# Presentation: 709015

## 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

- 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 Levels2nd National Report on Human Exposure to Environmental Chemicals*

| Agent | Level | Threshold | Sample |
| --- | --- | --- | --- |
| Mercury - 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
- Conclusions
- Many risks to children are poorly characterized
- Need 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 Study

- Asthma

- Birth Defects

- Development & Behavior

- Growth

- Fertility & Pregnancy

- Social Environ

- Physical Environ

- Infection

- Chemical Expos.

- Medicine & Pharm

- Health Care

- Gene expression

## 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

- 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 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

## 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](http://nationalchildrensstudy.gov/)_
- 	E mail:
- 	_ncs@mail.nih.gov_