DNA Methylation, Inflammation, and Neurobehavior in Preterm Infants.

Area of Science:

• Neuroscience
• Developmental Biology
• Epigenetics

Background:

• Inflammation is linked to neurodevelopmental disparities in preterm infants.
• DNA methylation may mediate inflammation's effects on gene expression, influencing neurodevelopment.
• Brain-derived neurotrophic factor (BDNF) and nuclear factor-kappa-B-inhibitor alpha (NFKBIA) are key genes in neurodevelopment and inflammation pathways.

Purpose of the Study:

• To investigate associations between inflammatory factors and DNA methylation of BDNF and NFKBIA.
• To examine the relationship between BDNF and NFKBIA methylation and early neurobehavior in preterm infants.
• To explore potential sex differences in these associations.

Main Methods:

• Longitudinal cohort study of preterm infants (28-31 weeks gestational age).
• Weekly blood sampling for inflammatory factor quantification.
• DNA methylation analysis of specific BDNF and NFKBIA CpG sites from saliva samples.
• Neurobehavioral assessment using the Neurobehavioral Assessment of the Preterm Infant.

Main Results:

• In females, inflammatory factors correlated positively with BDNF methylation and negatively with NFKBIA methylation at certain sites.
• In males, interleukin-6 showed negative associations with both BDNF and NFKBIA methylation.
• Female infants showed inverse associations between BDNF methylation and motor performance; male infants showed an inverse association between NFKBIA methylation and motor performance.

Conclusions:

• Evidence supports a mechanistic link between inflammation, DNA methylation, and neurobehavior in preterm infants.
• Sex-specific differences in methylation patterns and neurobehavioral outcomes were observed.
• Female infants may exhibit increased vulnerability to inflammation's neurodevelopmental impact, meriting further investigation.