Neonatal Respiratory Distress Syndrome

Overview

Neonatal respiratory distress syndrome (RDS), previously called hyaline membrane disease, is a disorder caused primarily by pulmonary surfactant deficiency and structural lung immaturity. It occurs mainly in premature infants and presents shortly after birth with tachypnoea, grunting, chest recession and increasing oxygen requirements. Severity increases as gestational age decreases.

Neonatal RDS is different from paediatric acute respiratory distress syndrome, which is an inflammatory lung injury occurring after insults such as pneumonia or sepsis.

Anatomy and Physiology

Transition from foetal life to neonatal life requires:

• Fetal lungs are filled with fluid from pulmonary secretions
• Most fluid moves out into amniotic fluid with breathing movements
• Labour onset causes release of catecholamines, fluid in lungs is largely squeezed out with passage of the chest through the birth canal
• With normal chest recoil, the infant’s lungs fill with air.
• Surfactant is released from type II pneumocytes to lower surface tension and establish residual lung volume
• Onset of regular breathing
• ↑pulmonary blood flow as a result of increased systemic vascular resistance and ↓pulmonary vascular resistance

Pulmonary Surfactant

• Pulmonary surfactant is a complex mixture of lipids and proteins
• The main function of surfactant is to decrease surface tension of the alveoli allowing for maintenance of functional residual capacity preventing atelectasis and lung injury.
• The surfactant proteins also contribute to natural immunologic defences and assist with the spreading of surfactant throughout the alveoli and the recycling of surfactant between cells and the airspaces.

Aetiology and Risk Factors

Major risk factor

• Prematurity, particularly birth before 32 weeks
• Risk increases substantially with decreasing gestational age.

Other risk factors

• Absence of antenatal corticosteroid exposure
• Maternal diabetes
• Caesarean birth without labour
• Male sex
• Multiple pregnancy, particularly the second-born twin
• Perinatal hypoxia or asphyxia
• Hypothermia
• Previous sibling affected by neonatal RDS
• Genetic abnormalities affecting surfactant production or function
• Very rapid delivery before normal physiological transition has occurred

Maternal diabetes can delay fetal surfactant maturation through fetal hyperinsulinaemia. Antenatal corticosteroids accelerate lung maturation and reduce RDS, intraventricular haemorrhage and neonatal mortality when preterm birth is anticipated

Pathophysiology

• The primary cause of RDS is deficiency of pulmonary surfactant, which is developmentally regulated.
• The fetal lung is filled with fluid and provides no respiratory function until birth
• Fetal alveolar development is occurring in utero. Week 20 of gestation, surfactant is slowly expressed.
  • Pre-term delivery → immature lungs/surfactant → RDS
  • Gene mutations for proteins in surfactant  → surfactant deficiency and/or dysfunction → RDS
• Insufficient surfactant stores leads to:
  • Decreased compliance of the lungs
  • Inability of the infant to maintain air in the lung at the end of expiration resulting in a tiny area of collapsed lung (microatelectasis).
    • ↑ effort on inhalation with microatelectasis → Ventilation and perfusion mismatch → Hypoxaemia, Tachypnoea, laboured breathing
  • Lung inflammation and respiratory epithelial injury, which may result in pulmonary oedema and increased airway resistance

Clinical Manifestation

Usually occur at or soon after birth (first 4-6 hours)

• Tachypnoea
• Laboured breathing
• Cyanosis
• Grunting
• Nasal flaring
• Intercostal and subcostal retraction

Diagnosis

Diagnosis is based on:

• Prematurity or another relevant risk factor
• Respiratory distress beginning shortly after birth
• Increasing oxygen or respiratory-support requirements
• Compatible chest imaging
• Exclusion of other causes of neonatal respiratory distress

Treatment should not be delayed until classical radiographic changes appear, because early CPAP and surfactant can prevent progression to severe radiographic disease.

Investigations

• Pulse oximetry
• Blood gas
• Chest X-ray
  • Classical findings include:
    • Reduced lung volumes
    • Diffuse fine reticulogranular or ground-glass appearance
    • Air bronchograms
    • Widespread atelectasis

Imaging also helps identify air leaks, pulmonary haemorrhage, pneumonia or incorrect tube and line positioning. Lung ultrasound is increasingly used to assess lung aeration and support decisions about surfactant treatment.

• FBC
• Blood cultures and inflammatory markers if sepsis is suspected
• Blood glucose
• Electrolytes, calcium and renal function
• Haematocrit
• Echocardiography if congenital heart disease, patent ductus arteriosus or pulmonary hypertension is suspected

Treatment

• Resuscitation
• Oxygen and respiratory support
  • Use the lowest FiO₂ required to maintain target oxygen saturation.
  • Avoid excessive oxygen because of retinopathy of prematurity and lung injury.
  • CPAP is the preferred initial respiratory support for spontaneously breathing premature infants.
• Surfactant therapy (decreases alveolar surface tension, improves lung compliance, and maintains functional residual capacity)
• +/- Intubation: mechanical ventilation
• +/- IV antibiotics
• Prophylactic caffeine is recommended for infants born before 32 weeks in current European guidance.

More info on Neonatal resuscitation

Indications for intubations

Failure of CPAP or non-invasive ventilation

Severe respiratory acidosis

Severe recurrent apnoea

Persistent hypoxaemia

Need for intubation during resuscitation

Exhaustion or poor respiratory effort

Prevention

• Transfer pregnancies at high risk of very premature delivery to a tertiary perinatal centre where possible.
• Give a single course of antenatal corticosteroids when preterm birth before 34 weeks is anticipated and active neonatal care is planned.
• The greatest benefit occurs when birth follows more than 24 hours but less than approximately 7–10 days after treatment.
• Maternal magnesium sulfate before anticipated birth below 32 weeks reduces the risk of cerebral palsy but does not directly treat RDS.

Complications and Prognosis

Prognosis 

• Dependent on general appearance at birth and severity of underlying lung disease. Long-term risks of chronic lung disease.
• Classically worsens for 2-3days, then diuresis occurs recovery over 3-4days. Subsequent improvement is coincident with increased production of endogenous surfactant with resolution of symptoms by one week of age.

Complications 

• Prolonged ventilation
• Increased risk of bronchopulmonary dysplasia
• Sudden deterioration
  • Pneumothorax
  • Endotacheal tube blockage or displacement
  • Mechanical failure with the ventilator
  • Increase in the severity of the underlying lung disease
  • Massive intraventricular haemorrhage
  • Necrotizing enterocolitis
  • Patent ductus arteriosus

References

1. Sweet DG, Carnielli VP, Greisen G, Hallman M, Klebermass-Schrehof K, Ozek E, et al. European consensus guidelines on the management of respiratory distress syndrome: 2025. Neonatology. 2026;1–26. doi:10.1159/000551062.
2. Queensland Clinical Guidelines. Respiratory distress and continuous positive airway pressure. Brisbane: Queensland Health; 2024.
3. Sweet DG, Carnielli VP, Greisen G, Hallman M, Klebermass-Schrehof K, Ozek E, et al. European consensus guidelines on the management of respiratory distress syndrome: 2022 update. Neonatology. 2023;120(1):3–23. doi:10.1159/000528914.
4. Polin RA, Carlo WA; Committee on Fetus and Newborn. Surfactant replacement therapy for preterm and term neonates with respiratory distress. Pediatrics. 2014;133(1):156–163. doi:10.1542/peds.2013-3443.
5. World Health Organization. WHO recommendations for care of the preterm or low-birth-weight infant. Geneva: World Health Organization; 2022.