Does preterm birth leave behind an epigenetic legacy?

Posted by Biome on 26th November 2013 - 0 Comments


Preterm birth is on the rise in most countries, as recently reported by the World Health Organisation in their ‘Born too soon’ report, and discussed in the ‘Born too soon’ supplement in Reproductive Health. The impact of preterm birth on long-term health is well known and includes cerebral palsy, intellectual impairment, chronic lung disease, and vision and hearing loss. However far less is known about the epigenetic effects of being born before 37 weeks of gestation. Jeffrey Craig from the Murdoch Childrens Research Institute, Australia, and colleagues examine epigenetic changes in survivors of preterm birth in their recent study published in Genome Medicine. Craig explains more about their novel findings on the epigenetic differences between term and preterm births, as well as the long lasting effects that preterm birth may have on the epigenome.

 

What interested you in characterising epigenetic changes through human development, and specifically in context of preterm birth?

What interests us is how plastic the epigenome is in early life, to what extent does it change during aging and how susceptible it is to environmental insults. Preterm birth is generally associated with a variety of specific environmental insults including maternal infection. Also, preterm babies are exposed to the external environment at stages of development when many organs, such as the lungs, are immature and not yet adapted to life outside the insulated environment of the womb.

 

What would you say are the most interesting findings of your study? Did any of the findings surprise you?

We found preliminary evidence that preterm birth leaves a long-lasting legacy on the epigenome. This wasn’t such a surprise when you consider previous findings of long-term effects of the early environment but nevertheless, is the first time that anyone has shown this for preterm birth. What surprised us was that we found evidence that DNA methylation doesn’t simply ‘drift’ with age. If we assume that the epigenomes of the terms and preterms in our study are representative of their respective gestational ages, our data supports the idea that the direction of change of methylation may change somewhere along the lifecourse between mid to late gestation and 18 years of age. We think this may reflect blood cell function during early neonatal life.

 

Your study showed loci involved in the immune system in particular differed between birth and 18 years of age. What are the implications of this finding on long-term health and preterm births?

Our results actually showed that genes involved in immune regulation were epigenetically dynamic during gestation and also during aging. It is possible that environmental perturbations, such as drug treatments for preterm infants, can alter the trajectory of these epigenetic changes during the life course. Therefore, alterations to the rate of change of methylation during aging may play a role in development of the immune system. With respect to stable methylation differences between preterm and term individuals, we found ten potentially persistent methylation variants, however these were not necessarily related to immune function. These genes were involved in development, cognition and metabolism.

 

Your study characterised epigenetic patterns at birth and at 18 years of age in individuals born at term or preterm. What could examining intermittent changes during this time period tell us?

I think that adding in intermediate timepoints would be able to answer further questions such as whether children born preterm ‘catch up’ epigenetically with those born at term and whether epigenetic change accelerates apace with developmental change during puberty. Furthermore, it would be great to investigate whether epigenetic signatures at birth would predict health outcomes at age 18 and the extent to which existing interventions alter epigenetic state.

 

How do you think your findings and similar studies will influence clinical practice in the future?

We would like to see a time where an infant’s epigenetic and genetic status were integrated to provide information on disease risk, providing both medical professionals and parents the chance to reverse some of these risks via interventions that reverse risk-associated epigenetic marks.

 

What is next for your research?

Our plans are to study the full cohort of over 200 children and search for risk-associated epigenetic marks at birth. We would also like to validate our findings in collaboration with similar human cohorts and with animal models of preterm birth.

 

More about the author(s)

Jeffery Craig, Group leader, Murdoch Childrens Research Institute, Australia.

Jeffrey Craig obtained his PhD in the field of molecular cytogenetics where he studied the structure-function relationships within chromosome banding patterns. He pursued his postdoctoral training in Germany, Scotland and finally the Murdoch Childrens Research Institute, Australia where he went on to establish the Developmental Epigenetics Group with Richard Saffery in 2006. The group focused on epigenetics in gestation, childhood and adolescence, and has investigated childhood leukaemia and prematurity, as well as being involved in the Peri/Postnatal Epigenetic Twins Study (PETS) cohort. In 2011 Craig established the Early Life Epigenetics group within Murdoch Childrens Research Institute, with a focus on epigenetic changes associated with early development, and the link between environmental factors, development and disease. The PETS project remains a central focus of Craig’s research.

Research

Analysis of epigenetic changes in survivors of preterm birth reveals the effect of gestational age and evidence for a long term legacy

Cruickshank MN, Oshlack A, Theda C, Davis PG, Martino D, Sheehan P, Dai Y, Saffery R et al.
Genome Medicine 2013, 5:96

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