Extreme folate levels in pregnancy linked to infant heart disease risk

Their findings suggested a link between low serum folate levels during pregnancy and an increased CHD risk in offspring.

They also found that excessively high levels of folate were associated with an elevated CHD risk, raising concerns over current recommendations governing folate supplementation and mandatory folic acid fortification in foods.

“Our findings of a potential U-shaped association between maternal folate levels during pregnancy and offspring CHD risk highlighted that excessive folate may not confer additional benefits and could potentially have adverse effects,” the authors, based in China and the US, wrote.

“Thus, the previous one-size-fits-all model of folate supplementation and fortification should be reconsidered with caution.”

Association most apparent during early to mid-pregnancy

The investigation, which appears in the journal JAMA Network Open, enrolled 129 CHD cases. A U-shaped association between maternal serum folate levels and CHD risk in offspring was identified at the early to mid-pregnancy stage.

Compared to the offspring in the second and third quartiles of maternal folate, those in the lowest and highest quartiles had increased odds of CHD.

Further analysis suggested that the adverse associations between low and high maternal folate and CHD risk might be magnified by vitamin B12 deficiency or elevated homocysteine.

“Both folate and vitamin B12 are needed to convert homocysteine to methionine; deficiencies in either can lead to elevated homocysteine levels, increasing CHD risk,” the authors wrote.

“Understanding their role in CHD causes will inform preventive nutritional strategies during pregnancy.”

Folate supplementation and mandatory folic acid fortification in foods across the globe

With widespread recommendations for folate supplementation and mandatory folic acid fortification in foods, folate intake among women of childbearing age has increased globally.

In 1998, the US Food and Drug Administration (FDA) mandated that folic acid be added to the country’s food supply of bread, cereals, flour, pasta, and rice.

The US Centers for Disease Control and Prevention (CDC) also recommends that all women of childbearing age take 400 micrograms (mcg) of folic acid daily, through diet or supplements.

According to the national public health agency, since fortification, the prevalence of neural tube defects in the US has decreased by around 35%.

In the European Union (EU), folic acid fortification is not mandatory in most countries, although several recommend supplementation for women of childbearing age.

Countries such as Ireland and the Netherlands have implemented voluntary fortification programmes in certain foods.

The European Food Safety Authority (EFSA) suggests 400 mcg of folic acid supplementation daily for women of reproductive age, especially those planning pregnancy.

‘Increasing portion’ of pregnant women take folic acid exceeding advised daily allowance

“Together with the increasing awareness of the importance of folate in the general population, an increasing portion of pregnant women take folic acid exceeding the recommended daily allowance of 0.4 mg or even the tolerable upper intake level of 1 mg per day,” the study’s authors wrote.

However, Dr Erica D Watson, associate professor in reproductive biology at the University of Cambridge, said: “It is important to be responsible when writing about this subject because folic acid supplementation has real benefits to foetal health, and we do not want to scare people off from taking their pregnancy vitamins.

“The study indicates that maternal folic acid supplementation largely benefits the development of the baby’s heart. However, the study also shows that in some cases high folate levels in the mother’s blood was associated with an increased risk of heart defects in the baby.”

Watson added that more research was needed to understand why this is, since it is difficult to predict exactly how much folic acid is too much.

“Genetics, metabolism, diet, and other aspects of the environment of both parents might interact to impact heart development. Importantly, moderate folic acid supplementation likely benefits foetal heart development,” she said.