BACKGROUND: Existing data on malformations associated with benzodiazepine use in pregnancy are conflicting.
OBJECTIVE: To assess the risk for major congenital malformations from first-trimester exposure to benzodiazepines.
DESIGN: Population-based U.S. cohort study.
SETTING: Medicaid (2000-2018) and Merative MarketScan (2003-2020) databases.
PARTICIPANTS: Pregnant persons enrolled from 90 days before pregnancy to 30 days after delivery, and their live-born infants enrolled for 90 days after birth.
MEASUREMENTS: Exposure was defined as at least 1 fill of a benzodiazepine in the first trimester. Primary outcomes were any major congenital malformation and organ-specific malformations previously associated with benzodiazepine exposure. The investigators estimated relative risks (RRs) comparing exposed versus unexposed pregnancies with propensity score fine stratification weights to control for confounders. An RR of 1.3 or higher was prespecified as clinically significant.
RESULTS: In total, 51 339 of 2 478 434 (2.1%) publicly insured and 27 779 of 1 750 721 (1.6%) commercially insured pregnancies had benzodiazepine exposure. The adjusted absolute risks for any malformation in exposed versus unexposed pregnancies were 4.0% versus 4.1% for Medicaid and 4.9% versus 4.8% for MarketScan. The pooled adjusted RR was 0.99 (95% CI, 0.96 to 1.03). Associations with organ-specific malformations were not consistently observed in sensitivity analyses, nor was a dose-response relationship observed. Analyses of different benzodiazepines yielded similar results. The risk for selected organ-specific malformations was increased in some analyses of coexposure to benzodiazepines and other psychoactive medications, but a consistent pattern did not emerge.
LIMITATIONS: Potential nondifferential exposure and outcome misclassification; analyses restricted to malformations prevalent at birth.
CONCLUSION: No substantial increase in the risk for malformations was consistently identified across data sources. Findings from coexposure analyses were inconsistent and warrant further study.
PRIMARY FUNDING SOURCE: National Institute of Child Health and Human Development.
| Discipline Area | Score |
|---|---|
| FM/GP/Mental Health |  |
| General Internal Medicine-Primary Care(US) | |
| Family Medicine (FM)/General Practice (GP) | |
| Obstetrics | |
| Psychiatry | |
This is a useful study for those who are faced with this clinical scenario that often occurs in difficult circumstances.
As a family physician involved in prenatal care, I found this article helpful in counselling patients who have used BZD in the first trimester and are very anxious about malformations. This study should provide reassurance to those patients, although I will not change my reluctance to prescribe BZD to pregnant patients as there are generally better alternatives.
This was a large observational cohort study investigating the use of benzodiazepines during the first trimester of pregnancy. The study did not demonstrate a substantial increase in the risk of congenital malformations among pregnancies exposed to benzodiazepines compared with unexposed pregnancies. However, several important limitations should be considered when interpreting the findings. These included the potential for non-differential misclassification of both drug exposure and outcomes. Furthermore, the analyses did not account for malformations associated with early pregnancy losses. Consequently, the findings may not fully reflect the risk of congenital malformations across all conceptions.
This extensive cohort analysis shows that exposure to benzodiazepines during the first trimester is not linked to a higher overall incidence of significant congenital defects. Counseling following early prenatal exposure can benefit from the findings.
This data provides convincing evidence to support what most psychiatrists already know: benzodiazepines are generally safe to use in pregnancy, when clinically indicated. While it is likely already known to most providers, this large sample size of a heterogeneous population provides clear and convincing evidence that would likely increase providers' comfort with using these medications early in pregnancy, if necessary. This is an important set of findings for psychiatrists to be aware of.
It would be nice to rename the article. At first glance of just the title, the assumption is that there is increased risk.
