Preterm Labor and Birth

Overview

Definitions

Preterm labor is defined as regular uterine contractions that lead to cervical change in dilation and/or effacement prior to 37 weeks of gestation.

Preterm birth is defined as birth at a gestational age of 20–37 weeks.

Epidemiology

Preterm labor:

• < 10% of women with preterm labor give birth within 7 days.
• 50% of patients hospitalized for preterm labor will ultimately deliver at term.

Preterm birth:

• Incidence: 12% of all live births
  • Spontaneous preterm birth: approximately 75%
  • Indicated preterm birth: approximately 25%
• Racial and ethnic bias: African American > Caucasians
• Impact:
  • 70% of neonatal deaths
  • 25%–50% of long-term neurological impairment

Etiology and Risk Factors

Etiology of spontaneous preterm birth

• Preterm labor
• Preterm prelabor rupture of membranes (PPROM)
• Cervical insufficiency

Etiology of indicated preterm birth

• Maternal indications:
  • Hypertensive disorders:
    • Severe preeclampsia
    • Poorly-controlled chronic hypertension
  • Severe infections
  • Hemodynamic instability
• Obstetric indications:
  • PPROM without labor after 34 weeks
  • Intra-amniotic infection (IAI)
  • Prior classical cesarean section
• Fetal indications:
  • Intrauterine growth restriction (IUGR)
  • Oligohydramnios
  • Multiple gestation
  • Congenital anomalies
• Placental indications:
  • Placenta previa (placenta near the cervical os)
  • Placenta accreta (placenta invading the myometrium)
  • Placental abruption (placental separation from the decidua)

Risk factors for preterm labor and birth

Because preterm labor is a major etiology of preterm birth, all risk factors for preterm labor are also risk factors for spontaneous preterm birth.

• Prior obstetric history:
  • Prior preterm birth:
    • Most important risk factor overall
    • Includes both spontaneous and indicated preterm births
  • Prior PPROM
  • Prior uterine evacuation 
• Age, race, and genetics:
  • Nonhispanic black women
  • Extremes of maternal age (young and old)
  • Genetic polymorphisms: contribute to risk (though environmental factors are likely more important)
• Fetal factors:
  • Congenital anomalies
  • Growth restriction 
• Cervical factors:
  • History of cervical surgery (e.g., conization)
  • Short cervix on ultrasound
  • Cervical dilation ≥ 1 cm prior to 24 weeks
• Uterine factors:
  • Congenital uterine anomalies (e.g., uterine septum)
  • Leiomyomas (fibroids)
  • Uterine overdistension:
    • Multiple gestation
    • Polyhydramnios
• Intrauterine bleeding:
  • Placental abruption
  • Decidual hemorrhage early in pregnancy
• Infections:
  • IAI (chorioamnionitis)
  • Genital tract infection:
    • Group B streptococcus (GBS)
    • STD
    • Bacterial vaginosis
    • Note: Candida is not a risk factor.
  • Pyelonephritis
  • Pneumonia 
  • Periodontal disease
  • Malaria
• Maternal chronic medical disorders:
  • Hypertension
  • Diabetes mellitus Type 1
  • Renal insufficiency
  • Autoimmune disease
• Other maternal factors:
  • Pregnant as a result of assisted reproductive technology
  • Abdominal surgery during pregnancy
  • Short interval between pregnancies
  • Poor prenatal care
  • Smoking and substance abuse
  • Undernutrition
  • Extremes of prepregnancy weight (low and high)
  • Occupational activity:
    • Prolonged standing and walking
    • Lifting heavy objects
    • Working night shifts
    • Working long hours
• Environmental factors:
  • Air pollution (fine particulate matter, ozone)
  • High environmental temperature
  • Phthalate exposure

Pathophysiology and Clinical Presentation

Preterm labor

Common final pathway for initiating preterm labor:

• Prostaglandin secretion:
  • Alters collagen and glycosaminoglycans in cervical tissue (cervical maturation, cervical ripening)
  • ↑ Uterine contractility
• Degradation of the extracellular matrix around fetal membranes
• Oxytocin → coordinated uterine contractions

Primary pathways (4) leading to the common final pathway:

• Stress:
  • Stress → ↑ placental corticotropin-releasing hormone (CRH) → ↑ prostaglandins
  • Fetal stress (more common): uteroplacental vascular insufficiency
  • Maternal stress (less common): psychosocial stress
• Infection and inflammation:
  • Bacteria can produce:
    • Phospholipase A2 → promote prostaglandin synthesis
    • Endotoxin → stimulate uterine contractions directly
    • Protease, collagenase, elastase → degrade fetal membranes → PPROM
  • Bacteria bind toll-like receptors (TLRs) on uterine, placental, and membrane tissue → trigger release of inflammatory mediators:
    • Interleukin (IL)-1, IL-6, and IL-8
    • Tumor necrosis factor (TNF)
    • Matrix metalloproteinase (MMP)
  • Effect of inflammatory mediators:
    • ↑ Prostaglandin secretion
    • ↑ Uterine contractility
    • Induce protease → PPROM
• Decidual hemorrhage:
  • Intrauterine bleeding → activation of the coagulation cascade
  • Thrombin → binds protease-activated receptor (PAR) 1 and 3:
    • ↑ Frequency, intensity, and tone of myometrial contractions
    • ↑ MMP 
    • ↑ IL-8 in decidual cells 
• Uterine overdistension:
  • Common causes: 
    • Multiple gestations
    • Polyhydramnios
  • Stretched myometrium:
    • Upregulates oxytocin receptors
    • ↑ Inflammatory cytokine, prostaglandin, and collagenase

Preterm birth

All pathways leading to preterm labor (above) can progress to preterm birth.

Preterm birth may also be caused by cervical insufficiency:

• Cervical dilation without contractions (not labor)
• Due to structural weakness of the cervix:
  • Prior cervical surgery 
  • Ehlers-Danlos syndrome
  • Inflammation

Clinical presentation

Pregnant women < 37 weeks’ gestational age who present with:

• Labor-like contractions or pain
• Menstrual-like cramping
• Back or lower abdominal pain
• Pelvic or vaginal pressure
• Vaginal discharge (mucus plug)
• Vaginal bleeding
• Leaking fluid (preterm labor associated with PPROM)

Diagnosis

The key to diagnosing preterm labor is to determine whether cervical change is occurring, and if regular contractions are causing those changes. The cervical length is also important in helping to predict preterm birth regardless of contractions.

Exam and initial monitoring

• Sterile speculum exam (SSE): always done 1st
  • Visually assess cervical dilation: ≥ 3 cm suggests preterm labor.
  • Assess membrane status: Pooling of fluid suggests PPROM.
  • Collected swabs for testing 
• Digital cervical examination (after SSE):
  • Exclude placenta previa and PPROM prior to cervical exams.
  • Often repeated to monitor for cervical change
• Fetal monitoring and tocometry:
  • Tocometry: records uterine contractions
  • Fetal heart rate monitor: verifies fetal well-being

Tests and imaging

• Testing for urogenital tract infections:
  • Rectovaginal culture for GBS (if not already obtained)
  • Microscopy (for vaginitis)
  • Chlamydia and gonorrhea test (high-risk patients only)
  • Urinalysis and urine culture
• Fetal fibronectin (fFN):
  • fFN: an extracellular matrix protein present at the interface between the decidua and chorion
  • Disruption of the interface releases fFN into cervical secretions.
  • Predicting preterm birth:
    • Detection of fFN helps to predict delivery within the next 7 days.
    • Most useful in cases with cervical lengths 20–30 mm 
    • ↑ Negative predictive value
    • ↓ Positive predictive value
  • False positives can be caused by:
    • Exposure to coital ejaculate within the last 24 hours
    • Blood
    • Digital cervical examinations
• Transvaginal ultrasound:
  • Cervical length: 
    • > 30 mm has ↑ negative predictive value for preterm birth.
    • < 30 mm predicts ↑ risk for preterm birth.
• Obstetric abdominal ultrasound:
  • Confirm placental location.
  • Assess fluid volume:
    • Single deepest pocket of fluid: Normal range is 2–8 cm.
    • Amniotic fluid index: Normal range is 5–25 cm.
    • Oligohydramnios: single deepest pocket ≤ 2 cm or amniotic fluid index ≤ 5 cm
    • Polyhydramnios: single deepest pocket ≥ 8 cm or amniotic fluid index ≥ 24 cm
  • Estimate fetal weight (helpful for the pediatrics team).

Diagnostic criteria

Diagnosing preterm labor requires uterine contractions plus cervical change:

• Uterine contractions:
  • ≥ 4 in 20 minutes, or ≥ 8 in 60 minutes
• Cervical change:
  • Dilation ≥ 3 cm
  • Cervical length < 20 mm on ultrasound
  • Cervical length 20–30 mm on ultrasound with a positive fFN

Management

Patients diagnosed with preterm labor should be hospitalized for observation of progressing labor and for treatment.

• Corticosteroids (betamethasone most commonly given):
  • Benefits: ↓ neonatal morbidity and mortality
    • ↑ Fetal lung maturity → ↓ risk of neonatal respiratory distress
    • ↓ Intraventricular hemorrhage
    • ↓ Necrotizing enterocolitis
    • ↓ Death
  • Dosage:
    • A single course: 2 doses, 24 hours apart
    • Maximum benefit: 48 hours to 7 days after the 1st dose
  • Give to:
    • All patients < 34 weeks
    • Patients 34–37 weeks when delivery is anticipated within 7 days 
• Magnesium sulfate:
  • Benefits:
    • Fetal neuroprotection → ↓ cerebral palsy
    • Beneficial when given at the time of delivery
  • Give to patients < 32 weeks’ gestational age.
• Tocolytics:
  • Benefits:
    • Lessen contraction strength and intensity
    • Given for up to 48 hours only → allows for maximal benefit of corticosteroids
  • Options:
    • Indomethacin
    • Nifedipine
    • Terbutaline
  • Contraindications:
    • Intra-amniotic infection
    • PPROM
    • Nonreassuring fetal status
    • Nonviable fetus
    • Maternal instability (e.g., maternal hemorrhage, severe preeclampsia)
• GBS prophylaxis:
  • IV penicillin or ampicillin
  • Treat during labor if GBS status is positive or unknown.
  • Patients with recent documented negative cultures do not require treatment.

Prevention

History of spontaneous preterm birth

• Progesterone supplementation
• Cerclage:
  • A permanent suture placed in a purse-string fashion around the cervix to keep it closed.
  • Transvaginal ultrasound screening in patients with a history of cervical insufficiency 
  • Indicated for patients < 24 weeks with a cervix < 25 mm
  • Cut in labor: Force of contractions will cause the suture to tear through the cervix.
• Preconception correction of any uterine malformations:
  • Myomectomy 
  • Resection of uterine septum
• Preconception optimization of:
  • Weight
  • Nutrition
  • Smoking cessation

History of indicated preterm birth

• Low-dose aspirin → reduces the risk of recurrent preeclampsia
• Preconception optimization of chronic medical conditions

Differential Diagnosis

• False labor/Braxton Hicks contractions: uterine contractions without cervical changes. Mild, irregular contractions are normal throughout pregnancy. Braxton Hicks contractions typically do not increase in intensity or duration but may occur more frequently with increased gestational age. No clear test or threshold exists to identify who will progress onto true labor. Therefore, serial assessment is often required for diagnosis. Dehydration and extended activity have been associated with false labor.
• Preterm prelabor rupture of membrane (PPROM): the rupture of membranes (chorion and amnion) before the onset of labor. Patients usually present with a “gush of fluid” from the vagina. The key difference between PPROM and preterm labor is the presence of contractions. Contractions will initially be absent in PPROM but often develop if infection is present. Preterm labor may be precipitated by PPROM. Patients are at high risk for ascending intra-amniotic infection once membranes have ruptured.