# Presentation: 242088

- October 6, 2004
- Peter Scheidt
- U.S. Department of Health and Human Services
**NICHD, CDC, NIEHS**
- U.S. Environmental Protection Agency

## Compared to adults, children are especially vulnerable to environmental exposures – metabolism, behavior
Exposures to some agents demonstrate potential for serious developmental effects – lead, prenatal alcohol
Current known exposures of high frequency – pesticides, violence, media
Numerous high burden conditions with suspected environmental contribution – learning disabilities, autism, diabetes, asthma, birth defects, premature birth
Existing research too limited in size and scope to answer the questions
Life-course (longitudinal) design needed to correctly link with multiple exposures and multiple outcomes

- Exposures to some agents demonstrate potential for serious developmental effects – lead, prenatal alcohol
- Current known exposures of high frequency – pesticides, violence, media
- Numerous high burden conditions with suspected environmental contribution – learning disabilities, autism, diabetes, asthma, birth defects, premature birth
- Existing research too limited in size and scope to answer the questions
- Life-course (longitudinal) design needed to correctly link with multiple exposures and multiple outcomes

- From The President’s Task Force on Environmental Health and Safety Risks to Children, 2000*

- Rationale for the National Children’s Study

- * Reappointed 2001 and 2003

## Children’s Health Act of 2000

- (a) Authorize NICHD to conduct a national longitudinal study of environmental influences (including physical, chemical, biological, and psychosocial) on children's health and development.
- (b) Established 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.

## Study Concepts

- Longitudinal study of children, their families and their environment
- National in scope
- Hypothesis driven
- Environment defined broadly (chemical, physical, behavioral, social, cultural)
- Study common range of “environmental” exposures and less common outcomes (n~100,000)

## Study Concepts (con’t)

- Exposure period begins in pregnancy
- Environment & genetic expression
- State-of-the-art technology – tracking, measurement, data management
- Consortium of multiple agencies
- Extensive public-private partnerships
- National resource for future studies

## Study Population - Issues

- Generalizability to U.S. population
- Additional study populations, e.g.
- Specific high-risk populations
- Agricultural
- Industrial
- Economically disadvantaged
- Women of child-bearing age - possible effects on fertility & pregnancy

## Population Size for Selected Outcomes

- Outcomes		Rate	 	 1.5	 1.75	   2
- Injuries-Hosp. (<18)	37.4/10K			42K		  20K		13K
- Fractures 	   10/10K		157K		  77K	 	47K
- Head injuries 	     5/10K		313K		153K	 	94K
- Autism Spectrum Disorders*   20/10K			78K		  38K	 	23K
- ADHD (school age)	 800/10K		 1.8K		 0.9K	 0.5K
- Asthma (<18)	  690/10K		    2K		    1K	  0.6K
- Hospitalizations (<15)	 27.7/10K		  56K		  28K	   17K
- Cancer incidence (<20) 	 1.54/10K	1019K		498K	 306K
- ALL (Acute Lymphoblastic Leukemia)	 0.27/10K 	5813K	2842K	1744K
- CNS tumors	 0.29/10K	5413K	2646K	1623K
- Hypospadias (males)		 20/10K			78K		  38K	 	23K
- Spina Bifida		   5/10K		313K		153K		 94K

- Relative Risk

- *prevalence

## Sample for the NCS

- National probability sample
- Center based structure – up to 50 centers, 100+ clusters
- For measures and observation requiring expertise and facilities
- Incorporate expertise and productivity of Academic Centers
- Multiple dense clusters
- Provide information about communities – chemical, physical, social
- Logistical and economical feasibility
- Selection
- Of clusters – probability or quota by characteristics
- Of participants in cluster – probability or 100%
- Feasibility/pilot study essential

## Priority Environmental Exposures

**Physical** environment: housing, neighborhoods and communities, climate, radiation...
**Chemical** exposures: air, water, soil, food, dust, industrial products, pharmaceuticals...
-           complex ubiquitous low-level exposures
-     	 	unique exposures (special sub-studies)
**Biological** environment: intrauterine, infection, nutrition; inflammatory and metabolic response...
**Genetics: **genetic components of disease; effects of environmental exposures on gene expression...
**Psychosocial** milieu: influence of family, socio-economics, community, stress...

## Priority Outcomes

**Pregnancy outcome**: preterm birth, birth defects, fetal influences on adult health. **EARLY results!**
**Neurodevelopment and Behavior**: cognitive development (IQ), autism, learning disabilities, schizophrenia, depression, adjustment, normal variation, resilience...
**Injury**: intentional and unintentional; violence...
**Asthma: **envir/genetic/infectious/immune factors..
**Obesity and Physical Development**: diabetes,pubertal/reproductive development,  growth, obesity ‘epidemic’...

## Hypotheses necessaryfor framing the study 

- No single hypothesis
- Assure answers to “big issue” questions
- 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

## Example Hypotheses

- low-level exposure to non-persistent pesticides *in utero* (or postnatally) increases risk of poor performance on neurobehavioral and cognitive examinations during infancy and later in childhood, among those with genetically decreased paraoxonase activity
- Asthma incidence and severity is associated with early life experience with infections
- Infection and mediators of inflammation during pregnancy and the perinatal period are associated with increased risk of schizophrenia

## Proposed vaccine related hypotheses*

- Altered timing of early childhood immunizations will lead to no increased rate or severity of disease later in life
- The receipt of childhood routine vaccination is not linked to Autism or other developmental disabilities identified during childhood and adolescence

- * Infections, immunity and vaccines working group

## Associations and Interactions

- Asthma

- Birth Defects

- Development & Behavior

- Growth

- Fertility & Pregnancy

- Social Environ

- Physical Environ

- Chemical Exposure

- Medicine & Pharm

- Health Care

- Gene Expression

- Infection

## How will Study size produce results not otherwise available?

- Exposures for “big issue” low frequency outcomes
- Autism
- Diabetes
- Still birth
- Birth defects, etc.
- Sub-groups and multi-factor interactions
- Obesity
- Asthma
- Behavior, etc

## 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

## Measures Anticipated: Outcomes

- Fetal growth and outcome of pregnancy
- Birth defects and newborn exam
- Growth, nutrition, and physical development
- Medical condition and history: illness (e.g. asthma, obesity), conditions, & injuries
- Cognitive and emotional development
- Mental, developmental and behavioral conditions

## Use of Data to Maximize Output

- Results available beginning ~2010
- 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

## Projected Time Line

- 2000-2005	Pilot study/methods development work
*Periodically:*	Meetings, peer reviews, consultations
- Mid 2004	Finalize specific hypotheses, develop study design
- Late 2005	Select initial centers or alternatives and pilot test core protocol
- Late  2006	Begin full study with initial centers
- 2006-2007	Enroll additional centers
- 2009-2010	First preliminary results available from pregnancy
- 2007-2030 	Analyze data as collection continues, publish results throughout: hypothesis specific, public use datasets, RFA’s

## Contact information

- Check the Web site: _[http://NationalChildrensStudy.gov](http://nationalchildrensstudy.gov/)_
- Join the listserv for news and communication
- Contact us at ncs@mail.nih.gov