Inflammatory mediators of stress exposure and neurodevelopment in very preterm infants: Protocol for the stress neuro-immune study.

Aims: (a) Determine relationships among stress exposure, inflammation, and neurodevelopment in very preterm infants and determine the mediated effect of inflammation on the relationship between stress exposure and neurodevelopment; (b) describe cytokine trajectories following birth and determine the effect of stress exposure on these trajectories; and (c) examine relationships between stress exposure and chronic stress responses in very preterm infants.

Design: Non-experimental, repeated measures.

Methods: Very preterm infants born 28-31 weeks post menstrual age will be enrolled. Cumulative stress exposure over the first 14 days of life will be measured using the Neonatal Infant Stressor Scale. Blood will be collected weekly for the quantification of cytokines. Neurodevelopment will be assessed using the Neurobehavioral Assessment of the Preterm Infant and hair for quantification of hair cortisol will be collected at 35 weeks post menstrual age. Multiple linear regression and conditional process analysis will be used to analyse the relationships among stress exposure, inflammation and neurodevelopment. Linear mixed models will be used to determine inflammatory trajectories over time. IRB approval for the study was received May 2017, and funding from the National Institute of Nursing Research was awarded July 2017.

Discussion: This study will determine the extent to which inflammation mediates the relationship between stress exposure and neurodevelopment. Interventions to attenuate inflammation in preterm infants may improve outcomes.

Impact: Determining the potentially modifiable mediators of stress exposure and neurodevelopment in preterm infants is critical to improving long-term outcomes.