AUTHOR=Provenzi Livio , Fumagalli Monica , Sirgiovanni Ida , Giorda Roberto , Pozzoli Uberto , Morandi Francesco , Beri Silvana , Menozzi Giorgia , Mosca Fabio , Borgatti Renato , Montirosso Rosario 

TITLE=Pain-related stress during the Neonatal Intensive Care Unit stay and SLC6A4 methylation in very preterm infants

JOURNAL=Frontiers in Behavioral Neuroscience

VOLUME=9

YEAR=2015

URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2015.00099

DOI=10.3389/fnbeh.2015.00099

ISSN=1662-5153

ABSTRACT=<p>Very preterm (VPT) infants need long-lasting hospitalization in the Neonatal Intensive Care Unit (NICU) during which they are daily exposed to pain-related stress. Alterations of DNA methylation at the promoter region of the <italic>SLC6A4</italic> have been associated with early adverse experiences in infants. The main aim of the present work was to investigate the association between level of exposure to pain-related stress during hospitalization and changes in <italic>SLC6A4</italic> DNA methylation at NICU discharge in VPT infants. In order to exclude the potential effect of birth status (i.e., preterm vs. full-term birth) on <italic>SLC6A4</italic> methylation, we preliminarily assessed <italic>SLC6A4</italic> epigenetic differences between VPT and full-term (FT) infants at birth. Fifty-six VPT and thirty-two FT infants participated in the study. The level of exposure to pain-related stress was quantified on the basis of the amount of skin-breaking procedures to which they were exposed. VPT infants were divided in two sub-groups: <italic>low-pain exposure</italic> (LPE, <italic>N</italic> = 25) and <italic>high-pain exposure</italic> (HPE, <italic>N</italic> = 31). DNA methylation was evaluated at birth for both VPT and FT infants, assessing 20 CpG sites within the <italic>SLC6A4</italic> promoter region. The same CpG sites were re-evaluated for variations in DNA methylation at NICU discharge in LPE and HPE VPT infants. No differences in <italic>SLC6A4</italic> CpG sites' methylation emerged between FT and VPT infants at birth. Methylation at CpG sites 5 and 6 significantly increased from birth to NICU discharge only for HPE VPT infants. Findings show that preterm birth <italic>per se</italic> is not associated with epigenetic alterations of the <italic>SLC6A4</italic>, whereas higher levels of pain-related stress exposure during NICU stay might alter the transcriptional functionality of the serotonin transporter gene.</p>