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2000 Progress Report: Growth and Development/Evaluation of Carcinogenic Risks
EPA Grant Number: R827027C002Subproject: this is subproject number 002 , 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: Growth and Development/Evaluation of Carcinogenic Risks
Investigators: Perera, Frederica P.
Institution: Columbia University
EPA Project Officer: Fields, Nigel
Project Period: August 1, 1998 through July 31, 2001 (Extended to October 31, 2004)
Project Period Covered by this Report: November 1, 1999 through October 31,2000
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 aims of the Growth and Development research remain unchanged. They are to test the hypotheses that: (1) prenatal and/or early postnatal exposure to polycyclic aromatic hydrocarbons (PAHs) and environmental tobacco smoke (ETS) are significant contributors to impaired fetal and early childhood growth and neurobehavioral development, after controlling for the effects of known neurodevelopmental toxicants (lead, mercury, polychlorinated biphenyls [PCBs]) 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 expansion in the number of biologic markers made last year also remains unchanged. The aim of the project on the evaluation of carcinogenic risk is to test the hypotheses that: (1) exposure to PAHs 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 organochlorine with carcinogenic potential. The new biologic markers that have been added include: (1) levels of organochlorines (PCBs, DDT/DDE, hexachlorobenzene, lindane, aldrin, dieldrin, endrin, endosulfan, mirex and chlordane), non-persistent pesticides (including chlorpyrifos, diazinon and propoxur) and 4-aminobiphenyl-hemoglobin adducts in umbilical cord blood samples; (2) cocaine levels in maternal urine samples collected at enrollment; and (3) metals (mercury, cadmium, chromium, arsenic, and nickel) in maternal urine samples collected during the third trimester.
Progress Summary:Screening and Enrollment
Research workers attending the prenatal clinics at Harlem Hospital and Columbia Presbyterian Medical Center on a daily basis have currently enrolled and completed 48 hours of personal ambient air monitoring on 334 non-smoking women during pregnancy. Of the enrolled women, 170/334 (51%) are from Washington Heights, 98/334 (29%) are from Harlem and 66/334 (20%) are from the South Bronx. To date, 277 babies are being followed after delivery (141 female and 136 male), of whom 126 have reached their first birthday and 15 their second birthday. Loss to follow-up during the first year has been minimal with 117 (93%) children remaining in the study at their first birthday. An average of 20 women/month continues to be enrolled.
Personal Monitoring and Interviewing
During the 32nd week of pregnancy, the women are asked to carry a portable personal exposure monitor for 48 hours to determine their inhalation exposure to PAHs. To date, monitoring has been completed on 334 women. Samplers are sent on a monthly basis to Southwest Research Institute (SwRI) for extraction. However, 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 PAHs—benz(a)anthracene, chrysene, benzo(b)fluoranthene, benzo(k)fluor anthene, benzo(a)pyene, indeno(1,2,3-cd)pyrene, dibenz(a,h)anthracene and benzo(g,h,i)perylene). Currently, SwRI has completed analysis of PAH levels in samples from 159 subjects from whom blood samples were collected at delivery. All analyzed samples have detectable levels of one or more carcinogenic PAH. These findings are similar to those reported last year when fewer women had been sampled. PAH exposures for these 159 women averaged 3.94 ng/m3 and varied significantly between the women, with a range of 0.02-44.81 ng/m3 (Kinney, et al., in preparation). These PAH concentrations can be compared to those in a prior study of non-smoking women who worked out-of-doors in the Czech Republic, a country with severe air pollution due to the use of brown coal for heating and the generation of electricity. Specifically, exposures to the eight carcinogenic PAHs there averaged 12.5 ± 6.8 ng/m3 (range 2.9-26 ng/m3) among women from one of the most highly polluted areas of the Czech Republic and 6.9 ± 4.4 ng/m3 (range 2.7-18.8 ng/m3) among women from a relatively less polluted area. The mean in the New York City population is lower than in the Czech study; however, the upper bound of concentrations seen in New York City is higher.
Personal air samples have also been analyzed for pesticides in 72 of the women who have been monitored for 48 hours during pregnancy. All of these women show exposure to at least three different neurotoxic pesticides—chlorpyrifos, diazinon, propoxur (see Table 1), which are widely used to control cockroaches and other pests in urban homes (Whyatt, et al., in preparation). These exposures are similar to those seen in the Non-Occupational Exposures to Pesticides Study (NOPES) among residents in Jacksonville, Florida, a location selected to represent an area with high household pesticide use (Whitmore, et al., 1994).
Table 1. Air Concentrations (ng/m3) of Non-Persistent Pesticides Over 48 Hours of Personal Ambient Air Monitoring During Pregnancy of African American and Dominican Women From Northern Manhattan and the South Bronx
|
Pesticide |
No. Detectable/Total No. (%) |
Mean ± SD* |
Range |
|
Chlorpyrifos |
72/72 (100%) |
21.1 ± 30.2 |
0.7-192.6 |
|
Diazinon |
71/71 (100%) |
159.3 ± 722.6 |
2.0-6005.8 |
|
Propoxur |
72/72 (100%) |
85.1 ± 198.2 |
3.8-1379.2 |
|
Piperonyl Butoxide |
59/71 (83%) |
1.1 ± 1.7 |
ND-11.1 |
|
Permethrin (cis and/or trans)*** |
53/130 (41%) |
1.3 ± 1.9 |
ND-9.8 |
|
Cyfluthrin |
7/70 (10%) |
NA |
ND-14.2 |
|
Methyl Parathion |
2/43 (5%)** |
NA |
ND-0.9 |
|
Dichlorfos |
1/46 (2%)** |
NA |
ND-2.8 |
|
Carbaryl |
1/48 (2%)** |
NA |
ND-0.7 |
| Malathion | 0/49 (0%)** | NA | NA |
| *Calculated if > 30% of samples had detectable levels; non-detectable levels set at 0.5 (detection limit). **Air concentration could not be calculated for remaining samples because of interference peaks. ***Cis and trans permethrin were calculated separately and summed. NA – not available; ND – non-detectable |
|||
Biologic Samples
Thus far, 315 women in the cohort have delivered. A delivery blood sample was collected in 277/315 (88%) of the deliveries: maternal blood in 272/315 (86%) and cord blood in 239/315 (76%). Subjects are removed from the cohort if neither a maternal nor child delivery blood sample is obtained (see R827027C003). Analysis of cotinine in the first 229 maternal and newborn blood samples analyzed so far show widespread exposure to ETS: 46 percent of infants and 48 percent of mothers have detectable levels of cotinine indicative of ETS exposure (>detectable<25 ng/mL). Cocaine levels have been measured in 145 urine samples collected from women at enrollment. Only one had detectable levels, indicating that our exclusion criteria are effective at eliminating prenatal cocaine users from the cohort. PAH-DNA adduct levels have been measured in blood samples from 199 mothers and 154 newborns; and 4-aminobiphenyl-hemoglobin adduct levels have been measured in blood samples from 93 newborns. Analyses of all stored samples are ongoing.
Follow-up Assessments
Cognitive and motor developmental tests are being administered under controlled conditions at the Center at infant ages 6 months (Denver II Developmental Test, Fagan Test of Infant Intelligence), 12 months (Bayley II Scales of Infant Development), and 24 months (Bayley II Scales of Infant Development). To date, the following assessments have been completed: 170 Denvers, 170 Fagans, 104 Bayleys at 12 months, and 8 Bayleys at 24 months. Six-month Denver results show that 16.5 percent of infants scored in the “suspect” range for developmental delay. Six-month Fagan results show that 14.9 percent of infants scored in the “at-risk” range. Twelve-month Bayley scores show that 13.5 percent were delayed.
Analysis of Biomarkers
Sample aliquots are sent to participating laboratories on a quarterly basis. Laboratory assays are ongoing and results are entered into the Central Database (see R827027C003).
Loss to Follow-Up
The steps put into place last year to reduce loss to follow-up were effective. Loss to follow-up was reduced and is currently: 5 percent between enrollment (with monitoring scheduled) and completion of the monitoring; 12 percent between monitoring through delivery; and 7 percent between delivery and the child’s first birthday.
Significance
This is the first study to measure the internal or molecular dose and biologic effects of such a comprehensive battery of environmental pollutants in inner city newborns in conjunction with detailed exposure assessment and personal monitoring. Thus, it will provide much needed data about cumulative exposures and their sequelae sustained by these infants during fetal and early childhood development.
Future Activities:We will continue enrollment, monitoring, interviewing, extraction of medical record data, analysis of PAH in samplers, and analysis of biologic markers in maternal and infant blood samples. The database has been structured and inputting of questionnaire and biomarker data is ongoing.
Supplemental Keywords:children, exposure, asthma, PM, particulate matter, ETS, allergen, infants. , Air, Scientific Discipline, Health, RFA, Susceptibility/Sensitive Population/Genetic Susceptibility, Biology, indoor air, Risk Assessments, genetic susceptability, Health Risk Assessment, Epidemiology, air toxics, Chemistry, Children's Health, particulate matter, Environmental Chemistry, Allergens/Asthma, Environmental Monitoring, tropospheric ozone, copollutants, exposure assessment, exposure and effects, environmental hazard exposures, diesel particulates, allergen, health effects, indoor air quality, inhalation, dust , nutrition, diesel exhaust particulates, diesel exhaust, dust mite, indoor environment, assessment of exposure, childhood respiratory disease, dust mites, human health risk, sensitive population, toxics, maternal exposure, epidemeology, cockroaches, home, infants, PM 2.5, respiratory, sensitive populations, biological response, airway disease, biological markers, children, stratospheric ozone, disease, exposure, human health, children's vulnerablity, asthma triggers, allergic response, asthma, human exposure, Human Health Risk Assessment, PM
Relevant Websites:
http://www.mailman.hs.columbia.edu/ccceh/index.html 
Progress and Final Reports:
Original Abstract
2001 Progress Report
2002 Progress Report
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