Title:Preterm Birth and the Risk of Neurodevelopmental Disorders - Is There a Role for Epigenetic Dysregulation?
Volume: 19
Issue: 7
Author(s): Eamon Fitzgerald, James P. Boardman and Amanda J. Drake*
Affiliation:
- University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, The Queen`s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ,United Kingdom
Keywords:
Preterm birth, Neurodevelopmental disorders, Epigenetic, DNA methylation, Epigenetic dysregulation,
α-ketoglutarate dependent dioxygenase.
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.