Tocolytics (also called anti-contraction medications or labor suppressants) are medications used to suppress premature labor (from Greek τόκος tókos, "childbirth", and λύσις lúsis, "loosening"). Preterm birth accounts for 70% of neonatal deaths. Therefore, tocolytic therapy is provided when delivery would result in premature birth, postponing delivery long enough for the administration of glucocorticoids (which accelerate fetal lung maturity) to be effective, as they may require one to two days to take effect.

Commonly used tocolytic medications include β<sub>2</sub> agonists, calcium channel blockers, NSAIDs, and magnesium sulfate. These can assist in delaying preterm delivery by suppressing uterine muscle contractions and their use is intended to reduce fetal morbidity and mortality associated with preterm birth. The suppression of contractions is often only partial and tocolytics can only be relied on to delay birth for a matter of days. Depending on the tocolytic used, the pregnant woman or fetus may require monitoring (e.g., blood pressure monitoring when nifedipine is used as it reduces blood pressure; cardiotocography to assess fetal well-being). In any case, the risk of preterm labor alone justifies hospitalization.

Indications

Tocolytics are used in preterm labor, which refers to when a baby is born too early before 37 weeks of pregnancy. As preterm birth represents one of the leading causes of neonatal morbidity and mortality, the goal is to prevent neonatal morbidity and mortality through delaying delivery and increasing gestational age by gaining more time for other management strategies like corticosteroids therapy that may help with fetus lung maturity. Tocolytics are considered for women with confirmed preterm labor between 24 and 34 weeks of gestation age and used in conjunction with other therapies that may include corticosteroids administration, fetus neuroprotection, and safe transfer to facilities.

Types of agents

There is no clear first-line tocolytic agent. Current evidence suggests that first line treatment with β<sub>2</sub> agonists, calcium channel blockers, or NSAIDs to prolong pregnancy for up to 48 hours is the best course of action to allow time for glucocorticoid administration.

According to a 2022 Cochrane review, the most effective tocolytics for delaying preterm birth by 48 hours, and 7 days were the nitric oxide donors, calcium channel blockers, oxytocin receptor antagonists and combinations of tocolytics.

{| class="wikitable" border="1"

|-

! Drug

! Mechanism of action

! Description

! Possible<br />contraindications

! Maternal side effects

! Fetal and neonatal side effects

|-

| Terbutaline (Brethine)

| β<sub>2</sub> agonist

| Off-label use, FDA has advised that injectable terbutaline should only be used in urgent situations, and that the oral form of the drug should never be used

| Cardiac tachyarrhythmias, poorly controlled diabetes mellitus, hyperthyroidism, prolonged tocolysis(>48 to 72 hours)

| Fetal tachycardia, hyperinsulinemia, hypoglycemia, myocardial and septal hypertrophy, myocardial ischemia

|-

| Ritodrine (Yutopar)

| β<sub>2</sub> agonist

| No longer FDA approved

| Poorly controlled thyroid disease, hypertension, and diabetes

| Metabolic hyperglycemia, hyperinsulinemia, hypokalemia, antidiuresis, altered thyroid function, physiologic tremor, palpitations, nervousness, nausea or vomiting, fever, hallucinations

| Neonatal tachycardia, hypoglycemia, hypocalcemia, hyperbilirubinemia, hypotension, intraventricular hemorrhage

|Palpitations, tachycardia, and chest pain

|Tachycardia, impaired carbohydrate tolerance, hyperinsulinaemia

|-

| Salbutamol <small>(INN)</small> or albuterol <small>(USAN)</small>

| β<sub>2</sub> agonist

|Shown to be less effective than nifedipine for tocolysis regarding neonatal outcome

| Diabetes, ischemic cardiopathy, cardiac arrhythmia, placenta praevia, hyperthyroidism, hypersensitivity to salbutamol (albuterol)

|Headache, palpitations, tachycardia, tremor, sweating, and shortness of breath

|Fetal tachycardia, hypoglycemia, hyperinsulinaemia

| Vertigo, anxiety, tremor, hyperhidrosis, tachycardia, hypotension, hyperglycemia, edema

| Hypoglycemia, bronchospasm, anaphylactic shock

| Hypotension, preload-dependent cardiac disease. It should not be used concomitantly with magnesium sulfate

| Flushing, headache, dizziness, nausea, transient hypotension. Administration of calcium channel blockers should be used with care in patients with renal disease and hypotension. Concomitant use of calcium channel blockers and magnesium sulfate may result in cardiovascular collapse

| Calcium channel blockers have the fewest neonatal adverse effects Fewer side effects than β<sub>2</sub> agonists. Although not FDA approved in the US, atosiban was developed specifically to delay preterm labor.

|No current contraindications

|No maternal adverse effects

|No adverse effects to the baseline fetal heart rate. No significant difference in neonatal side effect compared to other treatments

| Late pregnancy (ductus arteriosus), significant renal or hepatic impairment

| Nausea, heartburn

| Constriction of ductus arteriosus, pulmonary hypertension, reversible decrease in renal function with oligohydramnios, intraventricular hemorrhage, hyperbilirubinemia, necrotizing enterocolitis

|-

| Sulindac

| NSAID

|Studies show that it has similar efficacy to that of indomethacin and has a milder effect on the fetal ductus arteriousus

| Coagulation disorders or thrombocytopenia, NSAID-sensitive asthma, other sensitivity to NSAID

|GI complications such as nausea, vomiting and stomach pain due to COX inhibition

|NSAIDs have been shown to be associated with constriction of the ductus arteriousus and oligohydramnios

| Myosin light chain inhibitor

| Probably effective in delaying preterm birth by 48 hours. Use as a tocolytic agent may result in death of the fetus or infant. found it was not effective.

|Pregnancy: no amount of ethanol is safe to the fetus

|Intoxication, withdrawal NSAIDs (such as indomethacin) and calcium channel blockers (such as nifedipine) are the most likely to delay delivery for 48 hours, with the least amount of maternal and neonatal side effects. Otherwise, tocolysis is rarely successful beyond 24 to 48 hours because current medications do not alter the fundamentals of labor activation. However, postponing premature delivery by 48 hours appears sufficient to allow pregnant women to be transferred to a center specialized for management of preterm deliveries, and thus administer corticosteroids for the possibility to reduce neonatal organ immaturity.

Contraindications to tocolytics

In addition to drug-specific contraindications, several general factors may contraindicate delaying childbirth with the use of tocolytic medications.

  • Fetus is older than 34 weeks gestation
  • Fetus weighs less than 2.5&nbsp;kg, or has intrauterine growth restriction (IUGR) More studies on the use of multiple tocolytics must be directed to research overall health outcomes rather than solely pregnancy prolongation.

See also

  • Labor induction

References