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. 2024 Oct;26(4):547-558.
doi: 10.1177/10998004241257664. Epub 2024 Jun 5.

DNA Methylation, Inflammation, and Neurobehavior in Preterm Infants

Marliese Dion Nist  1 , Rita H Pickler  1 , Abigail B Shoben  2 , Yvette P Conley  3
Affiliations

DNA Methylation, Inflammation, and Neurobehavior in Preterm Infants

Marliese Dion Nist et al. Biol Res Nurs. 2024 Oct.

Abstract

Objectives: 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 (BDNF) and nuclear factor-kappa-B-inhibitor alpha (NFKBIA) are important genes for targeted DNA methylation analysis. The aims of this study were to (1) identify associations between inflammatory factors and BDNF and NFKBIA methylation, and (2) identify associations between BDNF and NFKBIA methylation and early neurobehavior in preterm infants. Methods: 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 BDNF cytosine-phosphate-guanine (CpG) sites and five NFKBIA CpG sites. Neurobehavior was assessed using the Neurobehavioral Assessment of the Preterm Infant. Results: Sixty-five infants were included in the analysis. In females, inflammatory factors were positively associated with BDNF methylation of most CpG sites. Interleukin-1 receptor antagonist was negatively associated with NFKBIA methylation at two CpG sites. In males, interleukin-6 was negatively associated with BDNF and NFKBIA methylation at most CpG sites. In females, BDNF methylation at two sites was inversely associated with motor performance. In males, NFKBIA methylation at one site was inversely associated with motor performance. Conclusion: 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.

Keywords: DNA methylation; brain-derived neurotrophic factor; inflammation; preterm infant.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Percentage Methylation for Analyzed CpG Sites of BDNF and NFKBIA Overall and by Infant Sex. Note. CpG, cytosine-phosphate-guanine; BDNF, brain-derived neurotrophic factor; NFKBIA, nuclear factor-kappa B inhibitor alpha.
Figure 2.
Figure 2.
Summary of Significant Associations and Proposed Relationships in Female and Male Infants. Note. Relationships among concepts in bold font (inflammation, methylation, neurobehavior) are depicted as upward-facing black arrows for higher levels and downward-facing gray arrows for lower levels. Specific, significant biomarkers are shown in boxes below each concept. Only the most consistent relationships are shown. ♀, female; ♂, male; IL, interleukin; RA, receptor antagonist; CpG, cytosine-phosphate-guanine.
See this image and copyright information in PMC

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