1. What every clinician should know
Clinical features and incidence
Preterm labor (PTL) is often defined as uterine contractions (four or more/20 minutes or eight or more/hour) and documented cervical change with intact membranes at 20-36 6/7 weeks. In addition to cervical change, many (including us) would consider as additional evidence of preterm labor a transvaginal ultrasound cervical length less than 20 mm or 20-29 mm with a positive fetal fibronectin (FFN).
Over 9.5% of all U.S. births in 2014 were preterm. The majority of preterm births are due to spontaneous etiologies such as PTL and preterm premature rupture of the membranes.
Symptoms of PTL are often non-specific and include cramps, abdominal “tightenings,” low backache, pelvic pressure, increased vaginal discharge and spotting. Nevertheless, because these symptoms are non-specific, the majority (70-80%) of women who present with signs and symptoms of preterm labor will deliver at term.
Treatment should be focused on prolonging the pregnancy with the intent of administering corticosteroids for fetuses less than 34 weeks’ gestation in the absence of indications for immediate delivery.
As the causes of preterm labor are multifactorial, it is most important to take a thorough history to assess for the presence of risk factors (e.g., prior history of spontaneous preterm birth, tobacco use, sexually transmitted infections, drug use, poor nutritional status, extremes of age) and ensure appropriate estimation of gestational age. (Table I)
Physical exam should include an assessment of vital signs, fetal status, and frequency of uterine contractions. If PPROM is suspected, a sterile speculum examination should be performed and the cervical dilation can be assessed visually. If PPROM has not occurred, manual cervical examination can be performed to assess for cervical changes consistent with labor.
Women without cervical change do not have PTL and should not receive tocolysis. Also, for practitioners who incorporate FFN or TVU CL into their assessment, women with symptoms of PTL, but negative FFN or TVU CL 30 mm or more have a 2% or less chance of delivering within 1 week and a greater than 95% chance of delivering at or after 35 weeks without therapy, and therefore should not receive any treatment.
In preparation for preterm delivery, women who are admitted for preterm labor should have a consultation with neonatology. In hospitals that cannot manage premature infants, consideration should be given to transferring the patient to a tertiary care center.
2. Diagnosis and differential diagnosis
We suggest making the diagnosis of PTL based on the algorithm shown in Figure 1. The gestational age should be between 23-3 6/7 weeks, and in the presence of symptoms of PTL, the TVU CL should be <20 mm, or 20-29 mm with positive FFN.
Because underlying infection can precipitate preterm labor, it is important to assess for potential infectious etiologies and treat women who are found to have an infection. A urinalysis with reflex culture should also be performed. Though chlamydia, gonorrhea, syphilis, trichomonas and bacterial vaginosis have been associated with PTL, there is insufficient evidence to recommend the effectiveness of routine screening for these conditions.
Recto-vaginal GBS cultures should be obtained, as this will direct GBS prophylaxis at time of delivery.
In some cases, preterm labor can present with generalized abdominal tenderness and nonspecific signs and symptoms. Appropriate laboratory tests and imaging studies should be ordered to assess for other diagnoses in the differential (e.g., renal ultrasound should be ordered if nephrolithiasis is suspected).
Preterm labor can be precipitated by chorioamnionitis which should be suspected in women with fever and uterine tenderness. If chorioamnionitis is suspected, an amniocentesis may be considered to assess intra-amniotic infection by evaluation of the amniotic fluid for the presence of white blood cells, glucose content, gram stain and culture indicative of bacterial infection. Amniocentesis can also be used to determine fetal lung maturity.
An ultrasound evaluation of the fetus may also be useful when admitting an obstetric patient; this should include assessment of fetal presentation, placental location, maximum vertical pocket of amniotic fluid and estimated fetal weight.
Before treatment is undertaken, the diagnosis of preterm labor must be established. Also, when presented with a patient with preterm labor, it is important to determine whether prolongation of the pregnancy would result in harm to either the fetus or the mother. For example, in cases of chorioamnionitis or non-reassuring fetal status, we would not recommend prolongation of the pregnancy.
If it is determined that potential benefits outweigh harms of pregnancy prolongation, then we would administer corticosteroids and consider tocolysis to allow for administration of the full course of corticosteroids. Corticosteroids (dexamethasone or betamethasone) reduce the frequency of respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis and neonatal mortality in infants born prematurely. There is insufficient evidence to justify the use of steroids for fetal maturity and tocolysis before 23 weeks and after 33 6/7 weeks.
Patients between 34 and 36 weeks should also be evaluated for the etiology of PTL, though not tocolyzed. Steroids can be considered, but their administration should not delay an indicated delivery.
It is important to note that no tocolytic has been shown to improve perinatal mortality. Calcium channel blockers, cyclooxygenase inhibitors and oxytocin receptor antagonists are the ones best supported by evidence for safety and effectiveness. There is no maintenance tocolytic that prevents PTB or perinatal morbidity/mortality, and therefore, maintenance tocolysis should not be used. Women with multiple gestations should not be treated differently than those with singletons, except that their risk of pulmonary edema is greater when exposed to beta-mimetics or magnesium sulfate.
If delivery is considered imminent, GBS prophylaxis with antibiotics should be started unless GBS status is known to be negative based on a recent rectovaginal swab.
Additionally, consider treatment with magnesium sulfate for fetal neuroprotection. Intravenous magnesium sulfate (loading dose of 6 g infused for 20-30 minutes followed by a maintenance infusion of 2 g per hour) given at 24-31 6/7 weeks when delivery is considered imminent is associated with a significant decrease in the incidence of moderate/severe cerebral palsy.
4. Prognosis and outcome
Counseling with regards to neonatal morbidity and mortality for preterm infants should reflect the latest and, if available, institutional data. Current survival at our institution ranges from 0% at 21 weeks to 75% at 25 weeks to more than 95% at 29 weeks, while intact survival at 18 months is about 50% after 25 weeks. Disabilities in mental and psychomotor development, neuromotor function (including cerebral palsy), or sensory and communication function are present in at least 50% of fetuses born at or before 25 weeks’ gestation.
5. What is the evidence for specific management and treatment recommendations
Martin, JA,, Osterman, MJK,, Sutton, PD. “Are preterm births on the decline in the United States? Recent data from the National Vital Statistics System.”. NCHS data brief, no 39. Hyattsville, MD: National Center for Health Statistics.. 2010. (National statistics regarding the trend for the preterm birth rate in the U.S.)
Berghella, V,, Baxter, JK,, Hendrix, NW. “Cervical assessment by ultrasound for preventing preterm delivery.”. Cochrane Database of Systematic Reviews 2009. (A meta-analysis of trials that assessed the utility of ultrasound cervical length assessment for prevention of preterm birth.)
Gomez, R,, Romero, R,, Medina, L,, Nien, JK,, Chaiworapongsa, T. “Cervicovaginal fibronectin improves the prediction of preterm delivery based on sonographic cervical length in patients with preterm uterine contractions and intact membranes.”. Am J Obstet Gynecol. vol. 192. 2005. pp. 350-9.
(Review based on the current standards of care as per ACOG.)
Berghella,, V. “Preterm Labor. Obstetric Evidence Based Guidelines.”. Informa Healthcare. 2007. (An evidence based review of the literature focused on preterm birth, i.e., screening and treatment.)
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