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2001 Progress Report: Centers of Excellence in Children's Environmental Health and Disease Prevention Research
EPA Grant Number: R826709Center: CECEHDPR - University of California at Berkeley
Center Director: Eskenazi, Brenda
Title: Centers of Excellence in Children's Environmental Health and Disease Prevention Research
Investigators: Eskenazi, Brenda
Institution: University of California - Berkeley
EPA Project Officer: Fields, Nigel
Project Period: August 1, 1998 through July 31, 2003
Project Period Covered by this Report: August 1, 2000 through July 31, 2001
Project Amount: $2,830,746
RFA: Centers for Children's Environmental Health and Disease Prevention Research (1998)
Research Category: Children's Health , Health Effects
Description:
Objective:The objectives of the Center projects are to:
- Estimate sources, pathways, and levels of in utero and postnatal pesticide exposures of farmworker children by measuring biological and environmental samples.
- Determine whether exposure to pesticides is associated with poorer neurodevelopmental functioning and behavioral problems, delayed growth, and increased respiratory symptoms and disease. To determine whether exposure to environmental allergens and respiratory irritants is associated with increased respiratory symptoms and disease.
- Evaluate the impact of “Healthy Homes” interventions on the reduction of pesticide exposure to farmworker children.
Enrollment closed October 30, 2000 (see Table 1). We completed 601 baseline interviews and 525 prenatal home visits. We have collected and processed approximately 2,350 urine, 778 maternal and cord blood samples, 495 breast milk samples, and 72 12-month child blood samples. Five hundred and twenty-eight babies have been born and Brazelton assessments were completed on 426. We have completed 354 6-month neurodevelopment assessments and 122 12-month neurodevelopment assessments. The 24-month assessments will begin in February 2002. All budgeted prenatal maternal urine samples have been shipped to the Centers for Disease Control and Prevention (CDC) for analysis. Preliminary data on pesticide urinary metabolites for 530 women have been returned from CDC. We are expecting urinary metabolite data for the remaining prenatal maternal urine samples in October 2001. At that time we will have a complete data set to finalize analyses of earlier, partially incomplete data sets. We also have taken steps with CDC laboratory co-investigators to speed up laboratory turnaround time (see below).
Table 1. Gender and Minority Inclusion Number of subjects enrolled in the study to date |
||||||||
American Indian or Alaskan Native |
Asian or Pacific Islander |
Black, not of Hispanic Origin |
Hispanic |
White, not of Hispanic Origin |
Other or Unknown |
TOTAL |
||
Female |
|
16 |
|
834 |
9 |
6 |
865 |
|
Male |
|
11 |
3 |
509 |
5 |
2 |
530 |
|
Unknown |
|
|
|
|
|
|
|
|
TOTAL |
|
27 |
3 |
1343 |
14 |
8 |
1395 |
|
General Activities in Support of Exposure, Health, and Intervention Components
- The study instruments (e.g., questionnaire, home walk-through form, food frequency questionnaire) for administration at the 12-month neurodevelopment assessment and home visit have been developed, translated, piloted, and implemented.
- Data entry has been completed for the baseline questionnaire and prenatal home visit. Data entry of Brazelton exams and prenatal medical records abstraction is in process. Other data entry is ongoing.
- Medical record abstraction for children will be initiated when the first children turn 24 months in February.
- Delivery contacts have been completed, including maternal interviews, urine and blood collections, cord blood collections, child Brazelton assessments, and paternal interviews and urine collection.
- Six hundred and one women have been enrolled. Ninety-five have dropped (16%). An additional 27 women dropped but have been re-enrolled on a limited basis (either medical records only or phone interview only.)
- The field laboratory protocol for collecting child urine samples was developed, piloted, and implemented in Year 3. Child urine collections from 6- and 12-month-old children have been very successful, with a success rate of approximately 98 percent.
- Blood collections from 12-month-old children have been moderately successful. To date, we have collected 72 samples, out of 223 children who turned 12 months. We have hired a pediatric phlebotomist, and we now expect to collect 70-80 percent of expected child blood samples. See below for a detailed summary of obstacles encountered in child blood collections.
- CDC urine analysis: Dr. Dana Barr of the CDC Environmental Health Laboratory has reported on 530 prenatal urine samples and has recently increased the number of samples being analyzed and thereby reduced turnaround time for current analyses (see Obstacles Encountered, below).
- Statistical analyses of the pesticide urinary metabolite data are in progress to address Specific Aims for both the Exposure and Health studies.
Quality Assurance and Control
- A manual detailing quality assurance and control (QA/QC) procedures for all Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) activities has been completed.
- Analytical laboratories (CDC and Batelle) are maintaining standard QA/QC procedures, including the use of laboratory blanks and standards, spiked samples, and field blank and spiked samples.
- A quality assurance study of maternal contamination of 10 cord blood samples, which utilized human leukocyte antigen (HLA) gene typing, was conducted by colleagues at the Children’s Hospital Oakland Research Institute. None of the cord blood samples contained any maternal contamination based on these results.
- To complement the HLA typing study, a study utilizing fluorescent in-situ hybridization (FISH) will be conducted to see if any XX (i.e., maternal) cells are found in the cord blood of 10 boys (i.e., XY cells). The absence of XX cells in the boys’ cord blood would confirm that no contamination of cord blood occurred during collection.
- A storage stability study was conducted to ensure the validity of stored allergen dust samples for endotoxin measurements. Results of this study indicate that endotoxin measurements on stored samples are consistent over time and that storage of the samples will not introduce bias.
- We have established a reference dust for both allergens and endotoxin that will be used as a control for future analysis of unknown participant samples. The allergen samples were analyzed by Indoor Biotech, and the endotoxin was measured by Dr. Don Milton’s laboratory at Harvard and Dr. Dan Lewis’s laboratory at the National Institute for Occupational Safety and Health (NIOSH) Morgantown.
- Pollen and fungi counts were determined for 15 Burkard slides. All slides were readable and pollen/fungi levels were quantifiable. Participant slides are now archived for use for the planned asthma case control study.
- All containers and pipettes used for processing, aliquoting, and storing whole blood to be used for blood lead measurements were tested for exogenous lead contamination by the California State Department of Health Services (DHS) Environmental Health Laboratory Branch. No contamination of any kind was detected.
Obstacles Encountered
- Available office space at Natividad Medical Center, where the field office is located, continues to be limited. Until July 2001, the field office was split between an office space and a temporary trailer. In July 2001, we moved into a new triple wide trailer that allowed for all field research staff to be housed in the same location, along with the laboratory and assessment and interview rooms.
- The fieldwork continues to be logistically complex and extremely demanding. This year has seen the continuing need for additional labor in the Field Office and the Laboratory Core to ensure proper processing and shipping of biological and environmental samples. We have been able to reduce labor costs in the field laboratory as the sample volume has declined.
- An additional psychometrician has been necessary to ensure neurobehavioral assessments are completed within the correct time frame. Presently, we have approximately 15 staff to conduct the fieldwork, whereas 4 were originally planned for in our original proposal (before implementation of managed care).
- Timely turnaround by the CDC laboratory for urine results has been an obstacle to completing some analyses and publications. Analysis of our urine samples have had to compete with CDC’s responsibility to analyze sample for National Health and Nutrition Examination Survey (NHANES). We have discussed these issues with the Environmental Health Laboratory and developed a plan to increase turnaround time.
- 12-month blood collections have been moderately successful. Originally, we planned to collect 12- and 24-month child bloods during state-mandated lead tests. We have discovered, however, that despite these requirements, less than one-half of the children actually get tested for lead. This deficit is due to a lack of phlebotomy staff, inadequate transportation available to families, poor education on lead testing requirements, and other factors. To address this problem, we have hired our own pediatric phlebotomist through Clinica de Salud to collect children’s blood for the state lead test and our study. Initially, we missed many children, and we are not yet able to fully ascertain the success of our efforts. It appears that we will be able to collect blood from approximately 70-80 percent of the children. Reduced blood collections could impact the success of the respiratory health study, described below.
- In our original proposal, we planned to measure immunoglobulin E (IgE) and determine Th1 and Th2 cytokine phenotypes of children in relation to early childhood allergen exposures. Because we may be unable to obtain blood samples for all children, we will have a reduced population of children available to complete the proposed nested case/control study. Additionally, adequate blood volumes may not be available to conduct the appropriate immune function tests, and it is proving logistically impossible to collect blood throughout the Salinas Valley and have it processed for sophisticated functional assays to determine cytokine phenotypes. We are addressing these challenges in several ways. We may focus immune function tests solely on total and specific IgE, and we are exploring the option of expanding the nested case control analysis from children with physician-diagnosed asthma to those children with any type of atopic disease or symptoms. Additionally, we are exploring grant opportunities with other child asthma cohorts to expand our resources to quantify allergens and endotoxin in environmental samples.
- Six- and 12-month Autonomic Nervous System (ANS) assessments have been less successful than planned. This is due to two primary factors. First, we have had repeated problems with equipment, including a broken cardiograph impedance machine, a broken cable box (connecting the machine and the computer), computer software problems, and difficulties with the suppliers of the electrode tape used during the assessment. At this point, all equipment has been repaired and is working again, and we have sorted out the problems with the electrode tape suppliers (and we are keeping a large amount on hand). Second, some babies and parents have been reluctant to undergo the assessment. The ANS is done at the end of the visit and the babies are often tired and/or cranky at that point. The ANS requires that the baby be sitting quietly on his/her lap, and some of the babies have not been able to do this. In addition, some parents have had to leave before the ANS could be completed or did not want the ANS to be completed after it was explained to them. As discussed above, we will be attempting to complete the ANS during all 6-month assessments through December to compensate for these difficulties.
- As expected, there has been some loss to follow up. In large part, this is due in part to participants moving and our being unable to locate them. A number of steps have been taken to maintain current enrollment levels: neurobehavioral assessments have been streamlined and we will be conducting a raffle at the end of all 24-month assessments. In addition, study interviewers, psychometricians, and ESTs are scheduling evening and weekend appointments when necessary and have traveled to outlying communities to complete assessments and home visits for willing participants. We have also made significant efforts to track down previously dropped and moved participants. We are now offering two options besides full enrollment, medical records-only enrollment and telephone enrollment. These will allow us to track key health outcomes in participants who have moved too far away to assess or who do not wish to continue participating fully in the CHAMACOS project. We are also exploring the possibility of sending assessment teams to the Central Valley in California and other locations to complete assessments with participants who have moved.
New Funded Research and Outreach Initiatives
To accomplish our objective to build a true Center for Children’s Environmental Research, we have initiated the following new research activities to fully utilize the specimens and expertise we have developed:
- In collaboration with the University of California at Berkeley (UCB) and University of Washington (UW) Environmental Health Science Centers and Children’s Centers, we have received a supplemental award to work with Clement Furlong, UW, to investigate paraoxonase polymorphisms and susceptibility to organophosphate pesticide exposure in pregnant women.
- As discussed above, we have initiated a vehicle dust sub study with U.S. Environmental Protection Agency (EPA) Region IX.
Community Interactions
Scientific Advisory Committee. We met with our Scientific Advisory Committee (SAC) on October 24, 2000, at the International Society Exposure Analysis Meeting in Monterey, California. This meeting resulted in a number of research changes, discussed above. We continue to consult individually with our scientific advisors, and we will be holding our next SAC meeting on October 30, 2001.
Significance
In the last few years, several studies have demonstrated pesticide contamination in the homes of young children living in both agricultural and suburban areas. However, to date, only a few studies have been conducted to assess the extent of children’s exposure to pesticides, and no studies have examined whether low-level chronic exposure can lead to adverse health consequences. Our goal is to translate research findings into sustainable strategies to reduce pesticide exposure to children and thus reduce the incidence of environmentally related childhood disease. Our proposed Center will also generate information critical for new Federal policy mandates regulating pesticides in food. Specifically, the proposed prospective research will: (1) characterize the organophosphate pesticide burden of high risk children; (2) quantitatively evaluate the relationship between non-occupational exposure risk factors, home contamination, and children’s exposure; and (3) evaluate the potential health effects of these exposures, which directly contributes to the information needed by Federal agencies to implement the Food Quality Protection Act. Additionally, this will be one of the first studies to examine the role of effect modification between pesticides and allergens on respiratory outcomes, including asthma.
Human Subjects
We have received approval from the human subjects committees at UCB, CDC, Natividad Medical Center, and Stanford for all planned research with the exception of the blood lead testing. Human subject approval for the lead testing is pending further review by the Internal Review Boards at the California State DHS and UCB.
Planned Publications
The urinary metabolite data have become available in the last 3 weeks. Several publications are in progress and will be submitted in the next year:
- Environmental and behavioral correlates of pesticide exposure in pregnant women living in an agricultural community.
- Approaches to risk assessment of organophosphate pesticide exposure to pregnant women.
- Descriptive statistics of respiratory health status of pregnant Latina women in an agricultural community.
- Relationship of pesticide exposure to neonatal neurodevelopment (Brazelton assessment).
- Relationship of pesticide exposure to low birth weight.
- Many additional publications are planned.
Honors and Awards
UC Berkeley School of Public Health Highlights, Fall 2001.
UC Berkeley Helps Guide New Parents. Cal Neighbors, Fall 2001.
Programs Receive Praise for Work to Improve Communal Well-Being. The Daily Californian, September 27, 2001.
Town-Gown Partnerships. Berkeleyan, September 27, 2001.
Study Examines Environmental Health Impacts on Salinas Valley Women and Children. Berkeleyan, September 27, 2001.
Hundreds Gather to Honor UC’s Community Partners. The Berkeley Daily Planet, September 28, 2001.
Future Activities:Future activities will include the following:
- Develop, pilot, translate, and implement 24-month study instruments.
- Implement 24-month neurobehavioral assessments.
- Plan and implement Quantitative Exposure Assessment for next pesticide application season (growing season).
- Continue with data entry and integration of data sources (study instruments, CDC urine data, state Pesticide Use Reporting data, etc).
- Continue data analysis.
- Initiate NIOSH grant investigating endocrine disruptors and neurobehavioral outcomes. Activities in Year 1 include CDC laboratory method development, shipment of stored samples, and preliminary data analysis.
- Initiate the Intervention Study activities, including focus groups, questionnaire development, data analysis, and pilot studies in support of the technical interventions.
- Finalize human subject approvals and initiate blood lead analyses by state health department.
- Ship stored blood samples to University of Washington for paroxonase polymorphism studies.
Journal Articles: 7 Displayed | Download in RIS Format
| Other center views: | All 110 publications | 7 publications in selected types | All 7 journal articles |
| Type | Citation | ||
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Bradman A, Eskenazi B, Sutton P, Athanasoulis M, Goldman LR. Iron deficiency associated with higher blood lead in children living in contaminated environments. Environmental Health Perspectives 2001;109(10):1079-1084. |
R826709 (2001) R826709 (2002) R831710 (2005) |
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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(14):1779-1782. |
R826709 (2001) R826709 (2002) R831710 (2004) R831710 (2005) R831710C001 (2004) |
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Castorina R, Bradman A, McKone TE, Barr DB, Harnly ME, Eskenazi B. Cumulative organophosphate pesticide exposure and risk assessment among pregnant women living in an agricultural community: a case study from the CHAMACOS cohort. Environmental Health Perspectives 2003;111(13):1640-1648. |
R826709 (2001) R826709 (2002) R831710 (2004) R831710 (2005) R831710C001 (2004) |
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Eskenazi B, Bradman A, Castorina R. Exposures of children to organophosphate pesticides and their potential adverse health effects. Environmental Health Perspectives 1999;107(Suppl 3):409-419. |
R826709 (2001) R826709 (2002) R826709C001 (1999) R826709C001 (2000) R826709C002 (1999) R826709C002 (2000) R826709C003 (1999) R826709C003 (2000) R831710 (2005) |
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Eskenazi B, Bradman A. Longitudinal investigation of pesticides and allergen exposures to children living in agricultural communities in California. Urban Health and Development Bulletin 2001;4(2):33-44. |
R826709 (2001) R826709 (2002) R831710 (2005) |
not available |
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Harley K, Eskenazi B, Block G. The association of time in the US and diet during pregnancy in low-income women of Mexican descent. Paediatric and Perinatal Epidemiology 2005;19(2):125-134. |
R826709 (2001) R826709 (2002) R831710 (2004) R831710 (2005) R831710C001 (2004) |
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Holland NT, Smith MT, Eskenazi B, Bastaki M. Biological sample collection and processing for molecular epidemiological studies. Reviews in Mutation Research 2003;543(3):217-234. |
R826709 (2001) R826709 (2002) R831710 (2004) R831710 (2005) |
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Water, Geographic Area, Scientific Discipline, Health, RFA, Risk Assessments, Analytical Chemistry, Health Risk Assessment, Epidemiology, Mercury, Ecological Risk Assessment, Children's Health, Biochemistry, State, exposure assessment, insecticides, risk assessment, California (CA), developmental neurotoxicology, neurodevelopmental toxicity, developmental disorders, health effects, epidemelogy, children's environmental health, prenatal exposure, farmworkers, age-related differences, harmful environmental agents, human health risk, epidemeology, developmental neurotoxicity, agricultural community, community-based intervention, dietary exposure, pesticide exposure, pregnancy, environmental health, children, environmental risks, pesticides, risk, latino, biomedical research, growth & development, children's vulnerablity, neurobehavioral effects, environmental health hazard, human exposure, Human Health Risk Assessment, neurotoxicity, farm worker
Relevant Websites:
Progress and Final Reports:
Original Abstract
2002 Progress Report
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