title: The plausibility of maternal toxicant exposure and nutritional status as contributing factors to the risk of autism spectrum disorders.
abstract: Recent research suggests the maternal environment may be especially important for the risk of developing autism spectrum disorders (ASD). In particular maternal infections, micronutrient deficiencies, obesity, and toxicant exposures are likely to interact with genetic risk factors to disrupt fetal brain development.
  
  
  OBJECTIVE
  The goal of this paper is to investigate the plausibility of maternal toxicant exposure and nutritional status as causal factors in the development of ASD.
  
  
  METHODS
  This paper reviews current research investigating the hypothesis that maternal toxicant exposure and prenatal micronutrient intake are important modifiable risk factors for ASD.
  
  
  RESULTS
  Zinc, copper, iron, and vitamin B9 are identified as specific micronutrients with relevance to the etiology of ASD. Specific toxicants induce a maternal inflammatory response leading to fetal micronutrient deficiencies that disrupt early brain development. Importantly, maternal micronutrient supplementation is associated with reduced risk of ASD. Furthermore, animal studies show that micronutrient supplementation can prevent the teratogenicity and developmental neurotoxicity of specific toxicants.
  
  
  CONCLUSIONS
  These findings lead to the hypothesis that maternal infection, obesity, and toxicant exposures (e.g. valproic acid, endocrine disrupting plasticizers, ethanol, and heavy metals) are all environmental risk factors for ASD that lead to fetal micronutrient deficiencies resulting from a maternal inflammatory response. It could be possible to use markers of inflammation and micronutrient status to identify women that would benefit from micronutrient supplementation or dietary interventions to reduce the risk of ASD. However, more research is needed to demonstrate a causal role of fetal micronutrient deficiencies and clarify the underlying mechanisms that contribute to ASD.
authors.affiliation: a Departments of Nutrition and Environmental Toxicology , University of California Davis , Davis , CA , USA.
authors.forename: Johnathan R
authors.initials: JR
authors.lastname: Nuttall
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000209:etiology*; D001559:Benzhydryl Compounds / Q000097:blood / Q000633:toxicity; D001921:Brain / Q000187:drug effects / Q000196:embryology; D004051:Diethylhexyl Phthalate / Q000097:blood / Q000633:toxicity; D004195:Disease Models, Animal; D000431:Ethanol / Q000097:blood / Q000633:toxicity; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications; D018811:Maternal Exposure / Q000009:adverse effects*; D019216:Metals, Heavy / Q000097:blood / Q000633:toxicity; D018977:Micronutrients / Q000097:blood / Q000172:deficiency*; D009752:Nutritional Status; D009765:Obesity / Q000097:blood / Q000150:complications; D010636:Phenols / Q000097:blood / Q000633:toxicity; D011247:Pregnancy; D012307:Risk Factors; D014635:Valproic Acid / Q000097:blood / Q000633:toxicity; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004051:Diethylhexyl Phthalate; D000431:Ethanol; D019216:Metals, Heavy; D018977:Micronutrients; D010636:Phenols; D014635:Valproic Acid; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: ASD; Developmental neurotoxicity; Inflammation; Maternal nutrition; Micronutrients; Risk factor