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Bouchard et al., 2011

Bouchard MF, Chevrier J, Harley KG, Kogut K, Vedar M, Calderon N, Trujillo C, Johnson C, Bradman A, Barr DB, Eskenazi B., “Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children.,” Environmental Health Perspectives, 2011, 119:8, DOI: 10.1289/ehp.1003185.

ABSTRACT:
CONTEXT: Organophosphate (OP) pesticides are neurotoxic at high doses. Few studies have examined whether chronic exposure at lower levels could adversely affect children’s cognitive development.

OBJECTIVE: We examined associations between prenatal and postnatal exposure to OP pesticides and cognitive abilities in school-age children.

METHODS: We conducted a birth cohort study (Center for the Health Assessment of Mothers and Children of Salinas study) among predominantly Latino farmworker families from an agricultural community in California. We assessed exposure to OP pesticides by measuring dialkyl phosphate (DAP) metabolites in urine collected during pregnancy and from children at 6 months and 1, 2, 3.5, and 5 years of age. We administered the Wechsler Intelligence Scale for Children, 4th edition, to 329 children 7 years of age. Analyses were adjusted for maternal education and intelligence, Home Observation for Measurement of the Environment score, and language of cognitive assessment.

RESULTS: Urinary DAP concentrations measured during the first and second half of pregnancy had similar relations to cognitive scores, so we used the average of concentrations measured during pregnancy in further analyses. Averaged maternal DAP concentrations were associated with poorer scores for Working Memory, Processing Speed, Verbal Comprehension, Perceptual Reasoning, and Full-Scale intelligence quotient (IQ). Children in the highest quintile of maternal DAP concentrations had an average deficit of 7.0 IQ points compared with those in the lowest quintile. However, children’s urinary DAP concentrations were not consistently associated with cognitive scores.

CONCLUSIONS: Prenatal but not postnatal urinary DAP concentrations were associated with poorer intellectual development in 7-year-old children. Maternal urinary DAP concentrations in the present study were higher but nonetheless within the range of levels measured in the general U.S. population. FULL TEXT


Bradman et al., 2003

Bradman A, Barr DB, Claus Henn BG, Drumheller T, Curry C, Eskenazi B, “Measurement of pesticides and other toxicants in amniotic fluid as a potential biomarker of prenatal exposure: a validation study,” Environmental Health Perspectives, 2003, 111:1779-1782. DOI:10.1289/ehp.6259.

ABSTRACT:

Prenatal pesticide exposures may adversely affect children’s health. However, exposure and health research is hampered by the lack of reliable fetal exposure data. No studies have been published that report measurements of commonly used nonpersistent pesticides in human amniotic fluid, although recent studies of pesticides in urine from pregnant women and in meconium indicate that fetuses are exposed to these chemicals. Amniotic fluid collected during amniocentesis is the only medium available to characterize direct fetal exposures early in pregnancy (approximately 18 weeks of gestation). As a first step in validating this exposure biomarker, we collected 100 amniotic fluid samples slated for disposal and evaluated analytical methods to measure organophosphate and carbamate pesticides and metabolites, synthetic pyrethroid metabolites, herbicides, and chlorinated phenolic compounds. The following six phenols were detected (detection frequency): 1- and 2-naphthol (70%), 2,5-dichlorophenol (55%), carbofuranphenol (5%), ortho-phenylphenol (30%), and pentachlorophenol (15%), with geometric mean concentrations of 0.72, 0.39, 0.12, 0.13, and 0.23 microg/L, respectively, for positive values. The organophosphate metabolites diethylphosphate and dimethylphosphate were detected in two (10%) samples, and dimethylthiophosphate was detected in one (5%) sample, with geometric mean concentrations of 0.31, 0.32, and 0.43 microg/L, respectively, for positive values. These levels are low compared with levels reported in urine, blood, and meconium in other studies, but indicate direct exposures to the young fetus, possibly during critical periods of development. Results of this pilot study suggest that amniotic fluid offers a unique opportunity to investigate fetal exposures and health risks.  FULL TEXT


Bradman et al., 2013

Bradman, Asa; Kogut, Katherine; Eisen, Ellen A; Jewell, Nicholas P; Quiros-Alcala, Lesliam; Castorina, Rosemary; Chevrier, Jonathan; Holland, Nina T;  Barr, Dana Boyd; Kavanagh-Baird, Geri; Eskenazi, Brenda, “Variability of organophosphorous pesticide metabolite levels in spot and 24-hr urine samples collected from young children during 1 week,” Environmental Health Perspectives, 2013, 121:118-124. DOI:10.1289/ehp.1104808.

ABSTRACT:

BACKGROUND: Dialkyl phosphate (DAP) metabolites in spot urine samples are frequently used to characterize children’s exposures to organophosphorous (OP) pesticides. However, variable exposure and short biological half-lives of OP pesticides could result in highly variable measurements, leading to exposure misclassification.

OBJECTIVE: We examined within- and between-child variability in DAP metabolites in urine samples collected during 1 week.

METHODS: We collected spot urine samples over 7 consecutive days from 25 children (3-6 years of age). On two of the days, we collected 24-hr voids. We assessed the reproducibility of urinary DAP metabolite concentrations and evaluated the sensitivity and specificity of spot urine samples as predictors of high (top 20%) or elevated (top 40%) weekly average DAP metabolite concentrations.

RESULTS: Within-child variance exceeded between-child variance by a factor of two to eight, depending on metabolite grouping. Although total DAP concentrations in single spot urine samples were moderately to strongly associated with concentrations in same-day 24-hr samples (r approximately 0.6-0.8, p < 0.01), concentrations in spot samples collected > 1 day apart and in 24-hr samples collected 3 days apart were weakly correlated (r approximately -0.21 to 0.38). Single spot samples predicted high (top 20%) and elevated (top 40%) full-week average total DAP excretion with only moderate sensitivity ( approximately 0.52 and approximately 0.67, respectively) but relatively high specificity ( approximately 0.88 and approximately 0.78, respectively).

CONCLUSIONS: The high variability we observed in children’s DAP metabolite concentrations suggests that single-day urine samples provide only a brief snapshot of exposure. Sensitivity analyses suggest that classification of cumulative OP exposure based on spot samples is prone to type 2 classification errors.  FULL TEXT


Eskenazi et al., 2004

Brenda Eskenazi, Kim Harley, Asa Bradman, Erin Weltzien, Nicholas P. Jewell, Dana B. Barr, Clement E. Furlong, and Nina T. Holland, “Association of in Utero Organophosphate Pesticide Exposure and Fetal Growth and Length of Gestation in an Agricultural Population,” Environmental Health Perspecitives, 112:10, 2004, DOI: 10.1289/ehp.6789

ABSTRACT:

Although pesticide use is widespread, little is known about potential adverse health effects of in utero exposure. We investigated the effects of  organophosphate pesticide exposure during pregnancy on fetal growth and gestational duration in a cohort of low-income, Latina women living in an agricultural community in the Salinas Valley, California. We measured nonspecific metabolites of organophosphate pesticides (dimethyl and diethyl phosphates) and metabolites specific to malathion (malathion dicarboxylic acid), chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridinyl) phosphoro-thioate], and parathion (4-nitrophenol) in maternal urine collected twice during pregnancy. We also measured levels of cholinesterase in whole blood and butyryl cholinesterase in plasma in maternal and umbilical cord blood. We failed to demonstrate an adverse relationship between fetal growth and any measure of in utero organophosphate pesticide exposure. In fact, we found increases in body length and head circumference associated with some exposure measures.
However, we did find decreases in gestational duration associated with two measures of in utero pesticide exposure: urinary dimethyl phosphate metabolites [βadjusted = –0.41 weeks per log10 unit increase; 95% confidence interval (CI), –0.75––0.02; p = 0.02], which reflect exposure to dimethyl organophosphate compounds such as malathion, and umbilical cord cholinesterase (βadjusted = 0.34 weeks per unit increase; 95% CI, 0.13–0.55; p = 0.001). Shortened gestational duration was most clearly related to increasing exposure levels in the latter part of pregnancy. These associations with gestational age may be biologically plausible given that organophosphate pesticides depress cholinesterase and acetylcholine stimulates contraction of the uterus. However, despite these observed associations, the rate of preterm delivery in this population (6.4%) was lower than in a U.S. reference population.   FULL TEXT


Goldman et al., 2004

Goldman L1, Eskenazi B, Bradman A, Jewell NP., “Risk behaviors for pesticide exposure among pregnant women living in farmworker households in Salinas, California,”  American Journal of Industrial Medicine, 45:6, 2004, DOI: 10.1002/ajim.20012

ABSTRACT:

BACKGROUND: Farmworkers and their families are at risk for pesticide exposure, however, little is known about behaviors that increase their risk. We determined the frequency of risky behaviors among pregnant farmworkers and characterized those at greatest risk.

METHODS: Participants included 153 pregnant farmworkers and 248 pregnant non-farmworkers who resided with farmworkers from the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study. We examined risky behaviors relating to handwashing, bathing, protective clothing, house cleaning, laundering of work clothes, wearing of work clothes and shoes into the home, and eating produce from the fields.

RESULTS: Between 25 and 60% of women demonstrated risky behavior on each item. Practices of households with pregnant farmworkers and non-farmworkers did not differ. Women who lived in the United States longer, and in crowded households demonstrated the most risky behavior overall.

CONCLUSIONS: Pregnant farmworkers and those living with farmworkers need to be educated to reduce potential take-home pesticide exposure.


Hertz-Picciotto et al., 2018

Hertz-Picciotto, Irva, Sass, Jennifer B., Engel, Stephanie, Bennett, Deborah H., Bradman, Asa, Eskenazi, Brenda, Lanphear, Bruce, & Whyatt, Robin, “Organophosphate exposures during pregnancy and child neurodevelopment: Recommendations for essential policy reforms,” PLOS Medicine, 2018, 15(10). DOI: 10.1371/journal.pmed.1002671.

SUMMARY POINTS:

• Widespread use of organophosphate (OP) pesticides to control insects has resulted in ubiquitous human exposures.
• High exposures to OP pesticides are responsible for poisonings and deaths, particularly in developing countries.
• Compelling evidence indicates that prenatal exposure at low levels is putting children at risk for cognitive and behavioral deficits and for neurodevelopmental disorders.
To protect children worldwide, we recommend the following:
• Governments phase out chlorpyrifos and other OP pesticides, monitor watersheds and other sources of human exposures, promote use of integrated pest management (IPM) through incentives and training in agroecology, and implement mandatory surveillance of pesticide-related illness.
• Health professions implement curricula on the hazards from OP pesticides in nursing and medical schools and in continuing medical education courses and educate their patients and the public about these hazards.
• Agricultural entities accelerate the development of nontoxic approaches to pest control through IPM and ensure the safety of workers through training and provision of protective equipment when toxic chemicals are to be used. FULL TEXT


Marks et al., 2010

Marks, A. R., Harley, K., Bradman, A., Kogut, K., Barr, D. B., Johnson, C., Calderon, N., & Eskenazi, B.; “Organophosphate pesticide exposure and attention in young Mexican-American children: the CHAMACOS study;” Environmental Health Perspectives, 2010, 118(12), 1768-1774; DOI: 10.1289/ehp.1002056.

ABSTRACT:

BACKGROUND:

Exposure to organophosphate (OP) pesticides, well-known neurotoxicants, has been associated with neurobehavioral deficits in children.

OBJECTIVES:

We investigated whether OP exposure, as measured by urinary dialkyl phosphate (DAP) metabolites in pregnant women and their children, was associated with attention-related outcomes among Mexican-American children living in an agricultural region of California.

METHODS:

Children were assessed at ages 3.5 years (n = 331) and 5 years (n = 323). Mothers completed the Child Behavior Checklist (CBCL). We administered the NEPSY-II visual attention subtest to children at 3.5 years and Conners’ Kiddie Continuous Performance Test (K-CPT) at 5 years. The K-CPT yielded a standardized attention deficit/hyperactivity disorder (ADHD) Confidence Index score. Psychometricians scored behavior of the 5-year-olds during testing using the Hillside Behavior Rating Scale.

RESULTS:

Prenatal DAPs (nanomoles per liter) 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: beta = 0.7 points; 95% confidence interval (CI), 0.2-1.2; ADHD: beta = 1.3; 95% CI, 0.4-2.1]. Prenatal DAPs were associated with scores on the K-CPT ADHD Confidence Index > 70th percentile [odds ratio (OR) = 5.1; 95% CI, 1.7-15.7] and with a composite ADHD indicator of the various measures (OR = 3.5; 95% CI, 1.1-10.7). Some outcomes exhibited evidence of effect modification by sex, with associations found only among boys. There was also limited evidence of associations between child DAPs and attention.

CONCLUSIONS:

In utero DAPs and, to a lesser extent, postnatal DAPs were associated adversely with attention as assessed by maternal report, psychometrician observation, and direct assessment. These associations were somewhat stronger at 5 years than at 3.5 years and were stronger in boys. FULL TEXT


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