AUTHOR=Klerk Daphne H. , van Avezaath Lisanne K. , Loeffen Erik A. H. , Hulscher Jan B. F. , Kooi Elisabeth M. W. 

TITLE=Fetal–neonatal exposure to antibiotics and NEC development: A systematic review and meta-analysis

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 10 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.1102884

DOI=10.3389/fped.2022.1102884

ISSN=2296-2360

ABSTRACT=Background: Fetal and neonatal exposure to antibiotics may contribute to development of necrotizing enterocolitis (NEC) in preterm infants. This systematic review and meta-analysis investigates whether exposure to third trimester maternal antibiotics (MAB) and/or prolongation of empirical antibiotics (PEAB) are associated with NEC development in preterms. 

Method: We included observational and randomized-controlled studies including preterm or VLWB infants, from MEDLINE and EMBASE, published between 1990 and June 2021. Exposure was defined as 3rd trimester MAB and/or PEAB. Two reviewers independently performed study selection, data extraction and quality assessment.

Results: Three cohort studies compared third trimester MAB with no antibiotics. MAB was associated with lower NEC incidence, unadjusted pooled OR is 0.57 (95%CI 0.35-0.93). Twelve cohort studies showed that PEAB was associated with an increased risk of NEC. Ten observational cohort studies show an unadjusted OR of 2.72 (1.65-4.47), two case-control studies show an unadjusted MD of 2.31 (0.94-3.68). Moderate to substantial heterogeneity was observed but decreased in studies with low risk of bias and high sample size.

Conclusion: Evidence suggests an association between MAB and decreased risk of NEC and an association between PEAB and increased risk of NEC. Further studies should confirm these associations and explore causality.