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

Children have increased vulnerability to environmental exposures

Critical windows of vulnerability during development

Immature mechanisms for detoxification and protection

Differences in metabolism and behavior that may yield higher exposure in the same environments

Known exposures of concern, and examples

Biological Infection in early life Metabolic

Physical Built environment Radiation

Psychosocial Abuse and neglect Family structure

Diet & Drugs Food additives Pharmaceuticals

Chemical Heavy metals Pesticides

Current Known Exposure Levels2nd National Report on Human Exposure to Environmental Chemicals*

Agent Level Threshold SampleMercury - Blood

0.34ug/L mean

15ug/L 705, 1-5 yrs

Phthlate, mono-ethyl (urine)

91.3ug/L mean

? 328, 6-11 yrs

PCB’s Not measured

<12 yrs.Phytoestrogen

Enterolactone

315ug/g creat.

(urine)

? 331, 6-11

Chlorpyrophos

metabolite

3.1ug/g creat.

(urine)

? 481, 6-11yrs

1 Napthol

90th %ile

4.5ug/g creat.

(urine)

? 483, 6-11yrs*http://www.cdc.gov/exposurereport/pdf/SecondNER.pdf

Important childhood conditions with suspected environmental components

Birth Defects Prematurity Autism Cerebral Palsy Type I diabetes Mental

retardation

Obesity Cancer Asthma Injuries Schizophrenia Learning

disabilities

President’s Task Force on Environmental Health Risks and Safety Risks to Children

Charged to develop strategies to reduce risk of environmental exposures to children

Co-chairs – Secretary HHS, Administrator USEPA

ConclusionsMany risks to children are poorly characterizedNeed for longitudinal study of environmental

effects New money would be required to carry out the

study

Rationale Converging factors

Increased vulnerability to environmental exposures in children in general

Exposures to some agents have caused serious developmental effects – lead, alcohol

Known current exposures of high frequency –

Existing research too limited in size & scope to answer the questions

Study needed to identify what is harmful, harmless and helpful to child development

Life-course design to correctly link with multiple exposures and multiple outcomes

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.

Study Concepts Longitudinal study of children, their families

and their environment

National in scope

Environment defined broadly (chemical, physical, behavioral, social, cultural)

Study of sufficient size to identify causal factors for important but less common outcomes (approx. 100,000 participants)

Application of the human genome project

Study Concepts (con’t)

State-of-the-art technology – tracking, measurement, data management

Consortium of multiple agencies

Extensive public-private partnerships

Hypothesis driven

National resource for future studies

Criteria for Core Hypotheses

No single hypothesis Hypothesis required for costly elements Important for child health & development

(prevalence, severity, morbidity, mortality, disability, cost, public health significance)

Reasonable scientific rationale Require the large sample size (~100,000)

Measurable with study of this size Requires longitudinal follow-up

Priority Outcome Areas (and example hypotheses)

Undesirable outcomes of pregnancy (Infection and mediators of inflammation during pregnancy are major causal factors associated with pre-term birth)

Neurobehavioral development (Low level pesticide exposure in utero is associated with impaired neurobehavioral and cognitive performance)

Injury (Repeated head trauma w/o anatomic damage is a causal factor for cumulative adverse effects on neurocognitive development)

Priority Outcome Areas (and example hypotheses)

Asthma (maternal stress during pregnancy is associated with the prevalence and severity of asthma in offspring)

Obesity 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)

Proposed Drug Abuse Hypotheses

Prenatal exposure to drugs will interact with family, child and other factors to influence cognitive, social/emotional and physical development.

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.

Associations and Interactions in the National

Children’s StudyAsthma

Birth Defects

Development &

Behavior

Growth

Fertility & Pregnancy

Social Enviro

n

Physical

Environ

Infection

Chemical

Expos.

Medicine & Pharm

Health Care

Gene expressio

n

Measures Anticipated - Exposures

Environmental Samples: air, water, dust Bio-markers for chemicals: blood, breast

milk, hair, tissue, etc. Interview and history Serology and medical data Housing & living characteristics Family and social experiences Neighborhood and community

characteristics

Fetal growth and outcome of pregnancy Birth defects and newborn exam Growth, nutrition and physical

development Medical condition and history: illness (e.g.

asthma), conditions, & injuries

Cognitive and emotional development Mental, developmental and behavioral

conditions

Measures Anticipated –Outcomes

Use of Data to Maximize Output

Results available beginning 2008 Targeted hypotheses-testing

analyses Successive public-use data sets

with support Successive funding for investigator

initiated research and analyses Expected translation of results into

related prevention initiatives

National Children’s Study Organization of Planning Phase

Interagency leadership and funding – HHS (NICHD, NIEHS, CDC) & EPA

Dedicated staff at NICHD for operations

Federal Consortium of all HHS agencies + 12 other Departments and independent agencies

Chartered Federal Advisory Committee for advice and peer review

Working Groups (20) with approx. 250 scientists and experts for consultation and guidance re: hypotheses, design, measures

Network of all interested parties, 2,000+

-Extensive multi-agency collaboration-Broad scientific and advocacy input

Projected Time Line2000-2004 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

Expected Benefits of the NCS

Condition Potential Reduction

Potential Annual Benefit

Pre-term Birth 10 % $0.6 Billion

Asthma 25 % $3.2 Billion

Obesity & Diabetes

12.5 % $14.5 Billion

Juvenile Diabetes

15 % $15 Billion

Injuries 10% $39 Billion

Schizophrenia 33 % $3.1 Billion

Reduced Learning

8% $100 Billion

The NCS will provide The answer to concerns about known exposures

during childhood to potential toxicants The power to determine absence of effects or benefit

of exposures to various products important for our economy

Causal factors for a number of diseases and conditions of children with suspected environmental causes

How multiple causes interact to result in multiple outcomes

Large sample size required to apply knowledge of the human genome to understand multifactoral genetic conditions

Identification of early life factors that contribute to many adult conditions

A national resource to answer future questions by using stored biological and environmental samples and the extensive data

Contact information

• Web site:

http://NationalChildrensStudy.gov

E mail: ncs@mail.nih.gov