Labor is the process of coordinated uterine contractions leading to progressive cervical effacement and dilatation by which the fetus and placenta are expelled. Preterm labor is defined as labor occurring after 20 weeks' but before 37 weeks' gestation. Although there is no strict definition in the literature regarding the amount of uterine contractions required for preterm labor, there is consensus that contractions need to be regular and at frequent intervals. Generally, more than 4 contractions per hour are needed to cause cervical change. The uterine contractions need not be painful to cause cervical change and may manifest themselves as abdominal tightening, lower back pain, or pelvic pressure. In addition, there must be demonstrated cervical effacement or dilatation to meet a diagnosis of preterm labor.
It is important to distinguish preterm labor from other similar clinical entities, such as cervical incompetence (cervical change in the absence of uterine contractions) and preterm uterine contractions (regular contractions in the absence of cervical change) because the treatment for these situations differs. Cervical incompetence may require cerclage placement, and preterm uterine contractions without cervical change is generally a self-limited phenomenon that resolves spontaneously and requires no intervention. If ruptured membranes accompany preterm labor, these cases are classified as preterm premature rupture of membranes (for discussion of diagnosis see Premature Rupture of Membranes).
Preterm birth complicates approximately 12% of all pregnancies in the United States. It is the number one cause of neonatal morbidity and mortality and causes 75% of neonatal deaths that are not due to congenital anomalies.
Thirteen percent of all infants are classified as low birth weight (<2500 g), of whom 25% are mature low-birth-weight infants and approximately 75% are truly premature. The latter group accounts for nearly two-thirds of infant deaths (approximately 25,000 annually in the United States). Approximately 30% of premature births are due to miscalculation of gestational age or to medical intervention required by the mother or fetus.
The care of premature infants is costly. Compared with term infants, those born prematurely suffer greatly increased morbidity and mortality (eg, functional disorders, abnormalities of growth and development). Thus every effort is made to prevent or inhibit preterm labor. If preterm labor cannot be inhibited or is best allowed to continue, it should be conducted with the least possible trauma to the mother and infant.
Many obstetric, medical, and anatomic disorders are associated with preterm labor. Some of the risk factors are listed in Table 14–1. Detailed discussions of these conditions are given in other chapters. The cause of preterm labor in 50% of pregnancies, however, is idiopathic. Although several prospective risk-scoring tools are in use, they have not been convincingly demonstrated to be of value.
Table 14–1. Risk Factors Associated with Preterm Labor. ||Download (.pdf)
Table 14–1. Risk Factors Associated with Preterm Labor.
|In previous or current pregnancy|
|Severe hypertensive state of pregnancy|
|Anatomic disorders of the placenta (eg, abruptio placentae, placenta previa, circumvallate placenta)|
|Premature rupture of membranes|
|Polyhydramnios or oligohydramnios|
|Previous premature or low-birth-weight infant|
|Low socioeconomic status|
|Maternal age <18 years or >40 years|
|Low prepregnancy weight|
|Short interval between pregnancies (<3 months)|
|Inadequate or excessive weight gain during pregnancy|
|Previous laceration of cervix or uterus|
|Pulmonary or systemic hypertension|
|Infection: pyelonephritis, acute systemic infection, urinary tract infection, genital tract infection (eg, gonorrhea, herpes simplex, mycoplasmosis), fetotoxic infection (eg, cytomegalovirus infection, toxoplasmosis, listeriosis), maternal systemic infection (eg, pneumonia, influenza, malaria), maternal intra-abdominal sepsis (eg, appendicitis, cholecystitis, diverticulitis)|
|Heavy cigarette smoking|
|Alcoholism or drug addiction|
|Malnutrition or obesity|
|Leaking benign cystic teratoma|
|Perforated gastric or duodenal ulcer|
|Maternal trauma or burns|
|Any intra-abdominal procedure|
|Conization of cervix|
|Previous incision in uterus or cervix (eg, caesarean delivery)|
|Genital tract anomalies|
|Bicornuate, subseptate, or unicornuate uterus|
|Congenital cervical incompetency|
Unfortunately, there are few interventions known to prevent preterm labor. For women with a history of a prior spontaneous preterm birth, there is evidence indicating that progestin administered via either vaginal suppositories of progesterone or weekly intramuscular injections of 17-α hydroxyprogesterone caproate starting at 16–20 weeks until approximately 36–37 weeks reduces the risk of recurrent preterm birth by approximately 30%. Furthermore, vaginal progesterone may also reduce the risk of preterm birth in women found to have a short cervix on transvaginal ultrasound in the midtrimester. But, aside from these specific interventions, there is little we can do to prevent preterm labor.
Regular uterine contractions at frequent intervals as documented by tocometer or uterine palpation, generally more than 2 in one-half hour.
Dilation and Effacement of Cervix
This can be established by clinical examination or by transvaginal ultrasound. Documented cervical change in dilation or effacement of at least 1 cm or a cervix that is well effaced and dilated (at least 2 cm) on admission is considered diagnostic. On transvaginal ultrasound, a cervical length less than the 10th percentile (generally ≤2.5 cm) is also suggestive of cervical effacement.
Many patients present with bloody mucous vaginal discharge, or “bloody show.” More significant vaginal bleeding should be evaluated for abruptio placentae or placenta previa. Additionally, patients may report an increase in vaginal discharge or passage of their mucus plug.
Evaluation should include determination of the following:
Gestational age must be between 20 0/7 and 37 0/7 weeks' estimated gestational age (EGA), which should be calculated based on the patient's last menstrual period (LMP) or date of conception, if known, or the previous sonographic estimation if these dates are uncertain.
Care must be taken to determine fetal size by ultrasonography.
The presenting part must be noted because abnormal presentation is more common in earlier stages of gestation.
Continuous fetal monitoring should be performed to ascertain fetal well-being.
Tocodynamometry should be performed to confirm the presence and frequency of contractions.
Physical examination should be performed to assess for cervical dilation, ruptured membranes (see section on Premature Rupture of Membranes), fundal tenderness, vaginal bleeding, and fever.
Complete blood count with differential.
Urine obtained by catheter for urinalysis, culture, and sensitivity testing.
Ultrasound examination for fetal size, position, and placental location.
Amniocentesis may be useful to ascertain fetal lung maturity in instances in which EGA is uncertain, the size of the fetus is in conflict with the estimated date of conception (too small, suggesting intrauterine growth restriction, or too large, suggesting more advanced EGA), or the fetus is more than 34 weeks' EGA. Specifically, the amniotic fluid can be tested for lecithin/sphingomyelin (L/S) ratio, the presence of phosphatidylglycerol, fluorescence polarization assay, or lamellar body count. Amniocentesis should also be performed in instances in which chorioamnionitis is suspected; the fluid should be tested for Gram's stain, bacterial culture, glucose levels, cell count, and, if available, interleukin-6 level.
Speculum examination should be performed. Cervical cultures should be sent for gonorrhea and chlamydia. A wet mount should be performed to look for signs of bacterial vaginosis. Group B streptococcus (GBS) cultures should be taken from the vaginal and rectal mucosa. A swab may also be used to test any fluid in the vaginal to see if it is amniotic fluid (see section on Premature Rupture of Membranes).
Hematologic workup in cases associated with vaginal bleeding (see Chapter 18).
Fetal fibronectin testing kits have been approved by the Food and Drug Administration (FDA) as a means to assess the risk of preterm birth in patients with preterm labor. A cervicovaginal swab is taken to look for the presence of fetal fibronectin. A negative test is effective at identifying women at low risk of imminent delivery (within 2 weeks). A positive test result, however, is less sensitive at predicting preterm birth. The test may be helpful in identifying patients at low risk of preterm birth who can be managed on an outpatient basis.
The differential diagnosis includes preterm contractions without labor (ie, without cervical change) and cervical insufficiency (ie, cervical dilation without uterine contractions). However, clinical examination and signs can help distinguish among these entities.
The primary complication of preterm labor is preterm birth and the resulting prematurity of the infant. Treatment is directed toward reducing the likelihood of preterm birth and reducing the risk of prematurity-related complications in the infant, such as respiratory distress syndrome and neurologic injury.
Decisions regarding management are made based on EGA, estimated weight of the fetus, and existence of contraindications to suppressing preterm labor. Table 14–2 lists factors indicating that preterm labor should be allowed to continue. Once the patient is determined to not have any of these contraindications, the management of preterm labor depends on fetal gestational age. Generally, management falls into 1 of 2 categories: expectant management (observation) or intervention. For pregnancies between 24 0/7 and 34 0/7 weeks' EGA, intervention with corticosteroids has been shown to be of benefit in reducing neonatal morbidity and mortality rates. Although the efficacy of tocolysis has been much debated, it is generally accepted that a delay in delivery of 48 hours may be achieved at a minimum. Because this window can be used for corticosteroid administration, tocolysis is favored in many centers.
Table 14–2. Some Cases in Which Preterm Labor Should Not Be Suppressed. ||Download (.pdf)
Table 14–2. Some Cases in Which Preterm Labor Should Not Be Suppressed.
Severe hypertensive disease (eg, acute exacerbation of chronic hypertension, eclampsia, severe preeclampsia)
Pulmonary or cardiac disease (eg, pulmonary edema, adult respiratory distress syndrome, valvular disease, tachyarrhythmias)
Advanced cervical dilatation (>4 cm)
Maternal hemorrhage (eg, abruptio placentae, placenta previa, disseminated intravascular coagulation)
Fetal death or lethal anomaly
Intrauterine infection (chorioamnionitis)
Therapy adversely affecting the fetus (eg, fetal distress due to attempted suppression of labor)
Estimated fetal weight ≥2500 g
Erythroblastosis fetalis or fetal hydrops
Severe intrauterine growth retardation
Extremes of preterm gestational age pose special problems. Fetuses of very preterm pregnancies (20–23 weeks; EGA or estimated fetal weight [EFW] less than 550 g) are generally not considered to be viable. If these pregnancies can be continued for several more weeks, the fetuses will become viable, but have a high risk for significant morbidity if they are born in this periviable period and survive. Furthermore, intervention carries significant risks to the mother, including the risks of prolonged bed rest and side effects of tocolysis. Given these risks, expectant management is an acceptable and, in certain instances, preferable alternative to intervention. Mothers who choose intervention as opposed to expectant management should be extensively counseled by a multidisciplinary team, including the neonatologist, obstetrician, and social worker.
Conversely, once a pregnancy has continued beyond 34–37 weeks' EGA or EFW greater than 2500 g, the fetal survival rate is within 1% of the survival rate at 37 weeks. Fetal morbidity is less severe and is rarely a cause of long-term sequelae. Furthermore, corticosteroids have not been shown to be of benefit in fetuses of this age or size. Therefore, expectant management is usually the recommended course of action. Several factors should be considered when deciding between intervention and expectant management, including the certainty of the patient's dates, EFW, presence of maternal problems that could delay fetal lung maturity such as diabetes mellitus, and family history of late-onset respiratory distress syndrome (RDS).
There are other cases in which maternal or fetal factors indicate that preterm labor should be allowed to continue regardless of gestational age. Table 14–2 lists cases in detail.
The following is a protocol for management of pregnancies with preterm labor between 24 and 34 weeks' gestation.
The role of bed rest in the management of preterm labor is controversial. Meta-analyses have failed to demonstrate prolongation of pregnancy. Bed rest is associated with an increased risk of maternal thromboembolism. At minimum, bed rest may be advised particularly during the initial evaluation of an episode of preterm labor to allow for close fetal and maternal monitoring.
The administration of corticosteroids to accelerate fetal lung maturity has become the standard of care in the United States for all women between 24 and 34 weeks' EGA at risk of preterm delivery within the following 7 days. It has been shown to decrease the incidence of neonatal respiratory distress, intraventricular hemorrhage, and neonatal mortality. Steroids can be given according to 1 of 2 protocols: (1) betamethasone 12 mg intramuscularly (IM) every 24 hours for a total of 2 doses; or (2) dexamethasone 6 mg IM every 12 hours for a total of 4 doses.
The optimal benefits of antenatal corticosteroids are seen 24 hours after administration, peak at 48 hours, and continue for at least 7 days. If therapy for preterm labor is successful and the pregnancy continues beyond 2 weeks, there are data suggesting that a single repeat course of steroids may be beneficial if the risk of preterm birth remains high and the patient is <33 weeks. More than 2 courses, however, may be associated with fetal growth abnormalities and delayed psychomotor development in the infant. In terms of safety of 1 or 2 courses of antenatal steroids, there does not appear to be an increased risk of infection or suppression of the fetal adrenal glands with steroid administration, and long-term follow-up of fetuses who received 1 or 2 courses of antenatal steroids shows no sequelae that can be attributed directly to steroid administration.
If the patient continues to contract and falls into a high-risk group based on a history of preterm birth, positive fibronectin, short cervix on transvaginal sonography, or changing dilatation on cervical examination, tocolytic therapy may be initiated. When using tocolysis to treat preterm labor, it is important to keep the following goals in mind. The short-term goal is to continue the pregnancy for 48 hours after steroid administration, after which the maximum effect of the steroids can be achieved. The long-term goal is to continue the pregnancy beyond 34–36 weeks (depending on the institution), at which point fetal morbidity and mortality are dramatically reduced, and tocolysis can be discontinued.
Tocolytic therapy should be considered in the patient with cervical dilatation less than 5 cm. Successful tocolysis is generally considered fewer than 4–6 uterine contractions per hour without further cervical change.
The beta-mimetics and nifedipine are the most commonly used tocolytic agents. The decision to use a specific tocolytic should be carefully considered because of contraindications and side effects associated with each agent (Table 14–3).
Table 14–3. Side Effects and Complications of Common Tocolytics. ||Download (.pdf)
Table 14–3. Side Effects and Complications of Common Tocolytics.
Beta-mimetics (ritodrine, terbutaline)
Possible increased risk for intraventricular hemorrhage
Generalized muscle weakness
Shortness of breath
Gastrointestinal effects: Nausea/vomiting, heartburn, bleeding
Elevated blood pressure in hypertensive patients
Postpartum patent ductus arteriosus
Premature constriction of ductus arteriosus in utero
Beta-Mimetic Adrenergic Agents
Beta-mimetic adrenergic agents act directly on beta receptors (β2) to relax the uterus. Their use is limited by dose-related cardiovascular side effects, including pulmonary edema, adult RDS, elevated systolic blood pressure and reduced diastolic blood pressure, and both maternal and fetal tachycardia. Other dose-related effects are decreased serum potassium level and increased blood glucose and plasma insulin levels and lactic acidosis. Maternal medical contraindications to the use of β-adrenergic agents include cardiac disease, hyperthyroidism, uncontrolled hypertension or pulmonary hypertension, asthma requiring sympathomimetic drugs or corticosteroids for relief, uncontrolled diabetes, and chronic hepatic or renal disease. Commonly observed effects during intravenous administration are palpitations, tremors, nervousness, and restlessness. The beta-mimetic in common use is terbutaline. Although it has been used in the past, ritodrine is no longer commercially available. Because of the side effects, beta-mimetic tocolysis in the United States is now limited almost exclusively to subcutaneous intermittent injections as a method of temporizing and triaging patients before definitive therapy with other agents.
Although not approved by the FDA for use as a tocolytic, terbutaline has been studied in the United States and is used widely as a tocolytic agent. For tocolysis, it is administered via subcutaneous boluses. Given the potential for maternal cardiac toxicity, terbutaline should only be used for a maximum of 48–72 hours and should only be used in an inpatient setting.
Although its exact mechanism of action is unknown, magnesium sulfate appears to inhibit calcium uptake into smooth muscle cells, reducing uterine contractility. The efficacy of magnesium is debated, but several small studies have shown an effect comparable to that of beta-mimetics, and it may be better tolerated than beta-mimetics. Magnesium sulfate may appear less likely to cause serious side effects than the beta-mimetics, but its therapeutic range is close to the range at which it will cause respiratory and cardiac depression. Therefore, patients receiving magnesium sulfate should be monitored closely for signs of toxicity, with frequent checks of deep tendon reflexes, pulmonary examinations, and strict calculations of the patient's fluid balance. These effects may be reversed by calcium gluconate (10 mL of a 10% solution given intravenously), and this antidote should be kept at the bedside when magnesium sulfate is used.
Calcium channel blockers such as nifedipine work as tocolytics by inhibiting calcium uptake into uterine smooth muscle cells via voltage-dependent channels, thereby reducing uterine contractility. Several studies have shown nifedipine to be equally or more efficacious than beta-mimetics in preterm labor. Other advantages are its low incidence of maternal side effects and ease of administration. Nifedipine can be given by mouth. A common regimen for tocolysis is nifedipine 20 mg by mouth, then 10–20 mg by mouth every 6 hours until contractions diminish sufficiently.
Prostaglandin Synthase Inhibitors
Prostaglandin synthase inhibitors such as indomethacin have been shown to be as effective as ritodrine for tocolysis, but their use has been limited by potentially serious fetal effects. Indomethacin works as a tocolytic by inhibiting prostaglandin synthesis, an important mediator in uterine smooth muscle contractility. The advantages of indomethacin are its ease of administration (it can be given by rectum or by mouth) and its potent tocolytic activity. However, it has been associated with oligohydramnios and premature closure of the ductus arteriosus. In preterm infants delivered before 30 weeks' EGA, some studies have demonstrated an increased risk of intracranial hemorrhage, necrotizing enterocolitis, and patent ductus arteriosus after birth. A common regimen for tocolysis is indomethacin 100 mg per rectum loading dose (or 50 mg by mouth), then 25–50 mg by mouth or rectum every 4–6 hours. Ultrasound should be performed every 48–72 hours to check for oligohydramnios. Because of the potentially serious fetal effects, many centers limit its use to infants less than 32 weeks' EGA and its duration of use to less than 48 hours.
Treatment with Multiple Tocolytics
All tocolytics have significant failure rates; therefore, if 1 tocolytic appears to be failing, that agent should be stopped and another agent should be tried. The use of multiple tocolytics at the same time appears to have an additive tocolytic effect, but also appears to increase the risk of serious side effects. For example, magnesium sulfate used in combination with nifedipine theoretically can cause serious maternal hypotension. Likewise, magnesium sulfate supplemented by 1–2 doses of subcutaneous terbutaline may be safe and effective, but sustained treatment with the 2 can increase the patient's risk of pulmonary edema. It should be remembered that the patient who is difficult to tocolyze may have an unrecognized chorioamnionitis or placental abruption, conditions that may be contraindications to use of any tocolysis at all.
Results of Tocolytic Therapy
With all tocolytics, a point may be reached where further therapy is not indicated. This may be due to adverse maternal or fetal response to the progress of labor. Thus, if cervical dilatation reaches 5 cm, the treatment should be considered a failure and abandoned. Conversely, if labor resumes after a period of quiescence, treatment should be carefully considered because the recrudescence of contractions may be a sign of intrauterine infection. In some cases, therapy may be reinstituted using the same or a different drug.
Antibiotic therapy as a treatment of preterm labor and a means of prolonging pregnancy has been studied and has shown no benefit in delaying preterm birth in this population of patients. Patients with preterm labor should be started on antibiotics for prevention of neonatal GBS infection if the patient's GBS status is positive or unknown. Penicillin or ampicillin is used as first-line agents; cefazolin, clindamycin, erythromycin, or vancomycin can be used if the patient is allergic to penicillin. If the patient is successfully tocolyzed and there is no sign of imminent delivery or if the patient's most recent rectovaginal GBS culture (within 5 weeks) is negative, GBS prophylaxis can be discontinued.
Magnesium Sulfate for Fetal/Neonatal Neuroprotection
Several recent large trials have shown a reduced risk of cerebral palsy in fetuses exposed to magnesium sulfate in utero. The largest trial from the United States demonstrated a significant reduction in moderate to severe cerebral palsy in children at or beyond 2 years of age who received magnesium sulfate immediately before delivery. The optimal candidates for magnesium for this indication are not well defined, but it is reasonable to offer magnesium sulfate to any woman between 24 0/7 and 32 0/7 weeks of gestation immediately before delivery to reduce the risk of adverse neurologic outcomes (Table 14–4).
Table 14–4. Protocol for Use of Magnesium Sulfate for Fetal Neuroprotection. ||Download (.pdf)
Table 14–4. Protocol for Use of Magnesium Sulfate for Fetal Neuroprotection.
Criteria for admission to protocol
Preterm birth anticipated within 2–24 hours.
Gestational age of 24–31 6/7 weeks has been confirmed.
Any specific contraindications to magnesium sulfate therapy have been ruled out.
Begin intravenous infusion of magnesium sulfate loading dose, 6 g over 20–30 minutes, followed by a maintenance infusion of 2 g per hour.
If delivery has not occurred after 12 hours and is no longer considered imminent, the infusion may be discontinued.
If more than 6 hours has passed since discontinuation of magnesium sulfate and delivery is again believed to be imminent, another loading dose may be given followed by maintenance infusion.
Conduct of Labor and Delivery
Premature infants younger than 34 weeks should be delivered in a hospital equipped for neonatal intensive care whenever possible, because inter-hospital transfer after birth is more hazardous. Although the route of delivery for very-low-birth-weight infants has been hotly debated, there is no conclusive evidence of a benefit to routine caesarean delivery. Indications for caesarean are the usual obstetrical indications, including nonreassuring fetal status, malpresentation, and history of prior caesarean.
If caesarean delivery is indicated, the decision to operate is based on maturity of the fetus and prognosis for survival. In borderline cases (23–24 weeks' gestation and 500–600 g EFW), the wishes of the parents with regard to intervention assume an important place. When performing a caesarean delivery, it is important to ascertain that the uterine incision is adequate for extraction of the fetus without delay or unnecessary trauma. This may require a vertical incision when the lower uterine segment is incompletely developed. Trauma to the newborn may be minimized by en caul delivery.
When birth follows the unsuccessful use of parenteral tocolytic agents, keep in mind the potential residual adverse effects of these drugs. β-Adrenergic agents may cause neonatal hypotension, hypoglycemia, hypocalcemia, and ileus. Magnesium sulfate may be responsible for respiratory and cardiac depression.
Apgar scores are often low in low-birth-weight babies. This finding does not indicate asphyxia or compromised status but merely reflects the immaturity of the physiologic systems. Therefore, it is crucial to obtain cord pH and blood gas measurements for premature (and other high-risk) infants in order to document the status at birth. Cord pH and blood gas measurements may also be helpful in reconstructing intrapartum events, clarifying resuscitative measures, and determining the need for more intensive neonatal care.
Excellent neonatal care in the delivery room and nursery will do much to ensure a good prognosis for the preterm infant (see Chapter 22). Lower-birth-weight babies have a lesser chance of survival and a greater chance of permanent sequelae in direct relationship to size. Making generalizations regarding survival rates and sequelae is difficult because of the many causes of preterm delivery, the different levels of perinatal care, and the institutional differences in reported series. However, general figures for survival and morbidity have been reported and are helpful in counseling patients (Table 14–5).
Table 14–5. Approximate Neonatal Survival of Preterm Infants.1 ||Download (.pdf)
Table 14–5. Approximate Neonatal Survival of Preterm Infants.1
Gestation Age (weeks)
Birth Weight (g)
Intact2 Survivors (%)
Rouse DJ, Hirtz DG, Thom E, et al. A randomized controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med
American College of Obstetricians and Gynecologists. Assessment of Risk Factors for Preterm Birth. Clinical Management Guidelines for Obstetrician-Gynecologists. ACOG Practice Bulletin No. 31. Washington, DC: American College of Obstetricians and Gynecologists; 2001.
American College of Obstetricians and Gynecologists. Use of Progesterone to Reduce Preterm Birth
. ACOG Committee Opinion No. 419. Washington, DC: American College of Obstetricians and Gynecologists; 2008.
American College of Obstetricians and Gynecologists. Magnesium Sulfate Before Anticipated Preterm Birth for Neuroprotection. ACOG Committee Opinion No. 455. Washington, DC: American College of Obstetricians and Gynecologists; 2010.
American College of Obstetricians and Gynecologists. Antenatal Corticosteroid Therapy for Fetal Maturation. ACOG Committee Opinion No. 475. Washington, DC: American College of Obstetricians and Gynecologists; 2011.
Guinn DA, Atkinson MW, Sullivan L, et al. Single vs weekly courses of antenatal corticosteroids for women at risk of preterm delivery: A randomized controlled trial. JAMA
Kenyon SL, Taylor DJ, Tarnow-Mordi W. ORACLE Collaborative Group. Broad-spectrum antibiotics for spontaneous preterm labour: The ORACLE II randomised trial. Lancet