About the Project

Background

Approximately 0.5% of all neonates (i.e., about 25,000 infants per year in Europe) are extremely low gestational age neonates (ELGANs), i.e. preterm infants born at a gestational age of <28 completed weeks (compared to a normal duration of pregnancy of 39-40 weeks). The vast majority of ELGANs require supplemental oxygen in addition to respiratory support provided by a ventilator. In the course of their in-hospital treatment, ELGANs frequently experience intermittent hypoxemic and (usually as a consequence of inappropriate adjustments of supplemental oxygen) hyperoxemic episodes. Intermittent hypoxemic episodes are predominantly caused by recurrent apnea occurring in premature infants due to immaturity of the respiratory neuronal network, but also secondary to active exhalation during mechanical ventilation. Observational data indicate that severe and prolonged hypoxemic episodes, i.e. wide fluctuations in blood oxygen levels, increase the risk of retinopathy of prematurity (ROP) and it is suggested that late deaths (i.e., deaths beyond 36 weeks postmenstrual age) and neurodevelopmental impairment (both cognitive and in particular motor impairment) are also linked to hypoxemic episodes, particularly those of more than 60s duration.

To protect premature babies from these hypoxemic episodes, despite inherent irregular breathing patterns, frequent adjustments of the inspired fraction of oxygen (FiO2, i.e. the proportion of supplemental oxygen in the respiratory gas mixture) are required. In times where personnel resources are limited, caregivers and manufacturers of neonatal ventilators thought that this time consuming and difficult process should be automated. They developed different ventilators with automated monitoring and FiO2-regulating systems (Closed-loop automated control of the inspiratory fraction of oxygen (FiO2-C)), which are currently being integrated into the standard care of premature babies.

Current study

Closed-loop automated control of the inspiratory fraction of oxygen (FiO2-C) applied in this research project are CE-marked systems (i.e., they comply with European standards for medical devices) and are intended to be used during the standard care of premature babies. The systems have previously undergone short-term studies of efficacy and safety, and it has repeatedly been shown by various study groups that FiO2-C reduces the burden of hyper- and hypoxemia episodes in infants while being safe and accurate.

It is known that inappropriate application of oxygen (with and without closed-loop automated control of oxygen) may be harmful and may adversely affect long-term outcome in ELGANs. The effects of closed-loop FiO2-C on such clinically relevant longer-term outcome measures and the safety of long-term continuous application have not been studied yet.

The investigators cooperating in this research project hope that this new technology will indeed improve the long-term outcome. But ELGANs are complex patients and hence the FiO2-C-investigators felt, that it is in the best interest of the preterm infants and their families that long-term safety and efficacy of this upcoming technology should be evaluated in an appropriately designed study before implementation in standard care.