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Estimating the causal effect of prenatal lead exposure on prepulse inhibition deficits in children and adolescents
Journal article   Peer reviewed

Estimating the causal effect of prenatal lead exposure on prepulse inhibition deficits in children and adolescents

Kalé Z. Kponee-Shovein, Marc G. Weisskopf, Rachel Grashow, Ran S. Rotem, Brent A. Coull, Lourdes Schnaas, Maria del Carmen Hernández-Chávez, Brisa Sanchez, Karen Peterson, Howard Hu, …
Neurotoxicology (Park Forest South), v 78, pp 116-126
May 2020
DOI: https://doi.org/10.1016/j.neuro.2020.02.013
PMID: 32126243
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://www.ncbi.nlm.nih.gov/pmc/articles/12042602View
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Abstract

Biomarker Causal inference Neurodevelopmental disorders Neurotoxicants Prenatal lead Prepulse inhibition
•Lead is a neurotoxicant associated with neurodevelopmental deficits.•Prepulse inhibition (PPI) deficits are associated with neurological disorders.•We estimated the causal effect of prenatal lead exposure on PPI in children.•Our findings suggest prenatal lead exposure causes PPI deficits in children.•PPI may be an objective biomarker of neurotoxicant effects on the brain. During pregnancy, maternal lead from earlier exposures mobilizes and crosses placental barriers, placing the developing fetus at risk for lead exposure and neurodevelopmental deficits. Some neuronal circuits known to be affected in neurodevelopment disorders can be probed with simple physiological behavioral paradigms. One such neural biomarker is Pre-Pulse Inhibition (PPI), an indicator of adequate sensorimotor gating processing. In clinical studies, deficits in PPI have been associated with neurodevelopmental disorders in human subjects. To our knowledge, no studies have examined the use of PPI as a biomarker of toxicant effects on the brain in epidemiological studies. We aimed to estimate the causal effect of prenatal lead exposure, assessed by maternal cortical bone lead concentrations, on PPI in 279 children from Mexico City. in vivo maternal cortical bone lead measurements were taken at four weeks postpartum at the mid-tibia shaft using a K-Shell X-ray fluorescence instrument. PPI recording occurred in an isolated clinical setting and eye blink responses were measured using electromyography. We assessed if the conditions for causal inference held in our study and used the results of our assessment to estimate the causal effect of prenatal lead exposure on PPI using an ordinary least squares regression model, a marginal structural model, and the parametric g-formula. Results were consistent across the three modeling approaches. For the parametric g-formula, a one standard deviation (10.0 μg/g) increase in prenatal lead significantly reduced PPI by approximately 19.0 % (95 % CI: 5.4 %, 34.3 %). This decrease is similar in magnitude to clinical studies on schizophrenia, which have observed PPI impairments in patients with schizophrenia as compared to controls. Our results are consistent with findings from other studies establishing an association between lead exposure and neurodevelopmental disorders in children and suggest that PPI may be useful as an objective biomarker of toxicant effects on the brain.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Neurosciences
Pharmacology & Pharmacy
Toxicology
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