Beta-blockers are often used during pregnancy to treat cardiovascular diseases. The described neonatal side effects of maternal beta-blocker use are hypoglycemia and bradycardia, but the evidence base for these is yet to be evaluated comprehensively. Hence, this systematic review and meta-analysis was performed to evaluate the potential increased risk for hypoglycemia and bradycardia in neonates exposed to beta-blockers in utero or during lactation. A systematic search of English-language human studies was conducted until 21 April 2021. Both observational studies and randomized controlled trials investigating hypoglycemia and/or bradycardia in neonates following beta-blocker exposure during pregnancy and lactation were included. All articles were screened by two authors independently and eligible studies were included. Pair-wise and proportion-based meta-analysis was conducted and the certainty of evidence (CoE) was performed by standard methodologies. Of the 1.043 screened articles, 55 were included in this systematic review. Our meta-analysis showed a probable risk of hypoglycemia (CoE—Moderate) and possible risk of bradycardia (CoE—Low) in neonates upon fetal beta-blocker exposure. Therefore, we suggest the monitoring of glucose levels in exposed neonates until 24 h after birth. Due to the limited clinical implication, monitoring of the heart rate could be considered for 24 h. We call for future studies to substantiate our findings.

IntroductionBeta-blockers are often used during pregnancy to treat diseases such as pre-existing hypertension, arrhythmias or pregnancy-related hypertension. Since beta-blockers are able to cross the placenta and can pass into breast milk, they could potentially harm the neonate. Known potential neonatal side effects of maternal beta-blocker use are hypoglycaemia and bradycardia. This systematic review and meta-analysis aims to investigate the risk for neonatal hypoglycaemia and bradycardia after exposure to beta-blockers in utero or through lactation.Methods and analysisWe will conduct a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic electronic search will be conducted using EMBASE, Medline, Cochrane Central Register of Trials and Web of Science from initiation to April 2021. Our primary outcome will be the risk for hypoglycaemia or bradycardia in neonates exposed to beta-blockers in utero or through lactation in comparison with unexposed neonates. All articles will be screened by title and abstract twice by different independent review authors. Next, standardised methodological quality assessment will be conducted for each included article and finally a meta-analysis will be performed.Ethics and disseminationEthical approval is not required. The results of this study will help to assess the need for postnatal glucose and heart rate monitoring of the neonate after maternal beta-blocker exposure. Our findings will be communicated to the target audience through peer-reviewed publication.PROSPERO registration numberCRD42021264269.