What are the potential causes of persistent respiratory distress in term neonates, excluding transient tachypnea of the newborn (TTNB)?

Causes of Persistent Respiratory Distress in Term Neonates (Excluding TTNB)

Primary Respiratory Causes

The most common causes of persistent respiratory distress in term neonates, excluding transient tachypnea of the newborn, are meconium aspiration syndrome, neonatal pneumonia/sepsis, persistent pulmonary hypertension of the newborn, and respiratory distress syndrome, with less common causes including pulmonary hemorrhage and congenital airway anomalies. 1, 2

Meconium Aspiration Syndrome (MAS)

• MAS occurs in approximately 3-5% of neonates born through meconium-stained amniotic fluid and is defined as respiratory distress with supplemental oxygen requirement in the absence of other identified etiology 3, 4
• Post-term status (≥42 weeks gestation) significantly increases risk, with meconium-stained fluid occurring in 5-15% of all deliveries 3
• MAS presents with severe respiratory failure often complicated by surfactant inactivation and persistent pulmonary hypertension 1
• Chest radiography shows hyperinflation with patchy infiltrates, distinguishing it from TTN which shows perihilar streaking and fluid in fissures 3
• Surfactant replacement improves oxygenation and reduces severity of respiratory failure, air leaks, and need for ECMO (RR: 0.64; 95% CI: 0.46-0.91; NNT: 6) 1

Neonatal Pneumonia and Sepsis

• Pneumonia/sepsis accounts for approximately 21-24% of hypoxic respiratory failure cases in term neonates 5
• Surfactant inactivation occurs with pneumonia, and rescue surfactant therapy improves oxygenation and reduces need for ECMO 1
• Group B streptococcal infection is a common infectious etiology associated with persistent pulmonary hypertension 6
• Empiric antibiotics must be administered within 1 hour of sepsis identification 7

Persistent Pulmonary Hypertension of the Newborn (PPHN)

• PPHN accounts for 17-30% of hypoxic respiratory failure in term neonates and can occur as idiopathic phenomenon or secondary to MAS, pneumonia, perinatal asphyxia, or congenital diaphragmatic hernia 5, 6
• Inhaled nitric oxide at 20 ppm is first-line treatment for PPHN, with ECMO reserved for refractory cases with oxygenation index >25 7, 5
• Surfactant improves oxygenation and reduces need for ECMO when parenchymal lung disease is present, though it does not significantly reduce ECMO need in severe primary PPHN without parenchymal disease 1
• Metabolic alkalinization is critical during initial resuscitation as PPHN can reverse when acidosis is corrected 7

Respiratory Distress Syndrome (RDS) in Term Infants

• RDS in term infants occurs as primary surfactant deficiency, secondary surfactant deficiency, or congenital surfactant dysfunction disorder 1, 8
• Chest radiography shows ground-glass appearance with air bronchograms, distinguishing it from MAS 3
• Surfactant dysfunction disorders (ABCA3 deficiency, surfactant protein deficiencies) can masquerade as MAS and PPHN 8
• Consider genetic surfactant dysfunction when there is significant family history of sibling death with severe neonatal respiratory disease 8

Pulmonary Hemorrhage

• Blood inhibits surfactant function, making surfactant treatment plausible, though only retrospective and observational reports document benefits 1
• Pulmonary hemorrhage is an unpredictable complication making randomized trials difficult to design 1

Structural and Surgical Causes

Congenital Diaphragmatic Hernia

• Associated with surfactant insufficiency due to altered pool sizes and kinetics despite normal synthetic rates 1
• Critical pitfall: Do not administer surfactant to infants with congenital diaphragmatic hernia, as this increases mortality, ECMO requirements, and chronic lung disease 1, 9

Airway Obstructive Lesions

• Bilateral choanal atresia occurs in 1 in 7,000-8,000 live births and is life-threatening immediately after birth since newborns are obligate nasal breathers during first 3-4 weeks of life 9
• Presents with periodic respiratory distress and cyanosis relieved by crying, severe feeding problems, and aspiration 9
• Diagnosis established by inability to pass catheter through either nostril into pharynx, confirmed by endoscopy and high-resolution CT 9
• Requires immediate oropharyngeal airway or intubation within first hours of life before surgical correction within first days 9
• CHARGE malformation is most frequent syndromal association (20% of cases) 9

Metabolic and Rare Causes

Inborn Errors of Metabolism

• Methylmalonic acidemia can present concomitantly with PPHN, representing a subset of "idiopathic" PPHN cases 10
• Metabolic acidosis from any inborn error of metabolism may produce pulmonary vasoconstriction and maintain pulmonary hypertension 10
• Consider aggressive search for underlying inborn error of metabolism in cases of PPHN without identifiable common causes, especially with metabolic acidosis 10

Critical Management Pitfalls to Avoid

• Do not perform routine tracheal intubation and suctioning in nonvigorous infants born through meconium-stained fluid, as this delays ventilation without improving outcomes 3
• Do not delay positive pressure ventilation to perform suctioning, as this leads to prolonged hypoxia and worse outcomes 3
• Ensure resuscitation team skilled in intubation is present at delivery when meconium-stained fluid identified, even though routine intubation is not indicated 3
• Reserve intubation for failure to respond to adequate bag-mask positive pressure ventilation, evidence of airway obstruction, or need for prolonged mechanical ventilation 3, 7