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OBJECTIVE: To evaluate the difference in 10-year neurocognitive outcomes between extremely low gestational age newborns without bacteremia and those with suspected or confirmed late-onset bacteremia. STUDY DESIGN: Neurocognitive function was evaluated at 10 years of age in 889 children born at <28 weeks of gestation and followed from birth. Definite (culture-positive) late-onset bacteremia during postnatal weeks 2-4 was identified in 223 children, and 129 children had suspected bacteremia. RESULTS: Infants with the lowest gestational age and birth weight z-score had the highest prevalence of definite and suspected late-onset bacteremia. Compared with peers with no or suspected bacteremia, infants with definite bacteremia performed worse on tests of general cognitive ability, language, academic achievement, and executive function, even after adjustment for potential confounders. Adjustment for low IQ attenuated the associations between bacteremia and all dysfunctions at age 10 years. Children with suspected bacteremia did not differ appreciably from those with no evidence of bacteremia. The motor domain was unaffected. CONCLUSIONS: Extremely low gestational age newborns who had definite late bacteremia during postnatal weeks 2-4 are at heightened risk of neurocognitive limitations at age 10 years.

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OBJECTIVE: To evaluate the hypothesis that elevated levels of inflammation-related proteins in early postnatal blood predict impaired mental and motor development in extremely preterm infants. STUDY DESIGN: We measured concentrations of 25 inflammation-related proteins in blood collected on postnatal days 1, 7, and 14 from 939 infants born before 28 weeks gestation. An elevated level was defined as a concentration in the highest quartile for gestational age and day of blood collection. We identified impaired development at age 24 months using the Bayley Scales of Infant Development, Second Edition. The primary outcomes were scores on the Mental Scale or the Motor Scale of <55 (more than 3 SDs below the mean). RESULTS: For 17 of the 25 inflammation-related proteins, 1 or more statistically significant associations (P<.01) was found between an elevated blood level of the protein and a developmental impairment. Elevations on multiple days were more often associated with developmental impairment than were elevations present for only 1 day. The highest number of predictive elevations was found in day-14 blood. CONCLUSION: In extremely preterm infants, elevated levels of inflammation-related proteins in blood collected on postnatal days 7 and 14, especially when sustained, are associated with impaired mental and motor development at age 2 years.

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OBJECTIVE: To evaluate whether concentrations of inflammation-related proteins are elevated in the blood of preterm newborns who develop cerebral white matter damage. STUDY DESIGN: We measured 25 proteins in blood collected on days 1, 7, and 14 from 939 infants born before the 28th week of gestation. Brain ultrasound scans were read by at least two sonologists, who agreed on the presence or absence of lesions. A protein concentration was considered elevated if it was in the highest quartile for gestational age and the day on which the specimen was collected. RESULTS: In time-oriented models, elevated concentrations of vascular endothelial growth factor receptor 1, serum amyloid A, and macrophage inflammatory protein 1ß on day 1 and interleukin-8 on day 7 were associated with increased risk of ventriculomegaly. Elevated concentrations of macrophage inflammatory protein 1ß on day 1 and intercellular adhesion molecule 1 on day 7 were associated with increased risk of an echolucent lesion. Infants with elevated concentrations of inflammation-related proteins on two separate days were at significantly increased risk for ventriculomegaly, but at only modestly increased risk for an echolucent lesion. CONCLUSIONS: Concentrations of inflammation-related proteins in the circulation in the first days after preterm birth provide information about the risk of sonographic white matter damage. The inflammatory process might begin in utero.

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OBJECTIVE: To evaluate neurodevelopment after necrotizing enterocolitis (NEC) and late bacteremia, alone and together. STUDY DESIGN: Sample included 1155 infants born at 23 to 27 weeks' gestation. NEC was classified by the modified Bell's staging criteria and grouped as medical NEC or surgical NEC. Late bacteremia was defined as a positive blood culture result after the first postnatal week. Neurodevelopment was assessed at 24 months corrected age. Multivariable models estimated the risk of developmental dysfunction and microcephaly associated with medical or surgical NEC with and without late bacteremia. RESULTS: Children who had surgical NEC unaccompanied by late bacteremia were at increased risk of psychomotor developmental indexes <70 (OR = 2.7 [1.2, 6.4]), and children who had both surgical NEC and late bacteremia were at increased risk of diparetic cerebral palsy (OR = 8.4 [1.9, 39]) and microcephaly (OR = 9.3 [2.2, 40]). In contrast, children who had medical NEC with or without late bacteremia were not at increased risk of any developmental dysfunction. CONCLUSION: The risk of neurodevelopmental dysfunction and microcephaly is increased in children who had surgical NEC, especially if they also had late bacteremia. These observations support the hypothesis that bowel injury might initiate systemic inflammation potentially affecting the developing brain.

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OBJECTIVES: To determine whether magnesium sulfate (MgSO(4)) exposure is associated with a reduced risk for neonatal intraventricular hemorrhage (IVH). STUDY DESIGN: In a randomized, controlled trial, women in preterm labor were randomly assigned to receive MgSO(4), "other" tocolytic, or saline control. At delivery, we collected maternal antecubital and umbilical cord blood for determination of serum ionized magnesium levels. Neonatal IVH was diagnosed by cranial ultrasonogram. RESULTS: Among 144 infants, 24 were diagnosed with IVH. Using crude intention-to-treat analysis, we found that 18% (13/74) of survivors exposed after birth to MgSO(4) had IVH compared with 16% (11/70) of babies who were not exposed. Infants who had IVH were more likely to have been delivered by mothers with higher serum ionized magnesium (Mg) levels (0.75 vs 0.56 mmol/L) (P =.01). Using multivariable logistic regression, we confirmed that higher Mg levels are a significant predictor of neonatal IVH (adjusted odds ratio, 15.8; 95% CI, 1.4-175.0) even when adjusted for birth weight, gestational age, antenatal hemorrhage, and neonatal glucocorticoid exposure. CONCLUSIONS: In mothers with preterm labor, our data indicate that antenatal MgSO(4) exposure may be associated with an increased risk for IVH among their newborns.

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OBJECTIVE: This case-control study of chronic lung disease (CLD) evaluated the hypothesis that chorioamnionitis promotes CLD and interacts with other risk factors for CLD, including mechanical ventilation and postnatal infection. STUDY DESIGN: We identified a population of 193 infants who met our case criteria for CLD whose birth weights were 7 days and culture-documented sepsis. In multivariable analyses, infants were at greatest risk for CLD when they had exposure to both chorioamnionitis and either mechanical ventilation >7 days (odds ratio, 3.2; 95% confidence interval, 0.9-11) or postnatal infection (odds ratio, 2.9; 95% confidence interval, 1.1-7.4). CONCLUSIONS: We conclude that prolonged mechanical ventilation or postnatal infection increases the risk of CLD among surviving preterm infants and that these 2 factors interact with antenatal infection to further increase the risk of CLD.

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