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Mukhopadhyay S, Puopolo KM, Hansen NI, Lorch SA, DeMauro SB, Greenberg RG, Cotten CM, Sanchez PJ, Bell EF, Eichenwald EC, Stoll BJ; NICHD Neonatal Research Network. Neurodevelopmental outcomes following neonatal late-onset sepsis and blood culture-negative conditions. Arch Dis Child Fetal Neonatal Ed. 2021 Jan 21:fetalneonatal-2020-320664. doi: 10.1136/archdischild-2020-320664. Epub ahead of print. PMID: 33478957.

Objective: Determine risk of death or neurodevelopmental impairment (NDI) in infants with late-onset sepsis (LOS) versus late-onset, antibiotic-treated, blood culture-negative conditions (LOCNC).

Design: Retrospective cohort study.

Setting: 24 neonatal centres.

Patients: Infants born 1/1/2006-31/12/2014, at 22-26 weeks gestation, with birth weight 401-1000 g and surviving >7 days were included. Infants with early-onset sepsis, necrotising enterocolitis, intestinal perforation or both LOS and LOCNC were excluded.

Exposures: LOS and LOCNC were defined as antibiotic administration for ≥5 days with and without a positive blood/cerebrospinal fluid culture, respectively. Infants with these diagnoses were also compared with infants with neither condition.

Outcomes: Death or NDI was assessed at 18-26 months corrected age follow-up. Modified Poisson regression models were used to estimate relative risks adjusting for covariates occurring ≤7 days of age.

Results: Of 7354 eligible infants, 3940 met inclusion criteria: 786 (20%) with LOS, 1601 (41%) with LOCNC and 1553 (39%) with neither. Infants with LOS had higher adjusted relative risk (95% CI) for death/NDI (1.14 (1.05 to 1.25)) and death before follow-up (1.71 (1.44 to 2.03)) than those with LOCNC. Among survivors, risk for NDI did not differ between the two groups (0.99 (0.86 to 1.13)) but was higher for LOCNC infants (1.17 (1.04 to 1.31)) compared with unaffected infants.

Conclusions: Infants with LOS had higher risk of death, but not NDI, compared with infants with LOCNC. Surviving infants with LOCNC had higher risk of NDI compared with unaffected infants. Improving outcomes for infants with LOCNC requires study of the underlying conditions and the potential impact of antibiotic exposure.

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