Preterm birth is defined as delivery prior to 37 weeks’ gestation, and spontaneous preterm labor with or without premature rupture of the fetal membranes is responsible for at least two-thirds of all preterm births. Prematurity is the largest single contributor to infant mortality, and survivors are at risk for a myriad of short- and long-term complications. Rates of infant death and long-term neurologic impairment are inversely related to gestational age at birth.
The cusp of viability in contemporary practice is 23–25 weeks’ gestation, and infants born prior to 23 weeks rarely survive. About two-thirds of the preterm births occur between 34 weeks and 36 weeks and 6 days (termed late preterm birth), and good outcomes are expected at these gestational ages. Importantly, however, even these late preterm infants are at significantly increased risk for both morbidity and mortality when compared to those infants born at term.
Major risk factors for spontaneous preterm labor include a past history of preterm birth and a short cervical length as measured by transvaginal ultrasound. Patients with one or both of these risk factors have largely been the focus of recent intervention trials aiming to prevent preterm birth. Other known risk factors are many but include black race, multi-fetal pregnancies, intrauterine infection, substance abuse, smoking, periodontal disease, and socioeconomic deprivation.
Signs and symptoms of preterm labor include:
- Regular or frequent sensations of abdominal tightening (contractions)
- Constant low, dull backache
- A sensation of pelvic or lower abdominal pressure
- Mild abdominal cramps
- Vaginal spotting or light bleeding
- Preterm rupture of membranes — in a gush or a continuous trickle of fluid after the membrane around the baby breaks or tears
- A change in type of vaginal discharge — watery, mucus-like or bloody
Patients must be educated to identify symptoms associated with preterm labor to avoid unnecessary delay in their evaluation. In patients who are believed to be at increased risk for preterm delivery, conventional recommendations are for limited activity and bed rest. Randomized trials, however, have failed to demonstrate improved outcomes in women placed on activity restriction.
Paradoxically, such recommendations may place a woman at an increased risk to deliver preterm. Women with preterm labor at the threshold of viability present unique ethical and obstetric challenges and are best managed in consultation with maternal-fetal medicine and neonatology specialists. The families in such situations should be actively and continually engaged about decisions regarding the aggressiveness of resuscitative efforts.
In pregnancies between 23- and 34-weeks’ gestation where preterm birth is anticipated, a single short course of corticosteroids should be administered to promote fetal lung maturity. Such therapy has been demonstrated to reduce the frequency of respiratory distress syndrome, intracranial hemorrhage, and even death in preterm infants.
Betamethasone, 12 mg intramuscularly repeated once 24 hours later, or dexamethasone, 6 mg intramuscularly repeated every 12 hours for four doses, both cross the placenta and are the preferred treatments in this setting.
A single repeat course of antenatal corticosteroids should be considered in women who are at risk for preterm delivery within the next 7 days, and whose prior dose of antenatal corticosteroids was administered more than 14 days previously. Rescue course corticosteroids could be provided as early as 7 days from the prior dose, if indicated by the clinical scenario.
Administration of betamethasone may be considered in pregnant women between 34 0/7 and 36 6/7 weeks of gestation at imminent risk for preterm birth within 7 days, and who have not received a previous course of antenatal corticosteroids.
delivery, women in preterm labor should receive antimicrobial prophylaxis against group B streptococcus.
Numerous tocolytic pharmacologic agents have been given in an attempt to forestall preterm birth, although none are completely effective, and there is no evidence that such therapy directly improves neonatal outcomes. Administering tocolytic agents, however, remains a reasonable approach to the initial management of preterm labor and may provide sufficient prolongation of pregnancy to administer a course of corticosteroids and (if appropriate) transport the patient to a facility better equipped to care for premature infants.
Maintenance therapy (continuation of treatment beyond 48 hours) is not effective at preventing preterm birth and is not recommended. Likewise, despite the finding that preterm labor is associated with intrauterine infection in certain cases, there is no evidence that antibiotics forestall delivery in women with preterm labor and intact membranes.
Magnesium sulfate is commonly used (but no longer recommended as a first-line agent) for tocolysis, and there is evidence that it may also be protective against cerebral palsy in infants from 24 weeks’ to 32 weeks’ gestation when given at time of birth.
Magnesium sulfate is given intravenously as a 4- to 6-g bolus followed by a continuous infusion of 2 g/h. Magnesium levels are not typically checked but should be monitored if there is any concern for toxicity. Magnesium sulfate is entirely cleared by the kidney and must, therefore, be used with caution in women with any degree of kidney disease.
Beta-adrenergic drugs such as terbutaline can be given as an intravenous infusion starting at 2.5 mcg/min or as a subcutaneous injection starting at 250 mcg given every 30 minutes. Oral terbutaline is not recommended because of the lack of proven efficacy and concerns about maternal safety. Serious maternal side effects have been reported with the use of terbutaline and include tachycardia, pulmonary edema, arrhythmias, metabolic derangements (such as hyperglycemia and hypokalemia), and even death.
Pulmonary edema occurs with increased frequency with concomitant administration of corticosteroids, large volume intravenous fluid infusion, maternal sepsis, or prolonged tocolysis. Because of these safety concerns, the US Food and Drug Administration warns that terbutaline be administered exclusively in a hospital setting and discontinued after 48–72 hours of treatment.
Nifedipine, 20 mg orally every 6 hours, and indomethacin, 50 mg orally once then 25 mg orally every 6 hours up to 48 hours, have also been used with limited success. Nifedipine should not be given in conjunction with magnesium sulfate.
Before attempts are made to prevent preterm delivery with tocolytic agents, the patient should be assessed for conditions in which delivery would be indicated. Severe preeclampsia, lethal fetal anomalies, placental abruption, and intrauterine infection are all examples of indications for preterm delivery. In such cases, attempts to forestall delivery would be inappropriate.
Strategies aimed at preventing preterm birth in high-risk women—principally those with a history of preterm birth or a shortened cervix (or both)—have focused on the administration of progesterone or progesterone compounds and the use of cervical cerclage.
Prospective randomized controlled trials have demonstrated reductions in rates of preterm birth in high-risk women with singleton pregnancies who received progesterone supplementation, although the optimal preparation, dose, and route of administration (intramuscular injection versus vaginal suppository) are unclear.
Although the issue has not been settled, there is also some evidence that progesterone therapy may decrease rates of preterm birth in nulliparous women who are found to have a shortened cervix as measured by transvaginal ultrasound. ACOG does not recommend universal transvaginal cervical length screening but acknowledges that this strategy may be considered.
There is also evidence that women with a previous spontaneous preterm birth and a shortened cervix (less than 25 mm before 24 weeks’ gestation) may benefit from placement of a cervical cerclage. Incidentally detected short cervical length in the second trimester in the absence of a prior singleton preterm birth is not diagnostic of cervical insufficiency, and cerclage is not indicated in this setting.
In twin and triplet gestations, however, neither progesterone administration nor cervical cerclage placement has been effective at prolonging pregnancy, and these therapies are not recommended in women with multi-fetal pregnancies.