Prenatal Exposure to Macrolides and Risk of Congenital Malformations: A Meta-Analysis
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.
We searched MEDLINE, EMBASE, and other databases until June 12, 2019. We assessed the quality of the studies and checked for heterogeneity and publication bias. We performed three different analyses and compared the effect of macrolides with each of the following unexposed populations: Group 1: babies unexposed to any medicine before birth, Group 2: babies exposed to non-macrolide antibiotics/non-teratogens, and Group 3: mixed population of the first and second comparators.
A weak association between macrolides and congenital malformation of any type was observed when macrolides were compared with 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]). The 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.
Our study suggests a weak association between prenatal use of macrolides 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.
Conception and design of the study: BT and ME; Conceptualization of the manuscript and review and synthesis of the literature: NM; Data extraction: NM and HT; Coordination and supervision of data extraction and analysis: BT and AF; All authors made substantial contribution to the interpretation of data, critically reviewed the manuscript, and approved its submission for publication.
Compliance with Ethical Standards
No specific funding for this work. Dr. Takkouche’s and Dr. Figueiras’ work is funded by a Grant from the Regional Ministry of Education, Universities and Vocational Training, Santiago de Compostela, Spain, ED431C 2018/20.
Conflict of interest
Narmeen Mallah, Hamid Reza Tohidinik, Mahyar Etminan, Adolfo Figueiras, and Bahi Takkouche declare that they have no conflict of interest.
All data generated or analyzed during this study are included in this published article and its Supplementary Information File (Online Resource 1, see ESM).
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