Life-Course Perspective A Primer for MCH Epidemiologist

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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

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Life-Course Perspective

• A way of looking at life not as disconnected
  stages, but as an integrated continuum

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Life Course Perspective
Lu MC, Halfon N. Racial and ethnic disparities in
birth outcomes a life-course perspective.Matern
Child Health J. 2003713-30.
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Life Course Perspective

• Early programming
• Cumulative pathways

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• Early Programming

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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
1997315396-400.
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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 199330624-27.
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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 19933662-67.
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Prenatal Programming of Childhood Obesity
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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
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Prenatal Programming ofChildhood Overweight
Obesity
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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 ß
Cells)
Intrauterine Hyperinsulinemia (Fetal Pancreatic ß
Cells)
Intrauterine Hyperinsulinemia (Fetal Pancreatic ß
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 ß- Cell Leptin Resistance
Pancreatic ß- Cell Leptin Resistance
Hypothalamic Leptin Resistance
Pancreatic ß- Cell Leptin Resistance
Hyperphagia
Hyperphagia
Hyperphagia
Hyperinsulinism
Hyperinsulinism
Hyperinsulinism
Adipogenesis
Adipogenesis
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• Cumulative Pathways

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Photo http//www.lam.mus.ca.us/cats/encyclo/smilo
don/
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Allostasis Maintain Stability through Change
McEwen BS. Protective and damaging effects of
stress mediators. N Eng J Med. 1998338171-9.
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Allostastic LoadWear and Tear from Chronic
Stress
McEwen BS. Protective and damaging effects of
stress mediators. N Eng J Med. 1998338171-9.
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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

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Allostasis Allostatic Load
McEwen BS, Lasley EN. The end of stress As we
know it. Washington DC John Henry Press. 2002
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Rethinking Preterm Birth
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• 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)

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Preterm Birth Maternal Ischemic Heart Disease
Smith et al Lancet 20013572002-06
Kaplan-Meier plots of cumulative probability of
survival without admission or death from
ischemic heart disease after first pregnancy in
relation to preterm birth
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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 .)