The National Children’s St

U.S. Department of Health and Human ServicesNational Institutes of HealthCenters for Disease Control and PreventionU.S. Environmental Protection AgencyDecember 2008
The National Children’s Stud

• Largest long-term study of children

and development ever to be conduU.S. 

• Longitudinal study of children, thei

and their environment (before birth age 21) 

• Approximately 100,000 children en

of important but less common outc
* Reappointed 2001 and 2003

Rationale for the National Children’s StudyFrom The President’s Task Force on Environmand Safety Risks to Children, 2000*

• Compared to adults, children are especially vuln

environmental exposures – metabolism, behavio

• Exposures to some agents demonstrate potentia

developmental effects – lead, prenatal alcohol

• Current known exposures of high frequency – pe

media

• Numerous high burden conditions with suspecte

contribution – learning disabilities, autism, diabedefects, premature birth

• Existing research too limited in size and scope to 

questions

• Life-course (longitudinal) design needed to corre

multiple exposures and multiple outcomes
* Reappointed 2001 and 2003

The President’s Task Force oEnvironmental Health and Safety Risks to Children – 19• To develop strategies to reduce risk of env

exposures to children

• Co-chairs: Secretary HHS, Administrator E• Members: 7 cabinet officers• Need for longitudinal study of effects of en

exposures

• Consultation (2000) endorsed study

• Large, bold, multiple agencies, public priva

• New money required
PL 106-310: 

Children’s Health Act of 2000

•(a) PURPOSE — ... to authorize NICHD to conduct a nationa

study of environmental influences (including physical, chemicand psychosocial) on children’s health and development.

•(b) IN GENERAL — The Director of NICHD shall establish a c

of representatives from appropriate Federal agencies (includinand EPA) to:

•(1) plan, develop, and implement a prospective cohort study, fro

adulthood, to evaluate the effects of both chronic and intermittenon child health and human development; and

•(2) investigate basic mechanisms of developmental disorders and 

factors, both risk and protective, that influence health and develo

•(e) AUTHORIZATION OF APPROPRIATIONS — There are auth

appropriated to carry out this section $18,000,000 for fiscal y

such sums as may be necessary for each the fiscal years 200
Study Concepts

• Study high priority and burdensome condi

(n~100,000)

• Hypothesis driven• Exposure period begins with pregnancy• Environment and genetic expression• State-of-the-art technology• Consortium of multiple agencies• Extensive public-private partnerships• National resource for future studies
Priority Health 

Outcomes

Pregnancy Outcomes Neurodevelopment and BehaviorInjuryAsthma Obesity and Physical Development

Priority Health Exposures, Outcomes

Priority 

Exposures

Examples

Physical Environment Housing quality, neighborhoodChemical Exposures Pesticides, phthalates, heavy metalsBiologic Environment Infectious agents, endotoxins, dietGenetics

Interaction between genes and environment 

Psychosocial milieu

Family structure, socio-economic status, parenting style, social networks, exposure to media and violence
Priority 

Environmental Exposures• Physical environment: housing, neighbor

communities, climate, radiation...

• Chemical exposures: air, water, soil, food

industrial products, pharmaceuticals...

• Complex ubiquitous low-level exposures• Unique exposures (special sub-studies)

• Biological environment: intrauterine, infe

nutrition; inflammatory and metabolic res

• Genetics: genetic components of disease

environmental exposures on gene express

• Psychosocial milieu: influence of family, 

economics, community, stress...
Examples of 

Hypothesis-defining Questio• How is asthma incidence and severity influ

interaction of early life infection and air qu

• Are assisted reproductive technologies (AR

increased risk of fetal growth restriction, band developmental disabilities?

• Does impaired maternal glucose metabolis

pregnancy cause obesity in children? 

• How does high level exposure to media co

infancy affect development and behavior i

• Does pre- and post-natal exposure to end

environmental agents alter age at onset, dcompletion of puberty?
Locations vs. Centers

• Locations—geographic locations (co

from which participants will be recr

• Selected by stratified probability samp

sampling units

• 105 locations

• Centers—entities or institutions tha

out Study at the locations

• Selected by a competitive process• Each will cover more than one location• Up to 40 centers
Sampling and Centers

• National probability sample importa

• Exposure-outcome relationship represe

the U.S.

• Key exposures with varied distributions • Clustered for community attributes, log

• Centers of excellence important

• Broad scientific input, top expertise an

• Probability sample by centers

• Unique combination• Requires flexibility and adaptation of ce

scientific design
National Children’s Study 

Sample

105 lSelecneighAll ohousneighAll elthe h~4 min 3,1

All Births 

in the Nation

Sample of Study 

Locations

Sample of Study 

Segments

Study

Households

Study Women
National Children’s Study 

Sample• National probability sample – known chan• Drawn by NCHS• 105 locations – corresponding to counties

79 metro, 26 rural

• 13 very large counties; other counties pla

based on:

• Metropolitan status• Geography• Average number of births per year• Race, ethnicity, percent low birth weight

*

•

Wave 1 Locations 

VanguarcllWave 1 

Locations 

• Wave 2 Locations 

@ Wave 3 Locations 

1:1 Locations Not Awarded

THE NATIONAL • 

CHILDREN'S STUDY 

HEALTH GP..OWTH ENVIIl..Of','MENT 

*Wave 1 locations 

Los Angeles County, CA
 

Sacramento County, CA
 

San Diego County, CA
 

New Haven County, CT
 

New Castle County, DE
 

DeKalb County, GA
 

Fayette County, GA
 

Honolulu County, HI
 

Bear Lake County, ID and Lincoln
 

and Uinta Counties, WY
 

Cook County, IL
 

Macoupin County, IL
 

Worcester County, MA
 

Baltimore County, MD
 

Wayne County, MI
 

Ramsey County, MN
 

St. Louis, MO
 

Hinds County, MS
 

Burke County, NC
 

Durham County, NC
 

Rockingham County, NC
 

Valencia County, NM
 

Nassau County, NY
 

Schuylkill County, PA
 

Westmoreland County, PA
 

Providence County, RI
 

Bexar County, TX
 

Cache County, UT
 

King County, WA
 

Marion County, WV
 

•	 VanguardlWave 1 Locations 

Orange County, CA 

Duplin County, NC 

New York City (Queens), NY 

Montgomery County, PA 

Salt Lake Cou nty, UT 

Waukesha County, WI 

Lincoln, Pipestone, and Yellow Medicine 

Counties, MN, and Brookings County, SD 

•	 Wave 2 Locations 

Benton County, AR 

Apache County, AZ 

Pinal County, AZ 

Kern County, CA 

San Bernardino County, CA 

Ventu ra County, CA 

Douglas County, CO 

Litchfield County, CT 

Baker County, FL 

Hillsborough County, FL 

Orange County, FL 

Baldwin County, GA 

Polk County, IA 

DuPage County, IL 

Johnson, Union, and Williamson 

Counties, IL 

Jefferson County, KY 

New Orleans, LA 

Bristol County, MA 

Montgomery County, MD 

Cumberland County, ME 

Grand Traverse County, MI 

Lenawee County, MI 

Jefferson County, MO 

Cumberland County, NC 

Burlington County, NJ 

Passaic County, NJ 

New York City (Manhattan), NY 

Monroe County, NY 

Cuyahoga County, OH 

Lorain County, OH 

Bradley County, TN 

Davidson County, TN 

Harris County, TX 

Hidalgo County, TX 

Lamar County, TX 

Grant County, WA 

@	 Wave 3 locations 

Maricopa County, AZ 

San Mateo County, CA 

Denver, CO 

Miami-Dade County, FL 

Will County, IL 

Genesee County, MI 

Macomb County, MI 

Buncombe County, NC 

Middlesex County, NJ 

Warren County, NJ 

New York City (Brooklyn), NY 

Marion County, OR 

Philadelphia County, PA 

Travis County, TX 

Thurston County, WA 

1:1	 locations Not Awarded 

Colbert County, AL 

Humboldt County, CA 

Marion County, IN 

Saline County, KS 

Jessamine County, KY 

Beauregard and Vernon Parishes, LA 

Becker, Clearwater, and Mahnomen 

Counties, MN 

Stearns County, MN 

Coahoma County, MS 

Gaston County, NC 

Stark County, ND 

Cleveland County, OK 

Comanche County, OK 

Spartanburg County, SC 

Cumberland and Morgan Counties, TN 

Childress, Collingsworth, Donley, 

and Hall Counties, TX 

Dallas County, TX 

Stephens and Young Counties, TX 

December 2008 
Study Centers Awarded 

Wave 2 Locations

Study Center 

(lead institution listed) 

*denotes new Study Centers

Study Location

Arkansas Children’s Hospital Research Institute*

Benton County, AR

Baylor College of Medicine* Harris County, TXBrown University Bristol County, MACase Western Reserve University School of Medicine*

Lorain County, OH Cuyahoga County, OH

Children’s Hospital of Philadelphia Burlington County, NJEmory University Bradley County, TN 

Baldwin County, GA

Johns Hopkins University Bloomberg School of Public Health

Montgomery County, MD

Maine Medical Center* Cumberland County, MEMichigan State University Grand Traverse County, MI 

Lenawee County, MI

Mount Sinai School of Medicine Monroe County, NY 

New York City (Manhattan), Passaic County, NJ
Wave 2 Locations (continued

Study Center

(lead institution listed) 

*denotes new Study Centers

Study Locatio

Northwestern University DuPage County, ILSaint Louis University School of Public Health

Jefferson County, MOJohnson, Union, and WilliaCounties, IL

Tulane University School of Public Health and Tropical Medicine, Center for Applied Environmental Public Health*

New Orleans, LA

University of Arizona* Apache County, AZ 

Pinal County, AZ

University of California, Irvine Kern County, CA 

San Bernardino County, C

University of California, Los Angeles Ventura County, CAUniversity of Colorado* Douglas County, COUniversity of Iowa* Polk County, IAUniversity of Louisville* Jefferson County, KY
Wave 2 Locations (continued

Study Center

(lead institution listed) 

*denotes new Study Centers

Study Locatio

University of Miami* Baker County, FL 

Orange County, FL Hillsborough County, FL

University of North Carolina at Chapel Hill, Carolina Population Center

Cumberland County, NC

University of Texas Health Science Center San Antonio

Hildalgo County, TX

University of Texas Southwestern Medical Center at Dallas*

Lamar County, TX

University of Washington Grant County, WAVanderbilt University Medical Center* Davidson County, TNYale University Litchfield County, CT
Study Centers Awarded 

Wave 1 Locations

Study Center

(lead institution listed)

Study Location

Brown University Providence County, RIChildren’s Hospital of Philadelphia Schuylkill County, PA 

New Castle County, DE

Emory University DeKalb County, GA 

Fayette County, GA

Johns Hopkins University Bloomberg School of Public Health

Baltimore County, MD

Michigan State University Wayne County, MIMount Sinai School of Medicine Nassau County, NYNorthwestern University Cook County, ILSaint Louis University School of Public Health

Macoupin County, IL St. Louis, MO

University of California, Davis Sacramento County, CAUniversity of California, Irvine San Diego County, CAUniversity of California, Los Angeles Los Angeles County, CA
Wave 1 Locations (continued

Study Center

(lead institution listed)

Study Locatio

University of Hawai’i at Manoa John A. Burns School of Medicine

Honolulu County, HI

University of Massachusetts Worcester County, MAUniversity of Minnesota Ramsey County, MNUniversity of Mississippi Hinds County, MSUniversity of New Mexico Valencia County, NMUniversity of North Carolina at Chapel Hill, Carolina Population Center

Rockingham County, NCBurke County, NC Durham County, NC

University of Pittsburgh Marion County, WV 

Westmoreland County, PA

University of Texas Health Science Center San Antonio

Bexar County, TX

University of Utah School of Medicine, Department of Pediatrics

Cache County, UTBear Lake County, ID and and Uinta Counties, WY

University of Washington King County, WAYale University New Haven County, CT
Study Centers Awarded 

Vanguard Centers/Wave 1 Locatiand Coordinating Center 

Study Center Study Locations

Children’s Hospital of Philadelphia Montgomery County, PAMount Sinai School of Medicine New York City (Queens), NYSouth Dakota State University Brookings County, SD and Linc

Pipestone, and Yellow Medicine MN

University of California, Irvine Orange County, CAUniversity of North Carolina at Chapel Hill, Carolina Population Center

Duplin County, NC

University of Utah School of Medicine, Department of Pediatrics

Salt Lake County, UT

University of Wisconsin, Madison and Medical College of Wisconsin

Waukesha County, WI

Coordinating Center: WESTAT with Harvard Medical School, University of Pennsylvania, and Daston Communications

As the Coordinating Center, suall Study locations
Selection of Segments

• Several options for defining bounda

segments

• Census boundaries• Neighborhood boundaries• School catchment areas

• Solicit input from the successful off

help define the segments

• To maintain the integrity of the sam

offerors will not be involved in the selection of segments
Recruitment of Study 

Participants• Household Recruitment Approach• Supplemented with recruitment thr

mechanisms

• Prenatal care providers• Community campaign• Births

• Offerors can suggest alternative ap

that would meet the goals of the S
Study Participation

• Recruit from pre-conception/early pregnan• Diverse populations: ethnicity, SES, family • Approximately 13 in-person home and clin

(pre-conception through 21)

• Contact by telephone, computer, mail-in q

every 3 months through the first year of lslightly longer intervals until the child reacof age

• Environmental (air, water, soil, dust) sam

child’s environment (home, school, day ca

• Psychosocial, demographic, neurodevelop

neighborhood and contextual data

• Biological samples from mother, father, ch
Who Will Be Enrolled?

• Household recruitment

• Women who are in the first trimester o• Women who are planning a pregnancy• Women of childbearing age who are no

pregnancy but could become pregnant enrollment period

• Supplemental recruitment

• Prenatal care providers• Community based recruitment of el
Schedule of Visits – Core Proto

Clinical Setting

Home

Preconception (high probability) – one face to faphone follow-up

1st Trimester 3 2nd Trimester UTZ 5 3rd Trimester 8 Delivery Visit 16 months 112 months 2

Other data collections• Diary• Phone• Mail-in Qs and samples
Participation Incentives

• For the benefit of our children• Monetary compensation for time, 

inconvenience, and expenses

• Membership and engagement with • Information about child’s and famil

• Health• Development• Environment
Study Milestones and Timeli

(as of December 2008)

2000–present Planning, pilot studies/methods development

2004 Developed Study design2005 Awarded initial contracts (Coordinating and Vanguar2007 Congress appropriated $69 M 2007 Completion of the first phase of pilot Study protocol2007 Awarded Wave 1 Study Centers2008 Congress appropriated $110.9 M2008+ Reviews and approvals (OMB, peer review, IRB’s)

2008 Awarded Wave 2 Study Centers2009 Full pilot begins at Vanguard Centers

2009 Repository and Laboratory procurements

2009 *+ Award Wave 3 Study Centers2010*+ Begin full Study for Vanguard and Wave 1 locations

2011*+ Begin full Study for Wave 2 locations

2011*+ First Study results become available (methods, pilots

preliminary findings)

2012 *+ Begin full Study for Wave 3 locations2016 Full data set for outcomes of pregnancy

* Pending funding + Pending OMB
Funding (as of December 2008)

• FY00–6: $50m from existing budgets of le

• Infrastructure: Study plan, Coordinating Ce

Vanguard Centers

• Scientific development: 30 workshops, 20 

reviews, 19 pilot studies; hypotheses, expooutcome measures, protocol

• FY07: $69m appropriated

• Prepare to recruit/enroll at Vanguard Cente• Information Management System• Establish 2007 Study Centers

• FY08: $110.9m appropriated

• Finalize recruitment at Vanguard Centers• Prepare to recruit/enroll at 2007 Study Cen

• To conduct the full Study: FY08–34 ~ $3 
So, the National Children’s 

Study Will Provide...• The answer to concerns about known exposure

to potential toxicants

• The power to determine absence of effects or b

to various products important for our society

• Causal factors for a number of diseases and con

with suspected environmental causes

• How multiple causes interact to result in multiple 

• Large sample size required to apply knowledge of 

genome to understand multi-factorial genetic condi

• Identification of early life factors that contribute t

conditions

• A national resource to answer future questions 

biological and environmental samples and the exten

decades to come
What Will the National Children’s 

Study Mean to Our Children’s Well-Being?• Identification of environmental factors wh

contribute to health, development, and beproblems

• Asthma, injury, obesity, autism, ADHD, pre

• Understanding the biology and genetics of 

development, and behavior

• Evidence-based information on which to b

about practice and policy regarding childreand mental health 

• Economic benefits: cost avoidance• Resource for future research
Contact Information

• Check the Web site: 

http://NationalChildrensStudy.gov

• Join the listserv (via the Web site) 

for news and communication

• Contact us at ncs@mail.nih.gov 

or 301-594-9147