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Basic Information ⬇

AUTHORS: Emily E. Nuss, MD and Anthony Sciscione, DO

Definition

Preterm labor is defined as regular contractions that result in cervical dilation or effacement prior to 37 wk gestation. Preterm birth is one that occurs after 20 wk gestation and before the completion of 37 wk gestational age.

Synonym

Premature labor

ICD-10CM CODES
O60.0Preterm labor without delivery
O60.1Preterm spontaneous labor with preterm delivery
O60.2Preterm spontaneous labor with term delivery
Epidemiology & Demographics
Incidence

The incidence of preterm births in the U.S. increased from 9.5% in 1981 to 12.7% in 2006 before falling gradually to 11.4% by 2013, then to 10% in 2019. The increase since 1981 is attributed to improvements in pregnancy dating by ultrasound, increased use of assisted reproductive technology, and increased preterm induction or preterm operative delivery for maternal or fetal indications. Between 40% and 45% of these births follow spontaneous preterm labor; either the remaining preterm births result from preterm premature rupture of membranes (PPROM), or they occur secondary to intentional delivery for maternal or fetal indications.

Predominant Age & Racial Differences

Pregnant women at the extremes of reproductive age (<17 yr and >35 yr) are at greatest risk. Black race is one of the most significant risk factors with the rate of preterm birth averaging 13.9% between 2016 and 2018 compared to 8.7% among Asian Americans and 9.6% in white women. The disparity between African-American and other ethnic American races persists after adjusting for income, education, and other medical risk factors.

Risk Factors

Risk factors for premature labor include a prior preterm delivery, intrauterine infection, systemic or genital tract infections, periodontal disease, short interpregnancy interval (<6 mo), short cervical length (<25 to 30 mm), low prepregnancy body mass index (BMI) (<19.8 kg/m2), age (<17 yr or >35 yr), a history of elective pregnancy termination, history of prior stillbirth, African-American race, vaginal bleeding, polyhydramnios or oligohydramnios, multiple gestation, structural abnormalities of the uterus, history of cervical cone biopsy or loop electrocautery excision, in vitro fertilization or ovulation induction, tobacco use, heavy alcohol consumption, cocaine use, heroin use, and psychologic or social stress. The strongest historic risk factor for preterm birth is a previous birth between 16 and 36 wk gestation.

Genetics

A genetic component has been suggested. Women with sisters who have had preterm births and women with grandparents who were born preterm may be at increased risk for having preterm deliveries themselves. Single-nucleotide polymorphisms have also been associated with preterm labor.

Physical Findings & Clinical Presentation

Presenting symptoms include increased pelvic pressure, abdominal cramping or contractions, increased vaginal discharge, vaginal bleeding or spotting, or leakage of fluid.

Etiology

Causes of premature labor are varied and often difficult to determine. Premature labor may be secondary to infection, systemic illness, trauma, anatomic abnormalities (i.e., uterine anomaly), or a combination of factors. It is thought that cervical ripening is the most common first step to premature labor or delivery. Subsequently, decidual-membrane activation occurs followed by contractions (Box 1).

BOX 1 Factors Linked to Preterm Labor

Demographic and Psychosocial

  • Extremes of age (>40 yr, teenagers)
  • Lower socioeconomic status
  • Tobacco use
  • Cocaine abuse
  • Prolonged standing (occupation)
  • Psychosocial stressors
Reproductive and Gynecologic

  • Prior preterm delivery
  • Diethylstilbestrol exposure
  • Multiple gestations
  • Anatomic endometrial cavity anomalies
  • Cervical incompetence
  • Low pregnancy weight gain
  • First-trimester vaginal bleeding
  • Placental abruption or previa
Surgical

  • Prior reproductive organ surgery
  • Prior paraendometrial surgery other than genitourinary (appendectomy)
Infectious

  • Urinary tract infections
  • Nonuterine infections
  • Genital tract infections (bacterial vaginosis)

From Marx JA et al: Rosen’s emergency medicine: concepts and clinical practice, ed 7, Philadelphia, 2010, Elsevier.

Diagnosis ⬆ ⬇

Differential Diagnosis

The differential diagnosis for preterm labor should include preterm rupture of membranes, preterm contractions (contractions before 37 wk gestation that do not result in cervical change), and abdominal pain or cramping secondary to other medical conditions. There are many medical conditions that may cause preterm contractions or premature labor. Treating some of these underlying conditions may improve the prognosis for stopping the preterm labor.

Possible medical conditions include:

  • Infection
    1. Chorioamnionitis
    2. Genital tract infections, including bacterial vaginosis, gonorrhea, chlamydia
    3. Urinary tract infections, including pyelonephritis, cystitis, or asymptomatic bacteriuria
    4. Gastroenteritis
  • Trauma
  • Placental abruption
  • Illicit drug use
  • Preterm premature rupture of membranes
  • Appendicitis
  • Nephrolithiasis
  • Pancreatitis
  • Cholelithiasis
  • Uterine fibroids
Workup

  • History and physical exam to rule out trauma, abuse, other causes of abdominal pain, and infection
  • Fetal heart rate monitoring and tocometry to determine fetal status and contraction frequency
  • Speculum exam to visually assess the cervix and assess for rupture of membranes, bleeding, infection, or advanced cervical dilation
    1. If the patient is <35 wk gestation, a Fetal Fibronectin (FFN) test should be collected prior to performing a digital exam or transvaginal ultrasound. A FFN test can help predict preterm delivery.
  • Digital exam in the unruptured patient with normal placentation to determine cervical dilation and effacement, and fetal station
Laboratory Tests

  • CBC
  • Urine analysis and culture
  • Urine toxicology screen
  • Collect tests for GBS, gonorrhea, and Chlamydia
  • Perform a wet prep for yeast, bacterial vaginosis, and Trichomonas
  • Fetal fibronectin swab as described earlier
  • Consider PT, PTT, INR, CMP, amylase, and lipase
  • Amniocentesis may be performed if an intraamniotic infection is suspected
Imaging Studies

  • A formal ultrasound is indicated to determine estimated fetal weight, fetal presentation, amniotic fluid volume, placental location and appearance, and cervical length.

The diagnosis of preterm labor is confirmed in the presence of regular contractions with subsequent cervical change. Suspicion for preterm labor may be heightened if FFN is positive.

Treatment ⬆ ⬇

Patients with premature labor should be delivered promptly when an intraamniotic infection is suspected or when they have advanced cervical dilation >5 cm, a persistently nonreassuring fetal heart rate tracing, or significant vaginal bleeding concerning for placental abruption having maternal or neonatal implications.

Nonpharmacologic Therapy

  • Bedrest, activity restriction, and pelvic rest are often recommended by clinicians, but there are insufficient data to support this practice, and it is currently not recommended.
Acute General Rx

  • Antenatal administration of corticosteroids between 24 wk and 33 6/7 wk gestation is recommended for women at risk of preterm delivery to prevent neonatal respiratory distress syndrome and decrease the incidence of intraventricular hemorrhage and necrotizing enterocolitis. It is also recommended between 34.0 and 36.6 wk gestation if there is no prior steroid exposure.
  • Numerous tocolytic agents have been used in an attempt to inhibit contractions (Box 2). Although efficacy is unclear, they can be utilized during an observation period in an effort to prolong gestation for administration and exposure of steroids or to transfer the mother to a facility capable of caring for preterm infants. This, of course, assumes there are no maternal or fetal medical contraindications to use of tocolytic drugs and no indications for rapid delivery. The most commonly used tocolytics are beta-mimetics (terbutaline), intravenous magnesium sulfate, calcium channel blockers (nifedipine), or prostaglandin synthetase inhibitors (indomethacin, ketorolac, sulindac). Table E1 summarizes side effect profiles of tocolytic agents.
  • Routine antibiotic use has failed to show benefit in the absence of a known infection. But all mothers in preterm labor (without a documented negative group B strep culture) should be given antibiotics to prevent neonatal GBS infection.
  • Intravenous magnesium sulfate has been shown to decrease cerebral palsy in children exposed antenatally with premature labor or premature rupture of the membranes at less than 32 wk gestation.

BOX 2 Commonly Used Tocolytic Agents

Magnesium sulfate

  • 4-6 g IV bolus over 30 min
  • 2-4 g/h IV infusion

Terbutaline

  • 5-10 mg PO q4-6h
  • 0.25-0.5 mg SC q30 min to 6 h
  • 10-80 μg/min IV

Ritodrine∗

  • 10 mg PO q2-4 h
  • 5-10 mg IM q2-4 h
  • 50-350 μg/min IV

Isoxsuprine

  • 20 mg PO q4-6 h
  • 0.05-0.5 mg/min IV

From Marx JA et al: Rosen’s emergency medicine: concepts and clinical practice, ed 7, Philadelphia, 2010, Elsevier.

TABLE E1 Side-Effect Profiles of Tocolytic Agents

Side Effects
Agent or ClassMaternalFetal or NeonatalContraindications
β-adrenergic receptor agonistsTachycardia and hypotension, tremor (39% vs. 4% with placebo), shortness of breath (15% vs. 1% with placebo), chest discomfort (10% vs. 1% with placebo), pulmonary edema (0.3%), hypokalemia (39% vs. 6% with placebo), hyperglycemia (30% vs. 10% with placebo)TachycardiaTachycardia-sensitive maternal cardiac disease, poorly controlled diabetes mellitus
Magnesium sulfateFlushing, diaphoresis, nausea, loss of deep-tendon reflexes (at serum levels of 9.6-12 mg/dl), respiratory paralysis (at serum levels of 12-18 mg/dl), cardiac arrest (at serum levels of 24-30 mg/dl); when used with calcium channel blockers, suppression of heart rate, contractility and left ventricular systolic pressure, and neuromuscular blockadeData conflict with regard to effect on perinatal mortalityMyasthenia gravis
Calcium channel blockersDizziness, flushing, hypotension when used with magnesium sulfate, suppression of heart rate, contractility, and left ventricular systolic pressure and neuromuscular blockade; elevation of hepatic aminotransferase levels, reflexive headacheHypotension, preload-dependent cardiac lesions (e.g., aortic insufficiency)
Cyclo-oxygenase inhibitorsNausea, esophageal reflux, gastritis, and emesis; platelet dysfunction (rarely of clinical significance in patients without underlying bleeding disorder)In utero closure of ductus arteriosus (risk associated with use for >48 hr), patent ductus arteriosus in neonate (conflicting data), oligohydramnios (reversible), NEC (conflicting data)Platelet dysfunction or bleeding disorder, hepatic or renal dysfunction, gastrointestinal or ulcerative disease, asthma (in women with hypersensitivity to aspirin)
Oxytocin receptor antagonistsHypersensitivity injection-site reactionsFor atosiban, an increased rate of fetal or infant death (may be attributable to the lower gestational age of infants in the atosiban group)None
Nitric oxide donorsDizziness, flushing, hypotensionHypotension, preload-dependent cardiac lesions (e.g., aortic insufficiency)

From Gabbe SG et al: Obstetrics: normal and problem pregnancies, ed 7, Philadelphia, 2017, Saunders.

Prophylactic Or Chronic Rx

  • Patients with a history of prior spontaneous preterm birth may be candidates for prophylactic use of 17 alpha-hydroxyprogesterone caproate between 16 wk and 36 wk gestation. These patients may also benefit from transvaginal cervical length screening in pregnancy to monitor for short cervix.
  • Patients with a history of preterm birth and short cervix may also be candidates for prophylactic or rescue cerclage.
  • Patients with a short cervix may be candidates for vaginal progesterone for prevention and, in some clinical studies, vaginal pessary.
  • There is no evidence supporting the use of maintenance tocolytic therapy.
Referral

  • Women who present in preterm labor should be referred to an obstetrician and transferred to a facility with a neonatal intensive care unit.
  • For women who present for prenatal care with a history of preterm delivery, early referral to an obstetrician is also recommended.
Related Content

Abruptio Placentae (Related Key Topic)

Breech Birth (Related Key Topic)

∗Ritodrine is currently discontinued in the U.S.

Suggested Readings ⬆

    1. 560: medically indicated late-preterm and early-term deliveriesObstet Gynecol. ;121(4):908-910, 2013.
    2. Purisch S.E., Gyamfi-Bannerman C. : Epidemiology of preterm birthSemin Perinatol. ;41(7):387-391, 2017.