NETwork Meta-analysis Of Trials of Initial Oxygen in preterm Newborns (NETMOTION): A Protocol for Systematic Review and Individual Participant Data Network Meta-Analysis of Preterm Infants <32 Weeks' Gestation Randomized to Initial Oxygen Concentration for Resuscitation

Background: Internationally recognized guidelines recommend the judicious use of low oxygen (21-30%), titrated to peripheral oxygen saturation targets, for the initiation of re- suscitation of very and extremely preterm infants (<32 weeks' gestation). However, despite more than 10 randomized controlled trials on this question, the ideal initial oxygen concentration for this group of vulnerable infants remains uncertain. Aims: This study aims to assess the effect of various initial oxygen concentrations on (1) all-cause mortality, chronic lung disease, intraventricular hemorrhage, and retinopathy of prematurity; and (2) reaching the prescribed oxygen saturation targets by 5 min after birth, in preterm infants requiring resuscitation. Methods: We will conduct a system- atic review and network meta-analysis using individual participant data. Studies of preterm infants <32 weeks' gestation, randomized to initial oxygen concentration, will be included. We will systematically search medical databases and trial registriesfor eligible studies (published or unpublished). Records will be screened by two independent reviewers, with conflicts resolved by the inclusion of a third reviewer. Identified initial oxygen concentrations will be grouped into the following nodes: low (<= 30%), intermediate (60%), and high (>= 90%) oxygen. A two-step random-effects contrastbased network meta-regression will be calculated to compare and rank different oxygen concentrations. Analyses will be intention-to-treat, with the primary outcome of all-cause mortality. Discussion: This is the first individual participant data network meta-analysis of initial oxygen concentrations for the resuscitation of preterm infants. This novel approach may address long-standing uncertainty regarding optimal oxygen supplementation practice for the resuscitation of preterm infants <32 weeks' gestation. (C) 2022 S. Karger AG, Basel

Automated summary

This study aims to evaluate the effects of different initial oxygen concentrations on the outcomes of preterm infants during resuscitation and compare the effectiveness of reaching the prescribed oxygen saturation targets. Individual participant data will be used in a systematic review and network meta-analysis. The ultimate goal is to provide strong evidence for optimal oxygen supplementation practice for preterm infants with a gestational age of less than 32 weeks.