E.W. "Al" Thrasher
Status: Funded - Open
The TO2RPIDO study: Targeted Oxygenation in the Resuscitation of Premature Infants and their Developmental Outcome
Ju Lee Oei, M.D.
BACKGROUND: Oxidative stress and toxicity are well-known problems in premature infants, leading to conditions such as Bronchopulmonary Dysplasia, Retinopathy of Prematurity, and Cerebral Palsy. Supplemental O2 is provided as part of the resuscitation process even though there is no data regarding optimal SaO2 values in infants with incomplete pulmonary alveolarisation, surfactant deficiency and insufficient anti-oxidant defenses. Giving less O2 during resuscitation obviously decreases the total O2 load delivered to the infant. The question is whether this is beneficial in real-life.
GAP: Pure or 100% oxygen has been administered to newborn infants as part of newborn resuscitation for more than a century without convincing evidence of either risk or benefit, especially in premature infants with significant lung disease. Ground-breaking studies in the 1990’s show that the use of room air (21% O2) instead of 100% O2 as an adjunct to ventilator support in depressed mature hypoxic infants significantly decreases the time required for the infant to breathe spontaneously and very importantly, to almost halve the risk of death without increasing significant neurodevelopmental disability. However, there is still little convincing data from large scale studies to support this practice in extremely preterm infants, especially in regards to long-term outcomes.
HYPOTHESIS: The aim of the To2rpido Study is to determine if there are any differences in the short and long-term outcomes of premature infants born below 31+6 completed weeks gestation who are resuscitated at birth with either 100% O2 or room air.
METHODS: This is an international, multi-centre, non-blinded, randomised, controlled clinical trial of live-born infants born at less than or equal to 31+6 weeks completed gestation. Infants are randomized to resuscitation in 100% O2 or room air and their saturations are targeted with either a graded reduction or an increase in oxygen administered over the first 20 minutes following birth.
RESULTS: Recruitment and data collection is in progress. Interim results will be reviewed by the Data and Safety Monitoring Committee at 250 patients. Preliminary oxidative marker results have been submitted for consideration to the Pediatric Academic Societies Meeting (May 4-7th 2013, Washington). Neurodevelopmental assessments are ongoing.
DISCUSSION: The To2rpido Study, using a modification of a basic health technique and equipment readily available in most newborn nurseries in the world, may help reduce the cost and mortality associated with premature birth regardless of the infant’s place of birth. This has the potential to affect more than 13 million preterm babies around the world each year and reduce the incidence of mortality and increase survival without severe morbidity (i.e. neurodevelopmental delay) of more than 1 to 2 million babies per year. The methodologies generated by our study will also be applicable to low-resourced countries that are least likely to be able to support children affected by the consequences of preterm birth.
Neuro-Cognitive Development, Retinopathy of Prematurity, BPD, Oxygen, Treatment, Human, Randomized Clinical Trial, Preterm Care