Preterm Birth and the Risk of Neurodevelopmental Disorders - Is There a Role for Epigenetic Dysregulation?

Abstract:

:Preterm Birth (PTB) accounts for approximately 11% of all births worldwide each year and is a profound physiological stressor in early life. The burden of neuropsychiatric and developmental impairment is high, with severity and prevalence correlated with gestational age at delivery. PTB is a major risk factor for the development of cerebral palsy, lower educational attainment and deficits in cognitive functioning, and individuals born preterm have higher rates of schizophrenia, autistic spectrum disorder and attention deficit/hyperactivity disorder. Factors such as gestational age at birth, systemic inflammation, respiratory morbidity, sub-optimal nutrition, and genetic vulnerability are associated with poor outcome after preterm birth, but the mechanisms linking these factors to adverse long term outcome are poorly understood. One potential mechanism linking PTB with neurodevelopmental effects is changes in the epigenome. Epigenetic processes can be defined as those leading to altered gene expression in the absence of a change in the underlying DNA sequence and include DNA methylation/hydroxymethylation and histone modifications. Such epigenetic modifications may be susceptible to environmental stimuli, and changes may persist long after the stimulus has ceased, providing a mechanism to explain the long-term consequences of acute exposures in early life. Many factors such as inflammation, fluctuating oxygenation and excitotoxicity which are known factors in PTB related brain injury, have also been implicated in epigenetic dysfunction. In this review, we will discuss the potential role of epigenetic dysregulation in mediating the effects of PTB on neurodevelopmental outcome, with specific emphasis on DNA methylation and the α-ketoglutarate dependent dioxygenase family of enzymes.

journal_name

Curr Genomics

journal_title

Current genomics

authors

Fitzgerald E,Boardman JP,Drake AJ

doi

10.2174/1389202919666171229144807

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

507-521

issue

7

eissn

1389-2029

issn

1875-5488

pii

CG-19-507

journal_volume

19

pub_type

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