PRETERM LABOR

Melissa Tebrock MD
MAJ, MC, USA
Dewitt Army Community Hospital
9 June 2005
Disponible en:http://www.usuhs.mil/fap/capcon/256,1,PRETERM LABOR

Preterm Labor
Definition
Incidence
Etiology
Prevention/Surveillance
Diagnosis
Management

Preterm Labor (PTL)

ACOG defines Preterm Labor as regular
contractions with cervical change before 37
weeks gestation

PTL: Incidence
10-12% of all pregnancies
Related to 80% of perinatal mortality
Single greatest cause perinatal morbidity
and mortality in western countries
Most common cause of hospitalization
during pregnancy

Preterm Delivery (PTD)

Despite medical advances, PTL and preterm
births rates not improving
Medical advances = greater # complicated
pregnancies and successful PTD
Rate of U.S. preterm birth increasing
1995: 25th in world infant mortality
Huge health care costs
Continued ethical concerns

PTL Outcomes

Developmental delay
Cerebral Palsy & neurological deficits
Poor school grades
Chronic pulmonary issues
vision//hearing impairment
Family, school, economic burden

PTL: Risk Factors

Maternal Factors:

Age (<18 and >40)

Race (nonwhite)
Poverty
Smoking
Drugs/EtOH
Prior preterm birth

Maternal Factors:
Prior 2nd trimester loss
or bleeding
Psychological stress
Poor nutrition
Low prepregnancy
weight and gain

PTL: Risk Factors:

Uterine:
Anatomic anomaly:
-fibroids, placenta previa

Increased volume:
-multiple gestation, polyhydramnois

Trauma/abruption
Cervical incompetence/short cervix
Oligohydramnios

PTL and Infection

History of previous genital infection
Current genital infection
Current systemic infection, i.e.
pneumonia, periodontal disease,
appendicitis

PTL: Genital Infections

Often subclinical
Correlate more w/ PTL/PTB < 31 wks
Anaerobes and genital mycoplasmas
Ascend vagina, cervix, triggers leukocyte
recruitment, cytokine production,
enzymes which weaken protective
cervical mucous, cause PTL & preterm
premature rupture of membranes

PTL: Genital Infections

Chorioamnionitis
Chlamydia & gonorrhea: irritate cervix
Group B Streptococcus: amniotic irritation
Asymptomatic bacturia, UTI, Pyelonephritis
+/- Trichomonas, Candida, Ureaplasma
urealyticum, Mycoplasma hominis

PTL and Bacterial Vaginosis

Known association between PTL and BV
Found in 10-25% pregnant women, <3%
will have issues
50% asymptomatic
Treatment of BV in high risk women
shown to PPROM, not necessarily PTL
Trials for screening and treatment have
varying results

Etiology PTL
Often multifactorial
Often idiopathic
No risk factors in 50% of preterm births

Preterm Premature Rupture

of Membranes (PPROM)
PPROM: rupture membranes prior to 37
weeks and at least 1 hour before onset labor
Ave 8% all pregnancies
20-40% before 37 weeks
Same Risk Factors as PTL
Infection often the culprit

PTL: Prevention and Early

Detection
Education Programs: no evidence of efficacy
in low risk pregnancy
Intensive education in high-risk groups has
not decreased PTD rates in US
Effective in Europe

Home Uterine Activity

Monitoring (HUAM)
Theory: patients may not recognize early
uterine activity associated with PTD
HUAM studied as method to predict
preterm labor in high risk women
Tocodynamometer readings, daily phone
calls from RN/provider
Mixed study results, insufficient data and
cost have limited applicability

Risk Scoring Systems

Multiple scoring systems devised
No one better than another
Unsuccessful in predicting PTL
May have role in predicting PTD

Transvaginal Cervical
Ultrasonography
Provides reliable length, dilation, effacement
More accurate than digital exam
Risk PTD w/ cervix length

PPV 43%, NPV 89% if > 2.5 cm for PTD, accepted

safe length is 3 cm
Not currently recommended for routine screening
Use in high risk/symptomatic patients
Cervical funneling also useful predictor for PTL/PTDmore study needed

Biochemical Markers
Multiple markers for PTL found:

Fetal fibronectin
Salivary Estriol
IL-6
Estradiol-17B
Progesterone

Not currently recommended as routine

screening tools

Fetal Fibronectin (FFN)

Present throughout body, in blood
Is a glue like substance that helps maintain
placental attachment to the decidua
Not detectable in vaginal secretions after 20
weeks to term
If present after 20 weeks in cervical/vaginal
fluids= disruption maternal-fetal boundaries
Negative if < 50g/ml

Fetal Fibronectin
High specificity: after a negative test, 124
of 125 women will not deliver in next 14
days
Positive result: 1 in 6 women will deliver
in next 14 days (does not=delivery)
May aid in early discharge vs. increased
vigilance
FDA approved

Progesterone and PTL

Prevention
Inhibits oxytocin effect of prostaglandin
F2a and stimulation of alpha adrenergics,
acting as a tocolytic
No known teratogenic effects
May cause pain, swelling, bruising from
injection, but no known maternal/fetal
metabolic or hemodynamic effects

Progesterone and PTL

Prevention
Multiple studies show weekly IM injection of 2501000 mg alpha-hydroxyprogesterone caproate
from 16-37 weeks in women at risk for PTL
reduced PTD rates, w/ NNT range 2.4-7
? Reduced NEC, IVH, perinatal morbidity
Other studies did not demonstrate benefit
NOT FDA approved & not ACOG recommended

Asymptomatic Infection
Screening and Antibiotic
Prophylaxis
Some evidence to screen for asymptomatic
bacturia, though not currently recommended
No recommendation to screen for BV
routinely
Screen, treat based on risk, symptoms,
personal comfort level
Prophylaxis in asymptomatic women not
recommended

PTL/PPROM Evaluation
History:
Ask about Risk Factors
Dating (preterm)
Onset symptoms (back pain, pressure, cramps,
contractions, fluid leak, bleeding)
Other medical history

PTL/PROM Exam

Maternal vitals: temp, BP, P, RR

Maternal quick physical
Fetal heart rate (FHR) pattern
Contraction pattern
Fetal size, presentation
DO NOT DO DIGITAL EXAM IF ROM
SUSPECTED OR WILL DO FFN TEST!

PTL/PPROM Exam
Sterile Speculum Exam:
Look for pooling, trailing membranes
Nitrazine, ferning

Cervix visualization
FFN if available
Wet prep, cultures (GBS, GC, Chl)

PTL/PPROM studies
Ultrasound:
cervix length, AFI, gestational age

CBC, UA: r/o infection

Preeclampsia labs as needed
Amniocentesis for lung maturity as needed

PTL
4 contractions in 20 minutes or
8 contractions in 60 minutes with

PROM
Progressive cervical change
Effacement greater than 80%
Cervical dilation greater than 1 cm

Dilation >3cm, positive FFN concerning

regardless of presence of contractions

Initial Thoughts
Hydration, bed rest, pelvic rest
No evidence this is beneficial

Consider early transfer

Is delivery imminent?
Condition mother and fetus
Capabilities your/transfer center

Medical Management of
Preterm Labor
Steroids
Tocolysis
Antibiotics

PTL: Steroids
Reduces RDS, IVH, NEC, infant mortality
Only treatment shown to improve fetal
survival in PTL
Criteria:
Delivery likely within 7 days
fetus 24-34 weeks
Able to delay delivery 24-48 hrs

PTL: Steroids
Use between 32-34 weeks arguable- may
no benefit RDS but may benefit IVH up
to 34 weeks
Regimens:
-Betamethasone 12 mg IM, 2 doses, q 24
hr
-Dexamethasone 6 mg IM, 4 doses, q 12 hr

PTL: Steroids
Maternal Adverse Effects
Short term: glucose control, pulmonary edema,
infection
Long term: no adverse effects

Fetal Adverse Effects

No long term effects of single course
Multiple course associated w/ infection,
abnormal development

Tocolysis
Only evidence showing acute tocolysis is
beneficial for short term PTL management,
and not for PTD
No evidence that maintenance tocolysis is
beneficial fro PTL or PTD at this time in
large studies

PTL: Tocolysis
Goal: prolong pregnancy 2-7 days for
steroid efficacy and transfer to higher
level of care,
Goal: reduce contractions (< 6/hr) and
stop cervical change

Tocolysis
Criteria:
-Assure maternal/fetal well being first
no contraindication to rx
no contraindication to prolonging pregnancy
Diagnosis clear
Cervix <4cm
24-34 weeks

Tocolysis
General Contraindications

Acute fetal distress

Chorioamnionitis
Severe preeclampsia/eclampsia
Fetal demise
Fetal maturity
Maternal hemodynamic instability

Tocolytic Agents
Beta-mimetics
Ritodrine, terbutaline

Magnesium Sulfate
Indocin
Nifedipine (CCBs)

Beta-mimetics
Function:
Stimulate beta2 receptors in uterus and lung, decrease
contractility
Cross react with beta2 in heart

Efficacy: shown to prolong labor 24-48 hours to

allow transfer and steroid benefits
Ritodrine (FDA approved) and Terbutaline
Neither beneficial to neonatal mortality, but
studies done prior to steroid use

Beta-mimetics
Terbutaline
IV and multiple SC dosing effective in temporarily
stopping contractions
SC 0.25 mg q 1-4 hours
IV 0.01 mg/min, 0.005 mg/min to maximum of 0.025
mg/min
Oral dose not effective in PTL (ok for PTCx)

Ritodrine: iv only, 0.1 mg/min, increase by 0.05

mg/min q 30 minutes, titrate down & stop 12 hours
after contractions stopped (max 0.35 mg/min)

Maternal Side Effects: Betamimetics

Tremor, nervousness, HA, N/V, anxiety,
SOB, palpitations, chest pain
Hyperglycemia, electrolyte abnormalities
Fluid retention, hyperkinesias
Hypotension, pulmonary edema,
arrhythmias, MI, tachyphylaxis

Fetal Side Effects of Betamimetics

Tachyarrhythmia, heart failure, MI,
hypotension
Hyper/hypoglycemia, hyperbilirubinemia
Death

Contraindications: Betamimetics
Absolute:
Maternal cardiac disease, eclampsia,
severe pre-eclampsia, hemorrhage,
uncontrolled hyperthyroid, diabetes
Relative:
Diabetes, hypertension, migraines,
sepsis

Magnesium Sulfate
Widespread use
No clear evidence showing efficacy in
delaying/preventing PTD
Controversy: ?may increase infant mortality, but
studies show less gross motor dysfunction in
infants
? Works by calcium antagonist activity
Load 4-6 gm IV, then 1-4 gm/hour, no wean
Oral dose not effective

Magnesium Sulfate
Side effects:
N/V, HA, warmth, sweating, flushing, hypocalcemia,
tetany, muscular paralysis, hypotension, palpitations,
pulmonary edema, respiratory arrest (toxic levels),
cardiac arrest (rare)
Pulmonary edema worse when used with terbutaline

Crosses placenta, no adverse fetal effects (may

have less reactivity)

Magnesium Sulfate
Contraindications:
Myasthenia Gravis, renal failure, hypocalcemia

Exam:

Fluid I/O, UOP, VS, mental status hourly

Pulm exam
Reflexes (loss when level >8)
Therapeutic level: 5.5-7.5 mg/dl, toxic >15
Antidote: calcium gluconate

Indocin

Inhibits prostaglandins/cytokines that trigger labor

Well studied, use limited by side effects
Can inhibit PTL for 48 hrs in <37 weeks
Use in cases w/ good dating, <32 weeks
Dosing:
100mg rectal dose, repeat x1 in 1-2 hours if
contractions persist
25-50 mg orally q4-6 hours <48 hours for cessation of
contractions

Indocin
Well tolerated by mom, causing usual
NSAID side effects
Does not decrease neonatal mortality, may
increase IVH, jaundice, NEC risk after 32
weeks
Can cause PPH, constrict fetal ductus
arteriosis, oligohydramnios

Nifedipine

Inhibit contraction of smooth muscle

Very efficacious
Nifedipine most widely studied CCB
Some studies show as efficacious or better
than beta-mimetics with less side effects
Gaining popularity as tocolytics of choice

Nifedipine
Fetal effects:
No adverse fetal effects
No increase congenital anomalies

Maternal effects:
Flushing dizziness, nausea, hypotension
Contraindicated if hypotensive, cardiac disease
or hemorrhage

Nifedipine
Dosing:
30 mg oral dose load
10-20 mg po q 4-6 hours

Antibiotics
If have specific infection, treat
If known GBS+, treat (no benefit PTL, but decrease
transmission to infant)
Empiric antibiotics in PTL w/ intact membranes:
Conflicting results: no short/long term benefits, delay of
PTD

Ampicillin 2 gms iv q 6 hours (macrolides also

effective) often used if unclear GBS/possible
infection
USE IN PPROM- beneficial

PROM/PPROM
If >36 weeks, manage as PROM
If <32 weeks, manage as PPROM
If 32/36 weeks, weight amniocentesis,
weight, options

PPROM Management
Delivery likely within 12-24 hours

Tertiary care center w/ NICU

Tocolysis, steroids
Antibiotics for GBS
Avoid digital exams

Expectant management in delivery not

imminent

Delivery of Premature Infant

Anticipate malpresentation
Limit narcotics
Delivery <10 cm dilation
NICU team

ACOG Recommendations for

PTL Management (5/03):
No clear first-line tocolytic drugs for PTL
Circumstances dictate treatment
Antibiotics do not appear to prolong gestation
and should be reserved for GBS
prophylaxis in imminent delivery
Neither maintenance tocolysis or repeated
acute tocolysis improve perinatal outcome

ACOG Recommendations for

PTL Management (5/03):
Tocolytic drugs may prolong pregnancy for 27 days, allowing for steroids administration
to improve fetal lung maturity and maternal
transport
Bed Rest, hydration and pelvic rest do not
appear to improve PTD rates and should not
be routinely recommended

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