A Longitudinal Study of Environmental Effects on Child Health and Development

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

• 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

3
(No Transcript)
4
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

5
Current Known Exposure Levels2nd National Report
on Human Exposure to Environmental Chemicals
http//www.cdc.gov/exposurereport/pdf/SecondNER.p
df
6
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

7
Presidents 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

8
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

9
PL 106-310 Childrens 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

• 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

11
Study Concepts (cont)

• State-of-the-art technology tracking,
  measurement, data management
• Consortium of multiple agencies
• Extensive public-private partnerships
• Hypothesis driven
• National resource for future studies

12
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

13
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)

14
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)

15
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.

16
Associations and Interactions in the National
Childrens Study
Chemical Expos.
Asthma
Infection
Birth Defects
Gene expression
Social Environ
Development Behavior
Physical Environ
Health Care
Growth
Fertility Pregnancy
Medicine Pharm
17
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

18
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), conditions, injuries
• Cognitive and emotional development
• Mental, developmental and behavioral conditions

19
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

20
National Childrens Study Organization of
Planning Phase
-Extensive multi-agency collaboration -Broad
scientific and advocacy input

• 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

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
23
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

24
Contact information

• Web site
• http//NationalChildrensStudy.gov
• E mail
• ncs_at_mail.nih.gov