1. Childhood Matters: Health and Early Childhood Experiences
Michael Gardner MD, MPH
Hillcrest Chairman and Professor of Obstetrics and Gynecology
School of Community Medicine
Jennifer Hays-Grudo, PhD
George Kaiser Family Foundation Chair in Community Medicine
Professor of Internal Medicine

2. Welcome to the womb…

4. You really can blame your mother?

5. Developmental Origins of Adult Health and Disease (DOHaD)
Barker hypothesis (Barker & Osmond, 1986; Barker, 1995)
Fetal undernutrition associated with adult obesity, CVD and type II diabetes (Law et al., 1992; Sayer et al., 2004)
Fetal undernutrition + rapid “catch-up growth” (Ong, 2006; Stettler et al., 2003, 2005)
Thrifty phenotype (Hales & Barker, 2001)
Adaptive response for deprived pretnatal environment maladaptive for postnatal environment
Developmental Origins of Adult Health and Disease (DOHaD) (Gluckman et al 2005; Taylor & Poston, 2007)
Fetal environment either nutritionally deprived or over-rich increases risk for child and adult obesity and its sequelae (Catalano, 2003; Oken & Gillman, 2003; Ehrenberg et al., 2004)

6. Barker Hypothesis
Based on medical archives from Preston, Hertfordshire, and Sheffield, England
16,000 men and women born in Hertfordshire, :
● 2-fold increase in coronary heart
disease from largest to smallest BW
● Impaired GT increased from 14% to 40%
Barker, et al
Clin Sci 1998; 115:118

7. Death Rates From Coronary Artery Disease According to Birthweight

8. Prevelance of Type II DM and Impaired Glucose Tolerance in Men Age 59-70

9. The Nurses Health Study
● 121,701 RNs aged yrs, followed since 1976
● BW self-reported, validated by birth certificate
Rich-Edwards, et al
BMJ 1997; 315:396

10. The Nurses Health Study
CAD MI
Stroke
< 2269 g
1.32
1.29
2.29 g
1.15
0.95
1.38 g
1.02
0.92
1.25 g
(ref) g
0.99
≥ 4537 g
0.68
0.66
Rich-Edwards, et al
BMJ 1997; 315:396

11. Thrifty Phenotype Hypothesis
During periods of starvation, the fetus reduces insulin secretion, and
increases peripheral insulin resistance, thus directing more glucose to the brain and heart, and less to skeletal muscle, etc.
Hales and Barker
Diabetologica 1992; 35: 595

13. What happens inside matters outside
Antenatal stress associated with:
Decreased cognitive function
Quebec Ice Storm loss of electricity & water for up to 5 weeks
Children had lower MDI scores
Lower language development scores
These held when controlling for Ob complications, birth weight , post partum depression (LaPlante et al, 2004)
Maternal exposure to traumatic events associated with:
Schizophrenia (OR – 1.5 in cohort from Dutch famine)
Depression in adulthood

14. Chinese Famine Rate of Schizophrenia
Year of birth
Adjusted risk P
1959
0.89 ( )
0.13
1960
2.30 ( )
<0.001
1961
1.93 ( )
1962
0.95 ( )
0.28
Proportion of familial cases unchanged (17-18%)
St. Clair, et al
JAMA 2005; 294:557

15. Childhood behaviors – Mom’s input
In pregnant women in the top 15% of symptoms of anxiety at 32 weeks
Children had double the risk of behavioral problems at age 4 and 7
Higher risk for ADHD, depression or conduct disorders
Attributable risk may be as high as 15%
If true – economic consequences for special education and even incarceration are stunning
annual societal ‘‘cost of illness’’ for ADHD is estimated to be between $36 and $52 billion – prenatal stress accounting for $5-7 billion per year

16. Pay attention Oklahoma!

17. How?
Epigenetic modifications represent a potential way that “metabolic programming” occurs
Alteration in the hypothalamic-pituitary-adrenal axis involving:
Mobilizing energy stores
Response to stress
Inhibiting inflammatory responses during stress
Post natal stress is cumulative with prenatal stress leading to increased vulnerability to stressors
Prenatal stress can lead to impaired fetal growth
Attention disorders and increased anxiety observed

18. Metabolic “Programming” via Genetic Imprinting
● Imprinting turns gene off
● Gene dosage effect- only one gene operational
● Some imprinting reflects gender of transmitting parent
● Many imprinted genes involve metabolism
i.e. Igf 2 , Igf 2r, H19

20. Programmed to be ill?

21. Tulsa - We’re Number 1!! Statistics published in Newsweek
Tulsa, Oklahoma Smokers: 24.6% Cigarettes per day: Tried to quit with gum: 26.9% Tried to quit with patch: 32.8% Tried to quit with support program: 7.4%

22. Smoking in Pregnancy Decreased fetal growth Increase in Preterm Birth
Increase in placental abruption

24. Children Born with IUGR (< 2.5K):
↓ Nephron number
Fewer glomeruli
↓ Renal volumes
Adult glomeruli : 1,400,000 / kidney in controls
700,000 / kidney in HTN
Rostand Nephol Dial Transplant 2003; 18:1434

25. Smoking effects Children exposed to tobacco prenatally:
Decreased memory skills at age 6
Deficits in auditory processing
Effects more pronounced then children who were exposed prenatally only to marijuana smoking (those children have decreased “executive function”)

26. Alcohol
Fetal Alcohol Syndrome – associated with 6 or more drinks per day
Leads to neurologic impairment
Post natal growth restriction
Microcephaly

27. Alcohol – other effects
alcohol ingestion during pregnancy represents a risk factor in terms of later alcohol-related problems in offspring
hypothesis that low to moderate levels of maternal ethanol intoxication during late pregnancy set the opportunity for fetal learning about ethanol

28. Meth exposure
Meth-exposed children scored lower on measures of visual motor integration, attention, verbal memory and long-term spatial memory
children exposed to Meth prenatally exhibit smaller subcortical volumes

29. Maternal Obesity Higher rates of macrosomia
Higher rates of pregnancy induced hypertension
Higher rates of Gestational Diabetes (a precursor for Type 2 DM)

30. DULCE Program
Provides culturally competent group prenatal care for Diabetic mothers
Education emphasizes diet and life style changes (i.e. just a 20 minute walk a day can smooth out blood sugars)
Teaches self reliance in managing DM
Early review of findings shows a decrease in LGA babies in the Group prenatal care as compared to traditional care

31. SUMMARY
●The intrauterine environment exerts a permanent influence on postnatal metabolism and growth
●The mother’s fetal life can affect the development of her own offspring
●Influential factors include calories, content of diet, micronutrients, stressors

32. Welcome to your childhood…

33. Poverty, children and health: Oklahoma

34. Two complementary theories
Critical periods (latency model)
Barker hypothesis
Organogenesis
Fewer beta cells in pancreas – type 2 diabetes
Fewer nephrons - hypertension
Cumulative experiences (pathways model)
Allostasis and allostatic load
Behavioral responses

35. Accumulation of insults
Poverty and health
Childhood SES
Critical periods
Adult SES
Accumulation of insults
Childhood health
Adult health
Conroy K et al. JDBP 2010;31:

36. Allostasis and Allostatic Load
The stress response and development of allostatic load are illustrated. Perception of stress is influenced by one’s experiences, genetics, and behavior. When the brain perceives an experience as stressful, physiologic and behavioral responses are initiated leading to allostasis and adaptation. Over time, allostatic load can accumulate, and the overexposure to neural, endocrine, and immune stress mediators can have adverse effects on various organ systems, leading to disease.
McEwen 1998

37. Let’s look at that again

38. Adverse Childhood Experiences (ACE) study
Felitti V, Anda R et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. Am J Prev Med 1998;14:
9,508 Kaiser-Permanente adults
7 categories of childhood exposure
Abuse: psychological, physical, sexual
Dysfunction: substance abuse, mental illness, domestic violence, criminality
10 health risk factors
Smoking, obesity, inactivity, depressed mood, suicide attempts, alcoholism, drug abuse, parenteral drug abuse, >50 sexual partners, history of STDs.
Disease conditions:
Ischemic heart disease, cancer, stroke, COPD, diabetes, hepatitis, skeletal fractures, general health rating

39. ACE results Childhood stressors linked to adult health risk behaviors
Childhood stressors linked to disease conditions (OR) diabetes (1.6), COPD (3.9), fractures (1.6), hepatitis (2.3), self-rated poor health (2.2)
Strong dose-response relationship between number of childhood stressors and each of 10 behavioral RFs (p<.05) and for heart disease, cancer, COPD, hepatitis, fractures, poor self-rated health (not for stroke or diabetes).
Risk Factors
Stressors
>4
56% 1%
14% 7%

40. More recent follow-up
At least 1 ACE was reported by 64% of respondents.
For persons with ≥ 4 ACEs, the risk of panic reactions, depressed affect, anxiety, and hallucinations were increased 2.5-, 3.6-, 2.4 and 2.7-fold, respectively
The mean number of comorbid outcomes in the study sample was 2.1 (range: 0–14); means are adjusted for age, sex, race, and educational attainment. The trend in the means is significant (P<0.0001); vertical error bars represent 95% confidence intervals
Anda et al Eur Arch Psychiatry Clin Neurosci (2006) 256 : 174–186

41. Implications of ACE Study
“Clearly, further research and training are needed to help medical and public health practitioners understand how social, emotional, and medical problems are linked throughout the lifespan.
Such research and training would provide physicians with the confidence and skills to inquire and respond to patients who acknowledge these types of childhood exposures.
The magnitude of the difficulty of introducing the requisite changes into medical and public health research, education, and practice can be offset only by the magnitude of the implications that these changes have for improving the health of the nation.”
Felitti et al.. Am J Prev Med 1998;14:

42. Health and stress in Tulsa families
Tulsa Educare – 2 sites
Yearly parent interviews at
Child’s health
“What happened to you last year” – 18 items
247 parents
Interviews conducted by family support specialists
Data analyzed for links to child health
Health issues
Allergies
Asthma
Eczema
Obesity (0)
4 categories of stressors
Financial
Relationship
ACE
Life Changes

43. Preschool health by demographics
Total
No health issue
At least one health issue X2 p
Gender
1.6
0.211
Male
141 (57.1%)
101 (59.8%)
40 (51.3%)
Female
106 (42.9)
68 (40.2%)
38 (48.7)
Age: M (SD)
2.5 (1.2)
2.5 (1.3)
2.3 (1.1)
1.1
0.255
Race
22.0
<0.001
White
27 (10.9%)
17 (10.1%)
10 (12.8%)
Black
94 (38.1%)
50 (29.6%)
44 (56.4%)
Biracial
17 (6.9%)
11 (6.5%)
6 (7.7%)
Other*
109 (44.1%)
91 (53.8%)
18 (23.1%)
Ethnicity
15.4
Hispanic
105 (42.5%)
86 (50.9%)
19 (24.4%)
Non-Hispanic
142 (57.5%)
83 (49.1%)
59 (75.6%)
*95 of the 105 Hispanic parents selected race as “other”

44. Family stress and child health
81% of healthy children had at least one stressor (M=2.6 [SD=2.4]) 95% of children with a health problem had at least one stressor (M=3.5 [SD=2.3]) (all p values < 0.05)

45. Health problem by stress category
Children with asthma, allergies and eczema were more likely to have experienced a family stress in the past year
Children with health problems were more likely to have stressors from multiple categories (2.1) than healthy children (1.5)

46. Tulsa Children’s Project
Based at Tulsa Educare
Community-based participatory research
Multiple partners
Interdisciplinary design
Highly integrated set of interventions
Funded by George Kaiser Family Foundation

47. TCP Partners TCP Annie Van Hanken Monica Basu GKFF Harvard CDC
UT-Austin
OU SCM
OU Educ
OU SW
FCS
Tulsa
Educare
Jack Shonkoff Bill Beardslee Snow, Yoshikawa
Chris King Bob Glover
Jennifer Hays-Grudo Jerry Root Juell Homco
Diane Horm, Lisa Monroe
Julie Miller-Cribbs Natalie O’Reilley Trishia Pratt Candice Weed
Ruth Slocum Elizabeth Miranda
Caren Calhoun, Vicki Wolfe Master Teachers

48. Intervention Model Current Situation Short-term outcomes
Children prepared to succeed in school (foundation for life-long success)
Low-income families
Children (0-5) enrolled in Tulsa Educare
Education
Medical Home
Nutrition
Physical activity
Early Childhood Education
Health
Healthy Competent Children in Healthy Competent Families
Social- Emotional Health
Low-opportunity communities
EduCareers: Adult Education and Workforce Training
Parents actively improving their own & their children’s life circumstances
Re the intervention component, I made a distinction between education and health care on the one hand and mental health and economic security on the other. It seems to me that we have two components with a geographic center of gravity (high quality education and good health care) and two modifier-type variables (good mental health/psychosocial functioning and economic security).
Economic security
Reduction in inter-generational poverty
Current Situation
Short-term outcomes
Long-term outcome
Intervention

49. Integrated components
Improve quality of classroom experience
Enhance curriculum and
Professional development for teachers and staff
Provide opportunities for parents
Adult education
Workforce training
Promote physical health
Health promotion for parents and staff
Improved access to care through on-site clinic

50. Early Childhood Education
Developed and implemented new curriculum – Catherine Snow from Harvard Graduate School of Education
Conducted monthly full or half-day professional development sessions with master teachers and Harvard consultants
Assisted teachers in developing plans for improved outdoor play program
Expected long-term outcomes:
improved language skills in children
improved effectiveness in teachers

51. Health and Health Promotion
Dr. Charlie Homer/NICHQ coaching
Increased clinic hours
Hired bilingual staff
Health promotion
Weekly yoga & Zumba classes (parents)
Bi-monthly yoga classes (staff)
Monthly parent nutrition “make and take” classes
Monthly health workshops
RECESS instructors in class
Expected long-term outcomes:
Increase utilization of clinic within community
Improved health and fitness in Educare community

52. EduCareers: adult education and workforce training for parents
Three options for parents:
Nursing cohort: 9
Adult Education
ESL: 30
GED: 8
Ind’l Career Coaching: 4
Established partnerships:
TCC and TTC
Workforce Oklahoma
Union Public Schools
Support meetings, gas cards, incentives, child care
Family Literacy class
Expected long-term outcomes:
Increased earned income/career opportunities in parents
Increased educational achievement in both generations

53. Nursing cohort 9 of 9 passed certification exam for CNA
8/9 completing CNA III classes at TCC
7/9 passed first block of LPN classes (Medical Terminology, Anatomy & Physiology 1 and 2) with A averages
Will start clinical blocks Fall 2011

54. Mental health Expected long-term outcomes:
Emphasized socioemotional development in curriculum
Taught teachers to recognize and address parental depression (Bill Beardslee’s program Family Connections)
Built relationships with Educare teachers, staff, parents and community
Assessed staff perceptions of Educare (physical, socio-emotional safety in variety of contexts)
Trained nursing cohort in life skills (building relationships, solving problems, resolving conflict, etc.)
Provided additional mental health support for parents and children as appropriate (K. Coon)
Expected long-term outcomes:
Improve interactions among teachers, parents, peers & children
Reduce negative impact of depression on children
Reduce staff absences and turnover

55. Welcome to your future…

56. tulsa county gini coefficient 2000 median income: $41,666 denmark 24.7
eur. union 31.0
canada 32.1
usa 45.0
oklahoma 46.0
mexico 46.1
tulsa county 47.4
swaziland 50.4
city of tulsa 50.4
peru 52.0
namibia 76.0
Data from the US Census Bureau and the CIA Factbook.

57. Social determinants of health
The World Health Organization Commission defined social determinants of health as the conditions in which people are born, grow, live, work and age, including the health system.”
“The structural determinants and conditions of daily life constitute the social determinants of health and are responsible for a major part of health inequities between and within countries”
(WHO Commission on Social Determinants of Health, Final Report, 2008).
WHO Commission on Social Determinants of Health, final report, 2008.

58. Interventions to address SDH
Downloading: what do we know? (health outcomes tied to SDH: education and income)
Seeing fresh: what are we not seeing? (programs don’t address root causes, not coordinated)
What do we sense is needed? (partners, communication, trust)
What are we called we do? (build relationships, develop organic programs)
What would it look like? (user friendly, responsive)
Let’s try it.

59. Usual approach to health problems
values
governments
insurers
health care
churches
Typical Disciplines Clinical medicine Behavioral science Public health Nutrition Exercise science
family
built environment
schools
genes
behavior
Individual
To date, efforts to increase health and wellness have been limited to programs that focus on ONE level—usually just a component of one level—at a time.
Why? Funding limitations, conceptual limitations
Result is a hodge-podge of wellness efforts: some programs that work, some that don’t, no progress in actually improving health status of given set of individuals anywhere.
A very inefficient system for improving health of a population. Imagine if space program in the 1960s were allowed to be conducted using the current grant funding mechanisms—peer group committees giving a little money here, a little money there, hoping that the recipients share their information at various academic meetings and in journal articles, with no coordinated effort to pull all the pieces of the enterprise together.
physical resources
Environment
Systems
retailers
Policy
norms
workplace
Culture
school boards
regulatory agencies

60. Ecological model of intervention
attitudes
government agencies
Academic Disciplines Behavioral sciences Clinical medicine Health promotion Education Social work Economics Public health Public policy /law Architecture/ Urban design Marketing & media
funders
economic environment
health care
churches
physical resources
family
schools
Community partners
Individual
What is needed is a comprehensive effort to understand the ways that each element supports healthy living and wellness.
How? Surest way to understand something is to try to change it.
A scientific discipline built around the assumptions that
a) healthy lifestyles are essential for good health and quality of life (i.e., even if a pill is developed to improve weight loss, people must move their bodies to have healthy bones, muscles and joints, people must be stimulated intellectually to have good brain function, babies must be held to develop social attachments, etc.) There are no short-cuts to health and wellness
AND
b) Healthy living must be built in to the fabric of a community in order to make it part of an individual’s lifestyle. Health and wellness will come about when the lifestyles that result in good health are at least as attractive as lifestyles that result in illness.
This requires a coordinated, systematic and scientific involvement of all aspects of society.
retailers
Systems
built environment
Environment
norms
Policy
school boards
Culture
values

61. TCP: Highly integrated engagement of community partners with common goals
Educare admin, staff and parents
Psychologists & social workers
Physicians
& mental health Clinical medicine & health promotion Education Social work Economics
Public policy /law Architecture/ Urban design Marketing & media
built environment
churches
family
economic environment
funders
attitudes
schools
Individual
health care
school boards
physical resources
values
What is needed is a comprehensive effort to understand the ways that each element supports healthy living and wellness.
How? Surest way to understand something is to try to change it.
A scientific discipline built around the assumptions that
a) healthy lifestyles are essential for good health and quality of life (i.e., even if a pill is developed to improve weight loss, people must move their bodies to have healthy bones, muscles and joints, people must be stimulated intellectually to have good brain function, babies must be held to develop social attachments, etc.) There are no short-cuts to health and wellness
AND
b) Healthy living must be built in to the fabric of a community in order to make it part of an individual’s lifestyle. Health and wellness will come about when the lifestyles that result in good health are at least as attractive as lifestyles that result in illness.
This requires a coordinated, systematic and scientific involvement of all aspects of society.
vendors
government agencies
Systems
norms
Environment
Policy
Culture

63. Post-natal nutritional programming
Gluckman & Hanson, 2004

64. Developmental Origins of Adult Health and Disease Hypothesis
From McMillen & Robinson 2005

65. McMillen & Robinson 2005