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Barbara J. Stoll, MD; Nellie I. Hansen, MPH; Ira Adams-Chapman, MD; Avroy A. Fanaroff, MD; Susan R. Hintz, MD; Betty Vohr, MD; Rosemary D. Higgins, MD; for the National Institute of Child Health and Human Development Neonatal Research Network

JAMA. 2004;292:2357-2365.

Context  Neonatal infections are frequent complications of extremely low-birth-weight (ELBW) infants receiving intensive care.

Objective  To determine if neonatal infections in ELBW infants are associated with increased risks of adverse neurodevelopmental and growth sequelae in early childhood.

Design, Setting, and Participants  Infants weighing 401 to 1000 g at birth (born in 1993-2001) were enrolled in a prospectively collected very low-birth-weight registry at academic medical centers participating in the National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth outcomes were assessed at a comprehensive follow-up visit at 18 to 22 months of corrected gestational age and compared by infection group. Eighty percent of survivors completed the follow-up visit and 6093 infants were studied. Registry data were used to classify infants by type of infection: uninfected (n = 2161), clinical infection alone (n = 1538), sepsis (n = 1922), sepsis and necrotizing enterocolitis (n = 279), or meningitis with or without sepsis (n = 193).

Main Outcome Measures  Cognitive and neuromotor development, neurologic status, vision and hearing, and growth (weight, length, and head circumference) were assessed at follow-up.

Results  The majority of ELBW survivors (65%) had at least 1 infection during their hospitalization after birth. Compared with uninfected infants, those in each of the 4 infection groups were significantly more likely to have adverse neurodevelopmental outcomes at follow-up, including cerebral palsy (range of significant odds ratios [ORs], 1.4-1.7), low Bayley Scales of Infant Development II scores on the mental development index (ORs, 1.3-1.6) and psychomotor development index (ORs, 1.5-2.4), and vision impairment (ORs, 1.3-2.2). Infection in the neonatal period was also associated with impaired head growth, a known predictor of poor neurodevelopmental outcome.

Conclusions  This large cohort study suggests that neonatal infections among ELBW infants are associated with poor neurodevelopmental and growth outcomes in early childhood. Additional studies are needed to elucidate the pathogenesis of brain injury in infants with infection so that novel interventions to improve these outcomes can be explored.

Author Affiliations: Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga (Drs Stoll and Adams-Chapman); Research Triangle Institute, Research Triangle Park, NC (Ms Hansen); Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio (Dr Fanaroff); Division of Neonatology, Stanford University Medical Center, Palo Alto, Calif (Dr Hintz); Department of Pediatrics, Brown University, Providence, RI (Dr Vohr); and the National Institute of Child Health and Human Development, Bethesda, Md (Dr Higgins).

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