Meta-analysis: Environmental pollutants are significant risk factors for autism

Another year and another analysis has found significant links between toxic environmental exposures and autism, this time a peer-reviewed meta-analysis of cohort studies published in BMC Public Health.

The study found positive associations between the development of Autism Spectrum Disorder (ASD) and exposures to nitrogen dioxide, copper, mono-3-carboxypropyl phthalate, monobutyl phthalate, and PCB 138, as well as with such pollutants as carbon monoxide, nitrogen oxides, metals, and more.

In the meta-analysis, 5,780 studies were identified; 27 were included in the systematic review, and 22 were included in the meta-analysis. The selected studies included 1,289,183 participants and 129 environmental pollutants. 

The study by Tatiana Duque‑Cartagena of the School of Medicine at the Pontifical Catholic University of Rio Grande do Sul (PUCRS), Brazil, and colleagues was published in 2024.

In the study, the researchers acknowledged ASD prevalence is now 1 in 100 among children worldwide and continues to rise. It is even higher in the United States — 1 in 36 children aged eight years, according to the Centers for Disease Control (CDC) — and wreaks economic damage across societies.

“In the United States, the economic burden of ASD was estimated to be $11.5 billion in 2011,” the researchers wrote. “A complex interplay of biological and environmental factors has been linked to autism spectrum disorder.”

As with other studies, the researchers did not exclude genetic factors in autism prevalence, but they pointed to the interaction between genetic and environmental factors as key.

“Environmental pollutants, including toxic metals, are linked to epigenetic modifications and de novo mutations, potentially contributing to ASD onset,” the study stated. “These pollutants, particularly during gestation and postnatal periods, pose health risks and are associated with ASD. Toxic heavy metals can disrupt enzymatic functions, interfere with cell signaling, and trigger oxidative stress, potentially leading to cell death pathways.”

Elevated levels of cadmium and mercury are frequently found in children with ASD, Duque-Cartagena wrote, but she cautioned that more research is needed to fully understand how metal-induced neurotoxicity might play a role in ASD.

The researchers acknowledged that recent systematic reviews and meta-analyses have evaluated the link between environmental pollutants and the development of ASD but they said those reviews exhibited notable limitations: Eighteen of 21 studies relied on four or fewer databases, 11 imposed language restrictions (English, French, or Chinese), and six confined their searches to brief periods of time.

In addition, the researchers wrote, their approaches overlooked some available evidence and concentrated on air pollutants, with fewer addressing metals, pesticides, polychlorinated biphenyls, or perfluoroalkyl substances. 

“This study aims to analyze the association between various environmental pollutants and ASD incidence through cohort studies, evaluating different pollutants and their effects on subgroups,” the researchers wrote, adding that the study was performed according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses – PRISMA and registered in the International Prospective Register of Systematic Reviews.

The meta-analysis combed through the Cochrane Central Register of Controlled Trials — considered a scientific gold standard — to find studies to review, from its inception through January 2023, as well as other medical libraries.

The results

For starters, the researchers were systematic in the selection criteria.

“A total of 5,780 studies were identified, of which 2,723 were duplicates,” the study stated. “Of the remaining 3,057 studies, 3,019 articles were excluded: 2,501 did not evaluate the association between environmental pollutants and ASD; 513 were studies with another type of design (cross-sectional, case studies, case series, experimental models, reviews, response letters or editorials); and five included participants older than 19 years.”

Thirty-eight articles were selected to read the full text, of which 11 were excluded, the researchers wrote: Eight did not evaluate the association between air pollutants and ASD, and three had another design. 

Finally, 27 articles were included in the systematic review, and 22 were included in the meta-analysis. Those 27 articles included 1,289,183 individuals ranging from childhood to adolescence. 

“Twenty-four studies were conducted on children, and three studies were conducted in adolescents,” the study stated. “The average exposure duration was 6.9 years, with follow-up times ranging from 2 years to 17 years across the studies.”

All totaled, the studies reported 129 pollutants that are air pollutants and toxic substances.

Individual studies reported a significant association of autism with a range of contaminants, including cadmium, bisphenol A, PCB, nitrogen dioxide, carbon monoxide, as well as sulfur dioxide, nitric oxide, and iron and manganese, among others.

“The first meta-analysis was performed separately for each pollutant, and a significant association was found with nitrogen dioxide, copper, mono-3-carboxypropyl phthalate, monobutyl phthalate and PCB 138,” the study stated. “Additionally, these meta-analyses suggest a potential association with PM 10. No associations were found with the other pollutants.”

Copper exposure displayed a significant association with ASD, the researchers found.

The researchers then classified the pollutants into 16 subgroups, such as sulfur dioxides, nitrogen oxides, pesticides, carbon monoxide, plastics and others.

“Positive associations were found with carbon monoxide, nitrogen oxides, and metals,” the study stated. “A negative association with organophosphates and carbamates was observed. Finally, (there were) potential associations with ozone, inorganic substances, pesticides, dioxins, furans, and PCBs. Also, the association between carbon monoxide and ASD was found to be significant.”

Nitrogen oxides, including nitrogen dioxide and nitric oxides, were also associated with ASD, the researchers reported, as were metal elements.

And what were the plain-language conclusions?

“The results indicated that exposure to individual pollutants such as nitrogen dioxide, copper, mono-3-carboxy propyl phthalate, monobutyl phthalate, and PCB 138 increases the risk of developing ASD,” the researchers concluded. “Subgroup analyses further linked carbon monoxide, nitrogen oxides, and metals to higher ASD risk.”

In addition, the researchers stated, trends suggested associations between ASD and exposure to particulate matter, inorganic substances, and pesticides. 

“The associations found in this study can be explained according to the pollutant type, individually or by subgroup,” Duque-Cartagena wrote. “The associations with PCB 138, carbon monoxide, nitrogen oxides, and metals and risk of ASD were consistent with findings from other systematic reviews. However, there were discrepancies between those with nitrogen dioxide, copper, mono-3-carboxypropyl phthalate and monobutyl phthalate and other reviews.”

Disrupting metabolism

The authors observed that it is recognized that environmental pollutants disrupt cellular metabolism through mechanisms like breaching cell membranes, intracellular accumulation, and inhibition of critical metabolic pathways, which can impede the neurodevelopmental process.

“For instance, heavy metals can trigger oxidative stress by generating reactive oxygen species, which can harm lipids, proteins, and DNA and compromise mitochondrial function, potentially leading to cell death, tissue damage, or neurological disorders,” the researchers reported. “Particulate matter and polycyclic aromatic hydrocarbons can breach the blood-brain barrier, initiating brain inflammation that may disrupt neurotransmitter systems and synaptic function. Persistent immune system activation by pollutants can induce chronic neuroinflammation, disrupting brain architecture connectivity and impeding normal brain development.”

Then, too, the researchers wrote, pollutants can cause DNA damage, leading to epigenetic alterations like DNA methylation and histone modifications that influence gene expression tied to brain development and function. 

“This, in turn, could potentially contribute to the pathophysiology of ASD,” the study stated. “Compelling evidence suggests that environmental contaminants significantly impact cellular metabolism and neurological well-being, connecting these molecular changes to broader neuro-developmental consequences.”

What’s more, the researchers continued, exposure routes to environmental pollutants are crucial in ASD pathogenesis. 

“Alterations in neuronal connectivity, occurring from prenatal to early adulthood, can result from genetic and epigenetic factors,” the researchers asserted. “The ENVIRONAGE cohort study found that increased PM 2.5 [tiny particulate matter that can be inhaled and that penetrates deep into the lungs] exposure during pregnancy was associated with relationship and prosocial behavior problems in preschoolers. These effects may be due to higher mutation rates and DNA repair alterations during fetal and neonatal stages.”

Conversely, the researchers reported, low-pollution maternal environments are associated with beneficial DNA methylation in neurodevelopmental genes, highlighting the importance of pollution levels and particulate matter composition in understanding ASD risk.

“The characteristics of the population may impact the associations identified in this meta-analysis study and the timing of exposure,” they wrote. “ASD symptoms typically manifest early in life, exerting significant developmental effects during the prenatal and early postnatal periods. Both acute and chronic exposure to environmental pollutants during these critical phases can influence neurogenesis and neuronal maturation.”

The evidence suggests, the researchers wrote, that prenatal and postnatal exposure to contaminants can bring about developmental alterations in children, with the developing nervous system being especially vulnerable to environmental toxins, even at low exposure levels.

“Accurate assessment of the timing of contaminant exposure is crucial for comprehending the underlying mechanisms and crafting effective interventions,” they wrote. “Recognizing that the absence of significant associations with specific contaminants, individually or in combination, or inconclusive findings does not imply their non-existence is crucial. Further research is imperative to pinpoint the risk factors contributing to our understanding of ASD and to inform the development of enhanced preventive measures.”

A journalist’s inquiry

As more scientific studies probe the probable connection between environmental toxins and autism and other neuro-developmental disorders, one independent journalist, former CBS reporter Sharyl Attkisson, has also been digging into the connections between common toxins — many listed in the meta-analysis above — and various emerging conditions.

“A tidal wave of health conditions is crashing over us, growing more common with each passing year,” Attkisson wrote recently on her Substack. “From autism to obesity, diabetes to depression, the numbers are staggering — and they’ve been climbing sharply since the 1990s. What’s driving this surge?”

The answer is rarely a single smoking gun, Attkisson asserts.

“Evidence points to the thousands of toxins and other exposures that we’re swimming in every day, from the air we breathe to the water we drink,” she wrote. “Scientific studies often examine one toxin’s role in one illness at a time. That approach tends to mask the fact that multiple exposures are often to blame.”

Sometimes the links are clear, Attkisson asserted, while other times they may be murky or debated. 

“But the fact is: real life doesn’t work like a lab experiment,” she wrote. “We’re not exposed to just one chemical at a time. We’re hit with a cocktail of them, day in and day out.”

To get to the bottom of what is happening in society, Attkisson said she dug into a sampling of health conditions that have exploded since 1990, then cross-referenced them with a small sampling of thousands of toxins and other exposures that are thought to cause, trigger, or worsen those ailments. 

“There are hundreds of conditions on the rise and thousands of potential culprits in our surroundings, way more than I could cover here,” she wrote. “But even with a limited scope and much debate, patterns emerge. Certain toxins and exposures keep popping up, especially when it comes to hormone-related and immune-related disorders. The takeaway: It’s rarely about one villain — it’s about the whole toxic brew.”

Attkisson said the common medical establishment’s insistence on pinning down a single culprit as “causal” before doctors will acknowledge any link is a smokescreen and one that conveniently hides the bigger picture. 

“And let’s be honest,” she wrote. “That’s exactly what some want, especially those who profit from keeping this unhealthy environment chugging along.”

Attkisson then laid out 52 conditions and their suspected relationships to toxic chemicals — which, she pointed out, “appear over and over again in association with illnesses that have become disturbingly common.”

“The exposures that appear most often are: vaccines, pharmaceuticals in water, PFAS, BPA, phthalates, pesticides, glyphosate, triclosan, mercury, lead, food additives/preservatives/chemicals/dye, and cellphone/microwave/EMF radiation,” she wrote.

Attkisson listed the conditions and proven and plausible toxins linked to those conditions in scientific peer-reviewed studies, with the toxin followed by its impact and source of study in parentheses. 

Autism was at the top of her list of conditions, linked with such proven toxins as mercury (neurotoxic, NIH), lead (neurodevelopmental, CDC); Chlorpyrifos Insecticide (neuro risk, EPA); organophosphate pesticides and insecticides (neurotoxicity, NIH); cellphone/microwave radiation/EMF (BMC Pediatrics, etc.); and fluoride (neurotoxicity, BMC Pediatrics).

Plausible toxins that she associated with autism included glyphosate herbicide (gut-brain axis, PNAS 2020); air pollution (PM2.5, JAMA Pediatrics); aluminum (antiperspirant exposure, neurotoxic via kidney filtration, J Trace Elem Med Biol); and various pharmaceuticals in water (aluminum-containing residues, potential neuro impact, USGS, Environmental Health Perspectives).

Another increasingly common condition on Attkisson’s list was juvenile diabetes (Type 1), immune-related. She cited a 25-50 percent rise in incidence, from 14.8 to 21.7 per 100,000 kids, according to the CDC, with plausible associated toxins including PFAS (immune disruption, ATSDR); BPA in plastics, resin (endocrine, NIH); phthalates in plastics (immune/endocrine, NIH); pesticides (autoimmune, Environ Health); vaccines (immune challenge, rare autoimmune reports); and pharmaceuticals in water (hormone disruptors, steroids, ATSDR, 2021).

Obesity was yet another all-too-common malady increasingly impacting America’s health, Attkisson wrote, with an increase in adult obesity from 12 percent to 42 percent of the adult population, or a 250-percent rise.

Proven toxins that she linked to obesity included BPA in plastics, resin (obesogen, NIH); and phthalates in plastics (metabolic, Environ Health). Plausible toxins included glyphosate herbicide (gut microbiome, Obesity Rev); PFAS (lipid metabolism, JAMA); vaccines (endocrine disruption warnings, adjuvant effects on metabolism, package inserts); and pharmaceuticals in water (endocrine disruptors).

She also cited triclosan antiseptic, which was banned in 2016 from household soap but remains in high concentrations in toothpaste and other consumer products. Attkisson says it disrupts thyroid hormones and metabolism, per 2008 and 2016 studies.

Richard Moore is the author of “Dark State” and may be reached at richardd3d.substack.com.