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Improving Maternal & Child Health in America: A Life-Course Perspective

Improving Maternal & Child Health in America: A Life-Course Perspective. 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 UCLA OB-GYN Grand Rounds

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Improving Maternal & Child Health in America: A Life-Course Perspective

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  1. Improving Maternal & Child Health in America:A Life-Course Perspective 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 UCLA OB-GYN Grand Rounds December 4, 2009

  2. Acknowledgment • National Institute of Child Health and Development • Community Child Health Network • National Children’s Study

  3. Acknowledgment

  4. Maternal Mortality Source: OECD Health Data 2008

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

  6. U.S. Rank in OECD • Maternal mortality • All races – 25th • Whites only – 19th • Infant mortality • All races – 22nd • Whites only – 22nd

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

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

  9. How Can This Be?

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

  11. 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.

  12. Life Course Perspective • Early programming • Cumulative pathways • Implications for research, practice, and policy

  13. Early Programming

  14. 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.

  15. 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.

  16. 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.

  17. Maternal Stress & Fetal Programming

  18. 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.

  19. 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.

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

  21. 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

  22. Prenatal Programming of Childhood Obesity

  23. 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

  24. Prenatal Programming ofChildhood Overweight & Obesity

  25. 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

  26. Cumulative Pathways

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

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

  29. 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.

  30. HPA Axis & Immune System Chikanza 2000

  31. 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

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

  33. Rethinking Preterm Birth

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

  35. Racial & Ethnic DisparitiesInfant Mortality Deaths Per 1,000 Live Births Year 2010 Goal NCHS 2007

  36. Racial & Ethnic DisparitiesPreterm Births < 37 Weeks Percent of Live Births Year 2010 Goal NCHS 2007

  37. Racial & Ethnic DisparitiesVery Preterm Births < 32 Weeks Percent of Live Singleton Births Year 2010 Goal NCHS 2007

  38. 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)

  39. 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

  40. Improving MCH in America

  41. Research

  42. Pre-disease Pathways Early and long-term biological, behavioral, psychological and social precursors to disease.

  43. Community Child Health Network(CCHN) • Longitudinal study of the causes of disparities in birth and child health outcomes • 4,000 families at 5 locations (LA, Baltimore, DC, NC, Chicago) recruited at birth of index child • One of the richest databases to study developmental origins of child health disparities • Community Based Participatory Research (CBPR) • A collaborative process that equitably involves all partners in the research process and recognizes the unique strengths that each brings. CBPR begins with a research topic of importance to the community with the aim of combining knowledge and action for social change to improve community health and eliminate health disparities(Minkler & Wallerstein 2003)

  44. National Children’s Study • Longitudinal study – from before birth to 21 years of age • Cohort of 100,000 children from 100 Study Locations • Study how children’s genes and their environments interact to affect their health and development • In Los Angeles, • 4,000 children • 56 neighborhoods • 67 birth hospitals • Followed for 21+ years

  45. Practice

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

  47. 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

  48. Optimal Health Development PED Primary Care NHV Prenatal Care FRC Family Planning 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

  49. Community Development Environment MCH Healthcare Education

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