We all know that taking folic acid before and during early pregnancy helps prevent neural tube defects like spina bifida and anencephaly. But I for one was surprised to learn that taking folic acid may also help prevent autism.
Studies Linking Folic Acid Supplementation During Early Pregnancy with Autism Risk
In a population-based, prospective Norwegian Mother and Child Cohort Study of 85,176 mothers, women who took folic acid within the first 8 weeks of pregnancy had half the risk of having a child with autism: 0.10% versus 0.21%. Taking folic acid in mid-pregnancy, on the other hand, had no apparent impact on the risk of autism.
Because this was a cohort study, not a randomized controlled trial, we cannot say that folic acid caused a lower risk of autism.
For one, women who took folic acid supplements during early pregnancy had other traits associated with lower-risk pregnancies. They were more educated, more likely to be of normal weight, more likely to be first-time mothers, more likely to have planned their pregnancies, and so on.
In an attempt to rule out these alternative explanations, the researchers also looked at fish oil supplements during early pregnancy. Women who took fish oil supplements in early pregnancy were similar to those who supplemented with folic acid, yet taking fish oil was not related to the risk of autism.
The Norwegian Mother and Child Cohort Study is not the only study to find that folic acid supplementation during early pregnancy predicts a lower risk of autism. An earlier, smaller California-based study found that the higher levels of folic acid during the first month of pregnancy, the lower the risk of autism, with the lowest risk seen among pregnant women taking in 1000 μg or more per day.
Not at all studies have found a relationship, however. A 2015 Danish registry-based study found no effect of supplementation on the risk of autism.
The studies conducted to date are provocative but hardly definitive. We don’t know whether the relationship between folic acid and the development of autism is real, let alone causal.
So why do I take these findings seriously? Because the idea that not supplementing with folic acid can contribute to the risk of autism is both biologically plausible and supported by several indirect lines of evidence.
I’ll get into this evidence in a moment, but first let’s back up a second to briefly review what folic acid is and why it’s important during pregnancy.
What is Folic Acid?
Folic acid is a shelf-stable form of folate (vitamin B9), a water-soluble vitamin found in foods such as broccoli, chickpeas, lentils, beans, avocados, oranges, and fortified grains. Folate needs rise dramatically during pregnancy and can exceed the amount taken in from a normal diet. A lack of folate during very early pregnancy can lead to neural tube defects and other birth defects, so all major medical organizations currently recommend that women who are pregnant or who are planning to become pregnant take at least 400 μg of folic acid a day.
Why Would Folic Acid Affect The Risk of Autism?
First, let’s talk about biological plausibility. Is there a biological mechanism by which low levels of folate would raise the risk of autism? As it happens, yes.
Folate plays a key role in DNA methylation (the fixing of key genes to the “off” position) during early brain development. Failure to turn off specific genes could lead to the faulty wiring of neural circuitry that results in autism.
Second, do we have reason to believe that low folate levels during early pregnancy affect the risk of autism? Again the answer is yes.
Consider the anti-seizure drug valproic acid. Valproic acid interferes with the normal metabolism of folate and, when taken during pregnancy, is associated with a 3 to 5-fold increase in risk of autism.
Genetic variants can also affect how efficiently folate is metabolized. The C>T variant in MTHFR gene (5-methylenetetrahydrofolate reductase) lowers the efficiency of folate-driven DNA methylation. Women who carry one or more copies of the variant version appear to be overrepresented among mothers of autistic children, according to a recent meta-analysis.
(The MTHFR C>T variant certainly reduces the efficiency of folate-driven DNA methylation. But whether it also increases the risk of having an autistic child is controversial. Most of the studies to date have been poor quality, so we really need better research before drawing firm conclusions.)
(23andMe customers can check whether they carry the MTHFR C>T variant here. Note that 23andMe reports the opposite strand. If you are AG or AA, you carry one or two copies of the less efficient version. This means you need a higher amounts of folic acid to achieve the normal physiological levels. Taking folic acid before conception and during early pregnancy is especially important for you.)
The Bottom Line
While the jury is still out on whether folic acid truly lowers the risk of autism, taking folic acid the month before conception and during early pregnancy is clearly a good idea. Early supplementation lowers the chances of a neural tube defect by 50-70%.
For pregnant women and women planning to become pregnant, the current recommended intake is 400-1000 μg per day. Either a multivitamin or a prenatal vitamin will cover this requirement. Most multivitamins contain 400 μg, while most prenatals contain 800 μg.
Women who have previously given birth to a baby with a neural tube defect, who have diabetes, or who are taking certain medications may need higher amounts of folic acid. (Here is a list of potential indications.) Most pregnant women will not need more folic acid than found in a standard prenatal vitamin.
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