Key messages

What is respiratory distress?

Respiratory distress is a breathing problem that frequently affects newborn babies. The causes vary depending on the baby's gestation (the length of time that a baby spends in the womb before delivery). The most common cause in babies born before their due date (preterm) is a lack of the lung's natural compound (surfactant) that prevents the air sacs (alveoli) from opening and closing easily. The commonest cause in babies born after 37 weeks gestation (term) is a condition called transient tachypnoea of the newborn (or wet lungs), which results from a delay in the clearance of lung fluid after birth, which leads to respiratory distress and fast breathing. There are many other cases of respiratory distress.

How is respiratory distress treated?

The usual treatment involves providing breathing support (mechanical ventilation), oxygen and administering a medication called surfactant directly into the newborn infant's breathing pipe (trachea).

Respiratory support can be provided via a tube called an endotracheal tube inserted into the infant's trachea (invasive ventilation) or via a mask or prong situated at the nose (non-invasive ventilation). Invasive ventilation is associated with an increased risk of lung damage called chronic lung disease. Non-invasive ventilation, with or without surfactant treatment, may reduce the need for mechanical ventilation and the risk of chronic lung disease in newborn infants with respiratory distress.

What is non-invasive high-frequency ventilation?

High-frequency ventilation delivers very small breaths at a very fast rate (6 to 15 hertz, equal to 360 to 900 breaths per minute). High-frequency ventilation helps with the opening of collapsed lung tissue by providing constant positive pressure in the trachea. High-frequency ventilation is usually delivered via an endotracheal tube. Non-invasive high-frequency ventilation is delivered via a mask or prong situated in the nose.

Why is non-invasive high-frequency ventilation important for newborn infants?

Non-invasive high-frequency ventilation in newborn infants is a relatively newer method of non-invasive ventilation compared to other forms of non-invasive ventilation that also use nasal prongs such as nasal continuous airway pressure, nasal intermittent positive-pressure ventilation, or heated humidified high-flow nasal cannula. Continuous positive airway pressure provides constant distending pressure to the infant's airway. Intermittent positive-pressure ventilation provides normal breaths, typically at the infant's normal breathing rate (30 to 60 breaths per minute). A high-flow nasal cannula delivers heated humidified air or oxygen at flow rates between three and eight litres per minute.

What did we want to find out?

We wanted to find out if non-invasive high-frequency ventilation compared to other forms of non-invasive ventilation via nasal prongs (e.g. nasal continuous airway pressure; nasal intermittent positive-pressure ventilation; heated humidified high flow nasal cannula) and invasive ventilation via an endotracheal tube could improve survival and reduce the rate of the need for an endotracheal tube and other outcomes in term and premature infants with or at risk of respiratory distress syndrome. We also wanted to determine if non-invasive high-frequency ventilation use had unwanted effects.

What did we do?

We searched for studies that compared non-invasive high-frequency ventilation to nasal continuous airway pressure, nasal intermittent positive-pressure ventilation, heated humidified high-flow nasal cannula, and invasive ventilation via an endotracheal tube in preterm infants with or at risk of respiratory distress syndrome. We compared and summarised the results of the included studies and rated our confidence in the evidence based on factors such as study method and size.

What did we find?

We identified 33 studies, mostly in low- to middle-income settings, that investigated this therapy in 5068 preterm and 46-term infants. For preterm infants with respiratory distress, the initial use of non-invasive high-frequency ventilation probably reduces the risk of intubation and ventilation compared to the use of nasal continuous airway pressure. For preterm infants with planned extubation following intubation and surfactant, using non-invasive high-frequency ventilation probably reduces the risk of endotracheal reintubation compared to nasal continuous airway pressure and nasal intermittent positive-pressure ventilation. Compared to nasal continuous airway pressure, using non-invasive high-frequency ventilation probably also reduces the risk of chronic lung disease. No differences were found in deaths or other newborn outcomes. Long-term outcomes were either not reported or only reported by a small trial. Large trials are needed to compare non-invasive high-frequency ventilation and nasal intermittent positive-pressure ventilation for initial respiratory support and planned extubation to determine the optimal respiratory support strategies for newborn infants.

Given the encouraging results from these trials, the use of non-invasive high-frequency ventilation in very preterm infants with or at risk of respiratory distress syndrome in selected clinical situations is justified.

What are the limitations of the evidence?

Large trials, particularly in high-income settings, are needed to determine the role of non-invasive high-frequency ventilation in initial respiratory support and following the failure of other types of non-invasive respiratory support. Therefore, further research trials are needed to identify optimal ventilation strategies and settings with non-invasive high-frequency ventilation.

How up-to-date is this evidence?

The evidence is up-to-date until 9 April 2023.