Early Antibiotic Exposure and Adverse Outcomes in Very Preterm Infants at Low Risk of Early-Onset Sepsis: The EPIPAGE-2 Cohort Study

J Pediatr. 2022 Apr:243:91-98.e4. doi: 10.1016/j.jpeds.2021.11.075. Epub 2021 Dec 21.


Objective: To assess the association between early empirical antibiotics and neonatal adverse outcomes in very preterm infants without risk factors for early-onset sepsis (EOS).

Study design: This is a secondary analysis of the EPIPAGE-2 study, a prospective national population-based cohort that included all liveborn infants at 22-31 completed weeks of gestation in France in 2011. Infants at high risk of EOS (ie, born after preterm labor or preterm premature rupture of membranes or from a mother who had clinical chorioamnionitis or had received antibiotics during the last 72 hours) were excluded. Early antibiotic exposure was defined as antibiotic therapy started at day 0 or day 1 of life, irrespective of the duration and type of antibiotics. We compared treated and untreated patients using inverse probability of treatment weighting based on estimated propensity scores.

Results: Among 648 very preterm infants at low risk of EOS, 173 (26.2%) had received early antibiotic treatment. Early antibiotic exposure was not associated with death or late-onset sepsis or necrotizing enterocolitis (OR, 1.04; 95% CI, 0.72-1.50); however, it was associated with higher odds of severe cerebral lesions (OR, 2.71; 95% CI, 1.25-5.86) and moderate-severe bronchopulmonary dysplasia (BPD) (OR, 2.30; 95% CI, 1.21-4.38).

Conclusions: Early empirical antibiotic therapy administrated in very preterm infants at low risk of EOS was associated with a higher risk of severe cerebral lesions and moderate-severe BPD.

Keywords: bronchopulmonary dysplasia; empirical antibiotics; late-onset sepsis; necrotizing enterocolitis; neonatal death; neonatal outcome; prematurity; preterm birth; severe cerebral lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / adverse effects
  • Bronchopulmonary Dysplasia* / drug therapy
  • Bronchopulmonary Dysplasia* / epidemiology
  • Cohort Studies
  • Female
  • Fetal Growth Retardation
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases* / drug therapy
  • Infant, Premature, Diseases* / epidemiology
  • Pregnancy
  • Prospective Studies
  • Sepsis* / drug therapy
  • Sepsis* / epidemiology


  • Anti-Bacterial Agents