Large ECHO cohort finds no link between prenatal organophosphate exposure and autism-related traits

A large prospective cohort study of 3,339 mother-child pairs across 20 US sites found no association between prenatal exposure to organophosphate pesticides (搜索)搜索该药品 and autism-related traits in children, according to findings published in JAMA Pediatrics. The work, led by Haleigh Cavalier and Akhgar Ghassabian at NYU Grossman School of Medicine (搜索)搜索该词条, represents the largest and most varied group of families yet assembled to examine the question.

Organophosphate pesticides (搜索)搜索该药品 are widely used in agriculture, and their metabolites are frequently detected in US population samples. Diet, including pesticide residues in fruits and vegetables, is the primary route of exposure for most people. In this study, 99% of the mothers had detectable pesticide metabolites in their urine, underscoring how ubiquitous the exposure is in the general population.

"While our findings suggest no link between exposure to pesticide and autism-like symptoms, these chemicals are shown to have several other health effects, whether at the levels commonly observed in the general population or at levels seen in the agricultural settings," the researchers said.

Study design and exposure measurement

The team pooled harmonised data from the Environmental influences on Child Health Outcomes (ECHO) cohort, a nationwide program bringing together long-running studies of American children followed from before birth. Mothers enrolled between January 1997 and December 2019, and autism-related outcomes were assessed in children ages 2 to 19 years. Data analysis was performed from April 2024 to November 2025.

Prenatal exposure was measured using urinary concentrations of 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite resulting from chlorpyrifos (搜索)搜索该药品 breakdown, and the sum of six dialkyl phosphate (ΣDAP) metabolites—three dimethyl phosphates and three diethyl phosphates. Each mother provided one urine sample during pregnancy.

The researchers emphasised that the direct biomarker measurement was central to the study's rigor. "We used urine levels of the metabolites of the pesticides, rather than a proxy measure, such as proximity of the residential address to a farm," they told Earth.com.

Outcomes and key findings

Parents reported autism-related traits using the Social Responsiveness Scale (SRS), a 65-item questionnaire capturing social communication and autistic traits. The SRS was administered at a mean age of 6.4 years, and 49.9% of the children were female.

Crude or minimally adjusted models initially suggested inverse associations between prenatal TCPy or ΣDAP levels and SRS scores—an apparent protective effect. However, these associations attenuated and lost statistical significance after full adjustment. Neither biomarker was linked with parent-reported autism-related traits (β per doubling of TCPy concentration = −0.13, 95% CI −0.57 to 0.31; β per doubling of ΣDAP = −0.42, 95% CI −1.03 to 0.19).

The apparent inverse association in unadjusted analyses reflected a confounding effect: women with the highest pesticide metabolite levels are those consuming the most fruits and vegetables, so a raw comparison mixes the chemical exposure with the diet that delivers it. Once the team adjusted for maternal backgrounds, habits, and diet, the apparent benefit disappeared.

Results were consistent across sex-stratified models, secondary analyses using quantile and logistic regressions, various sensitivity analyses, and after adjustments for dietary confounders. There was no evidence of effect modification by maternal diet quality.

Interpreting the null result

The researchers pointed to the study's size and prospective design as key strengths, particularly important when a study reports no association. The design measured exposure during pregnancy and followed children over subsequent years at sites across the country, rather than looking back at families after the fact.

"This study adds another piece to a large and complex puzzle, bringing us closer to understanding how environmental exposures shape neurodevelopment," Cavalier said.

However, the authors were explicit about the limits of their confidence. Exposure in this group ran low, and the work "does not rule out an association at higher levels or among vulnerable populations such as those with genetic susceptibilities."

"While the findings suggest that organophosphate pesticides (搜索)搜索该药品 were not a major driver of autism-related traits at the exposure levels observed in our study, that should not be taken to mean these chemicals are safe," Cavalier said. "Rather, the results inform future work that should focus on chemical mixtures and other factors that may influence risk, such as genetic susceptibility or high-exposure occupations."

Study limitations

Several limitations temper the findings. Parents supplied every rating, and a questionnaire such as the SRS catches children who show autism traits without a formal diagnosis while also stopping short of a diagnosis. A single urine sample must stand in for an entire pregnancy, and the measured metabolites are short-lived in the body, meaning a single reading depends on what a woman ate in the days prior and how quickly her body metabolises the chemicals. The team acknowledged the markers may not capture the full picture of a pregnancy's exposure.

Context and next steps

Earlier research suggested organophosphate pesticides (搜索)搜索该药品 raise children's risk for neurodevelopmental issues such as IQ loss and attention-deficit/hyperactivity disorder (ADHD). A meta-analysis suggested high prenatal organophosphate pesticide exposure may be a risk factor for autism, and studies such as CHARGE and CHAMACOS reported links between prenatal exposure and neurodevelopment. By contrast, researchers in The Netherlands found no relationship with autistic traits or ADHD, and an Ohio-based study also showed no link.

"Differences between study populations are likely to reflect variations in exposure levels, timing, and sources; the presence of agricultural co-exposures; and differences in population characteristics or underlying risk factor distributions," the authors noted. "Our results therefore contribute to an emerging pattern: positive associations tend to appear where exposures are high and associated with an agricultural context, whereas null associations are more common in general population settings characterised by low exposure occurring primarily through diet."

The team is now expanding the work to incorporate genetic information, since the effect of pesticides could differ depending on an individual's genetic make-up. They also flagged growing concern around other exposures, including phthalates used in plastics and the herbicide glyphosate.

The researchers said they would still recommend choosing organic produce where possible and washing or peeling produce before eating it, while noting that "conventional produce consumption is one of the strongest predictors of organophosphate pesticide biomarker concentrations, and organophosphate metabolites decrease substantially after adoption of an organic diet."