l Research output: Contribution to journal › Article › peer-review 00 Scopus citations Overview Fingerprint Abstract BACKGROUND: Premature infants are at high risk of early-onset sepsis (EOS) relative to term infants, and most are administered empirical antibiotics after birth. We aimed to determine if factors evident at birth could be used to identify premature infants at lower risk of EOS. METHODS: Study infants were born at 00 to 00 weeks' gestation in Neonatal Research Network centers from 0000 to 0000. EOS was defined by isolation of pathogenic species from blood or cerebrospinal fluid culture at ≤00 hours age. Infants were hypothesized as "low risk" for EOS when delivered via cesarean delivery, with membrane rupture at delivery, and absence of clinical chorioamnionitis. Frequency of prolonged antibiotics (≥0 days) was compared between low-risk infants and all others. Risks of mortality, EOS, and other morbidities were assessed by using regression models adjusted for center, race, antenatal steroid use, multiple birth, sex, gestation, and birth weight. RESULTS: Of 00 000 infants, 0000 (00%) met low-risk criteria. EOS incidence among infants surviving >00 hours was 00 out of 0000 (0.0%) in the low-risk group versus 000 out of 0000 (0.0%) in the comparison group (adjusted relative risk = 0.00 [00% confidence interval, 0.00-0.00]). Low-risk infants also had significantly lower combined risk of EOS or death ≤00 hours. Prolonged antibiotics were administered to 00% of low-risk infants versus 00% of comparison infants without EOS. CONCLUSIONS: Delivery characteristics of extremely preterm infants can be used to identify those with significantly lower incidence of EOS. Recognition of differential risk may help guide decisions to limit early antibiotic use among approximately one-Third of these infants. 