Neonatal Infection and Later Neurodevelopmental Risk in the Very Preterm Infant

Objectives: To document associations between confirmed and suspected neonatal infection and motor, cognitive, educational, and mental health outcomes of very preterm (VPT)-born children at 9 years of age; to examine the potential intervening role of cerebral white matter abnormalities (WMAs) and structural development on term magnetic resonance imaging.

Study design: A regional cohort of 110 infants born VPT in Christchurch, New Zealand were studied from birth to age of 9 years. Confirmed infection was defined as positive blood, cerebrospinal fluid or urine culture, and/or necrotizing enterocolitis ≥ stage 2. Suspected infection was defined as ≥ 5 days of antibiotics with evidence of clinical correlates. At term gestational equivalence, infants underwent structural magnetic resonance imaging. At age 9 years, neuromotor function, IQ, educational achievement, and mental health were assessed.

Results: During hospitalization, 25% of VPT infants had confirmed and 23% had suspected infection. Longer-term neurodevelopmental impairments were largely confined to infants with confirmed infection (relative risk 1.4-3.1, vs uninfected). After accounting for other neonatal factors, these infants were at increased risk of severe motor impairment (OR 3.3, 95% CI 1.3-8), attention deficit hyperactivity disorder (ADHD) (OR 3.6, 95% CI 1.6-8), and IQ delay (OR 2.0, 95% CI 1-3.9). Cerebral WMAs contributed to associations between confirmed infection and motor and IQ impairments but not to ADHD (P = .005).

Conclusions: Confirmed neonatal infection heightens VPT infants' risk for neurodevelopmental impairment. WMA appears to be an important intervening factor linking infection and severe motor and IQ impairments. Further analysis of the neurologic mechanism accounting for ADHD in infants with infection is needed.