Respiratory Complications of Prematurity

NICE guideline [NG124] Specialist neonatal respiratory care for babies born preterm. Published: Apr 2019.

NICE guideline [NG25] Preterm labour and birth. Last updated: Jun 2022.

Article Last Updated:06/09/2026

Respiratory Complications of Prematurity

This article covers 3 main respiratory complications of prematurity:

Neonatal respiratory distress syndrome (NRDS)
Apnoea of prematurity (AOP)
Bronchopulmonary dysplasia (BPD) (chronic lung disease of prematurity)

Neonatal Respiratory Distress Syndrome (NRDS)

Pathophysiology ^[Ref]	NRDS results predominantly from insufficient pulmonary surfactant Normal function of surfactant: reduce alveolar surface tension In preterm babies: ↓ surfactant → ↑ surface tension → alveolar collapse (atelectasis) → impaired gas exchange → hypoxaemia Surfactant is normally produced by type II pneumocytes, starting from ~22 weeks of gestation, increasing progressively up to ~35 weeks of gestation
Clinical features ^[Ref]	Onset of respiratory distress soon after birth: Tachypnoea Expiratory grunting Nasal flaring Intercostal / subcostal recession Cyanosis Non-respiratory related signs Poor feeding Lethargy
Investigation and diagnosis ^[Ref]	Typical chest X-ray findings: Diffuse, symmetrical ground-glass appearance (fine reticulogranular opacities) Air bronchograms Reduced lung volumes Severe disease: diffuse “white-out” opacification Blood gas may demonstrate hypoxaemia +/- hypercapnic respiratory acidosis
Prevention ^{[NICE NG25]}	Main preventive intervention is antenatal corticosteroids (IM dexamethasone) Offer if 24 – 33+6 weeks of gestation Consider if 34 – 35+6 weeks of gestation To be given within 7 days prior to preterm birth Also see the PROM, P-PROM, and Preterm Labour article Antenatal corticosteroids are given by IM injection to the mother, not directly to the fetus MoA: crosses the placenta to accelerate fetal lung maturation and stimulate surfactant production
Active treatment (general respiratory management in preterm babies) ^{[NICE NG124]}	Respiratory support if required (e.g. hypoxia, respiratory acidosis, respiratory failure) 1st line: non-invasive respiratory support (typically nasal CPAP or nasal high-flow therapy) Give supplemental oxygen via nasal cannula or incubator oxygen Careful oxygen titration is important, excess oxygen exposure can increase risk of ROP and BPD Humidification is necessary at higher flow rates (e.g. ≥2 L/min) If adequate ventilation/oxygenation cannot be maintained → endotracheal intubation + invasive mechanical ventilation For infants requiring oxygen therapy after initial stabilisation, target SpO₂ at 91-95% to balance the risks of hyperoxia and hypoxia. ^{[NICE NG124]} Excess oxygen exposure is associated with increased risk of retinopathy of prematurity and bronchopulmonary dysplasia. Other medical therapy: Exogenous surfactant – indicated in preterm babies who require invasive ventilation Dexamethasone – consider in preterm babies aged ≥8 days who still require invasive ventilation (to reduce risk of BPD) NB use of dexamethasone in preterm babies who are younger than 8 days old increases the risk of GI perforation Do NOT combine dexamethasone with NSAIDs due to risk of GI perforation Caffeine citrate – give routinely in preterm babies born at ≤30 weeks of gestation + consider in those with apnoea of prematurity Do NOT routinely offer nitric oxide in preterm babies who need respiratory support, unless there are other indications (e.g. pulmonary hypoplasia, pulmonary hypertension)

NRDS vs TTN

^[Ref]

	NRDS (neonatal respiratory distress syndrome)	TTN (transient tachypnoea of the newborn)
Cause and mechanism	Surfactant deficiency → alveolar collapse + impaired gas exchange	Delayed clearance of fetal lung fluid
Typical baby	Preterm baby	At term (or late pre-term), associated with Caesarean delivery
Clinical features	Usually more significant respiratory distress: tachypnoea, grunting, nasal flaring, recession +/- cyanosis and hypoxaemia	Usually milder respiratory distress: predominantly tachypnoea +/- mild recession, nasal flaring, grunting
Chest X-ray	Diffuse ground-glass opacification Reduced lung volume Air bronchogram	Normal / hyperinflated lungs Perihilar vascular / interstitial markings Fluid in interlobar fissures
Clinical course	May progress to respiratory failure	Self-limiting, typically resolving within 72 hours
Treatment principle	Respiratory support +/- exogenous surfactant	Supportive management (supplemental oxygen if required)

Apnoea of Prematurity (AOP)

Pathophysiology ^[Ref]	Apnoea of prematurity: recurrent episodes of absent breathing in a preterm infant, typically lasting ≥15-20 seconds Primary mechanism: immature brainstem respiratory control The strongest risk factor is the degree of prematurity All infants <28 weeks develop AOP-related symptoms ~20% at 34 weeks; <10% at >34 weeks
Clinical features ^[Ref]	Typical episodes involve: Apnoea (typically defined as absence of breathing for ≥15-20 seconds) +/- Hypoxaemia Bradycardia Periodic breathing / shorter respiratory pauses may also occur
Diagnosis ^[Ref]	Clinical diagnosis Do NOT automatically attribute all new or worsening apnoea to AOP Consider other important causes, esp. if the infant is unwell: Sepsis Hypoglycaemia Hypothermia Respiratory disease (e.g. NRDS, pneumonia, airway obstruction) Drug exposure (e.g. neonatal opioid withdrawal) Neurological pathology (e.g. seizures, intracranial pathology)
Active treatment (general respiratory management in preterm babies) ^{[NICE NG124]}	Key intervention for AOP is caffeine citrate (stimulates respiratory drive): Caffeine citrate should be routinely given in all preterm babies born ≤30 weeks (to reduce apnoea and improve long-term outcomes, including risk of BPD, cerebral palsy, and blindness) Consider caffeine citrate to manage those who developed AOP (if not already given prophylactically) Respiratory support if required (e.g. hypoxia, respiratory acidosis, respiratory failure) 1st line: non-invasive respiratory support (typically nasal CPAP or nasal high-flow therapy) Give supplemental oxygen via nasal cannula or incubator oxygen Careful oxygen titration is important, excess oxygen exposure can increase risk of ROP and BPD Humidification is necessary at higher flow rates (e.g. ≥2 L/min) If adequate ventilation/oxygenation cannot be maintained → endotracheal intubation + invasive mechanical ventilation For infants requiring oxygen therapy after initial stabilisation, target SpO₂ at 91-95% to balance the risks of hyperoxia and hypoxia. ^{[NICE NG124]} Excess oxygen exposure is associated with increased risk of retinopathy of prematurity and bronchopulmonary dysplasia. Other medical therapy: Exogenous surfactant – indicated in preterm babies who require invasive ventilation Dexamethasone – consider in preterm babies aged ≥8 days who still require invasive ventilation (to reduce risk of BPD) NB use of dexamethasone in preterm babies who are younger than 8 days old increases the risk of GI perforation Do NOT combine dexamethasone with NSAIDs due to risk of GI perforation Do NOT routinely offer nitric oxide in preterm babies who need respiratory support, unless there are other indications (e.g. pulmonary hypoplasia, pulmonary hypertension)

Bronchopulmonary Dysplasia (BPD) (Chronic Lung Disease of Prematurity)

BPD is a chronic respiratory complication of prematurity, occurring predominantly in very / extremely preterm infants.

Causes and risk factors	Key mechanism: immature lung is exposed to ventilator injury, oxidative stress, inflammation and abnormal pulmonary blood flow → disruption of normal alveolar and vascular development → chronic gas exchange impairment Key risk factors: ^[Ref] Extreme prematurity (<28 weeks) – strongest risk factor Low birth weight Oxygen toxicity (from oxygen exposure) Invasive ventilation (esp. with prolonged ventilation) Neonatal infection (including sepsis) PDA Poor nutrition Additional associations: ^{[NICE NG124]} Male sex Core body temperature <35°C on admission to neonatal unit Feeding with formula milk Treated with surfactant or PDA NB surfactant treatment and PDA treatment should NOT be interpreted as harmful interventions NICE states that these associations reflect greater underlying illness severity, and both treatments should still be used when clinically indicated
Clinical features and diagnosis ^[Ref]	BPD typically occurs in an extremely preterm infant with persistent respiratory disease Ongoing need for oxygen and/or respiratory support Difficulty weaning from oxygen and/or respiratory support Tachypnoea ↑ Work of breathing (e.g. nasal flaring, intercostal / subcostal recession, grunting) BPD is primarily a clinical diagnosis in a preterm infant with persistent oxygen and/or respiratory support requirements Relevant investigations: Chest X-ray may be used to support the diagnosis by demonstrating chronic lung abnormalities and help assess alternative / concurrent pathology Echocardiography is indicated if pulmonary hypertension is suspected
Complications ^[Ref]	Pulmonary hypertension Long-term impaired lung function (e.g. reduced exercise tolerance, ↑ risk of recurrent wheeze and respiratory symptoms, ↑ respiratory infections) Growth failure Neurodevelopmental impairment (increased risk of cerebral palsy and motor / cognitive impairment)
Prevention	Minimise lung injury ^[Ref] Carefully titrate oxygen to avoid oxygen toxicity Avoid unnecessary and prolonged invasive mechanical ventilation Pharmacological therapy ^{[NICE NG124]} Caffeine citrate – routinely indicated in preterm infants born at ≤30 weeks Dexamethasone – consider in preterm infants aged ≥8 days who still require invasive ventilation NB use of dexamethasone in preterm babies who are younger than 8 days old increases the risk of GI perforation Do NOT combine dexamethasone with NSAIDs due to risk of GI perforation
Management ^[Ref]	Management principles for established BPD: Respiratory support as required Avoid unnecessary prolonged invasive ventilation where possible Titrate oxygen therapy to avoid both hypoxaemia and excessive oxygen exposure Severe BPD may require prolonged respiratory support (e.g. including tracheostomy in infants with repeated failed extubation attempts) Optimise nutrition and growth (due to increased energy requirements) Assess for and manage pulmonary hypertension Consider echo to assess for pulmonary hypertension when clinically suspected For management, see the Pulmonary Hypertension article Use adjunctive drugs according to the infant’s phenotype (do NOT give routinely) Diuretics for pulmonary oedema or fluid-related respiratory compromise Bronchodilators in selected infants who demonstrate airway reactivity

References

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Respiratory Complications of Prematurity

Respiratory Complications of Prematurity

Neonatal Respiratory Distress Syndrome (NRDS)

NRDS vs TTN

Apnoea of Prematurity (AOP)

Bronchopulmonary Dysplasia (BPD) (Chronic Lung Disease of Prematurity)

References

Share Your Feedback Below Cancel reply

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