What are the tocolytics (tocolytic agents) of choice for delaying preterm birth?

Tocolytics of Choice for Delaying Preterm Birth

Nifedipine and indomethacin are the tocolytics of choice for delaying preterm birth, with nifedipine being preferred as first-line therapy due to its oral administration and favorable side effect profile. 1, 2

Evidence-Based Selection of Tocolytic Agents

• Tocolytic therapy aims to delay delivery for 48-72 hours to allow for administration of antenatal corticosteroids and maternal transfer to a tertiary care facility with appropriate neonatal intensive care capabilities 1, 3
• Studies suggest that nifedipine and indomethacin may delay delivery between 48 and 72 hours in women with preterm labor and intact membranes after 26 weeks of gestation 1
• Calcium antagonists, particularly nifedipine, have been shown to be more effective than beta-2-sympathomimetics in delaying delivery and have been associated with reduced perinatal morbidity 2

Specific Tocolytic Recommendations

First-Line Options:

• Nifedipine (calcium channel blocker):

  • Benefits include oral administration, effectiveness in delaying delivery, and fewer maternal side effects compared to beta-mimetics 2, 4
  • Most common side effects include maternal hypotension and tachycardia 4
  • Preferred in Europe as first-line therapy along with atosiban 5

• Indomethacin (prostaglandin synthetase inhibitor):

  • Effective for tocolysis, particularly before 32 weeks of gestation 6
  • Should be limited to short-term use (up to 48 hours) due to potential fetal side effects 6
  • Potential fetal/neonatal concerns include ductal constriction and oligohydramnios 4

Alternative Options:

• Magnesium sulfate:
  • While used as a tocolytic, its primary benefit in the periviable period is for fetal neuroprotection 1
  • Reduces the incidence of cerebral palsy when administered before anticipated early preterm birth 1
  • Potential side effects include fluid overload and rarely pulmonary edema 4

Clinical Application and Considerations

• Tocolytic therapy should be considered when:

  • Gestational age is between 24-34 weeks 1, 3
  • There is a need to administer antenatal corticosteroids 1, 3
  • Maternal transfer to a tertiary care facility is required 3

• Tocolytic therapy is generally not recommended in:

  • Preterm labor with intact membranes when antibiotics are being considered (no evidence of benefit) 1
  • Cases where delivery would be beneficial for maternal or fetal indications 1

Important Caveats and Considerations

• Despite their ability to delay delivery temporarily, no tocolytic has been consistently shown to improve neonatal outcomes or reduce the overall rate of preterm birth 1, 6

• The primary benefit of tocolytics is to gain time for corticosteroid administration and maternal transfer 3

• The choice of tocolytic should consider:

  • Gestational age (limited data for use before 26 weeks) 1
  • Maternal comorbidities and contraindications 4, 5
  • Fetal status and potential side effects of the medication 4

• Emergency cerclage may be considered as an alternative to tocolysis in cases of cervical dilation with visible membranes at less than 24 weeks, in the absence of contractions, PROM, or infection 1