Effects of Freshly Irradiated vs Irradiated and Stored Red Blood Cell Transfusion on Cerebral Oxygenation in Preterm Infants: A Randomized Clinical Trial.

Importance: Gamma irradiation of leukoreduced red blood cells (RBCs) prevents transfusion-associated graft-vs-host disease but also exacerbates storage lesion formation in RBCs. It is unknown whether freshly irradiated RBCs are more efficacious than irradiated and stored RBCs in preterm infants with high transfusion requirements. Objective: To examine whether transfusion of freshly irradiated vs irradiated and stored RBC components improves cerebral oxygen delivery in preterm infants with anemia. Design, Setting, and Participants: This single-center, double-blinded, proof-of-concept randomized clinical trial was conducted at the neonatal intensive care unit of Wellington Regional Hospital in Wellington, New Zealand, between December 1, 2017, and November 30, 2018. Participants were preterm infants (<34 weeks' gestation at birth) who were at least 14 days of age and had anemia. Participants underwent nonurgent transfusions, and these episodes were randomized to the intervention group (in which the infants received a transfusion of RBCs that were freshly irradiated on the day of transfusion) or control group (in which the infants received a transfusion of RBCs that were irradiated and stored for up to 14 days). Data were analyzed using the evaluable population approach. Intervention: Transfusion of freshly irradiated RBCs. Main Outcomes and Measures: The prespecified primary outcome was the change in cerebral regional oxygen saturation (crSO2) from baseline (immediately before) to immediately after the transfusion. The prespecified secondary outcomes were the change in cerebral fractional tissue oxygen extraction (cFTOE) at different time points (immediately after, 24 hours after, and 120 hours or 5 days after transfusion). Outcomes were measured by blinded clinicians using near-infrared spectroscopy. A covariate-adjusted linear mixed model was used to quantify mean treatment effects and account for multiple transfusions in some infants. Results: A total of 42 infants (mean [SD] gestational age, 26 [10] weeks and 3 days; 29 [69%] boys) were enrolled in the trial and underwent 64 transfusion episodes, which were randomized to the intervention (n = 31) or control (n = 33) group. Compared with infants in the control group, those in the intervention group showed a covariate-adjusted mean increase in crSO2 (2.0 percentage points; 95% CI, 1.2-2.8 percentage points) and a mean decrease in cFTOE (0.02; 95% CI, 0.01-0.04) immediately after transfusion. These differences were sustained up to 120 hours or 5 days after transfusion. There were negligible mean changes in crSO2 or cFTOE in infants in the control group at any of the follow-up time points. Conclusions and Relevance: Results of this trial showed that transfusion of freshly irradiated RBCs conferred a small advantage in cerebral oxygenation for at least 5 days after transfusion compared with transfusion of irradiated and stored RBC components. On-demand irradiation of RBC components may be considered to optimize oxygen delivery in the recipient, but this physiological finding requires further research. Trial Registration: ANZCTR Identifier: ACTRN12617001581358.

Management of anaemia in pre-term infants.

Pre-term infants have one of the highest transfusion requirements within the hospital-setting. The vast majority of blood transfusions performed in Neonatal Intensive Care Units (NICUs) are for medically stable pre-term infants with anaemia of prematurity, with the aim of improving oxygen delivery to the vital organs during the crucial phase of growth and development. However, despite the frequency of transfusion in this population, the potential benefits and harms of 'top up' transfusion are not fully understood, leading to practice variation between clinicians, institutions and countries. Significant advances have been made in the prevention of anaemia of prematurity, with recent emphasis on optimising infants' circulatory volume at birth via placental transfusion and preserving infants' own blood volume through innovative minimal sampling techniques. More research is urgently needed to establish optimal transfusion thresholds for these high-risk pre-term infants, for whom benefits as well as adverse outcomes may have consequences that extend for decades throughout the recipients' life-course. In this review, we will discuss some of the consensus and controversies regarding optimal management of anaemia in pre-term infants and highlight potential areas for future research.

Impact of Education on Hypothermia Delivery during Neonatal Transport.

BACKGROUND: Moderate therapeutic hypothermia (TH) initiated within 6 h of life reduces adverse neurodevelopmental outcomes in infants after perinatal hypoxic ischaemic insult. For infants born in non-tertiary centres, TH may be initiated manually en route to a neonatal intensive care unit (NICU). However, both over- and undercooling is reported with this strategy, precluding some infants from the benefits of TH. OBJECTIVES: To evaluate the impact of a region-wide educational programme on the safety and efficacy of manual cooling administered by the Wellington Neonatal Transport Service (NeTS). METHODS: Clinical records of infants with hypoxic ischaemic encephalopathy (HIE) retrieved by the Wellington NeTS for TH between January 2012 and June 2017 were reviewed retrospectively. Temperature outcomes of infants retrieved before and after the education programme were compared. RESULTS: A total of 101 infants were cooled manually by Wellington NeTS for TH during the study period. Education and training significantly reduced the rate of overcooling to ≤32.0°C (4/43 [9%] vs. 0/58, p = 0.02). However, there was no difference in the proportion of infants who achieved target rectal temperature within 6 h of life (29/43 [65%] vs. 35/58 [60%], p = 0.57). CONCLUSIONS: Introduction of a region-wide educational programme may have improved the safety of manual cooling during neonatal transport but it had a negligible impact on its efficacy. The use of servo-controlled cooling during transport should therefore be considered to improve access to the optimal neuroprotective benefits of TH for outborn infants with HIE.

Blood transfusion for anaemia of prematurity: Current practice in Australia and New Zealand.

AIM: To characterise the current transfusion practice among clinicians in Australasian neonatal units and factors that influence their decision-making. METHODS: Members of the Australia and New Zealand Neonatal Network (ANZNN) and practitioners at their local institutions were invited to participate in a 15-question web-based survey between 1 June and 31 July 2016. The survey was designed to assess (i) haemoglobin-based transfusion thresholds; (ii) presence of local guidelines; (iii) preference for a restrictive or liberal transfusion policy; (iv) perceived benefits and risks of transfusion; and (v) use of clinical adjuncts to assist decision-making. RESULTS: Overall, 130 participants responded to at least one question. Haemoglobin transfusion thresholds for anaemia of prematurity (AOP) varied significantly from <60 to <120 g/L. Of 103 participants, 36 (35%) reported that they do not have access to local transfusion guidelines. The majority utilise multiple clinical and haematological parameters to guide their decision-making, and approximately half (45/84, 54%) believe that tissue hypoxia detected by near-infrared spectroscopy (NIRS) may better inform transfusion thresholds. Of 102 participants, 51 (50%) support a restrictive rather than liberal transfusion policy. The most commonly reported perceived risks of transfusion for AOP were suppression of endogenous erythropoiesis and increased rates of necrotising enterocolitis. CONCLUSIONS: There is a significant variation in transfusion practice in Australasian neonatal units. Quality and safety initiatives may assist with improved consistency of transfusion practice across the ANZNN. However, further research is required to better define optimal transfusion thresholds, quantify potential risks of transfusion and determine clinical utility of newer adjuncts such as NIRS.

Storage after gamma irradiation affects in vivo oxygen delivery capacity of transfused red blood cells in preterm infants.

BACKGROUND: Gamma irradiation of red blood cells (RBCs) is well recognized to exacerbate storage lesion formation, but the effect of storage after irradiation on in vivo oxygen delivery capacity of transfused RBCs is currently not known. STUDY DESIGN AND METHODS: In 24 preterm infants with anemia receiving nonurgent transfusion of irradiated RBCs, we examined cerebral regional tissue oxygenation (crSO2 ) and time spent with peripheral arterial saturation (SpO2 ) less than 88%. Physiologic data were obtained immediately before, immediately after, and 5 days after transfusion. RESULTS: We observed linear negative moderate correlations between time since irradiation and the magnitude of change in crSO2 (r = -0.60; 95% CI, -0.81 to -0.27; p = 0.0018) and time spent with SpO2 of less than 88% (r = -0.42; 95% CI, -0.71 to 0.003; p = 0.04) immediately after transfusion. In infants (n = 9) who received fresher RBCs (irradiated <10 days before transfusion), there was a sustained increase in mean crSO2 up to 5 days after transfusion (3.0%; 95% CI, 0.3% to 5.7%; p = 0.04). Conversely, in infants (n = 15) who received older RBCs (irradiated ≥10 days before transfusion), there were negligible changes in crSO2 after transfusion at any time point. CONCLUSION: Our findings indicate that storage after gamma irradiation may have a detrimental effect on the oxygen delivery capacity of RBCs given to anemic preterm infants.

Outcomes of 23- and 24-weeks gestation infants in Wellington, New Zealand: A single centre experience.

Optimal perinatal care of infants born less than 24 weeks gestation remains contentious due to uncertainty about the long-term neurodevelopment of resuscitated infants. Our aim was to determine the short-term mortality and major morbidity outcomes from a cohort of inborn infants born at 23 and 24 weeks gestation and to assess if these parameters differed significantly between infants born at 23 vs. 24 weeks gestation. We report survival rates at 2-year follow-up of 22/38 (58%) at 23 weeks gestation and 36/60 (60%) at 24 weeks gestation. Neuroanatomical injury at the time of discharge (IVH ≥ Grade 3 and/or PVL) occurred in in 3/23 (13%) and 1/40 (3%) of surviving 23 and 24 weeks gestation infants respectively. Rates of disability at 2 years corrected postnatal age were not different between infants born at 23 and 24 weeks gestation. We show evidence that with maximal perinatal care in a tertiary setting it is possible to achieve comparable rates of survival free of significant neuroanatomical injury or severe disability at age 2 in infants born at 23-week and 24-weeks gestation.

Ectopia cordis: a novel palliative care technique.

Complete ectopia cordis in the newborn represents a significant management challenge. There are minimal data available to inform optimal clinical care for those infants with coexisting complex congenital heart disease who are therefore not candidates for surgical intervention. The exteriorisation of the heart and absence of the pericardial sac requires meticulous wound care to prevent desiccation of the myocardium and to minimise infection risk. Additionally, the technique selected must address the risk of occlusion of the cardiac vascular pedicle and abrasion between the mobile myocardium and dressing surface. We report a novel approach to wound management and integrated palliative care that enabled community-based care. Our patient, a full-term male infant with complete ectopia cordis was born in good condition by assisted vaginal delivery. He was discharged from hospital on day 8 and was cared for in the community until his demise from cardiac failure on day 15.

Shwachman-Diamond syndrome (SDS) in a preterm neonate.

A preterm neonate at 29-week gestational age was born with intrauterine growth restriction, severe pancytopaenia and gross skeletal dysplasia. Antenatal screening bloods, TORCH/parvovirus tests and karyotype were unremarkable. Postnatally, he had normal microarray comparative genomic hybridization and serum B12/folate levels, and human immunodeficiency virus and cytomegalovirus polymerase chain reaction and antoimmune screening were negative. Targeted gene testing for Shwachman-Diamond syndrome (SDS) revealed the pathognomic mutation (c.183_184delTAinsCT). His postnatal clinical course was complicated by: (i) Ventilator dependency because of a combination of a pathologically compliant chest wall and preterm-associated chronic lung disease. (ii) Progressive bone marrow failure, resulting in transfusion dependence and profound neutropenia associated with recurrent sepsis. (iii) Gastrointestinal failure and TPN dependency. (iv) Poor postnatal growth with weight/length/head circumference all <3rd centile. (v) Prognostication was complicated by the lack of published literature on the presentation of SDS in a preterm infant. However, because of inexorable progression of multiorgan failure, intensive care was withdrawn on day 54 of life. SDS is a rare autosomal recessive disorder characterised by haematological abnormalities, skeletal dysplasia and exocrine pancreatic dysfunction. Neonatal presentation is thought to be extremely rare. However, with the availability of genetic testing, it has now become clear that because of overlap in clinical presentation, term-born infants with skeletal dysplasia and severe respiratory distress may initially be misdiagnosed as asphyxiating thoracic dystrophy. This case report highlights the complexities of preterm birth complicating clinical manifestations of SDS.