Premature Birth Can Leave Epigenetic Marks on Child’s DNA

According to the World Health Organization (WHO), the annual figure for preterm births is 15 million babies, which is somewhere in between 5% and 10% of all births worldwide. These babies are born before 37 weeks’ gestation, and are known to be at higher risk for health complications at birth that include: respiratory issues, eye problems, and even neurodevelopmental disorders.

But what are the specific molecular mechanisms that drive these health problems? After all, once born, premature babies are given everything they need not just to survive, but to grow and thrive. What is stopping them from healthy development outside of the womb?

This is a big enough question that the Pregnancy and Childhood Epigenetics (PACE) consortium worked to try to find an answer. Turns out, that answer might lie within field of epigenetics.

What did the study methods entail?

The data and findings from 26 different studies and a grand total of 11,000 participants were combined into this one study. DNA methylation levels were assessed in newborn DNA as well as at different time points throughout childhood and into adolescence. Complex data analyses were performed to examine specific cohorts at particular time periods, as well as to perform longitudinal studies wherever the data were available.

In particular, researchers were looking for differentially methylated regions (DMRs) as well as CpGs, or cytosines followed by guanines since these cytosines are top candidates for methylation.

Findings show evidence of differential methylation in preterm babies

Based on the results of their analyses, the research team found that DNA methylation at many specific CpG sites as well as DMRs showed variability based on the individual’s gestational age at birth. The CpGs noted have associations with known pathways that contribute to specific diseases, and so further study might show how gestation age sets the stage for the development of disease. Similarly and perhaps less surprisingly, many of these CpG sites were tied to fetal development; however, documenting and quantifying these patterns is still critical as researchers work to piece together the origins of disease—and potential ways to intervene, whether for treatment or even prevention. More research is also needed to clarify if these methylation changes are echoed across different tissues over the course of development.

Another interesting finding was that the methylation of DNA in the blood changed over time at most CpG sites, at least from birth through after children began school. It has been established that the rates of epigenetic change have overall stabilized by adulthood.

Greater Access for Research On Epigenetics of Gestation Age and Development

Because of the volume of data points analyzed as part of this study, the PACE consortium has assembled a catalog of changes that can now be leveraged as a jump-off point for further study by other teams. These findings are particularly helpful for anyone trying to clarify the starting points in development for what eventually becomes adult disease. This catalog can help facilitate this data access to more research groups around the world, which is a powerful—and commendable—leadership step to take, both on behalf of research as well as for the community.

Context is everything, and it’s no different in the case of epigenetics research. These findings present a large-scale frame of reference for comparing epigenetic findings at other timepoints over the course of an individual’s life. By comparing to the trends observed in the PACE data, scientists might be able to gain further clarity on what factors make epigenetic changes slow down or persist, as well as facilitate a better understanding of the role an individual’s environment plays on their development.

“Now we need to investigate whether the DNA changes are linked to the health problems of those born prematurely,” notes Erik Melén, a professor at the Department of Clinical Science and Education, at Södersjukhuset, a hospital in Stockholm, Sweden. “We hope that our new findings will contribute valuable knowledge about fetal development, and in the long term new opportunities for better care of premature babies to avoid complications and adverse health effects.”

Source:  Merid, S.K et al. (2020) “Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age Clinical Epigenetics 12. 25.

Reference: Karolinska Institutet “Length of pregnancy alters the child’s DNA” Karolinska Institutet News. 02 Mar. 2020. Web.