title: Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood.
abstract: BACKGROUND
  Prenatal exposure to organophosphate pesticides has been shown to negatively affect child neurobehavioral development. Paraoxonase 1 (PON1) is a key enzyme in the metabolism of organophosphates.
  
  
  OBJECTIVE
  We examined the relationship between biomarkers of organophosphate exposure, PON1, and cognitive development at ages 12 and 24 months and 6-9 years.
  
  
  METHODS
  The Mount Sinai Children's Environmental Health Study enrolled a multiethnic prenatal population in New York City between 1998 and 2002 (n = 404). Third-trimester maternal urine samples were collected and analyzed for organophosphate metabolites (n = 360). Prenatal maternal blood was analyzed for PON1 activity and genotype. Children returned for neurodevelopment assessments ages 12 months (n = 200), 24 months (n = 276), and 6-9 (n = 169) years of age.
  
  
  RESULTS
  Prenatal total dialkylphosphate metabolite level was associated with a decrement in mental development at 12 months among blacks and Hispanics. These associations appeared to be enhanced among children of mothers who carried the PON1 Q192R QR/RR genotype. In later childhood, increasing prenatal total dialkyl- and dimethylphosphate metabolites were associated with decrements in perceptual reasoning in the maternal PON1 Q192R QQ genotype, which imparts slow catalytic activity for chlorpyrifos oxon, with a monotonic trend consistent with greater decrements with increasing prenatal exposure.
  
  
  CONCLUSIONS
  Our findings suggest that prenatal exposure to organophosphates is negatively associated with cognitive development, particularly perceptual reasoning, with evidence of effects beginning at 12 months and continuing through early childhood. PON1 may be an important susceptibility factor for these deleterious effects.
authors.affiliation: Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York, USA. Stephanie.Engel@unc.edu
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Engel
authors.forename: James
authors.initials: J
authors.lastname: Wetmur
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.forename: Chenbo
authors.initials: C
authors.lastname: Zhu
authors.forename: Dana Boyd
authors.initials: DB
authors.lastname: Barr
authors.forename: Richard L
authors.initials: RL
authors.lastname: Canfield
authors.forename: Mary S
authors.initials: MS
authors.lastname: Wolff
mesh_terms: D043303:Aryldialkylphosphatase / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D010755:Organophosphates / Q000633:toxicity*; D010465:Perception / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
chemical_list: D010755:Organophosphates; D043303:Aryldialkylphosphatase