Air versus supplemental oxygen for resuscitation of term or late preterm infants at birth

Approximately 1% to 5% of newly born infants require some form of respiratory support, including supplemental oxygen for the respiratory transition immediately after birth. Despite a long-standing debate, the optimal concentration of oxygen at initiation of resuscitation of late preterm and term infants immediately after birth is still unknown.

Primary objective To assess the benefits and harms of air compared with supplemental oxygen for resuscitation of term or late preterm infants at birth in reducing rates of mortality and long-term neurodevelopmental impairment (NDI). Secondary objectives To assess whether the benefits and harms of air compared with supplemental oxygen differ according to different oxygen concentrations, gestational age (GA), whether oxygen was titrated to saturation targets and the income of the study country.

We searched CENTRAL, MEDLINE, Embase, CINAHL, two trials registries, Epistemonikos and the Directory of Open Access Journals (DOAJ) up to 12 January 2026. We checked reference lists of included studies and other publications related to the topic of this review, and conducted forward/backward citation searching.

We included randomised controlled trials (RCTs), quasi-RCTs or cluster-RCTs in term and late preterm infants who received respiratory support at birth comparing air with any supplemental oxygen. We excluded studies of oxygen saturation targeting, studies not taking place in the delivery room and studies of infants with antenatally diagnosed congenital anomalies.

Our outcomes of interest were all-cause mortality prior to discharge, in-hospital hypoxic-ischaemic encephalopathy (HIE) (Sarnat stage II to III), post-discharge moderate to severe NDI based on pre-specified criteria, number of days on invasive (endotracheal) respiratory support, length of hospitalisation (days), all-cause mortality of infants followed beyond hospital discharge and moderate to severe NDI based on best available data.

We used the Cochrane RoB 2 tool to assess risk of bias.

We synthesised results for each outcome using meta-analysis where possible. We calculated risk ratio (RR) and risk difference, each with its 95% confidence interval (CI), for categorical outcomes. We used a fixed-effect model to combine data for meta-analysis. Where this was not possible due to the nature of the data, we synthesised results by summarising any available effect estimates. We used GRADE to assess the certainty of evidence for each outcome.

We included a total of 12 studies with 2054 participants. The included studies enrolled term (born at a gestational age of 37 weeks 0 days to 43 weeks 6 days) and late preterm (born at a gestational age of 35 weeks 0 days to 36 weeks 6 days) infants who received any form of invasive (endotracheal) or non-invasive respiratory support at birth.

Using air compared to supplemental oxygen for resuscitation of term and late preterm infants may reduce all-cause mortality prior to discharge (RR 0.72, 95% CI 0.57 to 0.91; I² = 0%; 10 studies, 1879 participants; low-certainty evidence). The evidence suggests that using air compared to supplemental oxygen for resuscitation of term and late preterm infants results in little to no difference in in-hospital HIE stage II to III (RR 0.88, 95% CI 0.71 to 1.10; I² = 0%; 5 studies, 1384 participants; low-certainty evidence). The evidence suggests that using air compared to supplemental oxygen for resuscitation of term and late preterm infants results in little to no difference in all-cause mortality among infants followed beyond hospital discharge (RR 0.82, 95% CI 0.58 to 1.16; I² = 0%; 3 studies, 668 participants; low-certainty evidence). The evidence is very uncertain about the effect of using air compared to supplemental oxygen for resuscitation of term and late preterm infants on moderate to severe NDI based on best available data (RR 1.24, 95% CI 0.74 to 2.10; I² = 0%; 3 studies, 414 participants; very low-certainty evidence). None of the studies reported the following outcomes: moderate to severe NDI after at least 12 months' postnatal age as defined in the protocol, the number of days on invasive (endotracheal) respiratory support and the length of hospitalisation (days). Overall, the risk of bias was high for most studies.

The use of air compared to 100% oxygen may reduce all-cause mortality prior to discharge, but there may be little to no difference in HIE stage II to III and NDI at 12 months or later based on best available data. No study reported moderate to severe NDI after at least 12 months' postnatal age, the number of days on invasive respiratory support or the length of hospitalisation. All 12 included studies compared air with 100% oxygen without titration to available oxygen saturation targets. Therefore, we are unable to draw conclusions about the optimal starting oxygen concentration when titration is available. Subgroup analyses based on gestational ages were not possible. There were no differences between studies from high-income and low- and middle-income countries.

This Cochrane review had no dedicated funding.

Protocol available via DOI: 10.1002/14651858.CD014781.