Effects of transfusion thresholds on neurocognitive outcome of extremely low birth weight infants (ETTNO) a blinded randomized controlled multicenter trial
Final Report Abstract
Untreated, preterm infants with birth weights less than 1000g uniformly develop very low levels of haemoglobin concentration in blood referred to as anemia of prematurity. Red blood cells, and specifically haemoglobin, the red colorant of blood, carry oxygen from the lungs to the organs, including the brain. Low levels in red blood cells or haemoglobin may result in brain injury due to oxygen deficiency, particularly if oxygen saturation is not optimal as during intermittent hypoxemia, which is frequently observed in preterm infants. As a previous randomized trial conducted in Canada indicated that there might be a benefit of more liberal transfusions of red blood cells on cognitive score achieved at 24 months corrected age, the ETTNO trial aimed to verify if liberal transfusions would improve outcome. The key result of the ETTNO trial was that, among 1013 infants with birth weights between 400g and 999g, the likelihood of death or disability at 24 months corrected age was 44% versus 43% with liberal blood transfusions compared with restrictive blood transfusions, a difference that was not statistically significant. All secondary and further outcome variables, as well as long-term growth were not different between the two groups. Hence liberal transfusion thresholds should not be applied with the intention to improve survival without disability, short-term perinatal outcomes, or longterm growth. However, these results may not apply to all babies (infants with birth weights less than 400g were not studied), all time points (the median age at enrolment was 2.5d) and all settings (most babies were recruited and cared for in Germany and Denmark). In particular, investigators chose to administer red blood cell transfusions in certain circumstances not meeting the pre-defined criteria of anemia, these events were more common in the lower birth weight stratum of the study.
Publications
- The „Effects of Transfusion Thresholds on Neurocognitive Outcome of Extremely Low Birth Weight Infants (ETTNO)“ Study: Background, Aims, and Study Protocol. Neonatology 2012;101:301-305
Franz AR, ..., Bassler D.
(See online at https://doi.org/10.1159/000335030) - Effects of Liberal vs Restrictive Transfusion Thresholds on Survival and Neurocognitive Outcomes in Extremely Low-Birth-Weight Infants: The ETTNO Randomized Clinical Trial. JAMA. 2020 Aug 11;324(6):560-570. Erratum in: JAMA. 2022 Jul 12;328(2):217
Franz AR, Engel C, Bassler D, Rüdiger M, Thome UH, Maier RF, Krägeloh-Mann I, Kron M, Essers J, Bührer C, Rellensmann G, Rossi R, Bittrich HJ, Roll C, Höhn T, Ehrhardt H, Avenarius S, Körner HT, Stein A, Buxmann H, Vochem M, Poets CF; ETTNO Investigators
(See online at https://doi.org/10.1001/jama.2020.10690)
