Where Is MCH In Relation to the 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 National MCH Life Course Meeting Oakland, CA June 9, 2008

Major Disconnects in MCH  Longitudinal Disconnect  Contextual Disconnect  Methodological Disconnect

Longitudinal Disconnect

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.

Developmental Programming

Programming  The process whereby a stimulus or insult, at a sensitive or ‘critical’ period, has lasting or lifelong impact on health or function. Barker DJP. Mothers, babies and health in later life. Edinburgh: Churchill Livingstone

Prenatal Programming of Childhood Obesity

Maternal Diabetes & Intrauterine Hyperglycemia Intrauterine Hyperinsulinemia (Fetal Pancreatic β Cells) Prenatal& Postnatal Hyperleptinemia Preadipocyte Differentiation Adipocyte Hyperplasia Hypothalamic Leptin Resistance Pancreatic β- Cell Leptin Resistance Hyperphagia Hyperinsulinism Programmed Insulin Resistance Postnatal Hyperinsulinemia Maternal Diabetes & Intrauterine Hyperglycemia Intrauterine Hyperinsulinemia (Fetal Pancreatic β Cells) Prenatal& Postnatal Hyperleptinemia Adipocyte Hyperplasia Hypothalamic Leptin Resistance Pancreatic β- Cell Leptin Resistance Hyperphagia Hyperinsulinism Programmed Insulin Resistance Postnatal Hyperinsulinemia Adipogenesis Dysregulation of the Adipoinsular Feedback System Maternal Diabetes & Intrauterine Hyperglycemia Intrauterine Hyperinsulinemia (Fetal Pancreatic β Cells) Prenatal& Postnatal Hyperleptinemia Preadipocyte Differentiation Adipocyte Hyperplasia Hypothalamic Leptin Resistance Pancreatic β- Cell Leptin Resistance Hyperphagia Hyperinsulinism Programmed Insulin Resistance Postnatal Hyperinsulinemia Adipogenesis Maternal Diabetes & Intrauterine Hyperglycemia Intrauterine Hyperinsulinemia (Fetal Pancreatic β Cells) Prenatal& Postnatal Hyperleptinemia Preadipocyte Differentiation Adipocyte Hyperplasia Hypothalamic Leptin Resistance Pancreatic β - Cell Leptin Resistance Hyperphagia Hyperinsulinism Programmed Insulin Resistance Postnatal Hyperinsulinemia Adipogenesis Prenatal Programming of Childhood Obesity

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

Epigenetics Same Genome, Different Epigenome R.A. Waterland, R.A. Jirtle, "Transposable elements: targets for early nutritional effects on epigenetic gene regulation," Mol Cell Biol, 23: , Reprinted in the New Scientist 2004

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

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.

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

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

“Weathering” The effects of social inequality on the health of populations may compound with age, leading to growing gaps in health status through young and middle adulthood that can affect fetal health. Geronimus AT (1996)

Contextual Disconnect

Epidemiological Model Environment Host Agent (Parasite)

Multiple Determinants Evans RG, Stoddart GL. Producing health, consuming health care. Soc Sci Med. 1990;31:

Ecological Model Bronfenbrenner U. Ecology of Human Development: Experiments by Nature and Design. Cambridge MA: Harvard University Press

Toxic Environments

Methodological Disconnect

Transdisciplinary Research  Multidisciplinary Research researchers from different fields work independently or sequentially, each from his or her own disciplinary perspective, to address a particular research topic  Interdisciplinary Research entails greater sharing of information and closer coordination among researchers from various fields than occurs in multidisciplinary projects, yet the participants remain anchored in their respective disciplinary models and methodologies  Transdisciplinary Research researchers work together to develop a shared conceptual framework that integrates and extends discipline-based concepts, theories, and methods to address a common research topic. Transdisciplinary research collaborations are intended to achieve the highest levels of intellectual integration across multiple fields and yield shared conceptual formulations that move beyond the disciplinary perspectives represented by team members. Stokols D. Toward a science of transdisciplinary action research. Am J Community Psychol Sep;38(1-2):63

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 M, Wallerstein N, eds. Community Based Participatory Research for Health. San Francisco, Calif: Jossey-Bass Publishers; 2003

Praxis  Integration of theory and practice

Now What?

Integration

 Longitudinal Integration Measurements Data Infrastructure  Data linkages  Longitudinal studies  National Children’s Study Longitudinal modeling  Contextual Integration Measurements Bias & confounding Multilevel modeling  Interactions  Gene-environment Cumulative risks  Methodological Integration Transdisciplinary Research Community-Based Participatory Research Praxis

Integrated Science of MCH Life Course  Theory  Research  Practice  Policy  Education