The risk of congenital malformations associated with exposure to β-blockers early in pregnancy: a meta-analysis

β-blockers are commonly used during the first trimester of pregnancy. Data about risks of congenital anomalies in offspring have not been summarized. We performed a meta-analysis to determine teratogenicity of β-blockers in early pregnancy. A systematic literature search was performed using PubMed, EMBASE, Cochrane Clinical Trials, and hand search. Meta-analyses were performed using random-effects models based on odds ratios (ORs). Prespecified subgroup analyses were performed to explore heterogeneity. Randomized controlled trials or observational studies examining risks of congenital malformations associated with first trimester β-blocker exposure compared with no exposure were included. Thirteen population-based case-control or cohort studies were identified. Based on meta-analyses, first-trimester oral β-blocker use showed no increased odds of all or major congenital anomalies (OR=1.00; 95% confidence interval, 0.91-1.10; 5 studies). However, in analyses examining organ-specific malformations, increased odds of cardiovascular defects (OR=2.01; 95% confidence interval, 1.18-3.42; 4 studies), cleft lip/palate (OR=3.11; 95% confidence interval, 1.79-5.43; 2 studies), and neural tube defects (OR=3.56; 95% confidence interval, 1.19-10.67; 2 studies) were observed. The effects on severe hypospadias were nonsignificant (1 study). Causality is difficult to interpret given the small number of heterogeneous studies and possibility of biases. Given the frequency of this exposure in pregnancy, further research is needed.