Beta-blocker Use in Pregnancy Doesn’t Up Birth Defect Risk, Study Suggests

Beta-blockers used to treat hypertension during the first trimester of pregnancy don’t appear to increase the risk that babies will be born with birth defects or cardiac malformations, according to an analysis of observational data on more than 18,000 women across five Nordic countries and the United States.

“Chronic hypertension is increasingly prevalent in pregnancy, likely because of the higher prevalence of obesity in women of reproductive age and increasing maternal age at the time of pregnancy. Thus, antihypertensive medication exposure has become common in early pregnancy,” lead author Brian T. Bateman, MD (Brigham and Women's Hospital and Harvard Medical School, Boston, MA), and colleagues write in their paper, which was published online today in the Annals of Internal Medicine.

“Beta-blockers are one of the most frequently used classes of antihypertensive medication in pregnancy,” they point out, noting that up to 1% of US pregnancies, for example, involve first-trimester exposure to the drugs.

Whether there is any link between beta-blocker use and subsequent birth defects is “controversial,” Bateman et al say. Animal models have hinted that the medications can harm fetal development, and a recent meta-analysis of “pregnant women did not find increased risk for congenital malformations overall but did report significantly increased risks for cardiac defects, cleft lip or palate, and neural tube defects,” the investigators write.

Indeed, there have been concerns, “because of some prior conflicting reports,” said Athena Poppas, MD (Rhode Island Hospital, Providence), who was not involved in the study.

“The overarching point that we try to make with patients, and to educate other clinicians, is we need a healthy mother to have a healthy baby. One of the problems we see sometimes is people undertreat pregnant women for fear that something will happen to the baby,” she told TCTMD. Pharmacists may also incorrectly tell pregnant patients that certain drugs are risky and dissuade them from taking something that’s been prescribed, Poppas commented, so it’s important that people understand the actual level of risk involved.

The new results “are very reassuring. . . . There’s really minimal to no increased risk,” she said, adding, “Physicians should feel confident in prescribing [beta-blockers].”

For their study, Bateman and colleagues analyzed registry data from Denmark, Finland, Iceland, Norway, Sweden, and the United States, looking at women with hypertension who were exposed to beta-blockers during the first trimester and whose pregnancies resulted in live births. In the Nordic cohort, 19.1% of the 3,577 women had filled prescriptions for beta-blockers. In the US cohort, 11.2% of the 14,900 women had done so. Women who received beta-blockers tended to be older, more likely to have previously given birth, and more apt to be taking medication for diabetes.

After adjustment for a range of possible confounders, there was no significant increase in the risk that babies would be born with malformations if their mothers had been on beta-blockers.

Risk Associated With First-Trimester Exposure to Beta-blockers

^aBased on US data only

These results exclude the possibility of a large increase in birth defects associated with beta-blocker use, the researchers conclude, adding, “The potential risks to the fetus must be balanced against the risks to the mother associated with untreated hypertension.”

Writing in an accompanying editorial, Joel G. Ray, MD (St. Michael's Hospital, University of Toronto, Canada), agrees.

“Whatever might confound the relation between the use of a specific medication in pregnancy and an adverse perinatal outcome, maternal health remains the priority of any clinician or parent. 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,” he advises. “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.”

The seeming uptick in risk among women taking beta-blockers that has been observed previously might be due to confounding, Ray points out, in that hypertension itself may be responsible for birth defects.

Clinicians should be mindful of two things when treating this population, he suggests. First, beta-blockers increase the risk of intrauterine fetal growth restriction, so ultrasound should be used to assess development starting in the early third trimester. Also, pregnant women with hypertension, diabetes, and obesity are at added risk of preeclampsia so should take 81 to 162 mg of aspirin daily, Ray says.

Poppas, too, noted that it can be hard to gauge what risk is carried by medications when other things are shifting. For example, women are having children at older ages and obesity and diabetes are on the rise, leading to an increase in hypertension. “We know all of those things actually increase the risk for complications of pregnancy. That’s always been one of the challenges is teasing out: is it the disease that increases the risk, particularly in an epidemiologic study, or is it the treatment that may have increased the risk?”

The large size of the current data set and other strengths of the included registries help ease some of that uncertainty, Poppas said. “They have these great, rich databases that are prospective, so I think it’s probably one of the best studies done in this area.”