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Compendium on Preterm Birth
Epidemiology & Biology

of 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
© March of Dimes 2006

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

Epidemiology & Biology of Preterm Birth © March of Dimes 2006
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
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)
delivery
 Extremely low birthweight (ELBW)
delivery
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
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
Preterm
Birthweight
Births Births
7.9% 12.3%
Among LBW:
2/3 are preterm
Among preterm:
more than 43% are
Birth Defects LBW (some preterm
~3-4% are not LBW)
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.

All Preterm Births by Gestational Age, U.S., 2003
71% of PTB is at 34, 35, 36 weeks 37.1%
(36 Weeks)
21.2%
(35 Weeks) 16.0%
(<32 Weeks)
13.0% 5.1%
7.7% (32 Weeks)
(34 Weeks) (33 Weeks)
Source: National Center for Health Statistics, 2003 natality file. Prepared by the March of Dimes Perinatal Data Center, 2006.

Preterm & Very Preterm Births
United States, 1993-2003
Percent of live births

14
11.6 11.8 11.6 11.9 12.1 12.3
12 11.0 11.0 11.0 11.0 11.4
10
7.6
8
6
4
2
0
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2010
Healthy
Very Preterm Preterm People
Objective
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.

Selected Leading Causes of Infant Mortality*
United States, 1992 & 2002
2002 Rate per 100,000 live births

Rank
183.2
1 Birth Defects
140
99.3
2 Preterm / LBW
115.3
1992
120.3 2002
SIDS
3 57.1
50.8
RDS
6 23.6
0 50 100 150 200
*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.

Preterm Births
Percent
14
12.3
12 11.0
9.6
10
7.6
8
6
4
2
0
1983 1993 2003 2010
Healthy
28 Percent Increase People
Objective

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

Preterm Births
by Maternal Age, United States, 2003
Percent
18
15.9 16.3
16
13.4 13.5
14
12.2 12.3
11.3 11.7
12
10
8
6
4
2
0
<18 18-19 20-24 25-29 30-34 35-39 40+ All Ages
Preterm is less than 37 completed weeks gestation


Preterm Births by Maternal
Race/Ethnicity, U.S., 1993-2003
Percent
20 18.6 18.2 17.8 17.5 17.6 17.6 17.6 17.4 17.6 17.7 17.8
15
11.4 11.4 11.4 11.6 11.9
11 10.9 10.9 10.9 11.2 11.2 11.3
10.2 10.5 10.4 10.8 11
9.4 9.5 9.9
10 9.1 9.3
0
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003
NH White NH Black Hispanic

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

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.

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
1Includes
2Defined
any diagnosis of prematurity/low birthweight
as having a principal diagnosis of prematurity
$77,000 compared to $1,700
Source: Agency for Healthcare Research and Quality, 2003 Nationwide
Inpatient Sample. for an uncomplicated
newborn stay.

Average Length of Stay for Selected
Inpatient Infant Hospitalizations, U.S., 2003
24.2
25
20
13.6
15
10
5 2.0
0
uncomplicated newborn any diagnosis of principal diagnosis of
prematurity/lbw prematurity/lbw
Agency for Healthcare Research and Quality, 2003. Nationwide Inpatient Sample.

Distribution of Hospital Stays
& Hospital Charges, U.S., 2003
100
80 All other Hospital charges

infant stays for all other infant
4,301,000 stays $18.6 billion
60 ~91%
Infant stays with any

40 diagnosis of
prematurity 12.9 Hospital charges for
413,000 ~9% infant stays with any
20 diagnosis of
prematurity
$18.1 billion
0
Infant Hospital Stays Infant Hospital Charges
Agency for Healthcare Research and Quality, 2003. Nationwide Inpatient Sample.

Percent of Hospital Charges for Preterm
Birth by Expected Payer, U.S., 2002
Medicaid
Uninsured/
46.3%
Self Pay
2.3%
Almost half of hospital charges

for premature infants, or about
$7.4 billion, were billed to employers
and other private insurers.
Private/ Other*
Commercial 3.6%
47.8
*Includes Medicare
Source: Agency for Healthcare Research and Quality, 2002. Nationwide Inpatient Sample.

Costs to Employers
Full-term Preterm
Delivery Delivery
Hospital
Expenses $1,210 $35,034
Physician
Office Visits $1,518 $ 6,079
Drug
Expenses $ 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 expenses
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.

Preterm Birth
A Common, Complex Disorder
 Genetic contribution
 Environmental influences
 Gene-environment interactions

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.

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
Neonatal Short term Long term
 Respiratory distress  Feeding and growth  Cerebral palsy
syndrome (RDS) difficulties  Sensory deficits
 Intraventricular  Infection  Special health care
hemorrhage (IVH) &  Apnea needs
periventricular  Neurodevelopmental  Incomplete catch-up
leukomalacia (PVL) difficulties growth
 Necrotizing enterocolitis  Retinopathy  School difficulties
(NEC)
 Transient dystonia  Behavioral problems
 Patent ductus
arteriosus (PDA)  Chronic lung disease
 Infection
 Metabolic abnormalities
 Nutritional deficiencies
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.

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
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.

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.

Demographic Characteristics of
Populations at Risk for Preterm Birth
 Maternal age (<18 and >35 years)

 Low socioeconomic status (SES)
 Unmarried
 African-American ancestry

Known Risk Factors for
Preterm Birth
Epidemiologic
– history of preterm birth – environmental toxins
– unintended pregnancy – low pre-pregnancy weight
– previous fetal or neonatal death – obesity
– 3+ spontaneous losses – anemia
– assisted reproductive technology – lack of social support
(ART) – tobacco use
– genetic predisposition – alcohol abuse
– folic acid deficiency – illicit drug use

Known Risk Factors for
Preterm Birth (continued)
Inflammation Decidual hemorrhage

– systemic maternal disease – fetal / placental anomalies
– infections – bleeding
– preterm premature rupture of – trauma
membranes (PPROM)
Overdistension/uterine problems Activation of maternal
– multifetal pregnancy hypothalamic pituitary
– overdistension adrenal
– stress
(HPA) axis / violence
– uterine abnormalities
– cervical abnormalities

Common Risk Factors for Preterm Birth
 Multiple gestation  Prior preterm birth

 Infection  Uterine factors
– Cervical length
 Stress – Contractions
 Bleeding – Anomalies
– Distention
 Nutrition
 Excessive  Ancestry and ethnicity
physical activity
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
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
Percent
100 93.7
75
59.3
50
25
10.6
0
Singletons Twins Higher order

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

Multiple Birth Ratios by Race*
Ratio per 1,000 live births

40
35 32.0
33.0 33.3
31.1
30.0 30.7
30 27.4
28.6
25.7 26.1
23.9 24.4 25.2
25 22.4 23.0
23.3
21.0 21.6 22.0
20.3 20.3
19.3 19.7 19.9
20
15
10
0
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
00
01
02
03
19
19
19
19
19
19
19
19
19
19
19
19
19
19
19
19
19
19
19
19
20
20
20
20
All Races White Black
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

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.

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
– Total preterm deliveries = 28.3% < 36 wk
 Of 1,084 black women w/ 1st delivery @ 20-31 weeks
– Total preterm deliveries = 36.8% < 36 wk
Source: Adams MM et al. JAMA 2000;283:1591-6.

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
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.

Relative Risk of Spontaneous Preterm Delivery < 35 Weeks
by Percentile of Cervical Length at 24 Weeks
NICHD MFMU Network
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
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.

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 %.
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
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%
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
Activation of Inflammation Decidual Pathological Uterine
Hemorrhage Distention
Maternal-Fetal
HPA Axis • Infection:
- Chorion-Decidual Abruption
• Multifetal Pregnancy
- Systemic
• Maternal-Fetal • Polyhydramnios
Stress Thrombin • Uterine Abnormality
Ils, Fas L Thrombin Rc
• Premature Onset TNF Mechanical Stretch
of Physiologic Gap jct
Initiators CRH PG synthase
Chorion
E1-E3 Oxt recep
Decidua
+ CRH
+
proteases uterotonins
PPROM
Uterine
Cervical Change PTD Contractions
Source: Lockwood CL. Unpublished data, 2002.


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Compendium on Preterm Birth

Epidemiology & Biology

© March of Dimes 2006

Compendium on Preterm Birth

Compendium on Preterm Birth

Compendium on Preterm Birth

 < 1,000 grams 0.7% (of live births)

Compendium on Preterm Birth

Compendium on Preterm Birth

Compendium on Preterm Birth

Percent of live births

Compendium on Preterm Birth

2002 Rate per 100,000 live births

0 50 100 150 200

Compendium on Preterm Birth

Preterm is less than 37 completed weeks gestation.

Compendium on Preterm Birth

Preterm is less than 37 completed weeks gestation

Compendium on Preterm Birth

NH White NH Black Hispanic

Preterm is less than 37 completed weeks gestation.

Compendium on Preterm Birth

U.S. Total = 12.3%

Compendium on Preterm Birth

Compendium on Preterm Birth

Compendium on Preterm Birth

80 All other Hospital charges

Infant stays with any

Compendium on Preterm Birth

Almost half of hospital charges

Compendium on Preterm Birth

Total $2,830 $41,610

Based on analysis of births in 2001 followed for 12 months.

Compendium on Preterm Birth

 Social service costs

Compendium on Preterm Birth

 Many women think a baby born prematurely

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

Compendium on Preterm Birth

Compendium on Preterm Birth

 #2 cause of infant mortality (<1 year) in the U.S.

Compendium on Preterm Birth

Compendium on Preterm Birth

Compendium on Preterm Birth

Compendium on Preterm Birth

 Clinically Indicated - 25%

Compendium on Preterm Birth

 Risk factors similar

 50% have no risk factors

Compendium on Preterm Birth

Compendium on Preterm Birth

 Maternal age (<18 and >35 years)

Compendium on Preterm Birth

Compendium on Preterm Birth

Inflammation Decidual hemorrhage

Compendium on Preterm Birth

 Multiple gestation  Prior preterm birth

Compendium on Preterm Birth

 Prior Preterm Delivery OR 4

 2nd Trimester Bleeding OR 2 or >

 Genito-Urinary (GU) Tract Infection OR 2

 Body Mass Index <19.8 kg/m2 OR 2

Compendium on Preterm Birth