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Preterm Labor
Kara M. Coassolo, MD
John C. Smulian, MD, MPH
image BASICS
Contractions occurring between 20 and 36 weeks' gestation at a rate of 4 in 20 minutes or 8 in 1 hour with at least one of the following: cervical change over time or dilation ≥2 cm
Preterm birth is the leading cause of perinatal morbidity and mortality in the United States.
10-15% of pregnancies experienced at least one episode of preterm labor.
˜12% of all births in the United States are preterm (9% spontaneous preterm births and 3% indicated preterm births).
  • Premature formation and activation of myometrial gap junctions
  • Inflammatory mediator-stimulated contractions
  • Weakened cervix (structural defect or extracellular matrix defect)
  • Abnormal placental implantation
  • Systemic inflammation/infections (e.g., UTI, pyelonephritis, pneumonia, sepsis)
  • Local inflammation/infections (intra-amniotic infections from aerobes, anaerobes, Mycoplasma, Ureaplasma)
  • Uterine abnormalities (e.g., cervical insufficiency, leiomyomata, müllerian anomalies, diethylstilbestrol exposure)
  • Overdistension (by multiple gestation or polyhydramnios)
  • Preterm premature rupture of membranes
  • Trauma
  • Placental abruption
  • Immunopathology (e.g., antiphospholipid antibodies)
  • Placental ischemic disease (preeclampsia and fetal growth restriction)
Familial predisposition
  • Demographic factors, including single parent, poverty, and black race
  • Short interpregnancy interval
  • No prenatal care
  • Prepregnancy weight <45 kg (100 lb), body mass index <20
  • Substance abuse (e.g., cocaine, tobacco)
  • Prior preterm delivery (common)
  • Previous 2nd-trimester dilation and evacuation (D&E)
  • Cervical insufficiency or prior cervical surgery (cone biopsy or loop electrosurgical excision procedure [LEEP])
  • Abdominal surgery/trauma during pregnancy
  • Uterine structural abnormalities such as large fibroids or müllerian abnormalities
  • Serious maternal infections/diseases
  • Bacterial vaginosis
  • Bacteriuria
  • Vaginal bleeding during pregnancy
  • Multiple gestation
  • Select fetal abnormalities
  • Intrauterine growth restriction
  • Placenta previa
  • Premature placental separation (abruption)
  • Polyhydramnios
  • Ehlers-Danlos syndrome
  • Patient education at each visit in 2nd and 3rd trimesters for those at risk and periodically in the last two trimesters for the general population
  • If previous preterm birth, evaluate if etiology is likely to recur and target intervention to specific condition.
    • Weekly injections of 17&agr;-hydroxyprogesterone (250 mg IM every week) from 16 to 36 weeks if previous spontaneous preterm birth
    • Consider cerclage placement before 24 weeks' gestation for those at high risk because of cervical insufficiency or significant or progressive cervical shortening (1)[A],(2)[C].
    • For women with a short cervix in the 2nd trimester (<20 mm on transvaginal US), progesterone 200 mg/day per vagina for 24 to 34 weeks may decrease the risk of preterm delivery (3)[A].
Diagnosis is generally based on a combination of significant cervical changes (such as dilation, effacement) with regular contractions. However, there is no single test that will reliably diagnose or predict true preterm labor. The diagnosis is based on a combination of physical findings and diagnostic tests that are interpreted in the context of the degree of risk to the patient.
  • Sterile speculum exam for membrane rupture evaluation, cultures, and cervical inspection
  • Bimanual cervical exam if intact membranes: dilation of the cervix >1 cm and/or effacement of the cervix >50%
  • Braxton-Hicks contractions/false labor
  • Round ligament pain
  • Lumbosacral muscular back pain
  • Urinary tract or vaginal infections
  • Adnexal torsion
  • Degenerating fibroid
  • Appendicitis
  • Dehydration
  • Viral gastroenteritis
  • Nephrolithiasis
Initial Tests (lab, imaging)
  • In symptomatic women from 22 to 34 weeks' gestation with intact membranes and no intercourse or bleeding in past 24 hours, obtain a fetal fibronectin (FFN) swab from the posterior vaginal fornix (4)[C]. FFN must be obtained prior to digital cervical exam.
    • If results are positive (≥50 ng/mL), patient is at a modest increased risk of preterm birth (positive predictive value [PPV] 13-30% for delivery within 2 weeks).
    • If results are negative, >97% of patients will not deliver in 14 days, so can consider avoiding complicated or high-risk interventions.
  • Urinalysis and urine culture
  • Cultures for gonorrhea and chlamydia
  • Wet prep for bacterial vaginosis evaluation (although evidence for improved outcomes with treatment is weak)
  • Vaginal introitus and rectal culture for group B Streptococcus
  • pH and ferning test of vaginal fluid to evaluate for rupture of membranes
  • CBC with differential
  • Drug screen when appropriate
  • US to identify number of fetuses and fetal position, confirm gestational age, estimate fetal weight, quantify amniotic fluid, and look for conditions making tocolysis contraindicated.
  • Transvaginal US to evaluate cervical length, funneling, and dynamic changes after obtaining FFN (if clinical assessment of the cervix is uncertain or if the cervix is closed on digital exam)
Follow-Up Tests & Special Considerations
  • Repeat FFN as indicated by symptoms.
  • After successful treatment, progressive changes of the cervix on repeat examination or US (in 1 to 2 weeks) may indicate need for hospitalization.
Diagnostic Procedures/Other
  • Monitor contractions with external tocodynamometer.
  • Consider amniocentesis at any preterm gestational age to evaluate for intra-amniotic infection (cell count with differential, glucose, Gram stain, aerobic, anaerobic, Mycoplasma, Ureaplasma cultures).
Test Interpretation
  • Placental inflammation
    • Acute inflammation usually caused by infection
    • Chronic inflammation caused by immunopathology
  • Abruption

  • Treat underlying risk factors (e.g., antibiotics for infections, hydration for dehydration).
  • Liquids only or NPO if delivery is imminent
  • Hospitalization is necessary if the patient is on IV tocolysis.
Tocolysis may allow time for interventions such as transfer to tertiary care facility and administration of corticosteroids but may not prolong pregnancy significantly (5)[A].
First Line
  • Tocolysis
    • Nifedipine: 30 mg PO loading dose; then 10 to 20 mg q6h for 24 hours; then 10 to 20 mg PO q8h (do not use sublingual route); check BP often and avoid hypotension. Concurrent use with magnesium sulfate should be avoided to avoid theoretic risk of neuromuscular blockade.
    • Indomethacin: 50 to 100 mg PO initial dose; then 25 to 50 mg q6-8h for 24 hours (or, if available, 100-mg suppository per rectum q12h for 2 doses); then 25 mg q6-8h; use for no longer than 72 hours due to risk of premature closure of ductus arteriosus, oligohydramnios, and possibly neonatal necrotizing enterocolitis. Use with caution in patients with platelet dysfunction, liver dysfunction, or allergy to aspirin.
    • Contraindications to tocolysis: severe preeclampsia, hemorrhage, chorioamnionitis, advanced labor, intrauterine growth retardation, fetal distress, or lethal fetal abnormalities
  • Antibiotics: antibiotics for group B Streptococcus prophylaxis if culture is positive or unknown
  • Steroids: If mother is at 23 to 34 weeks' gestation with no evidence of systemic infection, give glucocorticoids to decrease neonatal respiratory distress, intraventricular hemorrhage, necrotizing enterocolitis, and overall perinatal mortality. Betamethasone 12 mg IM for 2 doses 24 hours apart (preferred choice) or dexamethasone 6 mg IM q12h for 4 doses (6)[A]
Second Line
  • Magnesium sulfate by IV infusion has not been shown to be superior to placebo in prolonging pregnancy beyond 48 hours. The side effects are generally greater compared with calcium channel blockers or NSAIDs. Therefore, this agent should be used cautiously if at all (standard dosages for tocolysis start with a 4- to 6-g IV bolus over 20 minutes followed by 2 to 3 g/hr infusion until contractions stop) (7)[C].
    • Magnesium may decrease the risk of cerebral palsy when 12-hour course is given prior to an anticipated preterm birth.
    • Relative contraindications to magnesium sulfate include myasthenia gravis, hypocalcemia, renal failure, or concurrent use of calcium channel blockers.
  • Terbutaline 0.25 mg SC q30min for up to 3 doses until contractions stop, then 0.25 mg SC q6h for 4 doses (optional); if contractions persist or pulse >120 bpm, change to another tocolytic agent (may be poorly tolerated by mothers).
  • Terbutaline PO or by infusion pump has been used in the past for treatment or prevention of preterm labor. Due to reports of serious cardiovascular events and maternal deaths, PO or long-term SC administration of terbutaline should not be given.
  • Significant possible interactions include pulmonary edema from crystalloid fluids and tocolytic agents, especially magnesium sulfate.
  • PO maintenance therapy with any agent is ineffective and is not recommended.
  • If delivery is inevitable but not immediate, consider transport to a tertiary care center or hospital equipped with a neonatal ICU.
  • Consider consultation with maternal-fetal medicine specialist.
  • Pelvic rest (e.g., no douching or intercourse) and activity restriction are often recommended; however, data to prove the efficacy are lacking. Some reduction in physical activity may be reasonable; this should be individualized.
  • Strict bed rest has not been demonstrated to be effective in most situations.
  • For malpresentation or fetal compromise, consider cesarean delivery if labor is progressing.
  • Cerclage for cervical insufficiency (until 24 weeks' gestation)
Admission Criteria/Initial Stabilization
Suspected/threatened preterm labor
  • IV access
  • Continuous fetal and contraction monitoring
  • Assess cervix for dilatation and effacement.
IV Fluids
Hydrate with 500 mL 5% dextrose normal saline solution or 5% dextrose lactated Ringer solution for first half hour; then at 125 mL/hr.
Monitor for fluid overload (input/output monitoring, symptoms, lung auscultation, pulse oximetry), especially with tocolysis and multiple gestations.
Discharge Criteria
  • Regular contractions and cervical change resolve
  • If cervix is dilated ≥3 cm or FFN is positive, individualize decision to discharge by gestational age and patient circumstances.
Patient Monitoring
  • Weekly office visits with contraction monitoring, cervical checks, or cervical US if at high risk for recurrence
  • Routine use of maintenance tocolysis is ineffective in preventing preterm birth.
Call physician or proceed to hospital whenever regular contractions last >1 hour, bleeding, increased vaginal discharge or fluid, decreased fetal movement.
  • If membranes are ruptured and no infection is confirmed, delivery often occurs within 3 to 7 days.
  • If membranes are intact, 20-50% deliver preterm.
1. Tita AT, Rouse DJ. Progesterone for preterm birth prevention: an evolving intervention. Am J Obstet Gynecol. 2009;200(3):219-224.
2. Simhan HN, Caritis SN. Prevention of preterm delivery. N Engl J Med. 2007;357(5):477-487.
3. Berghella V, Rafael TJ, Szychowski JM, et al. Cerclage for short cervix on ultrasonography in women with singleton gestations and previous preterm birth: a meta-analysis. Obstet Gynecol. 2011;117(3):663-671.
4. Goldenberg RL, Goepfert AR, Ramsey PS. Biochemical markers for the prediction of preterm birth. Am J Obstet Gynecol. 2005;192(5)(Suppl):S36-S46.
5. Haas DM, Caldwell DM, Kirkpatrick P, et al. Tocolytic therapy for preterm delivery: systematic review and network meta-analysis. BMJ. 2012;345:e6226.
6. Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2006;(3):CD004454.
7. American College of Obstetricians and Gynecologists Committee on Obstetric Practice; Society for Maternal-Fetal Medicine. Committee Opinion No. 455: magnesium sulfate before anticipated preterm birth for neuroprotection. Obstet Gynecol. 2010;115(3):669-671.
  • O60.00 Preterm labor without delivery, unspecified trimester
  • O60.02 Preterm labor without delivery, second trimester
  • O60.03 Preterm labor without delivery, third trimester
Clinical Pearls
  • Treatment of preterm labor may delay delivery to facilitate short-term interventions.
  • Steroids improve neonatal outcomes.
  • Progesterone therapy can prevent recurrence of preterm birth in next pregnancy.