Neurobehavior Related to Epigenetic Differences in Preterm Infants

Lester, Barry M.; Marsit, Carmen J.; Giarraputo, James; Hawes, Katheleen; LaGasse, Linda L.; Padbury, Jamés F.

doi:10.2217/epi.15.63

Cited by 77 publications

(35 citation statements)

References 71 publications

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“…Thus, Profile 1 represents an optimal profile characterized by generally positive neurobehavioral responses, while Profile 6 represents a infants with atypical neurobehavioral responses. These findings are similar to profiles observed previously by others (21) and in our own research (26). To limit the number of tests being performed, the current study focused on the optimal (Profile 1) and atypical (Profile 6) profiles, while using the combination of Profiles 2-5 as the referent category in downstream analyses.…”

Section: Study Population and Nnns Profile Resultssupporting

confidence: 87%

“…These methylation marks can be inherited, established in-utero and/or affected by the environment throughout life, thus representing a truly integrated measure of exposure and disease susceptibility. In preterm infants, variability in (DNAm) of candidate genes have been related to medical complications such as sepsis (22), pain related stress (23,24), medical and neurobehavioral risk (25,26), and as a potential moderator of NICU environment stress on serotonergic tone and temperament (27). We have also used an epigenome-wide scan of (DNAm) in the placenta to demonstrate relationships between methylation of the FHIT and ANDKR11 genes, which had been previously linked to neurodevelopmental and behavioral outcomes, and performance on the NNNS attention scale in a cohort of term newborns (28).…”

Section: Epigenetics Refers To Mitotically and Meiotically Heritable mentioning

confidence: 99%

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Epigenome-wide Analysis Identifies Genes and Pathways Linked to Neurobehavioral Variation in Preterm Infants

Everson

Marsit

Burt

et al. 2018

Preprint

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36Background & Objectives: Neonatal neurobehavioral performance measures, such as the NICU Network 37 Neurobehavioral Scale (NNNS), have been developed to assess the neurobehavioral characteristics of 38 infants and provide insights into future developmental trajectories. The identification of molecular 39 biomarkers of very early life neurobehavioral experiences could lead to better predictions of the long-term 40 developmental outcomes of high-risk infants including preterm infants. To this end, we aimed to examine 41 whether variability in DNA methylation (DNAm) or epigenetic age from surrogate tissues are associated 42 with NNNS profiles in a cohort of infants born less than 30 weeks postmenstrual age (PMA). 43Methods: This study was performed within the Neonatal Neurobehavior and Outcomes in Very Preterm 44 Infants (NOVI) Study and included those infants with complete NNNS assessment data and DNAm 45 measured from buccal cells, collected at near term-equivalent age using the Illumina EPIC array (N=536). 46We tested whether epigenetic age and age acceleration differed between infants based on their NNNS 47 profile classifications. Then we performed an epigenome-wide association study, to test whether DNAm at 48 individual epigenetic loci varied between these NNNS profile groupings. Models were adjusted for 49 recruitment site, infant sex, postmenstrual age, and estimated tissue heterogeneity. 50Results: We found that infants with an optimal NNNS profile had slightly older epigenetic age than other 51 NOVI infants (β1 = 0.201, p-value = 0.026), and that infants with an atypical NNNS profile had differential 52 methylation at 29 CpG sites (FDR < 10%). The genes annotated to these differentially methylated CpGs 53 included PLA2G4E, TRIM9, GRIK3, and MACROD2, which have previously been associated with 54 neurological structure and function, or with neurobehavioral disorders. 55Conclusions: Greater epigenetic age is associated with optimal NNNS responses while altered DNAm of 56 multiple genes are associated with an atypical neurobehavioral profile at near-term equivalent age. These 57 findings build upon the existing evidence that epigenetic variations in buccal cells may serve as markers of 58 neonatal neurobehavior and might facilitate early identification of children at risk for abnormal 59 developmental outcome. are born less than 37 weeks of gestation (1). Survival of infants born extremely preterm, less than 30 week 63 postmenstrual age (PMA), has improved due to technological and medical advancements (1-3). 64Nonetheless, these infants have increased risk for morbidity and mortality. Children born extremely preterm 65 term are more likely to suffer from chronic illnesses, potentially devastating brain injuries, and adverse 66 neuromotor, cognitive, and behavioral outcomes that persist through adulthood (4-15). These serious health 67 consequences require extensive healthcare, educational and psychosocial community resources, in addition 68 to increased burden on the families and caregivers of these childre...

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Section: Study Population and Nnns Profile Resultssupporting

confidence: 87%

Section: Epigenetics Refers To Mitotically and Meiotically Heritable mentioning

confidence: 99%

Epigenome-wide Analysis Identifies Genes and Pathways Linked to Neurobehavioral Variation in Preterm Infants

Everson

Marsit

Burt

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

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“…1 We 8 and others 7 have observed that methylation of the human glucocorticoid receptor promoter region, including the nerve growth factor binding site is associated with maternal mood disorders during pregnancy and infant behavior in term infants and aberrant neurobehavior in preterm infants. 20 We found altered methylation at CpG sites 7, 10, 12 and 13. This region of the human glucocorticoid receptor gene promoter is involved in the regulation of the HPA system.…”

Section: Discussionmentioning

confidence: 70%

Epigenetic Programming by Maternal Behavior in the Human Infant

et al. 2018

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Objective: We sought to determine if variations in maternal care alter DNA methylation in term, healthy five- month-old infants. This work was based on landmark studies in animal models demonstrating that nurturing care by dams would alter their newborn’s stress responses through epigenetic mechanisms. We used breastfeeding as a proxy for animal maternal behavior. We hypothesized alterations in DNA methylation of the glucocorticoid receptor gene and less hypothalamic stress response in infants of mothers who breastfed their infants versus infants of mothers who did not breastfeed. Methods: A cohort study of term, healthy infants and their mothers who did (n=21) or did not (n=21) breastfeed for the first 5 months was utilized in this analysis. Cortisol stress reactivity was measured in infant saliva using a mother-infant interaction procedure, and DNA methylation of an important regulatory region of the glucocorticoid receptor gene. Changes in DNA methylation of this gene in the human were compared to homologous regions of the rat gene. DNA samples were prepared from cheek swabs and subjected to quantitative analysis of extent of methylation using sensitive sequencing techniques. Results: Breastfeeding decreased DNA methylation of the glucocorticoid receptor promoter and decreased cortisol reactivity in 5-month-old infants. Decreased DNA methylation occurred in the promoter region involved in regulation of the hypothalamic-pituitary-adrenal (HPA) and immune system responses. Conclusions: Maternal care in humans may impact HPA stress response through behavioral programming and manifest as offspring epigenetic change. These results explain, in part, some of the positive effects observed in children with breastfeeding.

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“…It is well known that too much or too little cortisol is related to changes in behavior including behavior disorders and psychopathology (Doom & Gunnar, ). There are numerous prenatal and postnatal biological, social, and environmental factors that have been related to DNA methylation of NR3C1 altering its expression resulting in overproduction or underproduction of cortisol levels (Glover, O'Connor, & O'Donnell, ; Lester, Conradt, & Marsit, ; Romens et al., ; Tyrka et al., ).…”

Section: Epigenetic Mechanismsmentioning

confidence: 99%

“…For example, the hypothalamic-pituitary-adrenal (HPA) axis is a consistent topic of studies of development and programming as it plays a central role in stress reactivity and can be programmed by various environmental factors. (Glover et al, 2010;Lester et al, 2015;Meaney, 2010). Although the GR (encoded by NR3C1) is a key gene in this pathway, a number of other genes also are involved.…”

Section: Approaches To the Study Of Dna Methylationmentioning

confidence: 99%

Introduction to the Special Section on Epigenetics

2016

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Epigenetics provides the opportunity to revolutionize our understanding of the role of genetics and the environment in explaining human behavior, although the use of epigenetics to study human behavior is just beginning. In this introduction, the authors present the basics of epigenetics in a way that is designed to make this exciting field accessible to a wide readership. The authors describe the history of human behavioral epigenetic research in the context of other disciplines and graphically illustrate the burgeoning of research in the application of epigenetic methods and principles to the study of human behavior. The role of epigenetics in normal embryonic development and the influence of biological and environmental factors altering behavior through epigenetic mechanisms and developmental programming are discussed. Some basic approaches to the study of epigenetics are reviewed. The authors conclude with a discussion of challenges and opportunities, including intervention, as the field of human behavioral epigenetics continue to grow.

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Neurobehavior Related to Epigenetic Differences in Preterm Infants

Cited by 77 publications

References 71 publications

Epigenome-wide Analysis Identifies Genes and Pathways Linked to Neurobehavioral Variation in Preterm Infants

Epigenome-wide Analysis Identifies Genes and Pathways Linked to Neurobehavioral Variation in Preterm Infants

Epigenetic Programming by Maternal Behavior in the Human Infant

Introduction to the Special Section on Epigenetics

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