Tocolytics (also called anti-contraction medications or labor suppressants) are medications used to suppress

premature labor Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is between ...

(from Greek τόκος ''tókos'', "

childbirth Childbirth, also known as labour and delivery, is the ending of pregnancy where one or more babies exits the internal environment of the mother via vaginal delivery or caesarean section. In 2019, there were about 140.11 million births globall ...

", and λύσις ''lúsis'', "loosening"). Preterm birth accounts for 70% of neonatal deaths. Therefore, tocolytic therapy is provided when delivery would result in

premature birth Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is between 2 ...

, postponing delivery long enough for the administration of

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...

s, which accelerate fetal lung maturity but may require one to two days to take effect. Commonly used tocolytic medications include β₂ agonists,

calcium channel blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

s, NSAIDs, and

magnesium sulfate Magnesium sulfate or magnesium sulphate (in English-speaking countries other than the US) is a chemical compound, a salt with the formula , consisting of magnesium cations (20.19% by mass) and sulfate anions . It is a white crystalline solid, ...

. These can assist in delaying preterm delivery by suppressing uterine muscle contractions and their use is intended to reduce fetal

morbidity A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...

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 Nifedipine (3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate), sold under the brand name Adalat and Procardia, among others, is a calcium channel blocker medication used to manage angina, high blood pressure, Ra ...

is used as it reduces blood pressure;

cardiotocography Cardiotocography (CTG) is a technique used to monitor the fetal heartbeat and the uterine contractions during pregnancy and labour. The machine used to perform the monitoring is called a cardiotocograph. Fetal heart sounds was described as earl ...

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 Preterm birth, also known as premature birth, is the Childbirth, birth of a baby at fewer than 37 weeks Gestational age (obstetrics), gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 we ...

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 In obstetrics, gestational age is a measure of the age of a pregnancy which is taken from the beginning of the woman's last menstrual period (LMP), or the corresponding age of the gestation as estimated by a more accurate method if available. Su ...

by gaining more time for other management strategies like

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...

s 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 Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal lo ...

, and safe transfer to facilities.

Types of agents

There is no clear first-line tocolytic agent. Current evidence suggests that first line treatment with β₂ 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. Various types of agents are used, with varying success rates and side effects. Some medications are not specifically approved by the

U.S. Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) for use in stopping uterine contractions in preterm labor, instead being used

off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...

. 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. Calcium-channel blockers (such as

) and oxytocin antagonists (such as

atosiban Atosiban, sold under the brand name Tractocile among others, is an inhibitor of the hormones oxytocin and vasopressin. It is used as an intravenous medication as a labour repressant (tocolytic) to halt premature labor. It was developed by Ferrin ...

) may delay delivery by 2 to 7 days, depending on how quickly the medication is administered. NSAIDs (such as

indomethacin Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation. It works by inhibiting the production of ...

) and

s (such as

) 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. The efficacy of β-adrenergic agonists, atosiban, and

is a decreased

odds ratio An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of A in the presence of B and the odds of A in the absence of B, or equivalently (due ...

(OR) of delivery within 24 hours of 0.54 (95%

confidence interval In frequentist statistics, a confidence interval (CI) is a range of estimates for an unknown parameter. A confidence interval is computed at a designated ''confidence level''; the 95% confidence level is most common, but other levels, such as 9 ...

(CI): 0.32-0.91) and 0.47 within 48 hours (OR 0.47, 95% CI: 0.30-0.75). Antibiotics were thought to delay delivery, but no studies have shown any evidence that using antibiotics during preterm labor effectively delays delivery or reduces neonatal morbidity. Antibiotics are used in people with

premature rupture of membranes Prelabor rupture of membranes (PROM), previously known as premature rupture of membranes, is breakage of the amniotic sac before the onset of labor. Women usually experience a painless gush or a steady leakage of fluid from the vagina. Complicati ...

, but this is not characterized as tocolysis.

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 gestationWong, Perry, and Hockenberry. Maternal Child Nursing Care. Mosby 2002. * Fetus weighs less than 2.5 kg, or has

intrauterine growth restriction Intrauterine growth restriction (IUGR), or fetal growth restriction, refers to poor growth of a fetus while in the womb during pregnancy. IUGR is defined by clinical features of malnutrition and evidence of reduced growth regardless of an infant's ...

(IUGR) or

placental insufficiency Placental insufficiency or utero-placental insufficiency is the failure of the placenta to deliver sufficient nutrients to the fetus during pregnancy, and is often a result of insufficient blood flow to the placenta. The term is also sometimes use ...

* Lethal congenital or chromosomal abnormalities *

Cervical dilation Cervical dilation (or cervical dilatation) is the opening of the cervix, the entrance to the uterus, during childbirth, miscarriage, induced abortion, or gynecological surgery. Cervical dilation may occur naturally, or may be induced surgically o ...

is greater than 4 centimeters *

Chorioamnionitis Chorioamnionitis, also known as intra-amniotic infection (IAI), is inflammation of the fetal membranes ( amnion and chorion), usually due to bacterial infection. In 2015, a National Institute of Child Health and Human Development Workshop expert ...

or intrauterine infection is present * Pregnant woman has severe

pregnancy-induced hypertension Gestational hypertension or pregnancy-induced hypertension (PIH) is the development of new hypertension in a pregnant woman after 20 weeks' gestation without the presence of protein in the urine or other signs of pre-eclampsia. Gestational hyperte ...

, severe

eclampsia Eclampsia is the onset of seizures (convulsions) in a woman with pre-eclampsia. Pre-eclampsia is one of the hypertensive disorders of pregnancy that presents with three main features: new onset of high blood pressure, large amounts of protein in ...

preeclampsia Pre-eclampsia is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. In severe cases of the disease ...

, active

vaginal bleeding Vaginal bleeding is any expulsion of blood from the vagina. This bleeding may originate from the uterus, vaginal wall, or cervix. Generally, it is either part of a normal menstrual cycle or is caused by hormonal or other problems of the reproductiv ...

placental abruption Placental abruption is when the placenta separates early from the uterus, in other words separates before childbirth. It occurs most commonly around 25 Gestational age (obstetrics), weeks of pregnancy. Symptoms may include vaginal bleeding, lower ...

, a

cardiac disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...

, or another condition which indicates that the pregnancy should not continue. * Maternal hemodynamic instability with bleeding *

Intrauterine fetal demise Stillbirth is typically defined as fetal death at or after 20 or 28 weeks of pregnancy, depending on the source. It results in a baby born without signs of life. A stillbirth can result in the feeling of guilt or grief in the mother. The term i ...

, lethal fetal anomaly, or non-reassuring fetal status

Future direction of tocolytics

Most tocolytics are currently being used off-label. The future direction of the development of tocolytics agents should be directed toward better efficacy in intentionally prolonging pregnancy. This will potentially result in less maternal, fetal, and neonatal adverse effects when delaying preterm childbirth. A few tocolytic alternatives worth pursuing include Barusiban, a last generation of oxytocin receptor antagonists, as well as

COX-2 inhibitor COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly targets cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration and i ...

s. More studies on the use of multiple tocolytics must be directed to research overall health outcomes rather than solely pregnancy prolongation.

References

{{Other gynecologicals Chemical substances for emergency medicine Obstetric drugs Obstetrics Obstetrical procedures Childbirth

Indications

Types of agents

Contraindications to tocolytics

Future direction of tocolytics

See also

References