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

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.