What is respiratory distress syndrome (RDS) in neonates, particularly those born prematurely?

Respiratory Distress Syndrome in Neonates

Definition and Core Pathophysiology

Respiratory distress syndrome (RDS) is a life-threatening respiratory disorder of preterm newborns caused by surfactant deficiency, leading to widespread alveolar collapse (atelectasis), impaired gas exchange, and progressive respiratory failure. 1, 2 The deficiency of pulmonary surfactant prevents stabilization of alveoli against collapse at resting transpulmonary pressures, resulting in poor lung expansion and inadequate oxygenation 2. High alveolar capillary permeability allows serum proteins to leak into airways, further inhibiting any residual surfactant function and creating a vicious cycle of worsening respiratory failure 1.

Epidemiology and Risk Factors

RDS predominantly affects premature infants, with incidence inversely proportional to gestational age 1:

• Infants born at <30 weeks gestation and weighing <1,000g have the highest incidence 1
• At ≤27 weeks gestation, 90-92% require surfactant therapy even after antenatal steroid exposure 1, 3
• Multiple gestation pregnancies increase risk 1
• Absence of antenatal corticosteroid administration is a major modifiable risk factor 1

Clinical Presentation

RDS presents with immediate onset at birth in premature infants, characterized by severe respiratory distress with grunting, nasal flaring, intercostal and subcostal retractions, and central cyanosis. 3 The respiratory distress typically appears within the first hours of life (mean onset 3.11 ± 3.59 hours) 4. The condition shows diffuse bilateral lung involvement without spared areas, distinguishing it from other causes of neonatal respiratory distress 3.

Diagnostic Approach

Preferred Imaging Modality

Lung ultrasound is the preferred diagnostic tool over chest X-ray for RDS, offering superior diagnostic accuracy with real-time bedside assessment. 5, 6 The characteristic ultrasound findings include 5, 3:

• Bilateral confluent B-lines throughout all lung fields (diffuse "white lung" appearance)
• Complete absence of A-lines
• Pleural line abnormalities and thickening
• Small subpleural consolidations
• No spared lung areas (critical distinguishing feature)

Differential Diagnosis

POCUS effectively distinguishes RDS from transient tachypnoea of the newborn (TTN), which shows 5, 3:

• Bilateral B-lines predominantly in dependent (lower) lung areas
• Normal or near-normal appearance in superior (upper) lung fields with preserved A-lines
• Alternating interstitial pattern with areas of near-normal lung

High inter-observer agreement has been demonstrated regardless of operator expertise, making this distinction reliable in clinical practice 5.

Prevention Strategies

Antenatal Interventions

Antenatal corticosteroids are the most effective preventive intervention, working synergistically with postnatal surfactant to reduce mortality, severity of RDS, and air leaks. 5, 1 This represents the single most important modifiable intervention for at-risk pregnancies 1.

Management Algorithm

Initial Respiratory Support

For all spontaneously breathing preterm infants with respiratory distress, initiate CPAP at 5-6 cm H₂O immediately after birth rather than routine intubation. 5, 1, 6 This approach:

• Prevents atelectasis by maintaining functional residual capacity 5, 1
• Reduces the combined risk of death or bronchopulmonary dysplasia compared to immediate intubation 1
• Represents less invasive support with superior outcomes 5

Surfactant Replacement Therapy

Surfactant replacement is the cornerstone of RDS treatment and should be administered as early rescue therapy (within 2 hours of birth) for confirmed RDS in infants <30 weeks gestation requiring mechanical ventilation. 5, 1, 6 The evidence supporting this approach is compelling 5, 2:

• Reduces overall mortality by 47% (RR 0.53, NNT=9) 1
• Decreases pneumothorax risk (RR 0.62, NNT=47) 1
• Reduces combined outcome of bronchopulmonary dysplasia or death (RR 0.85, NNT=24) 1
• Multiple-dose regimens (initial 200 mg/kg followed by up to two 100 mg/kg doses) reduce mortality more than single-dose therapy 2

The recommended dosing regimen is: 2

• Initial dose: 2.5 mL/kg (200 mg/kg poractant alfa)
• Subsequent doses: 1.25 mL/kg (100 mg/kg) every 12 hours as needed
• Maximum: three total doses

Mechanical Ventilation Strategy

When mechanical ventilation is required 1:

• Use PEEP (positive end-expiratory pressure) to prevent lung collapse at end-expiration 1
• Apply gentle ventilation strategies to minimize barotrauma and oxygen toxicity 1
• These approaches reduce the risk of bronchopulmonary dysplasia development 1

Treatment Algorithm Summary

1. Immediate CPAP (5-6 cm H₂O) for all spontaneously breathing preterm infants 5
2. If requiring mechanical ventilation with FiO₂ ≥0.60, administer surfactant within 2 hours 5, 1
3. Consider additional surfactant doses every 12 hours based on ongoing oxygen requirements 2
4. Maintain gentle ventilation with PEEP if intubated 1

Critical Pitfalls to Avoid

Never administer surfactant empirically without confirming RDS diagnosis—surfactant is contraindicated in TTN and will not benefit pneumonia alone 3, 6. Lung ultrasound confirmation is essential before treatment 5, 3.

Do not delay CPAP initiation—early application immediately after birth is critical for preventing initial alveolar collapse 5.

Avoid prolonged mechanical ventilation when possible—the INSURE strategy (intubation, surfactant, extubation to CPAP) may be appropriate for rapid extubation candidates, though early CPAP with selective surfactant shows superior outcomes 5.

Complications and Long-term Outcomes

RDS is the primary precursor to bronchopulmonary dysplasia (BPD), a chronic condition characterized by alveolar simplification in the modern era. 1 Long-term sequelae include 1:

• Airway obstruction and hyperreactivity persisting into childhood
• Average FEV₁ approximately 80% of control subjects at 6-15 years of age
• Multisystem complications beyond respiratory system

Pulmonary hemorrhage is a known complication of premature birth and has been reported in infants receiving surfactant therapy 2.

Special Populations

Full-term Neonates with RDS

While RDS predominantly affects preterm infants, it can occur in full-term neonates with different clinical characteristics 4:

• Associated with severe perinatal infections, elective cesarean section, severe birth asphyxia, or maternal diabetes 4
• Higher likelihood of developing persistent pulmonary hypertension and multiple organ system failure 4
• Requires comprehensive management with early mechanical ventilation and broad-spectrum antibiotics when infection is suspected 4

Secondary Surfactant Deficiency

Rescue surfactant may be considered for infants with hypoxic respiratory failure attributable to secondary surfactant deficiency (meconium aspiration syndrome, pulmonary hemorrhage, or sepsis/pneumonia) 5. For severe meconium aspiration syndrome, surfactant improves oxygenation and reduces ECMO need (RR 0.64, NNT=6) 6.

Expertise Requirements

Preterm and term neonates receiving surfactant must be managed by personnel with technical and clinical expertise to administer surfactant safely and manage multisystem illness—providers without expertise should await transport team arrival 5.