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  • Defined as delivery before completion of 37 weeks
  • Increasing in frequency in the United States: 9.4% (1981), 10.7% (1992), 12.3% (2003), 12.8% (2006)
  • Pathophysiology:
    • Excessive myometrial and fetal membrane overdistention:
      • Multiple gestation
      • Polyhydramnios
    • Decidual hemorrhage
    • Precocious fetal endocrine activity
    • Intrauterine infection or inflammation
  • Clinical diagnosis: regular, painful uterine contractions + cervical dilatation or effacement
  • Outcome:
    • Thirty percent diagnosed as “preterm labor” will deliver full term
    • Fifty percent hospitalized for “preterm labor” will deliver full term
    • Therapeutic interventions seldom effective in prolonging pregnancy

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  • Most tocolytic drugs are only effective to prolong pregnancy for 24–48 hours
  • Delay delivery to allow corticosteroid (betamethasone) delivery and effect to mature pulmonary surfactant:
    • Typical dose 12 mg IM once daily (two doses total)
    • Initial benefit at 18 hours after first dose
    • Maximum benefit at 48 hours of therapy
    • Decrease risk of neonatal respiratory distress, intraventricular hemorrhage, necrotizing enterocolitis, and perinatal death
  • Permit transport of mother to regional facility

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See following table.

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Tocolytic Agents
MedicationMechanismEfficacySide effects
Beta-2 agonists (terbutaline, ritodrine)
  • Beta-2 stimulation inhibits myosin light chain kinase via a G-protein-coupled increase in intracellular cAMP
  • Bolus dose of terbutaline is 250 μg IV push; this achieves uterine relaxation for a few minutes duration
  • For suppression of preterm labor an infusion is started at 2.5 μg/min and increased by 2.5 μg/min every 20 min until the contractions stopped; maximum rate is 25 μg/min
  • Ritodrine is no longer available in the United States
  • Decrease immediate (within 48 h) birth rate
  • No decrease in delivery rates at 7 days
  • No change in perinatal or neonatal mortality
  • Hypotension due to beta-2-mediated vasodilation
  • Tachycardia, atrial fibrillation/flutter
  • Myocardial ischemia
  • Pulmonary edema
  • Hyperglycemia secondary to glucagon-mediated glycogenolysis and gluconeogenesis
  • Hypokalemia/rebound hyperkalemia (intracellular transfer)
  • Increased fetal heart rate
  • Fetal hypoglycemia
Calcium channel blockers (nifedipine)
  • L-type calcium channel inhibition reduces intracellular calcium levels in uterine smooth muscle
  • Nifedipine is the most commonly used agent
  • Usual starting oral dose is 10–20 mg
  • Repeat dosing and frequency is less clear
    • High doses have been associated with pulmonary edema
  • Reduce delivery rates within 7 days of treatment
  • Reduce frequency of neonatal respiratory distress, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal jaundice
  • Pulmonary edema (possible high-output heart failure?)
  • Hypotension
  • Fetal death
  • Heart block
  • Neuromuscular block in combination with magnesium sulfate therapy
Magnesium sulfate
  • Mechanism of action is poorly understood
  • Decreases the frequency of depolarization of muscle by modulating calcium uptake, binding, and distribution
  • High concentrations needed for effect
  • Loading dose is 6 g (as opposed to 4 g in preeclampsia) and infusion of 2 g/h for maintenance
  • No difference in the risk of birth within 48 h
  • No difference in perinatal mortality compared with placebo
  • May have neuroprotective effects in newborn if administered to mother prior to preterm birth
  • Nausea, vomiting, and lethargy
  • Volume overload
  • Shortness of breath
  • Pulmonary edema
  • Chest pain
  • Respiratory arrest
  • Cardiac arrest
  • Neonatal paralytic ileus
  • Interference with neuromuscular monitoring
  • Enhances effects ...

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