Use of the Life Course Perspective to Improve Maternal & Child Health Outcomes

1. Use of the Life Course Perspectiveto Improve Maternal & Child Health Outcomes 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 Tulsa, Oklahoma October 11, 2011

3. “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

4. “If you want to grow healthy people, you start by improving MCH.” Not a Chinese proverb

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 • Use of the life course perspective to improve MCH outcomes

8. Early Programming

10. 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.

11. 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.

12. 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.

13. Maternal Stress & Fetal Programming

14. 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.

15. 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.

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

17. 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

18. Prenatal Programming of Childhood Obesity

19. 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

20. Prenatal Programming ofChildhood Overweight & Obesity

21. 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

22. Cumulative Pathways

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

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

25. 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.

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. Preterm Birth 36% Infant Mortality 12.3% 50% Neurologic Disabilities NCHS 2010

30. Racial & Ethnic DisparitiesPreterm Births < 37 weeks Percent of Live Births Year 2010 Goal NCHS 2010

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

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

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. Use of the Life Course Perspective To Improve MCH Outcomes

36. 1. Invest Early

37. “If you want to grow healthy people, you start by improving MCH.” Not a Chinese proverb

39. Too Much, Too Late?

40. Public Expenditures Children 0-17, Sweden, 1995

41. “If you want to improve MCH, you start by improving women’s health.” Not a Chinese proverb

42. Put the W Back in MCH

43. Not Only During Pregnancy, But Before, Between, and Beyond Pregnancy

44. PRECONCEPTION & INTERCONCEPTION CARE

45. 2. Improve Healthcare Quality

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

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

48. Prenatal Care 3.0 High Risk OB OB Hospitalist Dietician & WIC Ultrasound Center Mental Health Oral Health Genetic Counseling & Prenatal Diagnosis Specialty Clinics Primary & Preventive Services Health Education Medical Home Family Support & Social Services Family Planning

49. 3. Reinvent Public Health

50. Not just create stop-gap services, But build integrated systems that work