Prenatal Exposure to Macrolides and Risk of Congenital Malformations: A Meta-Analysis

Abstract

Introduction: Macrolides are widely used during pregnancy; however, their fetal safety remains uncertain. We performed a meta-analysis to assess the relation between prenatal exposure to macrolides and occurrence of congenital malformations. Methods: We searched MEDLINE, EMBASE and other databases until June 12th, 2019. We assessed the quality of the studies and checked for heterogeneity and publication bias. We performed 3 different analyses and compared the effect of macrolides to each of the following unexposed populations: Group 1: babies unexposed to any medicine before birth, Group 2: babies exposed to non-macrolides antibiotics/non-teratogens, and Group 3: mixed population of the first and second comparators. Results: A weak association between macrolides and congenital malformation of any type was observed when macrolides were compared to the mixed population [ORgroup 3: 1.06 (95%CI 1.01, 1.10)]. Subgroup analysis showed that this weak association is restricted to fetus exposure in the first trimester of pregnancy [OR: 1.06 (95%CI: 1.01, 1.11)] and to cohort studies [OR: 1.07 (95%CI: 1.02, 1.13). Digestive system malformations were found to be slightly associated with prenatal exposure to macrolides [ORgroup 3: 1.14 (95%CI: 1.02, 1.26)]. Musculoskeletal system was also found to be potentially affected [ORgroup 2: 1.21 (95%CI: 1.08, 1.35) and ORgroup 3: 1.15 (95%CI: 1.05, 1.26)]. European studies showed a slightly stronger association than American studies in these two comparisons. Conclusions: Our study suggests a weak association of macrolides’ prenatal use and congenital malformations, limited to exposure in early pregnancy, and musculoskeletal and digestive systems. In addition to studies with a larger control of confounding, risk-benefit research is needed to determine the usefulness of macrolides during pregnancy.