Skeptics question study suggesting folate link to autism – Outside experts call for caution

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MIAMI, May 12, (Agencies): Skeptics were quick to urge caution Wednesday about US research that suggested too much of an important B vitamin, folate, in pregnancy may raise the risk of autism.

The findings were presented at a conference in Baltimore, Maryland by researchers at Johns Hopkins Bloomberg School of Public Health, and have not yet been published or peer-reviewed.

Some experts dismissed the claims as “irresponsible”, unlikely to be replicated, and showing perhaps a correlation, but not a cause and effect.

“On the basis of their data, which has not been peer-reviewed, the authors are going way out on a limb,” said Max Davie of Royal College of Paediatrics and Child Health, who was not involved in the study.

Davie added that the researchers “are being quite irresponsible in undermining decades of public health work to increase the numbers of women taking folate before and during pregnancy, in order to prevent potentially devastating neurological conditions.”

Folate is a B vitamin that is naturally present in fruits and vegetables. A synthetic version, folic acid, is commonly used to fortify cereals and breads, and is contained in vitamin supplements.

When pregnant women do not get enough folate, their babies face a higher risk of brain and spinal cord defects.

The study tracked 1,391 mothers and their children from the Boston Birth Cohort, a predominantly low-income minority population.

The mothers’ blood folate was checked once only, and that measurement was taken within the first one to three days of delivery.

Mothers with very high folate right after giving birth faced twice the risk that the child would develop an autism spectrum disorder.

Women with high vitamin B12 levels saw triple the risk of autism in their offspring.

If both levels were extremely high, the risk that a child would develop the disorder increased 17.6 times, according to the research presented at the 2016 International Meeting for Autism Research in Baltimore.

“This could be the case of too much of a good thing,” lead author Ramkripa Raghavan, a researcher at Johns Hopkins, said in a statement released ahead of the presentation.


“We tell women to be sure to get folate early in pregnancy. What we need to figure out now is whether there should be additional recommendations about just what an optimal dose is throughout pregnancy.”

Most of the mothers reported taking prenatal vitamin supplements.

Very few — one in 10 — had what researchers consider an excessive amount of folate in their blood, or more than 59 nanomoles per liter.

Six percent had an excess amount of vitamin B12 (more than 600 picomoles per liter).

The World Health Organization says the adequate amount of folate for a woman in her first trimester of pregnancy is between 13.5 and 45.3 nanomoles. Ideal vitamin B12 levels are not well established.

Outside experts cautioned that the study measured folate at birth, while the crucial window for supplementation to prevent neural tube defects such as spina bifida is in the first weeks and months of pregnancy.

“This research does not suggest any harmful effects of recommended folate supplements taken in early pregnancy which are beneficial,” said Andrew Shennan, a professor of obstetrics at King’s College London.

“Women should continue to take these,” added Shennan, who was not involved in the study.

James Cusack, research director at Autistica, agreed.

“Although this finding is striking, it is vital to remember that this research is at a very early stage. In fact, this information has simply come from a single poster at a conference,” Cusack said.

“It is far too early to say whether this finding is correct and so families should not be overly concerned.”

Craig Newschaffer, professor at the Drexel University School of Public Health, said the research calls for a better understanding of the role of folate throughout pregnancy.

“The role of folic acid supplementation in neurodevelopment may be quite complex,” he said.

About one in four women in the United States do not get enough folate in pregnancy, according to the US Centers for Disease Control and Prevention.

Autism spectrum disorder is a neurodevelopmental condition that affects as many as one in 68 children in the United States.


Its causes remain poorly understood, but researchers say it is likely a result of some combination of genetic and environmental factors.

Other research points to an opposite relationship between folic acid and autism, showing that adequate amounts of the vitamin at the time of conception can significantly reduce the risk.

Indeed, some experts raised questions about the new research. They note the findings are preliminary numbers, and based on a small number of families seen at only one hospital.

Also, the analysis is based on measures of the vitamin in mothers’ blood at the time of delivery, which may not reveal much about what was going on in the women’s body at the time of early fetal brain development.

Even the researchers themselves said there’s no cause to change current public health recommendations. “We are not suggesting anyone stop supplementation,” said one of the researchers, M. Daniele Fallin of Johns Hopkins University’s school of public health.

But it raises an intriguing question that should be explored in other research, Fallin said. Two outside experts agreed.

“It’s a finding that has plausibility,” said Dr Ezra Susser, a Columbia University professor of epidemiology and psychiatry. He said other researchers have wondered whether too much folic acid can cause problems.

Decades ago, researchers found certain levels of folic acid could prevent major birth defects of the baby’s brain and spine. In the early 1990s, US health officials began recommending that all women who might become pregnant should take 400 micrograms of folic acid daily. And in the late 1990s, federal regulations began mandating that folic acid be added to flour, bread and other grain products.

Those steps are considered one of the great public health success stories of the last half-century. Officials estimate that 1,000 birth defects are prevented each year because of it.

The new researchers followed 1,391 children who were born at Boston University Medical Center in 1998 through 2013. About 100 of them were later diagnosed with an autism spectrum disorder.

The researchers went back and looked at levels of folate and vitamin B12 in the blood of the children’s mothers at the time of childbirth. They found that 16 of them had very high levels of folate, and 15 had extremely high levels of vitamin B12.

Those are very small numbers of cases. But they represent significantly higher proportions than were seen in moms whose children who didn’t develop autism.

If both levels are extremely high, there is more than a 17-fold greater risk that a child will develop autism, the researchers said.

Most of the moms in the study said they took multivitamins — which would include folic acid and vitamin B12 — throughout their pregnancy. But the researchers say they don’t know why some women had such high levels in their blood.

It may be related to taking too many supplements and eating too many fortified foods. Or there could be a genetic reason that caused some women to absorb more folate than others. Or there could be a combination, they said.

Many studies of autism focus largely on white children in middle- and upper-income families. This one drew mainly from low-income and minority families, the researchers noted.




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