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2005 Progress Report: Growth and Development Research Project: Prenatal and Postnatal Urban Pollutants and Neurobehavioral Developmental Outcomes
EPA Grant Number: R832141C001Subproject: this is subproject number 001 , established and managed by the Center Director under grant R832141
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Columbia Center for Children’s Environmental Health
Center Director: Perera, Frederica P.
Title: Growth and Development Research Project: Prenatal and Postnatal Urban Pollutants and Neurobehavioral Developmental Outcomes
Investigators: Rauh, Virginia , Davidson, Leslie , Greenhill, Larry , Perera, Frederica P. , Whyatt, Robin M.
Current Investigators: Rauh, Virginia
Institution: Columbia University
EPA Project Officer: Fields, Nigel
Project Period: November 1, 2003 through October 31, 2008
Project Period Covered by this Report: November 1, 2004 through October 31, 2005
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003)
Research Category: Children's Health , Health Effects
Description:
Objective:The specific objectives of this research project are to: (1) quantify the impact of pre-/postnatal exposures to polycyclic aromatic hydrocarbons (PAHs), environmental tobacco smoke (ETS), and pesticides on neurobehavioral development through 7 years of age; (2) refine measurement of exposure to chronic social stressors to assess the impact of chronic stressors on child neurobehavioral development at 5 and 7 years of age, and interactive effects of between environmental toxicants and sociodemographic conditions; (3) investigate the modifying role of micronutrients and genetic polymorphisms on the association of PAH and ETS with fetal growth and neurodevelopment through 7 years of age; (4) collaborate with the Community Outreach, Translation and Application Core to translate and apply findings to education initiatives; and (5) investigate associations between neurodevelopmental deficits and asthma morbidity at 5 and 7 years of age. We posit that children exhibiting asthma symptoms are more likely to manifest neurodevelopment deficits as compared to children without symptoms.
Progress Summary:Screening and Enrollment
Since December 1998, research workers have screened 1,097 women eligible and willing to participate in the study. Thus far, 648 women are now fully enrolled (i.e., completed prenatal monitoring, prenatal questionnaire, and maternal or newborn blood sample at delivery), with 536 remaining in the study, resulting in a retention rate of 82.72 percent. Assessments completed so far are: 461 12-month, 378 24-month, 331 36-month, 161 48-month, 194 60-month, and 47 72-month.
Interview and Demographics
To date, 755 women have completed the prenatal interview (contents reported previously). Average maternal age at delivery is 25.0 (+ 4.9) years, 34.9 percent are African American, 65.1 percent are Dominican, 69.8 percent have never been married, 34.6 percent have not graduated from high school, 39.1 percent receive public assistance, and 91.3 percent currently are on Medicaid.
Biological Samples/Biomarkers
To date, a blood sample at the time of delivery has been collected from 652 women and/or newborns. In addition to the biomarkers of exposure described in the Exposure Assessment Facility Core progress report, umbilical cord lead levels were analyzed and ranged from nondetectable to 7.6 μg/dL, with a mean of 1.068 μg/dL. Cord blood mercury levels were analyzed and ranged from nondetectable to 17.90 μg/dL. Almost one-half of mothers and infants had levels of cotinine in maternal or cord blood at the time of delivery (between 0.0250 and 25 ng/mL), indicating that they had been exposed to secondhand smoke within 48 hours. The association between ETS and cotinine levels was significant and of comparable magnitude for both African American (χ2 = 26.89, p < 0.001) and Hispanic women (χ2 = 19.16, p < 0.001). Almost 20 percent (19.7%) of women were in the highest quartile of chlorpyrifos exposure during pregnancy, and 40 percent of newborns had detectable levels of PAH-DNA adducts in cord blood.
Birth Outcomes
Birth weight (bw), length (bl), and head circumference (hc) were abstracted from the medical record following delivery. Mean bw for the cohort is 3369.7 (±482.6) g and 39.3 (±1.5) weeks gestational age. A significant inverse association was seen between PAH levels in maternal personal air samples and both bw (p = 0.003) and hc (p = 0.01) in African American but not Dominican infants. Maternal personal air PAH levels during pregnancy were significantly associated with stable chromosomal aberrations in umbilical cord lymphocytes measured in a subset by fluorescence in situ hybridization (p < 0.01, n = 60). Self-reported ETS exposure was associated with smaller hc (ß = -0.01, p = 0.04) after adjusting for potential confounders. Cotinine was significantly associated with bl (ß = -0.01, p = 0.05). B[a]P-DNA alone was not significantly associated with any birth outcome; however, the interaction between high/low adducts and ETS was significant using either adduct variable. There was a 233 g (6.8%) reduction in bw and 1 cm (2.9%) reduction in hc among the high benzo[a]pyrene (B[a]P)-DNA/ETS+ compared with the low B[a]P-DNA/ETS- correlated (rs > 0.9, p < 0.001). Of those who self-reported moderate or high ETS exposure (125 or 38.8% of those with cotinine values), 91 (72.8%) screened positive for the detectable group. Prenatal pesticide exposure also reduced fetal growth. Among newborns born prior to the January 1, 2001, U.S. Environmental Protection Agency ban, an inverse and highly significant association was seen between (ln)cord plasma chlorpyrifos levels and both bw (B = -67.3 gm/unit, p = 0.008) and length (B = -0.43 cm/unit, p = 0.004). Among newborns born after January 1, 2001, the relationships were no longer significant (p > 0.5). Similarly, among newborns born prior to January 1, 2001, a significant inverse association (p < 0.01) was seen between the (ln)combined levels of cord plasma chlorpyrifos and diazion (in chloryrifos-equivalents) and both bw and bl. Birth weight averaged 215.1 grams less among those with the highest compared to lowest 26 percent of exposure levels (p = 0.03); after 2001, the magnitude of effect was not significant.
Neurodevelopmental Outcomes
Data entry has been completed for: 426 Denver II Developmental Tests; 385 Fagan Tests of Infant Intelligence, 6-month; 418 Bayley Scales of Infant Development, 12-month; 346 Bayley, 24-month; 283 Bayley, 36-month; 101 Wechsler Preschool and Primary Scale of Intelligence, 60-month. Children in mild-moderately delayed range for development: 14.3 percent cognitive and 16.3 percent motor, 12-month; 50 percent cognitive and 15.2 percent motor, 24-month; 32.3 percent cognitive, and 13.5 percent motor, 36-month. Overall mean Mental Development Index scores: 12-month, 94.03 (sd = 9.78); 24-month, 85.1 (sd = 12.41); 36-month, 89.58 (sd = 11.41). Overall mean Psychomotor Development Index scores: 12-month, 96.22 (sd = 12.21), 24-month, 97.04 (sd = 12.47), 36-month, 100.46 (sd = 12.98). The cohort demonstrated a dip in cognitive development scores during the toddler years (frequently reported in low-income populations followed by an increase in the later preschool period). The Child Behavior Checklist measure of behavior problems classified 3.4 percent as having attentional problems and 3.9 percent having Attention-Deficit/Hyperactivity Disorder (ADHD) at 3 years.
Significant adverse effects of prenatal pesticide exposure on neurodevelopment were seen at 36 months but not before. Specifically, after adjustment for gender, ethnicity, gestational age at birth, quality of home caretaking environment, prenatal exposure to ETS, and maternal education and intelligence, a significant negative chlorpyrifos effect on psychomotor development was apparent at 36 months (p < 0.01). Race (p = 0.034), home caretaking environment (p = 0.057), and gender (p = 0.077) had larger effects on motor development at 36 months as compared to earlier points in time, reflecting either stabilizing of the social and caretaking environments, or increasing reliability of the Bayley test over time. In addition, gestational age remained a significant predictor of development at 36 months. The lack of a significant interaction between chlorpyrifos exposure level and Home Inventory score suggests that the magnitude of the 36-month prenatal pesticide effect is not affected by the quality of the caretaking environment. The adverse effect of prenatal chlorpyrifos exposure on cognitive development was marginally significant at 36 months (p = 0.06). Altogether, exposures and covariates accounted for approximately 25 percent of the variance in cognitive scores by 36 months. In addition, highly exposed children were 2.3 times as likely to manifest cognitive developmental delays by 36 months and almost 5 times as likely to manifest psychomotor problems at 36 months.
Using repeated measures analysis of pesticide effects on cognitive and motor development over the 3-year follow-up period, there was a significant interaction effect of age and chlorpyrifos on motor development (p < 0.01), confirming the age-specific regression findings of a significant adverse effect of prenatal pesticide exposure on psychomotor development emerging over time. Highly exposed children also were more likely to have certain types of behavior problems. Specifically, significant chlorpyrifos effects found for the Attention profile and the ADHD syndrome showed children prenatally exposed to high levels of chlorpyrifos were 1.9 times and 6.1 as likely to score in the clinical range on Attention profile and ADHD scale, respectively.
Loss to Followup
Overall loss-to-followup in the study is 17.28 percent.
Significance
This study is providing much-needed data on the effects of cumulative exposures. It is one of the first to measure molecular dose and biologic effects of a comprehensive set of common environmental pollutants on a range of neurodevelopmental domains from birth through age 7 in a cohort of inner-city children and assess interactive effects of material deprivation with toxic environmental exposures.
Future Activities:Enrollment, data collection, and analyses will continue as planned through children’s seventh birthdays.
Journal Articles on this Report: 3 Displayed | Download in RIS Format
| Other subproject views: | All 3 publications | 3 publications in selected types | All 3 journal articles |
| Other center views: | All 100 publications | 89 publications in selected types | All 86 journal articles |
| Type | Citation | ||
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Bocskay KA, Tang D, Orjuela MA, Liu X, Warburton DP, Perera FP. Chromosomal aberrations in cord blood are associated with prenatal exposure to carcinogenic polycyclic aromatic hydrocarbons. Cancer Epidemiology Biomarkers & Prevention 2005;14(2):506-511. |
R832141 (2006) R832141C001 (2005) R827027 (2002) |
not available |
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Perera FP, Tang D, Tu YH, Cruz LA, Borjas M, Bernert T, Whyatt RM. Biomarkers in maternal and newborn blood indicate heightened fetal susceptibility to procarcinogenic DNA damage. Environmental Health Perspectives 2004;112(10):1133-1136. |
R832141C001 (2005) R827027 (2002) |
not available |
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Perera F, Tang DL, Whyatt R, Lederman SA, Jedrychowski W. DNA damage from polycyclic aromatic hydrocarbons measured by benzo[a]pyrene-DNA adducts in mothers and newborns from Northern Manhattan, the World Trade Center area, Poland, and China. Cancer Epidemiology Biomarkers & Prevention 2005;14(3):709-714. |
R832141 (2006) R832141C001 (2005) R827027 (2002) |
not available |
children’s health, children’s environmental health, genetics, health effects, health risk assessment, air pollutants, exposure assessment, national exposure, pesticides, PAHs, ETS, tobacco smoke,
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HUMAN HEALTH, ENVIRONMENTAL MANAGEMENT, INTERNATIONAL COOPERATION, Scientific Discipline, Health, RFA, Health Effects, Risk Assessment, Health Risk Assessment, Epidemiology, Children's Health, Biochemistry, Environmental Policy, Genetics, exposure assessment, genetic risk factors, children's environmental health, diesel exhaust, assessment of exposure, prenatal exposure, genetic susceptibility, maternal exposure, nutritional risk factors, genetic mechanisms, environmental risks, asthma
Relevant Websites:
Progress and Final Reports:
2004 Progress Report
Original Abstract
2006 Progress Report
Main Center Abstract and Reports:
R832141 Columbia Center for Children’s Environmental Health
Subprojects under this Center:
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832141C001 Growth and Development Research Project: Prenatal and Postnatal Urban Pollutants and Neurobehavioral Developmental Outcomes
R832141C002 Research Project on Asthma: Prenatal and Postnatal Urban Pollutants and Childhood Asthma
R832141C003 Mechanistic Research Project
R832141C004 Community-Based Intervention Project: Reduction of Exposure and Risk from Pesticides and Allergens
R832141C005 Community Translation and Application Core (COTAC)
R832141C006 Exposure Assessment Facility Core
R832141C007 Data Management, Statistics and Community Impact Modeling Core
R832141C008 Administrative Core