Very Preterm Birth is Associated with PLAGL1 Gene Hypomethylation at Birth and Discharge

Livio Provenzi,Rosario Montirosso,Silvana Beri,Andrea Citterio,Renato Borgatti,Francesco Morandi,Sharon Casavant,Amy D'Agata,Fabio Mosca,Pietro De Carli,Monica Fumagalli,Roberto Giorda

doi:10.2217/epi-2017-0123

Abstract

Recent findings show that DNA methylation is susceptible to very preterm (VPT) birth and to the experience of the early stay in the neonatal intensive care unit. The aim of the study was to compare PLAGL1 methylation between VPT and full-term (FT) infants at birth as well as between VPT infants at discharge and FT infants at birth. DNA was collected from cord blood of 56 VPT and 27FT infants at birth and from peripheral blood in VPT infants at neonatal intensive care unit discharge. Sociodemographic and neonatal variables were considered. PLAGL1 methylation at birth and at discharge were highly correlated in VPT infants. Lower methylation emerged in VPT infants at birth and discharge compared to FT counterparts. PLAGL1 hypomethylation emerged as a potential epigenetic mark of VPT birth. Future research is warranted to assess the functional consequences of PLAGL1 diminished methylation in VPT infants' development.

Highlights

Even in the absence of severe comorbidities, very preterm (VPT) infants need long-lasting hospitalization in the Neonatal Intensive Care Units (NICU) [1] and are at risk for altered socio-emotional development [2]
We extended previous research assessing the potential links between SLC6A4 CpG-specific methylation and brain volumes at term equivalent age (TEA)
The goodness of the model was assessed separately for each region of interest (ROI) according to: non-significant chisquare statistic; comparative fit index (CFI) and Tucker-Lewis index (TLI) close to .95 [34]; Root Mean Squared Error of Approximation (RMSEA) smaller than .05; Square Residual Root Mean (SRMR) smaller than .08 [35]; non-significant p value associated with the CI of RMSEA [36]

Summary

Introduction

Even in the absence of severe comorbidities, very preterm (VPT) infants (gestational age at birth < 32 weeks) need long-lasting hospitalization in the Neonatal Intensive Care Units (NICU) [1] and are at risk for altered socio-emotional development [2]. During NICU stay, VPT infants are exposed to life-saving yet invasive interventions including mechanical ventilation and painful skin-breaking procedures These sources of NICU-related stress have been found to contribute to VPTs’ socio-emotional development during infancy [3, 4] and childhood [5, 6]. Using data from a longitudinal research study, we examined potential links between early NICU stress exposure and socio-emotional development at 12 months corrected age (CA) in VPT children, assessing both epigenetic variations (i.e., serotonin transporter gene (SLC6A4) methylation [9]) and brain growth (i.e., anterior temporal lobe volume [10, 11]). Through a path analysis, we speculatively tested the hypothesis that an altered ATL volume might mediate the association between early NICU-related SLC6A4 epigenetic alterations (i.e., increased CpG methylation) and socio-emotional development at 12 months CA

Participants

Procedures

Results

Discussion