The National Prematurity Campaign:The National Prematurity Campaign:A Call to Action A Call to Action

Karla Damus RN MSPH PhDDept OB/GYN and Women’s Health

Albert Einstein College of Medicine, Bronx, NYOffice of the Medical Director

National March of Dimes, White Plains, NYkdamus@marchofdimes.com 914 997 4463

March of Dimes National Prematurity Campaign

2003-2007

5 year $75 million initiative

National Professional PartnersNational Professional Partners

• ACOG

• AAP

• AWHONN

• Many national professional health group alliances

Campaign Goals

1. Increase public awareness of the problems of prematurity to at least 60%

2. Decrease the rate of preterm birth in the U.S. by at least 15%

March of Dimes Prematurity Campaign2003-2007

5 Campaign Aims:

1. Raise public awareness

2. Educate women as to signs of premature labor

3. Assist practitioners

4. Invest to identify causes and promising interventions

5. Seek guaranteed access to health care

www.cdc.gov/brfss

Preterm Birth/Prematurity• Single most important cause of perinatal mortality (28 weeks gestation through

6 days of life) in US (about 75% of these losses) • Leading cause of neonatal mortality (0-27 days) in US• Second leading cause of infant mortality in US• Leading cause of infant mortality in GA and leading cause of infant mortality for

black infants in the US• Major determinant of neonatal and infant illness:

– Neurodevelopmental handicaps (CP, mental retardation)– Chronic respiratory problems– Intraventricular hemorrhage– Periventricular leukomalacia – Infection– Retrolental fibroplasia– Necrotizing enterocolitis– Neurosensory deficits (hearing, visual)

Prematurity Generates Enormous Health Care Costs

• Average newborn hospital charges: $4,300 vs. $58,000 for a preterm baby*

• Total U.S. hospital charges for infant stays due to prematurity/low birth weight: $11.9 Billion*

• Maternity & related expenses:– Often the largest cost to employers’ health care

plans

* Source: Agency for Healthcare Research and Quality, 2000 Nationwide Inpatient SamplePrepared by March of Dimes Perinatal Data Center, 2003

March of Dimes Birth Defects Foundation

Mission:• To improve infant health by preventing infant mortality

and birth defects

The Continuum of Reproductive Health• Improving health of infants requires focusing on the

entire spectrum of reproductive health which extends from prior to conception through the first year of an infant’s life and throughout the woman’s childbearing years

• Preconceptional health is the cornerstone of healthy infants, children, families and communities

Conceptio

n

Birth

1 Yea

rFetal Infancy

20 wks 28 wks 4 wks

Spontaneous Abortion

Early Fetal

Late Fetal Neonatal

Postneonatal

Infant

Feto-Infant

Perinatal

I

II

III

Age at Loss

Ectopic

Critical Periods of Development

4 5 6 7 8 9 10 11 12Weeks gestation from LMP

Central Nervous SystemCentral Nervous System

HeartHeart

ArmsArms

EyesEyes

LegsLegs

TeethTeeth

PalatePalate

External genitaliaExternal genitalia

EarEar

Missed Period Mean Entry into Prenatal Care

Most susceptible time for major malformation

Unintended Pregnancies Unintended Pregnancies United States, 1994United States, 1994

78.0

58.5

39.733.1

40.8

50.7

0

20

40

60

80

15-19 20-24 25-29 30-34 35-39 >=40

Maternal Age

Percent

Source: National Survey of Family Growth, 1995Prepared by March of Dimes Perinatal Data Center, 2000

www.marchofdimes.com or peristats.modimes.org

www.health.state.ok.us

Percent of Births by Race/Ethnicity Oklahoma and US 1999-2001 Average

Infant MortalityUnited States, 1915-2000

0

20

40

60

80

100

120

1915 1925 1935 1945 1955 1965 1975 1985 1995

Rate per 1,000 live births

Source: National Center for Health Statistics, final mortality data

Prepared by March of Dimes Perinatal Data Center, 2002

Infant Mortality Rates Oklahoma and US, 1990-2000

OK IMR decrease 31.4% US IMR decrease 25.0%

Annual Black/White Infant Mortality Rate RatioUnited States, 1980-2000

2

2.1

2.2

2.3

2.4

2.5

2.6

Source: NCHS, final mortality data

Alexander G., SACIM, 2001.

1995-97 Birth Weight-Specific Infant Mortality Rates by Race

1

10

100

1000

White Black

Source: NCHS, final mortality data

Alexander G., SACIM, 2001.

Selected Leading Causes of Infant Mortality United States, 1990 and 2000

24.8

62.1

108.4

141.8

68.5

130.3

96.5

198.1

0 50 100 150 200 250

RDS

SIDS

Preterm / LBW

Birth Defects

1990

2000

Rate per 100,000 live births

Source: National Center for Health Statistics, 1990 final mortality data and 2000 linked birth/infant death data

Prepared by March of Dimes Perinatal Data Center, 2002

1

2

3

6

2000

Rank

Leading Causes of Infant Mortality Oklahoma and US, 2000

7

11.7

74.4

8.511.9

69.0

4.5

7.6

90

1

10

100

IMR Preterm Adeq/+ PNC

United States Oklahoma HP2010

State Rankings : 43 32 41

IMR, PTB, and Adequate/+ PNCUS and OK, 1998-2000 avg and HP2010

Low Birthweight

Births7.8%

Preterm Births12.0%

Birth Defects~3-4%

Overlap in LBW, Preterm and Birth Defects U.S. (2002)

Among LBW: 2/3 are preterm

Among preterm: almost 50% are LBW (some preterm

are not LBW)

9.410.8

11.9 12.0

10.1

7.6

0

4

8

12

1981 1991 2001 2002 2007 2010

Preterm BirthsPreterm BirthsUnited States, 1981, 1991, 2001, 2002United States, 1981, 1991, 2001, 2002

Source: National Center for Health Statistics, final natality dataPrepared by March of Dimes Perinatal Data Center, 2003

Percent

Healthy People Objective

March of Dimes Objective

27 Percent Increase 1981-2001

Preterm Births (<37 weeks)by Maternal Race/Ethnicity, US, 2001

11.0

17.5

13.2

10.311.4 11.9

0

6

12

18

White Black NativeAmerican

Asian orPacific

Islander

Hispanic All Races

Percent

Preterm is less than 37 weeks gestation

Hispanics can be of any race

Source: National Center for Health Statistics, 2000 final natality data

Prepared by March of Dimes Perinatal Data Center, 2002

Preterm Delivery (<37 wks) Oklahoma and US, 1991-2001

OK PTB increase 0.8% US PTB increase 10.2%

Singleton Preterm Births by Race/EthnicityUnited States, 1990 and 2000

10.3

7.5

17.9

10.38.7

15.9

0

5

10

15

20

Hispanic Non-Hispanic White Non-Hispanic Black

1990

2000

Percent

Source: National Center for Health Statistics, 1999 final natality data

Prepared by March of Dimes Perinatal Data Center, 2002

Very Preterm (<32 wks) by Maternal Age Oklahoma and US, 1999-2001 average

Types of Preterm BirthTypes of Preterm Birth

SpontaneousPreterm Labor

SpontaneousPremature Ruptureof the Membranes

MedicalIntervention

PretermBirth

While this suggests distinct pathways, many of the risk factors for all 3 are similar

Risk Factors for Preterm Labor/Delivery• The best predictors of having a preterm birth are:

current multifetal pregnancya history of preterm labor/delivery or prior low birthweightmid trimester bleeding (repeat) some uterine, cervical and placental abnormalities

• Other risk factors:

–multifetal pregnancy

–maternal age (<17 and >35 yrs)

–black race

–low SES

–unmarried

–previous fetal or neonatal death

–3+ spontaneous terminations

–uterine abnormalities

–incompetent cervix

–genetic predisposition

–low pre-pregnant weight–obesity–infections–bleeding –anemia –major stress –lack of social supports–tobacco use–illicit drug use–alcohol abuse–folic acid deficiency

Folic Acid Deficiency

• Predisposes to:• NTDs

• Other birth defects (cleft lip/palate, cardiac,

limb reduction, urinary tract, omphalocele, trisomies)

• Early and recurrent pregnancy loss

• Low birth weight and prematurity

• ?Gestational hypertension

• Atherosclerotic vascular disease (stroke, CAD)

• Colorectal and cervical cancer

• Acute Lymphocytic Leukemia

• Alzheimer’s Disease

Folic Acid RecommendationsPrevent Recurrence, 1991• All women with a previous NTD pregnancy should

take 4 mg or 4000mcg interconceptionally

Prevent Occurrence, USPHS September, 1992• All women of childbearing potential should

consume 0.4 mg (400 micrograms) of folic acid daily

Food & Nutrition Board of IOM, 1998• Men (14 yr & older) 400 µg any source• Women (14 yr & older) 400 µg synthetic + food• Pregnancy 600 µg synthetic + food• Lactation 500 µg any source

www.cdc.gov/brfss

Folic Acid Knowledge and Behavior 1995 and 2003

32

10

21

79

28

2

4

52

0 10 20 30 40 50 60 70 80 90

Take folic aciddaily

Knew folic acidshould be taken

before pregnancy

Knew folic acid canprevent birth

defects

Aware of folic acid

1995

2003

Percentage of women ages 18-45

Reasons Why Women Do Not Take a Multivitamin Daily March of Dimes Folic Acid Survey, 2003

4

4

9

16

22

24

0 5 10 15 20 25 30

Costs too much

Don’t like taking pills

Already get balanced nutrition

Don't feel I need them

No particular reason

Forget to take

Percentage of women ages 18-45who do not take vitamins daiily

Things Women Reported Might Encourage them to Take a Multivitamin Daily

March of Dimes Folic Acid Survey, 2003

4

4

4

4

4

4

9

33

0 5 10 15 20 25 30 35

I f not in pill form

I f pregnant

Someone to remind me

Remembered to take

Needed vitamins

Feeling run down

Change in health

Advised by a health care provider

Percentage of women ages 18-45who do not take vitamins daiily

Factors that Contribute to Increasing Rates of Preterm Birth

• Increasing rates of births to women 35+ years of age• Increasing rates of multiple births• Indicated deliveries

– Epidurals– Induction (What happened to labor support?)– Enhanced management of maternal and fetal conditions– Patient preference/consumerism

• Substance abuse– Tobacco– Alcohol– Illicit drugs

• Bacterial and viral infections • Increased stress (catastrophic events, DV, racism)

Percent of Births by Maternal Age Oklahoma and US 1999-2001 Average

Multiple Birth Ratios Oklahoma and US, 1996-2001

Multiple Birth Ratios by Race*United States, 1980-2001

19.3 19.7 19.9 20.3 20.3 21.0 21.6 22.0 22.4 23.0 23.3 23.9 24.4 25.2 25.7 26.127.4

28.630.0 30.7 31.1

32.0

0

5

10

15

20

25

30

35

All Races White Black

Ratio per 1,000 live births

*Race of child from 1980-1988; Race of mother from 1989-2001Source: NCHS, final natality data, 1980-2001Prepared by March of Dimes Perinatal Data Center, 2003

Multiple Birth Ratios by Maternal Age Oklahoma and US, 1999-2001 average

Higher Order Birth Ratios by Race*United States, 1980-2001

37.0 38.2 40.3 43.3 45.151.2 48.3

56.2 61.069.2 72.8

81.4

95.5104.2

116.2127.5

152.6

173.6

193.5184.9 180.5 185.6

0

40

80

120

160

200

240

1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000

All Races White Black

Ratio per 100,000 live births

*Race of child from 1980-1988; Race of mother from 1989-2001Source: NCHS, final natality data, 1980-2001Prepared by March of Dimes Perinatal Data Center, February 2003

Risks of Adverse Pediatric Outcomes with ART

MultiplesTwins - 20-40% Triplets - 0.5-9.3%

• Prematurity• Low birth weight

Birth Defects? Complicated analysis

• Maternal: Low birth weight, Birth defects• Paternal: Chromosomal abnormalities• Procedures:

ICSI - Imprinting defects ?

Singletons Preterm Delivery Oklahoma and US, 1991-2001

Total and Primary Cesarean and VBAC Rates, United States, 1989-2001

All Delivery Methods Categories Oklahoma and US, 2001

Singleton Preterm Births by Delivery MethodUnited States, 1990 and 2000

9.3 9.2

11.2

13.2

9.89.3

0

5

10

15

Vaginal VBAC C-Section

1990

2000

Percent

All Substance Use Categories Oklahoma and US, 2001

Impact of Smoking• Smoking during pregnancy is responsible for:

– 20% of all LBW– 8% of preterm births – 5% of all perinatal deaths

• Pregnant smokers compared to nonsmokers are:– 2.0-5.0 times as likely to experience PPROM– 1.2-2.0 times as likely to deliver preterm– 1.5-10 times as likely to deliver a SGA infant– 1.5-3.5 times as likely to deliver a LBW infant

• Smoking increases risk of stillbirth (RR=1.4-1.6)– Risk increases with increased amount smoked

• Smoking during and after pregnancy increases risk for SIDS by 3-fold

The 5 A’s

1. Ask about tobacco use

2. Advise to quit

3. Assess willingness to make a quit attempt

4. Assist in quit attempt

5. Arrange follow-up

A Clinician’s Guide to Helping Pregnant Women Quit Smoking

www.cdc.gov/brfss

www.cdc.gov/brfss

Brain of healthy baby Brain of baby with FAS

Effects of Alcohol on Pregnancy

• Miscarriage• Premature birth• Low birth weight• FAS• ARBD - Alcohol-Related Birth Defects• ARND - Alcohol-Related

Neurodevelopmental Disorders• Birth complications

www.cdc.gov/brfss

www.cdc.gov/brfss

www.cdc.gov/brfss

www.cdc.gov/brfss

Can Preterm Labor be Prevented?

• Primary prevention is the goal– especially risk reduction in the preconceptional period

and early in pregnancy

• Preterm prevention programs have focused on risk assessment or prediction of preterm labor– risk assessment identifies only half of preterm births– during pregnancy most biomarkers, even in

combination with risk factors, do not have good positive predictive values

• Causation is the great unknown

What interventions may work?

“Most efforts to prevent preterm labor have not proven to be effective, and equally frustrating, most efforts at arresting preterm labor once started have failed”.

“The most important components of management, therefore, are aimed at preventing neonatal complications through the use of corticosteroids, and antibiotics to prevent GBS and avoiding traumatic deliveries.”

Goldenberg RL. The management of preterm labor. Obstet Gynecol 100 (5):1020-36, 2002.

Evidence Based Guidelines• Management of Preterm Labor, Evidence Report /Technology

Assessment, No 18, AHRQ, 2000 (www.ahrq.gov)• Assessment of Risk Factors for Preterm Birth,

ACOG Practice Bulletin, No 31, October 2001 (www.acog.gov)

• Perinatal Care at the Threshold of Viability,ACOG Practice Bulletin, No 38, September 2002

• Criteria for Determining Disability in Infants and Children: Low Birth Weight, Evidence Report/Technology Assessment No 70, AHRQ, 2003

• VBAC, Evidence Report/Technology Assessment, No 71, AHRQ, 2003

• Management of Preterm Labor, ACOG Practice Bulletin, No 43, May 2003

• Use of Progesterone to Reduce Preterm Birth ACOG Committee Opinion, No 291, November 2003

Management of Preterm LaborACOG Practice Bulletin, No 43, May 2003

• Level A (good and consistent scientific evidence)– There are no clear “first line” tocolytic drugs to manage PTL.

Clinical circumstances and physician preferences should dictate treatment

– Abs do not appear to prolong gestation and should be reserved for GBS prophylaxis in patients in whom delivery is imminent

– Neither maintenance treatment with tocolytic drugs nor repeated acute tocolysis improve perinatal outcome; neither should be undertaken as a general practice

– Tocolytics may prolong pregnancy for 2-7 days, which may allow for administration of steroids to improve fetal lung maturity and the consideration of maternal transport to a tertiary care facility

Management of Preterm LaborACOG Practice Bulletin, No 43, May 2003

• Level B (limited or inconsistent scientific evidence)

– Cervical ultrasound exam and fFN testing have good negative predictive value; thus, either approach or both combined may be helpful in determining which patient do not need tocolysis

– Amniocentesis may be used in women in PRL to assess fetal lung maturity and intraamniotic infection

– Bed rest, hydration and pelvic rest do not appear to improve the rate of preterm birth and should not be routinely recommended.

Recent Developments in Obstetrics

• Preelampsia– 5-11% of pregnancies (3% in England), 15% of pregnancy-related

deaths, 25% of VLBW

– uterine artery Doppler ultrasound can identify women at risk

– prophylactic low dose aspirin will reduce risk of preeclampsia and fetal death by 15%

– Antioxidants (vitamin C and E) promising

• Second trimester use of ultrasound to measure cervical length and the detection of vaginal fFn are better predictors of preterm birth than previous history

• There is no evidence that asymptomatic women with abnormal vaginal flora benefit from antimicrobials

Shennan HS. BMJ 327:604-608, 2003.

Recent Developments in Obstetrics• Evidence regarding prophylactic abs use is contradictory since

benefit may be related to the choice, route and timing of treatments• External cephalic version should be offered to women with term

breech presentation (3% increased risk of death or serious morbidity to their baby with breech delivery)

• Intrapartum interventions can be reduced by avoiding unnecessary electronic fetal monitoring, encouraging vaginal delivery with previous cesarean section and using low dose epidurals.

• ?fish oils- prospective trials needed• The biggest impact to prevent prematurity is probably simple: avoid

smoking

Shennan HS. BMJ 327:604-608, 2003.

March of Dimes Investment in the Science and Public Health of Preterm Delivery

• Toward Improving the Outcome of Pregnancy (TIOP I)- regionalization of perinatal care

• TIOP II - regionalization, continuum, elimination of health disparities• >$15 Million for research since 1985, 200 grants• Innovative community intervention trials (late-80’s)• Pittsburgh health community, contemporary intervention (P4

Project)• Six innovative epidemiology research initiatives to define

biomarkers and mechanisms (1998-2004)– Perinatal Epidemiological Research Initiative

(PERI)

March of Dimes PERIPerinatal Epidemiological Research Initiative

1998-2004

• Epidemiologic approaches to test biologically plausible hypotheses for the major determinants of preterm birth

• Examine the interactions of risk factors associated with prematurity and relevant biologic samples

Pathways to Preterm Labor/Delivery• Infection (ascending), 40%

– cytokines• Stress (maternal/fetal), 25%

– CRH• Bleeding (decidual hemorrhage,

abruption), 25%– thrombin

• Stretching (uterine distention), 10%

proteases

PTD

Uterine Contractions

Cervical change

• Infection: - Chorion-Decidual - Systemic

DecidualHemorrhageAbruption

CRHE1-E3

ThrombinThrombin Rc

PathologicalUterine

Distention

• Multifetal Preg• Polyhydram• Uterine abnorm

Inflammation

• Maternal-Fetal Stress

•Premature Onset of Physiologic Initiators

Activation of Maternal/Fetal

HPA Axis

CRH

+

+ChorionDecidua

uterotonins

Mechanical stretch

Gap jct

Oxt recepPG synthase

PROM

Ils, Fas LTNF

Lockwood CL. Unpublished data. 2002.

Prevention of Preterm Labor, Preterm Delivery and Prematurity

• Primary prevention– identifying and managing risks– risk reduction approach and strategies to reproductive health– prevent PTL

• Secondary prevention– prevent preterm delivery

• Tertiary prevention– prevent/minimize complications of prematurity

Innovative Perspectives

“The prevention of preterm delivery will require intervention at an earlier stage in the processes that lead to it.”

• Strategies are needed to prevent infections• Therapies should be rigorously evaluated in women who

have recurrent PTD due to disturbances in uterine blood vessels and blood flow

• Refine assisted reproductive techniques (ART) to reduce the occurrence of twin and higher-order multifetal pregnancies

Lockwood CJ. Predicting premature delivery--No easy task. NEJM, 2002, 346 (4):282-4.

Interventions that Work

• Early, comprehensive, accessible prenatal care• Educate all pregnant women about preterm labor

signs and symptoms• Screen and treat all UTIs and STIs

• Identify cigarette smokers and intervene (5As)

• Assess for alcohol use and intervene

• Identify illicit substance users and intervene

• Assess for domestic violence and intervene

• Eliminate folic acid deficiency

• Reduce major stress levels early and throughout pregnancy

Interventions that Work

• Provide culturally sensitive, age appropriate preconceptional care (risk reduction focus)

- www.marchofdimes.com preconceptional curriculum for ob/gyns, pediatricians, internists, family practitioners

• Promote optimal weight

• Exercise and activity

• Good mental health

• Manage all chronic conditions (hypertension, diabetes)

• Oral health and periodontal disease

• ?Omega 3 fatty acid

www.cdc.gov/brfss

• Progesterone study (high risk by history)– Multisite US, Meis, et, al MFMU-NICHD (preliminary)

by ~ 30%– da Fonesca (preliminary)

by 50%+• Clotting abnormalities (Thrombophilia) - Yale

• Genetic • Can screen • Can treat

• Stress research - CDC, MOD (PERI), Others

Promising Research DirectionsPromising Research Directions

Take Home Message

• All pregnant women are at risk for preterm labor and birth

• Intervene throughout the continuum of reproductive health for women and men

• Everyone can make a difference

March of Dimes

www.marchofdimes.com

askus@marchofdimes.com

Premature Birth:The answers can’t come soon enough

Thank you for your attention

Additional Resources

www.marchofdimes.com www.jjpi.com

this continuing education presentation is sponsored by the

March of Dimes - Johnson & Johnson Pediatric Institute Grand Rounds Program

as part of the

March of Dimes National Prematurity Campaign