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Table 2 Summary of systematic reviews of environmental risk factors for autism spectrum disorders

From: Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses

Risk factors Design Summary of findings Comments
Maternal immigration [53], 2015 10 population-based The adjusted results showed higher rates of ASD if children had migrant mothers (2.69%) compared with children of non-migrant mothers (0.91%). Six out of ten studies found that giving birth postmaternal migration significantly raised risks of ASD, with the exception of children born to Hispanic migrant mothers who had lower rates of ASD (compared to all other migrant groups) A meta-analysis by another group supports these findings
Preconceptional chemical exposure [49], 2014 3 case-control All studies showed an increased rate of ASD in children whose parents were exposed to chemicals The studies were limited by retrospective design and small sample sizes
Pesticide exposure during pregnancy [49], 2014 1 retrospective case-control; 3 prospective cohort All showed an increased rate of ASD in children with gestational exposure to chemicals including two prospective studies of organophosphates The studies provide enough evidence to justify larger studies of pesticide exposure in ASD
Pesticide exposure during childhood [49], 2014 1 retrospective cross-sectional; 1 prospective cohort; 1 computer model One study showed an association between organophosphate exposure; one between DDE exposure and ASD, and one between phosphine exposure and ASD  
Air pollution during prenatal period [49], 2014 6 retrospective All studies showed an increased rate of ASD associated with air pollution (with particulate matter in three studies and with NO2 in two studies) A meta-analysis of four prospective European cohorts showed no association between air pollution and ASD
Air pollution during childhood [49], 2014 3 retrospective case-control All studies showed some association between air pollution and ASD (association with NO2 is replicated in two studies)  
Exposure to other chemicals [49], 2014 2 prospective cohort; 4 retrospective case-control No effect in prospective studies; retrospective studies found some effects for solvents and other toxicants Retrospective studies used questionnaires
Toxic waste sites [49], 2014 2 case series, ecological Association of Superfund site with ASD in both studies  
Water pollutant [49], 2014 2 ecological No association between water chlorination and ASD in either studies  
Heavy metals [49], 2014 8 ecological 7 studies showed association between Hg and ASD, one showed no association Ecological studies are limited by indirect measures of exposure
In-house flooring [49], 2014 1 cohort Polyvinyl chloride vs. wood floor increases the risk of ASD  
Mercury levels [49], 2014 29 case-control 12 studies with elevation in at least one tissue in patients with ASD Studies measuring levels of heavy metals were limited by cross-sectional design and small sample size. Furthermore, it is unclear how much cross-sectional measurements of metals in the body reflect the causal effect of such exposures on ASD risk.
Lead levels [49], 2014 25 case-control 11 studies with elevation in at least one tissue in patients with ASD
Cadmium levels [49], 2014 14 case-control 5 studies with elevation in at least one tissue in patients with ASD
Aluminum levels [49], 2014 11 case-control 3 studies with elevation in at least one tissue in patients with ASD
Arsenic [49], 2014 8 case-control 5 studies with elevation in at least one tissue in patients with ASD
Nickel [49], 2014 3 case-control 2 studies with elevation in at least one tissue in patients with ASD
Uranium levels [49], 2014 2 case-control 1 studies with elevation in at least one tissue in patients with ASD
Tin levels [49], 2014 1 case-control 1 studies with elevation in at least one tissue in patients with ASD
Heavy metals and severity [49], 2014 7 correlational studies All studies showed some correlation between ASD severity and heavy metal levels (particularly Hg and Pb) These studies suggest a dose-response relationship between metal exposure and ASD.
Heavy metals and chelation [49], 2014 12 uncontrolled studies All showed improvement in symptoms of ASD following chelation treatment The studies are limited by lack of the control group
Urine porphyrin studies [49], 2014 4 case-series; 7 case-control All studies showed some association with severity, prediction, or oxidative stress The studies are limited by retrospective nature
Solvents, pesticides, and PCB [49], 2014 2 case series; 2 case-control Case series showed levels above normal adult range for children with ASD; case-control studies showed no association between PCB and ASD The studies were limited by either lack of proper control group or small sample size
Phthalate [51], 2016 2 cohort; 3 case-control Three studies showed association between phthalate exposure and ASD; two studies showed no association  
PBDE [49], 2014 1 case-control PBDE resulted in higher activation of immune response in patients with ASD  
Valproate [37], 2014 1 population-based prospective; 2 prospective case series; 1 retrospective All studies found significant and strong association between prenatal valproate exposure and ASD The association between valproate and ASD is likely to be causal given the strength of association and evidence for biological plausibility
Folic acid [44], 2016 11 studies The findings were inconsistent; some studies provide support for the beneficial effect of folic acid on risk of ASD, whereas others show the opposite effect Observational studies were limited by self-report, whereas RCTs were limited by use of multivitamin
Camel milk [115], 2016 2 small short-term RCTs Results showed beneficial effects on ASD symptoms It is unclear whether this benefit is clinical and whether it extends to longer period of treatment
Casein and gluten-free diet [116], 2014 16 studies Findings are inconsistent Studies with positive findings were mostly of low quality
Omega-3 [43], 2011 2 RCTs Studies found no evidence for beneficial effects of omega-3 on ASD symptoms  
Assisted reproductive technologies [36], 2013 2 cohort; 5 case-control 3 studies showed positive association between ART and ASD, 3 studies showed no association, and 1 study showed a negative association between ART and ASD. The authors concluded that at present, no evidence supports the association between ART and ASD There are several sources of heterogeneity such as study design, exposure definition, data source, and confounders.
  1. ART assisted reproductive technology, ASD autism spectrum disorder, DDE dichlorodiphenyldichloroethylene, NO2 nitrogen dioxide, RCT randomized controlled trial