Maternal lifestyle and environmental risk factors for autism spectrum disorders

Abstract

Background: Over the past 10 years, research into environmental risk factors for autism has grown dramatically, bringing evidence that an array of non-genetic factors acting during the prenatal period may influence neurodevelopment.

Methods: This paper reviews the evidence on modifiable preconception and/or prenatal factors that have been associated, in some studies, with autism spectrum disorder (ASD), including nutrition, substance use and exposure to environmental agents. This review is restricted to human studies with at least 50 cases of ASD, having a valid comparison group, conducted within the past decade and focusing on maternal lifestyle or environmental chemicals.

Results: Higher maternal intake of certain nutrients and supplements has been associated with reduction in ASD risk, with the strongest evidence for periconceptional folic acid supplements. Although many investigations have suggested no impact of maternal smoking and alcohol use on ASD, more rigorous exposure assessment is needed. A number of studies have demonstrated significant increases in ASD risk with estimated exposure to air pollution during the prenatal period, particularly for heavy metals and particulate matter. Little research has assessed other persistent and non-persistent organic pollutants in association with ASD specifically.

Conclusions: More work is needed to examine fats, vitamins and other maternal nutrients, as well as endocrine-disrupting chemicals and pesticides, in association with ASD, given sound biological plausibility and evidence regarding other neurodevelopmental deficits. The field can be advanced by large-scale epidemiological studies, attention to critical aetiological windows and how these vary by exposure, and use of biomarkers and other means to understand underlying mechanisms.

Keywords: Autism; air pollution; environmental chemicals; environmental risk factors; maternal alcohol use; maternal nutrition; maternal smoking.

Figure 1.

Critical periods of susceptibility indicated from studies of autism spectrum disorders. Neuropathology (autopsy and imaging) studies of brains of individuals with autism spectrum disorders found evidence of dysregulated neurogenesis, neuronal migration and neuronal maturation compared with brains of typically developed individuals, processes that generally occur in the first half of pregnancy. Figure shows windows of critical periods indicated by evidence from epidemiological studies of environmental factors demonstrating an association with autism spectrum disorders. Not all exposures shown in the figure are covered in this review, but they are included as exemplary of critical time windows. Time periods of higher risk within pregnancy have variable results, but tend to congregate in the first half of pregnancy. Days = fetal days after conception. For exposures with more than one study, dark blue indicates overlapping period and light blue indicates timing suggested by one but not all studies. Images adapted from those in The Developing Human: Clinically Oriented Embryology, 6th edition (1998). This material is reproduced with permission of John Wiley and Sons. ^aThe study by Suren et al. indicated that up to 6 weeks prior to (and 6 weeks after) conception (4 weeks before LMP to 8 weeks after) was important. ^bThe study by Rai et al.collected information on use since becoming pregnant at the first antenatal visit which usually takes place before the end of the first trimester (median 10 weeks of gestation).