November 13, 2007) Autism is on the rise, both in prevalence and incidence, and there is growing evidence that environmental insults, such as pesticides, are linked to this developmental disability. According to the latest study, published in the October issue of Environmental Health Perspectives, children born to mothers living near fields where pesticides are applied are more likely to develop autism spectrum disorders (ASDs). The authors of “Maternal Residence Near Agricultural Pesticide Applications and Autism Spectrum Disorders among Children in the California Central Valley” compared maternal pesticide exposure for 465 children with ASDs and 6,975 children without ASDs living in the same area. The research reveals that mothers who lived within 500 meters of fields sprayed with organochlorine pesticides, specifically endosulfan and dicofol, during their first trimester of pregnancy had a six times higher chance of having children with autism compared to mothers who did not live near the fields. Mark Horton, M.D., director of the California Department of Health, said the findings are exploratory and indicate that more research of the relationship between organochlorines and ASDs is needed. (See Daily News Blog posting from July 31, 2007 for further reactions from health care officials and more details about this study.)
ASDs include a range of developmental disabilities that are characterized by substantial impairments in social interaction and communication and the presence of unusual behaviors and interests. The symptoms range from mild to very severe, appearing before the age of 3 and lasting throughout a person’s life. According to the Centers for Disease Control and Prevention (CDC), one of every 150 eight-year old children has an ASD, a prevalence rate of almost 7 per 1,000 children that is the same across multiple areas of the US. ASD prevalence shot up in 1990s, reaching levels of 2.0-7.0 per 1,000 children, greater than a tenfold increase from the prevalence rates identified in the 1980s, 0.1-0.4 per 1,000 children. There are indications that the rates, while still rising, may be leveling off at present, but this may reflect improvements in diagnostic screening and increased parental awareness as much as changes in the underlying factors. ASDs were first identified as a specific disorder in 1943, and since then the criteria for diagnoses have changed many times. Comparisons of rates over time may not be entirely consistent or thoroughly systematic, but the prevalence has reached a point where it is a condition of concern for parents and school officials.
Federal health authorities believe that ASDs probably result as an interaction between genetics and environmental factors. Despite the high degree of heritability of ASDs, genetic factors cannot completely account for the incidence of autism. After extensive genetic testing, researchers have not been able to pinpoint a specific genetic locus or set of genes linked to autism. Among identical twins, if one child has autism, there is a 75% chance that the other child is affected, but there can be significant differences in the symptoms displayed in twins. Because the concordance rate among identical twins is not 100% and the number of autism cases is rising, it seems likely that environmental causes are key factors. A 2000 report by the National Academy of Sciences indicates that as many as 25 percent of all developmental disabilities in children may be caused by environmental factors.
The relative rarity of autism in the Amish community around Middlefield, Ohio, where only one per 15,000 children has an ASD, provides promise for uncovering environmental factors that cause the disorder. One explanation for the lower prevalence was that Amish children, who are religiously exempt from immunizations, were not exposed to thimerosal, a mercury-based preservative in vaccines. While the CDC acknowledges the possibility of a link between thimerosal and autism, they point out that there have been studies that discredit this causal relationship. (See Daily News from June 13, 2005 for more on Amish rates of autism).
Other substances that have been implicated as risk factors for autism include viruses, industrial chemicals and electromagnetic radiation. A few individual cases of ASDs have been linked to prenatal exposure to valproic acid, as well as to infectious agents such as the rubella and influenza viruses. Some drugs taken by mothers during pregnancy are also linked to a higher risk of autism in children, especially the prescription drug thalidomide, which in the past was administered as a sleeping pill and used to treat morning sickness. Yet, for all these factors, there is less than perfect concordance, which suggests that a genetic predisposition is necessary for the chemical or microbial factors to lead to autism.
However, the role of environmental insults in the development of autism has been documented and cannot be ignored in future research. Research of autistic children in the San Francisco Bay area, “Autism spectrum disorders in relation to distribution of hazardous air pollutants in the San Francisco bay area”, found a potential association between autism and concentrations of mercury, cadmium, nickel, trichloroethylene, and vinyl chloride in ambient air around birth residence.A 1998 article in Toxicology and Industrial Health, “Autism: xenobiotic influences”, looked at 18 autistic children and found that 16 of these children had levels of toxic chemicals in their blood that exceeded the adult maximum tolerance. Similarly, the authors of “Porphyrinuria in childhood autistic disorder: implications for environmental toxicity” describe how urninary levels of porphyrin, a biomarker of environmental toxicity, were elevated in autistic children relative to control groups. Porphyrin levels were not significantly different in children with Asperger’s disorder, distinguishing it from autism.
“Men, Boys and Environmental Threats”, a 2007 report by the Canadian Partnership for Children’s Health and Environment, highlights how boys are more susceptible to environmental risks than girls, which is especially relevant to autism. Boys are four times more likely than girls to be diagnosed with autism, in addition to outnumbering girls in the incidence of learning disabilities overall, Attention Deficit Hyperactivity Disorder (ADHD), Tourette’s syndrome, cerebral palsy and dyslexia. For several reasons, boys’ brains may be more vulnerable during development to damaging substances found in the environment, including lead, mercury, arsenic, radiation, dioxins, PCBs, solvents and some pesticides, and (See Daily News from July 16, 2007 for more information on why boys are more prone to environmentally related health conditions.)
Gustavo C. Román, M.D., suggests that substances that interfere with thyroidal activity may produce morphological brain changes leading to autism, in a 2007 article, “Autism: transient in utero hypothyroxinemia related to maternal flavonoid ingestion during pregnancy and to other environmental antithyroid agents”. Scientists have identified specific changes to brain cells during development that are particular to autism, and these processes are regulated by hormones produced by the mother’s thyroid gland. Dr. Román notes that environmental contaminants interfere with thyroid function, including 60% of all herbicides, in particular 2,4-dichlorophenoxyacetic acid (2,4-D), acetochlor, aminotriazole, amitrole, bromoxynil, pendamethalin, mancozeb, and thioureas. Other antithyroid agents include polychlorinated biphenyls (PCBs), perchlorates, mercury, and coal derivatives such as resorcinol, phthalates, and anthracenes. Mercury acts as an antithyroid substance by causing inhibition of deiodinases and thyroid peroxidase. A leading ecological study in Texas, “Environmental mercury release, special education rates, and autism disorder: an ecological study of Texas”, correlated higher rates of autism in school districts affected by large environmental releases of mercury from industrial sources.
Warren Porter, Ph.D. argues that the connections among the nervous, endocrine and immune systems need to be looked at when asking how do pesticides affect learning and behavior. “Studies show that pesticides can function as nerve poisons and as pseudo hormones, modify hormone levels, and/or impact immune system function,” he writes. Learning is dependent on immune system processes & hormonal changes, so any changes to these systems could lead to developmental disabilities. Dr. Porter was first drawn to the relationship between pesticides and learning when he looked at a 1997 survey of student disabilities in the Madison Metropolitan School District (WI). From 1990-1995, the number of children in Madison with learning disabilities increased 70%, children that were emotionally disturbed increased 87%, and children with birth defects increased 83%. Dr. Porter writes that similar changes are seen globally, and that the data from Madison are indicative of a worldwide phenomenon of increasing behavioral and learning disabilities among children, who face more and more contaminants and toxic chemicals in the environment.
To address the public health concern that autism has become and explore the potential environmental factors related to the developmental disorder, the National Institute of Environmental Health Sciences (NIEHS) and the Environmental Protection Agency (EPA) created four new children’s environmental health research centers in 2001. Over the past five years, twelve such research centers nationwide were funded $1 million a year. Additionally, CDC’s Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) have teamed up on a large, population-based study, the Study to Explore Early Development (SEED), to uncover the risk factors for and causes of autism. If successful, researchers will better know how to develop strategies to prevent this complex disorder.
Irva Hertz-Picciotto, epidemiologist at the University of California, Davis, and a member of the Interagency Autism Coordinating Committee (IACC) panel, believes that the government’s proposed projects can provide some answers, but not a definite cause for autism. “I’m optimistic that we will have identified some environmental risk factors, and may have excluded a few others, between 2008 and 2010””but by no means will we have the final word. The genetics and the gene—environment interactions may be even tougher. Unfortunately, I don’t see enough groups working on the environmental contribution to autism, so it may be slower than projected,” she says. Mark Blaxill, vice president of SafeMinds, a parent-led advocacy group, also thinks that more attention should be paid to environmental risk factors. “The CDC has not addressed the crisis in autism responsibly,” he says. “They should be raising the alarm, and they have failed to do so. They should be asking why so many children are sick. Instead, they’ve tried to suggest a degree of doubt about the increases, and that diverts attention and funding from environmental causes.”