WEDNESDAY, July 4, 2018 -- Investigators say they've found an unanticipated but welcome twist in a decades-long effort to reduce birth defects by boosting folate levels among pregnant women.
Beyond protecting against serious defects such as spina bifida, fortifying the grain supply with folic acid may also enhance fetal brain development and lower the long-term risk for developing psychosis, a new study suggests.
Psychosis is typically characterized by paranoia, social withdrawal and hallucinations.
"Folate is a B vitamin that is important for a host of biochemical processes in the body, from making and repairing DNA to controlling how and when genes are turned on/off," said study corresponding author Dr. Joshua Roffman.
He's an associate professor of psychiatry at Harvard Medical School and co-director of psychiatric neuroimaging at Massachusetts General Hospital in Boston.
"Because the body cannot synthesize it, it must be consumed either from natural sources -- like leafy green vegetables -- or in a synthetic form [folic acid]," Roffman said.
In the 1980s, low folate levels in pregnant women were linked to a higher risk for disabling, sometimes fatal neural tube disorders that affect the spinal cord, including spina bifida. This is when the spinal column fails to form a complete circle around the spinal cord.
That led to a 1996 decision to fortify grain with folic acid and a recommendation for all women of childbearing age to take a daily supplement containing at least 400 micrograms of folic acid. Together, the moves led to a significant drop in neural tube defects.
"What we and others are showing is that prenatal folic acid may also confer protection against severe mental illness in youth, which was not anticipated," Roffman said. "And there are no guidelines as of yet for minimum dosage that could effectively help prevent these disorders."
The researchers noted that half of all pregnancies in the United States are unplanned, and that neural tube defects occur before a woman may even know she's expecting.
For the current study, Roffman and his team reviewed 1,400 MRI brain scans of children aged 2 to 18 who were born before or after folic acid fortification began. All had been patients at Massachusetts General or participants in one of two major health studies.
Children born after fortification went into effect were found in the study to have had significantly thicker brain tissue than those born earlier.
The fortified group also had delayed thinning of the cerebral cortex in regions linked to schizophrenia risk. Over time such thinning is normal, the team noted. But early thinning has been linked to an increased risk for autism and psychosis.
In turn, psychiatric data for participants in one of the major health studies showed that children exposed to fortification in the womb ended up with a far lower risk for future psychosis.
Roffman described the observations as "the first biological support" for a link between folate and reduced mental health risk. But the research only found an association, and he said more work is needed to prove cause and effect.
The findings were published in the July 3 online edition of JAMA Psychiatry.
Dr. Tomas Paus is a senior scientist with the Rotman Research Institute at the University of Toronto. He wrote an editorial accompanying the study, and had reservations about the findings.
Paus said he would expect that folate mainly affects the brain's early growth and that brain size develops early on. As such, he expressed surprise that the study team focused on how folic acid might affect cortical thickness and not brain surface size.
"There are not so many changes in surface area after birth. But cortical thickness is different, in that there are many changes after birth," he said. "So I'm somewhat skeptical about the findings, and I would like to see more data."
Paus said the findings should not affect current recommendations for folic acid food fortification or supplementation.
"We know that in terms of neural tube risk the current recommendations are highly effective, and I see no reason that this paper would change anything," he said.
Learn more about U.S. recommendations for folic acid at the U.S. Centers for Disease Control and Prevention.
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