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2002 Progress Report: The Epidemiological Investigation of the Effects of Pesticide Exposure on Neurodevelopmental, Growth, and Respiratory Health of Farmworker Children

EPA Grant Number: R826709C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R826709
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: CECEHDPR - University of California at Berkeley
Center Director: Eskenazi, Brenda
Title: The Epidemiological Investigation of the Effects of Pesticide Exposure on Neurodevelopmental, Growth, and Respiratory Health of Farmworker Children
Investigators: Eskenazi, Brenda
Institution: University of California - Berkeley
EPA Project Officer: Fields, Nigel
Project Period: January 1, 1998 through January 1, 2002
Project Period Covered by this Report: January 1, 2001 through January 1, 2002
Project Amount: Refer to main center abstract for funding details.
RFA: Centers for Children's Environmental Health and Disease Prevention Research (1998)
Research Category: Children's Health , Health Effects

Description:

Objective:

The objective is to estimate sources, pathways, and levels of in utero and postnatal pesticide exposures of farmworker children by measuring biological and environmental samples.

Progress Summary:

Neurodevelopmental and Growth Components

Association of Urinary Pesticide Metabolites and Birth Weight. We have conducted detailed analyses to investigate the association of urinary pesticide metabolites with birth weight in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) population. Because of their relationship to birth weight, we excluded from the analyses women with gestational or pre-existing diabetes (N = 26), hypertension (N = 15), twin births (N = 5), or stillbirths (N = 3). Additionally, women were not included in the current analysis either because birth weight data were unavailable (N = 63), because pesticide levels were unavailable (N = 2), or because their gestational age at delivery could not be accurately determined (N = 24), leaving a final sample size of 463.

We examined several outcomes related to birth weight, including birth weight (as a continuous variable), birth weight among term infants only, low birth weight, gestational age at birth, small for gestational age, and large for gestational age. We also looked at different measures of pesticide exposure, including urinary metabolites individually at 13 weeks gestation, 26 weeks gestation, and delivery; as an average over the three time points; and using the highest single value of the three time points.

Figure 1 presents a scatterplot of the crude relationship between birth weight and dimethyl and diethyl pesticide metabolites using a Lowess curve. There is no obvious decrease in birth weight associated with increased dimethyl or diethyl metabolite levels. Conversely, there is a slight increase in birth weight with increasing diethyl metabolite levels.

Figure 1

Figure 1. Relation of Dimethyl (DM) and Diethyl (DE) Pesticide Metabolites in Urine and Birthweight (bwt) Using LOESS

In general, there were no strong associations between pesticide metabolite levels and birth weight. Multiple regression analysis revealed a (borderline significant) 85 gram increase in birth weight per log unit increase associated with diethyl metabolite levels averaged over the three time points and with the highest metabolite level. The strongest relationship between birth weight and diethyl metabolite levels were those from around the end of the second trimester, the period of the greatest fetal growth. There was a slightly stronger increase in birth weight of about 100 grams associated with diethyl metabolite levels when the analyses are restricted to term births. The increase in birth weight result appears to be in the predominant part of the birth weight distribution, since there was no concomitant decrease in the risk for low birth weight. There was also no clear decrease in risk for small for gestational age, although most of the adjusted odds ratios are between 0.6 and 0.8. Nor was there a clear increased risk with large for gestational age, although most of the adjusted odds ratios are between 1.2 and 1.5.

We found no association between dimethyl or diethyl metabolite levels and length of gestation in days or preterm delivery.

These analyses will be submitted for publication in October.

Association of Plasma Acetylcholinesterase and Birth Weight. Preliminary analyses suggest an association of decreased acetylcholinesterase with decreased birth weight. We will be conducting more detailed analyses of this association and exploring the possibility of using acetylcholinesterase levels as a measure of pesticide exposure. See Figure 2.

Figure 2

Figure 2. Acetylcholinesterase (Three Tertiles) and Birth Weight (g) at Three Time Points (26 Weeks Gestation, Delivery, and Cord Blood)

Association of Acculturation and Dietary Intake During Pregnancy. We have also analyzed dietary intake during pregnancy in the CHAMACOS population using the food frequency questionnaire that was administered at the 26-week visit. The analyses were restricted to women of Mexican descent (97% of the total population) to examine the effect of acculturation on diet. A comparison of first-generation, Mexico-born women and second-generation, U.S.-born women found that Mexico-born women consumed a more healthful diet containing significantly higher intakes of vitamins A, C, and E; folate; calcium; and zinc. Mexico-born women also had higher total caloric intake on average than U.S.-born women. No differences were seen in vitamin supplement use between the two groups. Additional analyses examined Mexico-born women to determine how diet changed with increasing years’ residence in the United States. Each additional year residing in the United States was associated with a decrease in intake of calories, fat and cholesterol, which is consistent with dietary guidelines. However, each additional year in the United States was also associated with a decrease in intake of fiber and zinc and non-significant decreases in vitamin A, vitamin E, folate, and calcium. These analyses were conducted by Kim Harley, a doctoral student working for CHAMACOS, as part of her dissertation and will be submitted for publication this fall.

Autonomic Reactivity. Autonomic reactivity data have been collected on 389 subjects, including both 6- and 12-month-old babies. The autonomic reactivity data are collected and stored on the two laptop computers in the van or office. The data are copied to a zip disk and then backed up in the University of California at Berkeley CHAMACOS office (Powerbar building) onto a PC at the Boyce/Alkon laboratory at the Harold E. Jones Child Study Center. The data are scored by Suzanne Lippert, Research Assistant at the Boyce/Alkon laboratory under the supervision of Dr. Abbey Alkon.

Data were lost on 43 subjects in December 2001 due to a computer problem. The hard drive on one laptop was corrupted due to a lack of working memory. Although some data were regularly copied to zip disks, we found that the majority of data was only stored on the hard drive. The computer problem occurred when Dr. Alkon tried to delete one file and, instead, all of the data stored on the laptop were deleted. The laptop was sent to a data recovery company, Data Savers, and they could not recover the data.

The majority of the data collected has been scored. There are 327 subjects with data scored for respiratory sinus arrythmia (RSA; a measure of the parasympathetic nervous system). Five percent of the RSA data collected were not scorable due to “noise” (loose bands, baby movement, etc.) Only 50 percent of the data have been scored for pre-ejection period (a measure of the sympathetic nervous system). The scoring of Autonomic Nervous System (ANS) assessment data will be completed by the end of October 2002.

The RSA data have been cleaned and preliminary analyses show the data are valid and there are different physiologic responses to the tasks in the protocol. The infants are more relaxed in the beginning of the protocol compared to the end. They respond to the emotional (baby cry) and physical (vibrator) tasks by showing changes in their parasympathetic responses.

Statistical analyses investigating the association of pesticide exposure with neo-natal Brazelton assessment are in progress.

Also see General Activities in the overall 2002 Annual Report for R826709.

Respiratory Component

We are preparing a manuscript describing the mothers’ respiratory health, focusing on the respiratory health of the Latinas (n = 577), though there were an additional 19 women who completed the baseline questionnaire. There have been few investigations of respiratory health status of Latina or Hispanic women living in the United States. To the extent that most (88%) of the women in CHAMACOS are of Mexican heritage, one would expect a relatively low prevalence of asthma (based on cross-sectional studies conducted in that country). In the CHAMACOS women, the prevalence of ever having received a physician’s diagnosis of asthma was 3 percent, while that for current active asthma was 2 percent. The prevalence of respiratory symptoms suggestive of asthma was likewise around 2 percent; in addition, most of the women reporting recent wheeze, nocturnal chest tightness, or shortness of breath were asthmatic. In contrast, about 12 percent of the women reported having hay fever; however, only 3 percent had had a confirming medical diagnosis. These preliminary descriptive statistics suggest a low prevalence of noninfectious respiratory morbidity in this population.

Household exposures are likely to influence the respiratory health of the birth cohort. One of the most important to examine is cigarette smoking. Although 11 percent of the women reported ever having smoked cigarettes, less than 1 percent were current smokers at intake. Approximately 7 percent reported exposure to others’ smoke at least 1 hour/day, with most presumably due to household exposure, as 6.4 percent had at least one regular smoker living in their households. Other common household exposures that may influence the birth cohort’s respiratory health are the presence of water damage (24%), visible indoor mold (46.5%), the presence of a gas stove (77%), and cockroaches (39%). Keeping cats or dogs as indoor pets may promote (or retard) the development of allergy and asthma; however, such pets were relatively uncommon at baseline, with frequencies of 2.8 and 4.2 percent, respectively.

In addition to drafting a manuscript on the mothers’ respiratory health and exposures, we will also be examining the respiratory health of the children as reported on the 6- and 12-month questionnaires, both descriptively and in relation to a variety of questionnaire variables (e.g., breastfeeding, diet, household environment, pesticide usage). Blood samples collected at approximately 12 months of age are being analyzed for total immunoglobulin E (IgE) using an enzyme-linked immunosorbent assay (ELISA) method; these results will be examined as both dependent and independent variables during the next year of the grant. Initial results (n = 269) indicate a typical log-normal distribution. We have also initiated a pilot examination of immunological characteristics—total IgE, Th1/Th2 cytokine profiles (interleukin-4 [IL-4], interferon-g [IFN-g], and IL-12)—of approximately 100 children, one-half of whom either have had a diagnosis of asthma or a history of wheezing respiratory illness during the first year of life, and “control” children who have had neither. Samples of house dust for these children will also be analyzed for several aeroallergens and endotoxin. We will then examine inter-relationships of the respiratory and immunological outcomes with a variety of laboratory and questionnaire variables, recognizing the limited statistical power of this exploratory analysis.

Home visits involving dust collection for allergen and endotoxin analysis have been completed for 6- and 12-month-olds. Dusts for 100 participants, including 50 cases with diagnosed asthma or respiratory symptoms and 50 controls, have been identified and shipped to a reference laboratory for allergen and endotoxin analysis. Results from these tests will form the basis for a nested case-control study of adverse respiratory disease in CHAMACOS participants.

In collaboration with the American Academy of Allergy, Asthma, and Immunology (AAAAI) and the Salinas Allergy Clinic, CHAMACOS staff continue to maintain a Burkard sampler to determine mold and pollen levels in ambient air. These data will be used for the respiratory component of the study and also provide a community service. Results are provided to the AAAAI and over 100 Salinas-area doctors and are also published online (http://www.salinasallergyclinic.com/information/chamacos.htm exit EPA ) and in the local newspaper. See Figure 3 below for recent ambient mold spore monitoring.

Also see General Activities in the 2002 Annual Report for R826709.

Figure 3

Figure 3. Mold Spores in the Salinas Valley

Research Changes

After discussions with the CHAMACOS Scientific Advisory Committee and Drs. Alkon, Boyce, and Johnson, we revised the test battery at the 24-month neurodevelopmental assessment for the child. As was originally proposed, we will be using the following measures at the 24-month assessment: the Bayley Scales of Infant Development Mental and Motor Scales, Home Observation for the Measurement of the Environment, and the Child Behavior Checklist. In addition, we are using the following measures: MacArthur Communicative Development Inventory, Piaget A not B test of visual memory and object permanence. At the 24-month assessment we are not using the Vineland Adaptive Behavior Scale; we are also not conducting the ANS at 24 months.

Journal Articles:

No journal articles submitted with this report: View all 16 publications for this subproject

Supplemental Keywords:

Toxics, Scientific Discipline, Health, RFA, Susceptibility/Sensitive Population/Genetic Susceptibility, Endocrine Disruptors - Environmental Exposure & Risk, Risk Assessments, genetic susceptability, Health Risk Assessment, endocrine disruptors, Epidemiology, Children's Health, Biochemistry, pesticides, Environmental Chemistry, Endocrine Disruptors - Human Health, insecticides, environmental hazard exposures, neurodevelopmental toxicity, developmental disorders, endocrine disrupting chemicals, health effects, respiratory problems, childhood development, assessment of exposure, childhood respiratory disease, growth and development, exposure prone behavior, pesticide residues, epidemeology, endotoxin, agricultural community, dietary exposure, pesticide exposure, sensitive populations, developmental toxicants, biological response, airway disease, children, exposure, growth & development, children's vulnerablity, environmental health hazard, asthma, human exposure, Human Health Risk Assessment, neurodevelopmental
Relevant Websites:

http://www.chamacos.org/ exit EPA

Progress and Final Reports:
1999 Progress Report
2000 Progress Report
2001 Progress Report
Original Abstract


Main Center Abstract and Reports:
R826709    CECEHDPR - University of California at Berkeley

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R826709C001 Community Based Intervention to Reduce Pesticide Exposures to Young Children
R826709C002 The Epidemiological Investigation of the Effects of Pesticide Exposure on Neurodevelopmental, Growth, and Respiratory Health of Farmworker Children
R826709C003 A Comprehensive Assessment of Sources of Pesticide Contamination, Concentrations in Pathways, and Exposure-prone Behavior

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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