PRENATAL ENVIRONMENTAL EXPOSURES AND CHILD HEALTH AND DEVELOPMENT: INSIGHTS FROM A NYC COHORT STUDY

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1 PRENATAL ENVIRONMENTAL EXPOSURES AND CHILD HEALTH AND DEVELOPMENT: INSIGHTS FROM A NYC COHORT STUDY Frederica Perera, MPH, DrPH Columbia University Mailman School of Public Health and The Columbia Center for Children s Environmental Health Aspen Institute July 23, 2012

COLUMBIA CENTER FOR CHILDREN S ENVIRONMENTAL

2 COLUMBIA CENTER FOR CHILDREN S ENVIRONMENTAL HEALTH (CCCEH) Research Overview Mission: Prevention of childhood asthma, neurodevelopmental impairment, obesity and cancer through early identification of environmental risk factors and translation to intervention Perera, 2012

City, USA (1998-present) N. Manhattan/S.

100+ siblings World Trade Center Cohort 329

~800 mothers & newborns Neurodevelopment

3 CCCEH: PARALLEL STUDIES OF IN UTERO EXPOSURES AND CHILDHOOD DISEASE New York City, USA (1998-present) N. Manhattan/S. Bronx Cohort 725 mothers & newborns and 100+ siblings World Trade Center Cohort 329 mothers & newborns Krakow, Poland (2000-present) 550 mothers & newborns Chongqing and Taiyuan, China (2001-present) ~800 mothers & newborns Neurodevelopment Asthma Obesity/metabolic disorders Cancer Risk Adult Diseases Perera, 2012

4 THE GROWING BURDEN OF ADVERSE BIRTH OUTCOMES, NEURODEVELOPMENTAL DISORDERS AND DISEASE IN CHILDREN 8% of U.S. babies born low birth weight; 14% of African American babies 12% of children in the United States ages 3 to 17 years are affected by neurodevelopmental disorders such as ADHD, learning disorders, or intellectual disability. 13.6% of US children have been diagnosed with asthma 17% of US children and adolescents aged 2 19 years are obese

5 THE GROWING BURDEN OF ADVERSE BIRTH OUTCOMES, NEURODEVELOPMENTAL DISORDERS AND DISEASE IN CHILDREN 8% of U.S. babies born low birth weight; 14% of African American babies 12% of children in the United States ages 3 to 17 years are affected by neurodevelopmental disorders such as ADHD, learning disorders, or intellectual disability. 13.6% of US children have been diagnosed with asthma 17% of US children and adolescents aged 2 19 years are obese Rates of all these conditions have increased in recent decades We are all exposed but disproportionately high rates of illness in underserved communities Complex multifactorial diseases; environmental factors are known or suspected to contribute and are preventable

6 MULTIPLE ENVIRONMENTAL EXPOSURES OCCUR DURING PREGNANCY AND EARLY CHILDHOOD PAH/air pollution Pesticides BPA Phthalates Metals ETS

7 PRENATAL EXPOSURES CAN HAVE CONSEQUENCES THROUGHOUT THE LIFE COURSE Prenatal Exposure Birth Child Adolescent Adult Metals: lead mercury arsenic PAH/air pollution Pesticides: CPF Fungicides: vinclozolin Chemicals: BPA phthalates Diet: folate deficiency nutrient deficiency Environ.tobacco smoke [Animal and/or human evidence]

Epigenetic alterations Gene switched on Gene switched off 4.

8 MECHANISMS BY WHICH IN UTERO EXPOSURES CAN AFFECT FETAL DEVELOPMENT 1. Genotoxicity: DNA damage and mutation 2. Oxidative Stress 3. Epigenetic alterations Gene switched on Gene switched off 4. Interference with normal hormonal pathways to disrupt the endocrine system 5. Gene-environment interactions

9 THE CCCEH COHORT STUDY MULTIPLE EXPOSURES: MULTIPLE OUTCOMES Birth Outcomes PAH Neurodevelopment BPA Phthalates Pesticides (CPF, pyrethroids) PBDEs Metals ETS Obesity/ metabolic disorders Asthma Cancer risk markers

10 ROLE OF EPIGENETIC MECHANISMS BPA PAH Phthalates Pesticides (CPF, pyrethroids) PBDEs Metals ETS Epigenetic Marks (CpG methylation) in cord blood Birth Outcomes Neurodevelopment Obesity/ metabolic disorders Asthma Cancer risk markers

11 PREGNANCY THROUGH CHILDHOOD: REPEAT MEASURES ON WOMEN AND CHILDREN SES/Exposure Assessment Monitoring Questionnaire SES Psychosocial stressors GIS Biomarkers of Exposure/ Effect/Susceptibility Pesticides Cotinine Lead, mercury PAH-DNA Adducts PAH metabolites BPA Phthalates Chromosomal Aberrations Immune Changes DNA methylation, Gene Expression Genetic Polymorphisms Antioxidants Outcomes Neurobehavioral Development Asthma Obesity/metabolic disorders Cancer Risk (chromosomal abnormalities)

THE MOTHER AND FETUS ARE EXPOSED TO MULTIPLE TOXICANTS (NYC) Air Monitoring/Questionnaire: 100% of pregnant mothers exposed to PAH in air 100% exposed to

12 THE MOTHER AND FETUS ARE EXPOSED TO MULTIPLE TOXICANTS (NYC) Air Monitoring/Questionnaire: 100% of pregnant mothers exposed to PAH in air 100% exposed to chlorpyrifos and other pesticides in air >40% of mothers and newborns exposed to second hand smoke Air Sampler [Perera et al. 2003, 2004, 2012; Rauh et al., 2004; Whyatt et al., 2002, 2003, 2012] Biomarkers: PAH-DNA adducts detected in 40% of maternal and newborn (cord) bloods Chlorpyrifos detected in 70-75% of maternal and cord blood samples. Cotinine detected in 45-50% of cord blood samples BPA in >90% maternal urine during pregnancy Phthalates in % maternal urine

PRENATAL EXPOSURES ADVERSELY AFFECT FETAL AND CHILD DEVELOPMENT PAH or PAH-DNA adducts associated

childhood Attentional/behavioral problems in children Reduced IQ Increased risk of asthma and

Developmental deficits, ADHD, decreased IQ AND brain anomalies by MRI anterior posterior Post MTG/ST

associated with: Reduction in birth weight Developmental deficits, ADHD Asthma dorsal SF G ventral G

13 PRENATAL EXPOSURES ADVERSELY AFFECT FETAL AND CHILD DEVELOPMENT PAH or PAH-DNA adducts associated with: Reduction in birth weight and/or head circumference Developmental deficits in infancy and childhood Attentional/behavioral problems in children Reduced IQ Increased risk of asthma and obesity Epigenetic changes in cord blood Chlorpyrifos associated with: Lower birth weight Developmental deficits, ADHD, decreased IQ AND brain anomalies by MRI anterior posterior Post MTG/ST G SF G SM IP G L PoC G right lateral S T G Pre Cu PoCG left lateral Post STG/M TG SF G ETS associated with: Reduction in birth weight Developmental deficits, ADHD Asthma dorsal SF G ventral G R right mesial C u left mesial [Perera et al 2003, 2006, 2009, 2011,2012; Herbstman et al. 2012; Rauh et al., 2004; 2006, 2011, 2012]

14 PRENATAL BPA AND PHTHALATES BPA and Phthalates associated with: -neurobehavioral problems [Whyatt et al., EHP, 2012; Perera et al. 2012; Horton et al, 2011; Rauh et al 2012] -childhood eczema, airway inflammation, and/or asthma [Just et al., 2012; Donohue et al., subm.] BPA Butyl benzyl phthalate (BBzP)

15 TRANSLATION OF SCIENCE TO POLICY Partnership with community organizations (WEACT and others) Outreach to community and to policymakers Healthy Home Healthy Child Campaign IPM intervention in cohort and in NYC to reduce pesticide exposure Monitoring of regulations

GOOD NEWS 10 10 Decline in CPF levels in cord blood (pg/g)(n=395)* 1999

2006 8 8 2000 6 6 2001* 44 22 00 2002 2003 2004 *EPA Ban on residential use

16 GOOD NEWS Decline in CPF levels in cord blood (pg/g)(n=395)* 1999 Personal Prenatal Exposure to PAH in the NYC Cohort Declined from 1998 to * *EPA Ban on residential use of chlorpyrifos took effect in 2001 [Whyatt et al., 2003] [Narvaez, et al. 2008]

17 SUMMARY The fetal period is a window of heightened susceptibility Prenatal exposures are associated with reduced fetal growth, and developmental impairment (and other effects) Early interventions work Identification of risks from early life environmental exposures is key to prevention of disease and impairment: -in childhood -adolescence -adulthood -future generations

18 I GRATEFULLY ACKNOWLEDGE THE CENTER INVESTIGATORS, RESEARCH WORKERS, AND STAFF: H. Andrews, F. Arias, G. Badia, R. Bansal, K. Barnabe, M. Borjas, L. Calero, F. Champagne, H. Chang, S. Chillrud, S. Chu, Y. Cheung, L. Cruz, B. Cortes, S. Darakjy, D. Diaz, S. Diaz, A. Divjan, K. Donohue, D. Evans, G. Freyer, W. Garcia, I. Goldstein, A. Hassoun, J. Herbstman, L. Hoepner, D. Holmes, M. Horton, C. Howe, L. Hua, F. Hua, S. Hsu, I. Ibrahimagic, H. Jiang, X. Jin, K. Jung, A. Just, P. Kinney, S. Lederman, B. Liu, G. Lovasi, L. Qu, A. Qu, C. Maher, R. Martinez, R. Miller, K. Moors, S. Nath, S. Oberfield, C. Olivo, M. Orjuela, M. Perzanowski, B. Peterson, L. Qu, J. Quinn, V. Rauh, J. Ramirez-Carvey, B. Rhodes, M. Reyes, M. Rosa, A. Rundle, B. Sheares, L. Stigter, D. Tang, V. Thomas, B. Thrastardottir, C. Tobon, T. Tong, I. Suen, M. Taha-Furst, Y. Tse, N. Uemura, J. Vishnevetsky, S. Wang, W. Wang, R. Whyatt, Y. Xiao, J. Yu, H. Zhang, D. Zhu, H. Zhou CONTRIBUTIONS OF: EXTERNAL PARTNERS: The Center s Lead Community Partner We Act for Environmental Justice: P. Shepard, O. Dotson-Newman CDC: D. Barr*, T. Bernert, D. A. Calafat, L. Needham, R. Schleicher, A. Sjodin, C. Sosnoff *formerly at CDC SWRI: D. Camann

19 THIS RESEARCH HAS BEEN MADE POSSIBLE BY JOINT FUNDING FROM: The National Institute of Environmental Health Sciences (NIEHS) U.S. Environmental Protection Agency (EPA) Private Foundations & Individuals I have no conflicts of interest to report.

20 SPECIAL THANKS TO THE WOMEN AND CHILDREN PARTICIPATING IN THE STUDIES

21 PRENATAL EXPOSURE CAN ALTER METHYLATION AS METHYLATION MARKS ARE BEING ESTABLISHED [Perera and Herbstman, Reprod. Tox. 2011]

PRENATAL EXPOSURE TO EDCS AND DEVELOPMENTAL AND HEALTH OUTCOMES IN A NEW YORK CITY COHORT

PRENATAL EXPOSURE TO EDCS AND DEVELOPMENTAL AND HEALTH OUTCOMES IN A NEW YORK CITY COHORT Frederica Perera DrPH, PhD The Columbia Center for Children s Environmental Health Columbia University Mailman