Table 2.

Epidemiological studies associating developmental exposures to OP insecticides and neurological deficits at different ages after birth.

Cohort	Subjects Age at Time of Testing	Biomarker of Exposure	Associated Significant Health Outcome	Reference
CHAMACOS cohort (California, U.S.)	Children at 7 years of age	Total DAP levels in urine sampled during pregnancy (~13 and 26 weeks of gestation) and from children at 6 months and 1, 2, 3.5, and 5 years of age	Maternal urine DAP levels associated with deficits in working memory, processing speed, verbal comprehension, perceptual reasoning, and FSIQ	Bouchard et al., 2011
Mount Sinai Children's Environmental Health Cohort, New York	Infants assessed within 5 days of delivery	OP metabolites in maternal urine sampled at ~31 weeks of gestation: DMP, DMTP, DMDTP, DEP, DETP, DEDTP, MDA	Abnormal reflexes	Engel et al., 2007
CHAMACOS cohort (California, U.S.)	Children at 6, 12 and 24 months of age	OP metabolites in urine sampled during pregnancy (~13 and 26 weeks of gestation) and from children at time of test: DAPs (DMP, DMTP, DMDP, DEP, DETP, DEDP), MDA, TCPY	Both prenatal and postnatal DAPs associated with risk of pervasive development disorder (Bayley Scales of Infant Development)	Eskenazi et al., 2007
CHAMACOS cohort (California, U.S.)	Children at 6-9 years of age	6 DAPs in maternal urine sampled once between 25 and 40 weeks of gestation: DMP, DMTP, DMDP DEP, DETP, DEDP	Working memory deficits	Furlong et al., 2017
Columbia Center for Children•s Environmental Health (New York, U.S.)	Children at 7 years of age	Chlorpyrifos in umbilical cord blood	Working memory deficits Reduced FSIQ (Wechsler Scales of Infant Intelligence)	Horton et al., 2012
Prospective birth cohort from rural Bangladesh	Children at 1 and 2 years of age	OP metabolites in maternal urine sampled at ~11 weeks of gestation: TCPY, 4-nitrophenol, MDA, IMPY	Reduced weight at birth Reduced length at birth Women in highest quartile of recorded 4-nitrophenol were at increased risk for preterm delivery or decreased child size Women with detectable IMPY were at increased risk of having a child with low birth weight	Jaacks et al., 2020
Pregnant women from three hospitals in Thailand	Children at 5 months of age	DAPs in maternal urine sampled at ~28 weeks of gestation: DMP, DEP, DETP, DEDTP (Total DAPs = DMP + DEP + DETP + DEDTP; total DEPs = DEP + DETP + DEDTP)	Reduced motor composite scores significantly associated with total DEP and total DAP levels Reduced cognitive composite scores significantly associated with total DEP levels (Bayley-III scoring)	Kongtip et al., 2017
Columbia Center for Children's Environmental Health (New York, U.S.)	Newborn children	Chlorpyrifos in plasma (maternal blood and umbilical cord blood at delivery)	Reduced weight at birth Reduced length at birth	Perera et al., 2003
MARBLES Cohort (California, U.S.)	Children at 3 years of age	OP metabolites in urine sampled in the 2nd and 3rd trimesters of gestation: DMP, DMTP, DMDP, DEP, DETP, DEDP, TCPY	Increased risk of clinically diagnosed autism spectrum disorder in girls	Philippat et al., 2018
Health Outcomes and Measures of the Environment Cohort (Cincinnati, U.S.)	Newborn children	6 DAPs in maternal urine sampled at ~16 and 26 weeks of gestation: DMP, DMTP, DMDTP, DEP, DETP, DEDTP	Reduced weight at birth Reduced length at birth	Rauch et al., 2012
Columbia Center for Children's Environmental Health (New York, U.S.)	Children at 1, 2, and 3 years of age	Chlorpyrifos in plasma (maternal blood and umbilical cord blood at delivery)	Deficits in Bayley Mental Development Index and Psychomotor Development Index Attention problems, ADD/ADHD problems and pervasive developmental disorder problems	Rauh et al., 2006
Columbia Center for Children's Environmental Health (New York, U.S.)	Children at 7 years of age	Chlorpyrifos in umbilical cord blood	Working memory deficits Reduced FSIQ (Wechsler Intelligence Scale for Children, 4th edition)	Rauh et al., 2011
Columbia Center for Children's Environmental Health (New York, U.S.)	Children at 6-11 years of age	Chlorpyrifos in plasma (umbilical cord blood at delivery)	Bilateral enlargement of superior temporal, posterior middle temporal and inferior postcentral gyri Enlargement of superior frontal gyrus, gyrus rectus, cuneus, and precuneus along mesial wall of right hemisphere only Frontal and parietal cortical thinning	Rauh et al., 2012
Columbia Center for Children's Environmental Health (New York, U.S.)	Children at 11 years of age	Chlorpyrifos in plasma (umbilical cord blood at delivery)	Mild or mild-to-moderate tremors	Rauh et al., 2015
CHAMACOS cohort (California, U.S.)	Children at 10 years of age	Residential proximity to commercial OP pesticide usage during pregnancy	Working memory deficits, reduced FSIQ, and perceptual reasoning deficits associated with mothers in the highest quartile of proximal pesticide usage (Wechsler Intelligence Scale for Children, 4th edition)	Rowe et al., 2016
CHAMACOS cohort (California, U.S.)	Children at 7, 10, and 14 years of age	DAPs in urine sampled during pregnancy (~13 and 26 weeks of gestation): DMP, DMTP, DMDP, DEP, DETP, DEDP	Increased odds of autism spectrum disorders-related traits (social behavior; no sex differences)	Sagiv et al., 2018
CHAMACOS cohort (California, U.S.)	Adolescents at 15-16 years of age	Residential proximity to commercial use of OP during pregnancy	Reduced activation of prefrontal cortex during testing of cognitive flexibility and working memory Increased activation of parietal regions during working memory tests	Sagiv et al., 2019
CHARGE cohort (California, U.S.)	Children at 2-5 years of age	Residential proximity to commercial use of OP during pregnancy and residential use of OP pesticides during pregnancy	Increased risk of clinically diagnosed autism spectrum disorder	Schmidt et al., 2017
CHARGE cohort (California, U.S.)	Children at 2-5 years of age	Residential proximity to commercial use of OP during pregnancy	Increased risk of clinically diagnosed autism spectrum disorder	Shelton et al., 2014
CHAMACOS cohort (California, U.S.)	Infants assessed at >3 days and <2 months of age	6 DAPs in urine maternal urine sampled at ~13 and 26 weeks gestation and 7 days postpartum: DMP, DMTP, DMDTP, DEP, DETP, DEDTP	Increased proportion of infants with more than three abnormal reflexes (Brazelton Neonatal Behavioral Assessment Scale)	Young et al., 2005

DAPs, dialkylphosphates; DMP, dimethylphosphate; DMTP, dimethyl thiophosphate; DMDTP, dimethyldithiophosphate; DEP, diethylphosphate; DETP, diethylthiophosphate; DEDTP, diethyldithiophosphate; IMPY, 2-isopropyl-4-methyl-6-hydroxypyrimidine; MDA, malathion diacarboxylic acid; TCPY, 3,5,6- Trichloro-2-pyridinol. MDA and TCPY are malathion- and chlorpyrifos-specific metabolites. IMPY is a specific metabolite of diazinon. 4-nitrophenol is a specific metabolite of parathion and methyl parathion. DAPs are non-specific OP metabolites. For instance, DMPs can be generated from malathion, chlorpyrifos methyl, and phosmet. DEP and DETP can be generated from chlorpyrifos, parathion, diazinon.