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2001 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, 2000 through October 31,2001
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 except that pesticides were added to Aim 1. They are to test the hypotheses that: (1) prenatal and/or early postnatal exposure to polycyclic aromatic hydrocarbons, 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 (lead, mercury, organochlorines) 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 polycyclic aromatic hydrocarbons (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 pesticides with carcinogenic potential. The new biologic markers that have been added include: (1) levels of organochlorines (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; and (2) metals (mercury, cadminum, chromium, arsenic, and nickel) in maternal urine samples collected during the third trimester.
Progress Summary:Screening and Enrollment
Since December 1998, research workers have screened 1,750 women, of whom 606 were eligible and willing to participate; 188 dropped out or were determined to be ineligible between screening and birth; and 46 women have not yet delivered. To date, 372 women have met the criteria for complete enrollment into the Mothers and Newborns Study cohort (i.e., underwent prenatal monitoring, provided a prenatal questionnaire, blood sample collected at delivery from either the mother and/or her newborn). Because 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 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 453 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 PAHs—benz(a)anthracene, chrysene, benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(a)pyrene, indeno(1,2,3-cd)pyrene, dibenz(a,h)anthracene and benzo(g,h,i)perylene. Analysis of PAH in air samples from an initial 250 subjects showed that all samples had detectable levels of one or more carcinogenic PAH. Total PAH exposures averaged 4.0 ng/m3 and varied significantly among the women with a range of 0.036-44.81 ng/m3. These concentrations can be compared to those measured in samples from nonsmoking women who worked out-of-doors in the Czech Republic, where air pollution arises from coal burning (average of 12.5 ± 6.8 ng/m3 in one of the most polluted areas; 6.9 ± 4.4 ng/m3, range 2.7-18.8 ng/m3 in a less polluted area). Thus, the mean PAH concentration in the NYC population is lower; but the range is wider and the upper bound is higher.
Non-persistent pesticides (NPP) have been measured in an initial subset of the stored maternal urine samples collected during pregnancy. DEP was detected in 49/60 (82%) (range ND-36.5 μg/g creatine), DETP in 60/60 (100%) (range 0.3-29.7 μg/g creatine), DEDTP in 19/60 (32%) (range ND-1.2 μg/g creatine), DMP in 56/60 (93%) (range ND-62.4 μg/g creatine), and DMDTP in 24/60 (40%) (range ND-27 μg/g creatine). DMTP levels are being quantified.
Biologic Samples
Thus far, 372 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 percent and a maternal blood sample for 98 percent. In collaboration with the Centers for Disease Control and Prevention (CDC), samples have been analyzed for cotinine, 4-ABP-Hb, lead and mercury, OCs and NPP. In the first samples analyzed, 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). Among the 279 mothers and 235 newborns with cotinine levels < 25 ng/m L, 45 percent of mothers and 47 percent of infants had levels indicative of ETS exposure (≥ 0.03-25 ng/mL). Maternal and newborn plasma 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). In the initial 137 samples analyzed, umbilical cord lead levels ranged from non-detectable to 7.6 μg/dL, while mercury levels ranged from non-detectable to 9.4 μg/ L. These levels are below the levels of immediate health concern for both contaminants (≥ 10 μg/d L for lead, ≥ 30 μg/ L for mercury); but thresholds have not been established for their neurotoxic effects. Analyses of organochlorines (PCBs, DDT/DDE, etc.) have been completed on 105 plasma samples. Because levels were generally non-detectable, 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. Eight of the 29 (28%) pesticides analyzed were detected in ≥ 25 percent of the maternal and/or cord blood samples (see Table 1). These included chlorpyrifos, propoxur, bendiocarb, carbaryl, and diazinon that are widely used for residential pest control in these minority communities. In general, levels of the pesticides in maternal and cord blood samples were similar and, with the exception of phthalimide, were highly correlated. Consistent with experimental data, these findings suggest that pesticides are readily transferred from the mother to the fetus. Collectively, these results show widespread but variable NPP exposure among the cohort and indicate that measurements of contemporary-use pesticides in blood samples collected at birth are useful biomarkers of prenatal exposure.
Table 1. Levels of 8/29 Contemporary-Use Pesticides Detected in ≥ 25% of Maternal and/or Cord Plasma (pg/g)
|
|
Maternal Plasma (n = 142) |
Cord Plasma (n = 155) |
Correlation |
||
|
|
# with detectable levels (%) |
Mean ± SD5 (range) |
# with detectable levels (%) |
Mean ± SD (range) |
r, p-value |
|
1-Naphthol1 |
40 (28%) |
16.6 ± 113.6 (ND-97) |
37 (24%) |
16.9 ± 15.7 (ND-120) |
r = 0.3, p = 0.002 |
|
2-Isopropoxphenol2 |
96 (68%) |
3.8 ± 2.5 (ND-16) |
106 (68%) |
3.7 ± 246 (ND-16) |
r = 0.5, p < 0.001 |
|
Bendiocarb |
95 (67%) |
4.7 ± 1.8 (ND-14) |
89 (57%) |
4.6 ± 3.0 (ND-28) |
r = 0.5, p < 0.001 |
|
Chlorpyrifos |
138 (97%) |
6.9 ± 5.4 (ND-35) |
148 (95%) |
6.8 ± 7.0 (ND-63) |
r = 0.6, p < 0.001 |
|
Diazinon |
77 (54%) |
1.1 ± 2.3 (ND-25) |
88 (57%) |
1.1 ± 1.8 (ND-13) |
r = 0.6, p < 0.001 |
|
Dichloran |
123 (87%) |
3.9 ± 4.2 (ND-29) |
143 (92%) |
412 ± 4.6 (ND-35) |
r = 0.7, p < 0.001 |
|
Phthalimide3 |
93 (65%) |
29.2 ± 27.6 (ND-270) |
84 (54%) |
24.9 ± 20.2 (ND-160) |
r = 0.1, p = 0.14 |
|
Tetrahydrophthalimide4 |
76 (54%) |
2.6 ± 5.2 (ND-43) |
81 (52%) |
2.2 ± 4.1 (ND-37) |
r = 0.5, p < 0.001 |
Metabolite of: 1Carbaryl, 2Propoxur, 3Folpet, 4Captan, 5ND set at 0.5 x detection limit, 6Mother/newborn pairs
Follow-up Assessments
Preliminary analyses have been completed for 248 Denver II Developmental Tests and 216 Fagan Tests of Infant Intelligence at 6 months, 207 Bayley Scales of Infant Development at 12 months, and 79 Bayleys at 24 months. At 6 months, 14.1 percent of infants scored in the “suspect” range for developmental delay on the Denver. At 6 months, 19.4 percent of infants were in the “at risk” range on the Fagan. At 12 months, 15.9 percent were in the mildly delayed range for cognitive development and 1 percent in the severely delayed range.
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 annual report for R827027C003).
Loss to Follow-Up
Follow -up assessments at 12 months have been completed on 223/249 (90%) of the fully enrolled infants who have reached their first birthday. Follow -up assessments at 24 months have been completed on 90/106 (85%) of the fully enrolled infants who have reached their second birthday, for an estimated 15 percent loss-to-follow up by age two.
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, personal monitoring, and clinical assessments. 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, and 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:
2000 Progress Report
Original Abstract
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