Mother's diet, genes raise birth defect risk in mice

Mothers who eat a high fat diet before and during pregnancy may be putting their offspring at risk of birth defects, scientists said on Tuesday.

British researchers studying mice found that a pregnant mother's diet may interact with the genes her unborn baby inherits and influence the type or severity of birth defects such as congenital heart disease and cleft palate.

"These are very important findings as we have been able to show for the first time that gene-environment interactions can affect development of the embryo in the womb," said Jamie Bentham of the Wellcome Trust Center for Human Genetics at the Oxford University, who led the study.

"We know that poor diet and defective genes can both affect development, but here we have seen the two combine to cause a much greater risk of developing health problems and more severe problems. We are excited by this as it suggests that congenital heart defects may be preventable by measures such as altering maternal diet," he said in a statement about the findings.

Congenital heart disease is the most common form of birth defect, and previous studies have shown that children born to mothers who have diabetes or who are overweight have an increased risk of it.

It is also known that certain genetic changes - such as deficiency in Cited2 - can give rise to congenital heart disease, but until now scientists did not know if external factors such as a mother's diet could interact with genetic changes to affect their babies.

The British researchers, whose findings were published in the journal Human Molecular Genetics, compared healthy mice with those lacking a gene called Cited2.

Cited2 deficiency results in heart defects in mice and in humans and can also lead to a serious type of heart defect called atrial isomerism, where the left-right asymmetry of the heart is disturbed.

Researchers fed the mice a high fat diet before and during pregnancy and then studied the development of their babies using magnetic resonance imaging. The results were compared to mice from a second group who were fed a balanced diet.

Among offspring mice that were deficient in Cited2, the risk of atrial isomerism more than doubled, the researchers found, and the risk of cleft palate increased more than seven-fold when the mothers were fed a high fat diet.

The changes did not happen in the genetically normal offspring of mothers who had a high fat diet, suggesting that it is the combination of high fat diet and the genetic defect that is responsible, they said.

Jeremy Pearson, associate medical director of the British Heart Foundation charity, which part-funded the study, said the findings could shed light on human birth defects.

"This research shows that diet during pregnancy can directly affect which genes get switched on in unborn offspring. The study was with mice, but a similar link may exist in humans, leading to some cases of congenital heart disease."