A new study reports that prenatal exposure to the insecticide chlorpyrifos is associated with lasting changes in the structure and metabolism of the brain in children and adolescents. The research also found a link between exposure to the chemical before birth and poorer performance on tasks measuring fine motor control. The findings, which suggest that the insecticide may produce widespread and enduring disturbances in brain development, were published in the journal JAMA Neurology.
Researchers pursued this investigation because chlorpyrifos has been one of the world’s most widely used insecticides, commonly applied to agricultural crops. Previous studies have shown that the chemical can cross the placenta from a pregnant mother to the developing fetus, where it can enter the brain. Animal research has indicated that chlorpyrifos can interfere with the generation and development of brain cells.
Some earlier studies in humans had also connected prenatal exposure to outcomes like smaller head size at birth, developmental delays in toddlers, and lower intelligence scores. Led by first author Bradley S. Peterson of the Keck School of Medicine at the University of Southern California, the research team used advanced brain imaging techniques to look for specific, long-term physical markers in the brains of youths who were exposed in the womb.
The investigation was a prospective, longitudinal cohort study, meaning it followed a group of individuals over a long period. Researchers recruited 727 pregnant women from northern Manhattan, New York, between 1998 and 2006. The women self-identified as either African American or Dominican. To measure prenatal exposure to chlorpyrifos, scientists collected blood from the mother or the umbilical cord at the time of delivery and measured the concentration of the insecticide. The study noted that before a residential ban in 2001, a primary source of exposure in this community was indoor spraying for pests.
Years later, when the children from this cohort were between the ages of 6 and 14, 270 of them participated in the brain imaging phase of the study. The researchers used several different kinds of magnetic resonance imaging to get a comprehensive picture of the brain. One technique measured the thickness of the cortex, the brain’s folded outer layer responsible for higher-level thinking. Another method, called diffusion tensor imaging, assessed the structure of the brain’s white matter, which contains the nerve fiber bundles that transmit signals between brain regions.
A third technique, arterial spin labeling, measured regional blood flow, which serves as an indicator of brain metabolism. Finally, magnetic resonance spectroscopic imaging was used to measure the levels of certain chemicals in the brain, including one called N-acetyl-l-aspartate, a marker of healthy neuron density. The children also underwent a series of behavioral tests to assess their motor skills, attention, and general intelligence.
The results showed a clear pattern: progressively higher levels of prenatal chlorpyrifos exposure were associated with progressively greater alterations in the brain. Anatomical scans revealed that higher exposure was linked to a thicker cortex in large areas of the frontal, temporal, and posteroinferior regions of the brain. At the same time, the volume of local white matter directly beneath these thickened areas was smaller. The scientists suggest this could indicate a shift in the boundary between the brain’s gray matter and white matter, possibly related to changes in the organization of the cortex or the myelination of nerve fibers.
The imaging of the brain’s white matter tracts showed that higher chlorpyrifos exposure was associated with changes in the internal capsule, a critical pathway that connects the cortex with deeper brain structures. These changes could represent either a higher density of nerve fibers or an alteration in the myelin sheath, the fatty insulation that helps signals travel efficiently.
The study also found that higher prenatal exposure was linked to significantly lower blood flow throughout most regions of the brain. This widespread reduction suggests a long-term decrease in brain metabolism. Adding to this, measurements of brain chemistry showed that higher exposure was connected to lower concentrations of N-acetyl-l-aspartate in certain deep white matter areas, pointing to a lower density of healthy neurons.
When the researchers looked at the behavioral test results, they found a significant link between prenatal chlorpyrifos exposure and motor function. Children with higher exposure levels performed more poorly on tests of fine motor speed, such as finger-tapping, and on motor programming tasks that involve complex finger sequences. These behavioral findings are consistent with the observed structural changes in the brain’s motor circuits. The study did not find significant associations between chlorpyrifos exposure and the other cognitive or behavioral domains that were tested.
The scientists propose a potential biological mechanism to explain their findings. They note that the pattern of brain changes observed in connection with chlorpyrifos is remarkably similar to what they found in a previous study on prenatal exposure to air pollution within the same group of children. Since the two exposures were not correlated with each other, this suggests that different environmental toxins might affect brain development through a final common pathway.
Preclinical studies indicate that chlorpyrifos, along with pollutants found in air pollution, can trigger inflammation and oxidative stress. In the developing fetal brain, this could impair the function of mitochondria, the energy-producing centers of cells. This damage could be especially toxic to the cells responsible for creating myelin, leading to the kinds of white matter abnormalities and altered brain structure seen in the scans.
“The disturbances in brain tissue and metabolism that we observed with prenatal exposure to this one pesticide were remarkably widespread throughout the brain. Other organophosphate pesticides likely produce similar effects, warranting caution to minimize exposures in pregnancy, infancy, and early childhood, when brain development is rapid and especially vulnerable to these toxic chemicals,” said first author Bradley Peterson, who is also the Vice Chair for Research and Chief of Child & Adolescent Psychiatry in the Department of Psychiatry at the Keck School of Medicine.
“Current widespread exposures, at levels comparable to those experienced in this sample, continue to place farm workers, pregnant women, and unborn children in harm’s way. It is vitally important that we continue to monitor the levels of exposure in potentially vulnerable populations, especially in pregnant women in agricultural communities, as their infants continue to be at risk,” said Virginia Rauh, a senior author on the study and a professor at Columbia University Mailman School of Public Health.
The study has some limitations. The participants were from a specific urban community of Dominican and African American families, so the findings may not be generalizable to all populations. As an observational study, it identifies associations but cannot prove that chlorpyrifos exposure directly caused the observed brain and behavioral differences.
The researchers did not measure exposure to the insecticide after birth, nor did they account for potential exposure to other pesticides or for genetic factors that can influence how the body metabolizes these chemicals. Future work could explore whether the effects seen with chlorpyrifos are caused by a shared mechanism of inflammation, which could open avenues for developing interventions to reduce or prevent the adverse effects of various neurotoxicants.
The study, “Brain Abnormalities in Children Exposed Prenatally to the Pesticide Chlorpyrifos,” was authored by Bradley S. Peterson, Sahar Delavari, Ravi Bansal, Siddhant Sawardekar, Chaitanya Gupte, Howard Andrews, Lori A. Hoepner, Wanda Garcia, Frederica Perera, and Virginia Rauh.
