Neonatal 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. Suspected diagnosis is based on clinical features and confirmed by evaluating the extent of atelectasis via an x-ray of the chest. Blood gases show respiratory and metabolic acidosis in addition to hypoxia. Treatment primarily involves emergency resuscitative measures, including nasal continuous positive airway pressure (CPAP) and the stabilization of blood sugar levels and electrolytes. Intratracheal surfactant should be administered if infants require an increased FiO₂ to maintain a sufficient oxygen saturation despite receiving noninvasive positive pressure ventilation. Intratracheal surfactant should be administered if ventilation alone is unsuccessful. Most cases resolve within 3–5 days of treatment. However, complications such as hypoxemia, tension pneumothorax, bronchopulmonary dysplasia, or sepsis may still occur. In rare cases, NRDS may lead to neonatal death. NRDS can be prevented by administering antenatal glucocorticoids to the mother if premature delivery is expected.

Neonatal respiratory distress syndrome is caused by impaired synthesis and secretion of surfactant. Risk factors include:

• Premature birth
• Maternal diabetes mellitus: leads to ↑ fetal insulin, which inhibits surfactant synthesis
• Hereditary ^[1]
• Cesarean delivery: results in lower levels of fetal glucocorticoids than vaginal delivery, in which higher levels are released as a response to stress from uterine contractions
• Hydrops fetalis
• Multifetal pregnancies
• Male sex

• Incidence ^[2]
  • 1% of all newborns
  • 10% of all preterm babies
• The risk of developing NRDS depends on gestational age. ^[2]
  • < 28 weeks of gestation: > 50%
  • > 37 weeks of gestation: < 5%

Epidemiological data refers to the US, unless otherwise specified.

Surfactant ^[3]

• Pulmonary surfactant is a mixture of phospholipids and proteins produced by lamellar bodies of type II alveolar cells. These phospholipids reduce alveolar surface tension, preventing the alveoli from collapsing.
• Surfactant deficiency is most likely to occur in preterm infants, because:
  • Surfactant production begins at approximately 20 weeks gestation.
  • Distribution throughout the lungs begins at 28-32 weeks' gestation and does not reach sufficient concentration until 35 weeks gestation.

Surfactant deficiency

• Little or no reduction of alveolar surface tension → increased alveolar collapse → atelectasis → decreased lung compliance and functional residual capacity → hypoxemia and hypercapnia
• Hypoxemia and hypercapnia → vasoconstriction of the pulmonary vessels (hypoxic vasoconstriction) and respiratory acidosis → 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)

• Maternal history of premature birth
• Onset of symptoms: usually immediately after birth but can occur up to 72 hours postpartum
• Signs of increased respiratory effort
  • Tachypnea
  • Nasal flaring and moderate to severe subcostal/intercostal and jugular retractions
• Characteristic expiratory grunting
• Decreased breath sounds on auscultation
• Cyanosis due to pulmonary hypoxic vasoconstriction

Reference:^[4]

• Physical examination: see “Clinical features” above
• Maternal history: previous preterm birth
• X-ray chest
  • Interstitial pulmonary edema with perihilar streaking
  • Diffuse, fine, reticulogranular (ground-glass) densities with low lung volumes and air bronchograms
  • Atelectasis
• Blood gas analysis
  • Hypoxia with respiratory acidosis; may lead to increased lactate levels
  • Evaluate for partial respiratory failure or global respiratory failure
• Amniocentesis for prenatal testing of NRDS: screening for markers of fetal lung immaturity
  • Lecithin-sphingomyelin ratio < 1.5 (≥ 2 is considered mature)
    • The amount of sphingomyelin in the amniotic fluid remains relatively consistent during pregnancy.
    • The amount of lecithin, which is the major component of surfactant, starts increasing after week 26 of gestation.
    • The lower the lecithin-sphingomyelin ratio, the more likely it is that the lungs are immature.
  • Foam stability index < 0.48
    • A semi-quantitative test used to assess fetal lung maturity
    • Amniotic fluid is mixed with ethanol until foam formation ceases to occur
    • The index refers to the highest quantity of ethanol that can be added to amniotic fluid still permitting the formation of foam.
  • Low surfactant-albumin ratio
• Histological findings ^[5]
  • Hyaline membranes lining the alveoli
    • Composed of fibrin, cellular debris, and red blood cells
    • Eosinophilic appearance, amorphous material lining the alveolar surface
  • Engorged and congested capillary vessels in the interstitium

References:^[2][6][7]

• Pulmonary hypoplasia
  • Underdevelopment of the lungs characterized by a decreased number of alveoli and small airways and reduced lung volumes in one or both lobes
  • Results in impaired gas exchange and severe respiratory distress that may require intubation
  • Associated with congenital diaphragmatic hernia (usually left-sided), oligohydramnios, and Potter sequence
• Congenital diaphragmatic hernia
• Pneumothorax
• Neonatal pneumonia

The differential diagnoses listed here are not exhaustive.

• Ventilation ^[8]
  • Nasal CPAP with a PEEP of 3–8 cm H₂O
  • If respiratory insufficiency persists, start 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%. A saturation of 100% is considered toxic for neonates!

Bronchopulmonary dysplasia (BPD) ^[16]

• Definition: chronic lung condition secondary to prolonged mechanical ventilation and oxygen therapy for NRDS
• Etiology: Pulmonary barotrauma and oxygen toxicity with subsequent inflammation of lung tissue due to ventilation of the immature lung (ventilation for more than 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
  • X-ray chest: diffuse, fine, granular densities, areas of atelectasis interspersed with areas of hyperinflation
  • Blood gas analysis: respiratory and metabolic acidosis
  • Histology: atelectasis, fibrosis, emphysematous alveolar changes (decreased number and septation of alveoli)
• Treatment: controlled oxygenation, diuretics, rarely glucocorticoids

Further complications

• Pneumothorax
• Patent ductus arteriosus (the persistently low partial pressure of oxygen in the blood contributes to PDA)
• Hypoxia
• Cardiovascular arrest
• Neonatal sepsis
• Complications of O₂ inhalation: retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage

Baby oxen have RIBs: Babys receiving too much oxygen get Retinopathy of prematurity, Intraventricular hemorrhage, and Bronchopulmonary dysplasia.

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

• Mortality rate: < 10% ^[17]
• Most cases resolve within 3–5 days if treated promptly

• Prevent premature birth if possible. See tocolysis.
• Antenatal corticosteroid therapy administered to the mother (stimulates infant lung maturation) ^[18]
  • Given 48 hours before delivery
  • 2 doses of IM betamethasone 24 hours apart or 4 doses of IM dexamethasone 12 hours apart