More about Prenatal Folic Acid and Autism

Tuesday, March 12, 2013 View Comments

Posted by Alycia Halladay, PhD, Autism Speaks senior director of environmental and clinical sciences and Jill James, PhD. Dr. James is a member of Autism Speaks Treatment Advisory Board, which reviews proposals for treatment studies. She is also a researcher with Autism Speaks Autism Intervention Research Network on Physical Health (AIR-P), which is funded by a federal grant to the Autism Speaks Autism Treatment Network (ATN).

Last month, Autism Speaks reported on a study that found reduced risk of autism in Norwegian children whose mothers took folic acid supplements around the time they became pregnant. (See our news story here and the full study here.)

Norway doesn’t require folic acid to be added to food, so prenatal vitamins are the only source of extra folic acid for many pregnant Norwegian women. By contrast, in the United States and Canada, flour and cereal have been fortified with folic acid since 1998.

Therefore, it’s reasonable to wonder whether prenatal folic acid supplements would have a similar effect here. It also raises the question of why autism rates have continued to increase in North America in the years since folic acid fortification of flour and cereals began.

In an editorial accompanying the study, three experts weighed in. They noted that in North America, a woman typically gets around 150 micrograms of folic acid daily from fortified foods. The Norwegian women got considerably more from their prenatal vitamins – 200 to 400 micrograms. These higher levels of folic acid may be important for lowering autism risk.

It’s important to see these results through the lens of “reducing risk,” not guaranteeing that a child won’t develop autism. In a previous blog post, researcher Martha Herbert likened the factors that increase or decrease the risk of autism with water being added to or drained from a bucket. These risk factors can be genetic (inherited) or environmental (nongenetic). When the bucket overflows, the analogy goes, brain development tips over into autism.

Prenatal folic acid supplements are an example of an environmental factor that may reduce autism risk. Using Dr. Herbert’s analogy, they remove water from the allegorical autism-risk bucket. While folic acid supplements may help drain the bucket, the volume of factors that increase a given child’s propensity for autism can still prove overwhelming. In other words, folic acid alone can’t prevent every child from developing autism. While folic acid may address some genetic and environmental factors, there may be others unaffected by folic acid supplementation.

It’s worth noting that, last year, researchers found a similar reduction in autism risk among the children of mothers who took prenatal vitamins before and after becoming pregnant. (Read more about that study here.) In the United States, prenatal vitamins typically contain 400 to 800 micrograms of folic acid. This suggests that the protective effect of prenatal vitamins with folic acid may indeed apply to American mothers. 

The experts who wrote the editorial on the Norwegian study made another important point. It didn’t analyze other factors that might influence how folic acid affects autism risk. A number of studies have suggested that the reduced autism risk associated with prenatal folic acid may pertain primarily to women and children with particular genetic risk factors. For example, certain genetic mutations appear to increase the requirement for folic acid in people who get too little folate (the natural form of folic acid) in their diets. Folate “deficiency” can likewise show up in individuals with gene mutations that interfere with how the body processes folate. 

Genetic testing is one way for women to find out if they’re at risk for folate deficiency. A less expensive approach may be a simple blood test: Elevated blood homocysteine is a clear indicator of problems in the way the body processes folate. In a recent study of mothers of children with autism, one of us (Jill James) found significant elevation in postnatal homocysteine levels associated with mutations in an important folate carrier gene. The good news is that elevated homocysteine levels are easily corrected with vitamin supplements that include folic acid.  

Bottom line: Taking prenatal vitamins before and after conception is an inexpensive and safe way to protect against a number of serious developmental disorders. The best known of these is neural tube defects. If you’d prefer not to take such supplements unless necessary, consider homocysteine testing as a potential indicator of their need. We encourage women who may become pregnant to discuss taking prenatal vitamins with their physicians.

Got more questions? Send them to GotQuestions@autismspeaks.org. Subscribe to Autism Speaks Science Digest to get all our science blogs and autism research news delivered to your inbox.