What a woman eats when she is pregnant can affect her child’s risk of obesity, regardless of how fat or thin she is, and what her baby weighs at birth, according to a new study published in the journal Diabetes recently.

The British Heart Foundation said the study provides strong evidence of the need to help women of child-bearing age follow a healthy lifestyle and diet.

Led by Southampton University in the UK, and including members from New Zealand and Singapore, the international team of researchers found that a process called epigenetic change alters the function of an unborn baby’s DNA in response to changes in the mother’s diet.

These changes can be detected by sampling the umbilical cord at birth for “epigenetic markers” of obesity risk.

Using these epigenetic markers, the researchers were surprised to find they could predict 25% of the variation of fatness in the 300 children when they reached the age of 6 or 9 years.

The children were born to mothers who had participated in two longitudinal studies based in Southampton.

Previous studies on animals had already shown that the mother’s diet in pregnancy affects offsprings’ body composition, and results in epigenetic changes in genes that control metabolic processes, but until this study, it was not clear whether this also happened in humans.

Study leader Keith Godfrey, Professor of Epidemiology and Human Development at the University of Southampton, told the press this was the first time a study has shown that it is not just genes and lifestyle that affects our risk of obesity, but also what happens while we grow in our mother’s womb, including what she ate.

“A mother’s nutrition while pregnant can cause important epigenetic changes that contribute to her offspring’s risk of obesity during childhood,” said Godfrey.

Epigenetic changes, which affect how DNA is expressed without actually changing the coding sequences passed down to the child from its biological parents, also influence how our bodies respond to lifestyle factors like diet and exercise.

For example, epigenetic changes can affect how DNA instructions are interpreted in the creation of cells, proteins and other building blocks in the body.

One process that changes the expression of DNA is methylation, and the researchers in this study scanned the methylation status of 68 locations (called CpGs 5′) on 5 candidate genes in the umbilical cord tissue DNA of the children at birth.

They replicated the results with a second independent cohort.

For the study, the researchers used childhood adiposity or amount of fat mass as a measure of obesity rather than BMI.

They found that the epigenetic markers explained at least 25% of the variance in childhood adiposity or fatness, and in the first cohort, methylation of a gene called RXRA and another called eNOS were independently linked to childhood fat mass.

They also found that higher methylation of RXRA, but not of eNOS, was linked to lower intake of maternal carbohydrate in pregnancy.

However, in the second cohort, eNOS methylation was not linked to childhood fat mass, but RXRA was.

Godfrey said their study shows the importance of targeting the mother’s diet and the development of her unborn child, as a way to prevent childhood obesity.

“These powerful new epigenetic measurements might prove useful in monitoring the health of the child,” he urged.

Co-author Mark Hanson, British Heart Foundation Professor and Director of the University of Southampton’s Human Development and Health Unit, said the study results were “compelling evidence that epigenetic changes, at least in part, explain the link between a poor start to life and later disease risk”.

He agreed that it strengthened the case for helping women of reproductive age to improve their nutrition, education and lifestyle, to ensure the health of the next generation, and “reduce the risk of the conditions such as diabetes and heart disease which often follow obesity”.

Most of the funds for the study came from the UK Medical Research Council (MRC), the National Institute for Health Research, WellChild (previously Children Nationwide), Arthritis Research UK and the University of Southampton.

Speaking for one of the sponsors, Professor Cyrus Cooper, who directs the MRC Lifecourse Epidemiology Unit, said population studies by the MRC have shown that factors in early life can affect risk of disease many years later.

“Now we can begin to see the mechanisms by which this happens, opening up new avenues for medical research and interventions,” he added.

“Epigenetic Gene Promoter Methylation at Birth Is Associated With Child’s Later Adiposity.”
Keith M. Godfrey, Allan Sheppard, Peter D. Gluckman, Karen A. Lillycrop, Graham C. Burdge, Cameron McLean, Joanne Rodford, Joanne L. Slater-Jefferies, Emma Garratt, Sarah R. Crozier, B. Starling Emerald, Catharine R. Gale, Hazel M. Inskip, Cyrus Cooper, and Mark A. Hanson.
Diabetes published online ahead of print 6 April 2011

Source: University of Southampton (press release 18 Apr 2011), BHF (press statement, 19 Apr 2011).

Written by: Catharine Paddock, PhD