The Science of Healthy Start

Michael C. Lu, MD, MPH Associate Administrator

Maternal and Child Health Health Resources and Services Administration

U.S. Department of Health and Human Services

2015 Healthy Start Convention November 16, 2015

We hold these truths to be self-evident, that all men are created equal ….

We hold these truths to be self-evident, that all men are created equal ….

Declaration of Independence 1776

I have a dream that one day … little black boys and black girls will be able to join hands with little white boys and white girls and walk together as sisters and brothers.

Martin Luther King, Jr (1963)

Racial & Ethnic Disparities Infant Mortality, 2013

0

2

4

6

8

10

12

11.11

5.06

Deaths Per 1,000 Live Births

NCHS 2015

Year 2010 Goal

Non-Hispanic Black Non-Hispanic White

Racial & Ethnic Disparities Low Birth Weight < 2500g

2013

0

2

4

6

8

10

12

14

13.1

7

NCHS 2015

Percent of Live Births

Non-Hispanic Black Non-Hispanic White

Racial & Ethnic Disparities Very Low Birth Weight <1500g

2013

0

0.5

1

1.5

2

2.5

3

2.96

1.13

NCHS 2015

Percent of Live Births

Non-Hispanic Black Non-Hispanic White

Racial & Ethnic Disparities Preterm Births < 37 weeks, 2013

0

2

4

6

8

10

12

14

16

18

16.3

10.2

Percent of Live Births

NCHS 2015

Non-Hispanic Black Non-Hispanic White

Racial & Ethnic Disparities Very Preterm Births < 32 Weeks, 2013

Non-Hispanic Black Non-Hispanic White 0

0.5

1

1.5

2

2.5

3

3.5

4

3.71

1.55

Percent of Live Singleton Births

NCHS 2014

Racial & Ethnic Disparities Infant Mortality, 2005, 2013

NCHS 2015

Racial & Ethnic Disparities Causes of Infant Deaths, 2013

Per 1,000 Live Births

0

0.5

1

1.5

2

2.5

3 Birth Defects Preterm/LBW SIDS

NCHS 2015

African Native Hispanic Asian/PI White American American

Why?

Genetics?

Genetics?

Infant Deaths Per 1,000 Live Births

NCHS 2015

7.04

11.65

Foreign-Born Black US-Born Black

Birth weight distribution of African-born blacks is more closely related to US-born whites than to US-born blacks

David RJ, Collins JW. Differing birth weight among infants of U.S.-born blacks, African-born blacks, and U.S.-born whites. N Engl J Med. 1997 Oct 23;337(17):1209-14.

Behavior

Maternal Smoking?

Percent of Women Who Reported Smoking During pregnancy

9.3%

13.6%

African American White NCHS 2002

Maternal Smoking?

Infant Deaths Per 1,000 Live Births

13.2

9.2

African American Non-Smokers White American Smokers

NCHS 2002

Prenatal Care?

Prenatal Care?

0 10 20 30 40 50 60 70 80 90

100 Percent of Live Births with First Trimester Prenatal Care

74%

85%

74%

84%

70%

African Native Hispanic Asian/PI White NCHS 2002 American American

Prenatal Care?

NCHS 1999 Infant Deaths Per 1,000 Live Births

12.7

5.2

African Americans First White Americans First Trimester Prenatal Care Trimester Prenatal Care

Prenatal Care?

NCHS 2002 Infant Deaths Per 1,000 Live Births

12.7

7.1

African Americans First White Americans Prenatal Trimester Prenatal Care Care After 1st Trimester or

None

SES?

Racial & Ethnic Disparities Infant Mortality & Education

NCHS 2002

Infant Mortality 12 or More Years of School

14.1

5.7

African American African

American

Hispanic

74% Hispanic

51%

SES? NCHS 2002

Infant Deaths Per 1,000 Live Births

10.2

6.8

African Americans 16+ years White Americans <9 years of of schooling schooling

Multiple Risk Factors?

Racial and Ethnic Disparities Multiple Determinants of Birth Outcomes

• Shiono et al AJPH 1997 • Controlled for 46 risk factors (demographic characteristics, medical risks,

level of living, psychological, social, exposures, “newly defined”) • 236 g mean birthweight difference between African Americans & whites

remained • Maternal age, smoking, BMI, housing & locus of control only significant

covariates • 46 risk factors explained less than 10% of variation in birthweight

Life Course Perspective

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 • Healthy Start

Early Programming

Developmental Origins of Health & Disease

Barker Hypothesis Birth Weight and Coronary Heart Disease

1.5

1.25

1

0.75

0.5

0.25

0

Age Adjusted Relative Risk

<5.0 5.0-5.5 5.6-7.0 7.1-8.5 8.6-10.0 >10.0 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 Hypothesis Birth Weight and Hypertension

155

160

165

170

Syst

olic

Pre

ssur

e (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 Hypothesis Birth Weight and Insulin Resistance Syndrome

0

2

4

6

8

10

12

14

16

18 Odds ratio adjusted for BMI

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

Maternal Stress & Fetal Programming

CRH

ACTH

Cortisol Norepinephrine

+

Hypothalamus

Pituitary

Adrenal

+

CRH

Placenta

(+) Cortisol DHEA-S

(+)

(+) Hypothalamus

Pituitary

Adrenal

(+)

11-B HSD II

CRH

ACTH

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

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, 23:5293-300, 2003.

Prenatal Programming of Childhood Obesity

Epidemic of Childhood Overweight & Obesity

Per

cen

t

25

20

15

10

5

0

Children 6-18 Overweight

1976-1980 1988-1994 1999-2002

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

O RIG IN AL PAPl!R

Prenata l Programming of Childhood Overweight and Obes ity

Jen~feirS. Huang. Tiffunr A. Lff. Michael C . Lu

© Sping.« Scie:oce-t8ua.e..MedJ4. U.C2006

AbJtrad Ob#n1\'r. lb rcvkw the scientific evidence for pn:mbl programmin& of childhood ovcn.~ight a_nd obc:siry. and dUc uss iLJ imp ticaliOOJ for MCH rcsca-.h. pnctiCC". ind policy.

J,fnltods: A .1y111emar_ic review of oNc:n ·atiai.al 11udic'1

cu.minins the rcl1lion.1hip between prcn::i1al expo.sure• and cbHdhood o .. -cl"\.\o'd.ghl a.ad obesity wu conducted usin,s MOOSE guidelines. The rcvi~· included litcr.uurc pc»tcd on PubMcd wid MOConsult and published bef'A>'t:CD

January 197S and OccC'mbcr 200S. Prenatal cxposu.ra 10

m.:ucmal diabetes, malnutri1io~ and c ig.nrcne smoking were cuunincd. and primary study outcome was chi ldhood cn-erwdghl or obes ity as mensun::d by body mass index

(BMI) for children~<• 5 to 21. /Usul1r. F'ouroflix in;ludcd studies ofpn::mnal C'Xposurc

to maternal diabetes found higher prc"o·alc:rrc o f childhood

overwdg.hl or obesity IUllODS offspring of diabc'tic ma.hers. with the highest quality 1tudy rcp:ming an odds rario of 4dolescen1 ovcn<.-cl~ht of I.~ (95% Cl 1.0-1.9). The Dutch famine study found thal cxpo1urc IO maternal mahlutrition in ewiy. bul no1 l 1tc.gcsLMion wuas1oci1tcd with increased

Di~ T\eopiaiou _,_.- t. ,_... p;apu-ao ._ldhon• ... d do mot MC _ _..1yrc.8ecttkTTi.,.,...Wpob0.oltlloiliflib.&'°4u:witb whki. t ..... i.on -·•lUlet. J. S. Hun,g· TA. Lee· ~L C. Lu Dc.putma:w; ol Obsktrin M4I ~. DlrYtd Oclll'm School ol MdciH .t UCLA. CA.USA

De:ponlnft't olC.ommumtyHcGlti. Scicece.1aod die Cuter kw UNkbie.r Childrm.. f'amilie.1 ud Comm unit*. lJCl..A Sc bool of Publle H cialt ... 8oJi. 9$ l 7n. lo1 A•pl-., CA 9009.5- l 712. USA o-m.U: 1ndu@u.:1Leclu

odds of childhood obesity (OR 1.9. 95% Cl 15--2.4). All eight included 11udk1 or prcnnlal CllJXllUl"C to m3fem.:ll

smoking sho....-cd significantly inc~ucd odds of childhood O'\'CJ'\o\r'Ci.J;ht and obC'sily. with molt odds ratios clustering

uound 1.5 to 2.0. The biolo,g:ica.1 mechanisms mcxliming these rdarionshipl an: unknown but may be partially ~lated to programming of insulin. lcptia. and ghtcocorticoid

rc.si.stancc 111 "'~"' · Co11chu1011: Our review .1upporu pn::R4lal programming

of childhood m."t':rwci,g.ht a.nd obesity. ""1CH n::scareh, practice, and policy nc:cd lo consider the: p~nalaJ period a window of opponunity forotcsity pf'C\o-cntion.

Klfywords Prcn.nta.I programming· Childhood obesity · Overweight· Developmental progrnmming · Fetal programming· Gestational diabetes · Maternal malnutrition· Cig~tte smokin,g

Childhood ovcr\•lcighl I.Rd obaity i.s a growing problem in the Unito:I States and ¥.-"Ork:l""'ide. The prn-akncc- of child­hood OVC'A-'Ci~ t in the U.S. criplo:I bctv.-ccn 1980 an.:12000 ( I ). Tbday "R'"'Xim3kly I in 6 (16.,,) U.S. chHdJCD °"' O\'Cl'\o\r"CiShl v.hh .1ignifkan1 racial..c-lhnic c::lisplritics. For ex­

ample. nearly I In 4 (23%) non-HisJXUJic black .¢rls a.gs 6 to 19 arc O''C""""ciShl . a p~·a.lcno: almost f'.A.;cc thal: of non-HisJXtnk w hite girls 11 J.

()vcrv."Cigbt and obesity has sig:nifican1 lifclo~ conse­quences on the health a.nd wcll-bcia,g of ('hildrcn [2. 3J. Childhood obesity isasscx:l:ltcd with early-onset 'T)'pc a dia­bc-tcs mclli tus~ hypcrtcuion. metabolic synd.rcmc. and sleep :apaca. II i.s also anociatcd with cognitive or intellectual im­

painTicnt and social exclusion and stigma1imtion as pans of a vicious cycle lrcludinQ a::hool avoidance (3J. Childhood obesity tracks 1trongly into adulthood (4, SJ; obesity beyond

Prenatal Programming of Childhood Obesity

Prenatal Programming of Childhood Obesity

Cumulative Pathways

Saber Tooth Tiger

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.

Stressed vs. Stressed Out

• Stressed

• Increased cardiac output

• Increased available glucose

• Enhanced immune functions

• Growth of neurons in hippocampus & prefrontalcortex

• Stressed Out

• Hypertension &cardiovascular diseases

• Glucose intolerance & insulin resistance

• Infection & inflammation

• Atrophy & death ofneurons in hippocampus &prefrontal cortex

McEwen BS. Stressed or stressed out: What is the difference? J Psychiatry Neurosci 2005; 30:315-8

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 & Infant Mortality, US, 2007

Births Infant Deaths <32 2% 32-33

2% 34-36 9%

37+ 32% <32

54%

34-36 37+ 10%87%

32-33 4%

Source: NCHS, linked birth/infant death data set

Rethinking Preterm Birth

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 (earlyprogramming & 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

Healthy Start

Healthy Start Strategic Priorities

• Improve women’s health • Promoting quality & safety • Strengthen family resilience • Achieve collective impact • Improve accountability

Improve Women’s Health Benchmarks

Increase the proportion of Healthy Start participants • with health insurance to 90% (Baseline: 82%) • who have a documented reproductive life plan to 90%

(Baseline 59%) • who receive a postpartum visit to 80% (Baseline 64%) • who have a medical home to 80% (Baseline 83%) • who receive annual well-woman visits to 80% (Baseline 65%)

Promote Quality Services Benchmarks

• Increase the proportion of HS participants who engage in safe sleep behaviors to 80% (Baseline 69%)

• Increase the proportion of HS infants who are ever breastfed to 82% (Baseline 56%)

• Increase the proportion of HS infants who breastfed at 6 months to 61% (Baseline 28%)

• Increase abstinence from cigarette smoking among HS pregnant women to 90% (Baseline 79%)

• Reduce the proportion of HS pregnancies conceived within 18 months of a previous birth to 30% (Baseline 25%)

• Increase proportion of well child visits (including immunization) for HS participants’ children between ages 0-24 months to 90% (Baseline 81%)

• Reduce the proportion of HS participants with elective delivery before 39 weeks to 10% (Baseline 11%)

Strengthen Family Resilience Benchmarks

• Increase the proportion of HS participants who receive perinatal depression screening and referral to 100% (Baseline 84%)

• Increase the proportion of HS participants who receive follow up services for perinatal depression to 90% (Baseline 63%)

• Increase the proportion of HS participants who receive intimate partner violence screening to 100% (Baseline 86%)

• Increase the proportion of HS grantees that demonstrate father and/or partner involvement (e.g., attend appointments, classes, infant/child care) during pregnancy to 90% (Baseline 54%)

• Increase the proportion of HS grantees that demonstrate father and/or partner involvement (e.g., attend appointments, classes, infant/child care) with child 0-24 months to 80% (Baseline 50%)

• Increase the proportion of family members that read daily to a HS child between the ages of 0-24 months to 50% (Baseline 42%)

Achieve Collective Impact Benchmarks

• Increase the proportion of HS grantees with a fully implemented Community Action Network to 100%

• Increase the proportion of HS grantees with at least 25% HS participant membership on their CAN membership to 100%.

• For Levels 2 and 3, increase the proportion of HS grantees that have a clear plan of action with a common agenda among Community Action Network and community partners for the collection of community-wide data and measurement targets to 90%.

• For Levels 2 and 3, increase the proportion of HS grantees that have a shared measurement system with indicator measures for collective impact to 90%.

Increase Accountability Benchmarks

• Increase the proportion of HS grantees who establish a quality improvement and performance monitoring process to 100%.

• For Level 3, increase the proportion of HS grantees who have a fully implemented CoIIN process to 90%.