Infection in ELBW infants linked with poor neurodevelopmental, growth outcomes

November 16, 2004

Extremely low-birth-weight (ELBW) infants who have an infection during their hospitalization following birth are more likely to have adverse neurodevelopmental outcomes than those infants who do not have an infection, according to a study in the November 17 issue of JAMA.

Infections are known to be a frequent complication among ELBW (14.2 ounces to 35.3 ounces) preterm infants, and are associated with short-term illness and increased risk of death, according to background information in the article.

Barbara J. Stoll, M.D., of the Emory University School of Medicine, Atlanta, and colleagues conducted a study to determine if neonatal (during the first 120 days of life) infections are associated with adverse neurodevelopmental and growth abnormalities in early childhood.

The study included infants, born 1993-2001, who were enrolled in a 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 (from conception) and compared by infection group. Eighty percent of survivors completed the follow-up visit and 6,093 infants were studied. Registry data were used to classify infants by type of infection: uninfected (n = 2,161), clinical infection alone (negative infection requiring 5 days or more of antibiotics; n = 1,538), sepsis (positive blood cultures requiring 5 days or more of antibiotic treatment; n = 1,922), sepsis and necrotizing enterocolitis (inflammation involving both the small intestine and the colon; n = 279), or meningitis with or without sepsis (n = 193).

The majority of ELBW survivors (65 percent) had at least 1 infection during their hospitalization after birth. The researchers found that 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 (40-70 percent increased risk), low Bayley Scales of Infant Development II scores on the mental development index (30-60 percent increased risk) and psychomotor development index (50 percent to 2.4 times increased risk), and vision impairment (30 percent to 2.2 times increased risk). Infection in the neonatal period was also associated with impaired head growth, a known predictor of poor neurodevelopmental outcome.

"Possible interventions to reduce brain injury associated with infection might include earlier diagnosis and improved therapies, including efforts to stabilize blood pressure and maintain adequate oxygenation, reduction of systemic inflammation and generation of proinflammatory cytokines [proteins of the immune system], and pharmacologic interventions to reduce the impact of reactive oxygen species on vulnerable oligodendroglial [tissue in the central nervous system] precursors. Ultimately, efforts to reduce the high rates of infection in ELBW infants are the most important interventions," the authors conclude.
(JAMA. 2004;292:2357-2365. Available post-embargo at

Editor's Note: This work was supported by grants from the National Institutes of Health.

Editorial: Developmental Vulnerability and Resilience in Extremely Preterm Infants

In an accompanying editorial, Michael E. Msall, M.D., of the University of Chicago, writes that the findings reported by Stoll et al present 3 important challenges.

"(1) to examine instrumentation and barrier practices so as to lessen the risk of infection; (2) to develop explicit hypotheses about inflammatory mediators, disruption of the blood-brain barrier, and mechanisms impairing cranial growth and emerging developmental processes; and (3) to define developmental variables and functional outcomes a priori so that the effects of new interventions on severe multiple disabilities and can be measured consistently. There is now a critical opportunity to examine whether neurodevelopmental impairment can be reduced by reducing rates of infection," he writes.

"By combining biomedical risk reduction strategies with biopsychosocial interventions, further progress can be made toward enhancing survival and optimizing developmental outcomes. Until prematurity can be prevented, it is important to meticulously analyze the impact of current practices on growth and development while these children are part of in-hospital care as well as when they return to their communities. Given the lifelong impact of these interventions, doing so should be one of the most important undertakings in neonatal care."

(JAMA. 2004;292:2399-2401. Available post-embargo at

Editor's Note: This research was supported by a grant entitled "NICHD Family and Child Well Being Network: Child Disability."

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