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Final Report: Markers of Individual Susceptibility and Outcome Related to Fetal and Infant Growth and Development
EPA Grant Number: R830827Title: Markers of Individual Susceptibility and Outcome Related to Fetal and Infant Growth and Development
Investigators: Wolff, Mary S. , Berkowitz, Gertrud S. , Canfield, Richard L , Engel, Stephanie M. , Wetmur, James G. , Yehuda, Rachel
Institution: Mount Sinai School of Medicine
EPA Project Officer: Deener, Kacee
Project Period: August 1, 2002 through July 31, 2005 (Extended to July 31, 2006)
Project Amount: $748,512
RFA: Biomarkers for the Assessment of Exposure and Toxicity in Children (2002)
Research Category: Health Effects , Children's Health
Description:
Objective:Epidemiologic studies have linked poor fetal and infant growth and development to risk of disease and impaired mental function later in life. Interplay between environmental exposures and genetically derived differences in individual metabolism influences fetal growth and development. To assess gene-environment effects, we proposed to investigate biomarkers of susceptibility (GSTT1, GSTM1 and PON1 polymorphisms), a biomarker of stress (maternal and infant salivary cortisol), two indices of abnormal fetal growth, two sensitive indices of early cognitive development, as well as global neurodevelopmental assessments. In addition, timing of exposures in utero was considered. Exposures were characterized using both polycyclic aromatic hydrocarbon (PAH)-DNA adducts and meticulously constructed historical assessments of plume exposures to each individual participant.
Summary/Accomplishments (Outputs/Outcomes):To evaluate whether exposures to environmental toxins and psychological stress were related to impaired fetal growth or other adverse pregnancy outcomes, we established a prospective epidemiologic study of 187 women who were pregnant and at or near the World Trade Center (WTC) on or about September 11, 2001 (9/11). Enrollment began in February 2002 and continued through January 2003. Details of this cohort have been published. Of the 187 women enrolled, 3 miscarried and 2 were initially lost to followup, leaving 182 women for analysis. One was subsequently located, and we have her postpartum and 2-year information. The information collected on the exposed cohort appears in Table 1.
Table 1. Assessments of the WTC Pregnancy Study
In the following sections we will describe our analyses to date, including those that have already been published and those that are in progress.
Women Exposed to the World Trade Center Collapse Experienced a Higher Risk of Having a Small-for-Gestational-Age Birth
We found that the WTC cohort had a two-fold increased risk of small-for-gestational-age (SGA) infants, defined as a birth weight below the 10th percentile for gestational age based on the nomogram by Brenner, et al. (1976) compared to a Mount Sinai cohort. Other potential confounders such as marital status, education, prepregnancy weight, and pregnancy-induced hypertension did not materially alter the results. Similar results were obtained when birth weight was assessed as a continuous outcome variable with gestational age included in the model. No significant difference in the frequency of SGA was observed according to the trimester of exposure to 9/11. This finding suggests that the WTC disaster had a detrimental impact on exposed pregnancies. Our findings were published as a Research Letter in The Journal of the American Medical Association on August 6, 2003, (Berkowitz, et al., 2003) and were highlighted in the December 2003 issue of Environmental Health Perspectives.
SGA is a potential marker of intrauterine growth restriction (IUGR). Previous studies have found associations between particulate air pollution and IUGR (Bobak, et al., 2001; Dejmek, et al., 1999); other investigations have linked air pollution to preterm births (Ritz, et al., 2000). High levels of PAH-DNA adducts in umbilical cord leukocytes have been associated with reduced birth size (Perera, et al., 1998). Prenatal exposure to cigarette smoke, which contains PAHs among other toxins, is a well-established risk factor for IUGR. Our observation of an apparent association between maternal exposure to the WTC disaster and SGA infants suggests that this event had a detrimental impact on exposed pregnancies, possibly mediated through PAH or particulate matter (PM). Analysis of the geocoded location and exposure for each participant may further elucidate this finding. The possible long-term effects on infant development are unclear and will require continuing prospective followup. Preliminary findings are described in section 5.
GIS-Based Exposure Data Suggest an Intense Bystander Exposure After the WTC Collapse
Women were divided into zones of exposure based on their reported location at 9:00 a.m. on September 11, 2001, and for the succeeding 4 weeks. These zones were based on the following geographic boundaries: Zone 1, south of Murray Street; Zone 2, south of Chambers Street and north of Murray Street; Zone 3, south of Canal Street and north of Chambers Street; Zone 4, Brooklyn Heights; and Zone 5, the easternmost part of New Jersey across the Hudson River from the WTC (Figure 1).
Figure 1. World Trade Center Exposure Zones
We assessed exposures using geographic information system (GIS)-based models, interviews, and biologic markers. Women recorded their locations from 9/11 until October 8, 2001 (4 weeks) using a time-activity log. Exposures were assessed by time spent in five zones around the WTC and by an exposure index (EI) based on plume reconstruction modeling of dust and smoke intensity multiplied by time spent-per-day at specific street addresses within these zones. The daily reconstructed dust levels were correlated (r 0.7-0.9) with reported PM2.5 or PM10 levels taken from September 26 through October 8, 2001, at four of six sites near the WTC whose data we examined. A large proportion (71%) of these women were within 8 blocks of the WTC at 9:00 a.m. on 9/11, and 12 were in one of the two WTC towers. Daily EIs were highest immediately after 9/11, and became lower but remained highly variable over the next 4 weeks. The 4-week summary EI (ΣEI) reflected time spent during site evacuation, living, and working in the WTC area after 9/11, and it was strongly associated with women’s perception of air quality from week 2 to week 4 after the collapse.
Biomarkers of Exposure, Using Samples Collected After February 2002
Based on reported chemical contamination near the WTC, we measured selected chemicals in biological specimens collected starting in February 2002. Biomarkers included PAH-DNA adducts in maternal blood mononuclear cells, organochlorines (OC) in maternal plasma, and heavy metals in maternal urine and blood. At the time of the baseline visit, 40cc of maternal blood and 50cc of maternal urine were obtained, as well as a sample of breast milk (if the patient had delivered and was breastfeeding). Maternal blood and urine were analyzed for a variety of environmental toxins present in the environment as a result of the WTC collapse and fire in a subset of 100 women by the Centers for Disease Control and Prevention (CDC).
PAH-DNA adducts were measured in 160 women. Most were nondetectable (88/160, 55%); the median of detectable values was 60 adducts/106 nucleotides (apmn). Eleven women had levels above 100 apmn, and nine of these women had blood drawn in February or March 2002, a time interval within the reported clearance times of PAH-DNA adducts from lymphocytes (Mooney, et al., 1995). Samples collected in February/March had a significantly greater number of detectable PAH-adducts (46; 64%) and a higher median value (46.7 apmn) compared with later samples (26, 30%; median 20.0 apmn). There were no consistent associations between PAH-adducts and EI, when considered overall or by various temporal windows of blood draw and EI-weekly sum. Neither ΣEI nor PAH-adducts were associated with dietary intake (e.g., broiled meat) or smoking, questions targeted for this purpose in the questionnaire.
The highest levels of PAH-DNA adducts were seen among women whose blood was collected sooner after 9/11, but levels showed no significant associations with EI or other potential exposure sources. Lead (Pb) and cobalt (Co) in urine were weakly correlated with ΣEI, but not among samples collected closest to 9/11. Plasma OC levels were low. PCB (sum of PCBs 118, 138, 153, 180) was 84 ng/g lipid (median) and had a nonsignificant positive association with ΣEI. 1234678-heptachlorodibenzodioxin levels (median 30 pg/g lipid) were similar to those reported in WTC-exposed firefighters but were not associated with EI. This report indicates intense bystander exposure after the WTC collapse and provides information about nonoccupational exposures among a vulnerable population of pregnant women. (Wolff, et al., 2005) Genotyping for GSTT1, GSTM1, and GSTP1 has been completed, and data are currently being analyzed.
Breast Milk
At the time of breast milk collection, exfoliated ductal epithelial cells were separated. DNA will be extracted from these samples and from exfoliated urothelial bladder cells collected from urine from the same participants. p32-Postlabeling and high-performance liquid chromatography will be used to determine levels of 4-aminobiphenyl (ABP) adducts in those cells and will be evaluated in relation to WTC exposures as well as to use of permanent hairdyes, using data collected by questionnaire at the time of specimen donation. We will also determine if 4-ABP adducts are higher among women with specific genotypes related to metabolism of 4ABP.
Relationship Between Post-Traumatic Stress Symptomology (PTSS) and Depression and Pregnancy Outcome
- The destruction of the WTC on September 11, 2001, was a source of enormous psychological trauma, which may have consequences for the health of pregnant women and their fetuses.
- The impact of stress resulting from ordinary life experiences may be different from that which results from extreme trauma. Post-traumatic stress disorder (PTSD) in particular is associated with depressed cortisol production in some studies (Yehuda, 2002), whereas brief and sustained periods of stress and major depression tend to be associated with increased cortisol production (Yehuda, 2002). Although the literature is somewhat mixed (Hoffman, et al., 1996; Whitehead, et al., 2002), it is commonly believed that prenatal stress increases risk of preterm delivery through alterations in the hypothalamic-pituitary-adrenal axis (Chan, et al., 1993; Hogue, et al., 2001; Wadhwa, et al., 2001); specifically, stress may increase the production of cortisol and corticotrophin-releasing hormone (CRH), which promote the biological cascade leading to delivery (Wadhwa, et al., 2001).
- We evaluated the impact of extreme trauma on the birth outcomes of women highly exposed to the WTC. Among women with singleton pregnancies, 52 completed at least one psychological assessment prior to delivery. In adjusted multivariate models, both post-traumatic stress symptoms (PTSS) and moderate depression were associated with longer gestational durations, although PTSS was also associated with decrements in infant head circumference at birth (β = -0.07, SE = 0.03, p = 0.01). This decrement in head circumference may influence subsequent neurocognitive development and function.
- PTSS may be related to lower cortisol levels. Therefore, our findings that PTSS is related to longer gestational durations are not inconsistent with the underlying biological mechanism. Moreover, prenatal PTSS may be more influential on infant neurocognitive development than depression or anxiety. Long-term followup of infants exposed to extreme trauma in utero is needed to evaluate the persistence of these effects. (Engel, et al., 2005)
Longitudinal Measurements of Psychopathology Over Time in WTC Exposed Women
Instruments to measure stress and depression were administered to participants at the baseline visit, the first anniversary of 9/11, and the 2-year visits. These instruments included the Post-Traumatic Stress Disorder Checklist, Beck Depression Index, Life Events Inventory, State-Trait Anxiety Inventory, Childhood Trauma Questionnaire, and Trauma History Questionnaire. Compared to estimates of probable PTSD in Manhattan residents living south of 110th Street 6 months after 9/11 (0.6%, n = 854 [Galea, et al., 2003]), the proportion suffering from probable PTSD 6 months after 9/11 in our population of women who were living or working south of Canal Street on or about 9/11 was substantially higher (10.7%, n = 37). Among the women in our study with probable PTSD within 9 months of 9/11/01 (10.7%, n = 149), there was a high probability of concurrent depression (37.5%, p < .0001). There were no apparent differences in risk of PTSD by the trimester of pregnancy in which 9/11 occurred.
In total, 175 women (96%) completed at least one series of psychological instruments, 138 women (76%) completed instruments at two visits, and 70 women (38%) completed instruments at all three visits to date. At the baseline visit, 8.2–10.7 percent of women reported symptoms consistent with probable PTSD. Of these women, all reported having symptoms for greater than 1 month, and over 80 percent reported having them for greater than 3 months. Moreover, 8.7 percent of women reported at least moderate functional impairment in at least three areas of their life.
At the 1-year anniversary of 9/11, 8.3–13.4 percent of women reported symptoms consistent with probable PTSD. All of these women reported having their symptoms for greater than 1 month and the majority (85–100%) for greater than 3 months. Functional impairment remained high, with 8 percent reporting at least moderate functional impairment in three areas of their life.
At the baseline visit, women who were in Zone 1 at 9:00 a.m. on 9/11 had almost a three-fold greater risk of a probable PTSD diagnosis (Odds Ratio [OR]= 2.9, 95% Confidence Interval [CI] 1.0, 8.7) relative to women in all other zones. At the first anniversary of 9/11, there was no longer any relationship between proximity to the WTC at 9:00 a.m. on September 11th and risk of probable PTSD. However, there was a strong relationship between the number of negative life events reported and having a probable PTSD diagnosis (OR = 5.4, 95% CI 1.3, 23.1).
Additional data analyses are ongoing which incorporate the third series of psychological instruments to determine time trends and patterns of maternal psychopathology up to the 2-year neurodevelopmental assessment of the child. Preliminary analyses indicate that the prevalence of probable PTSD may have declined slightly; however, symptoms of moderate/severe depression remain unchanged (Figure 2).
Figure 2. Depression and Post-Traumatic Stress Disorder Over Time in Women Pregnant on 9/11
Babies of Mothers Who Experienced Traumatic Stress Resulting From the WTC Exposure Had Lower Cortisol Levels at 9 Months Postpartum
Reduced cortisol levels have been linked with vulnerability to PTSD and the risk factor of parental PTSD in adult offspring of Holocaust survivors. The purpose of this study was to report on the relationship between maternal PTSD symptoms and salivary cortisol levels in infants of mothers directly exposed to the World Trade Center collapse on September 11, 2001, during pregnancy. Mothers (n = 38) collected salivary cortisol samples from themselves and their 1-year-old babies at awakening and at bedtime. Lower cortisol levels were observed in both mothers (F = 5.15, df = 1, 34; P = 0.030) and babies of mothers (F = 8.0, df = 1, 29; P = 0.008) who developed PTSD in response to September 11 compared with mothers who did not develop PTSD and their babies. Lower cortisol levels were most apparent in babies born to mothers with PTSD exposed in their third trimesters. The data suggest that effects of maternal PTSD related to cortisol can be observed very early in the life of the offspring and underscore the relevance of in utero contributors to putative biological risk for PTSD (Yehuda, et al., 2005).
Preliminary Analysis of Neurodevelopmental Assessments: Preliminary Analysis of Behavioral, Cognitive, and Psychomotor Development at 2 Years of Age Using the Bayley Scales of Infant Development and the Toddler Behavior Assessment Questionnaire (TBAQ revised 2003 version, Goldsmith HH 1996):
We have completed 132 child neurodevelopmental assessments at 2 years of age. The Bayley Scales includes both a Mental Development (MDI) and Psychomotor Development (PDI) index. The MDI assesses sensory-perception, memory, learning, problem-solving ability, understanding of object constancy, vocalizations, and language development. The PDI measures gross motor and fine motor development. The Toddler Behavior Assessment Questionnaire (TBAQ) is a standardized questionnaire that measures temperamental dimensions on 11 scales: activity level, anger, attention, inhibitory control, interest, object fear, pleasure, sadness, sensory defensiveness, social fear, and soothability. Each scale consists of 10 items, which parents rate from 1 (never) to 7 (always).
The mean age of testing was slightly under 2 years 1 month. The mean (SD) MDI and PDI scores were 97.7 (13.5) and 93.8 (13.8) respectively. Zone of exposure was significantly associated with the MDI, such that children born to women who were in either Zone 1 or Zone 2 at 9:00 a.m. on September 11, 2001, had lower mean scores (-7.7 points, p < 0.01). The effect of zone was modestly diminished after excluding the 11 children who exhibited a high rate of refusal during their assessment, which may have impacted their overall MDI score. Additionally, children born to women who were in their first trimester on September 11 were significantly delayed on their PDI (-6.6 points, p = 0.02) (Table 2). In preliminary analyses of stress and depression in relation to neurodevelopment at age 2, we found that mild depression seemed to be associated with a modest advancement in psychomotor development. Additional analyses are underway (Table 3).
Table 2. Preliminary Analysis of Neurodevelopment at 2 Years of Age of Children Born to Mothers Exposed to the World Trade Center Attacks Using the Bayley Scales of Infant Development (n = 127) |
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MDI1 |
PDI 2 |
|||
Variables of Interest |
Difference in Means (SD) |
p-value |
Difference in Means (SD) |
p-value |
Zone of Exposure at 9:00 a.m. on |
|
|
|
|
Trimester on September 11th |
-3.7 (2.8) 0.1 (2.9) Reference |
0.19 0.99 |
-6.6 (2.8) -2.4 (3.0) Reference |
0.02 0.42 |
1 Models adjusted for maternal education, child gender, age at 2-year followup (range 1.8 – 2.5 years), and parity. Models exclude three children whose MDI scores may have been affected by internal factors, such as hunger or sleepiness during the testing period. |
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Table 3. Preliminary Analysis of Neurodevelopment at 2 Years of Age of Children Born to Mothers Exposed to the World Trade Center Attacks Using the Bayley Scales of Infant Development (n = 127) |
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MDI1 |
PDI2 |
|||
Variables of Interest |
Difference in Means (SD) |
p-value |
Difference in Means (SD) |
p-value |
PTSD at baseline |
-0.3 (4.7) 9.6 (5.4) |
0.95 0.08 |
3.0 (5.2) 4.5 (6.1) |
0.56 0.47 |
Depression at baseline |
4.7 (4.7) 3.2 (2.6) Reference |
0.31 0.23 |
5.4 (5.0) 6.4 (2.8) Reference |
0.29 0.02 |
State-Trait Anxiety at baseline |
2.8 (2.7) 3.8 (2.6) |
0.30 0.15 |
-1.2 (3.0) -0.6 (3.0) |
0.70 0.84 |
1 Models adjusted for maternal education, child gender, and race/ethnicity. Models exclude three children whose MDI scores may have been affected by internal factors, such as hunger or sleepiness during the testing period. |
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Previous studies have linked alterations in infant behavior, such as emotional and physiologic state dysregulation and hyperactivity, to prenatal exposure to maternal stress and/or depression (Van den Bergh, et al., 1989). We conducted preliminary analyses of the TBAQ, in which women rate the behavior and temperament of their children in the month prior to their interview. Women who were in zone 1 on 9/11 at 9:00 a.m. rated their child as being more prone to anger (crying, protesting, hitting, pouting in situations involving conflict with their mother or another child) (p < 0.01) or sadness (negative affect and lowered mood and energy related to suffering, disappointment, and object loss) (p < 0.05) than women who were not in zone 1, adjusted for child gender and race/ethnicity. Additionally, women who were in their first trimester on 9/11 reported that their child had a higher level of object fear (distress, withdrawal, and fearful vocalizations when exposed to a variety of objects and nonsocial situations), relative to women who were in later stages of pregnancy on 9/11 (p < 0.05). This finding is consistent with our findings from the Infant Behavior Questionnaire, that infants of women who were in zone 1 on 9/11 at 9:00 a.m. had a higher level of fearfulness.
We have finished the 3-year follow-up evaluations of the infants in the WTC-exposed cohort that included assessment of childhood growth, the Bayley Scales of Infant Development, a brief follow-up questionnaire, and the Home Inventory (which assesses the quality of the home environment and parent/child interaction). We also collected infant urine at this visit.
A control group of 9-month-old infants has been recruited from two private pediatric groups near Mount Sinai Medical Center. The sociodemographic characteristics of the mothers of these infants appear to be similar to those of the WTC mothers. The same questionnaires, stress instruments, growth assessments, and neurodevelopment tests have been administered.
Additional data analyses are ongoing, including the examination of the exposure biomarker data with respect to pregnancy; the examination of longitudinal psychopathology among the women exposed to the WTC; and the examination of the relationship between exposure and developmental and behavioral outcomes at 9-months and 2-years of age.
Genetic polymorphisms have been determined in maternal and child DNA for four genes related to the WTC exposures and fetal growth (Table 4). No relationships were observed between maternal PAH-DNA adducts and these genotypes.
Table 4. Genotype Frequencies Among WTC Mothers and Children
All the 9-month and 2-year assessments on the WTC cohort have been completed, including administration of the Fagan Infantest and the Visual Expectation Paradigm test, the Bayley Scales of Infant Development, and assessment of growth. We also have collected buccal samples from the infants for genotyping and obtained saliva for cortisol assessment.
Analysis of the cortisol data is ongoing. Data analyses are underway on the neurodevelopment outcomes.
References:
Bobak M, Richards M, Wadsworth M. Air pollution and birth weight in Britain in 1946. Epidemiology 2001;12:358-359.
Brenner WE, Edelman DA, Hendricks CH. A standard of fetal growth for the United States of America. American Journal of Obstetrics and Gynecology 1976;126:555-564.
Chan EC, Smith R, Lewin T, Brinsmead MW, Zhang HP, Cubis J, et al. Plasma corticotropin-releasing hormone, beta-endorphin and cortisol inter-relationships during human pregnancy. Acta Endocrinologica (Copenh) 1993;128:339-344.
Dejmek J, Selevan SG, Benes I, Solansky I, Sram RJ. Fetal growth and maternal exposure to particulate matter during pregnancy. Environmental Health Perspectives 1999;107:475-480.
Galea S, Vlahov D, Resnick H, Ahern J, Susser E, Gold J, et al. Trends of probable post-traumatic stress disorder in New York City after the September 11 terrorist attacks. American Journal of Epidemiology 2003;158:514-524.
Hoffman S, Hatch MC. Stress, social support and pregnancy outcome: a reassessment based on recent research. Paediatric Perinatal Epidemiology 1996;10:380-405.
Hogue CJ, Hoffman S, Hatch MC. Stress and preterm delivery: a conceptual framework. Paediatric Perinatal Epidemiology 2001;15(S2):30-40.
Perera FP, Whyatt RM, Jedrychowski W, Rauh V, Manchester D, Santella RM, et al. Recent developments in molecular epidemiology: a study of the effects of environmental polycyclic aromatic hydrocarbons on birth outcomes in Poland. American Journal of Epidemiology 1998;147:309-314.
Ritz B, Yu F, Chapa G, Fruin S. Effect of air pollution on preterm birth among children born in Southern California between 1989 and 1993. Epidemiology 2000;11:502-511.
Van den Bergh BR, Mulder EJ, Visser GH, Poelmann-Weesjes G, Bekedam DJ, Prechtl HF. The effect of (induced) maternal emotions on fetal behaviour: a controlled study. Early Human Development 1998;19:9-19.
Wadhwa PD, Culhane JF, Rauh V, Barve SS, Hogan V, Sandman CA, et al. Stress, infection and preterm birth: a biobehavioural perspective. Paediatric Perinatal Epidemiology 2001;15(S2):17-29.
Whitehead N, Hill HA, Brogan DJ, Blackmore-Prince C. Exploration of threshold analysis in the relation between stressful life events and preterm delivery. American Journal of Epidemiology 2002;155:117-124.
Yehuda R. Post-traumatic stress disorder. North England Journal of Medicine 2002;346:108-114.
Journal Articles on this Report: 5 Displayed | Download in RIS Format
| Other project views: | All 26 publications | 5 publications in selected types | All 5 journal articles |
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Berkowitz GS, Wolff MS, Janevic TM, Holzman IR, Yehuda R, Landrigan PJ. The World Trade Center disaster and intrauterine growth restriction. Journal of the American Medical Association 2003;290(5):595-596 (research letter). |
R830827 (2003) R830827 (2004) R830827 (Final) |
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Engel SM, Berkowitz GS, Wolff MS, Yehuda R. Psychological trauma associated with the World Trade Center attacks and its effect on pregnancy outcome. Paediatric and Perinatal Epidemiology 2005;19(5):334-341. |
R830827 (Final) |
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Landrigan PJ, Lioy PJ, Thurston G, Berkowitz G, Chen LC, Chillrud SN, Gavett SH, Georgopoulos PG, Geyh AS, Levin S, Perera F, Rappaport SM, Small C, NIEHS World Trade Center Working Group. Health and environmental consequences of the World Trade Center disaster. Environmental Health Perspectives 2004;112(6):731-739. |
R830827 (2004) R830827 (Final) R827351 (2003) R827351 (Final) R831711C002 (2004) R832141 (2005) |
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Wolff MS, Teitelbaum SL, Lioy PJ, Santella RM, Wang RY, Jones RL, Caldwell KL, Sjodin A, Turner WE, Li W, Georgopoulos P, Berkowitz GS. Exposures among pregnant women near the World Trade Center site on 11 September 2001. Environmental Health Perspectives 2005;113(6):739-748. |
R830827 (2004) R830827 (Final) R831711 (2005) |
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Yehuda R, Engel SM, Brand SR, Seckl J, Marcus SM, Berkowitz GS. Transgenerational effects of posttraumatic stress disorder in babies of mothers exposed to the World Trade Center attacks during pregnancy. The Journal of Clinical Endocrinology & Metabolism 2005;90(7):4115-4118. |
R830827 (Final) |
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prenatal exposure, effects, infant neurodevelopment, infant growth, in utero exposure, 9/11, World Trade Center, genetic polymorphisms, exposure assessment, cortisal, buccal cells, neurodevelopmental assessment, PAH, biomarker,
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ENVIRONMENTAL MANAGEMENT, Scientific Discipline, Health, RFA, PHYSICAL ASPECTS, Susceptibility/Sensitive Population/Genetic Susceptibility, Risk Assessment, Risk Assessments, genetic susceptability, Health Risk Assessment, Physical Processes, Children's Health, Biochemistry, Environmental Chemistry, endocrine disrupting chemicals, health effects, children's environmental health, assessment of exposure, childhood respiratory disease, growth and development, stress, harmful environmental agents, human health risk, infants, environmental triggers, air pollution, airway disease, children, adolescence, exposure, biomarker, children's vulnerablity, human susceptibility, genetic predisposition, human exposure
Progress and Final Reports:
2003 Progress Report
2004 Progress Report
Original Abstract