Nigel Paneth MD MPH

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The National Childrens Study in
MichiganOpportunities for Obstetric Research

• Nigel Paneth MD MPH
• Pediatric Grand Rounds
• William Beaumont Hospital
• Department of Obstetrics and Gynecology
• Sept 3, 2009
• www.epi.msu.edu/faculty/paneth.htm

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THE CHARGE FROM CONGRESS PL 106-310. Childrens
Health Act of 2000

• The Director of NICHD shall establish a
  consortium from appropriate Federal agencies
  (including the CDC and EPA) to
• (1) plan, develop, and implement a prospective
  longitudinal 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.

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THE RESPONSEThe National Childrens Study

• The NCS is a longitudinal study of a nationally
  representative sample of 100,000 children, their
  families, and their environment from before birth
  through age 21.
• It is the largest longitudinal study of
  childrens health and development ever conducted
  in the U.S.
• It may be the largest study combining all forms
  of measurement in depth (self-report, clinical
  examinations, biological samples) ever conducted
  on any human population.

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WHY ARE PROSPECTIVE LONGITUDINAL STUDIES SO
VALUABLE?

• If we know what happens to people before disease
  develops, we can figure out what causes disease
  and how disease can be prevented.
• The Framingham Heart Study followed healthy
  adults for many years, and taught us that factors
  such as high blood pressure, diabetes, smoking
  and high cholesterol predispose to heart disease.
  
• Applying those lessons has played a major role in
  the 60 reduction in the heart disease death
  rate, the 42 reduction in the overall death
  rate, and the extra 9 years of life attained
  since 1950 in the US.
• The US needs a Framingham for kids!

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WHAT IS BEING STUDIED?
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SOME STUDY QUESTIONS OF INTEREST TO OBSTETRICIANS

• Do assisted reproductive technologies (ART)
  increase the risk of fetal growth restriction,
  birth defects, and developmental disabilities?
• Does impaired maternal glucose metabolism during
  pregnancy cause obesity in children?
• Does pre-and post-natal exposure to
  endocrine-active environmental agents alter age
  at onset, duration, and completion of puberty?
• Do inapparent infections contribute to risk of
  preterm delivery?

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DATA TO BE COLLECTED PRIOR TO BIRTH

• Study begins with a home visit prior to
  conception (when possible) or in the first
  trimester of pregnancy
• Two additional clinic visits and three phone
  contacts during pregnancy.
• In one of the clinic visits, a third trimester
  study ultrasound is obtained.

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PRE-CONCEPTIONAL OR FIRST TRIMESTER HOME VISIT

• Questionnaires Household Composition and
  Demographics Perceived Stress Social Support
  Family Processes Health Behaviors Diet and
  Toxicant Exposure through Food Environmental
  exposures
• Biospecimens from both partners if available
  blood, hair, urine, nail, saliva. Vaginal fluid
  from woman.
• Environmental samples dust, air, water, soil
• Physical measurements height, weight, skinfolds,
  other anthropmetry, blood pressure

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DATA TO BE COLLECTED AT BIRTH
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DATA TO BE COLLECTED AFTER BIRTH

• Home visits at six and twelve months and frequent
  phone contacts.
• Further collection of biological and
  environmental specimens at home visits (breast
  milk, formula, baby urine)
• Health surveys obtained at all visits
• Abstraction of medical records
• Continued follow-up to age 21, though full
  protocol beyond age 2.5 not yet developed

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BIOLOGICAL STORAGE AND INFORMATICS

• All material collected in the study
  (environmental and biological specimens) will be
  stored in duplicate in two locations
• After aliquotting, an estimated 32 million
  specimens will be stored in the first seven years
  of the study, most in vapor phase liquid nitrogen
  at -150 or less.
• All survey and health data collected will be
  protected by the highest levels of security

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WHERE DOES THE NCS TAKE PLACE?
All Births in the Nation
4 million births in 3,141 counties
Sample of Study Locations
105 Locations
Selection of neighborhoods
Sample of Study Segments
All or a sample of households within neighborhoods
Study Households
All eligible women in the household
Study Women
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7 Vanguard sites 29 Wave 1 sites 36 Wave
2 sites 15 Wave 3 sites 18 unassigned sites
TOTAL 105 SITES
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HOW ARE PARTICIPANTS ENROLLED?

• In sampled segments of counties (specific
  neighborhoods selected to be representative of
  the counties), all women of child-bearing age are
  contacted first by mail, then phone, then in
  person.
• If the woman is at high risk of pregnancy or in
  the first trimester, consenting and enrollment
  takes place at first contact. Otherwise,
  enrollment is deferred but contact is maintained
  with the woman.
• Surveillance of prenatal care sites is used to
  detect first-trimester pregnant women from
  segments.
• Infants can be enrolled at birth if mother lives
  in segment and was not previously enrolled.

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WHEN DOES THE STUDY TAKE PLACE?

• 105 study locations to enroll in four waves
  Vanguard, and Waves 1 -3.
• Seven Vanguard locations began enrolling in 2009.
  
• Wave 1 (includes Wayne) to start in 2011
• Wave 2 (includes Lenawee and Grand Traverse) to
  start in 2012
• Wave 3 (includes Macomb and Genesee) to start in
  2013

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WORK BEFORE ENROLLMENT

• Selection of segments
• Estimating N of births to obtain 250 births
  per county for each of four years
• Aiming for county representativeness
• Engaging the community
• Making arrangement with hospitals and
  prenatal care providers
• Dealing with IRBs
• Hiring and training staff

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The Michigan Alliance for the National
Childrens Study (MANCS)
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Michigans 5 NCS Study Counties
WAVE 1 Wayne WAVE 2 Grand Traverse
Lenawee WAVE 3 Genesee Macomb
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THE FIVE MANCS PARTICIPATING INSTITUTIONS

• Henry Ford Health System (HFHS)
• Michigan Department of Community Health (MDCH)
• Michigan State University (MSU)
• University of Michigan (UM)
• Wayne State University (WSU) Childrens Hospital
  of Michigan (CHM)
• Plus the health departments of each of the
• five counties

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CHALLENGES IN CONDUCTING THE NCS

• Population-based survey research has rarely, if
  ever, been combined with data collection in
  clinical settings. Yet from identifying
  non-pregnant women at home
• Pregnancies must be identified in the first
  trimester
• Births must be identified when they occur in any
  hospital in which a segment woman delivers
• Intense protocol
• Many IRBs to obtain consent from
• Increasing resistance to general population
  medical research. We also cannot take
  physicians help for granted.

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A MANCS IRB

• We are trying to get a single IRB in Michigan
  to review all MANCS protocols (including any
  adjunct studies)
• All institutions and hospitals would send
  representatives to this IRB
• MSU is setting up a special IRB for large,
  multicenter studies in Michigan, which would
  review all MANCS-related protocols
• Other four institutions have agreed to this
  arrangement

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OBSTETRIC PROVIDERS PLAY A KEY ROLE

• In helping us to ascertain women in prenatal
  care
• In helping us to collect birth specimens

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ID LIKE TO INTRODUCE -

• Gwen Norman RN, who is our hospital negotiator
  who is in charge of
• communications with hospitals
• communications with prenatal care providers

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PREGNANCY ASCERTAINMENT VIA PRENATAL CARE
PROVIDERS

• We plan surveillance in prenatal care to
  identify women from the study segments
• We will provide address-matching software to
  clinics and providers (or an 800 number to call)
  to identify women eligible for the NCS
• We will then need providers to alert us to the
  presence of NCS-eligible women

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LABOR ASCERTAINMENT BY HOSPITALS

• We will develop a system by which hospitals will
  notify us if an eligible woman is admitted in
  labor.
• We will also develop arrangements with each
  hospital to collect the required specimens
• We spend a great deal of time working to bring
  hospitals on board.

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HELPING WOMEN WITH THE PROTOCOL THE PARTICIPANT
ADVOCATE COORDINATOR (PAC)

• We budgeted an additional staff member, the PAC.
  This is a woman from the community with
  experience of pregnancy and labor issues whose
  role is to assist the participant to complete the
  protocol. She does not collect data (though she
  may help with birth collections)
• She keeps in touch with the participant reminding
  her of the protocol requirements
• The PAC will go with subjects to study visits,
  and to LD with mother, if required
• In Wayne County, we have one PAC per 30 women per
  7 months (from first trimester visit to delivery)

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HOW IS BEAUMONT INVOLVED?

• In 2005, 23 of all Wayne resident births
  delivered outside of Wayne County
• Beaumont Hospital (Royal Oak) was the third
  largest deliverer of Wayne County births outside
  of Wayne County, with 803 Wayne County births (3
  of all Wayne County births)
• Therefore Beaumont Hospital would be expected to
  be the birth hospital for 30 study births
• It is likely that some of you see Wayne County
  women in prenatal care

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ADJUNCT STUDIES

• Not every hypothesis in the childrens study
  needs 100,000 subjects!
• A great deal of useful work could be done with
  our 5,000 Michigan participants or even
  sub-samples of them
• The NCS is encouraging special studies of smaller
  groups of participants to answer special
  questions of interest
• Given the very large amount of obstetric data and
  samples being collected, this could be a great
  opportunity to answer questions of interest to
  obstetricians.
• If you would like to develop an adjunct study or
  participate in one, please contact me at
  paneth_at_msu.edu

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WILL YOU HELP US WITH A BRIEF SURVEY?

• The survey you have received will soon be sent
  to all obstetric providers in Wayne County. It is
  designed to learn about prenatal care and
  delivery practices and how they can intersect
  with the NCS.
• It would help us a great deal if you could take
  five minutes now to complete this survey.
• We would also like to know how to contact you
  electronically so that we can identify NCS
  participants from Wayne who might be seen in your
  practice, so we ask for your email address.
• Many thanks in advance!

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EXTRA SLIDES FROM HERE ON
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COMMUNITY ENGAGEMENT IS KEY

• We must make sure that women know about the NCS
  in our communities.
• We must make sure that people women trust (health
  care providers, religious and political leaders)
  also know about the study.
• We must make sure that women get a positive image
  of the NCS.
• We must make the value of the NCS to the
  community is clear.
• We should measure these attitudes periodically to
  see how well we are doing.

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PILOT WORK WITH PREGNANT WOMEN IN GRAND RAPIDS,
MI SUMMER 2006

• Provider attitudes
• Mudd L et al MCH Journal 2008 12(6)684-91
• Attitudes of pregnant women
• Nechuta S et al Paed Perinat Epid
  200923424-30.

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PRENATAL CARE STAFF WILLINGNESS TO HELP IN NCS
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DELIVERY ROOM STAFF WILLINGNESS TO HELP IN NCS
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PRENATAL AND DELIVERY STAFF BARRIERS TO THE NCS
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PREGNANT WOMENS ACCEPTANCE OF NCS PROCEDURES
WITH AND WITHOUT COMPENSATION