Neonatal infections are frequent complications of extremely-low-birth-weight infants in intensive care, and are associated with prolonged hospitalization and death. In the current study, investigators wanted to find out whether the adverse outcomes of neonatal infections continue into early childhood. Led by Barbara J. Stoll, MD, professor and chair of pediatrics at Emory School of Medicine, the research team used data collected on very-low-birth-weight infants by academic medical centers participating in the National Institute of Child Health and Human Development Neonatal Research Network.
The infants studied were born between 1993 and 2001 and weighed between 14.2 ounces and 35.3 ounces (401-1,000 grams) at birth. Sixty-five percent of the low-birth-weight infants in the study had at least one infection during their hospitalization after birth. After leaving the hospital, they returned for follow-up between 18 and 22 months after conception and were assessed for cognitive and neuromotor development, neurologic status, vision and hearing, and growth (weight, length, and head circumference).
Compared with uninfected infants, infected infants were significantly more likely to have adverse neurodevelopmental outcomes at follow-up, including cerebral palsy, low scores in mental development and psychomotor development on the Bayley Scales of Infant Development II test, or vision impairment. Neonatal infection also was associated with impaired head growth, which is known to be a predictor of poor neurodevelopmental outcome.
The registry data were used to classify infants by type of infection, including uninfected (2,161); clinical infection alone (1,538); sepsis (1,922); sepsis and necrotizing enterocolitis (279); or meningitis with or without sepsis (193). Sepsis is an infection of the bloodstream, and necrotizing enterocolitis (NEC) is a severe intestinal disease linked to infection.
Overall, 41 percent of the assessed infants had at least one adverse neurodevelopmental outcome. Infants without infection were least likely to have adverse outcomes, while those with sepsis/NEC were most likely. Overall, 62 percent of the infants had weight, length, or head circumferences less than the 10th percentile. Significant differences for all the neurodevelopmental outcomes except hearing impairment were found between children in most infection groups and the uninfected group. Only infants who had sepsis or sepsis/NEC were at increased risk of hearing impairment.
The investigators considered several possible reasons for the detrimental effects of infections of neonatal infections on the brains of newborns. An inflammatory response by immune signaling proteins called cytokines, either in the fetus or amniotic fluid, reflecting an infection in utero, appears to increase the risk for neonatal brain injury. Newborns with infections also are at risk for circulatory or respiratory problems that could contribute to difficulties with regulation of blood flow in the brain. Interventions to reduce brain injury associated with infection could include earlier diagnosis, efforts to stabilize blood pressure and maintain adequate oxygen supply, and therapies to reduce systemic inflammation.
"As the mortality rate for extremely-low-birth-rate infants continues to decrease, we are increasing our efforts to assess and improve the long-term outcomes associated with prematurity," Dr. Stoll said. "Additional studies will be important to find out exactly how the brain is injured during neonatal infections. We also need to determine whether our findings are applicable to larger preterm infants or to full-term infants, and also to assess the long-term impact of neonatal infections later on in childhood. Most importantly, though, it will be essential to develop interventions to reduce the high rates of infection in extremely-low-birth-weight infants."
The research was supported by grants from the National Institutes of Health.
Journal
JAMA