A major study reveals that prenatal exposure to chlorpyrifos, once widely used in homes and farms, may have lasting effects on children’s brains, from disrupted metabolism to weaker motor skills.
Study: Brain Abnormalities in Children Exposed Prenatally to the Pesticide Chlorpyrifos. Image credit: hedgehog94/Shutterstock.com
A JAMA Neurology study used a sample of school-aged children to examine the associations between prenatal chlorpyrifos (CPF) exposure and brain abnormalities. CPF exposure during prenatal development was associated with changes in neuronal tissue differentiation, enhanced myelination of the internal capsule, reduced fine motor speed and motor programming skills, and significantly disrupted regional blood flow and localized neuronal metabolism throughout the brain.
Chlorpyrifos exposure and brain development
CPF is a very common insecticide used globally, so it is typically found everywhere, including in non-organic grains, vegetables, and fruits, as well as in air and dust. In this study’s New York City cohort, prenatal exposure largely came from indoor residential spraying before its 2001 U.S. residential ban. In pregnant women, it has been seen to cross the placenta and reach the fetal brain. In rodent models, prenatal and neonatal CPF exposure has adversely impacted the brain, hampering neuron and glia generation and interfering with neuronal differentiation. Early exposure to CPF is more toxic to glial cells than to neurons.
The adverse effects of CPF exposure could be mediated at the molecular level, including neuroinflammation, oxidative stress, altered responses to neurotrophins, and impaired mitochondrial function. Research using rodent models has shown that these molecular effects lead to motor hyperactivity, learning and memory problems, and adulthood behaviors resembling anxiety and depression.
Prenatal exposure to CPF in humans has been linked to lower fetal growth, lower birth weight, smaller head size, abnormal newborn reflexes, and other disorders. The preclinical and clinical research conducted so far has shed light on the neurotoxicity of prenatal CPF exposure, but its effects on the human brain are unknown.
About the study
This prospective, longitudinal pregnancy cohort study examined the impact of prenatal CPF exposure on offspring brain metabolism, structure, and function in middle childhood. The study was conducted between January 1998 and July 2015 among pregnant women (N = 727) of African American or Dominican descent aged between 18 and 35.
During pregnancy, women completed questionnaires and self-identified their race and ethnicity. These data were collected to assess the representativeness of the sample. Within one day postpartum, maternal blood was collected, and umbilical cord blood was also obtained at delivery; CPF plasma levels from either source were measured. Of the original 727 women, 512 had CPF levels measured, and MRI analyses were conducted on 270 children aged 6-14.
Cortical thickness and local white matter volumes at the cerebral surface were evaluated using anatomical MRI measures. The direction and rate of water diffusion were assessed by diffusion tensor imaging (DTI). Fractional anisotropy (FA) in DTI represented the directional preference of diffusion, and the mean diffusion rate over three spatial directions was represented using the average diffusion coefficient (ADC).
Furthermore, regional cerebral blood flow (rCBF) was measured using arterial spin labeling (ASL), and the brain metabolite concentrations were measured using magnetic resonance spectroscopic imaging (MRSI).
Study findings
A positive association was observed between prenatal CPF exposure and cortical thickness in frontal, temporal, and posteroinferior regions. An inverse association was noted between CPF exposure and cortical thickness in the dorsal parietal region. Concerning local white matter volumes in the frontal, temporal, and posteroinferior regions, an inverse association was noted with CPF exposure.
CPF exposure is inversely associated with ADC and positively associated with FA values in the internal capsule (IC). This was particularly true for IC’s anterior limb and genu for FA, and for the anterior limb, genu, and posterior limb for ADC. The long axis of IC fiber bundles exhibited reduced diffusion in both the radial and axial directions, contributing to lower ADC values. Across most brain regions, there was an inverse association between prenatal CPF exposure and rCBF values.
The concentration of N-acetylL-aspartate (NAA), an index of healthy neuron density, was measured using MRSI. Within deep white matter tracts and gray matter of the insular cortex, NAA was inversely associated with CPF exposure. The findings for other metabolites were sparse. A positive association was found between CPF and glutamate/glutamine (Glx) concentrations in the anterior cingulate cortex, after normalizing metabolite concentrations to creatine. The association between CPF and MRI measures in any modality was not significantly moderated by age or sex.
Concerning behavioral outcomes, a significant inverse association was noted between CPF values and fine motor speed and motor programming in both hands. The effects were disproportionate in the nondominant hand for motor programming.
Conclusions
Prenatal CPF exposure was associated with higher myelination of the internal capsule, changed differentiation of neuronal tissue into cortical white and gray matter, and poorer fine motor and motor programming performance. Widespread reductions in brain blood flow and scattered, localized reductions in neuronal density (NAA) suggest metabolic disruption. Some of the observed associations are accounted for by the molecular and cellular effects of CPF, including oxidative stress, inflammation, impaired mitochondrial functioning, and oligodendrocyte dysregulation.
A key limitation of the current study is the lack of generalizability of the findings, as the sample consisted of urban Dominican and African American women. There could have been selection bias regarding which individuals in the cohort could be contacted and who agreed to participate in MRI scanning. Furthermore, postnatal CPF exposure and exposure to other insecticides were not accounted for and could have influenced the results.
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