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Nutrition and the Lifelong Continuum

Nutrition and the Lifelong Continuum. 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 ASTPHND 2010 Annual Meeting Baltimore, MD June 14, 2010.

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Nutrition and the Lifelong Continuum

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  1. Nutrition and the Lifelong Continuum 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 ASTPHND 2010 Annual Meeting Baltimore, MD June 14, 2010

  2. “If you want 1 year of prosperity, grow grain. If you want 10 years of prosperity, grow trees. If you want 100 years of prosperity, grow people.” Chinese Proverb

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

  4. 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.

  5. Life Course Perspective • Early programming • Cumulative pathways • Prevention of childhood obesity

  6. Early Programming

  7. 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.

  8. 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.

  9. 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.

  10. Maternal Stress & Fetal Programming

  11. 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.

  12. 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.

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

  14. 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

  15. Prenatal Programming of Childhood Obesity

  16. 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

  17. Prenatal Programming ofChildhood Overweight & Obesity

  18. 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

  19. Cumulative Pathways

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

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

  22. 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.

  23. HPA Axis & Immune System Chikanza 2000

  24. Stressed vs. Stressed Out • 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

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

  26. Rethinking Preterm Birth

  27. Sequelae of Preterm Birth 75% Perinatal Mortality 12.3% 50% Neurologic Disabilities

  28. Racial & Ethnic DisparitiesPreterm Births Percent of Live Births Year 2010 Goal NCHS 2009

  29. Racial & Ethnic DisparitiesVery Preterm Births Percent of Live Singleton Births Year 2010 Goal NCHS 2009

  30. Racial & Ethnic DisparitiesInfant Mortality Deaths Per 1,000 Live Births Year 2010 Goal NCHS 2009

  31. 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)

  32. 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

  33. Prevention of Childhood Obesity

  34. Preventing Childhood Obesity 1. Prevention has to begin before birth

  35. White House Task Force on Childhood Obesity • Recommendation 1.1: Pregnant women and women planning a pregnancy should be informed of the importance of conceiving at a healthy weight and having a healthy weight gain during pregnancy, based on the relevant recommendations of the Institute of Medicine

  36. Prenatal Care 1.0 Receptionist Medical Assistant OB Nurse Manager Ultrasound Tech

  37. Prenatal Care 2.0 High Risk OB Primary & Specialty Care Nutritional Counseling Teratogen Information Services Mental Health Social Services Oral Health Family Support Receptionist Medical Assistant OB Nurse Manager Ultrasound Tech

  38. Prenatal Care 3.0 High Risk OB WIC Family Planning Teratogen Information Services Preconception & interconception Care Prenatal care Oral Health Mental Health Primary & Preventive Services Nutrition Counseling Medical Home Family Support Health Education

  39. Optimal Health Development Nutrition PED NHV FRC Prenatal Care 3.0 Lower Health Development Trajectory Reproductive Potential Medical Home for Women’s Health Medical Home for Adolescent Health Pediatric Medical Home 0 10 20 30 40 Years

  40. White House Task Force on Childhood Obesity • Recommendation 1.3: Hospitals and health care providers should use maternity care practices that empower new mothers to breastfeed, such as the Baby-Friendly hospital standards

  41. White House Task Force on Childhood Obesity • Recommendation 1.4: Health care providers and insurance companies should provide information to pregnant women and new mothers on breastfeeding, including the availability of educational classes, and connect pregnant women and new mothers to breastfeeding support programs to help them make an informed infant feeding decision

  42. White House Task Force on Childhood Obesity • Recommendation 1.5: Local health departments and communitybased organizations, working with health care providers, insurance companies, and others should develop peer support programs that empower pregnant women and mothers to get the help and support they need from other mothers who have breastfed

  43. Preventing Childhood Obesity 2. Prevention has to begin before conception

  44. Early Prenatal Care Is Too LateTo Prevent Some Birth Defects • The heart begins to beat at 22 days after conception • The neural tube closes by 28 days after conception • The palate fuses at 56 days after conception

  45. Early Prenatal Care Is Too LateTo Prevent Implantation Errors Norwitz ER, Schust DJ, Fisher SJ. Implantation and the survival of early pregnancy. N Engl J Med. 2001 Nov 8;345(19):1400-8.

  46. Early Prenatal Care Is Too LateTo Prevent Obesogenic Chemical Exposures • Dioxins • Endocrine disruptors • Disrupt neruodevelopment • Disrupt immune development • May promote development of childhood obesity and diabetes • Lipophilic • Half life of up to 7 years • Crosses the placenta easily

  47. White House Task Force on Childhood Obesity • Recommendation 1.7: Federal and State agencies conducting health research should prioritize research into the e!ects of possibly obesogenic chemicals.

  48. Early Prenatal Care Is Too LateTo Restore Allostasis & Optimize Fetal Programming McEwen BS, Lasley EN. The end of stress: As we know it. Washington DC: John Henry Press. 2002

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