Inflammatory predictors of neurobehavior in very preterm infants

Abstract

Background: Preterm infants are at risk for impaired neurodevelopment. Inflammation may be an important modifiable mediator of preterm birth and neurodevelopmental impairment, but few studies have examined longitudinal measures of inflammation.

Objective: To determine the relationship between longitudinal measures of inflammation and neurobehavior in very preterm infants.

Study design: Non-experimental, repeated measures cohort study.

Methods: Very preterm infants were enrolled between October 2017 and December 2018. Blood was collected weekly until 35 weeks post-menstrual age for the quantification of plasma cytokines. Neurobehavior was assessed at 35 weeks post-menstrual age using the cluster scores for motor development and vigor and alertness/orientation from the Neurobehavioral Assessment of the Preterm Infant. Multiple linear regression models with robust standard errors were used to analyze the data. Average levels of individual cytokines, cytokine trends, and composite scores were used as measures of inflammation.

Results: Seventy-three infants were enrolled in the study. Interleukin-1 receptor antagonist was associated with motor development and vigor scores. Interleukin-6 was associated with alertness/orientation scores. Tumor necrosis factor-alpha and composite scores of inflammation were associated with motor development and vigor and alertness/orientation scores. There were interactions with post-menstrual age at birth and infant sex.

Conclusion: Inflammation may be an important predictor of short-term neurobehavior in preterm infants. Interleukin-1 receptor antagonist, interleukin-6, and tumor necrosis factor-alpha are key cytokines for studies of preterm infants, but composite scores may be a better measure of inflammation than individual cytokines. Inflammation can be damaging to the immature brain and may be a specific target for future interventions to improve outcomes.

Keywords: Cytokine; Inflammation; Neurobehavior; Neurodevelopment; Preterm infant.