Subscribe to eTOC

CDC-Backed Study Suggests Possible Link Between Autistic Disorders, Maternal Pesticide Exposure in California

ARTICLE IN BRIEF

  • ✓ Among 29 mothers who lived during their first pregnancy trimester near the fields where the highest levels of organochlorines were used, eight had children later diagnosed with autistic spectrum disorders.

Children born to women who lived near fields where organochloride pesticides were applied in California's Central Valley were more than six times more likely to have autistic spectrum disorders than those whose mothers lived further away, according to a study by the state's public health department.

The study, which was funded by the Centers for Disease Control and Prevention (CDC), is the first to report an association between indirect environmental pesticide exposure and autistic spectrum disorders (ASD). The study was published online July 30 in an advance publication of Environmental Health Perspectives, which is sponsored by the National Institute for Environmental Health Sciences.

FU1-5

Dr. Isaac Pessah said he was not surprised that maternal organochlorine exposure might result in ASD, given what is known about how the compounds work and ASD symptoms. Nevertheless, he said that it is premature to tell if there is any clear association between these pesticides and ASD.

STUDY PROTOCOLS

Investigators collected data from the health records of 465 children with ASD born between 1996 and 1998 in the San Joaquin and Sacramento River valleys and compared them with the records of nearly 7,000 normal, full-term infants.

Of 19 pesticides, only endosulfan and dicofol, both organochlorines, were positively associated with ASD. The highest rates of ASD were in children of women who had lived near farms where records showed organochlorines, most often endosulfan, were used within 500 meters of their home.

Among 29 mothers who during their first pregnancy trimester lived near the fields where the highest levels of organochlorines were used, eight had children later diagnosed with ASD. The risk increased with proximity to treated fields and decreased proportionately with distance from the fields.

“This study is initial research into possible environmental factors in California that may contribute to autism,” said Mark Horton, MD, director of the California Department of Public Health, in a statement released with the study. “It's important to understand that these preliminary findings do not establish a causal relationship between exposure to these pesticides and autism.”

Nonetheless, because only the two organochlorines appeared to have any association with elevated ASD rates, the findings support arguments against such pesticides. Endosulfan has been banned by many countries, and while its use in the US has declined as less toxic products have become available, it is still widely used in parts of the country to protect cotton crops and fruit trees.

NEUROTOXIC EFFECTS

Toxicologist and autism researcher Isaac Pessah, PhD, professor and chair of the department of molecular biosciences and director of the Children's Center for Environmental Health and Disease at the University of California-Davis, was not surprised that maternal organochlorine exposure might result in ASD, given what is known about how the compounds work and ASD symptoms.

Like organophosphates, which were introduced as an alternative to organochlorines because they break down much more rapidly in the environment, he said, organochlorines are excitotoxic to the CNS. They work primarily through phosphorylation of the acetylcholinesterase enzyme, which helps control impulse transmission in the CNS or at the neuromuscular junction.

Loss of enzyme function results in the accumulation of acetylcholine, which causes unregulated impulses, he explained; the major characteristic of neurotoxicity is overstimulation of the CNS. Higher levels of acetylcholine result in sensory and behavioral disturbances, coordination difficulties, and depressed motor function.

By contrast, endosulfans block gamma-aminobutyric acid (GABA) receptors, he said, and many children with ASD have deficits in the inhibition functions these receptors mediate in the brain. “Anything that upsets the balance of the excitation-inhibitory regulatory process might be harmful from a neurological standpoint,” he said.

“We're always surprised when a study suggests a possible environmental link with autistic spectrum disorder, because this hasn't been the accepted viewpoint,” he told Neurology Today. However, if additional research confirms the data in the current study, that view could change. But, he said, “it's much too soon to tell if there is any clear association between these pesticides and ASD.”

FU2-5

Dr. Andrew S. Rowland: “Perhaps the best way to view this paper is as a hypothesis-generating study. More studies are needed to test the specific hypothesis that exposure to organochlorine pesticides during pregnancy increases the risk of having a child with ASD.”

STUDY LIMITATIONS

Andrew S. Rowland, PhD, who conducts environmental epidemiology research, raised questions about the study methodologies. It was unclear if the women who lived near the fields were exposed by working in them, or how the pesticides were applied on those particular crops, said Dr. Rowland, associate professor in the department of family and community medicine at the University of New Mexico in Albuquerque.

“The researchers were concerned about pesticide drift into the homes during application of the pesticides; but without more information about how the chemicals were applied, it is hard to know which women in the study were most likely to be exposed,” he told Neurology Today in a telephone interview.

In addition, he noted, the researchers evaluated several hundred chemical exposure scenarios and were aware that there was a potential multiple testing problem. “Perhaps the best way to view this paper is as a hypothesis-generating study,” he said. “More studies are needed to test the specific hypothesis that exposure to organochlorine pesticides during pregnancy increases the risk of having a child with ASD.”

Dr. Rowland pointed out that the study is part of a national effort by the CDC to link exposure databases with disease registries to see if new insights into environmental hazards can be identified.

“This study is an interesting result from that effort because it looked at two sets of information that are not usually linked,” he said. “But that also means that it is important to be cautious about interpreting the results. The possible downside of linking unrelated databases like this is that you will generate many false positives that are difficult to explain.”

“These are good scientists who did the work,” he said. “Although the methodology was somewhat convoluted, even for someone familiar with environmental epidemiology research, it's a good first step, and points to the need to better understand the long-term effects of pesticide exposure on the developing nervous system.”

REFERENCE

• Roberts E, English P, Grether J, et al. Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley. Environ Health Perspect 2007. E-pub 2007 July 30.