High folate levels during pregnancy doubles risk of autism, Johns Hopkins study finds

While folate is essential for healthy baby development, excessive amounts could be harmful.

The study, released today by Johns Hopkins University, analyzed data from 1,391 mother-child pairs. The women who had both excessive folate and vitamin B12 levels were over 17 times more likely to have children that develop the autism spectrum disorder. Those with excessive folate levels – four times above what is considered adequate – faced double the risk. We talked to the study’s senior author, Daniele Fallin, to discuss why both too little and too much folate can be detrimental, and what the study means for expecting mothers.  

ResearchGate: Could you tell us what folate is and what role it plays in pregnancy?

Daniele Fallin: Folate is an essential B vitamin that is critical to early life development and the health of both mother and child. Deficiencies in folate have been shown over many years to be important factors to health – having too-low folate levels can lead to things like neural tube defects, congenital heart defects, fetal growth restriction, and even low birth weight and preterm birth delivery.

RG: What were the main findings from your study?

Fallin: We set out to examine whether amounts of folate and B12 in mothers’ blood around the time of birth would be associated with the later onset of autism in their infant babies. We measured folate and B12 in the days after birth, and we think this reflects the same levels that the mother would have had during late pregnancy.

We then looked at the medical records of these children over time and saw that the women who had very high levels of B12 or folate in their blood right after birth were more likely to have a child that developed autism. Our data show that adequate levels of supplementation are critical to normal development of children –  too little could increase the risk for autism, and that is why supplementation is so critical. But a fairly rare number of moms have extremely high levels, and this may also be problematic.

RG: Can you explain why some women had such high folate levels?

Fallin: We don’t know exactly why some women had such high levels. It’s possible that they consumed too many folic acid-fortified foods or supplements. However, it may be possible that some women are just genetically predisposed to absorb greater quantities of folate, or that they metabolize it slower. We plan on researching this further.

RG: What were the limitations of your study?

Fallin: Our biomarker measures of folate and B12 were taken right after birth and likely reflect late pregnancy. We would have liked to measure folate and B12 levels in mothers' blood earlier in pregnancy. We also did not have diet information on mothers to understand the contributions of both diet and supplementation to folate levels.

RG: What are the next steps in this research?

Fallin: We want to confirm our findings that very high levels of folate and B12 in pregnant women are related to later autism spectrum disorder in children. If this is confirmed, we will work to identify the sources of these extremely high levels, which will help to inform guidelines about optimal levels and how to achieve them.

RG: For women who are currently pregnant, how would you recommend they best manage their folate intake?

Fallin: We are deeply concerned about this particular messaging: Our work is very consistent with previous work showing that supplementation is critical to maternal health and child development and health, so at this point the recommendation is definitely to continue supplementation. What this study finds is that while maintaining adequate levels of folate is important, extreme levels may be harmful. As we move forward, we want to understand if that is consistently true – that extreme levels are harmful – and if so, how we would go about optimizing dosage in ways that achieve maximum benefit without additional risk.

RG: If women are concerned about their folate levels, can they ask their doctor to test them throughout the pregnancy? Would you recommend this?

Fallin: I think it is too soon to make blanket recommendations like implementing testing during pregnancy. Women should talk to their doctors if they are concerned and discuss together the value of testing in their particular case.

RG: Should folic acid still be added to cereals and breads?

Fallin: The value of fortification and supplementation is not at all in question. These have been successful public health initiatives that should be continued without a doubt.  Our work highlights that there is a subset of women with extremely high levels of these essential B vitamins, and that this may harmful. We should strive to find out if this is true, and if so, what are the sources of these very high levels in such women, and how can we best advise them.

Featured image courtesy of Yimix.