Does early pregnancy exposure to macrolide antibiotics lead to major birth defects? A systematic review and meta-analysis

Background: Macrolide antibiotics are frequently used to treat infections in women during early pregnancy. However, the association between early pregnancy exposure to macrolide antibiotics and major birth defects remains uncertain. Clarifying this risk is crucial for public health and clinical decision-making. Methods: This study systematically searched five databases-Web of Science, PubMed, Embase, Cochrane, and Scopus-for studies exploring the relationship between early pregnancy exposure to macrolide antibiotics and major birth defects. Two independent researchers conducted the literature screening, data extraction, and bias risk assessment. Meta-analysis was performed using the metan command in STATA 16 to pool the data. Results: Nine studies were included, selected from 6,002 articles, comprising seven cohort studies and two case-control studies. These studies covered 40,218 patients exposed to macrolide antibiotics in early pregnancy. Due to low heterogeneity among studies, a fixed-effects model was used for the meta-analysis. The results showed no significant association between early pregnancy exposure to macrolide antibiotics and the risk of major birth defects (OR = 1.05, 95% CI [0.97, 1.13]). Subgroup analysis of 11 types of major birth defects also found no such association, particularly for birth defects of the heart (OR = 1.09, 95% CI [0.96, 1.23]). Low heterogeneity and reduced risk of bias further enhanced the reliability of the findings. Conclusion: Existing evidence suggests that early pregnancy use of macrolide antibiotics does not increase the risk of major birth defects. In clinical practice, healthcare providers and pregnant women can use these antibiotics cautiously based on the specific infection situation.