SUMMARY:

Preterm birth (delivery between 20w0d to 36w6d) is the leading cause of neonatal mortality, affecting 12% of all deliveries, with 50% preceded by preterm labor. Preterm labor includes regular uterine contractions with cervical dilation, effacement or both. Preterm birth accounts for a significant burden of poor neonatal outcomes, including 70% of neonatal deaths, 36% of infant deaths, and up to 50% of long-term neurological impairment with a heavy financial burden. Of note, half of all patients hospitalized for preterm labor will deliver at term.

Definition

• Regular uterine contractions with cervical dilation and/or effacement
• Initial presentation of >2 cm dilation with contractions

Tests to Stratify Risks of Preterm Birth

Fetal Fibronectin

• Protein that is present in the decidual-chorionic interface
• Poor positive predictive value |Should not be used alone | Consider full clinical context
• Does not decrease the rates of hospitalization or preterm birth
• Screening performance: ≥50 ng/mL for delivery within 7 to 10 days
  • Sensitivity 76% | Specificity 82%
• Positive predictive value is higher if a higher cutoff is used
• False positive results: Semen | Blood | Digital examination | Some lubricants | Other medications
• Predictive and not a diagnostic test

Cervical Length

• Limited data
• A length of >30mm has a high negative predictive value
• Combination fetal fibronectin and cervical length
  • ACOG states that this combination should not be used exclusively to direct management in setting of acute symptoms
  • Some use this combination by obtaining fetal fibronectin in selected patients with cervical length between 2 and 3 cm

Common Interventions

Tocolysis

• Provides short-term prolongation of pregnancy
• Tocolysis only appropriate for pregnancies (singleton and multiple gestations) that would benefit from 48-hour delay in delivery (i.e., administration of steroids or magnesium sulfate)
• Maintenance therapy is ineffective for preventing preterm birth and can have potential maternal risks
• Does not improve neonatal outcomes
• Contraindications
  • Intrauterine fetal demise
  • Lethal fetal anomaly
  • Non-reassuring fetal status
  • Severe preeclampsia or eclampsia
  • Maternal bleeding with hemodynamic instability
  • Chorioamnionitis
  • Preterm premature rupture of membranes | Consider for maternal transfer and/or steroids)
  • Agent specific maternal contraindications (see below)

Note: Women with preterm contractions without cervical change generally should not be treated with tocolytics

Tocolytic Agents

• Calcium Channel Blockers
  • Decreases the levels of intracellular free calcium causing relaxation of the myometrium
  • Medication
    • Nifedipine 10mg Instant Release PO 20 to 30mg loading dose followed by 10 to 20mg every 4 to 6 hours
  • Maternal Side Effects
    • Dizziness | Hypotension | Suppression of heart rate contractility and left ventricular systolic pressure | Elevation of transaminases
  • Fetal Side Effects
    • No known adverse effects
  • Contraindications
    • Hypotension | Preload-dependent cardiac lesions (aortic insufficiency)
• Non-steroidal anti-inflammatory drugs (NSAIDs)
  • Decreases the levels of prostaglandins, which cause labor
  • Medication
    • Indomethacin 50 to 100mg loading dose followed by 25mg every 4 to 6 hours
  • Maternal Side Effects
    • Nausea, gastritis, platelet dysfunction (rare)
  • Fetal Side Effects
    • Constriction of ductus arteriosus | Oligohydramnios | Necrotizing enterocolitis
    • Not recommended for use after 32 weeks GA
  • Contraindications
    • Bleeding disorder | Hepatic dysfunction | Renal dysfunction | GI ulcerative disease | Asthma (if hypersensitivity to aspirin)

• Beta adrenergic agonist
  • Increases intracellular levels of cAMP, causing relaxation of myometrium
  • Medication
    • Terbutaline 0.25mg subcutaneous every 20 to 30 minutes for up to 4 doses
    • Maintenance dose is 0.25mg every 4 hours
    • Should not be used >48 hours
  • Maternal side effects
    • Tachycardia | Palpitations | Shortness of breath | Pulmonary edema | Hypokalemia | Hyperglycemia
  • Fetal Side Effects
    • Fetal tachycardia
  • Contraindications
    • Tachycardia-sensitive cardiac disease | Poorly controlled diabetes

Note: First line agents for tocolysis are beta-adrenergic agonists, calcium channel blockers or NSAIDs

• Magnesium sulfate
  • Precise mechanism of action is unknown
  • Primary utilization is for fetal neuroprotection, but may also inhibit myometrial activity
  • Magnesium is ineffective at delaying or preventing preterm birth
  • See protocols for neuroprotection
  • Maternal Side Effects
    • Flushing | Diaphoresis | Loss of deep tendon reflexes | Respiratory depression | Cardiac arrest
  • Fetal Side Effects
    • Neonatal depression
  • Contraindications
    • Myasthenia gravis

Magnesium Sulfate for Neuroprotection

• Predelivery administration of magnesium sulfate <32 weeks reduces the rate of cerebral palsy
• Different regimens have been studied | Each hospital should decide their protocol
• Suggested protocols
  • 4g loading (20 minutes) and 1 gr/hour maintenance for maximum of 24 hours or
  • 6g loading (20 minutes) and 2 gr/hour maintenance for maximum of 12 hours or
  • 4g loading without maintenance

Note: If magnesium sulfate is being used for neuroprotection, ACOG recommends that beta-adrenergic receptor agonists and calcium-channel blockers “should be used with caution in combination with magnesium sulfate for this indication” | <32 weeks, indomethacin is a potential option for tocolysis

Antenatal Corticosteroids

• Improved neonatal outcomes including decreased severity and/or frequency of
  • RDS | Intracranial hemorrhage | Necrotizing enterocolitis | Death
• Recommended for
  • <34 weeks
  • At risk for delivery within 7 days irrespective of membrane status and fetal number
• Rescue course suggested
  • High risk of delivering within the next 7 days
  • <34 weeks
  • Received a prior course of corticosteroids >7 days before
  • Current evidence suggests a reduction of RDS rates after a rescue course of corticosteroids
• Antenatal corticosteroids can be considered as early at 22w0d after a discussion on counseling and resuscitation
• Late Preterm
  • Single antenatal corticosteroids course is recommended between 34w0d and 36w6d in women at high risk of delivering within the next seven days and meet inclusion criteria for the ALPS trial

Note: For more on antenatal steroids and the SMFM guidance on late preterm steroids, see ‘Related ObG Topics’ below

Interventions Not Recommended

• Antibiotics
  • Should not be used to prolong gestation 
  • Antibiotics are indicated for preterm premature rupture of membranes and GBS prophylaxis
• Nonpharmacologic Interventions such as bed rest and hydration
  • Have not been shown to be effective for prevention of preterm birth

KEY POINTS:

• Preterm birth is the leading cause of neonatal mortality
• Currently there is no diagnostic test that should be used exclusively to direct management in setting of acute symptoms
• Tocolysis are appropriate for pregnancies that would benefit from 48-hour delay in delivery for fetal lung maturity
• Magnesium sulfate and corticosteroid course should be administered based on current guidelines

Learn More – Primary Sources

ACOG Practice Bulletin 171: Management of Preterm Labor

ALPS Trial: Antenatal Betamethasone for Women at Risk for Late Preterm Delivery

Related ObG Topics:

Antenatal Corticosteroids – When to Administer?

SMFM Guidance on Antenatal Corticosteroid Use and Late Preterm Delivery

MgSO4 and Neuroprotection: What is the Relationship Between Maternal Dose and Fetal Levels?

Does Magnesium Sulfate Provide Neuroprotection in Preterm Fetuses with Growth Restriction?

Prediction and Prevention of Preterm Birth

RCT Results: Nifedipine for Acute Tocolysis and Preterm Birth Prevention