Prenatal Exposure to Pesticide Linked to Brain Abnormalities

Higher prenatalexposure to a common pesticide, chlorpyrifos (CPF), was associated with a greater likelihood of brain abnormalities and poorer motor function among children aged 6 to almost 15 years in a prospective, longitudinal study.

MRIs revealed widespread brain changes, including thicker frontal, temporal, and posterior inferior cortices; reduced white matter volumes; and lower diffusivity of internal capsule white matter.

Researchers also observed that prenatal CPF exposure levels were linked to lower indices of neuronal density in white matter tracts and lower performance on fine motor and motor programming tasks.

Previous preclinical and clinical studies supported the neurotoxicity of CPF, but this is the first research to look at specific brain changes in people.

“These are very strong associations such that progressively higher levels of exposure are associated with progressively greater disruptions in development of brain structure and metabolism, as well as greater disruptions in motor control,” lead author Bradley S. Peterson, MD, division chief of psychiatry and behavioral sciences at Children’s Hospital Los Angeles, Los Angeles, told Medscape Medical News.

The study was published online on August 18 in JAMA Neurology.

Measuring an Enduring Effect

CPF is a chlorinated organophosphate and one of the most common pesticides used globally. It enters the bloodstream through ingestion or skin contact or after breathing it in.

In pregnant women, the pesticide crosses the placenta, enters the fetal bloodstream, reaches concentrations up to four times higher than those in the mother’s circulation, and crosses the fetal blood-brain barrier.

“Pregnancy is an exquisitely sensitive period of brain development that is vulnerable to environmental exposures, including CPF,” Peterson said. “Protecting unborn children by advocating for restrictions on pesticide use and by educating prospective parents on measures to reduce exposure is essential.”

From January 1998 to July 2006, investigators recruited 727 pregnant African American or Dominican women living in northern New York City. Between 2007 and 2015, MRI scans were performed on 332 of their children aged 6-14.7 years.

Researchers compared MRI findings to CPF levels in umbilical cord or maternal blood, analyzing data between February 2018 and November 2024 on a final cohort of 270 children (median age, 10.38 years).

Maternal exposure to CPF in participants was primarily from spraying indoors for pests, which was prevalent in this inner-city neighborhood before residential use was banned in 2001, the authors noted.

Widespread Brain Changes

Peterson said a surprising study outcome was “how strong and widespread across the brain these associations were” spanning measures of cortical thickness, white matter myelination, neuronal density, and metabolism.

On an MRI, for example, CPF exposure was associated significantly and positively with cortical thickness in frontal regions, including the superior, middle, and inferior frontal gyrus; the anterior cingulate cortex; gyrus rectus; and the middle orbitofrontal and lateral orbitofrontal gyrus.

The same associations were seen in temporal brain regions, including the superior, middle, and inferior temporal gyrus, and the parahippocampus. Posteroinferior regions altered the same way, including the posterior cingulate cortex, cuneus, and the inferior occipital, lingual, and fusiform gyrus.

In contrast, CPF levels were associated with lower cortical thickness in the dorsal parietal region, specifically the superior parietal gyrus, and with lower white matter volumes in multiple frontal, temporal, and posteroinferior regions.

In addition to the anatomic MRI findings, magnetic resonance spectroscopic imaging showed that CPF exposure associated inversely with N-acetyl-L-aspartate, which reflects neuron density, in scattered foci within deep white matter tracts and in gray matter of the insular cortex.

Diffusion tensor imaging also positively linked CPF exposure to fractional anisotropy and inversely with average diffusion coefficient values in the internal capsule. Furthermore, arterial spin labeling revealed higher CPF exposure was associated with a lower regional cerebral blood flow.

“In this cohort study, progressively higher prenatal CPF exposure levels associated significantly with progressively greater alterations in brain measures in each MRI modality, suggesting that prenatal exposure may produce enduring disturbances in brain structure, function, and metabolism in direct proportion to exposure level,” investigators wrote.

Inflammation and Oxidative Stress Likely Culprits

Another unexpected result for Peterson was how similar the CPF findings were to those linked to other prenatal exposures, including air pollution, despite being extremely different chemicals.

This suggests a common pathway for disrupting brain development, “most likely by producing inflammation and oxidative stress in the brain, which are toxic to brain cells early in development,” he said.

Asked about treating children already affected by CPF, Peterson replied, “Unfortunately, we don’t know yet of ways to help children who are already exposed. The only ways we know currently to mitigate risk to unborn children is to minimize exposures.”

He added, “Perhaps in the future, novel therapeutics may reduce inflammation and oxidative stress from CPF and other pesticide exposures and thereby attenuate their adverse effects on brain development.”

Use Remains Controversial

CPF is “ubiquitous” on nonorganic fruit, vegetables, and grains, added Peterson, who is also vice chair for research and chief of the Division of Child and Adolescent Psychiatry at the Keck School of Medicine of USC in Los Angeles. The pesticide is also carried by outdoor air and is often used in agriculture.

“Farm families are at particularly high risk because pregnant women not only work in the fields but also live in nearby communities, where pesticide drift is common,” said senior investigator Virginia A. Rauh, ScD, the Jane and Alan Batkin Professor of Population and Family Health at Columbia Mailman School of Public Health in New York City.

“This is an area where public health policy changes would have a significant impact,” she added.

There are federal and state restrictions. In August 2021, the US Environmental Protection Agency (EPA) removed all “tolerances” or acceptable levels of CPF on food. Several agricultural groups challenged the action, and in December 2023, a US Circuit Court vacated the earlier EPA decision.

The agency is now considering a final rule that would restrict exposures for farm workers and vulnerable populations and set limits for the pesticide on 11 specific crops: alfalfa, apple, asparagus, tart cherry, citrus, cotton, peach, soybean, strawberry, sugar beet, and spring and winter wheat.

State laws on CPF use vary. “Surprisingly,” Rauh said, “CPF is banned in only five states: California, Hawaii, New York, Maryland, and Oregon.”

The National Institute of Environmental Health Sciences, the EPA STAR program, the National Institute of Mental Health, and the John and Wendy Neu Family Foundation supported the research. The study was also supported by an anonymous donor, Patrice and Mike Harmon, the Inspirit Fund, and the Robert Coury family. Peterson, Rauh, and Thompson reported no relevant financial relationships.