DNA Methylation, Inflammation, and Neurobehavior in Preterm Infants.

<bold>Objectives:</bold> Inflammation contributes to disparate neurodevelopmental outcomes between preterm and term-born infants. In this context, DNA methylation may contribute to inflammation by affecting gene expression. Brain-derived neurotrophic factor (<italic>BDNF</italic>) and nuclear factor-kappa-B-inhibitor alpha (<italic>NFKBIA</italic>) are important genes for targeted DNA methylation analysis. The aims of this study were to (1) identify associations between inflammatory factors and <italic>BDNF</italic> and <italic>NFKBIA</italic> methylation<italic>,</italic> and (2) identify associations between <italic>BDNF</italic> and <italic>NFKBIA</italic> methylation and early neurobehavior in preterm infants. <bold>Methods:</bold> In a longitudinal cohort study of preterm infants born 28–31 weeks gestational age, blood samples were collected weekly for the quantification of inflammatory factors. We extracted DNA from saliva samples and quantified methylation of six <italic>BDNF</italic> cytosine-phosphate-guanine (CpG) sites and five <italic>NFKBIA</italic> CpG sites. Neurobehavior was assessed using the Neurobehavioral Assessment of the Preterm Infant. <bold>Results:</bold> Sixty-five infants were included in the analysis. In females, inflammatory factors were positively associated with <italic>BDNF</italic> methylation of most CpG sites. Interleukin-1 receptor antagonist was negatively associated with <italic>NFKBIA</italic> methylation at two CpG sites. In males, interleukin-6 was negatively associated with <italic>BDNF</italic> and <italic>NFKBIA</italic> methylation at most CpG sites. In females, <italic>BDNF</italic> methylation at two sites was inversely associated with motor performance. In males, <italic>NFKBIA</italic> methylation at one site was inversely associated with motor performance. <bold>Conclusion:</bold> This study provides evidence for the relationship between inflammation and neurobehavior in preterm infants, working mechanistically through DNA methylation. The finding of a difference between males and females suggests that female infants are potentially more vulnerable to inflammation and warrants future study. [ABSTRACT FROM AUTHOR]