Maternal beta-blocker dose and risk of small-for gestational-age in women with heart disease

Abstract

Introduction: Beta-blockers are prescribed for many pregnant women with heart disease, but whether there is a dose-dependent effect on fetal growth remains to be examined. We aimed to investigate if antenatal beta-blocker use and dose were associated with delivering a small-for-gestational-age infant among women with heart disease.

Material and methods: Our cohort included women with heart disease who delivered at Oslo University Hospital between 2006 and 2015. Maternal heart disease was classified into modified WHO risk scores. Women with beta-blocker treatment were dichotomized into whether they had been treated with a low or high dose based on clinical factors. We compared the risk of delivering a small-for-gestational-age infant in women exposed to high doses, low doses, or with no exposure to antenatal beta-blockers while adjusting for severity of maternal heart disease in logistic regression models.

Results: Of a total of 540 pregnancies among women with heart disease, 163 (30.2%) were exposed to beta-blocker treatment. The majority were treated with metoprolol (86.5%). Almost twice as many babies in the beta-blocker group were small-for-gestational-age, compared with the non-exposed group (19.8 vs 9.5%, P < 0.001). Women using a high-dose beta-blocker had a five-fold increased risk of delivering a small-for-gestational-age infant compared with non-exposure (adjusted odds ratio [aOR] 4.89, 95% confidence interval [CI] 2.22-10.78, P < 0.001). Women using a low dose of beta-blocker had a two-fold increased risk of delivering a small-for-gestational-age infant; however, the confidence interval included the null (aOR 1.75, 95% CI 0.83-3.72, P = 0.143). Results when restricting the analyses to metoprolol showed the same pattern, but with attenuation of risks.

Conclusions: We found a five-fold increased risk of delivering a small-for-gestational-age infant in women with heart disease treated with a high dose of beta-blocker, and a two-fold increased risk among those treated with a low dose, showing an apparent dose-response relation. Close monitoring of fetal growth is warranted among women with heart disease treated with beta-blockers. As drug therapy in pregnancy concerns both mother and fetus, an optimum balance for both should be the goal.

Keywords: beta-blocker; birthweight; heart disease; modified World Health Organization risk score; pregnancy; small-for-gestational-age; z score.

FIGURE 1

The z score among infants exposed and not exposed to maternal beta‐blocker use among 540 pregnancies in women with heart disease

FIGURE 2

Proportion of small‐for‐gestational‐age infants according to maternal antenatal beta‐blocker use among 540 pregnancies in women with heart disease. High dose includes ≥75 mg metoprolol, ≥200 mg labetalol, >100 mg atenolol, >50 mg carvedilol, >80 mg nadolol, or >80 mg sotalol. Low dose includes <75 mg metoprolol, <200 mg labetalol, ≤100 mg atenolol, ≤50 mg carvedilol, ≤80 mg nadolol, or ≤80 mg sotalol