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

• Published in: The Journal of pediatrics 2022-04, Vol.243, p.91-98.e4
• Main Authors: Letouzey, Mathilde, Lorthe, Elsa, Marchand-Martin, Laetitia, Kayem, Gilles, Charlier, Caroline, Butin, Marine, Mitha, Ayoub, Kaminski, Monique, Benhammou, Valerie, Ancel, Pierre-Yves, Boileau, Pascal, Foix-L'Hélias, Laurence, Gras-Le Guen, Christèle, Kuhn, Pierre, Maisonneuve, Emeline, Sibiude, Jeanne, Torchin, Héloïse
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - adverse effects; bronchopulmonary dysplasia; Bronchopulmonary Dysplasia - drug therapy; Bronchopulmonary Dysplasia - epidemiology; Cohort Studies; empirical antibiotics; Female; Fetal Growth Retardation; Human health and pathology; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases - drug therapy; Infant, Premature, Diseases - epidemiology; late-onset sepsis; Life Sciences; necrotizing enterocolitis; neonatal death; neonatal outcome; Pediatrics; Pregnancy; prematurity; preterm birth; Prospective Studies; Santé publique et épidémiologie; Sepsis - drug therapy; Sepsis - epidemiology; severe cerebral lesions
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2021.11.075

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