Neurodevelopmental Outcome and Epigenetic Changes at 2 Years Associated with the Oxygen Load Received upon Postnatal Stabilization: A Pilot Study
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Published on: November 20, 2015
Sheila Lorente-Pozo1, Nuria Boronat2, Anna Parra-Llorca1,2
1Neonatal Research Group, Health Research Institute La Fe, Valencia, Spain.
Insights
High oxygen exposure in preterm infants alters DNA methylation, specifically in the TRAPPC9 gene. This epigenetic change is linked to lower motor scores at two years, suggesting a potential mechanism for neurodevelopmental issues.
Area of Science:
- Neonatal epigenetics
- Developmental neuroscience
Background:
- Postnatal oxygen administration is crucial for preterm infants but can impact the epigenome.
- DNA methylation changes in preterm infants may influence long-term neurodevelopmental outcomes.
Purpose of the Study:
- To investigate the association between DNA methylation modifications and neurodevelopmental outcomes in preterm infants.
- To determine if oxygen load during stabilization affects specific gene methylation patterns.
Main Methods:
- Followed preterm infants until 2 years of age.
- Measured DNA methylation in dried blood spots using MassARRAY technology.
- Assessed neurodevelopmental outcomes using the Bayley-III scale.
Main Results:
- Identified 74 significant CpG sites differentially methylated after birth, with 14 correlating to oxygen load.
- Found significant TRAPPC9 hypermethylation at 2 years in infants receiving a higher oxygen load (>500 mL O2/kg).
- Infants with higher oxygen exposure showed significantly lower motor composite scores.
Conclusions:
- Higher oxygen load in preterm infants is associated with TRAPPC9 hypermethylation and reduced motor function.
- Epigenetic alterations in TRAPPC9 may contribute to neurodevelopmental delays observed in preterm infants.
- Further research with larger cohorts is warranted to confirm these findings.
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.
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