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Reinventing Maternal & Child Health: A Life-Course Perspective

Reinventing Maternal & Child Health: A Life-Course Perspective. Michael C. Lu, MD, MPH Associate Professor of Obstetrics, Gynecology, and Public Health UCLA Schools of Medicine and Public Health UCLA Center for Healthier Children, Families and Communities

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Reinventing Maternal & Child Health: A Life-Course Perspective

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  1. Reinventing Maternal & Child Health:A Life-Course Perspective Michael C. Lu, MD, MPH Associate Professor of Obstetrics, Gynecology, and Public Health UCLA Schools of Medicine and Public Health UCLA Center for Healthier Children, Families and Communities National Center for Infancy & Early Childhood Health Policy MCHB-AIM Child & Adolescent Policy Support Center Alameda County Building Blocks for Healthy Babies, Healthy Families, & Healthy Communities September 10, 2009

  2. The definition of insanity is doing the same thing over and over and expecting different results Benjamin Franklin

  3. Mario Drummond Neal Halfon Milt Kotelchuck Cheri Pies Acknowledgment

  4. Acknowledgment

  5. Life-Course Perspective • A way of looking at life not as disconnected stages, but as an integrated continuum

  6. Life Course Perspective Lu MC, Halfon N. Racial and ethnic disparities in birth outcomes: a life-course perspective.Matern Child Health J. 2003;7:13-30.

  7. Life Course Perspective • Early programming • Cumulative pathways • Reinventing MCH

  8. Early Programming

  9. Barker HypothesisBirth Weight and Coronary Heart Disease Age Adjusted Relative Risk Rich-Edwards JW, Stampfer MJ, Manson JE, Rosner B, Hankinson SE, Colditz GA et al. Birth weight and risk of cardiovascular disease in a cohort of women followed up since 1976. Br Med Jr 1997;315:396-400.

  10. Barker HypothesisBirth Weight and Hypertension Law CM, de Swiet M, Osmond C, Fayers PM, Barker DJP, Cruddas AM, et al. Initiation of hypertension in utero and its amplification throughout life. Br Med J 1993;306:24-27.

  11. Barker HypothesisBirth Weight and Insulin Resistance Syndrome Odds ratio adjusted for BMI Barker DJP, Hales CN, Fall CHD, Osmond C, Phipps K, Clark PMS. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (Syndrome X): Relation to reduced fetal growth. Diabetologia 1993;36:62-67.

  12. Maternal Stress & Fetal Programming

  13. Prenatal Stress & Programming of the Brain • Prenatal stress (animal model) • Hippocampus • Site of learning & memory formation • Stress down-regulates glucocorticoid receptors • Loss of negative feedback; overactive HPA axis • Amygdala • Site of anxiety and fear • Stress up-regulates glucocorticoid receptors • Accentuated positive feedback; overactive HPA axis Welberg LAM, Seckl JR. Prenatal stress, glucocorticoids and the programming of the brain. J Neuroendocrinol 2001;13:113-28.

  14. Prenatal Programming of the Hypothalamic-Pituitary-Adrenal Axis Welberg LAM, Seckl JR. Prenatal stress, glucocorticoids and the programming of the brain. J Neuroendocrinol 2001;13:113-28.

  15. Epigenetics Gibbs WW. The Unseen Genome: Beyond DNA. Scientific American 2003

  16. EpigeneticsSame Genome, Different Epigenome R.A. Waterland, R.A. Jirtle, "Transposable elements: targets for early nutritional effects on epigenetic gene regulation," Mol Cell Biol, 23:5293-300, 2003. Reprinted in the New Scientist 2004

  17. Prenatal Programming of Childhood Obesity

  18. Epidemic of Childhood Overweight & Obesity Children 6-18 Overweight Source: National Center for Health Statistics, National Health and Nutrition Examination Survey Note: Estimate not available for 1976-1980 for Hispanic; overweight defined as BMI at or above the 95th percentile ofr the CDC BMI-for-age growth charts

  19. Prenatal Programming ofChildhood Overweight & Obesity

  20. Maternal Diabetes & Intrauterine Hyperglycemia Intrauterine Hyperinsulinemia (Fetal Pancreatic β Cells) Prenatal& Postnatal Hyperleptinemia Preadipocyte Differentiation Programmed Insulin Resistance Adipocyte Hyperplasia Postnatal Hyperinsulinemia Hypothalamic Leptin Resistance Pancreatic β- Cell Leptin Resistance Hyperphagia Hyperinsulinism Adipogenesis Prenatal Programming of Childhood Obesity Dysregulation of the Adipoinsular Feedback System Maternal Diabetes & Intrauterine Hyperglycemia Maternal Diabetes & Intrauterine Hyperglycemia Maternal Diabetes & Intrauterine Hyperglycemia Intrauterine Hyperinsulinemia (Fetal Pancreatic β Cells) Intrauterine Hyperinsulinemia (Fetal Pancreatic β Cells) Intrauterine Hyperinsulinemia (Fetal Pancreatic β Cells) Prenatal& Postnatal Hyperleptinemia Prenatal& Postnatal Hyperleptinemia Preadipocyte Differentiation Programmed Insulin Resistance Programmed Insulin Resistance Prenatal& Postnatal Hyperleptinemia Preadipocyte Differentiation Programmed Insulin Resistance Adipocyte Hyperplasia Adipocyte Hyperplasia Adipocyte Hyperplasia Postnatal Hyperinsulinemia Postnatal Hyperinsulinemia Postnatal Hyperinsulinemia Hypothalamic Leptin Resistance Hypothalamic Leptin Resistance Pancreatic β- Cell Leptin Resistance Pancreatic β- Cell Leptin Resistance Hypothalamic Leptin Resistance Pancreatic β- Cell Leptin Resistance Hyperphagia Hyperphagia Hyperphagia Hyperinsulinism Hyperinsulinism Hyperinsulinism Adipogenesis Adipogenesis

  21. Cumulative Pathways

  22. Photo: http://www.lam.mus.ca.us/cats/encyclo/smilodon/

  23. Allostasis: Maintain Stability through Change McEwen BS. Protective and damaging effects of stress mediators. N Eng J Med. 1998;338:171-9.

  24. Allostastic Load:Wear and Tear from Chronic Stress McEwen BS. Protective and damaging effects of stress mediators. N Eng J Med. 1998;338:171-9.

  25. HPA Axis & Immune System Chikanza 2000

  26. Stressed Increased cardiac output Increased available glucose Enhanced immune functions Growth of neurons in hippocampus & prefrontal cortex Stressed Out Hypertension & cardiovascular diseases Glucose intolerance & insulin resistance Infection & inflammation Atrophy & death of neurons in hippocampus & prefrontal cortex Stressed vs. Stressed Out

  27. Allostasis & Allostatic Load McEwen BS, Lasley EN. The end of stress: As we know it. Washington DC: John Henry Press. 2002

  28. Rethinking Preterm Birth

  29. Sequelae of Preterm Birth 75% Perinatal Mortality 12% 50% Neurologic Disabilities

  30. Racial & Ethnic DisparitiesInfant Mortality, 2005 Deaths Per 1,000 Live Births NCHS 2008 NCHS 2008

  31. Racial & Ethnic DisparitiesPreterm Births < 37 Weeks Percent of Live Births Year 2010 Goal NCHS 2008

  32. Racial & Ethnic DisparitiesVery Preterm Births < 32 Weeks Percent of Live Singleton Births Year 2010 Goal NCHS 2008

  33. Rethinking Preterm Birth Vulnerability to preterm delivery may be traced to not only exposure to stress & infection during pregnancy, but host response to stress & infection (e.g. stress reactivity & inflammatory dysregulation) patterned over the life course (early programming & cumulative allostatic load)

  34. Preterm Birth &Maternal Ischemic Heart Disease Smith et al Lancet 2001;357:2002-06 Kaplan-Meier plots of cumulative probability of survival without admission or death from ischemic heart disease after first pregnancy in relation to preterm birth

  35. Reinventing MCH

  36. Why Reinvent MCH?

  37. Maternal Mortality Source: OECD Health Data 2008

  38. Infant Mortality Source: United Nations. Table 4. In: United Nations Demographic Yearbook, 2004. New York, NY: United Nations; 2007:73–93.

  39. Racial & Ethnic DisparitiesPregnancy-Related Mortality Ratio, 1991-1999 Deaths Per 1,000 Live Births Chang et al MMWR 2003

  40. Racial & Ethnic DisparitiesInfant Mortality, 2005 Deaths Per 1,000 Live Births NCHS 2008

  41. Racial & Ethnic DisparitiesInfant Mortality, Alameda County, 2001-03 Deaths Per 1,000 Live Births Alameda County Health Status Report, 2006: http://www.acgov.org/health/disparitiesStudy.pdf

  42. Racial & Ethnic DisparitiesLow Birth Weight, Alameda County, 2001-03 Percentage of Live Births Alameda County Health Status Report, 2006: http://www.acgov.org/health/disparitiesStudy.pdf

  43. How Can This Be?

  44. How Can This Be? First, the pathways to better health do not generally depend on better health care, and second, even in those instances in which health care is important, too many Americans do not receive it, receive it too late, or receive poor-quality care. Schroeder SA. NEJM 2007;357:1221-8

  45. How Can We Do Better? Transform maternal and child healthcare Assure the conditions in which all mothers and children can be healthy

  46. 1. Transforming Maternal & Child Healthcare

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