compendium on preterm birth epidemiology & biology of preterm birth produced in cooperation...

Compendium on Preterm BirthCompendium on Preterm Birth

Epidemiology & Biology Epidemiology & Biology of Preterm Birthof Preterm Birth

Produced in cooperation with:American Academy of PediatricsAmerican Academy of Pediatrics

The American College of Obstetricians and GynecologistsThe American College of Obstetricians and Gynecologists

Association of Women’s Health, Obstetric and Neonatal NursesAssociation of Women’s Health, Obstetric and Neonatal Nurses

© March of Dimes 2006

Compendium on Preterm Birth© March of Dimes 2006Epidemiology & Biology of Preterm Birth

Objectives

At the completion of this section, participants should be able to:– Describe the epidemiologic and economic factors

associated with preterm birth– Recognize:

• Definitions• Major risk factors• Pathways leading to preterm birth • Clinical diagnosis

– Express the significance of preterm birth as an important public health issue


Preterm (or premature) infant– infant born before 37 completed weeks of gestation

Late preterm infant (a recently identified category)– infant born between 34 and 36 weeks gestation

Moderately preterm infant– infant born between 32 and 36 completed weeks of

gestation Very preterm infant

– infant born before 32 completed weeks of gestation

Definitions

Sources: Iams JD, Creasy RK. Preterm labor and delivery, Chapter 34. In: Maternal-Fetal Medicine: Principles and Practice, 5th ed., 2004; Davidoff MJ et al. Semin Perinatol 2006;30:8-15.


Definitions

Low birthweight (LBW)– infant who weighs less than 2,500 grams at

delivery Very low birthweight (VLBW)

– infant who weighs less than 1,500 grams at delivery

Extremely low birthweight (ELBW)– infant who weighs less than 1,000 grams at

delivery

Source: Iams JD, Creasy RK. Preterm labor and delivery, Chapter 34. In: Maternal-Fetal Medicine: Principles and Practice, 5th ed., 2004.


< 1,000 grams 0.7% (of live births)– Most (99.3%) are preterm

1,000-2,500 grams 7.2%– 63.9% are preterm

> 2,500 grams 92.1%– 7.6% are preterm

Prematurity & Low Birthweight, U.S., 2003

Low birthweight is less than 2,500 grams (5 1/2 pounds). Preterm is less than 37 completed weeks gestation.

Source: National Center for Health Statistics, 2003 natality filePrepared by March of Dimes Perinatal Data Center, 2006.


Low birthweight is less than 2,500 grams (5 1/2 pounds). Preterm is less than 37 completed weeks gestation.Source: National Center for Health Statistics, 2003 natality file. Prepared by the March of Dimes Perinatal Data Center, 2006.

Overlap in LBW, Preterm & Birth Defects, U.S., 2003

Low Birthweight

Births7.9%

Preterm Births12.3%

Birth Defects~3-4%

Among LBW: 2/3 are preterm

Among preterm: more than 43% are LBW (some preterm are not LBW)


All Preterm Births by Gestational Age, U.S., 2003

Preterm is less than 37 completed weeks gestation. Source: National Center for Health Statistics, 2003 natality file. Prepared by the March of Dimes Perinatal Data Center, 2006.

13.0%

21.2%

5.1%7.7%

16.0%

37.1%

(34 Weeks) (33 Weeks)(32 Weeks)

(<32 Weeks)

(35 Weeks)

(36 Weeks)

71% of PTB is at 34, 35, 36 weeks


Preterm & Very Preterm BirthsUnited States, 1993-2003

Preterm is less than 37 completed weeks gestation. Very preterm is less than 32 completed weeks gestation.Source: National Center for Health Statistics, final natality data. Prepared by March of Dimes Perinatal Data Center, 2006.

11.6 11.8 11.6 11.9 12.1 12.3

7.6

11.011.011.0 11.0 11.4

0

2

4

6

8

10

12

14

1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2010

Very Preterm Preterm

Percent of live births

Healthy People

Objective


Selected Leading Causes of Infant Mortality*United States, 1992 & 2002

*Deaths to infants less than one year of age. Source: National Center for Health Statistics, 1992 final mortality data and 2002 period-linked birth/infant death data. Prepared by the March of Dimes Perinatal Data Center, 2006.

23.6

57.1

115.3

140

50.8

120.3

99.3

183.2

0 50 100 150 200

RDS

SIDS

Preterm / LBW

Birth Defects

1992

2002

Rate per 100,000 live births

1

2

3

6

2002

Rank


Preterm BirthsUnited States, 1983-2003

Preterm is less than 37 completed weeks gestation. Source: National Center for Health Statistics, 2003 final natality data. Prepared by March of Dimes Perinatal Data Center, 2006.

9.611.0

12.3

7.6

0

2

4

6

8

10

12

14

1983 1993 2003 2010

Percent

Healthy People

Objective28 Percent Increase


Preterm Birthsby Maternal Age, United States, 2003

Preterm is less than 37 completed weeks gestation

Source: National Center for Health Statistics, 2003 final natality data. Prepared by March of Dimes Perinatal Data Center, 2006.

15.9

13.412.2

11.3 11.7

13.5

16.3

12.3

0

2

4

6

8

10

12

14

16

18

<18 18-19 20-24 25-29 30-34 35-39 40+ All Ages

Percent


Preterm Births by Maternal Race/Ethnicity, U.S., 1993-2003

18.6 18.2 17.8 17.5 17.6 17.6 17.6 17.4 17.6 17.7 17.8

11 10.9 10.9 10.9 11.2 11.4 11.4 11.2 11.4 11.6 11.9

9.49.1 9.3

11.31110.810.410.510.29.99.5

0

5

10

15

20

1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

NH White NH Black Hispanic

Percent

Preterm is less than 37 completed weeks gestation.Source: National Center for Health Statistics, final natality data.

Prepared by March of Dimes Perinatal Data Center, 2006.


Preterm Birth Rates by StateUnited States, 2003

Note: Value in ( ) = number of states (includes District of Columbia). Value ranges are based on equal counts.

Source: National Center for Health Statistics, 2003 final natality data. Prepared by March of Dimes Perinatal Data Center, 2005.

U.S. Total = 12.3%

Percent of Live Births

Over 13.0 (16)

11.6 to 13.0 (18)

Under 11.6 (17)


Economic Consequences of Preterm Birth

Hospital charges for premature infants1 totaled $18.1 billion in 2003.

Premature infants accounted for half of the hospital charges for all infants($36.7 billion).

The average charge for the most severe stays2 was $77,000 compared to $1,700 for an uncomplicated newborn stay.

1Includes any diagnosis of prematurity/low birthweight2Defined as having a principal diagnosis of prematuritySource: Agency for Healthcare Research and Quality, 2003 Nationwide Inpatient Sample.Prepared by March of Dimes Perinatal Data Center, 2006.


Average Length of Stay for Selected Inpatient Infant Hospitalizations, U.S., 2003

0

5

10

15

20

25

uncomplicated newborn any diagnosis ofprematurity/lbw

principal diagnosis ofprematurity/lbw

2.0

13.6

24.2

Agency for Healthcare Research and Quality, 2003. Nationwide Inpatient Sample.Prepared by March of Dimes Perinatal Data Center, 2006.


0

20

40

60

80

100

Infant Hospital Stays Infant Hospital Charges

Distribution of Hospital Stays & Hospital Charges, U.S., 2003

All other infant stays

4,301,000

~91%

Agency for Healthcare Research and Quality, 2003. Nationwide Inpatient Sample. Prepared by March of Dimes Perinatal Data Center, 2006.

12.9

Infant stays with any diagnosis of prematurity

413,000 ~9%

Hospital charges for all other infant stays $18.6 billion

Hospital charges for infant stays with any

diagnosis of prematurity

$18.1 billion


Percent of Hospital Charges for Preterm Birth by Expected Payer, U.S., 2002

*Includes MedicareSource: Agency for Healthcare Research and Quality, 2002. Nationwide Inpatient Sample.

Prepared by March of Dimes Perinatal Data Center, 2006.

Almost half of hospital charges

for premature infants, or about

$7.4 billion, were billed to employers

and other private insurers.

Medicaid46.3%

Other*3.6%

Private/Commercial

47.8

Uninsured/Self Pay

2.3%


Costs to Employers

Full-termDelivery

PretermDelivery

HospitalExpenses $1,210 $35,034

PhysicianOffice Visits $1,518 $ 6,079

DrugExpenses $ 102 $ 497

Total $2,830 $41,610

Based on analysis of births in 2001 followed for 12 months. Expenditures have been adjusted to 2004 dollars using the medical component of the CPI.

Data largely from self-insured U.S. employers.Research conducted and underwritten by Thomson Medstat.


Long-term Care Costs Health-care costs

– e.g., monetary value related to use of community health services

Educational costs – e.g., additional assistance (such as special education) required as a

result of school failure & learning problems

Social service costs – e.g., utilization of developmental services such as day care programs,

case management & counselling, or respite care & residential care

Out-of-pocket expenses – e.g., additional travel costs related to going to health & social care

providers or accommodation expensesSources: Petrou S et al. Child Care Health Dev. 2001;27:97-115; Petrou S et al. Early Hum Dev. 2006;82:77-84.


Many women think a baby born prematurely is “meant to be,” and its preterm birth can’t be prevented.

U.S. adults do not perceive preterm birth to be a serious public health problem.

Source: Massett HA et al. Am J Prev Med 2003; 24:120-7.

Public Opinion About Prematurity


Preterm Birth A Common, Complex Disorder

Genetic contribution Environmental influences Gene-environment interactions


#1 cause of neonatal mortality (<28 days) in the U.S.

#2 cause of infant mortality (<1 year) in the U.S.– #1 cause of infant mortality for non-Hispanic black

infants in the U.S.

Sources: Mathews TJ, MacDorman MF. Natl Vital Stat Rep 2006;54:1-29; National Center for Health Statistics, 2003 period- linked birth/infant death data. Prepared by March of Dimes Perinatal Data Center, 2006.

Preterm Birth


Perinatal Mortality & Gestational Age

Source: Mercer BM. Preterm premature rupture of the membranes. Obstet Gynecol 2003;101:178-93. Reproduced with permission from Lippincott Williams & Wilkins.


The Morbidity of PrematurityNeonatal Respiratory distress

syndrome (RDS) Intraventricular

hemorrhage (IVH) & periventricular leukomalacia (PVL)

Necrotizing enterocolitis (NEC)

Patent ductus arteriosus (PDA)

Infection Metabolic abnormalities Nutritional deficiencies

Long term Cerebral palsy Sensory deficits Special health care

needs Incomplete catch-up

growth School difficulties Behavioral problems Chronic lung disease

Short term Feeding and growth

difficulties Infection Apnea Neurodevelopmental

difficulties Retinopathy Transient dystonia



Perinatal Morbidity & Gestational Age

Source: Mercer BM. Preterm premature rupture of the membranes. Obstet Gynecol 2003;101:178-93. Reproduced with permission from Lippincott Williams & Wilkins.


What are the conditions leading to preterm birth?

Spontaneous - 75%– Preterm labor– Preterm premature rupture of membranes (PPROM)– Multiple gestation– Cervical insufficiency– Other related diagnoses

Clinically Indicated - 25%– Mother or fetus at risk

Classification of Preterm Birth

Sources: Goldenberg RL et al. Am J Public Health 1998;88:233-8; Meis PJ et al. Am J Obstet Gynecol 1995;173:597-602; Meis PJ et al. Am J Obstet Gynecol 1998;178:562-7.


Clinical presentations– Preterm labor - 50-60%– Preterm premature rupture of membranes (PPROM) -

40-50%

Risk factors similar– PPROM

• More often smokers, 2nd trimester bleeding, low socioeconomic status (SES)

50% have no risk factors

Sources: Goldenberg RL et al. Am J Public Health 1998;88:233-8; Meis PJ et al. Am J Obstet Gynecol 1995;173:597-602; Meis PJ et al. Am J Obstet Gynecol 1998;178:562-7.

Spontaneous Preterm Births


Preeclampsia 43%

Fetal distress 28%

Inadequate intrauterine fetal growth 10%

Abruption 7%

Fetal demise 7%Source: Meis PJ et al. Am J Obstet Gynecol 1998;178:562-7.

Clinical Indications for Preterm Deliveries


Demographic Characteristics of Populations at Risk for Preterm Birth

Maternal age (<18 and >35 years) Low socioeconomic status (SES) Unmarried African-American ancestry


– history of preterm birth– unintended pregnancy– previous fetal or neonatal death– 3+ spontaneous losses– assisted reproductive technology

(ART)– genetic predisposition– folic acid deficiency

– environmental toxins– low pre-pregnancy weight– obesity– anemia – lack of social support– tobacco use– alcohol abuse– illicit drug use

Known Risk Factors for Preterm Birth

Epidemiologic



– systemic maternal disease– infections– preterm premature rupture of

membranes (PPROM)

– fetal / placental anomalies

– bleeding

– trauma

Known Risk Factors forPreterm Birth (continued)

Inflammation

Overdistension/uterine problems– multifetal pregnancy– overdistension– uterine abnormalities– cervical abnormalities

Decidual hemorrhage

– stress / violence

Activation of maternal hypothalamic pituitary adrenal(HPA) axis



Common Risk Factors for Preterm Birth

Multiple gestation

Infection

Stress

Bleeding

Nutrition

Excessive physical activity

Prior preterm birth Uterine factors

– Cervical length– Contractions– Anomalies– Distention

Ancestry and ethnicity

Source: Martin JA et al. Natl Vital Stat Rep. 2005;54:1-116; Iams JD, Creasy RK. Preterm labor and delivery, Chapter 34. In: Maternal-Fetal Medicine: Principles and Practice, 5th ed., 2004.


Multiple Gestation OR 6 – compared to singleton births

Prior Preterm Delivery OR 4– compared to no history of preterm birth

2nd Trimester Bleeding OR 2 or >– compared to no early bleeding (before 28 weeks)

Genito-Urinary (GU) Tract Infection OR 2– compared to no GU infection

African-American OR 2– compared to non African-American ancestry

Body Mass Index <19.8 kg/m2 OR 2– compared to body mass index 19.8 kg/m2

Epidemiology of Spontaneous PTB



Preterm Births by PluralityUnited States, 2003

Preterm is less than 37 completed weeks gestation. Source: National Center for Health Statistics, 2003 final natality data. Prepared by March of Dimes Perinatal Data Center, 2006

10.6

59.3

93.7

0

25

50

75

100

Singletons Twins Higher order

Percent


Multiple Birth Ratios by Race*United States, 1980-2003

Multiple births include twins, triplets, and higher order births. *Race of child from 1980-1988; race of mother from 1989-2003. Source: National Center for Health Statistics, 1980-2003 final natality data. Prepared by March of Dimes Perinatal Data Center, 2006

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

33.0 33.3

0

5

10

15

20

25

30

35

40

All Races White Black

Ratio per 1,000 live births


Rises with increased number of preterm

deliveries (PTDs)

Rises as gestational age of prior PTD declines

Most recent birth is more predictive

Risk greater in African-Americans

Source: Mercer BM et al. Am J Obstet Gynecol 1999;181:1216-21.

Recurrence Risk of Preterm Birth


Population-based cohort study — Georgia 1980 to 1995

122,722 white women and 56,174 black women

Of 1,023 white women w/ 1st delivery @ 20-31 weeks– 8.2% delivered 2nd at 20-31 weeks– 20.1% delivered 2nd at 32-36 weeks – Total preterm deliveries = 28.3% < 36 wk28.3% < 36 wk

Of 1,084 black women w/ 1st delivery @ 20-31 weeks– 13.4% delivered 2nd at 20-31 weeks– 23.4% delivered 2nd at 32-36 weeks – Total preterm deliveries = 36.8% < 36 wk36.8% < 36 wk

Source: Adams MM et al. JAMA 2000;283:1591-6.

Recurrent Preterm Delivery


Transvaginal Cervical Sonography

Source: Reprinted from Ultrasonography in Obstetrics and Gynaecology, 4th ed., Callen PW, Copyright 2000, with permission from Elsevier.


Cervical Effacement = T Y V U

Source: Zilianti M et al. Monitoring the effacement of the uterine cervix by transperineal sonography: a new perspective. J Ultrasound Med 1995;14:719-24. Reproduced with permission from the American Institute of Ultrasound in Medicine.

T Y

UV


Relative Risk of Spontaneous Preterm Delivery < 35 Weeks by Percentile of Cervical Length at 24 Weeks

Iams JD, Goldenberg RL, Meis PJ, et al. The length of the cervix and the risk of spontaneous premature delivery. N Engl J Med 1996;334:567-72. Copyright 1996 Massachusetts Medical Society. All rights reserved.

NICHD MFMU Network


Risk of Spontaneous Preterm Delivery < 35 weeks by Cervical Length at 24 weeks

Iams JD, Goldenberg RL, Meis PJ, et al. The length of the cervix and the risk of spontaneous premature delivery. N Engl J Med 1996;334:567-72. Copyright 1996 Massachusetts Medical Society. All rights reserved.

NICHD MFMU Network


Cervical length is a bell curve.

The risk of spontaneous preterm delivery increases as cervical length decreases.

This occurs across the entire range of cervical length, not just < 10th %.

Cervical LengthNew Information from Ultrasound

Source: Iams JD et al. N Engl J Med 1996;334:567-72; Taipale P, Hiilesmaa V. Obstet Gynecol. 1998;92:902-7; Goldenberg RL et al. Am J Public Health 1998;88:233-8.


Cervical function is variable and relative– Long cervix = Low risk of preterm birth, more likely

to carry twins to term– Short cervix = Greater risk of preterm birth– Very short cervix = Greatest risk of early preterm

birth

Why is the cervix short?– Individual or combined effect of:

• Biological variation • Inflammation• Contractions • Surgery/procedure

A Continuum of Cervical Function



Inflammation Infection - ~40%

Activation of the maternal-fetal hypothalamic– pituitary–adrenal (HPA) Axis Stress - ~30%

Decidual hemorrhage Abruption - ~20%

Uterine distension Stretching - ~10%

Pathways to Preterm Birth

Sources: Lockwood CJ, Iams JD. Preterm labor and delivery. Precis: Obstetrics, 3rd ed. ACOG, 2005; Lockwood CJ, Kuczynski E. Paediatr Perinat Epidemiol 2001;15:78-89.


Pathways to Preterm Birth

Source: Lockwood CL. Unpublished data, 2002.

proteases

PTDUterine

ContractionsCervical Change

• Infection: - Chorion-Decidual - Systemic

DecidualHemorrhage

CRHE1-E3

ThrombinThrombin Rc

Pathological UterineDistention

• Multifetal Pregnancy• Polyhydramnios• Uterine Abnormality

Inflammation

• Maternal-Fetal Stress

• Premature Onset of Physiologic Initiators

Activation of Maternal-Fetal

HPA Axis

CRH+

ChorionDecidua

uterotonins

Mechanical StretchGap jctPG synthaseOxt recep

PPROM

Ils, Fas LTNF

+

Abruption

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