Association between macrolide exposure in early pregnancy and major congenital malformations: a large French population-based study during 2010-20 period

Monday, August 26, 2024

2:00 PM – 2:15 PM CEST

Location: Room XV

Presenting Author(s)

Anh Tran, BPharm, MSc (she/her/hers)

PhD Candidate
EPI-PHARE, France

Slides

Co-Author(s)

MZ

Mahmoud Zureik, Phamacoepidemiology professor

Phamacoepidemiology professor
EPI-PHARE, French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM), 143-147 Boulevard Anatole France, 93285, Saint-Denis, France
Saint-Denis, France
JS

Jeanne SIBIUDE

IAME, INSERM, France
Sara Miranda, PharmD

Epidemiologist
EPI-PHARE (ANSM/CNAM), France
JD

Jérôme Drouin

EPI-PHARE, French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM), 143-147 Boulevard Anatole France, 93285, Saint-Denis, France, France
LM

Lise Marty, PhD

Biostatistician
EPI-PHARE (ANSM/CNAM), France
Alain Weill, MD

deputy director
EPI-PHARE, French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM), 143-147 Boulevard Anatole France, 93285, Saint-Denis, France, France
RD

Rosemary Dray-Spira

EPI-PHARE, French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM), 143-147 Boulevard Anatole France, 93285, Saint-Denis, France, France
XD

Xavier Duval

IAME, INSERM, France
ST

Sarah Tubiana

IAME, INSERM, France

Background: While macrolides are among frequently prescribed antibiotics for pregnant women, evidence on their fetal safety remains conflicting.

Objectives: To evaluate the association between first-trimester exposure to macrolides and risk of major congenital malformations (MCMs), focusing on specific malformation subtypes.

Design, setting, and participants: Data used from Mother-Child EPI-MERES Register nested in the French Health Data System (SNDS). We included pregnancies resulting in singleton live-born infants from 2010 to 2020.

Exposure: One or more first trimester prescription filled for any macrolide, and each of six individual macrolides authorized in France. The comparator group was pregnancies exposed to amoxicillin during the first trimester.

Main outcomes and measures: MCMs identified during the first year after delivery. Propensity score based fine stratification approach was used to control potential confounders. Adjusted relative risks (aRRs) and 95%CI were estimated by log-binomial regression for MCMs with a prevalence of at least one per 10,000 infants exposed to any macrolide in utero.

Results: Among 7,644,579 eligible pregnancies, 140,708 exposed to any macrolide and 592,652 exposed to amoxicillin linked with their infants were included in the study cohort. There were 2,432 (172.8 per 10,000) infants having at least one MCM among those exposed to any macrolide and 10,176 (171.7 per 10,000) among those exposed to amoxicillin. Exposure to any macrolide was associated with an increased risk for syndactyly (aRR 1.68, 95%CI 1.11 to 2.55, based on 31 events in the any macrolide exposure group) and spina bifida (1.80, 1.22 to 2.67, 36 events) compared with amoxicillin. We found no increased risk for other specific MCMs. Sensitivity and subgroup analyses for individual macrolides consistently yielded elevated point estimates for syndactyly and spina bifida, which were similar to those of the main analysis, although confidence intervals were wide.

Conclusions: In this study, although exposure to macrolides in early pregnancy are not associated with an increased risk for most MCMs considered, an increase in the risks of syndactyly and spina bifida associated with their exposure is possible. Further studies are needed to confirm as evidence continues to accumulate.