Neonatal respiratory distress syndrome (Infant respiratory distress syndrome…)

Neonatal respiratory distress syndrome (NRDS), or surfactant deficiency disorder, is a lung disorder in infants that is caused by a deficiency of pulmonary surfactant. It is most common in preterm infants, with the incidence and severity decreasing with gestational age. Surfactant deficiency causes the alveoli to collapse, resulting in impaired blood gas exchange. Symptoms manifest shortly after birth and include tachypnea, tachycardia, increased breathing effort, and/or cyanosis. The diagnosis is suspected based on clinical features and confirmed by evaluating the extent of atelectasis via chest x-ray. Blood gases show respiratory and metabolic acidosis in addition to hypoxia. Treatment primarily involves emergent resuscitative measures, which include nasal CPAP and stabilizing blood sugar levels and electrolytes. Additionally, intratracheal surfactant is administered if ventilation alone is not successful. Most cases resolve within 3–5 days of treatment. However, complications like hypoxemia, tension pneumothorax, bronchopulmonary dysplasia, sepsis, and neonatal death may still occur. NRDS can be prevented by administering antenatal glucocorticoids to the mother if premature delivery is expected.

• Impaired synthesis and secretion of surfactant
• Risk factors
  • Premature birth
  • Genetic predisposition
  • Scheduled cesarean section
  • Maternal diabetes mellitus
  • Hydrops fetalis
  • Multifetal pregnancies
• Rarely, hereditary

References:^[1]

• Surfactant
  • Pulmonary surfactant is a mixture of phospholipids and proteins produced by lamellar bodies of type II alveolar cells. These phospholipids reduce alveolar surface tension and thereby prevent the alveoli from collapsing.
  • Surfactant production occurs early, at around 20 weeks' gestation. However, its distribution throughout the lungs begins around weeks 28–32 and does not reach sufficient concentration until week 35. Thus, any infant born before term is vulnerable to surfactant deficiency.
• Surfactant deficiency → little or no reduction of alveolar surface tension → reduced pulmonary unfolding → atelectasis → decreased lung compliance and functional residual capacity → hypoxemia and hypercapnia
  • Hypoxemia and hypercapnia → vasoconstriction of the pulmonary vessels (hypoxic vasoconstriction) and acidotic metabolism → intrapulmonary right-to-left-shunt → increased permeability due to alveolar epithelial damage → fibrinous exudation within the alveoli → development of hyaline membranes in the lungs (hyaline membrane disease)

References:^[1][3]

• History of premature birth
• Onset of symptoms: usually manifests immediately after birth
• Signs of increased breathing effort
  • Tachypnea
  • Nasal flaring and moderate to severe subcostal/intercostal and jugular retractions
• Typical expiratory “grunting”
• Auscultation: decreased breath sounds
• Cyanosis due to peripheral hypoxic vasoconstriction

References:^[4][1][5]

• Chest x-ray: diffuse, fine, reticulogranular (ground-glass) densities, with low lung volumes and air bronchograms
• Blood gas analysis
  • Hypoxia with respiratory acidosis; can also lead to increased lactate levels
  • Evaluation of partial respiratory failure or global respiratory failure if NRDS is suspected
• Prenatal testing for NRDS: Amniocentesis. Markers of fetal lung immaturity:
  • Lecithin-sphingomyelin ratio < 1.5
  • Foam stability index < 0.48
  • Low surfactant-albumin ratio
• Microscopic findings
  • Hyaline membranes lining the alveoli with engorged and congested capillary vessels
    • Composed of fibrin, cellular debris, and red blood cells
    • Appear as eosinophilic, amorphous material lining the alveolar surface

References:^{[4][1][2][6][7][8]}

• Lung hypoplasia
  • Premature rupture of the membranes is often associated with oligo-/anhydramnios.
  • After birth, the neonate presents with severe respiratory distress and requires intubation, as in respiratory distress due to surfactant deficiency.
  • Reduced lung volumes in one or both lobes
• Transient tachypnea of the newborn (wet lung disease)
  • Reversible respiratory disorder
  • Most commonly occurs in full-term neonates delivered by cesarean section. These infants often have fluid-filled lungs.
  • Diffuse crackles are heard on examination.
  • X-ray shows fluid in the lung fissures and increased lung volumes.
  • Treatment: supportive care (e.g., supplemental oxygen, neutral thermal environment, adequate nutrition)
• Congenital diaphragmatic hernia
• Pneumothorax
• Meconium aspiration syndrome: Neonates with meconium aspiration are usually post-term rather than preterm infants
  • An unresponsive neonate and green amniotic fluid establish the diagnosis and serve as indications for emergency intubation and endotracheal drainage.
  • Other signs include:
    • Increased lung volume
    • Asymmetric, patchy opacities
    • Pleural effusion
• Neonatal pneumonia

References:^[9][10]

The differential diagnoses listed here are not exhaustive.

• Ventilation
  • Nasal CPAP with a PEEP of 3–8 cm H₂O
  • If respiratory insufficiency persists, intubation with mechanical ventilation and O₂ inhalation
• Endotracheal administration of artificial surfactant within 2 hours postpartum
• Supportive measures: IV fluid replacement; stabilization of blood sugar levels and electrolytes

Physiologic O₂ saturation in neonates is around 90% instead of 100%. A saturation of 100% is considered toxic for the neonate!

References:^[1][10][11]

Bronchopulmonary dysplasia (BPD)

• Definition: chronic lung disease primarily found in premature infants exposed to prolonged mechanical ventilation and oxygen therapy for neonatal RDS
• Etiology: immature lung with exposure to ventilation → barotrauma, oxygen toxicity, inflammation
  • History of infant requiring mechanical ventilation > 28 days
• Clinical features
  • Seen in infants < 32 weeks
  • Persistence of symptoms similar to NRDS (e.g., tachypnea, grunting, nasal flaring); episodes of desaturation
• Diagnostics
  • Chest x-ray: diffuse, fine granular densities; atelectasis
  • Histology: atelectasis, fibrosis, emphysematous alveolar changes
• Therapy: controlled oxygenation, diuretics, consider glucocorticoids

Further complications

• Pneumothorax
• Hypoxia
• Patent ductus arteriosus
• Cardiovascular arrest
• Neonatal sepsis
• Complications of O₂ inhalation: retinopathy, bronchopulmonary dysplasia, and intraventricular hemorrhage.

References:^{[4][1][12][13]}

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

• Prevent premature birth if possible. See tocolysis in the Preterm labor and birth learning card.
• Antenatal corticosteroid therapy administered to the mother (stimulates infant lung maturation)
  • Given 48 hours before delivery
  • 2 doses of IM betamethasone 24 hours apart, or four doses of IM dexamethasone 12 hours apart

References:^[14]