Neonatal effects of intrauterine metoprolol/bisoprolol exposure during the second and third trimester: a cohort study with two comparison groups

J Hypertens. 2020 Feb;38(2):354-361. doi: 10.1097/HJH.0000000000002256.

Abstract

Objectives: Our aim was to evaluate the effects of beta-blockers during the second and third trimester on fetal growth, length of gestation and postnatal symptoms in exposed infants.

Methods: The current prospective observational cohort study compares 294 neonates of hypertensive mothers on metoprolol or bisoprolol during the second and/or third trimester with 225 methyldopa-exposed infants and 588 infants of nonhypertensive mothers. The risks for reduced birth weight, prematurity, neonatal bradycardia, hypoglycaemia and respiratory disorders were analysed.

Results: The rate of small-for-gestational-age children was significantly higher in long-term beta-blocker exposed infants (24.1%) compared with the methyldopa cohort [10.2%, odds ratio (OR)adj 2.5, 95% confidence interval (CI) 1.2-5.2] and the nonhypertensive cohort (9.9%, ORadj 4.3, 95% CI 2.6-7.1). The risk for preterm birth was significantly increased compared with nonhypertensive pregnancies (ORadj 2.2, 95% CI 1.3-3.8) but not compared with the methyldopa cohort. Neonatal adverse outcomes occurred more frequently in the study cohort (11.5%) compared with the nonhypertensive comparison group (6.5%) and the methyldopa cohort (8.4%), but without statistical significance (ORadj 1.5, 95% CI 0.7-3.0 and ORadj 1.5, 95% CI 0.7-3.3, respectively).

Conclusion: Long-term intrauterine exposure to metoprolol or bisoprolol may increase the risk of being born small-for-gestational-age. It is still a matter of debate to which extent maternal hypertension contributes to the lower birth weight. Serious neonatal symptoms are rare. Altogether, metoprolol and bisoprolol are well tolerated treatment options, but a case-by-case decision on close neonatal monitoring is recommended.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / adverse effects
  • Adrenergic beta-Antagonists / pharmacology*
  • Adrenergic beta-Antagonists / therapeutic use
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / pharmacology*
  • Antihypertensive Agents / therapeutic use
  • Birth Weight / drug effects*
  • Bisoprolol / adverse effects
  • Bisoprolol / pharmacology*
  • Bisoprolol / therapeutic use
  • Cohort Studies
  • Female
  • Humans
  • Hypertension / drug therapy
  • Infant
  • Infant, Newborn
  • Infant, Small for Gestational Age
  • Male
  • Metoprolol / adverse effects
  • Metoprolol / pharmacology*
  • Metoprolol / therapeutic use
  • Pregnancy
  • Pregnancy Trimester, Second
  • Pregnancy Trimester, Third
  • Premature Birth / chemically induced*
  • Prenatal Exposure Delayed Effects*
  • Risk Factors

Substances

  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Metoprolol
  • Bisoprolol