Birthweight is associated with health outcomes throughout life. For example, children who are born heavier or lighter than average have a higher risk of developing diabetes and cardiovascular diseases. A new large study reveals that epigenetics is closely associated with children’s birthweight.
A major international research project has now shown that birthweight is closely associated with epigenetic alterations in the child’s DNA. As the fetus develops, specific epigenetic molecules switch genes on and off, making them accessible or inaccessible to the molecular machinery of cells. This influences the weight of newborn babies.
This new large meta-analysis included almost 1000 children in Denmark from the Danish National Birth Cohort (Better Health in Generations).
”The study has been designed to be large to enable the researchers to see the statistical links that are not visible in smaller studies because epigenetics varies randomly between humans. Carrying out such a large study can provide greater insight into the molecular biological mechanisms that link birthweight with possible influences on the fetus through the mother, such as smoking, which changes birthweight,” explains a Danish contributor to the international research project, Thorkild I.A. Sørensen, Professor, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.
The study was published recently in Nature Communications.
Small molecules alter DNA
The international study included 8825 newborns from 24 cohorts in the Pregnancy and Childhood Epigenetics Consortium. The researchers studied the DNA in blood samples taken from the umbilical cords of newborns to map where the methyl groups are located in the newborn child’s DNA.
Methyl groups are small molecules that attach themselves to DNA at sites at which cytosine-guanine base pairs are present. The genome has millions of these, and the methyl groups bind to cytosine, thereby changing the opportunities the cells’ molecular machinery has to decode the DNA. This often means that genes are silenced.
As the fetus develops, epigenetic alterations constantly switch various genes on and off to very precisely orchestrate the formation of the fetus. The result, if all goes well, is that the fetus grows and develops the various organs, tissues and brain in a very predictable pattern that ultimately results in the birth of a healthy child.
Epigenetic differences and variation in birthweight
The new study shows that DNA methylations are associated with differences in children’s birthweight at 914 sites in the genome.
The more methylations the fetus has at any of these 914 sites on the genome, the greater the average birthweight. Conversely, average birthweight is lower if there are more methylations elsewhere in the genome.
The researchers deduced that a 10% decrease or increase in the degree of methylation is associated with a birthweight difference of between 183 grams lower and 178 grams higher than average.
“The DNA activity during fetal development influences a child’s birthweight, and epigenetics plays a role. We can therefore link the activity at the 914 sites in the genome with their birthweight,” says Thorkild I.A. Sørensen.
Understanding fetal development better
Thorkild I.A. Sørensen explains that the study goes deeper towards understanding what happens at the DNA level as the fetus develops.
Once the researchers have obtained an overview of how activating or deactivating various genes influences birthweight, they hope that this will enable them to understand the risk of developing numerous chronic diseases and perhaps reduce the risk of later disease at this early stage in life.
“In the long term, we can improve our understanding of how fetal development affects children’s health for the rest of their lives. One example might be that, in the future, we hope to see which genes are switched on and off as the fetus develops for a child who later develops asthma, obesity, diabetes or another disease. In addition to the genetic differences between people, this is the overall key to the differences between us,” says Thorkild I. A. Sørensen.
Smoking alters the methylation of DNA
The big question is: what affects the epigenetics of a fetus?
The more researchers understand how epigenetics affects children’s risk of being born overweight and their risk of developing various diseases, the better they can also understand how environmental factors influence epigenetic alterations and cause problems.
Smoking is one example.
Everyone knows that smoking is unhealthy for mothers but especially for their unborn children, who end up with a lower birthweight. Pregnant women should therefore definitely not smoke.
Research has already shown that a mother’s smoking during pregnancy changes the methylation of the child’s DNA, and this is probably why children whose mothers smoke are at increased risk of being born underweight.
”Many environmental factors influence the epigenetics of the fetus, and smoking is just one. Obesity is another, but exercise, alcohol consumption, eating habits and various chemicals can also affect the activity of various genes as the fetus develops. We have much more to discover,” says Thorkild I.A. Sørensen.
This new study is a meta-analysis of data from 24 birth cohorts. One was the Danish National Birth Cohort, which included 100,000 pregnant women, with blood samples being taken from the umbilical cords of the newborns of about 60% of these women. The international study included almost 1000 children from the Danish National Birth Cohort.
In addition to Denmark, Norway was a major contributor to the study, with three cohorts totalling almost 2000 children.
“Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight” has been published in Nature Communications. Researchers from the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen contributed to the study.
