Hserv 482 Session 6

1. Hserv 482 Session 6 Human development & early life effects on later health FIRST DISSEMINATION EXERCISE Due in 2 weeks

2. LAST CLASS Summary • Subjective well-being (SWB), happiness as a national indicator is culture dependent • SWB has not improved over time or with increasing wealth this past century • SWB correlates with equality, human rights, fulfillment of basic human needs • US SWB has declined since the early 1970s, and the declines have been greater in women • USA does not fare well in most health outcomes in comparison with other rich countries, happiness not doing so well either and trends are in the unfortunate direction • NEXT: EARLY LIFE effects

3. Summary to here • Defining health, considering what produces it • Mortality (objective), well-being happiness (subjective) • US not that healthy compared to other countries in many health outcomes, including well-being. • Range of hierarchy (gap between rich and poor) is related to health in a society) and this reflects amount of caring and sharing present there • WHEN DOES HIERARCHY MATTER MOST?

4. Agenda • Look at comparative data on child health • Fetal development and programming • Infancy and biological embedding • Population health perspective • Intergenerational aspects

5. impact of early life on adult health? • STUDENT THOUGHTS? • How important?

6. impact of early lifeon adult health? • STUDENT THOUGHTS? • How to study?

7. In any discussion 3 questions to ask: • What are the facts? • What are the interpretations of those facts. • What are the presuppositions behind the interpretations.

8. Making Transition Work for Everyone: Poverty and Inequality in Europe and Central Asia, World Bank 2001

9. BETTER HEALTH MORE EQUALITY Child Health among rich countries Collison et. al. 2007 Public Health

10. Child Poverty Olympics (2005)

11. UNICEF League Table of Child Abuse Deaths

12. UNICEF League Table of Child Well-Being

13. UNICEF League Table of Child Well-Being

15. UNICEF League Table of Child Well-Being

16. UNICEF League Table of Child Well-Being

17. Pickett et. al. 2007

18. Studies on outcomes in childhood • CDC states (US health 1998) : "A healthy childhood is a foundation of success and health in later life. pg 46 • Infants born to mothers of lower socioeconomic status tended to have poorer health, as measured by their rates of low birth weight and infant mortality." • "Several measures of health status ... indicated that children from lower SES families had worse health status and more risk factors for poor health"

19. Hispanic Paradox Roseto issues?

21. most important factor influencing child health is SES • behaviors can't have much to do with the health of a child, or infant-- • they don't smoke, drink, shoot guns (much) • Expect downstream effects from SES: • environmental quality (more exposure to lead among US poor) • nurturing child rearing environments (fewer in US poor) • poor more likely to undertake adverse health behaviors • smoking • drinking • injection drug use • AT WHAT LEVEL DOES SES ACT?

22. BASIC IDEA SO FAR • SES matters for children's health • our children don't seem to be doing so well lately

23. Next step: • What might this have to do with adult health? • seems obvious that it should, • does what happens in early childhood impact adult health? • Study fetal programming (life long changes) of adult disease • Biological embedding (after birth)

24. David Barker in UK • Coronary Heart Disease mortality rates correlated with birth weights • UK archives in Hertfordshire, Preston and Sheffield had detailed records going to early 1900s • have birth weights, obstetrical records with body proportions and placenta weights and growth in infancy, • (birth data from 1911-1930 followed to present) • conditions in early life PROGRAM later effects in adults (fetal origins hypothesis) • animal experiments show that undernutrition (stress)in utero leads to persisting changes in variety of metabolic, endocrine and immune functions (in later life)

25. Barker • newborns small at birth (for dates, because they failed to grow, rather than premature), were at risk for adult heart disease • highest prevalence of Type 2 Diabetes in people who were small at birth and obese as adults • studies replicated in US, Finland and South India and see similar association with hypertension, and diabetes (UK, US, Sweden)

26. Barker • have critical periods of fetal development (coincide with rapid cell division), • If lack of nutrients or oxygen (or stress), rate of cell division is slowed • poor fetal growth (thinness) results in insulin resistance • thin neonate lacks skeletal muscle and fat, but brain is spared (fetus, when stressed, tries to make sure brain gets enough nutrients, sparing muscle) • fetal Glucocorticoids (cortisol) • Fetal cortisol effects cell differentiation • placenta is barrier to maternal glucocorticoids but can have deficiency in enzyme establishing barrier so get fetal glucocorticoid elevations in response to maternal stress

27. Newsweek September 27, 1999

28. fetal nutrition • poor nutrition (stress) impairs growth during critical periods of fetal life and permanently affects structure and physiology of endocrine pancreas, liver, blood vessels • fetal nutrition depends on: • mother's dietary intakes • mother's nutrient stores • sheep studies show that maternal undernutrition in mid-pregnancy has profoundly different effects on fetal and placenta growth depending on whether mother entered pregnancy with high or low nutritional stores

29. fetal nutrition • 3. fetal nutrition depends on • mother's nutritional state AT TIME OF CONCEPTION • conditions then reflects particular sensitivity of early embryo growth to concentration of nutrients • in fetus with fast growth trajectory, placenta may consume fetal amino acids to maintain lactate (energy) production, • nutrient delivery to placenta • placenta's transfer capabilities • 4. Age of mother • mature mothers optimize flow of nutrients to fetus • adolescent mothers may thrive at expense of fetus • Hormonal programming (fetus produces cortisol) • WOMB WITH A VIEW

30. womb with a view

31. Maternal nutrition (stress) in pregnancySUMMARY • Early pregnancy undernutrition (stress) leads to large placenta • Nutrition (stress) in mid-trimester effect depends on maternal stores (stress) when entered pregnancy • maternal stores conditioned by mother's early life, and her mother (intergenerational---fetus' grandmother) • Nutrition (stress) in third trimester effect depends on whether fetus is growing rapidly or not • Rapid growth rates could result in placenta consuming fetal protein to produce lactate energy stores and resulting fetal wasting

32. Biological embedding Growth in infancy • Growth mainly from development and enlargement of existing cells, rather than addition of new ones • Babies short at birth tend to grow slowly after birth • Low rates of infant weight gain predict CAD in men • (not sure if growth in later childhood can be protective) • low weight gain leads to LV hypertrophy in childhood and adulthood

33. Biological embedding of early life experiences • Rapid neuronal (brain) cell growth in fetus and by birth have pretty well all your neurons (Central Nervous System CNS) • Neurons are then "sculpted" ie neuron-to-neuron connections reinforced, others suppressed • Child's early years spend in unstimulating, emotionally and physically unsupportive environments adversely affects brain development • leads to cognitive, social & behavioral delays • results in acute & chronic stress in school • CNS "talks to" hormone, immune and clotting systems leading to systematic differences in experience of life to increase or decrease resistance to disease via long-term function of vital organs as expression of SES (gradient) • BIOLOGICAL EMBEDDING is effect of human experience on health over life course (Hertzman)

34. Biological embedding mechanisms • HPA axis (hypothalamo pituitary adrenal) • handling in rats, during early life permanently changes way HPA axis responds over life course (handling reduces total lifetime exposure of corticosterone to brain) (Meany) • highly reactive rhesus monkeys have higher cortisol (Suomi) • later show more depressive-like behaviors with separation, longer HPA activation, rapid noradrenergic turnover (related to maternal attachment) which remain stable throughout development & appear heritable (epigenetic) • Baboons (Sapolsky) four factors lead to variation in basal cortisol levels in the wild • rank of a baboon • troop social stability & its enforcement • lack of violence and coercion • animal's experience of rank, stability and enforcement • personality and coping styles

35. Social Emotional Regulation via early attachment to a mother figure Harlow and wire-cloth mother overcame food as need See quieter stress response, lower cortisol levels when monkey in front of mother leading to secure attachment (Suomi)

38. Gorilla Orangutan Bonobo Gibbon

39. Synaptic Density Rivkin, 2000: 70

40. Summary so far: • Health in early childhood patterns SES of the mother/(father) • Early childhood has profound impacts on adult health • Fetal programming is a major mechanism through fetal-placenta relationship endocrine aspects early growth retardation, and compensatory catch-up later leads to obesity • Biological embedding (early life experiences)

41. population health perspective • cross-sectional studies like the UNICEF charts, demonstrate there is a problem, but hard to tease out where it comes from • Ideally: cohort studies, following people from before birth, gathering data at conception, or before • best available is at first ante-natal visit • Birth-onwards cohort studies

42. prospective cohort studies to look at life course issues, What matters over various parts of a life, from being a gleam in your parents' eyes to death?

43. 1958 British Birth Cohort Study • Everyone born in UK (England, Scotland and Wales) in week of March 3-9, 1958 • included more than 17,000 subjects • follow up at age 7, 11, 16, 23, and most recently at 33 years

44. Impacting health at age 33 years from early childhood? • Latent effects • impacts adult health independent of intervening experience • Pathway effects • early life sets trajectories that affect health status over time, such as education • Cumulative effects • intensity and duration of exposure of unfavorable environments adversely affects health, (usually dose-response)

45. “pathway” factors: “cumulative” factors: “latent” factors: Contributions to Self-rated Health at Age 33, 1958 British Birth Cohort Death Birth

46. Contributions to Self-rated Health at Age 33, 1958 British Birth Cohort microSocial Network Meso Civil Society Death Birth MACROSocio-Economic Environment

47. Contributions to Self-rated Health at Age 33, 1958 British Birth Cohort “pathway/cumulative” factors:OR=6.15 “latent” factors: OR=5.03 Death Birth

48. Contributions to Self-rated Health at Age 33, 1958 British Birth Cohort microSocial Network OR=N.S. Meso Civil Society OR=2.05 Death Birth “Intersecting” factors: OR=3.83 MACROSocio-Economic Environment OR=1.87

49. Contributions to Self-rated Health at Age 33, 1958 British Birth Cohort microSocial Network OR=N.S. “pathway/cumulative” factors: OR=6.15 “latent” factors: OR=5.03 Meso Civil Society OR=2.05 Death Birth “Intersecting” factors: OR=3.83 MACROSocio-Economic Environment OR=1.87

50. socio-economic circumstances birth to age 16 • Latent factors that matter most: • read to consistently • how easily adjusted to school • fraction of adult health reached by age 7 HIERARCHY?