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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