Preterm labor and birth

Preterm labor is defined as regular uterine contractions and cervical changes before 37 weeks of pregnancy. Preterm birth is defined as live birth between 20 0/7 weeks and 36 6/7 weeks of gestation. Approximately half of patients who deliver prematurely are diagnosed with preterm labor. Risk factors include a previous preterm birth, a short cervical length during pregnancy, and multiple gestation. Clinical features include early onset of contractions, premature cervical changes, or premature rupture of membranes. The diagnosis is usually clinical and can be supported by a cervical ultrasound and/or fetal fibronectin detection test. Treatment includes tocolysis, antenatal steroids to improve fetal lung maturity, and magnesium sulfate to provide fetal neuroprotection. Tocolytic agents are used to prolong pregnancy to gain time for steroids and magnesium sulfate to take effect. Complications of the preterm infant include intraventricular hemorrhage, neonatal respiratory distress syndrome, and necrotizing enterocolitis. Avoidance of modifiable risk factors, management of cervical insufficiency, and vaginal progesterone supplementation can help prevent preterm labor in certain risk groups.

• Preterm labor: Regular uterine contractions with cervical effacement, dilation, or both before 37 weeks gestation.
• Preterm birth
  • Live birth between 20 0/7 weeks and 36 6/7 weeks of gestation
  • WHO subcategories
    • Extremely preterm (< 28 weeks)
    • Very preterm (28 to < 32 weeks)
    • Moderate to late preterm (32 to < 37 weeks)

Reference:^[1]

• Complications of preterm birth are the leading cause of death in children < 5 years of age worldwide. ^[1]
• About half of patients who deliver prematurely are diagnosed with preterm labor. ^[2]
• Preterm birth rate in the US: ∼ 12% of all live births ^[3][4]
• African-American women are 50% more likely to give birth prematurely compared to white women.

Epidemiological data refers to the US, unless otherwise specified.

The exact mechanisms underlying premature labor are not well understood, but certain risk factors have been identified. ^[5]

• High-risk factors
  • History of preterm birth
  • Cervical insufficiency
  • Multiple gestation
• Low-risk factors
  • Maternal and fetal medical conditions
    • Infections (e.g., urinary tract infections, STIs, vaginal infections )
    • Polyhydramnios
    • Malaria
    • Hypertensive pregnancy disorders (e.g., preeclampsia, HELLP syndrome)
    • Diabetes mellitus, gestational diabetes
    • Uterine anomalies (e.g., anomalies of Mullerian duct fusion, uterine fibroids)
    • Placenta previa
    • Placental abruption
    • Congenital abnormalities of the fetus
  • Lifestyle and environmental factors
    • Smoking
    • Substance use (e.g., alcohol or drugs)
    • Maternal or fetal stress
    • Maternal age (≤ 18 years, > 35 years) ^[6]
    • Low maternal prepregnancy weight

• Regular uterine contractions and associated symptoms of labor (e.g., lower back pain, increased vaginal mucus production or blood-tinged vaginal mucus, pressing sensation in the vagina)
• Cervical dilation, effacement, or both
• Preterm premature rupture of membranes
• For more information, see “Childbirth”.

• Clinical diagnosis based on preterm contractions and cervical changes (see “Childbirth”)
• Tests to evaluate the risk of preterm delivery ^[7]
  • Cervical length measurement on transvaginal ultrasound: A short cervix increases the risk of preterm birth.
  • Cervicovaginal fetal fibronectin (fFN) detection test
    • Elevated fFN levels support the diagnosis of preterm labor, which increases the risk of preterm birth.
    • Primarily used in patients with symptoms of labor to differentiate between true preterm labor and false labor

• Induction of fetal lung maturity: single course of antenatal steroids (IM betamethasone ; or IM dexamethasone ; ) ^[8][9]
  • Indication: 24 0/7 weeks to 33 6/7 weeks gestation with a risk of delivery within the next 7 days
  • Improves neonatal survival, fetal lung maturity, and surfactant production
  • Repeat the course if the last dose of corticosteroids was > 14 days previously.
  • The American College of Obstetricians and Gynecologists recommends a single course of betamethasone for pregnant women between 34 0/7 weeks and 36 6/7 weeks of gestation at risk of delivery within 7 days and who have not received a course of antenatal corticosteroids previously. ^[9][10]
• Tocolysis: administration of tocolytics to inhibit uterine contractions and prolong pregnancy ^[11]
  • Indication: recommended for up to 48 hours to enable administration of antenatal corticosteroids in preterm labor and/or transportation to another medical center
  • First-line: NSAIDs (e.g., indomethacin) or calcium channel blockers (e.g., nifedipine)
    • 24–32 weeks gestation: indomethacin (for < 72 hours)
    • 32–34 weeks gestation: nifedipine
  • Second-line: beta-2 adrenergic agonists (e.g., terbutaline), nifedipine
    • 24–32 weeks gestation: nifedipine , magnesium sulfate , terbutaline
    • 32–34 weeks gestation: terbutaline
  • Contraindications
    • Maternal drug contraindications (e.g., myasthenia gravis for magnesium sulfate, aortic insufficiency for calcium channel blockers)
    • Nonreassuring fetal cardiotocography
    • Intrauterine fetal demise
    • Chorioamnionitis
    • Antepartum hemorrhage with hemodynamic instability
    • Severe preeclampsia or eclampsia
    • Lethal fetal anomaly
• Fetal neuroprotection: administration of magnesium sulfate ^[12]
  • Indication: if birth < 32 weeks is anticipated
  • Reduces the risk and severity of neurological disorders (e.g., cerebral palsy).

Antibiotics for group B streptococcus (GBS) prophylaxis is recommended in preterm labor, preterm premature rupture of membranes, and when GBS infection is evident.

Pulmonary and cardiovascular

• Neonatal respiratory distress syndrome
• Patent ductus arteriosus (PDA)
• Bronchopulmonary dysplasia (BPD)

Neurological

Periventricular leukomalacia (PVL)

• Definition: symmetrical, periventricular injury of cerebral white matter (necrosis and cystic formation) caused by ischemia and/or infection
• Epidemiology: mainly affects premature infants
• Clinical features: features of spastic cerebral palsy, intellectual impairment, and visual disturbances
• Diagnostics: brain imaging using ultrasound, cranial CT, or MRI

Intraventricular hemorrhage (IVH) ^[13]

• Definition: Bleeding into the ventricles from the germinal matrix, a highly vascularized region within the subventricular zone of the brain from which cells migrate out during brain development.
• Etiology: associated with a number of risk factors
  • Birth weight < 1500 g and delivery before 32 weeks gestation due to the fragility of the germinal matrix and/or impaired autoregulation of blood pressure
  • Maternal chorioamnionitis
  • Hypoxia during or after birth
• Pathophysiology
  • Immaturity of the basal lamina and lack of astrocytic glial fibrillary acidic protein within the germinal matrix leads to abnormal cerebral autoregulation.
  • Alterations in an infant's blood pressure (e.g., during birth, intubation) → failure of cerebral autoregulation to compensate for the change in blood pressure → rupture of and bleeding from vessels in the germinal matrix → rupture of ependyma → blood flows into the ventricles
• Clinical features
  • Usually occurs within the first days of life (up to day 5)
  • Most infants are asymptomatic, but saltatory (for several days) or, more rarely, catastrophic (over minutes to hours) courses are also possible.
  • Lethargy, hypotonia, irregular respirations, seizures, bulging anterior fontanelle
  • Cranial nerve abnormalities (e.g., pupils react sluggishly to light) and changes in eye movement (e.g., roving eye movements)
• Diagnostics
  • Cranial ultrasound: allows grading of IVH based upon the location and extent to assess severity ^[14]
    • Grade I: bleeding confined to germinal matrix and ≤ 10% of the ventricular area
    • Grade II: 10–50% of the lateral ventricle volume occupied by germinal matrix and IVH
    • Grade III: > 50% of the lateral ventricle volume occupied by germinal matrix and IVH, ventricular distortion
    • Periventricular hemorrhagic infarction: hemorrhagic infarction in periventricular white matter ipsilateral to IVH
  • Since most patients are asymptomatic, screening ultrasounds are routinely performed in infants with a birth weight < 1500 g and delivery before 30 weeks gestation. ^[15]
• Treatment
  • Supportive
  • Lumbar puncture, diuretics, and/or ventriculoperitoneal shunt in severe IVH

Other

• Cerebral palsy
• Learning disabilities
• Developmental delays
• ADHD

Homeostasis

• Hypothermia of prematurity ^[16]
  • Definition: impaired ability to produce an adequate body temperature due to a high surface area: volume ratio
  • Clinical features: body temperature < 97.7°F (< 36.5°C), lethargy, cyanosis
  • Treatment: rewarming in an incubator or radiant warmer
• Apnea, bradycardia
• Hypoglycemia, hyperglycemia

Other

• Anemia of prematurity
  • Definition: impaired ability to produce adequate erythropoietin (EPO)
  • Clinical features: usually asymptomatic, possible symptoms include tachycardia, poor weight gain, increased episodes of apnea
  • Pathophysiology: onset of breathing and closure of ductus arteriosus → ↑ tissue oxygenation → ↓ erythropoiesis
  • Diagnostics: should be suspected in premature infants with low hemoglobin, hematocrit, and reticulocyte count
  • Treatment: iron supplementation, blood transfusions (severe cases)
• Retinopathy of prematurity (ROP)
• Necrotizing enterocolitis (NEC)
• Infection and sepsis (e.g., neonatal sepsis, neonatal pneumonia)

Morbidity and mortality in preterm infants increase with decreasing birth weight and gestational age.

We list the most important complications. The selection is not exhaustive.

• Mothers should avoid modifiable risk factors (see “Etiology” above)
• Manage cervical insufficiency, if present (see “Complications” in “Pregnancy”)
• Vaginal progesterone supplementation ^[17]
  • Women with a singleton pregnancy at 16–24 weeks gestation with a prior singleton preterm birth, regardless of cervical length and/or cervical cerclage
  • Women ≤ 24 weeks gestation with a short cervical length (≤ 25 mm)