Urgent need for research on maternal folate status and autism
Last year two studies suggested the heritability of autism spectrum disorders (ASD) was about 50%, begging the question: What non-heritable risk factors make up the other 50%?
This latest review published in the British Journal of Nutrition looked at emerging epidemiological evidence suggesting maternal folate status early in pregnancy may influence the risk of ASD in the child.
The researchers from the Karolinska Institute in Sweden and the Drexel Autism Institute and the Drexel University School of Public Health in the US said ASD was “complex, heterogeneous and multi-causal” meaning environmental factors should be looked at alongside relevant genes to identify further subsets of possible causes.
“If one-carbon metabolism is involved in the aetiology of ASD, this provides a potential route for prevention through nutritional intervention in the pre- and peri-conceptional periods, especially for the subgroup of children having specific genetic risk factors for ASD,” they wrote.
The review included 11 papers from Hungary, Nepal, India, the US, Spain, Norway and the Netherlands.
What did they find?
The papers suggested insufficient folate intake could result in the epigenetic process DNA hypomethylation, which is associated with neurodevelopment and gene expression.
DNA methylation depends on dietary methyl ‘donors’ such as folate, choline and methionine – which are metabolised through one carbon. Changes to the availability of these donors could affect DNA methylation capacity and potentially downstream neurodevelopment.
“This raises the intriguing prospect that, much like with neural tube defects, the incidence of ASD may be decreased through interventions that enrich maternal folate status,” they wrote.
However, they urged caution and greater quality research on the area, saying the weight of evidence linking maternal folate status and ASD was “far from unequivocal”.
“In light of an apparent rising prevalence along with the profound individual, familial and societal burden of ASD, there is an urgent need to fill in the gaps in what is currently known of the relationship between folate and ASD,” they said.
Large historical archives of existing prospective, population-based cohorts could be used to fill these blanks, they said, as well as complete assessments of maternal folate, vitamin B12 and homocysteine levels throughout the first trimester of pregnancy and folate-relevant genetic variants involved in one-carbon metabolism and epigenetic mechanisms.
ASD is a condition that affects social interaction, communication, interests and behaviour and includes Asperger syndrome and childhood autism.
The researchers said ASD prevalence in the US was no greater than five per 10,000 individuals in the 1980s, but this had risen to an estimated one in 68 children in 2010.
Meanwhile the European Commission estimated there were between 3.3 and 16.0 cases of ‘classical autism’ (the most severe form of ASD) per 10,000 people in the EU – which could increase to between 30 and 63 per 10,000 once all forms of ASD were included.
The Commission said: “Recent surveys reveal much higher rates than 30 years ago, but this does not give an accurate picture of the extent to which ASDs are increasing in the EU.
“It is as much a reflection of today's broader concept of autism, which is now recognised among normally intelligent subjects, diagnosed according to different criteria, and better identified thanks to better health and social services.”
Source: British Journal of Nutrition
Published online ahead of print, doi:10.1017/S0007114515002470
“Maternal folate status as a risk factor for autism spectrum disorders: a review of existing evidence”
Authors: E. A. DeVilbissa, R. M. Gardnera, C. J. Newschaffera and B. K. Leea
