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

Michael C. Lu, MD, MPHAssociate Professor

Department of Obstetrics & GynecologyDavid Geffen School of Medicine at UCLA

Department of Community Health SciencesUCLA School of Public Health

UCLA OB-GYN Grand RoundsDecember 4, 2009

Acknowledgment

National Institute of Child Health and Development Community Child Health Network National Children’s Study

Acknowledgment

Finland, 12.2

Denmark, 9.2

Portugal, 8.2

Czech Republic, 8

United Kingdom, 7.7

France, 7

New Zealand, 6.8

Canada, 5.9

Slovak Republic, 5.6

Switzerland, 5.5

Netherlands, 5.2

Germany, 5.2

Poland, 4.8

Spain, 4.6

Japan, 4.4

Hungary, 4.2

Australia, 3.9

Austria, 3.8

Greece, 2.8

Belium, 2.5

Ireland, 1.6

Sweden, 1

USA, 13.1

Norway, 0

Icleand, 0

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Maternal MortalitySource: OECD Health Data 2008

New Zealand, 5.6

Canada, 5.3

United Kingdom, 5.3

Ireland, 4.9

Belgium, 4.7

Austria, 4.5

Netherlands, 4.4

Australia, 4.4

Denmark, 4.4

Switzerland, 4.2

Italy, 4.1

Germany, 4.1

France, 4

Portugal, 3.8

Czech Republic, 3.7

Spain, 3.5

Sweden, 3.1

Japan, 2.8

USA, 6.8

Greece, 4

Finland, 3.3

Norway, 3.2

0 1 2 3 4 5 6 7 8

Infant Mortality

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

U.S. Rank in OECD Maternal mortality

All races – 25th

Whites only – 19th

Infant mortality All races – 22nd

Whites only – 22nd

Racial & Ethnic DisparitiesPregnancy-Related Mortality Ratio, 1991-

1999

30

8.1

0

5

10

15

20

25

30

African American White

Deaths Per 1,000 Live Births

Chang et al MMWR 2003

Racial & Ethnic DisparitiesInfant Mortality, 2005

13.7

5.7

0

2

4

6

8

10

12

14

African American White

Deaths Per 1,000 Live Births

NCHS 2008

How Can This Be?

Life-Course Perspective

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

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.

Life Course Perspective

Early programming Cumulative pathways Implications for research, practice, and

policy

Early Programming

Barker HypothesisBirth Weight and Coronary Heart Disease

0

0.25

0.5

0.75

1

1.25

1.5

<5.0 5.0-5.5 5.6-7.0 7.1-8.5 8.6-10.0 >10.0

Birthweight (lbs)

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.

Barker HypothesisBirth Weight and Hypertension

155

160

165

170

Sys

toli

c P

ress

ure

(m

mH

g)

<=5.5 5.6-6.5 6.6-7.5 7.6-8.5 >8.5

Birthweight (lbs)

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.

Barker HypothesisBirth Weight and Insulin Resistance Syndrome

0

2

4

6

8

10

12

14

16

18

<5.5 5.6-6.5 6.6-7.5 7.6-8.5 8.6-9.5 >9.5

Birthweight (lbs)

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.

Maternal Stress & Fetal Programming

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.

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.

Epigenetics

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

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

Prenatal Programming of Childhood Obesity

Epidemic of Childhood Overweight & Obesity

0

5

10

15

20

25

1976-1980 1988-1994 1999-2002

Perc

en

t

Black Hispanic White

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

Children 6-18 Overweight

Prenatal Programming ofChildhood Overweight & Obesity

Maternal Diabetes & Intrauterine Hyperglycemia

Intrauterine Hyperinsulinemia (Fetal Pancreatic β Cells)

Prenatal& PostnatalHyperleptinemia

Preadipocyte Differentiation

Adipocyte Hyperplasia

HypothalamicLeptin Resistance

Pancreatic β- Cell Leptin Resistance

HyperphagiaHyperinsulinism

Programmed Insulin

Resistance

Postnatal Hyperinsulinemia

Adipogenesis

Prenatal Programming of Childhood Obesity

Cumulative Pathways

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

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.

HPA Axis & Immune SystemChikanza 2000

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

Rethinking Preterm Birth

Sequelae of Preterm BirthSequelae of Preterm Birth

Term Births

Preterm Birth

75%Perinatal Perinatal MortalityMortality

NeurologicNeurologicDisabilitiesDisabilities

50%

12%

Racial & Ethnic DisparitiesInfant Mortality

13.6

5.7

0

2

4

6

8

10

12

14

African American White

Deaths Per 1,000 Live Births

NCHS 2007

Year 2010 Goal

Racial & Ethnic DisparitiesPreterm Births < 37 Weeks

18.4

11.7

0

2

4

6

8

10

12

14

16

18

20

African American White

Percent of Live Births

NCHS 2007

Year 2010 Goal

Racial & Ethnic DisparitiesVery Preterm Births < 32 Weeks

4.17

1.64

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

African American White

Percent of Live Singleton Births

Year 2010 Goal

NCHS 2007

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)

Preterm Birth &Maternal Ischemic Heart Disease

Kaplan-Meier plots of cumulative probability of survival without admission or death from ischemic heart disease after first pregnancy in relation to preterm birth

Smith et al Lancet 2001;357:2002-06

Improving MCH in America

Research

Pre-disease Pathways

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

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)

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

Practice

Prenatal Care 1.0

ReceptionistMedical

Assistant

UltrasoundTechNurse Manager

Prenatal Care 2.0

Oral Health

TeratogenInformationServices

Primary &Specialty Care

SocialServices

Mental Health

NutritionalCounseling

ReceptionistMedical

Assistant

Ultrasound TechNurse Manager

High RiskOB

Family Support

0 10 20 30 40 Years

Prenatal Care 3.0

NHVFRCPED

Rep

rodu

ctiv

e P

oten

tial

Optimal Health Development

Lower Health Development

Trajectory

Medical Home for Women’s Health

Medical Home for Adolescent Health

Pediatric Medical Home

HealthcareEducation

CommunityDevelopment

Environment

MCH

NMPPMCH Life-Course

Organization

Policy

Closing the Black-White Gap in Birth Outcomes:A 12-Point Plan

1. Provide interconception care to women with prior adverse pregnancy outcomes2. Increase access to preconception care for African American women3. Improve the quality of prenatal care4. Expand healthcare access over the life course5. Strengthen father involvement in African American families6. Enhance service coordination and systems integration7. Create reproductive social capital in African American communities8. Invest in community building and urban renewal9. Close the education gap10. Reduce poverty among Black families11. Support working mothers and families12. Undo racism

Lu MC, Kotelchuck M, Hogan V, Jones L, Jones C, Halfon N. Closing the Black-White gap in birth outcomes: A life-course approach. Ethnicity and Disease Forthcoming in 2009.

All this will not be finished in the first 100 days. Nor will it be finished in the first 1,000 days, nor in the life of this Administration, nor even perhaps in our lifetime on this planet. But let us begin.

John F Kennedy (1961)