Project summary
Autism spectrum disorders (ASD) which are multifactorial complex disorders characterized by communication
deficits and repetitive behaviors affect between 1 and 2% of children in the US and Canada. Air pollutants,
phthalates, and pesticides are suspected of contributing to the etiology of ASD, whereas folic acid
supplementation has been shown to play a protective role, particularly in genetically susceptible individuals
with inefficient folate metabolism. Despite these critical findings from a few studies, several questions remain
unanswered: 1) No previous study investigated these modifiable factors in a comprehensive way; 2) no
previous study investigated the critical windows of susceptibility to these exposures; and 3) the interplay
between environmental, nutritional, and genetic factors in the etiology of autism is still unclear. Our preliminary
data show that folic acid supplementation is associated with lower autistic traits, but only in children of mothers
with genetic susceptibility. In addition, we found that adequate folic acid supplementation in first trimester of
pregnancy may prevent the detrimental effects of phthalates exposures regarding autistic traits. Building on
these findings and a large comprehensively characterized pregnancy and birth cohort implemented in ten
Canadian cities, we will examine the individual and joint contribution of identified modifiable risk factors of
autism and its associated traits. We will measure phthalates and organophosphate pesticides across the three
trimesters of pregnancy, and we will estimate monthly exposures to individual air pollutants such as nitrogen
dioxide and particulate matter and its composition across pregnancy and during child’s first year. Additionally,
we will measure folate autoantibodies that have been shown to be highly prevalent in mothers of autistic
children, and folate levels in maternal blood sample during 1st and 3rd trimesters of pregnancy. Using
sophisticated statistical models that can take into account complex mixtures of pollutants and time-varying
exposures, we will 1) quantify the individual and cumulative effects of early exposure to multiple air pollutants,
phthalates, and organophosphate pesticides on autistic traits; 2) identify whether these contaminants are
associated with lower plasma folate levels in pregnant women; and 3) clarify the role of folate-related genetic
polymorphisms, folate autoantibodies, and plasma folate in the associations between environmental
contaminants and autistic traits. By answering these research questions, we will gain a better understanding of
how strongly multiple pollutants and folic acid supplementation are associated with autistic traits, whether
these chemicals are associated with circulating folate concentrations, and how these effects of multiple
pollutants differ based on folic acid intake, genetic susceptibility, and the presence folate autoantibodies.
These findings will have great clinical and public health implications and will be critical in informing better
prevention strategies both at the individual and population level.
