Preterm labor (PTL) include the following:
Regular uterine contractions with cervical change (dilation, effacement, or both) before 37 weeks' gestation
Initial presentation with regular contractions and cervical dilation of 2 cm or more
Preterm birth (PTB) is delivery between 20 0/7 and 36 6/7 weeks' gestation.
Late PTB is delivery between 34 0/7 and 36 6/7 weeks' gestation.
In 2015, 9.6% of the approximately four million deliveries in the United States were PTBs, which is the leading cause of neonatal morbidity (Figure 6-1). PTL accounts for 40% to 50% of PTB. Other causes of PTB include preterm prelabor (premature) rupture of membranes (PPROM), placental abruption, and indicated preterm deliveries.
It is difficult to identify which women who present with PTL will give birth preterm. Approximately 50% of patients admitted to the hospital with a diagnosis of PTL give birth after 37 weeks.
Short-term neonatal morbidity associated with PTB includes respiratory distress syndrome, hypothermia, hypoglycemia, jaundice, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and patent ductus arteriosus.
Long-term morbidity includes cerebral palsy, intellectual disability, and retinopathy of prematurity.
Causes of PTL are often multifactorial. Additionally, PTL is not the only cause of PTB. There are no tools with which clinicians can accurately predict occurrence of PTL. However, there are known maternal and pregnancy risk factors for PTL, which include the following:
Previous PTB: most strongly associated with PTL, recurrence risk 17% to 30%
Infection:
Systemic or local infections including urinary tract infections, pyelonephritis, bacterial vaginosis, sexually transmitted infections, pneumonia, appendicitis, periodontal disease
Chorioamnionitis affects 25% of preterm deliveries. Release of cytokines from endothelial cells, including interleukin-1, interleukin-6, and tumor necrosis factor-α stimulates a cascade of prostaglandin production that stimulates contractions.
Uterine overdistension: multiple gestation, polyhydramnios
Short cervix (see “Steps to Minimize Risk of Preterm Labor and Delivery”)
History of cervical surgical manipulation: loop electrosurgical excision procedure or cold knife cone.
Uterine malformations: bicornate uterus, leiomyomata, uterine didelphys
Second- or third-trimester bleeding; placenta previa or placental abruption
Social characteristics and health behaviors associated with PTL include African American race, maternal age <18 or >35 years, low socioeconomic status, anxiety, depression, stressful life events, tobacco use, and alcohol or drug abuse.
Any discussion regarding interventions to minimize risk of PTL must contain the caveat that the most significant risk factor for PTL, which is prior PTB, is not modifiable.
Education of patients regarding signs and symptoms of PTL and clear directions regarding when to call providers with questions and/or present for evaluation
Treat infections during pregnancy, such as urinary tract and lower genital infections (see chapter 8).
Chorioamnionitis is an indication for delivery, regardless of gestational age.
Treatment of infection may not alleviate risks as mechanism of influence may be from associated inflammation rather than the infection itself.
Bacterial vaginosis: Bacterial vaginosis is present in approximately 20% of women during pregnancy. It represents an overgrowth of normal vaginal flora rather than pathogenic infection. Routine screening is not recommended, and diagnosis is reserved to diagnose and treat symptomatic individuals. The presence of bacterial vaginosis is associated with increased risk of PTB, but causal relationship has not been established, and treatment has not been shown to reduce this risk. Treatment with metronidazole 500 mg orally twice a day for 7 days, 250 mg orally thrice a day for 7 days, or 2% clindamycin cream per vagina nightly for 7 days is effective at eradicating discharge symptoms but does NOT reduce risk of PTB. Recurrence can occur.
Among women with intact membranes, empiric broad-spectrum antibiotics have not been shown to reduce risk of PTL and delivery, are associated with increased neonatal morbidity, and are not recommended for routine use.
Progesterone therapy
Intramuscular (IM) progesterone therapy was previously universally recommended for singleton pregnancies in women with a prior PTB to reduce the risk of recurrent PTB, although more recently, its benefit has been called into question based on large-scale evaluation. Further study is needed to demonstrate definitive benefit of this therapy, and evolution of its recommended use is likely in the near future at time of this publication.
There have not been long-term neonatal risks associated with progesterone use, but study in this regard is limited and ongoing.
Women at highest risk of PTB would seem most likely to benefit based on clinical study to date (eg, very PTB history or multiple prior PTBs), although definitive benefit remains unclear.
Use of IM progesterone therapy should be individualized, considering the uncertain benefits and potential risks of using a limited studied medication in pregnancy. An algorithm for progesterone therapy, if employed, is shown in Figure 6-2.
Singleton pregnancy with prior spontaneous PTB, if IM progesterone is employed (considering the risks and benefits as outlined on previous page).
17-α hydroxyprogesterone caproate (Makena) or 17-P: 250 mg IM weekly
Begin between 16 and 20 weeks until 36 weeks.
If initiated, suggested to start at <21 weeks but also has shown benefit up to initiation at 27 weeks.
There is mixed data regarding vaginal progesterone's effectiveness at preventing PTB patients with prior PTB. However, initiation of vaginal progesterone may be reasonable in certain clinical circumstances or when IM 17-P is unavailable.
Singleton pregnancy with no prior history of PTB BUT cervical length ≤20 mm at ≤24 weeks
Vaginal progesterone: 90 mg gel or 200 mg suppository daily
Begin from diagnosis of short cervical length until 36 weeks
In women with singleton pregnancies and risks associated with cervical insufficiency or PTL, consider following with serial transvaginal ultrasound in second trimester between 16 and 24 weeks' gestation.
Progesterone has not been shown to be effective in singleton pregnancies, without history of prior PTB and normal or unknown cervical length, multifetal gestation, or in symptomatic (active) PTL or PPROM.
Cerclage
Cervical insufficiency is the inability of the cervix to retain a pregnancy in the absence of signs or symptoms of PTL (see chapter 5).
Clinical requirements and considerations of history-indicated, physical examination–indicated, and ultrasound-indicated cerclage as defined by American College of Obstetricians and Gynecologists are outlined in Table 6-1.
There is no current evidence to support cerclage in multifetal gestation.
Transvaginal cervical cerclage removal is indicated at 36 to 37 weeks' gestation and removal is not an indication for delivery.
Patients who will undergo cesarean delivery at 39 weeks may keep cerclage in place until that time with removal at the time of surgery. However, clinician must weigh risks of cervical trauma if preterm or early term contractions occur and counsel patients regarding signs of labor.
Abdominal cerclage may be considered in patients with previous failed transvaginal cervical cerclage (ie, previous placement in pregnancy that ultimately resulted in second trimester pregnancy loss).
Performed in late first trimester and early second trimester or in nonpregnant patient.
May be kept in place between pregnancies with planned cesarean deliveries
Pessary may be considered as an alternative to cerclage, although data are mixed regarding effectiveness.
Counseling should include that pessaries are typically well tolerated, are associated with increased vaginal discharge, do not have to be removed for cleaning, and do not increase risk of infection.
When placing a pessary, insert the pessary so the smallest diameter is upward toward the cervix. Confirmation of the patients ability to void following placement is recommended.
For the patient presenting with signs and symptoms of PTL:
Establish best dating: use last menstrual period, fundal height, ultrasound data, and available prenatal records.
Collect history regarding prior PTB; duration and quality of PTL symptoms; precipitating factors such as abdominal trauma; and presence of other associated symptoms including leakage of fluid, abdominal pain, subjective fevers.
Obtain vital signs.
Temperature >38°C or fetal or maternal tachycardia may indicate underlying infection.
Hypotension with fetal or maternal tachycardia may suggest placental abruption.
Physical examination
Fundal tenderness may suggest chorioamnionitis or placental abruption.
Costovertebral angle tenderness may suggest pyelonephritis.
Initiate continuous fetal heart monitoring and tocodynamometry. Nonreassuring fetal heart tracing may indicate chorioamnionitis, abruption, or cord compression.
Sterile speculum examination
Inspect visually for bleeding, amniotic fluid pooling, advanced dilation, bulging membranes, and purulent cervical discharge.
Consider collecting fetal fibronectin (fFN) swab.
The fFN is an optional adjunct and may assist in risk stratification of patient with preterm contractions. The fFN is a component of the extracellular membranes of the amniotic sac and is typically not present between 22 and 34 weeks' gestation.
Should be first test performed during exam: Insert speculum without gel and collect sample from posterior fornix (rotate swab across posterior fornix for approximately 10 s); may collect from 24 to 34 weeks' gestation
Valid if cerclage in place
Invalid with vaginal bleeding, ruptured membranes, cervical dilation >3 cm, or history of cervical manipulation (eg, intercourse or vaginal examination) within 24 hours
Negative predictive value is approximately 99.5% for delivery within 7 days and 99.2% for delivery within 14 days.
Positive predictive value for delivery within 7 days is as low as 14%; thus, a positive result provides little clinical insight.
May consider obtaining a cervical length in order to aid in risk stratification of patient in certain clinical circumstances
Membrane status (intact or ruptured) alters management and should be determined during early evaluation.
Pooling: If pooling not apparent, have the patient cough or Valsalva to see whether apparent amniotic fluid accumulates in the vagina.
Nitrazine: Normal vaginal pH is <4.5, with amniotic fluid pH usually 7.0 to 7.5. Vaginal pH >6.5 or blue on nitrazine paper is consistent with rupture of membranes. However, be cognizant that false-positive tests can be observed with blood, semen, Trichomonas or other infection, cervical mucus, or urine contamination.
Ferning: The presence of ferning of vaginal fluid on a slide can indicate rupture of membranes. Ferning may be falsely absent (falsely negative) in presence of blood. Avoid swabbing cervical mucus because it can result in a false positive.
Amniotic fluid index <5th percentile for gestational age, maximum vertical pocket <2 cm, or change in amniotic fluid index measurement from previous and recently documented measurement is suspicious for rupture of membranes but is not diagnostic.
If assessment for rupture of membranes is negative but clinical suspicion remains high, consider repeating examination after multiple hours and have patient lay supine between exams. Alternatively, amniocentesis with indigo carmine injection can confirm the presence of ruptured membranes and may be helpful in certain clinical circumstances
Obtain Group B Streptococcus (GBS) anovaginal culture because the result of culture will determine need for prophylactic antibiotics in labor.
Obtain cervical or vaginal cultures for gonorrhea and chlamydia.
Evaluate wet mount for bacterial vaginosis, Trichomonas, and yeast.
AFTER ascertaining intact membranes, digital examination is performed to assess cervical dilation, effacement, and station.
Obtain laboratory studies including complete blood count, urinalysis with microscopic evaluation, and cultures obtained in the sterile speculum examination. Obtain cultures before administration of antibiotics.
Perform an ultrasound to assess for multiple gestation, fetal presentation, estimated fetal weight (EFW), placental location, amniotic fluid index (per above), and fetal or uterine anomalies.
Goals of management:
Ultimate goal in managing PTL is to optimize outcomes with administration of corticosteroids and use of magnesium sulfate for fetal neuroprotection.
These intervention and management recommendations must be tailored to each patient and pregnancy; risks or prolonging pregnancy to mother must be weighed against risk of prematurity to fetus and fetal morbidity associated with worsening clinical status of mother.
Oral or intravenous (IV) hydration can be used as an initial approach to preterm contractions due to dehydration.
Randomized trials have shown that hydration does not reduce the incidence of PTB.
Clinical judgment will guide initial treatment and consideration for admission.
Bed rest is not clinically indicated for patients hospitalized with PTL, and there are no data to support its use. There are significant risks of bed rest including increased risk of venous thromboembolism. In the setting of concomitant ruptured membranes, cervical dilation, and fetal malpresentation, bed rest may help avoid umbilical cord prolapse. There is limited evidence that associates prolonged standing, strenuous activity, or sexual activity with PTL.
Thromboembolic prophylaxis should be considered and a physical therapy consult obtained for all patients with activity limitations.
Antenatal corticosteroids
Administration of corticosteroids is the most beneficial intervention to improve neonatal outcomes. Preterm infants between 24 0/7 and 33 6/7 weeks' gestation who receive antenatal corticosteroids have lower risk of respiratory distress syndrome, intracranial hemorrhage, necrotizing enterocolitis, and death. Late preterm infants between 34 0/7 and 36 6/7 weeks who receive their first course of corticosteroids during that time have decreased respiratory morbidity.
Treatment benefit is seen >24 hours after administration; still administer if delivery anticipated sooner than 24 hours.
Greatest benefit of steroid administration is 2 to 7 days after administration.
Maternal side effects include (1) transient hyperglycemia of mother, beginning approximately 12 hours after first administration, with effect peaking around 2 to 3 days, and lasting up to 5 days and (2) leukocytosis within first 24 hours that generally resolves in approximately 3 days. Exercise caution when interpreting lab values during this time period.
Poorly controlled diabetes mellitus is not a contraindication for corticosteroid administration prior to 34 weeks of gestation. Inpatient observation and glucose management may be considered for the patient who receives betamethasone and has poorly controlled gestational diabetes mellitus or pregestational diabetes in order to avoid morbidity associated with hyperglycemia.
Recommendations for administration
Administer a single course of corticosteroids if fetus is between 24 0/7 and 33 6/7 weeks and preterm delivery in next 7 days is likely. A provider may consider administration beginning at 23 weeks' gestation depending on clinical circumstances and patient preferences. In the event of PTL and periviability with possible delivery within the next 7 days, a discussion with the patient regarding fetal prognosis and patient's preferences for intervention and resuscitation should be carried out before corticosteroid, tocolytic, or magnesium administration.
Dosing
Betamethasone 12 mg IM every 24 hours for 2 doses
Dexamethasone 6 mg IM every 12 hours for 4 doses
A single rescue course of steroids may be administered 7 to 14 days after initial steroid course if patient did not deliver, is deemed clinically at risk for delivery within next 7 days, and is still <34 weeks' gestation.
There is no data supporting or refuting use of rescue course of steroids in the event of PPROM.
Rescue steroids have not been studied and are not indicated in the late preterm period (34-37 wk).
Serial courses of additional doses are not indicated and are associated with growth restriction and neonatal morbidity.
Late preterm steroids (between 34 0/7 and 36 6/7 wk gestation) may be administered if patient has not previously received corticosteroids and may deliver in next 7 days.
Administration of late preterm steroids reduces the need for respiratory support in first 72 hours, respiratory distress syndrome, transient tachypnea, bronchopulmonary dysplasia, and need for surfactant.
Tocolysis should not be performed in order to delay delivery to facilitate administration of late preterm steroids and indicated late preterm deliveries should not be delayed for administration.
Magnesium should be considered prior to 32 weeks' gestation for fetal neuroprotection when patient is thought to be at risk for delivery between next 30 minutes to 24 hours. Risk of moderate to severe cerebral palsy of fetus is decreased by approximately 40%. The number needed to treat to prevent one case of cerebral palsy is 1:63.
There are multiple regimens for magnesium sulfate for neuroprotection that were included in the meta-analysis that demonstrated this benefit.
4-g bolus over 30 minutes × 1
1 g/h for 24 hours
2 g/h for 12 hours
It is generally accepted to use any of these proposed regimens.
Consider restarting magnesium infusions that have been discontinued for the fetus <32 weeks' gestation if delivery is thought to be imminent.
The GBS prophylaxis is continued until cervical exam is stable and risk for progression to PTB is lower.
Prophylactic antibiotics for GBS are not indicated outside of concern for active PTL.
Prolonged risk of empiric antibiotics in the case of intact membranes may increase neonatal risk of sepsis.
Tocolysis
The goal of tocolysis is to prolong pregnancy to administer steroids and magnesium sulfate for neuroprotection. Also may consider tocolysis in order to facilitate maternal transport. There is no data to suggest that tocolysis for longer than 48 hours improves fetal or maternal outcomes.
Tocolytic agents include nifedipine and indomethacin, both of which have been shown to increase likelihood of completion of betamethasone administration. Terbutaline is a tocolytic but has not demonstrated efficacy in this regard. Magnesium has been historically used for tocolytic benefit but has been shown ineffective in this regard (Table 6-2). After 32 weeks, nifedipine, rather than indomethacin, is used for tocolysis in the absence of maternal contraindications.
Indomethacin is contraindicated after 32 weeks or in the setting of oligohydramnios.
Nifedipine is contraindicated in the setting of hypotension. There is a theoretical risk of pulmonary edema with concurrent use of magnesium and nifedipine, although this interaction has not been supported in large-scale studies to date and is not considered a contraindication to combination therapy if indicated.
Magnesium is not routinely an evidence-based tocolytic but is frequently used in this population for neuroprotective benefit until 32 weeks of gestation.
Terbutaline is a β-sympathomimetic agent administered in 0.25-mg subcutaneous dose that causes smooth muscle relaxation in the acute setting. It has not been shown to prolong pregnancy for steroid or magnesium administration.
Contraindications to tocolysis include intrauterine fetal demise, lethal fetal anomaly, nonreassuring fetal status, preeclampsia with severe features or eclampsia, maternal bleeding with hemodynamic instability, chorioamnionitis, and agent-specific maternal contraindications to tocolysis.
Special considerations
Tocolysis may be considered in PPROM in the absence of signs of maternal infection in order to facilitate administration of steroids or for maternal transport.
Tocolysis is generally not indicated:
Before neonatal viability. Tocolysis may be considered in the previable or periviable neonate when a known precipitant of PTL (such as abdominal surgery) has occurred. It may also be considered in periviable period based on family's wishes regarding resuscitation.
In presence of preterm contractions without cervical change
Fetal monitoring
No optimal schedule has been established.
Maintain external fetal monitoring and tocodynamometry until active PTL has resolved.
Once PTL has subsided, patient does not need to undergo continuous monitoring for this indication.
If <26 weeks or EFW <750 g, vaginal delivery is appropriate depending on clinical circumstances.
Breech delivery may be considered depending on clinical circumstances
There is limited data to suggest cesarean delivery improves neonatal outcomes at this early gestation in part because of generally poor neonatal outcomes regardless of delivery method.
A frank discussion of the risks and benefits of cesarean delivery for fetal intolerance of labor or otherwise should take place, given the increased maternal morbidity and poor neonatal prognosis. The risks and future implications of classical cesarean delivery should be discussed. Document your discussion carefully in the chart, and revisit the issue as gestation progresses.
If the fetus is malpresenting and is either >26 weeks or EFW is >800 g, cesarean delivery should be considered to minimize neonatal morbidity.
Disproportionate head-to-body ratio after this gestational age contributes to an increased risk of fetal head entrapment and associated morbidity.
Preterm gestation alone is not an indication for cesarean delivery in cephalic presenting fetuses.