Review question
Does NIPPV confer greater short-term and long-term benefits without harm to preterm infants with or at risk of respiratory distress compared with NCPAP?
Background
Nasal intermittent positive pressure ventilation (NIPPV) may increase the effectiveness of nasal continuous positive airway pressure (NCPAP) in preterm babies who have respiratory difficulties or are at risk of such difficulties. Preterm babies with breathing problems often require help from a machine (ventilator) that provides regular breaths through a tube in the windpipe. Pediatricians caring for these preterm infants try to avoid the use of ventilators, as they can damage the growing immature or premature lung. NCPAP and NIPPV are ways of supporting babies' breathing in a less invasive way - the tubes are shorter and go only to the back of the nose, thereby causing less damage to the lungs. NCPAP and NIPPV may be used early after birth to reduce the number of babies needing the assistance of a ventilator for breathing. NCPAP provides steady pressure to the back of the nose that is transmitted to the lungs, helping the baby breathe more comfortably. NIPPV provides the same support but also adds some breaths through the ventilator.
Study characteristics
We searched scientific databases for studies comparing NCPAP with NIPPV in preterm infants (born before 37 completed weeks of pregnancy) who needed respiratory support shortly after birth. We looked at the need for a breathing tube and long-term side effects.
Key results
We found 17 trials (enrolling 1958 infants) comparing NCPAP with NIPPV. When applied within six hours after birth, NIPPV likely reduces the risk of respiratory failure and the need for intubation and endotracheal tube ventilation in very preterm infants (gestational age of 28 weeks and above) with respiratory distress syndrome (RDS) or at risk for RDS. It may also decrease the rate of chronic lung disease slightly. Compared to NCPAP, NIPPV may result in little to no difference on the risk of dying, developing an air leak in the thoracic cage, or a severe brain bleed. However, there was a lack of data for the most premature infants that are born at less than 28 weeks of gestational age. Additional studies are needed to determine how NIPPV can be best delivered to infants. The evidence is up-to-date to January 2023.
Certainty of the evidence
The overall certainty of the studies included in this review was moderate to low.
When applied within six hours after birth, NIPPV likely reduces the risk of respiratory failure and the need for intubation and endotracheal tube ventilation in very preterm infants (GA 28 weeks and above) with respiratory distress syndrome or at risk for RDS. It may also decrease the rate of CLD slightly. However, most trials enrolled infants with a gestational age of approximately 28 to 32 weeks with an overall mean gestational age of around 30 weeks. As such, the results of this review may not apply to extremely preterm infants that are most at risk of needing mechanical ventilation or developing CLD. Additional studies are needed to confirm these results and to assess the safety of NIPPV compared with NCPAP alone in a larger patient population.
Nasal continuous positive airway pressure (NCPAP) is a strategy to maintain positive airway pressure throughout the respiratory cycle through the application of a bias flow of respiratory gas to an apparatus attached to the nose. Early treatment with NCPAP is associated with decreased risk of mechanical ventilation exposure and might reduce chronic lung disease. Nasal intermittent positive pressure ventilation (NIPPV) is a form of noninvasive ventilation delivered through the same nasal interface during which patients are exposed to short inflations, along with background end-expiratory pressure.
To examine the risks and benefits of early (within the first six hours after birth) NIPPV versus early NCPAP for preterm infants at risk of or with respiratory distress syndrome (RDS).
Primary endpoints are respiratory failure and the need for intubated ventilatory support during the first week of life. Secondary endpoints include the incidence of mortality, chronic lung disease (CLD) (oxygen therapy at 36 weeks' postmenstrual age), pneumothorax, duration of respiratory support, duration of oxygen therapy, and intraventricular hemorrhage (IVH).
Searches were conducted in January 2023 in CENTRAL, MEDLINE, Embase, Web of Science, and Dissertation Abstracts. The reference lists of related systematic reviews and of studies selected for inclusion were also searched.
We considered all randomized and quasi-randomized controlled trials. Eligible studies compared NIPPV versus NCPAP treatment, starting within six hours after birth in preterm infants (< 37 weeks' gestational age (GA)).
We collected and analyzed data using the recommendations of the Cochrane Neonatal Review Group.
We included 17 trials, enrolling 1958 infants in this review. NIPPV likely reduces the rate of respiratory failure (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.54 to 0.78; risk difference (RD) -0.08, 95% CI -0.12 to -0.05; 17 RCTs, 1958 infants; moderate-certainty evidence) and needing endotracheal tube ventilation (RR 0.67, 95% CI 0.56 to 0.81; RD -0.07, 95% CI -0.11 to -0.04; 16 RCTs; 1848 infants; moderate-certainty evidence) amongst infants treated with early NIPPV compared with early NCPAP.
The meta-analysis demonstrated that NIPPV may reduce the risk of developing CLD compared to CPAP (RR 0.70, 95% CI 0.52 to 0.92; 12 RCTs, 1284 infants; low-certainty evidence) slightly. NIPPV may result in little to no difference in mortality (RR 0.82, 95% CI 0.62 to 1.10; 17 RCTs; 1958 infants; I2 of 0%; low-certainty evidence), the incidence of pneumothorax (RR 0.92, 95% CI 0.60 to 1.41; 16 RCTs; 1674 infants; I2 of 0%; low-certainty evidence), and rates of severe IVH (RR 0.98, 95% CI 0.53 to 1.79; 8 RCTs; 977 infants; I2 of 0%; low-certainty evidence).