Transcript Health Disparities – Then & Now Preterm Birth

Margaret Lynn Yonekura, M.D. FACOG
Definitions
 Gestational Age
 Preterm birth (PTB): < 37 completed weeks of gestation
 Late preterm birth: 34-36 completed weeks of gestation
 Very preterm birth: < 32 completed weeks of gestation
 Birth Weight
 Low birth weight (LBW): < 2500 gm or 5.5 lb
 Very low birth weight (VLBW): < 1500 g. or 3.3 lb
Overlap in LBW, Preterm & Birth Defects, U.S., 2003
Low
Birthweight
Births
7.9%
Preterm
Births
12.3%
Among LBW:
2/3 are preterm
Birth Defects
~3-4%
Among preterm:
more than 43% are
LBW (some preterm
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.
Pathways to Preterm Birth
Activation of
Maternal-Fetal
HPA Axis
• Maternal-Fetal
Stress
• Premature Onset
of Physiologic
Initiators
Inflammation
• Infection:
- Chorion-Decidual
- Systemic
Pathological Uterine
Distention
Abruption
• Multifetal Pregnancy
• Polyhydramnios
• Uterine Abnormality
Thrombin
Thrombin Rc
Ils, Fas L
TNF
CRH
E1-E3
Decidual
Hemorrhage
Chorion
Decidua
+
proteases
Mechanical Stretch
Gap jct
PG synthase
Oxt recep
+
CRH
uterotonins
PPROM
Cervical Change
PTD
Uterine
Contractions
Source: Lockwood CL. Unpublished data, 2002.
The Consequences 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 Mortality & Gestational Age
Source: Mercer BM. Preterm premature rupture of the membranes. Obstet Gynecol 2003;101:17893. Reproduced with permission from Lippincott Williams & Wilkins.
March of Dimes Prematurity Campaign
 Launched January 30, 2003
 Goals:
 To raise public awareness of the problems of prematurity
 To decrease the rate of PTB in the United States
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.
Women’s Perceptions Regarding
the Safety of Births at Various GAs
 “What is the earliest point in pregnancy that it is safe
to deliver the baby, should there be no other medical
complications requiring early delivery”
 51.7%
 40.7%
 7.6%
34-36 weeks
37-38 weeks
39-40 weeks
Obstet Gynecol 2009; 114:1254-8
March of Dimes Prematurity Campaign
Milestones
 2004: Created the Prematurity Research Initiative
which funds promising, innovative research into
causes of prematurity
 2005: IOM published its report on Preterm Birth.
Funded in part by March of Dimes
 2005: March of Dimes initiated the PREEMIE Act that
became law in 2006
 2008: first Surgeon General’s Conference on
Prevention of PTB. March of Dimes staff and
volunteers were key participants in 6 work groups
Complex Interactions in Preterm Birth
OUTCOMES
lG
Preterm Labor / pPROM
PRETERM BIRTH
FACTORS
Psychosocial
Medical Conditions
Nutrition
Medical Interventions
External Environment
Am J Obstet Gynecol 2005; 193:626-35
Bleeding / Thrombophilias
Im mune Status
Maternal / Fetal Stress
Behaviors
Inflammation / Infection
Genetics / Family History
Abnormal Uterine Distention
Racial / Ethnic Disparities
YS
A
HW
T
PA
Others: Hormones? Toxins?
ta
Fe
h
wt
ro
Research Agenda for PTBs
 Focus primarily on cause and prevention of very PTB
(< 32 wk GA)
 Better define the etiologic mechanisms responsible for
PTB
 Identify biomarkers for PTB to improve clinical risk
assessment
 Develop clinical interventions that lead to reduction in
rates of PTB
 Eliminate disparities in PTB among racial/ethnic
groups in the United States
Am J Obstet Gynecol 2005; 193:626-35
March of Dimes Prematurity Campaign
Milestones
 2004: Created the Prematurity Research Initiative
which funds promising, innovative research into
causes of prematurity
 2005: IOM published its report on Preterm Birth.
Funded in part by March of Dimes
 2005: March of Dimes initiated the PREEMIE Act that
became law in 2006
 2008: first Surgeon General’s Conference on
Prevention of PTB. March of Dimes staff and
volunteers were key participants in 6 work groups
Preterm Birth: Causes,
Consequences, and Prevention
 Preterm birth and its consequences constitute a major
public health problem in the U.S.
 In 2004, over 500,000 infants or 12.5% of all births were
preterm (< 37 completed weeks of gestation)
 This rate has increased steadily in the past decade
 Significant, persistent, and very troubling racial, ethnic,
and socioeconomic disparities
 Preterm birth is a leading cause of infant mortality and
long-term morbidity
 The annual societal economic burden associated with
PTB in U.S. was $26.2 billion in 2005.
March of Dimes Prematurity Campaign
Milestones
 2004: Created the Prematurity Research Initiative
which funds promising, innovative research into
causes of prematurity
 2005: IOM published its report on Preterm Birth.
Funded in part by March of Dimes
 2005: March of Dimes initiated the PREEMIE Act that
became law in 2006
 2008: first Surgeon General’s Conference on
Prevention of PTB. March of Dimes staff and
volunteers were key participants in 6 work groups
PREEMIE Act, 2006
 Public Law 109-450 was cited as the Prematurity Research
Expansion and Education for Mothers who deliver Infants
Early Act
 Purpose of this Act to:
 Reduce rates of preterm labor and delivery
 Work toward an evidence-based standard of care for pregnant
women at risk of preterm labor or other serious
complications, and for infants born preterm and at a low
birthweight
 Reduce infant mortality and disabilities caused by
prematurity
 Called on Surgeon General to convene a conference on
prevention of PTB
Surgeon General’s Conference of Prevention
of Preterm Birth, June 16-17, 2008
 Purpose of conference:
 Increase awareness of PTB as a serious, common, and
costly public health problem
 Review key findings and reports issued by experts in the
field
 Establish an agenda for activities in both the public and
private sectors to mitigate this problem
 First day devoted to deliberations of 6 work groups
 Recommendations of work groups were discussed and
modified based on public input on second day
Obstet Gynecol 2009: 113:925-30
1. Biomedical Research
 Identify improved biomarkers to predict PTB, identify
better methods to assess antenatal fetal maturity, and
investigate risks and benefits associated with indicated
early and late PTB.
 Enhance understanding of physiology of normal labor &
delivery; the pathological processes leading to PTB,
including genetic, epigenetic, and environmental
interactions; and the mechanism of action for promising
prenatal & preconception therapies
 Identify factors influencing the rise in PTBs with a focus on
late PTB, multiple gestations, and non-medically indicated
PTB and support studies relating PTB to other adverse
pregnancy outcomes - stillbirth, preeclampsia, congenital
anomalies, and placental abruption
2. Epidemiological Research
 Identify multidisciplinary research on racial and
ethnic disparities as a priority
 Study differential outcomes of PTB by cause and
conduct epidemiological research that investigates
clinical, biological, social, genetic, and behavioral
factors simultaneously
 Examine the effect of various types of infertility
treatments, including ovulation stimulation and
assisted reproductive technologies on PTB and
evaluate programs aimed at decreasing multiple
gestation rates
3. Psychosocial and Behavioral Considerations
 Research on effects of race, racism, and social injustice
for African Americans must be a priority as they bear
the highest burden of prematurity
 Develop a blue-ribbon panel for studying the
definition, conceptualization, measurement, and
biological correlates of stress in prematurity research
and improve measurement of other psychosocial and
behavioral risk factors to promote consistency in
research
3. Psychosocial and Behavioral Considerations
 Evaluate existing large-scale intervention programs
and maximize the use of existing data to better
understand psychosocial and behavioral determinants
of PTB and its prevention
 Promote community-based participatory research on
PTB, utilizing both qualitative and quantitative
research methods
 Develop methods to study causes and prevention of
PTB across the life course in a multiple-determinant
framework
4. Professional Education & Training
 All health professionals need to be trained in core risk
factors for PTB
 Professionals need to incorporate a life course
perspective into care to emphasize the different
psychosocial and behavior risk factors and the
importance of preconceptional and interconceptional
care
 Clinical team education including curriculum
development, on-site educational opportunities, and
ongoing evaluation is important
5. Public Communication & Outreach
 Develop a national education and action program to
communicate what is known about PTB and how to
reduce the incidence in high-risk populations
 Establish partnerships across public, private, and
professional organizations to encourage collaboration
and shared dissemination networks to implement
communication strategies, treatment plans, and best
practices
6. Quality of Care and Health Services
 Make prevention of PTB, management of PTL, and
care of preterm infants and their families a
coordinated national health priority across federal,
state, and local agencies
 Assure access to appropriate preventive and
intervention measures and access to health care
coverage and care for all women of childbearing age;
preconception, interconception, and early prenatal
care; and access to health care coverage and services
for all children
Cross-Cutting Issues & Conclusions
 The Interagency Coordinating Council on Prematurity
and Low Birthweight should be reactivated to monitor
progress on this national action agenda and advise the
Secretary of Health and Human Services and Congress
about ongoing issues related to prematurity and its
prevention.
 The conference concluded with the request to the
Surgeon General to make prevention of PTB a national
public health priority.
March of Dimes Prematurity Campaign
Milestones
 2008: a March of Dimes board resolution extended the
Prematurity Campaign to 2020 and established
prematurity prevention as a global campaign
 2009: March of Dimes sponsored Symposium on
Quality Improvement to Prevent Prematurity.
 2009: March of Dimes issued the white paper, The
Global and Regional Toll of PTB.
Joint Commission Perinatal Core Measures
 PC-01
Elective Delivery
 PC-02 Cesarean Section
 PC-03 Antenatal Steroids
 PC-04 Health Care-Associated
Bloodstream Infections in Newborns
 PC-05 Exclusive Breast Milk Feeding
November 2009
Prevention of PTL, PTB, and Prematurity
 Primary prevention
 Identifying and managing risks


Preconception/interconception
During pregnancy
 Prevent preterm labor (PTL)
 Secondary prevention
 Prevent preterm birth (PTB)
 Tertiary prevention
 Prevent/minimize complications of prematurity
Classification of Preterm Birth
What are the conditions leading to PTB?
Spontaneous
Preterm Labor
Spontaneous
Premature Rupture
of the Membranes
50%
25-30%
Preterm
Birth
25-30%
Iatrogenic
(Medical
Indication)
While this suggests distinct pathways,
many of the risk factors for all 3 are similar
What are the conditions leading to PTB?
 Spontaneous – 75%
 Preterm labor
 Preterm premature rupture of membranes
 Multiple gestation
 Cervical insufficiency
 Other related diagnoses
 Clinically indicated – 25%
 Mother or fetal at risk
Clinical Indications for Preterm Deliveries
 Preeclampsia
 Fetal distress
 Inadequate intrauterine fetal growth
 Abruption
 Fetal demise
43%
28%
10%
7%
7%
Risk Factors for Spontaneous PTB
Non-modifiable risk factors
 Prior preterm birth
 African-American race
 Age <18 or >40 years
 Poor nutrition/low
prepregnancy weight
 Low SES
 Cervical injury or anomaly
 Uterine anomaly or fibroid
 Premature cervical dilatation or
effacement
 Over-distended uterus (multiple
pregnancy, polyhydramnios)
 Vaginal bleeding
 ? Excessive uterine activity
Modifiable risk factors
 Cigarette smoking
 Substance abuse
 Absent prenatal care
 Short interpregnancy intervals
 Anemia
 Bacteriuria/urinary tract
infection
 Genital infection
 Periodontal disease
 High personal stress
 ? Strenuous work
“Non-modifiable” risk factors
amenable to preconception care
Epidemiology of Spontaneous PTB
 Multiple gestation
OR 6
 Compared to singleton births
 Prior preterm birth
OR 4
 Compared to no history of PTB
 Second trimester bleeding
OR > 2
 Compared to no bleeding < 28 wk
 Genitourinary tract infection
OR 2
 Compared to no GU infection
 African American
 BMI < 19.8
OR 2
OR 2
The Preterm Parturition Syndrome
Uterine
Overdistension
Vascular
Cervical
Disease
Hormonal
Immunological
Infection
© VR RR MM
Unknown
Multiple Gestation
 Multiple gestation accounts for:
 2-3%
of all births
 17%
of preterm births (< 37 wk)
 23%
of very preterm births (<32 wk)
 Mechanism for PTL in multiple gestations, especially
higher order multiple gestations, is related to uterine
over-distention
 Assisted reproductive technology has been associated
with a 30-fold increase in multiple gestations
compared with the rate of spontaneous twin
pregnancies (1% in general white population)
Preterm Births by Plurality, United States, 2003
Percent
93.7
100
75
59.3
50
25
10.6
0
Singletons
Twins
Higher order
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
Multiple Birth Ratios by Race*,U.S., 1980-2003
Ratio per 1,000 live births
40
35
30
25.7 26.1
24.4 25.2
23.9
23.3
22.4 23.0
21.6 22.0
21.0
20.3 20.3
19.3 19.7 19.9
25
20
27.4
28.6
31.1
30.0 30.7
32.0
33.0 33.3
15
10
5
All Races
White
03
20
02
20
01
20
00
20
99
19
98
19
97
19
96
19
95
19
94
19
93
19
92
19
91
19
90
19
89
19
88
87
19
86
19
85
19
84
19
83
19
82
19
81
19
19
19
80
0
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
Uterine Fibroids and PTB
 Presence of a large fibroid
(> 5-6 cm) correlates best with
increased risk for PTB
 Incidence is 3-4 fold greater in
blacks than whites
 Natural history differs by race
 Whites become symptomatic in
their 30-40s whereas blacks
become symptomatic 4-6 yr
earlier, sometimes even in their
20s
 Typically grow at slower rate > 35
yr in whites but not in blacks
 Blacks have more severe disease than
whites
History of Spontaneous PTB:
The Most Important Known Risk Factor
 Recurrence risk rises with  number of PTB:
 14-22% after one PTB
 28-42% after two PTBs
 67%
after three PTBs
 Recurrence risk rises as GA of prior PTB :
 Risk of PTB < 28 wk GA if prior PTB at:



23-27 wk
28-34 wk
35-36 wk
5%
3%
1%
 Most recent birth is most predictive
Am J Obstet Gynecol 1999; 181:1216
Recurrence Risk of Preterm Birth
 Risk greater in African Americans
 Population-based cohort study – Georgia 1980-1995
 122,722 white and 56,174 black women
 Of 1,023 white women with 1st delivery at 20-31 wk:



8.2% delivered 2nd at 20-31 wk
20.1% delivered 2nd at 32-36 wk
Total PTBs = 28.3% < 36 wk
 Of 1,084 black women with 1st delivery at 20-31 wk:



13.4% delivered 2nd at 20-31 wk
23.4 delivered 2nd at 32-36 wk
Total PTBs = 36.8% < 36 wk
 PTBs to a woman’s mother, full sisters or maternal half-sisters
modestly increases risk
What Do Genes Have to Do with It?
 PTBs are more common is some family pedigrees and
racial groups
 Concordance of timing of parturition higher in
monozygotic vs. dizygotic twin mothers
 Modest increased risk for PTB if mother herself was
born preterm
 Risk of PTB also increased in first degree relatives of
woman who had a PTB
Obstet Gynecol 2010; 115:1125
What Do Genes Have to Do with It?
 African American ancestry consistently associated with
increased risk of PTB
 Genetic polymorphisms play a role




Susceptibility locus on chromosome 7
Certain polymorphisms in genes responsible for innate immunity 
PTB and PPROM
Polymorphisms in IL-1, TNF-α, IL-6, IL-8, TLR-4 and MLB genes
Gene-environment interactions (CYP1A1- and smoking, GSTT1- and
smoking)
 E.g., altered genetic regulation of cervicovaginal cytokine
production and greater proinflammatory response to altered
vaginal flora (i.e., BV)  SPTB
Obstet Gynecol 2011; 117:1078 and 118:1081
The Preterm Parturition Syndrome
Uterine
Overdistension
Vascular
Cervical
Disease
Hormonal
Immunological
Infection
© VR RR MM
Unknown
Subclinical Infection as a Cause of PTB
 Histologic chorioamnionitis  in PTB
 Clinical infection in mother & neonate  after PTB
 Significant associations of some lower genital tract
organisms/infections with PTB or PPROM
 Positive cultures of amniotic fluid or membranes from
some patients with PTL/PTB
 Markers of infection in PTB
 Bacteria or their products induce PTB in animal
models
 Some antibiotic trials have  rate of PTB or have
delayed PTB
Risk of PTB with Selected Infections
Infection
Odds Ratio (95% CI)
Bacterial vaginosis < 16 wk
7.55 (1.8-31.7)
N. Gonorrhoae
5.31 (1.57-19.0)
Asymptomatic bacteriuria
2.08 (1.45-3.03)
Chlamydia trachomatis
at 24 wk
at 28 wk
2.2 (1.03-4.78)
0.95 (0.36-2.47)
Trichomonas vaginalis
1.3 (1.1-1.4)
U.Urealyticum
1.0 (0.8-1.2)
Am J Obstet Gynecol 2004; 190:1493
Bacterial Vaginosis and PTB
 Prevalence
 29% of women ages 14-49 yr
 50% of African American women
 Definition
 Complex change in vaginal flora characterized by  H2O2
producing lactobacilli and  in other organisms, especially
anaerobic GNRs
 Risk factors
 Women who have sex with women
 Multiple or new sexual partners
 Douching
 Cigarette smoking
Bacterial Vaginosis and PTB
 50-75% of women with BV are asymptomatic
 Diagnosis
 Requires microscopy or Gram stain of vaginal secretions
 New diagnostic test cards
 Cure rates are ~80-90%
 Metronidazole 500-mg bid x 7 d
 Metronidazole 250-mg tid x 7 d
 Clindamycin 300-mg bid x 7 d – this is only regimen that
consistently  risk of PTB, RR 0.39 (95% CI 0.2-0.76),
when used in asx women < 22 wk GA
STDs in African American Community
 Consultation to Address STD Disparities in African
American Communities, Atlanta, GA, June 5-6, 2007
 STD disparities reflect socioeconomic disparities, which
in turn reflect deep-rooted racial inequalities that
continue to exist and are metastasizing throughout
American society
 To achieve a complete and lasting solution will require
uprooting inequality that is deeply entrenched in
America’s institutions-its educational, criminal justice
and correctional, and public health systems
 All Americans must face head-on the difficult issues of
race and sex that perpetuate STD disparities.
Multi-level Approach to understanding
health disparities and STDs
General population
African American community
Sexual networks
Infectious
agent
Sexual partnerships
Biomedical & health
service interventions
Individual Behavior
Socioeconomic &
cultural
factors
Multi-level Approach to understanding
health disparities and STDs
 Why are African American populations different from
others in terms of sexual partnering patterns?
 Pervasive economic & racial oppression
 Lack of employment opportunities
 Lack of community recreation, boredom, & resultant substance
abuse
 Shortages of black men-high rates of mortality & incarceration
remove many from community
 Residential segregation
 Consequences:


Dissortative mixing – low risk woman with high-risk man
Concurrent sexual partnerships
Multi-level Approach to understanding
health disparities and STDs
 Access & quality of health services
 Nearly one-fifth of African Americans do not have
health insurance (especially men < 65) and a quarter of
African American families live in poverty
 African Americans use medical services/treatment less
than whites due to a general mistrust of the medical
system – legacy effects of social discrimination and lack
of cultural competence among health care providers
 Less access to high quality services
Follow-up Of Consultation Report
 CDC’s Division of STD Prevention formed STD
disparities workgroup and developed a strategic plan
 In 2010 STDs Disparities Workgroup and others
gathered to discuss a “values strategy” (framing)
conversation on the issue  STD/STI Framing
Conversation Report
 Actionable items for consideration for CDC to combat
this persistent high burden of STDs
African Americans and STDs, 2011
 Chlamydia: 48% of reported cases among blacks
 Women bear a heavier chlamydia burden than men
 Untreated chlamydia can lead to infertility in women
 CDC recommends annual screening for sexually active young
women
 Gonorrhea: lowest national rate ever recorded yet major
differences remain by race/ethnicity
 Since 2006, the decrease has been smaller for blacks (15%) than for
Hispanics (21%) or whites (25%)
 Like chlamydia, undiagnosed and untreated GC can lead to
infertility in women.
 CDC recommends annual screening for high-risk sexually active
women
Lifestyle Issues and PTB
 No dietary fish or fish oil
consumption
 Rate of PTB in women who
never consumed fish was
significantly higher than in
those who did, 7.1% vs. 3.4%
OR (95% CI)
Cigarettes/
PTB
day
33-36 wk
 Smoking
 Cigarette smoking has dosedependent relationship with
risk of PTB
Am J Obstet Gynecol 1998; 179:1051
PTB
<32 wk
1-9
1.1
(1.1-1.2)
1.3
(1.2-1.5)
> 10
1.4
(1.3-1.4)
1.6
(1.4-1.8)
Lifestyle Issues and PTB
 Substance abuse
 Polysubstance abuse associated with a 25-63% risk of
PTB
 Selected substances known to increase risk of PTB:



Alcohol
Cocaine
Toluene
 Stress
 An association between stress & PTB is biologically
plausible
 Maternal psychosocial stress associated with modest
increased risk of PTB (~1.5-2 fold)
Am J Obstet Gynecol 2011; 205:402
The Preterm Parturition Syndrome
Uterine
Overdistension
Vascular
Cervical
Disease
Hormonal
Immunological
Infection
© VR RR MM
Unknown
Short Cervix and PTB
Cervical
Length, mm
Centile
RR of PTB
95% CI
< 35
50
2.35
1.42-3.89
< 30
25
3.79
2.32-6.19
< 26
10
6.19
3.84-9.97
< 22
5
9.49
5.95-15.5
< 13
1
13.99
7.89-24.78
N Engl J Med 1996; 334:567
Relative Risk of Spontaneous Preterm Delivery < 35
Weeks by Percentile of Cervical Length at 24 Weeks
NICHD MFMU Network
Source: 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 Surgery and PTB
 Higher incidence of cervical
cancer in African American
women
 Ablative or excisional
procedures for treatment of
cervical intraepithelial
neoplasia are associated
with increased risk of
late miscarriage and PTB
Risk Scoring Systems and PTB
 Risk scoring is a qualitative method used to identify
women at increased risk of PTB
 Proposed systems typically calculate an additive score
based on points assigned to arbitrarily selected or
weighted epidemiological, historical, and clinical risk
factors
 A systematic review concluded that there were no
effective risk scoring systems for prediction of PTB
J Matern Fetal Med 2001; 10:102
Prevention of PTL, PTB, and Prematurity
 Primary prevention
 Identifying and managing risks


Preconception/interconception
During pregnancy
 Prevent preterm labor (PTL)
 Secondary prevention
 Prevent preterm birth (PTB)
 Tertiary prevention
 Prevent/minimize complications of prematurity
What Works to Prevent PTB?
Preconception/Interconception Care
 Unintended pregnancy
 Anemia
 Interpregnancy interval:
 Substance use






> 18 mo and <59 mo
Maternal age < 18 or >
40 yr
ART
Folic acid deficiency
Poor nutrition
Low pre-pregnancy
weight
Obesity
 Infections
 Stress/violence
 Chronic medical
condition
 Uterine abnormalities
 Uterine fibroid(s)
What Works to Prevent PTB?
 Treat infections: ASB, bacterial vaginosis, gonorrhea,
chlamydia
 Do not treat asymptomatic Trichomonas infection in
pregnancy
 Abstain from smoking, alcohol, illicit drug abuse
 Limit the number of pre-embryos transferred in each
ART cycle
 CenteringPregnancy™ (group prenatal care)
 Evidence-based perinatal home visiting programs
Progesterone & PTB Prevention: Translating
Clinical Trials into Clinical Practice
 In women with singleton pregnancies, no prior SPTB,
and short TVU CL < 20 mm at < 24 wk, vaginal
progesterone, either 90-mg gel or 200-mg suppository,
is associated with a reduction of PTB and perinatal
morbidity and mortality, and can be offered.
 2 cost-effectiveness analyses evaluating universal CL
screening in singleton gestations to identify those with
short CL eligible for vaginal progesterone demonstrated
significant cost-savings,  quality-adjusted life years, 
neonatal deaths, and  long-term neurologic deficits.
 Incidence of CL < 20 mm at 22-24 wk = 5%
Am J Obstet Gynecol 2012; 206:376-86
Transvaginal Cervical Sonography
Source: Reprinted from Ultrasonography in Obstetrics and Gynaecology, 4th ed., Callen PW,
Copyright 2000, with permission from Elsevier.
Nonsonographic Method for Measuring
Cervical Length: Cervilenz
Seminars in Perinatology 2009; 33:312-16
Proposed Mechanisms of Action
for Progestogens to Prevent PTB
 An antiinflammatory effect that counteracts the
inflammatory process leading to PTB
 A local increase in progesterone in gestational tissues
that counteracts the functional decrease in
progesterone leading to PTB
Am J Obstet Gynecol 2012; 206:376-86
Progesterone & PTB Prevention: Translating
Clinical Trials into Clinical Practice
 In singleton pregnancies with prior SPTB 20-36 6/7
wk, 17-alpha-hydroxy-progesterone caproate (17P) 250
mg IM weekly, preferably starting at 16-20 wk until 36
wk, is recommended.
 Start screening these women with TVU CL at 16 wk and
every 2 wk until 23 wk.
 In these women with prior SPTB, if TV CL shortens to
< 25 mm at < 24 wk, cervical cerclage may be offered.
Am J Obstet Gynecol 2012; 206:376-86
Cervical Cerclage
Progesterone & PTB Prevention: Translating
Clinical Trials into Clinical Practice
 Progestogens have not been associated with
prevention of PTB in women, with or without a short
CL, who have in the current pregnancy:
 Multiple gestation
 Preterm labor
 Preterm premature rupture of membranes
Prevention of PTL, PTB, and Prematurity
 Primary prevention
 Identifying and managing risks


Preconception/interconception
During pregnancy
 Prevent preterm labor (PTL)
 Secondary prevention
 Prevent preterm birth (PTB)
 Tertiary prevention
 Prevent/minimize complications of prematurity
Diagnosis of Preterm Labor
 Symptoms
 Signs
 Contractions
 Spotting
 Pressure
 Contractions – 6-8/hr
 Discharge
 Change in cervical
 Premenstrual-like
dilation and effacement
cramping
Traditional diagnostic criteria = contractions + cervical
change
False positive diagnosis: 40%  unnecessary treatment
False negative diagnosis: 20%  missed chance for
treatment
Diagnostic Tests for PTL in Symptomatic
Women: CL by TVU
 Cervix > 30 mm
 not preterm labor
 Cervix 20−30 mm
 maybe preterm labor
 Cervix < 20 mm
 probably preterm labor
Sources: ACOG Practice Bulletin. #43, 2003; Iams JD. Preterm birth, Chapter 23. In: Obstetrics: Normal and Problem
Pregnancies, 4th ed., 2002; Iams JD, Creasy RK. Preterm labor and delivery, Chapter 34. In: Maternal-Fetal Medicine: Principles
and Practice, 5th ed., 2004; Mercer BM. Assessment and induction of fetal pulmonary maturity, Chapter 25. In: Maternal-Fetal
Medicine: Principles and Practice, 5th ed., 2004; Preterm birth, Chapter 36. In: Williams Obstetrics, 22nd ed., 2005.
Tests to Diagnose Preterm Delivery < 7 d
All had symptoms or signs of preterm labor & Cx < 3 cm
Predictor Sens % Spec % PPV % NPV %
FFN
93
82
29
99
Bleeding
36
89
21
97
Cx > 1cm 29
Contrxns
82
11
94
= 4 / hr
58
45
7
94
= 6 / hr
58
55
9
95
= 8 / hr
42
67
9
94
Source: Iams JD et al. Am J Obstet Gynecol 1995;173:141-5.
Diagnostic Tests for Preterm Labor in Women
with Symptoms: Fetal Fibronectin
 Negative test, < 3 cm
 99% undelivered at 7 days
 95% undelivered at 14 days
 90% undelivered at 21 days
 Positive test, < 3 cm
 10-30% delivered < 7 days
 Useful if short turnaround time
 If a negative result will avoid treatment
Sources: Iams JD et al. Am J Obstet Gynecol 1995;173:141-5; Peaceman AM et al. Am J Obstet Gynecol 1997;177:13-8.
Prevention of PTL, PTB, and Prematurity
 Primary prevention
 Identifying and managing risks


Preconception/interconception
During pregnancy
 Prevent preterm labor (PTL)
 Secondary prevention
 Prevent preterm birth (PTB)
 Tertiary prevention
 Prevent/minimize complications of prematurity
Prevent/Minimize Complications
of Prematurity
 Antenatal Corticosteroid Therapy for Fetal Maturation
 ACOG Committee Opinion February 2011; #475
 Magnesium Sulfate Before Anticipated Preterm Birth
for Neuroprotection
 ACOG Committee Opinion March 2010; #455
 Very early (within first hour) surfactant use down ET
tube in infants treated with nasal continuous positive
pressure, 2008
First CDC Health Disparities &
Inequalities Report, 2011
 Social determinants of
health
 Education & income
 Environmental hazards
 Inadequate and unhealthy
housing
 Unhealthy air quality
 Health-care access &
preventive health services
 Health insurance coverage
 Influenza vaccination
coverage
 Colorectal cancer screening
 Health Outcomes –
Behavioral risk factors
 Binge drinking
 Adolescent pregnancy and
childbirth
 Cigarette smoking
First CDC Health Disparities &
Inequalities Report, 2011
 Health outcomes – Mortality
 Infant deaths
 Motor vehicle-related deaths
 Suicides
 Drug-induced deaths
 Coronary heart disease and
stroke
 Homicides
 Health outcomes – Morbidity
 Obesity
 Preterm births
 Potentially preventable
hospitalizations
 Current asthma prevalence
 HIV infection
 Diabetes
 Hypertension and hypertension
control
First CDC Health Disparities &
Inequalities Report: Preterm Birth
 ~1 of every 5 infants born to black mothers in 2007 was
born preterm, compared to 1 in 8 to 9 infants born to
white and Hispanic women
 In 2007 preterm birth rate for black infants was 59%
higher than the rate for white infants and 49% higher
than the rate for Hispanic infants
Preterm births, U.S. 1999-2009
Preterm is less than 37 completed weeks gestation. Very preterm is less than 32 completed weeks
gestation. Moderately preterm is 32-36 completed weeks of gestation.
Source: National Center for Health Statistics, final natality data. Retrieved March 29, 2012, from
www.marchofdimes.com/peristats.
Preterm births by maternal
race/ethnicity
US, 2009
All race categories exclude Hispanics. Preterm is less than 37 completed weeks gestation. Very preterm is
less than 32 completed weeks gestation. Moderately preterm is 32-36 completed weeks of gestation.
Source: National Center for Health Statistics, final natality data. Retrieved March 29, 2012, from
www.marchofdimes.com/peristats.
Multiple deliveries by maternal
race/ethnicity
US, 1999-2009
All race categories exclude Hispanics. Multiple deliveries include twin, triplet and higher order deliveries.
Source: National Center for Health Statistics, final natality data. Retrieved March 29, 2012, from
www.marchofdimes.com/peristats.
First CDC Health Disparities &
Inequalities Report: Infant Mortality
 In 2006, the overall U.S. infant mortality rate was 6.68
infant deaths per 1,000 live births
 The highest infant mortality rate was for black women
with a rate 2.4 times that for white women.
 Analysis on trends and variations reveals considerable
differences among racial/ethnic groups and
persistence of disparities over time.
 Prevention of PTB is critical to both lowering overall
infant mortality rate and reducing racial/ethnic
disparities
Infant mortality rates by maternal race/ethnicity
US, 1998-2007
All race categories exclude Hispanics. An infant death occurs within the first year of life.
Source: National Center for Health Statistics, period linked birth/infant death data. Retrieved March 29,
2012, from www.marchofdimes.com/peristats.
Infant mortality rates by maternal race/ethnicity
US, 2007
All race categories exclude Hispanics. An infant death occurs within the first year of life.
Source: National Center for Health Statistics, period linked birth/infant death data. Retrieved March 29,
2012, from www.marchofdimes.com/peristats.
Leading cause-specific infant
mortality rates by maternal
race/ethnicity
All race categories exclude Hispanics. An infant death occurs within the first year of life. SIDS is Sudden Infant Death Syndrome. RDS is
Respiratory Distress Syndrome. "Maternal Preg. Comp." stands for "Maternal Complications of Pregnancy." "Prem./LBW" stands for
"Prematurity/Low Birthweight." "Placenta/Cord Comp." stands for "Complications of the Placenta, Cord, and Membranes."
Source: National Center for Health Statistics, period linked birth/infant death data. Retrieved March 29, 2012, from
www.marchofdimes.com/peristats.
Obesity among women ages 18-44
US, 2000-2010
Obesity is defined as a Body Mass Index of 30 or more. Hawaii did not conduct BRFSS surveillance in 2004
and is not included in the U.S. rate for this year.
Source: Behavioral Risk Factor Surveillance System, Centers for Disease Control and Prevention. Retrieved
March 29, 2012, from www.marchofdimes.com/peristats.
Health insurance coverage among
women ages 15-44, U.S., 2010
Medicaid includes State Children's Health Insurance Program.
Source: US Census Bureau. Data prepared for the March of Dimes using the Current Population Survey
Annual Social and Economic Supplements. Retrieved March 29, 2012, from
www.marchofdimes.com/peristats.