It’s only been a few days since Johns Hopkins released the preliminary results of a study on folate levels and autism, and we have already received calls and emails regarding the findings.  Unfortunately the headlines in many of the news articles have been incredibly misleading.  Take for instance, “A Study Asks: Too Much Folic Acid a Cause of Autism?” (Fox News).

Before I discuss the details of the Johns Hopkins study, I want to review why it is so vitally important for reproductive age women to take folate (also called folic acid).

Folic acid is a B-vitamin needed for proper cell growth which is found in many multivitamins, as well as many food sources, such as lentils, dried beans and peas, and dark green vegetables.  Not so surprisingly, many women do not consume diets with adequate amounts of naturally occurring folic acid.  Because folate deficiency in pregnant women has been associated with an increased risk of neural tube defects, including anencephaly and spina bifida, it is recommended that women take folic acid supplements during pregnancy.  It is estimated that by taking these supplements, pregnant women reduce their risk of having a child with a neural tube defect by 50% – 70%.

Since 1998, the Food and Drug Administration (FDA)  has required the addition of folic acid to many enriched breads and cereals in order to increase the amount of folic acid in our diets.  Since this FDA recommendation was put into place, there has been about a 65% reduction in the prevalence of neural tube defects in the general population.

Because folic acid is needed during the first weeks of pregnancy, even before a woman may know she’s pregnant and because 50% of all pregnancies are unplanned, any woman who could potentially become pregnant should be taking folic acid daily.  Once a woman is pregnant, she should continue to take at least 400 micrograms or 0.4 milligrams of folic acid during the first 3 months of pregnancy.

Folate Levels and Risk of Autism

These data were presented at the International Society for Autism Research (INSAR) by researchers from Johns Hopkins. Remember that these findings are preliminary and have not yet been published in a peer-reviewed journal.  The primary goal of the study was to examine the impact of prenatal nutrition on the development of Autism Spectrum Disorder (ASD).

Researchers recruited pregnant women at the time of delivery and analyzed data from 1,391 mother-child pairs in the Boston Birth Cohort, a predominantly low-income minority population.  The mother’s blood was tested 1-3 days after delivery, and the children were followed for several years.  Using electronic medical records, children ever diagnosed with autism, Asperger syndrome and/or pervasive developmental disorder not otherwise specified were categorized as having ASD (n=107).

Most of these women reported that they used multivitamin supplements during pregnancy.  What many of the news reports failed to highlight was the fact that the women who reported taking multivitamin supplements (which contain folic acid) 3-5 times per week had a markedly lower risk of having a child with an autism spectrum disorder across all trimesters (adjusted hazard ratio (HR): 0.33, 0.38 and 0.43 for 1st, 2nd and 3rd trimester use, respectively).  This finding is consistent with other studies .

Around 10% of the women had very high folate levels (more than 59 nmol/L) and 6% had high levels of vitamin B12 (more than 600 pmol/L).  If the mother had high levels of vitamin B12, she had significantly increased risk of having a child with ASD (HR: 3.01; 95% CI: 1.64 – 5.52; p value: 0.001).  High maternal folate levels were also associated with increased risk of ASD (HR: 2.27; 95% CI: 1.26 – 4.09; p value: 0.007). The risk was the highest for those children whose mothers had both high plasma folate and vitamin B12 levels (HR: 17.59; p value: <0.001).

These findings are striking.  However, so many questions remain, and the answers to these questions are very important in terms of understanding the clinical significance of these findings.

Do folate and vitamin B12 levels drawn after delivery  reflect what has gone on during pregnancy?

Why did 10% of the women have such high folate and B12 levels?  Some of them may have been taking higher than recommended doses of these supplements, but I would also wonder about genetic factors that may cause some women to process folate and B12 differently.  Are there specific issues in this population that may affect risk for ASD?

Why was the prevalence of autism spectrum disorder so high in this population?  If you do the math, 107 out of 1391  — or 7.7% — of the children were diagnosed with ASD.  That is much higher than the one out of 68 children or 1.5% in the United States (as estimated by the CDC).  

Obviously it will take time to fully understand the data from the Johns Hopkins study, but we can’t lose sight of the importance of folic acid for women of reproductive age.  By discouraging the use of folic acid supplements in this population, we may be causing more harm than good.  Without adequate folic acid supplementation, we would expect to see higher rates of neural tube defects and, down the road, increased rates of autism spectrum disorder.

How Much Folate?

The U. S. Public Health Service and CDC recommend that all women of childbearing age consume 0.4 mg (400 micrograms) of folic acid daily to reduce the risk of serious birth defects and long-term neurodevelopmental disorders.  (Most prenatal vitamins contain 0.8 mg or 800 mcg of folic acid.)

Ruta Nonacs, MD PhD

Johns Hopkins University Bloomberg School of Public Health. “Too much folate in pregnant women increases risk for autism, study suggests: Researchers say that while folate deficiency is bad for developing fetus, excessive amounts could also be harmful.” ScienceDaily. ScienceDaily, 11 May 2016.


Learn more:

American College of Obstetricians and Gynecologists (ACOG)

March of Dimes

Updated Estimates of Neural Tube Defects Prevented by Mandatory Folic Acid Fortification — United States, 1995–2011


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