title: Urinary 3,5,6-trichloro-2-pyridinol (TCPY) in pregnant women from Mexico City: distribution, temporal variability, and relationship with child attention and hyperactivity.
abstract: Attention Deficit Hyperactivity Disorder (ADHD) is the most commonly diagnosed and studied cognitive and behavioral disorder in school-age children. The etiology of ADHD and ADHD-related behavior is unclear, but genetic and environmental factors, such as pesticides, have been hypothesized. The objective of this study was to investigate the relationship between in utero exposure to chlorpyrifos, chlorpyrifos-methyl, and/or 3,5,6-trichloro-2-pyridinol (TCPY) and ADHD in school-age Mexican children using TCPY as a biomarker of exposure. The temporal reliability of repeated maternal urinary TCPY concentrations across trimesters was also explored (N=21). To explore associations with ADHD-related outcomes in children, third trimester urinary TCPY concentrations in were measured in 187 mother-child pairs from a prospective birth cohort. Child neurodevelopment in children 6-11 years of age was assessed using Conners' Parental Rating Scales-Revised (CRS-R), Conners' Continuous Performance Test (CPT), and Behavior Assessment System for Children-2 (BASC-2). Multivariable linear regression models were used to test relationships for all children combined and also stratified by sex. Intraclass correlation coefficients (ICC) calculations were based on a random effects model. The ICC was 0.41 for uncorrected TCPY, and ranged from 0.29 to 0.32 for specific gravity-corrected TCPY. We did not observe any statistically significant associations between tertiles of maternal TCPY concentrations and ADHD-related outcomes in children. However, compared to the lowest tertile we found suggestive evidence for increased ADHD index in the highest TCPY tertile in boys (β=5.55 points; 95% CI (-0.19, 11.3); p=0.06) and increased attention problems for the middle tertile in girls (β=5.81 points; 95% CI (-0.75, 12.4); p=0.08). Considering the continued widespread agricultural and possible residential use of chlorpyrifos and chlorpyrifos-methyl in Mexico and the educational implications of cognitive and behavior deficits, these relationships deserve further study.
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
authors.forename: Gamola Z
authors.initials: GZ
authors.lastname: Fortenberry
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA. Electronic address: meekerj@umich.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Meeker
authors.affiliation: Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
authors.forename: Brisa N
authors.initials: BN
authors.lastname: Sánchez
authors.affiliation: Department of Environmental Health, Emory University, Atlanta, GA, USA.
authors.forename: Dana Boyd
authors.initials: DB
authors.lastname: Barr
authors.affiliation: Department of Environmental Health, Emory University, Atlanta, GA, USA.
authors.forename: Parinya
authors.initials: P
authors.lastname: Panuwet
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Bellinger
authors.affiliation: Division of Research on Public Health, National Institute of Perinatology, Mexico City, Mexico.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Schnaas
authors.affiliation: Center for Evaluation Research and Surveys, National Institute of Public Health, Cuernavaca, Morelos, Mexico.
authors.forename: Maritsa
authors.initials: M
authors.lastname: Solano-González
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA; Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA; Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
authors.forename: Adrienne S
authors.initials: AS
authors.lastname: Ettinger
authors.affiliation: Ministry of Health, Distrito Federal, Mexico.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Hernandez-Avila
authors.affiliation: Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
authors.forename: Howard
authors.initials: H
authors.lastname: Hu
authors.affiliation: Division of Statistics, Center for Surveys and Evaluation Research, National Institute of Public Health, Cuernavaca, Morelos, Mexico.
authors.forename: Martha Maria
authors.initials: MM
authors.lastname: Tellez-Rojo
mesh_terms: D000328:Adult; D000383:Agriculture; D001288:Attention / Q000187:drug effects*; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced*; D002648:Child; D002652:Child Behavior / Q000187:drug effects; D002657:Child Development / Q000187:drug effects*; D004390:Chlorpyrifos / Q000009:adverse effects / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D008800:Mexico; D016273:Occupational Exposure / Q000009:adverse effects; D010575:Pesticides / Q000009:adverse effects* / Q000652:urine; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies; D011728:Pyridones / Q000009:adverse effects* / Q000652:urine; D012737:Sex Factors; D055815:Young Adult
chemical_list: D010575:Pesticides; D011728:Pyridones; C012587:3,5,6-trichloro-2-pyridinol; D004390:Chlorpyrifos; C007031:chlorpyrifos-methyl
keywords: ADHD; Biomarker; Children; Exposure; Organophosphates; Pesticides