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Life-Course Perspective A Primer for MCH Epidemiologist

Life-Course Perspective A Primer for MCH Epidemiologist. Michael C. Lu, MD, MPH Associate Professor Department of Obstetrics & Gynecology David Geffen School of Medicine at UCLA Department of Community Health Sciences UCLA School of Public Health MCH Epidemiology Conference Atlanta, GA

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Life-Course Perspective A Primer for MCH Epidemiologist

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  1. Life-Course PerspectiveA Primer for MCH Epidemiologist Michael C. Lu, MD, MPH Associate Professor Department of Obstetrics & Gynecology David Geffen School of Medicine at UCLA Department of Community Health Sciences UCLA School of Public Health MCH Epidemiology Conference Atlanta, GA December 13, 2007

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

  3. 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.

  4. Life Course Perspective • Early programming • Cumulative pathways

  5. Early Programming

  6. 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.

  7. 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.

  8. 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.

  9. Prenatal Programming of Childhood Obesity

  10. 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

  11. Prenatal Programming ofChildhood Overweight & Obesity

  12. 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

  13. Cumulative Pathways

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

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

  16. 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.

  17. 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

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

  19. Rethinking Preterm Birth

  20. 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)

  21. 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

  22. Life Course PerspectiveImplications for MCH Epidemiology • Research • What are life-course influences on perinatal outcomes • What are perinatal influences on life-course outcomes • Practice • What are data systems needs for MCH life-course epidemiology in Health Departments? • Policy • What is the return on investment over the life course? (For every dollar spent on prenatal care (or preconception care), X dollars are saved on (childhood obesity, early-onset Type II diabetes, autism, learning disabilities, asthma ….)

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