Maternal use of beta-blockers has no risk of cardiac birth defects

Maternal use of β-blockers in the first trimester is not associated with increased risk for cardiac or other major birth defects, according to a new study published in the Annals of Internal Medicine.

Brian T. Bateman, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, and colleagues conducted the analysis of two large cohorts to estimate the risks for major congenital malformations associated with first-trimester exposure to β-blockers.

The research team evaluated 3,577 women in a Nordic cohort with hypertensive pregnancies, of whom 19.1% were exposed to beta-blockers in the first trimester. The group consisted of women from Denmark, Finland, Iceland, Norway, and Sweden who had a pregnancy with a single, live-born infant.

The study also looked at the U.S. MAX database of all hypertensive pregnant women aged 12 to 55 years continuously receiving Medicaid from the 3 months prior to their last menstrual cycle to 1 month after delivery. Of the 14,900 women in this group, 11.2% were exposed to beta-blockers in the first trimester.

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Key Findings:

• The excess risks with exposure to β-blockers were not significant for major congenital malformations (adjusted RR 1.07, 95% CI 0.89-1.30) or cardiac malformations (aRR 1.12, 95% CI 0.83-1.51).


• The absolute excess risks per 1,000 persons exposed were 3.0 (95% CI -6.6 to 12.6) and 2.1 (95% CI -4.3 to 8.4), respectively, which at the very least excluded a large increase.


• For cleft lip or palate, the pooled adjusted relative risk linked with beta-blockers was 1.97 (95% CI 0.74-5.25), and the risk difference per 1,000 persons (RD₁₀₀₀) exposed was 1.0 (95% CI -0.9 to 3.0).


• For central nervous system malformations, the aRR was 1.37 (95% CI 0.58-3.25) and the RD₁₀₀₀ was 1.0 (95% CI -2.0 to 4.0).

"In the setting of small numbers of outcomes, our study cannot exclude an increase in the relative risk (RR) for the less common malformation types, cleft lip or palate, and CNS malformations," the authors cautioned. "However, the point estimates from our analysis suggest a more modest increase in the RR for these malformations than earlier publications have reported."

Those prior studies had significant limitations like bias and confounding by the mother's hypertension, Bateman and co-authors emphasized. The present study restricted the assessment to pregnancies with a diagnosis of hypertension in order to lessen potential confounding by indication.

"The potential risks to the fetus must be balanced against the risks to the mother associated with untreated hypertension," they concluded.

Maternal health is a priority for clinicians and parents, Joel Ray, University of Toronto, agreed in an accompanying editorial. "Moreover, fetal well-being depends on maternal well-being, and untreated maternal disease both jeopardizes the health of a fetus and may shorten a pregnancy," the editorialist wrote.

"Accordingly, beta-blockers should be used in pregnancy when indicated for the treatment of various maternal medical conditions, and labetalol should be a first-line treatment choice for chronic hypertension," Ray continued.

Another one of the study's limitations was that the U.S. population assessed was not representative of the entire obstetric population, he added.

"Future studies should examine the risk associated with individual beta-blockers and how it may vary with dose," the investigators said.