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Updated: Dec 19, 2025
Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
Published on: August 25, 2014
Inflammatory predictors of neurobehavior in very preterm infants
Marliese Dion Nist1, Rita H Pickler1, Tondi M Harrison1
1The Ohio State University, College of Nursing, 1585 Neil Avenue, Columbus, OH 43210, USA.
Insights
Inflammation markers in preterm infants are linked to neurodevelopmental outcomes. Specific cytokines like IL-1RA, IL-6, and TNF-alpha, and composite inflammation scores, predict motor and alertness behaviors in very preterm infants.
Area of Science:
- Neonatal research
- Neuroscience
- Immunology
Background:
- Preterm infants face risks for impaired neurodevelopment.
- Inflammation is a potential modifiable factor in preterm birth complications and neurodevelopmental issues.
- Longitudinal inflammation data in this population is scarce.
Purpose of the Study:
- To investigate the association between longitudinal inflammation markers and neurobehavioral development in very preterm infants.
Main Methods:
- A cohort study tracked very preterm infants from October 2017 to December 2018.
- Plasma cytokines were measured weekly until 35 weeks post-menstrual age.
- Neurobehavior was assessed at 35 weeks using the Neurobehavioral Assessment of the Preterm Infant, analyzing motor development, vigor, alertness, and orientation.
Main Results:
- Interleukin-1 receptor antagonist (IL-1RA) correlated with motor development and vigor.
- Interleukin-6 (IL-6) was associated with alertness and orientation.
- Tumor necrosis factor-alpha (TNF-α) and composite inflammation scores related to both motor/vigor and alertness/orientation outcomes.
- Interactions were observed with post-menstrual age at birth and infant sex.
Conclusions:
- Inflammation may predict short-term neurobehavioral outcomes in preterm infants.
- IL-1RA, IL-6, and TNF-α are key cytokines, but composite scores may offer a more comprehensive measure of inflammation.
- Targeting inflammation could be a strategy for improving brain development and outcomes in preterm infants.
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.
