2002 Progress Report: Research Project on Asthma

EPA Grant Number: R827027C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R827027
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: CECEHDPR - Columbia University School of Public Health
Center Director: Perera, Frederica P.
Title: Research Project on Asthma
Investigators: Perera, Frederica P.
Institution: Columbia University in the City of New York
EPA Project Officer: Callan, Richard
Project Period: August 1, 1998 through July 31, 2001 (Extended to October 31, 2004)
Project Period Covered by this Report: August 1, 2001 through July 31, 2002
Project Amount: Refer to main center abstract for funding details.
RFA: Centers for Children's Environmental Health and Disease Prevention Research (1998) RFA Text |  Recipients Lists
Research Category: Children's Health , Health Effects , Health

Objective:

The objectives of the Growth and Development research remain unchanged. They are to test hypotheses that: 1) prenatal and/or early postnatal exposure to polycyclic aromatic hydrocarbons (PAH), environmental tobacco smoke (ETS) and pesticides are significant contributors to impaired fetal and early childhood growth and neurobehavioral development, after controlling for the effects of known neurodevelopmental toxicants and other potential confounding variables; and 2) impaired nutritional status (inadequate levels of micronutrients) and social stressors act as susceptibility factors to increase the effects of the environmental exposures and biomarkers on these adverse outcomes. The aim of the project on the evaluation of carcinogenic risk is to test the hypotheses that: 1) exposure to PAH and other aromatic pollutants is associated with procarcinogenic genetic damage in cord blood; and 2) effects are modulated by the nutritional factors. Another aim is to estimate exposure to pesticides with carcinogenic potential. The number of biomarkers has been expanded as described previously to include non-persistent pesticides (NPP), and additional metals.

Progress Summary:

STUDIES AND RESULTS:

Screening and Enrollment: Since 12/98, research workers have screened over 2000 women, of whom 743 were eligible and willing to participate; 265 dropped out or were determined to be ineligible between screening and birth; and 16 women have not yet delivered. To date, 462 women have met the criteria for complete enrollment (i.e., underwent prenatal monitoring, provided a Prenatal questionnaire, and had a blood sample collected at delivery from either the mother and/or her newborn). Since the costs of expanding screening are minimal, we have successfully augmented the number of women initially screened to compensate for the exclusions and dropouts between screening and full enrollment at delivery.

Personal Monitoring and Interviewing: During the 32d week of pregnancy, the women are asked to carry a portable personal exposure monitor for 48-hours to determine their inhalation exposure to PAH and pesticides. To date, monitoring has been completed on 559 women. Samplers are sent on a monthly basis to Southwest Research Institute (SwRI) for extraction. Extracts are held until after the woman delivers and are analyzed only if a delivery blood sample (maternal and/or infant) is obtained. The air extracts are then analyzed for levels of eight carcinogenic PAH (benz(a)anthracene, chrysene, benzo(b)fluoroanthene, benzo(k)fluoroanthene, benzo(a)pyrene, indeno(1,2,3-cd)pyrene, dibenz(a,h)andiracene and benzo(g,h,i)perylene) and pyrene. Analysis of PAH in air samples from an initial 348 subjects showed that all samples had detectable levels of one or more carcinogenic PAH. Mean PAH concentrations ranged from 0.06 ng/M3 for disbenz(a,h)anthracene to 4.1 ng/M3 for pyrene. Ten NPP have been measured in 48-hour personal air samples collected from the mothers during pregnancy. The organophosphates chlorpyrifos and diazinon, the carbamate propoxur, and the fungicide ortho phenylphenol, were detected in 100% of the initial 260 samples analyzed (range 0.7-6010 ng/m3). Diazinon and propoxur levels were significantly higher in the personal air of women reporting use during pregnancy of high toxicity pesticides (an exterminator, can sprays, and/or pest bombs) compared to women reporting no pesticide use or use of low toxicity methods only (gels, traps, and boric acid). Personal air levels of chlorpyrifos, diazinon, and propoxur decreased significantly between 1998 and 2000 (p<0.05, test for linearity, ANOVA). This decrease may be attributed in part to the regulatory action taken by the U.S. EPA to phase out residential uses of chlorpyrifos and diazinon. However, other factors may be operating as well, as propoxur has not been the subject of regulatory action. Thus, there may be a general reduction in residential pesticide use as a result of concerns over health effects of residential exposures. Questionnaire data on pesticide use have been gathered from 420 women: 84% report using pest control measures during pregnancy and 34% report using an exterminator. Use of can sprays was also reported in nearly a third of pest control users. The level of housing disrepair reported by the women was a significant predictor of both whether pests were sighted in the home and whether pest control measures were used (p qreater than or equal to 0.001). Women with pests in the home were significantly more likely to be pest control users (p<0.001). In a pilot study, phthalate levels were measured in personal air and urine samples collected from a subset of women during pregnancy (n=30). All had detectable exposures. A significant correlation between personal air and urinary levels was seen for diethyl, dibutyl and butylbenzyl phthalate (r qreater than or equal to 0.4, p<0.05).

Biologic Samples/biomarkers: Thus far 462 women in the cohort have delivered and a delivery blood sample was collected from the newborn and/or the mother. Of these fully enrolled mother/newborn pairs, a cord blood sample is available for 85% and a maternal blood sample for 98%. In collaboration with CDC, samples have been analyzed for cotinine, 4-ABP-Hb, lead and mercury, organochlorines and NPP. Plasma cotinine levels at delivery averaged 1.8±10.6 ng/ml in maternal plasma (N=285) and 2.3±12.0 ng/ml in newborn blood plasma (N=242). Maternal and newborn levels were highly correlated (r=0.9, p<0.001). Maternal and newborn cotinine levels were significantly higher if the mother reported smoking by household members or regular visitors, compared to mothers who reported no smoking in the house (p<0.001). PAH-DNA adducts have been analyzed as described below. In the initial 137 samples analyzed, umbilical cord lead levels ranged from non-detectable to 7.6 µg/dI, while mercury levels ranged from non-detectable to 9.4 µg/I. These levels are below the levels of immediate health concern for both contaminants (> 10 µg/dl for lead, qreater than or equal to 30 µg/l for mercury); but thresholds have not been established for their neurotoxic effects. OrganochIorines (PCBS, DDT/DDE etc.) were generally non-detectable and we have discontinued this analysis. Levels of 29 NPP have been measured in 142 maternal blood samples and 155 cord blood samples, including 142 mother/newborn pairs: 8 (28%) pesticides were detected in qreater than or equal to 25% of samples, including chlorpyrifos, propoxur, bendiocarb, carbaryl, and diazinon that are widely used for residential pest control in these communities. In general, levels of the pesticides in maternal and cord blood samples were similar and highly correlated, indicating that the pesticides are readily transferred frorn the mother to the fetus. Collectively, these results show widespread but variable NPP exposure among the cohort and indicate that measurements in blood samples collected at birth are useful biomarkers of prenatal exposure.

Developmental analyses and outcomes: Birth weight length and bead circumference are evaluated at delivery. In the initial sample of 234 infants, prenatal PAH exposure was associated with reduced birth weight (p=0.003) and reduced head circumference (p=0.01) among African Americans but not Dominicans, and prenatal chlorpyrifos exposure was associated with reduced birth weight and length overall (p<0.05) and with lower birth weight among African Americans (p=0.04) and length among Dominicans (p=0.02). Postnatal development is being assessed at 6, 12, 24, 36, 48 and 60 months. Preliminary analyses have been completed for the initial 362 Denver II Developmental Tests and 266 Fagan Tests of Infant Intelligence at 6 months, 307 Bayley Scales of Infant Development at 12 months, 183 Bayleys at 24 months, and 85 Bayleys at 36 months. At 6 months, 11% of infants scored in the "suspect" range for developmental delay on the Denver and 19.9% were in the "at risk" range on the Fagan. At 12 months. 13.5% were in the mildly delayed range for cognitive development and 6.1% in the severely delayed range.

Evaluation of carcinogenic risks: Analyses of intermediate biomarkers of genetic damage/procarcinogenic risk, evidenced by carcinogen-DNA (PAH-DNA) adducts and carcinogenic protein (4-ABP-Hb) adducts are ongoing. They are measured in maternal and cord blood obtained at delivery and in children's blood (aromatic-DNA) postnatally. DNA from maternal (n=376) and cord blood (n=250) collected at delivery have been analyzed for benzo(a)pyrene-DNA adducts by HPLC; adducts were detected in 60% of samples. In addition, ETS and certain pesticides are known or suspected carcinogens and internal dosimetry data are being obtained on these pollutants.

Future Activities:

This is the first study to measure the internal or molecular dose and biologic effects of a comprehensive battery of environmental pollutants in inner city newborns, in conjunction with detailed exposure assessment, personal monitoring and clinical assessments. Thus it will provide much needed data on cumulative exposures and their sequelae during fetal and early childhood development.

Investigators will continue enrollment, monitoring, interviewing, extraction of medical record data and analysis of pollutants in air samples and analysis of biologic markers in maternal and infant blood samples. Analyses of the association between exposures, biomarkers and infant growth, and neurocognitive development is ongoing. Funds have been obtained to continue follow-up through the children's 5th birthdays.

Publications and Presentations:

Please refer to the main center progress report.

Supplemental Keywords:

Children's Health, Disease and Cumulative Effects, Ecological Risk Assessment, Epidemiology, Health Risk Assessment, air pollutants, air toxics, airway disease, airway inflammation, ambient particulates, carcinogenic risk, pesticides, environmental tobacco smoke., RFA, Health, Scientific Discipline, Environmental Chemistry, Health Risk Assessment, Epidemiology, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Children's Health, genetic susceptability, Biology, health effects, particulate matter, sensitive populations, infants, prenatal exposure, airway disease, respiratory problems, biological response, socioeconomic status, air pollution, children, Human Health Risk Assessment, PAH, human exposure, children's vulnerablity, assessment of exposure, childhood respiratory disease, growth and development, epidemeology, environmentally caused disease, environmental health hazard, growth & development, acute exposure, developmental disorders, disease, exposure assessment

Relevant Websites:

Columbia Center for Children's Environmental Heath
https://cfpub.epa.gov/ncer_abstracts/index.cfm/fuseaction/outlinks.centers

Progress and Final Reports:

Original Abstract
  • 1999
  • 2000 Progress Report
  • 2001 Progress Report
  • 2003
  • 2004
  • Final

  • Main Center Abstract and Reports:

    R827027    CECEHDPR - Columbia University School of Public Health

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R827027C001 Community-Based Intervention: Reducing Risks of Asthma
    R827027C002 Growth and Development/Evaluation of Carcinogenic Risks
    R827027C003 Research Project on Asthma