Risk of congenital malformations in offspring of women using β-blockers during early pregnancy: An updated meta-analysis of observational studies

Abstract

Aims: Beta-blockers are commonly used to treat hypertension that arises during pregnancy. However, reproductive safety concerns have been expressed. Here, we investigated whether the use of β-blockers during early pregnancy increased the risk of congenital malformations. Methods: A systematic literature search was performed in PubMed, Embase and Cochrane Library to identify relevant studies published from database inception until February 2020. Observational studies evaluating associations between maternal β-blocker use and congenital malformations were included in this meta-analysis. Two reviewers independently extracted data and assessed study quality. Meta-analysis of outcomes was performed and a summary odds ratio (OR) was calculated with consideration of heterogeneity. Results: Twenty observational studies were identified. Beta-blocker use during early pregnancy was not associated with an increased risk of congenital malformations (OR = 1.01, 95% confidence interval [CI] = 0.93–1.09). Subgroup analysis of organ-specific malformations revealed that β-blocker use was associated with an increased risk of heart malformations (OR = 1.29, 95% CI = 1.02–1.63) and an increased risk of cleft lip or palate (OR = 1.5, 95% CI = 1.18–1.91); however, these associations (OR = 1.11, 95% CI = 0.94–1.32 for heart malformations; OR = 1.34, 95% CI = 0.98–1.85 for cleft lip or palate) disappeared when the adjusted data were pooled. Beta-blocker use was not associated with increased risks of central nervous system malformations, neural tube defects or hypospadias. Conclusion: Exposure to β-blockers during early pregnancy does not appear to be associated with congenital malformations or heart malformations in offspring. Other organ-specific congenital malformations should be evaluated in further studies.