Early inflammatory measures and neurodevelopmental outcomes in preterm infants.

BACKGROUND: Inflammation may be an important predictor of long-term neurodevelopment in preterm infants. The identification of specific inflammatory biomarkers that predict outcomes is an important research goal.

OBJECTIVES: The purpose of this analysis was to identify associations between an early measure of inflammation and neurodevelopment in very preterm infants and to identify differences in the relationship between inflammation and neurodevelopment based on infant sex and race.

METHODS: We conducted a secondary analysis of data from a randomized controlled trial of a caregiving intervention for preterm infants born less than 33 weeks post-menstrual age. Plasma was collected with a clinically-indicated lab draw by neonatal intensive care unit nurses and analyzed by multiplex assay for cytokines, chemokines, and growth factors. Neurobehavior was assessed by research nurses at the time of discharge from the neonatal intensive care unit using the motor development and vigor and alertness/orientation clusters from the Neurobehavioral Assessment of the Preterm Infant. Neurodevelopment was assessed at six months corrected age by the developmental specialist in the hospital's neonatal follow-up clinic using the Bayley Scales of Infant Development, 3 Edition. We used linear regressions to estimate the effect of cytokine levels on neurodevelopment and allowed the effects to differ by infant sex and race.

RESULTS: In a sample of 62 preterm infants with discharge neurobehavioral assessments and a sample of 40 preterm infants with six month neurodevelopmental assessments, we found inconsistent associations between single-timepoint inflammatory measures and neurobehavior or neurodevelopment in analyses of the total sample. However, regressions with interactions revealed effects for multiple inflammatory measures on early neurobehavior and neurodevelopment that differed by infant sex and race.

DISCUSSION: Although early single-timepoint measures of inflammation may be insufficient to predict neurodevelopment for all preterm infants, the effect of inflammation appears to differ by infant sex and race. These demographic factors may be important considerations for future studies of inflammation and neurodevelopment as well was the development of future interventions to optimize outcomes.