurance on malformations. It is not a reason to start one in pregnancy, and it does not address neonatal withdrawal or sedation from use late in pregnancy, which remain real concerns. Abrupt stopping carries its own risks, including withdrawal seizures.

• Reassure women exposed in early pregnancy that malformation risk was not raised in this large cohort.
• Do not stop a benzodiazepine abruptly on discovering pregnancy; taper with a plan if stopping.
• Review the indication and use the lowest effective dose for the shortest time.
• Warn the paediatric team about use near delivery, because of neonatal sedation and withdrawal.
• Take extra care with combinations of psychoactive drugs, where signals were inconsistent.

Why it matters

Fear of malformations still drives abrupt benzodiazepine withdrawal and requests to end wanted pregnancies.

Don't overread it

This is observational and covers malformations at birth only — not late-pregnancy effects or longer-term development.

The statistics, in plain English

A relative risk of 0.99 with an interval of 0.96 to 1.03 means the data rule out more than about a 3% relative increase — far below the 30% the authors set as clinically important. In absolute terms, both groups had a 4–5% background malformation rate.

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