Appendix 5: Summary Table of Children’s Health Cohort Data

Page 1 of 12

Author, Year, 

Sample Size

Outcome 

Assessed

Exposure 

Measurement

Potential confounders 

considered

Primary Result Conclusions/Uncertainties Strengths and Weaknesses 

Article 1: Whyatt et al. 

(2004) Columbia U. 

(N=314)

Birth length, Birth

weight, head 

circumference

Four cord plasma 

chlorpyrifos exposure 

groups and four 

chlorpyrifos and 

diazinon exposure 

groups. Chlorpyrifos 

only categories, Group 

1: levels below LOD 

(32% of participants); 

Group 2: lowest 1/3 of 

detectable levels (20 

%); Group 3: middle 

1/3 (24%), Group 4: 

highest 1/3 (25%.) 

Chlorpyrifos and 

diazinon together: 

Group 1: 26%, Group 

2: 22 %, Group 3: 26%, 

Group 4: 26%.

Gestational age, maternal prepregnancy weight, maternal net 

pregnancy weight gain, gender 

of newborn, parity, 

race/ethnicity, ETS in home, 

season, cesarean section

For each log unit increase in 

cord plasma chlorpyrifos levels, 

birth weight decreased by 42.6 g 

(95% CI: –81.8 to –3.8) and birth 

length decreased by 0.24 cm 

(95% CI: –0.47 to –0.01). Birth 

weight averaged 186.3 g less 

(95% CI: –375.2 to –45.5) among 

newborns with the highest 

compared with lowest 26% of 

exposure levels (p = 0.01).

Associations between birth 

weight and length and cord 

plasma chlorpyrifos were 

statistically significant (p ≤ 

0.007) among newborns born 

before the January 2001 policy 

change. Among newborns born 

after January 2001, exposure 

levels were substantially lower, 

and no associations with fetal 

growth outcomes were 

observed (p > 0.8). 

Strengths: prospective nature of 

the study; direct measurement 

of chlorpyrifos in cord blood and 

personal air samples, rather 

than non-specific markers of 

organophosphate pesticide 

exposure; consideration of 

other pesticides and 

environmental contaminants as 

covariates in the multivariate 

models. 

Limitations: single exposure 

sampling period; the authors did 

not present nor discuss 

regression diagnostics to assess 

the degree to which their 

models met or violated the 

assumptions implicit in linear 

models. 

Article 2: Berkowitz et 

al.(2004) Mt. 

Sinai (N=404)

Birth length, birth 

weight, head 

circumference, 

gestational age

LOD: 11 ug/L (57% 

<LOD TCPy)

Race/ethnicity, infant sex, and 

gestational age. The authors also 

controlled for birth weight or 

birth length in their assessment 

of head circumference and 

pesticide exposure.

Mean levels of birth weight, 

length, head circumference, and 

gestational age did not differ 

between those with urinary 

pesticide metabolite levels 

below and above the level of 

detection.

Similarly, no statistically 

significant associations were 

observed between reported 

pesticide exposure and mean 

indices of fetal growth and 

gestational age. 

PON1 activity also predictor of 

smaller head circumference; 

creatinine corrected

Very well conducted study with 

numerous strengths and very 

few weaknesses. 

The questionnaire-based 

pesticide exposure questions 

are subject to imperfect recall. 

Errors would, on average, 

attenuate associations between 

these exposure metrics and 

fetal development. 

Recall-based exposure 

assessments were fortified by 

objective measures of 

pesticides/pesticide 
Appendix 5: Summary Table of Children’s Health Cohort Data

Page 2 of 12

Author, Year, 

Sample Size

Outcome 

Assessed

Exposure 

Measurement

Potential confounders 

considered

Primary Result Conclusions/Uncertainties Strengths and Weaknesses 

metabolites.

A metabolite specific for 

chlorpyrifos (TCPy) was 

assessed. 

Statistical analysis was 

appropriate. 

Observed mean reductions in 

the outcome parameters appear 

to be small in magnitude and 

may be of little clinical 

significance. 

Assessment and control for 

confounding were appropriate. 

However, confounding by 

unmeasured (and mismeasured) 

risk factors for abnormal growth 

that are related to pesticide 

exposure would bias the results 

in this study. Such factors may 

be related to socioeconomic 

status of the study participants, 

a cofactor which is difficult to 

define, no less measure in an 

epidemiologic study.

Limited external validity 

(generalizability) due to the 

particular study population 

recruited and the numerous 

exclusion criteria applied.

Article 3: Eskenazi et 

al. (2004) 

CHAMACOS (N=488)

Birth length, birth 

weight, head 

circumference, 

Gestation Length, 

Ponderal index

Total DAPs: median 

136 nmol/L (range: 

10–6,854); DEP: 

median 22 nmol/L 

(range: 2–680 nmol/L); 

TCPy: median 3.3 

nmol/L (range: 0.2–

56.1nmol/L) (76% 

>LOD)

Gestational age, gestational age 

squared, maternal age, 

pregnancy weight gain, week of 

initiating prenatal care, parity, 

infant sex, mother's country of 

birth, body mass index, family 

income, poverty level, smoking, 

alcohol, illicit drug use, 

environmental tobacco smoke, 

Decreases in gestational 

duration associated with two 

measures of in utero pesticide 

exposure: levels of metabolites 

of dimethyl phosphate pesticide 

compounds and whole blood 

ChE.

Maternal urine collection 

averaged wks.14, 26, not 

creatinine-corrected

Strengths in the study design 

include the longitudinal design, 

the use of multiple exposure 

biomarkers, including 

quantification of non-specific 

(DAPs), chlorpyrifos-specific 

(TCPy) metabolites, and other 

environmental co-exposures. A 

reasonable set of exclusion 
Appendix 5: Summary Table of Children’s Health Cohort Data

Page 3 of 12

Author, Year, 

Sample Size

Outcome 

Assessed

Exposure 

Measurement

Potential confounders 

considered

Primary Result Conclusions/Uncertainties Strengths and Weaknesses 

caffeine, history of low birth 

weight, and history of pre-term 

delivery.

criteria were applied.The 

selection of the CHAMACOS 

population, which consists 

mostly of children from lowincome families, served to 

increase the relative statistical 

efficiency of the study, as this 

population is at high risk of 

neurodevelopmental deficits, 

compared to the general 

population.The statistical 

analysis used to assess the 

associations between the 

markers of exposure and 

neurodevelopment were 

appropriate.Errors in the 

assignment of exposure in this 

prospective study will likely 

have resulted in attenuation of 

observed associations.

Article 4: Harley et al. 

(2011) 

CHAMACOS (N=329)

Birth length, birth 

weight, head 

circumference, 

gestational age 

The geometric mean 

for the DAP 

concentrations during 

pregnancy (for the 

average of the two 

sampling periods) was 

146 nmol/L (95% CI: 

133, 160); of this, a 

larger proportion was 

DMP metabolites (GM 

= 109 nmol/L; 95% CI 

=98, 120) than DEPs 

(GM= 23 nmol/L; 95% 

CI = 21, 25). Allele 

frequencies: PON1 192 

Q allele= 50%; PON1 -

108 T allele= 

46%.Mean 

arylesterase activity: 

For infants: 33.6 U/mL 

(SD = 16) For mothers: 

136.6 U/mL (SD = 44). 

Mean paraoxonase 

Maternal intelligence (Peabody 

Picture Vocabulary Test (PPVT)), 

measures of how stimulating the 

environment is, and known or 

suspected neurotoxins were 

measured prenatally. To 

measure the quality and extent 

of stimulation available to a 

child in the home environment, 

the Infant-Toddler HOME (Home 

Observation for Measurement 

of the Environment) inventory 

was completed at the 6-month, 

1, 2, 3.5, 5, and 7 year visits; 

known or suspected 

neurotoxicants, polybrominated 

diphenyl ethers (PBDEs), 

polychlorinated biphenyls 

(PCBs), p,p’-

dichlorodiphenyltrichlorethane 

(DDT), p,p’-

dichlorodiphenyltrichlorethylene 

(DDE), and lead. 

The authors observed evidence 

of an association between 

prenatal exposure to OP 

pesticides as measured by 

urinary DAP metabolites in 

women during pregnancy, is 

associated with decreased 

cognitive functioning in children 

at age 7.

Infants whose PON1 genotype 

and enzyme activity levels 

suggested that they might be 

more susceptible tothe effects 

of OP pesticide exposure had 

decreased fetal growth and 

length of gestation. PON1 may 

be a contributing factor to 

preterm or low birth weight 

birth.

This study has many strengths, 

the longitudinal design, the 

measurement of urinary DAP at 

multiple time points and 

following children to age seven 

when tests of cognitive function 

are reportedly more reliable. 

The authors were able to adjust 

for or consider many factors 

related to cognitive function, 

such as prenatal exposure to 

other environmental agents, 

socioeconomic indicators, 

maternal intelligence and

education, and child 

stimulation. The cohort had a 

relatively homogenous 

socioeconomic profile, reducing 

the potential for uncontrolled 

confounding. 
Appendix 5: Summary Table of Children’s Health Cohort Data

Page 4 of 12

Author, Year, 

Sample Size

Outcome 

Assessed

Exposure 

Measurement

Potential confounders 

considered

Primary Result Conclusions/Uncertainties Strengths and Weaknesses 

activity: For infants: 

256.6 U/L (SD = 165); 

For mothers: 989.0 

U/L (SD = 616).

Article 5: Engel et al. 

(2007) Mt. Sinai 

(N=311)

Brazelton Neonatal 

Behavioral Assessment 

Scale (BNBAS) , 

primitive reflexes 

(neurological integrity) 

measured before 

hospital discharge.

Diethylphosphates 

(DEP): 24.7 nmol/L; 

Total DAP: 82 nmol/L

Maternal age, race, marital 

status, education, cesarean 

delivery, delivery anesthesia, 

infant age at examination, infant 

gender, infant jaundice, smoking 

(yes/no), alcohol consumption, 

caffeine consumption, illicit drug 

use during pregnancy, and the 

examiner. 

No adverse associations were 

found for DAPs and any 

measured behavior. Relative to 

the first quartile, quartiles 2–4 

of total DEPs, DMPs, and DAPs 

were associated with an 

increased proportion of 

abnormal reflexes, although the 

associations did not increase 

monotonically and varied in 

their strength and precision. 

Used non-specific biomarker 

DEP/DAP

This was a well conducted 

prospective study conducted in 

a young, predominantly 

minority population. The study 

design, analytic approach, and 

statistical analyses were 

appropriate. Pesticide 

metabolites evaluated are not 

specific for chlorpyrifos. The 

BNBAS was administered before 

hospital discharge only on a 

subset of children in the cohort 

(n =311/404). Factors related to 

weekend delivery (e.g., fewer 

inductions) would be 

underrepresented among the 

tested subjects, and may induce 

bias, reduce the degree of 

precision with which 

associations were estimated, 

and limit the generalizability of 

the study findings.The statistical 

analysis was largely appropriate. 

Imputing of missing data may 

affect precision of association 

estimates and result in 

attenuated effect estimates as a 

result of exposure measurement 

error.Assessment and control 

for confounding were 

appropriate. However, 

confounding by unmeasured 

(and mi-asured) risk factors for 

abnormal growth that are 

related to pesticide exposure 

would bias the results in this 

study. Such factors may be 

related to socioeconomic status 

of the study participants, a 
Appendix 5: Summary Table of Children’s Health Cohort Data

Page 5 of 12

Author, Year, 

Sample Size

Outcome 

Assessed

Exposure 

Measurement

Potential confounders 

considered

Primary Result Conclusions/Uncertainties Strengths and Weaknesses 

cofactor which is difficult to 

define, no less measure in an 

epidemiologic study.

Article 6: Young et al. 

(2005) CHAMACOS 

(N=381)

Neurodevelopment, 

Brazelton Neonatal 

Behavioral 

AssessmentScale 

(BNBAS), abnormal 

reflexes

DAP (ave. during 

pregnancy): median 

222nmol/L (range: 7–

21,867 nmol/L); DEP 

(ave. pregnancy): 

median 21nmol/L 

(range: 2–680 nmol/L)

Maternal age, BMI, any 

smoking/alcohol/drug use 

during pregnancy, gestational 

age at which prenatal care was 

initiated, total number of 

prenatal care visits, mean 

pregnancy blood pressure, 

parity, method of delivery, 

general anesthesia used during 

delivery, breastfeeding initiated 

after delivery, poverty level, 

infant sex, age in days at BNBAS, 

minutes since last feed at 

BNBAS, and BNBAS examiner.

Among the >3 day old infants, 

increasing average prenatal 

urinary metabolite levels were 

associated with both an 

increase in number of abnormal 

reflexes (total DAP: adjusted 

beta = 0.53, 95% CI = 0.23, 0.82; 

dimethyls: adjusted beta = 0.41, 

95% CI = 0.12, 0.69; diethyls: 

adjusted beta = 0.37, 95% CI = 

0.09, 0.64), and the proportion 

of infants with more than three 

abnormal reflexes (total DAP: 

adjusted OR = 4.9, 95% CI = 1.5, 

16.1; dimethyls: adjusted OR = 

3.2, 95% CI = 1.1, 9.8; diethyls: 

adjusted OR = 3.4, 95% CI = 1.2, 

9.9).

Associations seen pre-natal OP, 

not post-natal OP exposure, 

Maternal urine collection 

averaged wks.14, 26

Strengths: Longitudinal design, 

measurement and consideration 

of many confounders, the 

prenatal exposure measures 

were, with some exceptions, the 

average of two measurements, 

and thus may better reflect 

chronic exposure during the 

pregnancyWeaknesses: 

Potential for residual 

confounding, potential for 

exposure misclassification, 

potential selection bias (not all 

children had the outcome 

measures), study population not 

generalizable to the whole US.

Article 7: Rauh et al. 

(2006) Columbia U. 

(N=254)

Neurodevelopment: 

The Bayley Scales of 

Infant Development II 

(BSID-II), Mental 

Development Index 

(MDI) and 

Psychomotor 

Development Index 

(PDI) at 12, 24, and 36 

months of age. • 

Behavior: Child 

Behavior Checklist 

(CBCL) at 12, 24, and 

36 months . • Quality 

of the child-care 

environment: The 

Home Observation for 

Measurement of the 

Environment (HOME) 

Exposure levels were 

categorized as low (< 

Data were collected regarding 

lead exposure, demographics, 

education and occupational 

history, income, active and 

passive smoking, alcohol and 

drug use during pregnancy, and 

residential pesticide use. Final 

models included prenatal 

environmental tobacco smoke 

(ETS) exposure, gender, 

ethnicity, gestational age at 

birth, quality of home caretaking environment, maternal 

education, and maternal IQ.

6.17 pg/g) or high 

(>6.17 pg/g) 

At the 36 month milestone, the 

likelihood of highly exposed 

children developing mental 

delays were 2.4 times greater 

(95% CI: 1.12-5.08, p = .02) and 

motor delays were 4.9 greater 

(95% CI: 1.78-13.72; p = .002) 

than those with lower prenatal 

exposure. The GLM analysis for 

PDI scores showed a significant 

effect of chlorpyrifos exposure 

over time with an estimated 

deficit of approximately 7 points 

by age 36 months (p = .01). 

The authors summarize three 

main findings: 1) by age 3, the 

more highly exposed children 

demonstrated mental and 

motor delays; 2) the observed 

developmental trajectories for 

PDI and MDI scores confirmed 

that the adverse impact on 

cognitive and motor 

development increased over 

time; and 3) by age 3, highly 

exposed children were more 

likely to demonstrate clinically 

significant attention problems.

• Only 53% of the children 

reached the three year 

milestone with study data 

collected. It is unclear what 

percentage of these children did 

not survive, were lost to followup, or too sick to participate. • 

Reliance on a single exposure 

level (prenatal/cord blood.) • 

No control for exposure over 

the subsequent 3 years • 

Creation of a dichotomous 

exposure variable brings 

limitations due to the amount of 

within-group variation. • 

Limitations of the sensitivity and 

predictive validity of the 

developmental tests, especially 

among children less than 3 years 

of age. • No discussion of 

whether this 7-point deficit is 
Appendix 5: Summary Table of Children’s Health Cohort Data

Page 6 of 12

Author, Year, 

Sample Size

Outcome 

Assessed

Exposure 

Measurement

Potential confounders 

considered

Primary Result Conclusions/Uncertainties Strengths and Weaknesses 

clinically relevant. • Due to the

pervasive, non-specific nature of 

neurological effects, it is difficult 

to attribute causality. 

Article 8: Lovasi et al. 

2010 Columbai U. 

(N=266)

Bayley scores 

(MDI/PDI) 12 mo., 24 

mo., 36 mo.

N/A Neighborhood characteristics: 

The percentage of housing units 

without complete plumbing, the 

percentage of vacant housing 

units, the percentage of 

residents below the federal 

poverty line, the percentage of 

residents older than 25 years of 

age who completed high school, 

the percentage of households 

receiving public assistance, the 

percentage of housing units with 

one or more residents per room, 

racial composition, the 

percentage of residents born 

outside the United States, the 

percentage of Spanish-speaking 

residents, and the percentage of 

residents who were linguistically 

isolated

Neighborhood characteristics 

did not confound the observed 

association between 

chlorpyrifos levels and cognitive 

development.

Hierarchal regression analysis of 

potential confounding by SES

Direct measurement of 

chlorpyrifos.The statistical 

analyses were generally 

appropriate. Missing data on 

covariates were estimated using 

multiple imputation, and the 

variance estimates presented 

appropriately reflect the degree 

of uncertainty caused by missing 

covariate data. Robust standard 

errors were used.The setting of 

the investigation in a sample 

drawn from low-income African 

American and Dominican 

communities is both a strength 

(increases the power, restriction 

of confounders) and a limitation 

of the study (reduced 

generalizability). 

Article 9: Engel et al. 

(2011) Mt. Sinai 

(N=276)

Bayley scores 

(MDI/PDI) at 12 mo., 

24 mo.

DEP: 24.7 nmol/L; 

Total DAP: 82 nmol/L 

(same as Engel 2007)

Maternal age, race/ethnicity, 

marital status, education, 

breast-feeding, child sex, 

alcohol, smoking, or drug use 

during pregnancy, maternal IQ, a 

score based on assessment of 

the home environment (HOME), 

season of urine collection, 

language spoken in the home, 

age at testing, examiner, and 

urinary creatinine level.

An observed association 

between prenatal total 

dialkylphosphate metabolite 

level and a decrement in mental 

development at 12 months 

among blacks and Hispanics. 

Used non-specific biomarker 

DEP/DAP; some evidence of 

effect modification by PON1 

genotype

Limitations include use of nonspecific markers of chlorpyrifos 

pesticide exposure (DAPs), use 

of only a single (third-trimester) 

urine sample, and the large 

proportion of loss to follow-up. 

Statistical analysis was 

appropriate. Imputing of 

missing data may affect 

precision of association 

estimates and result in 

attenuated effect estimates as a 

result of exposure measurement 

error, although these are offset 

by the further categorization of 

the exposure levels (at the 

median). However, binning of 

exposure levels reduces 
Appendix 5: Summary Table of Children’s Health Cohort Data

Page 7 of 12

Author, Year, 

Sample Size

Outcome 

Assessed

Exposure 

Measurement

Potential confounders 

considered

Primary Result Conclusions/Uncertainties Strengths and Weaknesses 

precision, relative to a 

continuously distributed 

measure of exposure. 

Assessment and control for 

confounding were appropriate. 

However, confounding by 

unmeasured (and mismeasured) 

risk factors for abnormal growth 

that are related to pesticide 

exposure would bias the results 

in this study. Such factors may 

be related to socioeconomic 

status of the study participants, 

a cofactor which is difficult to 

define, no less measure in an 

epidemiologic study.

Article 10: Eskenazi et 

al. (2007) CHAMACOS 

(N=372)

Neurodevelopment, 

Bayley Index (MDI, 

PDI), Maternal 

behavior checklist at 6, 

12, and 24 months

DEP: geom. Mean in 

mother 18.1 nmol/L 

(95% CI 16.7–19.7); 

DEP geom mean in 

child at 24 months 

10.5 nmol/L (95% CI 

8.8–12.6); TCPy 

median 3.54 ug/l

Psychometrician, location of 

assessment, exact age at 

assessment, sex, breast-feeding 

duration (months), HOME score, 

and household income, parity, 

maternal PPVT, maternal age, 

education, depressive 

symptoms, active/passive 

smoking exposure during 

pregnancy, regular alcohol use 

during pregnancy, marital 

status, father’s presence in 

home, housing density, maternal 

work status, ≥ 15 hours out-ofhome childcare/week, birth 

weight, gestational age, 

abnormal reflexes, PCBs, lead, 

DDT, β-hexachlorocyclohexane, 

and hexa-chlorobenzene 

DAP metabolite levels during 

pregnancy, particularly from 

dimethyl phosphate pesticides, 

may be negatively associated at 

24 months with mental 

development (MDI) on the 

Bayley Scales and an increase in 

risk of maternally reported PDD. 

No strong associations identified 

with DE or TCPy, Maternal urine 

collection averaged wks.14, 26

Strengths: Longitudinal design, 

measurement and consideration 

of many confounders (including 

other environmental chemicals); 

the prenatal exposure measures 

were, with some exceptions, the 

average of two measurements, 

and thus may better reflect 

chronic exposure during the 

pregnancy

Weaknesses: Potential for 

residual confounding, potential 

for exposure misclassification, 

potential selection bias (not all 

children had the outcome 

measures), study population not 

generalizable to the whole US.

Article 11: Eskenazi et 

al. (2010) 

CHAMACOS (N=371)

Neurodevelopment, 

Bayley Index (MDI, 

PDI), Maternal 

behavior checklist at 6, 

12, and 24 months, 

PON1 gene and 

enzyme levels

The geometric mean 

for the DAP 

concentrations during 

pregnancy (for the 

average of the two 

sampling periods) was 

146 nmol/L (95% CI: 

Psychometrician, location of 

assessment, exact age at 

assessment, sex, breast-feeding 

duration (months), HOME score, 

and household income, parity, 

maternal PPVT, maternal age, 

education, depressive 

Decrease MDI (24 mo.) 

PON1108TT –5.7 (–9.0 to –2.5) 

9=0.01; Decrease PDI (24 mo.) 

PON1108TT –2.8 (–5.7 to 0.2) 

p=0.07; increased odds PDD 2.0 

(0.8 to 5.1) p=0.14; no 

association PON1192; no 

In this study population, 

evidence PON1 may influence 

MDI score, but not PDI or PDD 

risk at two-years. Nonsignificant evidence of 

decreasing MDI score by 

increasing DAP levels across 

Strengths: Longitudinal design, 

measurement and consideration 

of many confounders (including 

other environmental chemicals); 

the prenatal exposure measures 

were, with some exceptions, the 

average of two measurements, 
Appendix 5: Summary Table of Children’s Health Cohort Data

Page 8 of 12

Author, Year, 

Sample Size

Outcome 

Assessed

Exposure 

Measurement

Potential confounders 

considered

Primary Result Conclusions/Uncertainties Strengths and Weaknesses 

133, 160); of this, a 

larger proportion was 

DMP metabolites (GM 

= 109 nmol/L; 95% CI 

=98, 120) than DEPs 

(GM= 23 nmol/L; 95% 

CI = 21, 25). Allele 

frequencies: PON1 192 

Q allele= 50%; PON1 -

108 T allele= 

46%.Mean 

arylesterase activity: 

For infants: 33.6 U/mL 

(SD = 16) For mothers: 

136.6 U/mL (SD = 44). 

Mean paraoxonase 

activity: For infants: 

256.6 U/L (SD = 165); 

For mothers: 989.0 

U/L (SD = 616).

symptoms, active/passive 

smoking exposure during 

pregnancy, regular alcohol use 

during pregnancy, marital 

status, father’s presence in 

home, housing density, maternal 

work status, ≥ 15 hours out-ofhome childcare/week, birth 

weight, gestational age, 

abnormal reflexes, PCBs, lead, 

DDT, β-hexachlorocyclohexane, 

and hexa-chlorobenzene 

association PON1 activity 

measured newborn, 2 years, 

maternal and MDI, PDI, PDD. 

Evidence of decreasing MDI 

score by number of PON1108

variant alleles: PON1108CC –3.2 (–

9.8 to 3.5), CT –3.7 (–8.0 to 0.6), 

TT –5.5 (–11.1 to 0.1), pinteraction 0.98.

strata of the number of PON1108

variant alleles, interaction nonsignificant. Similar trend with 

prenatal DEP levels and MDI, 

PDI by PON108 alleles, but less 

pronounced. Overall, limited, 

non-definitive evidence of effect 

modification by PON1 status in 

the relation between mental 

and psychomotor effects and 

prenatal DAPs. 

and thus may better reflect 

chronic exposure during the 

pregnancyWeaknesses: 

Potential for residual 

confounding, potential for 

exposure misclassification, 

potential selection bias (not all 

children had the outcome 

measures), study population not 

generalizable to the whole US. 

Study may be under-powered to 

evaluate effect modification by 

PON1 status.

Article 12: Marks et al. 

(2010) 

CHAMACOS (N=348)

CBCL; K-CPT; ADHD 

confidence index; 

Hillside behavioral 

rating scale; 

composite ADHD 

indicator

DAP (geom mean) 

pregnancy 109.0 

nmol/L; DEP 17.7 

nmol/L

Psychometrician, exact age at 

assessment, sex, maternal 

education, depressive 

symptoms, PPVT (continuous), ≥ 

15 hr out-of-home child 

care/week, breast feeding 

duration (months), maternal 

age, parity, marital status, 

active/passive smoking exposure 

and regular alcohol use during 

pregnancy, presence of father in 

home, maternal work status, 

and household income

Prenatal DAPs were nonsignificantly associated with 

maternal report of attention 

problems and ADHD at age 3.5 

years, but were significantly 

related at age 5 years [CBCL 

attention problems: β = 0.7 

points; 95% confidence interval 

(CI), 0.2-1.2; ADHD: β = 1.3; 95% 

CI, 0.4-2.1]. 

Marked effect modification by 

gender: 11-fold increase ADHD 

composite indicator in boys, less 

than 2-fold in girls, however 

unstable estimates; weak 

evidence of association DAPs at 

3.5, 5 yrs. and attention 

Strengths: Longitudinal design, 

measurement and consideration 

of many confounders (including 

other environmental chemicals); 

the prenatal exposure measures 

were, with some exceptions, the 

average of two measurements, 

and thus may better reflect 

chronic exposure during the 

pregnancy

Weaknesses: Potential for 

residual confounding, potential 

for exposure misclassification, 

potential selection bias (not all 

children had the outcome 

measures), study population not 

generalizable to the whole US.

Article 13: Rauh et al. 

(2011) Columbia U. 

(N=265)

• Wechsler Scales of 

Intelligence for 

Children (WISC-IV) • 

Child Behavior 

• Chlorpyrifos levels in 

umbilical cord blood 

samples, N=256 

newborns• If no cord 

Data were collected regarding 

lead exposure, demographics, 

education and occupational 

history, income, active and 

Full-Scale IQ: (B) of -0.003, CI -

0.006, 0.001, p= 0.064 Working 

Memory Index: (B) of -0.006, CI -

0.009, -0.002, p<0.001. The 

For each standard deviation 

increase in exposure (4.61pg/g) 

there is a 1.4% reduction in FullScale IQ and a 2.8% reduction in 

Strengths• Direct assessment of 

chlorpyrifos levels using 

maternal serum and cord blood 

• Analysis using a continuous 
Appendix 5: Summary Table of Children’s Health Cohort Data

Page 9 of 12

Author, Year, 

Sample Size

Outcome 

Assessed

Exposure 

Measurement

Potential confounders 

considered

Primary Result Conclusions/Uncertainties Strengths and Weaknesses 

Checklist (CBCL). blood (12% of 

subjects), levels were 

imputed from 

mothers’ values. • 

Values for samples 

with non-detectable 

chlorpyrifos levels 

(N=115, 43%) were 

imputed by using 

assay-specific limit of 

detection (LOD) values 

to impute an 

approximate level. 

passive smoking, alcohol and 

drug use during pregnancy, and 

residential pesticide use. Final 

models included prenatal 

environmental tobacco smoke 

(ETS) exposure, gender, 

ethnicity, gestational age at 

birth, quality of home caretaking environment, maternal 

education, and maternal IQ.

investigators articulated these 

results as showing that a 1 pg/g 

increase in chlorpyrifos 

exposure was associated with a 

0.006 point decrease in the logtransformed Working Memory 

score and a 0.003 point 

decrease in the log-transformed 

Full-Scale IQ score. The 

investigators concluded that for 

each standard deviation 

increase in exposure (4.61pg/g) 

there is a 1.4% reduction in FullScale IQ and a 2.8% reduction in 

Working Memory.

Working Memory. CPF level, which, in contrast to 

dichotomous CPF levels, 

provides a more meaningful 

look at potential threshold 

effects and dose-response 

trends.• The investigators 

rigorously evaluated their 

methods for imputing values for 

undetectable CPF levels which in 

the end, were validated.• The 

authors describe an elegant and 

methodologically sound 

statistical analysis, addressing 

many of the potential 

shortcomings of their exposure 

data and 

covariates.Weaknesses• The 

use of a single snapshot of 

prenatal chlorpyrifos exposure 

may not be an accurate 

surrogate for full prenatal 

exposure levels. • There is no 

control for exposure over the 

subsequent 7 years which may 

be critical, especially as the 

process of neurocognitive 

development is fluid and rapid 

during these early childhood 

years. • Possibility of that an 

increased awareness of the risks 

of pesticide exposures could 

disproportionately affect 

postnatal exposure behavior.• 

Complicating this analysis is the 

pervasive, non-specific nature of 

neurological effects and the 

difficulty in attributing causal 

pathways. • when closely 

reviewed, the 95% CI for Full 

Scale IQ for both techniques 

contain 0 (LASSO: -0.006, 0.001, 

p=0.064; fully-adjusted: -0.006, 

0.001, p=0.048• The authors do 
Appendix 5: Summary Table of Children’s Health Cohort Data

Page 10 of 12

Author, Year, 

Sample Size

Outcome 

Assessed

Exposure 

Measurement

Potential confounders 

considered

Primary Result Conclusions/Uncertainties Strengths and Weaknesses 

not address the clinical 

relevance of the 1.4% and 2.8% 

reductions and how this may 

impact a child or his/her 

psychological or educational 

plans. 

Article 9: Engel et al. 

(2011) 

Mt. Sinai (N=169)

Wechsler Preschool 

and Primary Scale of 

Intelligence, 3rd 

edition (WPPSI-III) at 

ages < 7 years; 

Wechsler-IV 

Intelligence Scale 

(verbal 

comprehension; 

perceptual reasoning, 

working memory, 

processing speed, full 

scale intelligence) at 

age 7-9 years

DEP: 24.7 nmol/L; 

Total DAP: 82 nmol/L 

(same as Engel 2007)

Maternal age, race/ethnicity, 

marital status, education, 

breast-feeding, child sex, 

alcohol, smoking, or drug use 

during pregnancy, maternal IQ, a 

score based on assessment of 

the home environment (HOME), 

season of urine collection, 

language spoken in the home, 

age at testing, examiner and 

urinary creatinine level.

At age 6-9 years, nonstatistically significant 

reductions in full scale IQ, 

perceptual reasoning, verbal 

comprehension, working 

memory and processing speed 

with increasing DAP, more 

profound with DEP than DMP; 

Used non-specific biomarker 

DEP/DAP; some evidence of 

effect modification by PON1 

genotype

Limitations include use of nonspecific markers of chlorpyrifos 

pesticide exposure (DAPs), use 

of only a single (third-trimester) 

urine sample, and the large 

proportion of loss to follow-up.

The statistical analysis was 

largely appropriate. Imputing of 

missing data may affect 

precision of association 

estimates and result in 

attenuated effect estimates as a 

result of exposure measurement 

error, although these are offset 

by the further categorization of 

the exposure levels (at the 

median).

Assessment and control for 

confounding were appropriate. 

However, confounding by 

unmeasured (and mismeasured) risk factors for 

abnormal growth that are 

related to pesticide exposure 

would bias the results in this 

study. Such factors may be 

related to socioeconomic status 

of the study participants, a 

cofactor which is difficult to 

define, no less measure in an 

epidemiologic study.

Article 14: Bouchard et 

al. (2011) 

CHAMACOS (N=329)

Wechsler-IV 

Intelligence Scale 

(verbal 

Total DAPs (quintiles): 

Q1 (39 nmol/L); Q2 75 

nmol/L; Q3 126 

Maternal intelligence, measures 

of how stimulating the 

environment is, and known or 

The authors observed evidence 

of an association between 

prenatal exposures to OP 

Prenatal measures taken later 

half of pregnancy more 

significantly associated 

This study has many strengths, 

the longitudinal design, the 

measurement of urinary DAP at 
Appendix 5: Summary Table of Children’s Health Cohort Data

Page 11 of 12

Author, Year, 

Sample Size

Outcome 

Assessed

Exposure 

Measurement

Potential confounders 

considered

Primary Result Conclusions/Uncertainties Strengths and Weaknesses 

comprehension; 

perceptual reasoning, 

working memory, 

processing speed, full 

scale intelligence) 

measured at age 7 

years

nmol/L; Q4 221 

nmol/L; Q5 508 

nmol/L. Geometric 

mean DAP 131 nmol/L

suspected neurotoxins were 

measured prenatally. Maternal 

intelligence was assessed via the 

Peabody Picture Vocabulary Test 

(PPVT). To measure the quality 

and extent of stimulation 

available to a child in the home 

environment, the Infant-Toddler 

HOME (Home Observation for 

Measurement of the 

Environment) inventory was 

completed at the 6-month, 1, 2, 

3.5, 5, and 7 year visits; known 

or suspected neurotoxicants, 

polybrominated diphenyl ethers 

(PBDEs), polychlorinated 

biphenyls (PCBs), p,p’-

dichlorodiphenyltrichlorethane 

(DDT), p,p’-

dichlorodiphenyltrichlorethylene 

(DDE), and lead. 

pesticides as measured by 

urinary DAP metabolites in 

women during pregnancy, and 

decreased cognitive functioning 

in children at age 7.

intelligence than early; little 

evidence post-natal OP 

exposure associated with 

intelligence; 7 point reduction in 

full scale intelligence DAP 

Q5/Q1 (SS)

multiple time points and 

following children to age seven 

when tests of cognitive function 

are reportedly more reliable. 

The authors were able to adjust 

for or consider many factors 

related to cognitive function, 

such as prenatal exposure to 

other environmental agents, 

socioeconomic indicators, 

maternal intelligence and 

education, and child 

stimulation. The cohort had a 

relatively homogenous 

socioeconomic profile, reducing 

the potential for uncontrolled 

confounding. 

Article 15: Whyatt et 

al. (2007) Columbia 

U. (N=102)

None Geometric mean, 6.9 ± 

17.0 ng/m3

; range < 

0.4–171 ng/m3

. 

Personal air monitor: 

median 2.8 ng/m3

, 

mean 6.2 ± 11.1 

ng/m3

, range < 0.4–

83.4 ng/m3

N/A There was little within-home 

variability and no significant 

difference in air concentrations 

within homes over time (p ≥ 

0.2); between-home variability 

accounted for 88% of the 

variance in the indoor air levels 

of propoxur, 92% in 

chlorpyrifos, 94% in diazinon, 

and 62% in piperonyl butoxide 

(p < 0.001). Indoor and maternal 

personal air insecticide levels 

were highly correlated (r = 0.7–

0.9, p < 0.001). 

Indoor and maternal personal 

air insecticide levels were highly 

correlated (r = 0.7–0.9, p < 

0.001). 

Strengths: study design and 

exposure assessment 

techniques, Limitations: only 

those cohort participants 

enrolled after 2011 were 

included in the analysis (most 

likely due to the lack of serial 

data from the earlier years.) 

Article 16: Whyatt et 

al. (2009) Columbia 

U. (N=102)

None The limit of detection 

(LOD) of chlorpyrifos 

in blood samples was 

0.5–1 pg/g plasma. 

The LOD of TCPy in 

urine samples was 

0.26 ng/mL urine. The 

N/A Meconium TCPy concentrations 

were positively correlated with 

chlorpyrifos in maternal and 

cord blood (r = 0.25–0.33, p < 

0.05) and with TCPy in maternal 

urine (r = 0.31, p < 0.01).

TCPy in maternal urine samples 

was not reliable, but the 

maternal and cord blood 

chlorpyrifos as well as the TCPy 

levels in meconium were 

reliable measures of exposure

Comprehensive exposure 

assessment including actual 

blood chlorpyrifos levels, the 

repeated sampling, and the 

environmental sampling.

Weaknesses: only included 
Appendix 5: Summary Table of Children’s Health Cohort Data

Page 12 of 12

Author, Year, 

Sample Size

Outcome 

Assessed

Exposure 

Measurement

Potential confounders 

considered

Primary Result Conclusions/Uncertainties Strengths and Weaknesses 

LOD for TCPy in 

meconium was 0.2 ng

based on a sample 

weighing 0.5 g. 

Exposure marker 

levels below the LOD 

were given a value of 

half the level of 

detection, and were 

then log10 

transformed.

participants recruited in the 

post-cancellation period, use of 

nonparametric, rank-based 

statistics is appropriate but the 

large number of observations 

below the level of detection 

receiving equal rank, may be 

problematic; no dietary 

assessment