β-Blockers in Early Pregnancy Not Linked to Significant Risk for Overall, Cardiac Malformations
A limitation of the study was inclusion of live births only.
Women with hypertension who used β-blockers in their first trimester of pregnancy did not experience a greatly increased risk for overall or cardiac malformations in their offspring, according to a study published in Annals of Internal Medicine.1
A group of investigators conducted an international cohort study to determine the association between maternal β-blocker use and the risk for major congenital malformations in early pregnancy. Data were obtained from health registries in Denmark, Finland, Iceland, Norway, and Sweden, as well as from the Medicaid database in the United States.
Main outcomes measured were any major congenital malformations, cardiac malformations, cleft lip or palate, and central nervous system malformations.
Of the pregnant women with hypertension in the Nordic cohort (n = 3577) and the US cohort (n = 14,900), a total of 682 (19.1%) and 1668 (11.2%), respectively, were exposed to β-blockers in the first trimester.
For any major malformation, the pooled adjusted relative risk (RR) linked to β-blocker use was 1.07; for any cardiac malformation and cleft lip or palate, the pooled adjusted RRs were 1.12 and 1.97, respectively.
The risk difference/100 persons exposed (RD1000) associated with β-blocker use was 3.0, 2.1, and 1.0 for any major malformation, any cardiac malformation, and cleft lip or palate, respectively.
Some limitations to the study were that β-blocker exposures were based on filled prescriptions (not consumption), only live births were included in the analysis, and imprecise estimations of risk for cleft lip or palate and neural tube defects.
“Future, well-controlled studies done in similarly large cohorts will be needed to further refine these risk estimates,” the researchers added.
“[T]he point estimates from our analysis suggest a more modest increase in the RR for these malformations than earlier publications have reported,” the authors wrote. “The potential risks to the fetus must be balanced against the risks to the mother associated with untreated hypertension.”
In a separate editorial, Joel G. Ray, MD, MSc, of St. Michael's Hospital at the University of Toronto, notes that maternal use of oral β-blockers in the first trimester may not increase the risk for congenital malformations but that the reason for the prescription of a β-antagonist may increase risk.2
Compared with women without hypertension, women with hypertension more frequently have a higher body mass index, are older, and have prepregnancy diabetes mellitus, all of which are risk factors for birth defects. He notes that both treated and untreated hypertension are linked to slightly elevated odds of fetal cardiac malformation. In addition, he notes that “fetal well-being depends on maternal well-being, and untreated maternal disease both jeopardizes the health of a fetus and may shorten pregnancy.”
“Accordingly, β-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,” Dr Ray concluded.
Disclosure: Some of the authors from this study have received grants for this and other studies from Lilly, GlaxoSmithKline, Baxalta, Pacira, and Pfizer.
- Bateman BT, Heide-Jørgensen U, Einarsdóttir K, et al. β-Blocker use in pregnancy and the risk for congenital malformations: an international cohort study [published online October 16, 2018]. Ann Intern Med. doi: 10.7326/M18-0338
- Ray JG. To β or not to β? Very likely OK to β [published online October 16, 2016]. Ann Intern Med. doi: 10.7326/M18-2500