Preterm Labor and Tocolysis

Key Points

Preterm labor (PTL) is defined as cervical change in response to uterine contractions, occurring between 20 and 36 weeks of gestational age. It may resolve spontaneously or progress to preterm birth with significant neonatal morbidity.
Patients with PTL are often managed with antenatal steroids to improve fetal lung maturation and magnesium sulfate for neuroprotection. They may receive a short (<48 hours) course of tocolytic agents to allow time for these therapies.
Tocolytic agents have significant maternal effects that can affect anesthetic management, including potential hypotension and other cardiovascular effects, muscle weakness, and potential post-partum uterine atony.

Epidemiology and Risk Factors

PTL is defined by the American College of Obstetricians and Gynecologists (ACOG) as cervical changes (at least 2 cm of dilation) that develop in response to uterine contractions occurring between 20 0/7 and 36 6/7 weeks of estimated gestational age.¹
Approximately 50% of preterm births are preceded by PTL. However, PTL does not always result in preterm birth. Approximately 30% of PTL resolve spontaneously, and 50% of patients hospitalized for PTL ultimately deliver at term.²
In the United States, preterm birth accounts for 12% of all live births. Preterm birth is associated with significant morbidity. It accounts for 70% of neonatal deaths, 36% of infant deaths, and 25-50% of long-term neurologic impairment in children.²
PTL is associated with conditions that cause decidual inflammation or hemorrhage, abnormal placental vascular perfusion, pathologic uterine distention, or increased fetal and maternal stress. These processes are complex, but they ultimately lead to the release of cytokines and prostaglandins that stimulate uterine contraction and cervical ripening.¹

Table 1. Risk factors for spontaneous preterm labor^1,3

Management of PTL

Management recommendations for PTL vary depending on the gestational age of the fetus, the anticipated risk of delivery, and the potential need for transfer to a higher level of care. ACOG recommendations are summarized in Table 2.
Administration of antenatal steroids for fetal lung maturation and magnesium for fetal neuroprotection is associated with improved neonatal outcomes.²
Tocolytic agents reduce uterine tone. In the setting of PTL, they are indicated for short-term (less than 48 hours) prolongation of pregnancy to initiation of other medical therapies or transfer to a higher level of care.²
A rescue cerclage may be placed for patients with cervical dilation and/or prolapsed membranes, though this recommendation is controversial. It is contraindicated for patients with impending delivery, chorioamnionitis, ruptured membranes, heavy vaginal bleeding, or fetal compromise.³
Fetal heart rate (FHR) monitoring may be used in patients with PTL with a viable fetus. Preterm fetuses exhibit decreased variability and lower acceleration magnitudes compared to term fetuses, which may complicate the interpretation of the FHR pattern.³

Table 2. Management of preterm labor² Abbreviations: PTL, preterm labor; GBS, Group B Streptococcus

Tocolytic Agents

Short-term tocolysis may be indicated during PTL. Contraindications are listed in Table 3.
Commonly used tocolytic agents and their side effects are listed in Table 4.
- Beta-adrenergic agonists, calcium channel blockers, and nonsteroidal anti-inflammatory drugs (NSAIDs) first-line tocolytic agents for PTL. Oxytocin receptor antagonists are commonly used in Europe, but they are unavailable in the United States.
- In the setting of PTL, magnesium sulfate administration is indicated to improve neonatal neurologic outcomes, not for tocolysis. It is included in the chart below because it has tocolytic effects and maternal/fetal side effects that are significant for anesthesiologists.
- Anesthesiologists may use other agents, such as volatile anesthetics and nitroglycerin, for tocolysis in the perioperative setting.

Table 3. Contraindications to tocolysis²

Table 4. Overview of tocolytic agents^1,3

Figure 1. Key molecular pathways regulating myometrial contraction and pharmacologic targets of tocolytics. Source: van Winden T, et al. A historical narrative review through the field of tocolysis in threatened preterm birth. Eur J Obstet Gynecol Reprod Biol X. 2024; 22:100313. ScienceDirect. CC BY 4.0 https://www.sciencedirect.com/science/article/pii/S2590161324000334

Anesthetic Implications for PTL³

Patients with PTL may require anesthesia for labor analgesia, cesarean delivery, or placement and removal of cerclages. As with term delivery, neuraxial anesthesia is generally preferred to general anesthesia unless it is contraindicated for the patient refuses it.
There is minimal evidence to support altering anesthetic technique for labor and delivery because the fetus is preterm. Early initiation of neuraxial labor analgesia may be beneficial, as the timing of delivery can be difficult to establish. Patients with PTL may have a prolonged latent phase of labor, but they often progress rapidly once active labor begins. In addition, established labor analgesia can be rapidly converted to surgical anesthesia if the patient requires emergency cesarean delivery.
Effects of tocolytic agents
- Calcium channel blockers and beta-adrenergic agonists may have significant cardiovascular effects, including vasodilation, myocardial depression, and changes in cardiac conduction. These may lead to intraoperative hypotension and hemodynamic instability.
- NSAIDs may affect platelet function. When used alone, they are not a contraindication to neuraxial anesthesia. Caution is recommended in patients receiving NSAIDs with other pharmacologic anticoagulants.
- Magnesium sulfate has significant perioperative effects, including hypotension, sedation, and muscle weakness. Magnesium potentiates the action of both depolarizing and non-depolarizing muscle relaxants. A standard intubating dose of a muscle relaxant should be used, as the extent of potentiation is variable. Subsequent nondepolarizing muscle relaxant should be administered only if necessary.
- Patients who are receiving tocolysis may be at increased risk for uterine atony and postpartum hemorrhage.

References

Jenkins SM, Mikes BA. Preterm Labor. In: StatPearls. Treasure Island (FL): StatPearls Publishing; February 8, 2025. PubMed
American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics. Practice Bulletin No 171: Management of Preterm Labor. Obstet Gynecol. 2016;128(4):e155-e164. Link
Bolden JR, Grobman WA. “Preterm Labor and Delivery”. Chestnut’s Obstetric Anesthesia, 6th ed. Editor Chestnut, et al. Elsevier, Inc. 2020.

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