Improving Preconception Health & Healthcare in Louisiana

Michael C Lu MD MPHMichael C. Lu, MD, MPHAssociate Professor

Department of Obstetrics & GynecologyDavid Geffen School of Medicine at UCLA

Department of Community Health SciencesDepartment of Community Health SciencesUCLA School of Public Health

Louisiana Family Impact SeminarBaton Rouge, LAMarch 4, 2011

“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 Chinese Proverb

“If you want to grow healthier people, you start by improving women’s health before pregnancy.”

Not A Chinese Proverb

Why Why Preconception Care?p

Why Preconception Care?

Early prenatal care is too late Early prenatal care is too late.

Early Prenatal Care Is Too LateEarly Prenatal Care Is Too LateTo Prevent Some Birth Defects

The heart begins to beat at 22 days after conception The heart begins to beat at 22 days after conception The neural tube closes by 28 days after conception The palate fuses at 56 days after conception

Early Prenatal Care Is Too LateEarly Prenatal Care Is Too LateTo Prevent Implantation Errors

Norwitz ER, Schust DJ, Fisher SJ. Implantation and the survival of early pregnancy. N Engl J Med. 2001 Nov 8;345(19):1400-8.

Life-Course Perspective

A way of looking at life not as disconnected 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 Early programming Cumulative pathways

Early Programming

Barker HypothesisBarker HypothesisBirth Weight and Coronary Heart Disease

1.5

1

1.25Age Adjusted Relative Risk

0.75

1

0.25

0.5

0<5.0 5.0-5.5 5.6-7.0 7.1-8.5 8.6-10.0 >10.0

Birthweight (lbs)Birthweight (lbs)

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 HypothesisBarker HypothesisBirth Weight and Hypertension

170

51

mm

Hg)

165

Pres

sure

(m

160

Syst

olic

P

155

<=5.5 5.6-6.5 6.6-7.5 7.6-8.5 >8.5Birthweight (lbs)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 HypothesisBarker HypothesisBirth Weight and Insulin Resistance Syndrome

18

12

14

16 Odds ratio adjusted for BMI

8

10

12

2

4

6

0

2

<5.5 5.6-6.5 6.6-7.5 7.6-8.5 8.6-9.5 >9.5Birthweight (lbs)Birthweight (lbs)

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 & e a a S ess &Programming of the Brain

Prenatal stress (animal model) 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 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 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.

EpigeneticsEpigenetics

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

EpigeneticsEpigeneticsSame 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 g gChildhood Obesity

Epidemic of Childhood Overweight & Obesity

25

20

25Children 6-18 Overweight

10

15

Per

cen

t

5

10

01976-1980 1988-1994 1999-2002

Black Hispanic Whitep

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

Prenatal Programming ofPrenatal Programming ofChildhood Overweight & Obesity

Prenatal Programming of Childhood e a a og a g o C d oodObesity

Maternal Diabetes & Intrauterine Hyperglycemia

Intrauterine Hyperinsulinemia (Fetal Pancreatic β Cells)β )

Prenatal& PostnatalHyperleptinemia

Preadipocyte Differentiation

Programmed Insulin

ResistanceAdipocyte

Hyperplasia

Hypothalamic Pancreatic β-

Postnatal Hyperinsulinemia

ypLeptin Resistance

a c eat c βCell Leptin Resistance

HyperphagiaHyperinsulinism

Adipogenesis

C l ti P thCumulative 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:os as c oadWear 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 Stressed Out Stressed

Increased cardiac output

Stressed Out

Hypertension & cardiovascular diseases

Increased available glucose Glucose intolerance &

insulin resistance

Enhanced immune functions

Infection & inflammation

Growth of neurons in hippocampus & prefrontal cortex

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

Preterm Birth

36%Infant

MortalityMortality

12.3%

50%

12.3%

Term Births

P t Bi th

NeurologicDisabilities

50%

Preterm Birth

NCHS 2010

Racial & Ethnic DisparitiesPreterm Births < 37 weeks

Percent of Live Births

Year 2010 Goal

NCHS 2010

Racial & Ethnic DisparitiespVery Preterm Births < 32 Weeks

P t f Li Si l t Bi thPercent of Live Singleton Births

Year 2010 Goal

NHS 2010

Racial & Ethnic DisparitiesInfant Mortality

Deaths Per 1,000 Live Births

Year 2010 Goal

NCHS 2010

Rethinking Preterm BirthRethinking 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 inflammatory dysregulation) patterned over the life course (early programming & cumulative allostatic load)

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

Preconception Health and Health Care: Preconception Health and Health Care: Why Is It Important?

Take Home Message #1

Even early prenatal care may be too late Even early prenatal care may be too late To prevent some birth defects To prevent implantation errors To restore allostasis quickly enough to optimize fetal

programming

Take Home Message #2

An important objective of preconception care is An important objective of preconception care is to restore allostasis and optimize women’s health before pregnancy

Take Home Message #3

If you want to grow healthier people in If you want to grow healthier people in Louisiana, you start by improving women’s health before pregnancy.

Interconception Interconception CareCare

The definition of insanity is doing the same The definition of insanity is doing the same thing over and over and expecting different results

Benjamin Franklin

"We must become the change we want to see ” We must become the change we want to see.

- MOHANDAS GANDHIMOHANDAS GANDHI