Sustained versus standard inflations during neonatal resuscitation to prevent mortality and improve respiratory outcomes.

Rationale: At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable gas exchange. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving a sustained lung inflation (SLI) at the start of PPV may help clear lung fluid and establish gas volume within the lungs. This is a review update; the last version was published in 2020.

Objectives: To assess the benefits and harms of an initial SLI (> 1 second duration) versus standard inflations (≤ 1 second) in newborn infants receiving resuscitation with intermittent PPV.

Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and two trial registries on 8 April 2024. We checked the reference lists of studies and other related papers.

Eligibility Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs comparing initial SLI versus standard inflations given to infants receiving resuscitation with PPV at birth.

Outcomes: Our critical outcomes were: death in the delivery room; death during hospitalisation. Other clinically relevant outcomes were: rate of mechanical ventilation; chronic lung disease, any grade; chronic lung disease, moderate to severe; pneumothorax during hospitalisation; intraventricular haemorrhage grade 3 or 4.

Risk Of Bias: We used the Cochrane risk of bias tool 1.0.

Synthesis Methods: We conducted meta-analyses using fixed-effect models to calculate risk ratios (RR) and 95% confidence intervals (CI). We summarised the certainty of the evidence according to GRADE methods.

Included Studies: Fourteen trials enrolling 1766 infants met our inclusion criteria. The studies were conducted on five continents, and published between 2005 and 2024. Investigators in 12 trials (1722 infants) administered SLI with no chest compressions; 10 studies reported that peak inspiratory pressure (PIP) was sustained for 15 seconds. Levels of PIP ranged from 20 to 30 cmH₂O. Investigators in seven studies provided additional SLIs in cases of poor response. We downgraded the overall certainty of evidence for all outcomes because of limitations in study design (e.g. selection bias due to lack of allocation concealment and performance bias due to unblinded intervention), and serious imprecision of results, with wide confidence intervals and few events. One trial is ongoing.

Synthesis Of Results: For each outcome, we downgraded the overall certainty of evidence because of limitations in study design and imprecision. Compared with intermittent ventilation, SLI with no chest compression may result in little to no difference in: • death in the delivery room (RR 1.72, 95% CI 0.82 to 3.63; I² = 0%; 6 studies, 639 participants; low-certainty evidence); • death before discharge (RR 0.99, 95% CI 0.81 to 1.21; I² = 37%; 12 studies, 1722 participants; low-certainty evidence); • chronic lung disease, any grade (RR 0.99, 95% CI 0.83 to 1.18; I² = 0%; 4 studies, 735 participants; low-certainty evidence); • moderate to severe chronic lung disease (RR 0.95, 95% CI 0.74 to 1.22; I² = 47%; 6 studies, 727 participants; low-certainty evidence); • pneumothorax during hospitalisation (RR 0.93, 95% CI 0.65 to 1.33; I² = 12%; 11 studies, 1641 participants; low-certainty evidence); • intraventricular haemorrhage grade 3-4 (RR 0.94, 95% CI 0.64 to 1.38; I² = 13%; 8 studies, 855 participants; low-certainty evidence). SLI with no chest compression may reduce the rate of mechanical ventilation (RR 0.90, 95% CI 0.80 to 1.01; I² = 0%; 7 studies, 1174 participants; low-certainty evidence).

Authors' Conclusions: Compared with intermittent ventilation, sustained inflation without chest compression may result in little to no difference in death in the delivery room and death before discharge. Sustained inflation may reduce the rate of mechanical ventilation, and may result in little to no difference in chronic lung disease, pneumothorax, and severe intraventricular haemorrhage. There is no evidence to support the use of sustained inflation based on evidence from our review. Future studies of SLI for infants receiving respiratory support at birth should provide more detailed monitoring of the procedure, such as measurements of lung volume and presence of apnoea before or during SLI. Future RCTs should aim to enrol infants who are at higher risk of morbidity and mortality, and should stratify participants by gestational age. Researchers should also measure long-term neurodevelopmental outcomes (e.g. Bayley Scales of Infant Development, administered at two years of corrected age).

Funding: This Cochrane Review had no dedicated funding.

Registration: Protocol (2004): doi.org/10.1002/14651858.CD004953 Original review (2015): doi.org/10.1002/14651858.CD004953.pub2 Review update (2017): doi.org/10.1002/14651858.CD004953.pub3 Review update (2020): doi.org/10.1002/14651858.CD004953.pub4.