From early stress to 12-month development in very preterm infants: Preliminary findings on epigenetic mechanisms and brain growth

Abstract

Very preterm (VPT) infants admitted to Neonatal Intensive Care Unit (NICU) are at risk for altered brain growth and less-than-optimal socio-emotional development. Recent research suggests that early NICU-related stress contributes to socio-emotional impairments in VPT infants at 3 months through epigenetic regulation (i.e., DNA methylation) of the serotonin transporter gene (SLC6A4). In the present longitudinal study we assessed: (a) the effects of NICU-related stress and SLC6A4 methylation variations from birth to discharge on brain development at term equivalent age (TEA); (b) the association between brain volume at TEA and socio-emotional development (i.e., Personal-Social scale of Griffith Mental Development Scales, GMDS) at 12 months corrected age (CA). Twenty-four infants had complete data at 12-month-age. SLC6A4 methylation was measured at a specific CpG previously associated with NICU-related stress and socio-emotional stress. Findings confirmed that higher NICU-related stress associated with greater increase of SLC6A4 methylation at NICU discharge. Moreover, higher SLC6A4 discharge methylation was associated with reduced anterior temporal lobe (ATL) volume at TEA, which in turn was significantly associated with less-than-optimal GMDS Personal-Social scale score at 12 months CA. The reduced ATL volume at TEA mediated the pathway linking stress-related increase in SLC6A4 methylation at NICU discharge and socio-emotional development at 12 months CA. These findings suggest that early adversity-related epigenetic changes might contribute to the long-lasting programming of socio-emotional development in VPT infants through epigenetic regulation and structural modifications of the developing brain.

Adverse childhood experiences, epigenetics and telomere length variation in childhood and beyond: a systematic review of the literature

“…Most reported study participants were adults (n = 7769) while far fewer were children (n = 727 aged between 2 and 18 and 633 under the age of 2). Of the 37 studies, only nine included data gathered in childhood, and seven of these included a longitudinal follow-up [7,9,[16][17][18][19][20]. Table 1 shows further details of these studies.…”

Physiology of Stress and Use of Skin-to-Skin Care as a Stress-Reducing Intervention in the NICU

“…Two glucocorticoids that play significant roles in neonatal outcomes are corticosterone and cortisol, both of which have properties that are beneficial when released in response to short-term stress but become detrimental when the body is exposed to elevated levels over a prolonged period of time. Elevated levels of corticosterone over a prolonged period of time have been found to result in increased levels of glutamate, which contributes to overstimulation of neurons, neuronal cell death (Mooney-Leber & Brummelte, 2017), and ultimately poor brain growth and structural changes to the brain (Fumagalli et al, 2018). These changes in response to prolonged stress likely contribute to some of the long-term neurodevelopmental abnormalities in infants who survive being critically ill (Cong et al, 2017;Fumagalli et al, 2018;Smith et al, 2011).…”

Early Intervention in preterm infants modulates LINE-1 promoter methylation and neurodevelopment

“…In addition, we demonstrate how the proposed early intervention strategy positively modulates short-term infants' neurodevelopment. In this regard, it is already reported that maternal separation and excessive sensory exposure, induced by NICU environment, represent adverse early life events experienced by preterm infants, that can affect the epigenetic regulation and impact on gene expression in the brain (56)(57)(58).…”