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Compendium on Preterm Birth. Produced in cooperation with: American Academy of Pediatrics The American College of Obstetricians and Gynecologists Association of Women’s Health, Obstetric and Neonatal Nurses. Epidemiology & Biology of Preterm Birth. © March of Dimes 2006. Objectives.

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compendium on preterm birth

Compendium on Preterm Birth

Produced in cooperation with:

American Academy of Pediatrics

The American College of Obstetricians and Gynecologists

Association of Women’s Health, Obstetric and Neonatal Nurses

Epidemiology & Biology of Preterm Birth

© March of Dimes 2006

objectives
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
definitions
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.

definitions4
Low birthweight (LBW)

infant who weighs less than 2,500 grams at delivery

Very low birthweight (VLBW)

infant who weighs less than 1,500 gramsat delivery

Extremely low birthweight (ELBW)

infant who weighs less than 1,000 gramsat delivery

Definitions

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

prematurity low birthweight u s 2003
< 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 file

Prepared by March of Dimes Perinatal Data Center, 2006.

overlap in lbw preterm birth defects 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 file. Prepared by the March of Dimes Perinatal Data Center, 2006.

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

Low

Birthweight

Births

7.9%

Preterm

Births

12.3%

Among LBW: 2/3 are preterm

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

Birth Defects

~3-4%

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.

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

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

(36 Weeks)

(35 Weeks)

(<32 Weeks)

(32 Weeks)

(34 Weeks)

(33 Weeks)

preterm very preterm births united 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.

Preterm & Very Preterm BirthsUnited States, 1993-2003

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.

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

2002

Rank

Rate per 100,000 live births

1

2

3

6

preterm births united 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.

Preterm BirthsUnited States, 1983-2003

Percent

Healthy People Objective

28 Percent Increase

preterm births by 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.

Preterm Birthsby Maternal Age, United States, 2003

Percent

preterm births by maternal race ethnicity u s 1993 2003
Preterm Births by Maternal Race/Ethnicity, U.S., 1993-2003

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.

slide13

Preterm Birth Rates by State

United States, 2003

U.S. Total = 12.3%

Percent of Live Births

Over 13.0 (16)

11.6 to 13.0 (18)

Under 11.6 (17)

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.

economic consequences of preterm birth
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 birthweight

2Defined as having a principal diagnosis of prematurity

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

24.2

13.6

2.0

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

distribution of hospital stays hospital charges u s 2003

100

80

60

40

20

0

Infant Hospital Stays

Infant Hospital Charges

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

All other infant stays 4,301,000

~91%

Hospital charges for all other infant stays $18.6 billion

Infant stays with any diagnosis of prematurity

413,000 ~9%

12.9

Hospital charges for infant stays with any diagnosis of prematurity

$18.1 billion

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

percent of hospital charges for preterm birth by expected payer u s 2002
Percent of Hospital Charges for Preterm Birth by Expected Payer, U.S., 2002

Medicaid46.3%

Uninsured/Self Pay2.3%

Almost half of hospital charges

for premature infants, or about

$7.4 billion, were billed to employers

and other private insurers.

Private/Commercial47.8

Other*3.6%

*Includes Medicare

Source: Agency for Healthcare Research and Quality, 2002. Nationwide Inpatient Sample.Prepared by March of Dimes Perinatal Data Center, 2006.

costs to employers
Costs to Employers

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 expenses

Long-term Care Costs

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

public opinion about prematurity
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

Preterm Birth A Common, Complex Disorder
preterm birth
#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
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 prematurity
The Morbidity of Prematurity

Neonatal

  • Respiratory distress syndrome (RDS)
  • Intraventricular hemorrhage (IVH) & periventricular leukomalacia (PVL)
  • Necrotizing enterocolitis (NEC)
  • Patent ductus arteriosus (PDA)
  • Infection
  • Metabolic abnormalities
  • Nutritional deficiencies

Short term

  • Feeding and growth difficulties
  • Infection
  • Apnea
  • Neurodevelopmental difficulties
  • Retinopathy
  • Transient dystonia

Long term

  • Cerebral palsy
  • Sensory deficits
  • Special health care needs
  • Incomplete catch-up growth
  • School difficulties
  • Behavioral problems
  • Chronic lung disease

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

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.

Perinatal Morbidity & Gestational Age
classification of preterm birth
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.

spontaneous preterm births
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
clinical indications for preterm deliveries
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

Demographic Characteristics of Populations at Risk for Preterm Birth
known risk factors for preterm birth
Known Risk Factors for Preterm Birth

Epidemiologic

  • 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

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

known risk factors for preterm birth continued
Known Risk Factors forPreterm Birth(continued)

Inflammation

Decidual hemorrhage

  • systemic maternal disease
  • infections
  • preterm premature rupture of membranes (PPROM)
  • fetal / placental anomalies
  • bleeding
  • trauma

Overdistension/uterine problems

Activation of maternal

hypothalamic pituitary adrenal

(HPA) axis

  • multifetal pregnancy
  • overdistension
  • uterine abnormalities
  • cervical abnormalities
  • stress / violence

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

common risk factors for preterm birth
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.

epidemiology of spontaneous ptb
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

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

preterm births by plurality 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

Preterm Births by PluralityUnited States, 2003

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

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

Ratio per 1,000 live births

recurrence risk of preterm birth
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
recurrent preterm delivery
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 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 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.

Transvaginal Cervical Sonography
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.

Cervical Effacement = T Y V U

T

Y

V

U

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.

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

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.

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

NICHD MFMU Network

cervical length new information from ultrasound
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.

a continuum of cervical function
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

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

pathways to preterm birth
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 birth45

Source: Lockwood CL. Unpublished data, 2002.

Pathways to Preterm Birth

Inflammation

Decidual

Hemorrhage

Activation of Maternal-FetalHPA Axis

Pathological Uterine

Distention

• Infection:

- Chorion-Decidual

- Systemic

Abruption

• Multifetal Pregnancy

• Polyhydramnios

• Uterine Abnormality

• Maternal-Fetal Stress

• Premature Onset of Physiologic Initiators

Thrombin

Thrombin Rc

Ils, Fas L

TNF

Mechanical Stretch

Gap jct

PG synthase

Oxt recep

CRH

E1-E3

Chorion

Decidua

+

CRH

+

proteases

uterotonins

PPROM

Uterine Contractions

Cervical Change

PTD