The association of early antibiotic exposure with subsequent development of late-onset sepsis in preterm infants: a systematic review
and meta-analysis studies

The association of early antibiotic exposure with subsequent development of late-onset sepsis in preterm infants: a systematic review
and meta-analysis studies

Preterm infants, Early antibiotic exposure, Late-onset sepsis, Meta-analysis

Abstract
Background Early antibiotic exposure in preterm infants may disrupt gut microbiome development, affecting
health. However, its link to late-onset sepsis (LOS) remains unclear. This meta-analysis aims to clarify the association
while addressing confounding bias.
Methods This systematic review and meta-analysis, conducted per PRISMA guidelines, utilized PubMed, Scopus,
Google Scholar, and Web of Science for comprehensive literature retrieval. Studies comparing preterm infants with
sterile blood cultures who received early antibiotics (short or prolonged) to those without, using LOS as the primary
outcome, were included. Comparisons between short- and prolonged-course antibiotics were also considered. Only
studies with adjusted analyses for confounders were considered. Adjusted odds ratios (aOR) were meta-analyzed, and
the prediction interval (PI) was calculated using R software.
Results Ten studies met the eligibility criteria, comprising a total sample size of 55,089 preterm infants. Among
these, nine studies included 33,549 preterm infants and compared prolonged antibiotic exposure to short exposure.
Prolonged exposure was not significantly associated with LOS (pooled aOR=1.2, 95% CI 0.99–1.46, P=0.066, PI=0.66
to 2.19, I2 = 67%). Limiting the analysis to five studies with sample sizes over 1,000 reduced heterogeneity (I2 = 30%)
and provided a more precise confidence interval (pooled aOR=1.03, 95% CI 0.91–1.15). Four studies, involving 41,938
preterm infants, examined preterm infants exposed to prolonged antibiotics versus those not exposed and found
no significant association (aOR=0.91, 95% CI 0.82–1.02, P=0.1, PI=0.72 to 1.16, I2 = 0). All four studies had sample

sizes exceeding 1,000. Additionally, these studies compared preterm infants with short antibiotic exposure to non-
exposure, revealing a slightly lower risk of LOS (aOR=0.87, 95% CI 0.77–0.98, P=0.024, I2 = 0) and a PI of 0.76 to 1.14.

YF Shamseldin1* , Heba Khaled2

, Muhammed Abdiwahab3 , Maha K. Abu Radwan4

, Abdalfattah Sabra5
,

Mona Mohammed6

, Sarah EL-Sayegh7

, Dina Abdel Rasoul Helal8

, Mahmoud E. Kamal9 , Ahmed Hassan10 and

Ahmed Azzam11

https://doi.org/10.1186/s12245-025-00869-5

2025

Peri Irawan

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