Preterm Labor and Delivery
UNC School of Medicine
Obstetrics and Gynecology Clerkship
Case Based Seminar Series
Objectives for Preterm Labor
 Identify the risk factors and causes for preterm labor
 Describe the signs and symptoms of preterm labor
 Describe the initial management of preterm labor
 List indications and contraindications of medications
used in preterm labor
 Identify the adverse outcomes associated with
preterm birth
 Counsel the patient regarding risk reduction for
preterm birth
Definition: Preterm Labor
 “Regular” uterine contractions
 With
 Cervical “change” or
 > 2 cm dilation or
 > 80% effacement
Preterm Delivery
 Preterm birth: < 37completed weeks
 Very Preterm birth: < 32 weeks
 Extremely Preterm birth: < 28 weeks
Incidence
 12.5% USA (2004)
 2% < 32 weeks
 Fetal growth
 Small for gestational age < 10th % for GA
 Birthweight:
 Low BWT
 Very low BWT
 Extremely low BWT
< 2500 grams
< 1500 grams
< 1000 grams
Incidence
 13% Rise in PTB since 1992
 Multiple gestation (20% increase)
 50 % twins, 90% triplets born preterm
 Changes in Obstetric management
 Ultrasound, induction
 Sociodemographic factors
 AMA!
 No improvement with physician interventions!
Leading Causes of Neonatal Death (USA)
Neonatal
deaths
Percentage of
neonatal deaths
Disorders related to prematurity and low birth weight
4,318
23.0
Congenital malformations, chromosomal abnormalities
4,144
22.1
Maternal complications
1,394
7.4
Placenta, cord, and membrane complications
1,049
5.6
Respiratory distress
929
4.9
Bacterial sepsis
737
3.9
Intrauterine hypoxia and birth asphyxia
589
3.1
Neonatal hemorrhage
563
3.0
Atelectasis
483
2.6
Necrotizing enterocolitis
313
1.7
Neonatal deaths: death within 28 days of birth .
Data adapted from: the Centers for Disease Control and Prevention, 2000.
Significance
 Infant mortality
 Over 50% of infant deaths occur among the 1.5% infants
< 1500 grams
 70 % of infant deaths occur among the 7.7% of infants
< 2500 grams
 Morbidity
 60%: 26 weeks
 30%: 30 weeks
Infant Mortality
Infant Morbidity
Infant Morbidity
Risk Factors for Preterm Birth
Non-modifiable
Modifiable
Prior preterm birth
Cigarette smoking
African-American race
Substance abuse
Age <18 or >40 years
Absent prenatal care
Poor nutrition/low pre-pregnancy weight
Short interpregnancy intervals
Low socioeconomic status
Anemia
Cervical injury or anomaly
Bacteriuria/urinary tract infection
Uterine anomaly or fibroid
Genital infection
Premature cervical dilatation (>2 cm)
or effacement (>80 percent)
? Strenuous work
Over distended uterus (multiple
pregnancy, polyhydramnios)
? Vaginal bleeding
? Excessive uterine activity
? High personal stress
Risk Factors for Preterm Birth
Stress
 Single women
 Low socioeconomic status
 Anxiety
 Depression
 Life events (divorce, separation, death)
 Abdominal surgery during pregnancy
Occupational fatigue
 Upright posture
 Use of industrial machines
 Physical exertion
 Mental or environmental stress
Excessive or impaired uterine distention
 Multiple gestation
 Polyhydramnios
 Uterine anomaly or fibroids
 Diethystilbesterol
Cervical factors
 History of second trimester abortion
 History of cervical surgery
 Premature cervical dilatation or
effacement
Infection
 Sexually transmitted infections
 Pyelonephritis
 Systemic infection
 Bacteriuria
 Periodontal disease
Placental pathology
 Placenta previa
 Abruption
 Vaginal bleeding
Risk Factors for Preterm Birth
Miscellaneous
 Previous preterm delivery
 Substance abuse
 Smoking
 Maternal age (<18 or >40)
 African-American race
 Poor nutrition and low body mass index
 Inadequate prenatal care
 Anemia (hemoglobin <10 g/dL)
 Excessive uterine contractility
 Low level of educational achievement
 Genotype
Fetal factors
 Congenital anomaly
 Growth restriction
Risk Factors for Preterm Birth
 Prior preterm birth:
 Increases risk in subsequent pregnancy
 Risk increases with
 more prior preterm births
 earlier GA of prior preterm birth (s)
Prediction/Recurrence
 Prior PTD @ (23-27 wks)
 Prior PPROM
27%
13.5%
Prediction/Recurrence
First Birth
Second Birth
Subsequent
Preterm Birth (%)
Not Preterm
4.4
Preterm
17.2
Not Preterm
Not Preterm
2.6
Preterm
Not Preterm
5.7
Not Preterm
Preterm
11.1
Preterm
Preterm
28.4
Pathogenesis
 80% of Preterm births are spontaneous
 50% Preterm labor
 30% Preterm premature rupture of the membranes
 Pathogenic processes
 Activation of the maternal or fetal hypothalamic pituitary
axis
 Infection
 Decidual hemorrhage
 Pathologic uterine distention
Activation of the HPA Axis




Premature activation
Major maternal physical/psychologic stress
Stress of uteroplacental vasculopathy
Mechanism
 Increased Corticotropin-releasing hormone
 Fetal ACTH
 Estrogens (incr myometrial gap junctions)
Inflammation
 Clinical/subclinical chorioamnionitis
 Up to 50% of preterm birth < 30 wks GA
 Proinflammatory mediators
 Maternal/fetal inflammatory response
 Activated neutrophils/macrophages
 TNF alpha, interleukins (6)
 Bacteria
 Degradation of fetal membranes
 Prostaglandin synthesis
Prediction of Preterm Delivery
 History: Current and Historical Risk Factors
 Mechanical
 Uterine contractions
 Home uterine activity monitoring
 Biochemical
 Fetal fibronectin
 Ultrasound
 Cervical length
Fetal Fibronectin (fFN)
 Glycoprotein in amnion, decidua, cytotrophoblast
 Increased levels secondary to breakdown of the
chorionic-decidual interface
 Inflammation, shear, movement
Fetal fibronectin as a predictor for delivery
within 7 and 14 days after sampling,
combined results
Delivery <7 days
Sensitivity
(percent),
95 percent CI
Delivery <14 days
Specificity
(percent), 95
percent CI
Sensitivity
Specificity
(percent), 95
(percent), 95
percent CI
percent CI
Study group
All studies
Women with
preterm labor
71 (57-84)
77 (67-88)
Asymptomatic 63 (26-90)*
(low risk or
high-risk)
women
89 (84-93)
67 (51-82)
89 (85-94)
87 (84-91)
74 (67-82)
97 (97-98)
51 (33-70)
.
.
87 (83-92)
96 (92-100)
CI: confidence interval.
* Only one study included in analysis. Fixed-effects model used (homogeneity test P >0.10).
Data from: Leitich, H, Kaider, A. Fetal fibronectin - how useful is it in the prediction of preterm birth? BJOG 2003; 110 (Suppl 20):66.
Fetal fibronectin vs. Clinical assessment
of Preterm Labor
Parameter
Sensitivity (percent)
PPV (percent)
NPV (percent)
Fetal fibronectin
93
29
99
Cervical
dilatation >1 cm
29
11
94
Contraction
frequency 8/h
42
9
94
PPV: positive predictive value; NPV: negative predictive value.
Data derived from symptomatic women and reflect the ability to predict delivery within
seven days.
Adapted from: Iams, JD, Casal, D, McGregor, JA, et al. Am J Obstet Gynecol 1995; 173:141.
Sonographic Assessment of Cervical Length
 Transvaginal
 Reproducible
 Simple
Sonographic Assessment of Cervical Length
(Dijkstra et al Am J Obstet Gynecol 1999)
Sonographic Assessment of Cervical Length
Assessment of Risk
 Integration of …..
 History
 Cervical length
 Fibronectin
Prediction of spontaneous preterm delivery before 35 weeks
gestation among asymptomatic low risk women
Cervical length < 25 mm
(percent)
Fetal fibronectin
(percent)
Both tests
(percent)
Positive test
result
8.5
3.6
0.5
Sensitivity
39
23
16
Specificity
92.5
97
99.5
Positive
Predictive Value
14
20
50
Negative
Predictive Value
98
98
94.4
Adapted from: Iams, JD, Goldenberg, RL, Mercer, BM, et al. Am J Obstet Gynecol 2001; 184:652.
Risk of Preterm Birth (< 35 wks)
History of Delivery
18-26
27-31
32-36
> 37
CL < 25
25%
25%
25%
6%
CL 26-35
14%
14%
13%
3%
CL > 35
7%
7%
7%
1%
CL < 25
64%
64%
63%
25%
CL 26-35
46%
45%
45%
14%
CL > 35
28%
28%
27%
7%
FFN (-)
FFN (+)
Clinical Diagnosis of Preterm Labor
 Clinical Criteria
 Persistent Ctx 4 q 20 min or 8 q 60 min
 Cervical change/80% effacement/> 2cm dil.
 Among the most common admission Dx
 Inexact diagnosis: PTL is not PTD
 30% PTL resolves spontaneously
 50% of hospitalized PTL deliver @ term
Management of Preterm Labor
 Two goals of management:
 Detection and treatment of disorders associated with PTL
 Therapy for PTL itself
 Bedrest, hydration, sedation
 NO evidence to support in the literature
Evaluation of Patient in Suspected PTL
• Prompt eval is critical
• Fetal heart monitor – to help quntify frequency and duration of
contractions
• Determine status of cervix – visual inspection with speculum*
– *perform first if suspected ROM b/c digital exam may increase the
risk of infection in the setting of PROM
• UA and urine culture
• Rectovaginal swab for GBS
• Gonorrhea and Chlamydia cultures if inidcated by history or PE
• Ultrasound exam – assess GA of fetus, cervical length, estimate
amniotic fluid volume, fetal presentation and placental location
• Monitor patients for bleeding – placental abruption and previa may be
associated with PTL
OPTIONS FOR MEDICAL
MANAGEMENT
Drug
Mechanism
Efficacy
Side Effects
Contraindications
Beta adrenergic
receptor agonist
(terbutaline )
Interferes w/
myosin light chain
kinase
? 48 hours.
Tachycardia,
palpitations,
hypotension, SOB,
pulmonary
edema,
hyperglycemia
Maternal cardiac
disease, uncontrolled
diabetes and
hyperthyroidism
Inhibits actin
myosin interaction
No change in
perinatal
outcome
Magnesium
Sulfate
Competes with
Unproven
Calcium at plasma
memb (?)
Diaphoresis,
Myasthesthenia gravis,
flushing,
renal failure
pulmonary edema
Ca Channel
Blocker
(nifedipine)
Directly block
influx of Ca thru
cell membrane
Unproven
Nausea, flushing,
HA, palpitations
Caution: LV
dysfunction, CHF
Cyclooxygenase
Inhibitors
(indomethacin)
Decrease
prostaglandin
production
Unproven
Nausea, GI reflux,
spasm fetal DA,
oligo
Platelet or hepatic
dysfunction, GI ulcer
Renal dysfunction,
asthma
Antenatal Steroids
 Recommended for:
 Preterm labor 24 – 34 weeks
 PPROM 24 – 32 weeks
 Reduction in:
 Mortality, IVH, NEC, RDS
 Mechanism of action:
 Enhanced maturation lungs
 Biochemical maturation
Antenatal Steroids
 Dosage:
 Dexamethasone 6 mg q 12 h
 Betamethasone 12.5 mg q 24 h
 Repeated doses - NO
 Effect:
 Within several hours
 Max @ 48 hours
Progesterone for History of PTB
 17 alpha OH Progesterone
 Women with prior PTB (singleton) (20-24 wks)– 36 wks
 (16 – 20 wks) – 36 weeks
 Reduces the risk of recurrent preterm birth
 < 37 wks 36% vs 55%
 < 35 wks 21% vs 31%
 < 32 wks 11% vs 20%
Case #1
 A 36 year old black female G2 P 0101 presents
at 8 weeks gestation.
 History: Chronic hypertension, no meds
 Smokes 1 ppd, Drugs (-) ETOH (+)
 STI – history of chlamydia, HIV positive
 Surgical history : LEEP, tubal ligation
Bottom Line Concepts
 Preterm labor - “Regular” uterine contractions, with cervical
“change” or > 2 cm dilation or > 80% effacement, occurring before
37 weeks
 There are numerous risk factors – both modifiable and nonmodifiable. Counsel patients regarding ways to reduce their
modifiable risk factors
 Clinical assessment of risk includes consideration and evaluation of
history, cervical length and fetal fibronectin
 There are a variety of tocolytic drugs available, though most have
unproven efficacy
 Antenatal steroids are recommended for: Preterm labor 24 – 34
weeks and PPROM 24 – 32 weeks
References and Resources
 APGO Medical Student Educational Objectives, 9th edition, (2009),
Educational Topic 24 (p50-51).
 Beckman & Ling: Obstetrics and Gynecology, 6th edition, (2010),
Charles RB Beckmann, Frank W Ling, Barabara M Barzansky, William
NP Herbert, Douglas W Laube, Roger P Smith. Chapter 20 (p201-205).
 Hacker & Moore: Hacker and Moore's Essentials of Obstetrics and
Gynecology, 5th edition (2009), Neville F Hacker, Joseph C Gambone,
Calvin J Hobel. Chapter 12 (p146-150).