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Objective: We sought to determine whether cumulative evidence of perinatal inflammation was associated with increased risk in a “multi-hit” model of neonatal white matter injury (WMI).

Methods: This retrospective cohort study included very preterm (gestational ages at delivery <32 weeks) live-born singleton neonates delivered at Hutzel Women’s Hospital, Detroit, MI, from 2006 to 2011. Four pathologists blinded to clinical diagnoses and outcomes performed histological examinations according to standardized protocols. Neurosonography was obtained per routine clinical care. The primary indicator of WMI was ventriculomegaly (VE). Neonatal inflammation-initiating illnesses included bacteremia, surgical necrotizing enterocolitis, other infections, and those requiring mechanical ventilation.

Results: A total of 425 live-born singleton neonates delivered before the 32^nd week of gestation were included. Newborns …