8th Edition APGO Objectives
for Medical Students
Preterm Labor
Rationale
Prematurity is the most common cause of
neonatal mortality and morbidity. The
reduction of preterm births remains an
important goal in obstetric care.
Understanding the causes and
recognizing the symptoms of preterm
labor provides the basis for management
decisions.
Objectives
The student will be able to cite:

Factors predisposing to preterm labor
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Signs and symptoms of premature uterine
contractions
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Causes of preterm labor
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Management of preterm labor, including:
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Tocolytics
Steroids
Antibiotics
Preterm Birth
Definition - any delivery occurring prior to
37 wk. gestation
 Incidence - 11% of live-births

 1/3
of preterm deliveries are due to
spontaneous rupture of membranes
 1/3 to obstetrical causes
 1/3 due to idiopathic preterm labor
Criteria for diagnosis of
preterm labor
Gestational age 20-37 wk.
 Documented uterine contractions (4/20
min.; 8/60 min.) accompanied by one or
more of the following:

 Documented
cervical change
 Cervical effacement of > 80%
 Cervical dilation of > 2 cm
Etiology
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Subclinical infection of fetal membranes with
subsequent spontaneous rupture
Amniotic fluid infection
Cervical factors - incompetent cervix, cervical trauma or
congenital anomalies
Cervicovaginal infection - bacterial vaginosis,
N.gonorrhoeae
Uterine factors - anomaly, hydramnios, fibroids
Trauma or surgery
Placenta previa or abruption
Maternal factors - preeclampsia (iatrogenic prematurity)
Fetal anomalies
Risk factors for preterm delivery
Non-pregnancy related
 Previous preterm delivery
 Low socioeconomic status
 Non-white
 Pre-pregnancy weight < 50 kg and possibly
prenatal weight gain < 15 lbs.
 Smoking
 Uterine malformations
 Vaginal infection
Risk factors for preterm delivery
Obstetric related
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Placenta previa
Placenta abruption
Polyhydramnios
Multiple gestation
Cervical effacement/dilatation
Maternal diseases
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Hypertension
Diabetes
Systemic lupus erythematosus
Renal disease
Other medical complications
Management
Tocolytics
 Beta mimetics
 Mechanism
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of action
Attachment of drug to β2-adrenergic receptor
Activation of adenyl cyclase
Increased cAMP
Decreased myosin light chain kinase activity
Interference with actin/myosin interaction
Management
Tocolytics - Beta mimetics
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Maternal side effects
• Cardiac arrhythmias
• Pulmonary edema - predisposing factors
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Increased intravascular volume
Decreased peripheral vascular resistance
Decreased blood viscosity
Increased heart rate
Decreased plasma colloid oncotic pressure
Increased pulmonary vascular permeability
Intrapartum volume shifts
• Hyperglycemia
Management
Tocolytics - Beta mimetics
 Fetal side effects
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Hypoglycemia
Hypocalcemia
Hypotension
Ileus
Mild tachycardia
Management
Tocolytics - Beta mimetics
 Dosage
• Ritodrine (50 μg/min. increased by 50 μg/min./20
min.; maximum dose 350 μg/min.)
• Terbutaline (infusion of 2.5 μg/min. with increases
of 2.5 μg/min. every 20 min. similar to ritodrine
protocol). Another optional therapy includes 250
μg subcutaneously/3 hr.; oral terbutaline should
be begun at 5 mg. every 4-6 hr. as necessary to
inhibit contractions.
Management
Tocolytics - Magnesium sulfate
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Mechanism of action - competitively inhibits
calcium, thereby blocking actin/myosin interaction
Maternal side effects
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Pulmonary edema
Chest pain and tightness
Nausea
Flushing
Drowsiness
Blurred vision
Management
Tocolytics - Magnesium sulfate
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Fetal side effects
Fetal depression
 Lower neonatal Apgar scores
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Dosage - 4 gm loading dose over 20 min.
followed by 1-2 gm/hr. increasing by 0.5 gm/hr.
every 30 min. until cessation of contractions.
Maximum dosage 3.5-4 gm/hr.
Management
Tocolytics

Prostaglandin synthetase inhibitors
 Mechanism of action
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Decreases prostaglandins
Decreases intracellular calcium
Decreases gap junction formation
Prevents cervical connective tissue changes with
overall effect of:
• Smooth muscle relaxation
• Decreased synchronization
• Decreased inhibition of cervical maturation
Management
Tocolytics - Prostaglandin synthetase inhibitors
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Maternal side effects
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Abdominal pain
Anorexia
Aplastic anemia
Diarrhea
Dizziness
Vertigo
Frontal headaches
Hepatitis and jaundice
Mental confusion
Nausea
Neutropenia
Postpartum hemorrhage
Retention of sodium and fluids
Thrombocytopenia Ulcerative lesions of bowel
Management
Tocolytics - Prostaglandin synthetase inhibitors
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Fetal effects
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Intracranial hemorrhage
Oliguria
Premature closure of ductus arteriosus
Pulmonary hypertension
Dosage - 50 mg indomethacin followed by 25 mg in
2 hr. if contractions did not cease. Then 25 mg
every 4 hr. for 24 hr.
Management
Tocolytics - Prostaglandin synthetase inhibitors
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Calcium channel blockers
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Mechanism of action - smooth muscle relaxation by
decreasing intracellular calcium
Maternal side effects
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Headache
Tachycardia
Vasodilation
Hypotension
Transient facial flushing
Fetal side effects - none observed
Dosage - nifedipine orally 30 mg followed by 20 mg q8h .
Management
Steroids
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History - used to enhance lung maturation ･
Short-term benefits
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Meta-analysis of 15 trials reported the following
decreased:
• Respiratory distress syndrome (RDS)(O.R; 95% CI = 0.40.6)
• Necrotizing enterocolitis (NEC)
• Intraventricular hemorrhage (IVH)(O.R. 0.5; 95% CI = 0.30.9)
• Neonatal mortality (O.R. 0.6; 95% CI 0.5-0.8)
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No increase in infections
Management
Steroids
 Long-term benefits
 Increased
survival
 Follow-up (3-6 yr.) - no effect on
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Growth
Physical development
Motor or cognitive skills
School progress
Management
Steroids
 Adverse Effects
 Short-term
- Neonatal
• No increase in infections
• No adrenal suppression (clinically)
Management
Steroids
 Adverse Effects
 Long-term
-Neonatal (follow-up 12 yr.) - no
change in:
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Motor skills
Language skills
Cognitive ability
No change in memory
? increase in pharyngeal and ear infections
Management
Steroids
 Adverse Effects
 Short-term
- maternal
• Pulmonary edema
• Questionable increase maternal infection,
especially with PROM
• Worsening of diabetes control
 Long-term
- maternal: none
Management
Steroids
 Types of Corticosteroids
 Dexamethasone
• Readily crosses placenta
• No mineralocorticoid activity
• 6 mg intramuscular every 12 hr. x 4 doses
Management
Steroids
 Types of Corticosteroids
 Betamethasone
• Crosses placenta
• No mineralocorticoid activity
• 12 mg intramuscular every 24 hr. x 2 doses
Management
Steroids
 Timing
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Best if given > 24 hr. and < 7 days prior to delivery
May be slight benefit if treatment given and delivery
< 24 hr.
Not enough data for delivery > 7 days to make
judgments
One round of steroids only per NIH consensus
statement
Management
Steroids
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Indications
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24-34 wk.
24-28 wk.
• Decreases RDS severity
• Decreases mortality
• Decreases IVH
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28-34 wk.
• Decreases RDS
• Decreases mortality
Management
Steroids
 NIH Consensus Recommendations 2000
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All fetuses 24-34 wk. at risk for preterm delivery
Should not be influenced by race or gender of fetus
If patient eligible for tocolytics, she is eligible for
corticosteroids
Treatment recommendations
• Betamethasone 12 mg intramuscular/24 hr. x 2 doses
• Dexamethasone 6 mg intramuscular/12 hr. x 4 doses
Management
Antibiotics
 Infection may play a significant role in
preterm labor in select patients
 Up
to 25% in some series
 Average is 16%

Common organisms include GBS, GC,
Listeria, mycoplasma, bacteroides, and
ureaplasma
Management
Antibiotics
 Markers of infection
 Bacterial
endotoxin (LPS) in amniotic fluid
may stimulate cytokines and prostaglandins
 Endogenous host products - cytokines such
as interleukin-1, interleukin-6, TNF, etc.
 These products may be the result, not the
cause, of preterm labor.
Management
Antibiotics
 Studies
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Multiple studies using various antibiotics show no
benefit in management of preterm labor
Ampicillin used intrapartum for prevention of
neonatal GBS
Some evidence that treatment of bacterial vaginosis
in 2nd trimester of pregnancy may decrease
likelihood of PTL/PROM in high risk women
References
Cunningham FG, Gant NF, Leveno KJ, Gilstrap LC, Hauth JC,
Wenstrom K. Williams Obstetrics 21st Ed., Chapter 27 pages 689727, 2001.
Beckman, CRB, Ling FW, Laube DW, Smith RP, Barzansky BM,
Herbert WNP. Obstetrics and Gynecology 4th ed., chapter 22,
pages 304-312, 2002.
Adapted from Association of Professors of Gynecology and Obstetrics
Medical Student Educational Objectives, 7th edition, copyright
1997.
Clinical Case
Preterm Labor
Patient presentation
A 20-year-old African-American, who is 28 weeks
pregnant, presents to the labor unit complaining
of contractions. The contractions began 8 hours
ago and have increased in frequency and
duration. She notes that, for the last two days,
she has had increased vaginal discharge and
some lower back pain. Her prior pregnancy was
complicated by preterm labor and premature
ruptured membranes at 26 weeks gestation. The
neonates course was complicated by intraventricular hemorrhage and necrotizing
enterocolitis.
Patient presentation
Past medical history
Medical
Surgical
Obstetric
neg
appendectomy age 11
gravida 3 para 2 one preterm
delivery, living children 2, one
with cerebral palsy
Patient presentation
Physical exam
Temp 36.5oC (97.8oF), pulse 64,
respiration 20, BP 100/60, wt 49 kg
General
Thin women of stated gestational
age
Cardiac
Regular rate and rhythm, no rubs,
gallops or clicks
Abdomen
No hepatosplenomegaly, fundal
height 27 cm
Vaginal examNo fluid per os; cervix – 3cm
dilated and completely effaced;
vertex presentation
Vital Signs
Diagnosis & Management
Preterm labor at 27 weeks gestation plan
for tocolysis, steroids and penicillin for
Group B streptococcus prophylaxis
Discussion
Preterm birth is one of the major health hazards of
our time. It is the leading cause of neonatal
morbidity and mortality. Approximately 11-12%
of births occur prior to 37 wk. gestation.
Roughly 1/3 is due to preterm labor, 1/3 to
preterm premature ruptured fetal membranes
and 1/3 to medical or fetal complications. Efforts
to reduce or prevent preterm birth are largely
unsuccessful.
Discussion
Preterm birth is defined as that occurring less than 37 wk.
in the presence of regular uterine contractions (4 per
20 min or 8 per 60 minutes) with cervical change or if
the cervix is 2 cm dilated and 80% effaced. There are
many possible causes of preterm labor, including
infection, faulty placentation, uterine factors
(leiomyomata, uterine didelphys), overdistension of the
uterus (multifetal gestation, polyhydramnios),
immunologic causes, drug use (such as cocaine), and
idiopathic. Risk factors for preterm birth can be
subdivided into pre-pregnancy (i.e. low maternal
weight and prior preterm birth) and pregnancy-related
(twins, abnormal placentation, maternal factors).
Discussion
Management of women with preterm labor
involves tocolytics to reduce or stop the
contractions (evidence is weak that tocolytics
works longer than 24-48 hours),
corticosteroids to enhance lung maturation
and decrease the likelihood of neonatal
respiratory distress syndrome and penicillin
intrapartum to prevent early onset neonatal
GBS infection.
Discussion
Tocolytics can be divided into major categories
with various degrees of efficacy, safety, side
effect profiles, costs, etc. Categories include
B-sympathomimetic (ritodrine and terbutaline),
magnesium sulfate, prostaglandin synthetase
inhibitors (indomethacin), calcium channel
blockers (nifedipine) and oxytocin inhibitors
(atosiban).
Teaching points
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Preterm birth is a common pregnancy
complication
Risk factors for preterm labor/birth are many;
however the most common risk factors are prior
preterm birth and low maternal weight
Diagnosis of preterm labor is difficult
Management includes hydration, tocolytics (a
high rate of failure to prevent preterm birth),
corticosteroids and antibiotics