1. A Longitudinal Study of Environmental Effects on Child Health and Development Duane Alexander, M.D. U.S. Department of Health and Human Services NICHD, CDC, NIEHS U.S. Environmental Protection Agency

2. Children have increased vulnerability to environmental exposures àCritical windows of vulnerability during development àImmature mechanisms for detoxification and protection àDifferences in metabolism and behavior that may yield higher exposure in the same environments

4. Known exposures of concern, and examples àBiological àInfection in early life àMetabolic àPhysical àBuilt environment àRadiation àPsychosocial àAbuse and neglect àFamily structure àDiet & Drugs àFood additives àPharmaceuticals àChemical àHeavy metals àPesticides

5. Current Known Exposure Levels 2 nd National Report on Human Exposure to Environmental Chemicals* AgentLevelThresholdSample Mercury - Blood0.34ug/L mean15ug/L705, 1-5 yrs Phthlate, mono- ethyl (urine) 91.3ug/L mean ? 328, 6-11 yrs PCB’sNot measured <12 yrs. Phytoestrogen Enterolactone 315ug/g creat. (urine) ? 331, 6-11 Chlorpyrophos metabolite 3.1ug/g creat. (urine) ? 481, 6-11yrs 1 Napthol 90 th %ile 4.5ug/g creat. (urine) ? 483, 6-11yrs *http://www.cdc.gov/exposurereport/pdf/SecondNER.pdf

6. Important childhood conditions with suspected environmental components àBirth Defects àPrematurity àAutism àCerebral Palsy àType I diabetes àMental retardation àObesity àCancer àAsthma àInjuries àSchizophrenia àLearning disabilities

7. President’s Task Force on Environmental Health Risks and Safety Risks to Children àCharged to develop strategies to reduce risk of environmental exposures to children àCo-chairs – Secretary HHS, Administrator USEPA àConclusions àMany risks to children are poorly characterized àNeed for longitudinal study of environmental effects àNew money would be required to carry out the study

8. Rationale àConverging factors àIncreased vulnerability to environmental exposures in children in general àExposures to some agents have caused serious developmental effects – lead, alcohol àKnown current exposures of high frequency – àExisting research too limited in size & scope to answer the questions àStudy needed to identify what is harmful, harmless and helpful to child development àLife-course design to correctly link with multiple exposures and multiple outcomes

9. PL 106-310 Children’s Health Act of 2000 (a) PURPOSE-... to authorize NICHD to conduct a national longitudinal study of environmental influences (including physical, chemical, biological, and psychosocial) on children's health and development. (b) IN GENERAL- The Director of NICHD shall establish a consortium of representatives from appropriate Federal agencies (including the CDC and EPA) to-- (1) plan, develop, and implement a prospective cohort study, from birth to adulthood, to evaluate the effects of both chronic and intermittent exposures on child health and human development; and (2) investigate basic mechanisms of developmental disorders and environmental factors, both risk and protective, that influence health and developmental processes.... (e) AUTHORIZATION OF APPROPRIATIONS- There are authorized to be appropriated to carry out this section $18,000,000 for fiscal year 2001, and such sums as may be necessary for each the fiscal years 2002 through 2005.

10. Study Concepts àLongitudinal study of children, their families and their environment àNational in scope àEnvironment defined broadly (chemical, physical, behavioral, social, cultural) àStudy of sufficient size to identify causal factors for important but less common outcomes (approx. 100,000 participants) àApplication of the human genome project

11. Study Concepts (con’t) àState-of-the-art technology – tracking, measurement, data management àConsortium of multiple agencies àExtensive public-private partnerships àHypothesis driven àNational resource for future studies

12. Criteria for Core Hypotheses àNo single hypothesis àHypothesis required for costly elements àImportant for child health & development (prevalence, severity, morbidity, mortality, disability, cost, public health significance) àReasonable scientific rationale àRequire the large sample size (~100,000) àMeasurable with study of this size àRequires longitudinal follow-up

13. Priority Outcome Areas (and example hypotheses) àUndesirable outcomes of pregnancy (Infection and mediators of inflammation during pregnancy are major causal factors associated with pre-term birth) àNeurobehavioral development (Low level pesticide exposure in utero is associated with impaired neurobehavioral and cognitive performance) àInjury (Repeated head trauma w/o anatomic damage is a causal factor for cumulative adverse effects on neurocognitive development)

14. Priority Outcome Areas (and example hypotheses) àAsthma (maternal stress during pregnancy is associated with the prevalence and severity of asthma in offspring ) àObesity and physical development (Obesity and insulin resistance is associated with impaired glucose metabolism in pregnancy, intrauterine growth restriction, and interacting factors in the physical and social environment)

15. Proposed Drug Abuse Hypotheses à Prenatal exposure to drugs will interact with family, child and other factors to influence cognitive, social/emotional and physical development. à Initiation of drug use, transition to abuse and addiction, and physical and mental consequences of drug use are influenced by certain environmental exposures including parent, child, and other factors.

16. Associations and Interactions in the National Children’s Study Asthma Birth Defects Development & Behavior Growth Fertility & Pregnancy Social Environ Physical Environ Infection Chemical Expos. Medicine & Pharm Health Care Gene expression

17. Measures Anticipated - Exposures àEnvironmental Samples: air, water, dust àBio-markers for chemicals: blood, breast milk, hair, tissue, etc. àInterview and history àSerology and medical data àHousing & living characteristics àFamily and social experiences àNeighborhood and community characteristics

18. àFetal growth and outcome of pregnancy àBirth defects and newborn exam àGrowth, nutrition and physical development àMedical condition and history: illness (e.g. asthma), conditions, & injuries àCognitive and emotional development àMental, developmental and behavioral conditions Measures Anticipated – Outcomes

19. Use of Data to Maximize Output àResults available beginning 2008 àTargeted hypotheses-testing analyses àSuccessive public-use data sets with support àSuccessive funding for investigator initiated research and analyses àExpected translation of results into related prevention initiatives

20. National Children’s Study Organization of Planning Phase àInteragency leadership and funding – HHS (NICHD, NIEHS, CDC) & EPA àDedicated staff at NICHD for operations àFederal Consortium of all HHS agencies + 12 other Departments and independent agencies àChartered Federal Advisory Committee for advice and peer review àWorking Groups (20) with approx. 250 scientists and experts for consultation and guidance re: hypotheses, design, measures àNetwork of all interested parties, 2,000+ -Extensive multi-agency collaboration -Broad scientific and advocacy input

21. Projected Time Line 2000-2004 Planning, pilot studies, gather input 2001-2002 Form advisory committee and working groups 2003 Finalize central hypotheses, develop study design 2004 Select NCS study sites across the U.S. 2005 Begin participant enrollment 2008 First research results available 2008-2030+ Results continue; Translate into disease prevention strategies

22. Expected Benefits of the NCS ConditionPotential Reduction Potential Annual Benefit Pre-term Birth10 %$0.6 Billion Asthma25 %$3.2 Billion Obesity & Diabetes12.5 %$14.5 Billion Juvenile Diabetes15 %$15 Billion Injuries10%$39 Billion Schizophrenia33 %$3.1 Billion Reduced Learning8%$100 Billion

23. The NCS will provide àThe answer to concerns about known exposures during childhood to potential toxicants àThe power to determine absence of effects or benefit of exposures to various products important for our economy àCausal factors for a number of diseases and conditions of children with suspected environmental causes àHow multiple causes interact to result in multiple outcomes àLarge sample size required to apply knowledge of the human genome to understand multifactoral genetic conditions àIdentification of early life factors that contribute to many adult conditions àA national resource to answer future questions by using stored biological and environmental samples and the extensive data

24. Contact information Web site: http://NationalChildrensStudy.gov E mail: ncs@mail.nih.gov