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. The suspected diagnosis is 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, including nasal continuous positive airway pressure (CPAP) and stabilizing blood sugar levels and electrolytes. In addition, intratracheal surfactant is administered if ventilation alone is unsuccessful. Most cases resolve within 3–5 days of treatment. However, complications such as 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.

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

References:^[1][2]

Epidemiological data refers to the US, unless otherwise specified.

• Impaired synthesis and secretion of surfactant
• Risk factors
  • Premature birth
  • Genetic predisposition
  • Cesarean delivery; : results in lower levels of fetal glucocorticoids than vaginal delivery (uterine contractions during vaginal delivery increase fetal stress levels, which cause glucocorticoids to be released as a physiologic response to stress)
  • Maternal diabetes mellitus: leads to ↑ fetal insulin, which inhibits surfactant synthesis
  • Hydrops fetalis
  • Multifetal pregnancies
• In rare cases, 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, preventing the alveoli from collapsing.
  • Any infant born preterm is vulnerable to surfactant deficiency for the following reasons:
    • Surfactant production occurs at around 20 weeks' gestation.
    • Distribution throughout the lungs begins around weeks 28–32 and does not reach sufficient concentration until week 35.
• 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 metabolic 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)

References:^[1][3]

• History of premature birth
• Onset of symptoms: usually immediately after birth but can occur within 48–72 hours postpartum
• 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 pulmonary hypoxic vasoconstriction

References:^[1][4][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 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 varying concentrations of ethanol and shaken in test tubes
    • Foam forms in the presence of adequate surfactant
    • The index refers to the highest quantity of ethanol that can be added to amniotic fluid with the formation of stable foam.
  • Low surfactant-albumin ratio
• Pathological findings ^[6]
  • Hyaline membranes lining the alveoli
    • Composed of fibrin, cellular debris, and red blood cells
    • Appear as eosinophilic, amorphous material lining the alveolar surface
  • Engorged and congested capillary vessels in the interstitium

References:^{[1][2][4][7][8][9]}

• 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
  • Result in impaired gas exchange
  • Associated with congenital diaphragmatic hernia (usually left-sided), oligohydramnios, and the Potter sequence
  • After birth, the neonate presents with severe respiratory distress and requires intubation, as in respiratory distress due to surfactant deficiency.
• Congenital diaphragmatic hernia
• Pneumothorax
• Neonatal pneumonia

The differential diagnoses listed here are not exhaustive.

• Ventilation
  • 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% instead of 100%. A saturation of 100% is considered toxic for neonates!

References:^[1][10][17]

Bronchopulmonary dysplasia (BPD)

• Definition: chronic lung disease primarily found in premature infants exposed to prolonged mechanical ventilation and oxygen therapy for neonatal RDS
• Etiology: An immature lung with exposure to ventilation leads to barotrauma, oxygen toxicity, and inflammation.
  • 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
  • Chest x-ray: diffuse, fine, granular densities, areas of atelectasis interspersed with areas of hyperinflation
  • Histology: atelectasis, fibrosis, emphysematous alveolar changes
• Therapy: controlled oxygenation, diuretics, possibly glucocorticoids

Further complications

• Pneumothorax
• Hypoxia
• Patent ductus arteriosus (due to a persistently low partial pressure of oxygen in the blood)
• 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.

References:^{[1][4][18][19]}

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

• If left untreated, NRDS has a case fatality rate of 30%.
• Most cases that are promptly treated resolve within 3–5 days.

• Prevent premature birth if possible. See tocolysis.
• 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 4 doses of IM dexamethasone 12 hours apart

References:^[20]