Lorente-Pozo S.a· Boronat N.b· Parra-Llorca A.a,b· Lara-Cantón I.a· Solaz-García A.a· Oltra Soler J.V.c· Busó E.J.d· Casabó-Vallés G.e· García-Giménez J.L.e,f,g· Pallardó F.V.f,g· Vento M.a,b

Author affiliations

aNeonatal Research Group, Health Research Institute La Fe, Valencia, Spain
bDivision of Neonatology, University and Polytechnic Hospital La Fe, Valencia, Spain
cGenetics Unit, University and Polytechnic Hospital La Fe, Valencia, Spain
dCentral Unit for Research in Medicine (UCIM), Faculty of Medicine and Dentistry, University of Valencia-INCLIVA, Valencia, Spain
eEpiDisease S.L. (Spin-off from the Center for Biomedical Network Research, CIBER-ISCIII, Spain), Valencia, Spain
fCIBERER (Health Institute Carlos III, Ministry of Science and Innovation), Valencia, Spain
gDepartment of Physiology, Faculty of Medicine and Dentistry, University of Valencia-INCLIVA, Valencia, Spain

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Article / Publication Details

First-Page Preview

Received: November 08, 2021
Accepted: May 20, 2022
Published online: June 27, 2022

Number of Print Pages: 10
Number of Figures: 4
Number of Tables: 2

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: https://www.karger.com/NEO

Abstract

Introduction: The oxygen load provided to preterm infants during postnatal stabilization caused significant modifications of DNA methylation in the preterm epigenome. We aimed to assess if there was an association between DNA methylation changes and neurodevelopmental outcomes. Methods: Preterm infants were followed until 2 years after birth. Dried blood spots were processed, and DNA methylation was measured using the MassARRAY technology of Sequenom. We selected specific genes that corresponded to differentially methylated CpG sites that correlated with the oxygen load at 2 h after birth. Neurodevelopmental outcome was blindly assessed using Bayley-III scale. Results: Of 32 eligible patients, we completed the methylation analysis in 19 patients and the neurodevelopmental evaluation in 22. Comparison of differential methylation analysis between time 0 (cord blood) and 2 h after birth showed 74 significant CpGs, out of which 14 correlated with the oxygen load received at birth. Out of these 14 genes, only TRAPPC9 showed statistically significant differences at 2 years of age between the infants who received >500 mL versus <500 mL O2/kg. Premature who received >500 mL O2/kg showed significantly lower motor composite scores. Discussion/Conclusions: Premature who received higher oxygen load scored lower motor composite scores and showed a hypermethylation pattern of TRAPPC9 at 2 years of age. TRAPPC9 mutations are associated with neurodevelopmental delay and intellectual disability, so changes in the CpG methylation of this gene and its subsequent expression alteration can produce a similar phenotype. Further studies with a greater sample size are needed to confirm these findings.

© 2022 S. Karger AG, Basel

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First-Page Preview

Received: November 08, 2021
Accepted: May 20, 2022
Published online: June 27, 2022

Number of Print Pages: 10
Number of Figures: 4
Number of Tables: 2

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: https://www.karger.com/NEO

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