Cerebral Oximetry Monitoring in Extremely Preterm Infants.

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).

Markers of platelet activation foR identification of late onset sEpsis in infaNTs: PARENT study protocol.

BACKGROUND: Newborns are at high risk of sepsis. At present there is no definitive "rule in" blood test for sepsis at the point of clinical concern. A positive blood culture remains the gold standard test for neonatal sepsis, however laboratory markers that correlate prospectively with culture positive sepsis could aid clinicians in making decisions regarding administration of empiric antibiotic therapies. METHODS: This multi-site, prospective observational study will take place in two neonatal intensive care units (National Maternity Hospital and Rotunda Hospital, Dublin). Neonates born at less than 34 weeks will be enroled and informed consent obtained prior to late onset sepsis work up. If at any point subsequently during their neonatal intensive care stay they develop signs and symptoms of possible sepsis requiring blood culture, an additional sodium citrate sample will be obtained. Infants will be categorised into three groups as follows: (i) culture positive sepsis, (ii) culture negative sepsis where an infant receives 5 days of antibiotics (iii) non sepsis. Our primary outcome is to establish if differential platelet/endothelial activation can prospectively identify neonatal culture positive late onset sepsis. TRIAL REGISTRATION NUMBER: NCT05530330 IMPACT: Preterm infants are a high risk group for the development of sepsis which is a major cause of mortality in this population. Platelets have been associated with host response to invasive bacterial infections both in animal models and translational work. A positive blood culture is the gold standard test for neonatal sepsis but can be unreliable due to limited blood sampling in the very low birth weight population. This study hopes to establish if platelet/endothelial associated plasma proteins can prospectively identify late onset neonatal sepsis.

Management of neonatal hypoglycaemia in a tertiary maternity unit-A multidisciplinary quality improvement project.

AIM: Improved identification and treatment of infants at risk of hypoglycaemia using evidence-based guidelines. METHODS: Design: Prospective, multidisciplinary quality improvement project (QIP). SETTING: Tertiary maternity hospital, Dublin (2016-2023). SUBJECTS: Infants at risk for neonatal hypoglycaemia. INTERVENTION: Plan-Do-Study-Act methodology. A hospital-wide survey and ongoing audit informed our initiatives including staff education, antenatal maternal education and standardisation of equipment. Our guidelines were continually evaluated and updated based on emerging evidence. MAIN OUTCOME MEASURES: Neonatal unit (NNU) admissions, adherence to guidelines and use of glucose gel. RESULTS: NNU admissions decreased by 70%, from 3% (118/3883) to 0.9% (34/3806 infants). The number requiring an IV glucose bolus reduced from 25% (29/118) to 6% (2/34). Improved antenatal education, antenatal expression of colostrum and early and frequent feeding also contributed to a reduction in glucose gel use of 94% (1009 tubes in 2018-v-62 in 2022). There were no adverse side effects related to hypoglycaemia. CONCLUSION: Our QIP resulted in a significant reduction in NNU admissions leading to significant cost reductions and NNU workload. More importantly, this resulted in less maternal-infant separation and potentially less parental anxiety and a more supportive environment for breastfeeding. These low-cost initiatives can be implemented in other tertiary maternity hospitals to improve maternity and newborn care.

Changes in inflammatory proteins following platelet transfusion in a neonatal population.

BACKGROUND: Studies have demonstrated increased morbidity and mortality with platelet transfusions in the neonatal period. Platelets are as important for host immunity and inflammation as for hemostasis. Increased inflammation may explain the dose-associated increase in mortality, bleeding, and lung disease. OBJECTIVE: This study aims to assess if there are any changes in inflammatory cytokines post-platelet transfusion in babies in NICU. METHODS: This prospective observational study recruited babies due to receive a non-emergency platelet transfusion. Dried whole blood samples were collected prior to and 2 h post-transfusion. Samples were processed using multiplex immunoassay to enable analysis of tiny blood volumes. Statistical analysis was performed using R. RESULTS: Seventeen babies underwent 26 platelet transfusions across two centers. Median birthweight was 1545 g (535-3960 g) and median birth gestation was 31 weeks and 1 day (23 + 1 to 40 + 5). Median pre-transfusion platelet count was 19.5 × 109/l. There was a significant increase in levels of CXCL5 (p < 0.001), CD40 (p = 0.001), and TGF-ß (p = 0.001) in neonatal blood samples post-platelet transfusion in the study group. CONCLUSION: The increase in the cytokines CXCL5, CD40 and TGF-ß after platelet transfusion in babies in NICU could potentiate existing inflammation, NEC, lung, or white matter injury. This could potentially explain long-term harm from platelet transfusion in babies. IMPACT: There is a change in levels of immunomodulatory proteins CXCL5, CD40, and TGF-ß after platelet transfusion in babies in NICU. Murine neonatal models have demonstrated an increase in cytokine levels after platelet transfusions. This is the first time that this has been demonstrated in human neonates. The increase in proinflammatory cytokines could potentially explain the long-term harm from platelet transfusion in babies, as they could potentiate existing inflammation, NEC, lung injury, or white matter injury.

Parents' understanding and experiences of blood component transfusion in the neonatal intensive care unit: A qualitative study.

AIM: Blood component transfusion is a common intervention in the neonatal intensive care unit (NICU). Parents consent on their babies' behalf. This study aimed to explore parents' understandings and experiences of consenting and the subsequent blood transfusion. METHODS: A "low inference" qualitative descriptive semi-structured interview approach was utilised. Grounded theory was employed. Parents described their memories of babies' transfusions, their responses to the consent process and assessed the written information they were given. RESULTS: A purposive sample of 17 parents whose babies required blood transfusion in the NICU participated. Parents talked about their initial fears of transfusion, later replaced by confidence in the process and results of transfusion and trust in the healthcare professional team. The main themes elicited by the interviews were parents' expectations and outcomes of transfusion, parents' prior and current opinions of transfusion, parents trust in healthcare professionals and how parents would like to receive information about transfusions in the NICU. CONCLUSION: Parents in our study trust information from the healthcare professionals caring for their baby and would like more specific information about how blood transfusion will impact their baby, in a variety of means. Parents felt that blood transfusions were beneficial for their babies.

Randomized Trial of Platelet-Transfusion Thresholds in Neonates.

BACKGROUND: Platelet transfusions are commonly used to prevent bleeding in preterm infants with thrombocytopenia. Data are lacking to provide guidance regarding thresholds for prophylactic platelet transfusions in preterm neonates with severe thrombocytopenia. METHODS: In this multicenter trial, we randomly assigned infants born at less than 34 weeks of gestation in whom severe thrombocytopenia developed to receive a platelet transfusion at platelet-count thresholds of 50,000 per cubic millimeter (high-threshold group) or 25,000 per cubic millimeter (low-threshold group). Bleeding was documented prospectively with the use of a validated bleeding-assessment tool. The primary outcome was death or new major bleeding within 28 days after randomization. RESULTS: A total of 660 infants (median birth weight, 740 g; and median gestational age, 26.6 weeks) underwent randomization. In the high-threshold group, 90% of the infants (296 of 328 infants) received at least one platelet transfusion, as compared with 53% (177 of 331 infants) in the low-threshold group. A new major bleeding episode or death occurred in 26% of the infants (85 of 324) in the high-threshold group and in 19% (61 of 329) in the low-threshold group (odds ratio, 1.57; 95% confidence interval [CI], 1.06 to 2.32; P=0.02). There was no significant difference between the groups with respect to rates of serious adverse events (25% in the high-threshold group and 22% in the low-threshold group; odds ratio, 1.14; 95% CI, 0.78 to 1.67). CONCLUSIONS: Among preterm infants with severe thrombocytopenia, those randomly assigned to receive platelet transfusions at a platelet-count threshold of 50,000 per cubic millimeter had a significantly higher rate of death or major bleeding within 28 days after randomization than those who received platelet transfusions at a platelet-count threshold of 25,000 per cubic millimeter. (Funded by the National Health Service Blood and Transplant Research and Development Committee and others; Current Controlled Trials number, ISRCTN87736839 .).

Relationship Between Postnatal Pulmonary Arterial Pressure and Altered Diastolic Function in Neonates with Down Syndrome.

OBJECTIVE: To assess the influence of diastolic dysfunction on the evolution of pulmonary hypertension in neonates with Down Syndrome over the early newborn period. STUDY DESIGN: This was a prospective observational cohort study. Echocardiography was performed three times over the first week of life in both Down syndrome and control cohorts. Measurements of pulmonary arterial pressure in addition to left ventricular (LV) and right ventricular systolic and diastolic function were collected. RESULTS: Seventy babies with Down syndrome and 60 control infants were enrolled. Forty-eight of the infants with Down syndrome (69%) were born with congenital heart disease (CHD). Echocardiography surrogates of pulmonary hypertension and myocardial function remained significantly impaired in the Down syndrome group in comparison with control infants (all P < .01). In the Down syndrome group, LV early diastolic strain rate was independently associated with measures of pulmonary hypertension while controlling for gestational age, cesarean delivery, and the presence of CHD (P < .01). CONCLUSIONS: Intrinsic LV diastolic impairment is directly associated with higher indices of pulmonary hypertension in infants with Down syndrome and may be a contributing factor to its evolution.

Preterm neonates benefit from low prophylactic platelet transfusion threshold despite varying risk of bleeding or death.

The Platelets for Neonatal Thrombocytopenia (PlaNeT-2) trial reported an unexpected overall benefit of a prophylactic platelet transfusion threshold of 25 × 109/L compared with 50 × 109/L for major bleeding and/or mortality in preterm neonates (7% absolute-risk reduction). However, some neonates in the trial may have experienced little benefit or even harm from the 25 × 109/L threshold. We wanted to assess this heterogeneity of treatment effect in the PlaNet-2 trial, to investigate whether all preterm neonates benefit from the low threshold. We developed a multivariate logistic regression model in the PlaNet-2 data to predict baseline risk of major bleeding and/or mortality for all 653 neonates. We then ranked the neonates based on their predicted baseline risk and categorized them into 4 risk quartiles. Within these quartiles, we assessed absolute-risk difference between the 50 × 109/L- and 25 × 109/L-threshold groups. A total of 146 neonates died or developed major bleeding. The internally validated C-statistic of the model was 0.63 (95% confidence interval, 0.58-0.68). The 25 × 109/L threshold was associated with absolute-risk reduction in all risk groups, varying from 4.9% in the lowest risk group to 12.3% in the highest risk group. These results suggest that a 25 × 109/L prophylactic platelet count threshold can be adopted in all preterm neonates, irrespective of predicted baseline outcome risk. Future studies are needed to improve the predictive accuracy of the baseline risk model. This trial was registered at www.isrctn.com as #ISRCTN87736839.

Flow cytometry for near-patient testing in premature neonates reveals variation in platelet function: a novel approach to guide platelet transfusion.

BACKGROUND: Neonatal haemorrhaging is often co-observed with thrombocytopenia; however, no evidence of a causal relationship with low platelet count has been reported. Regardless, the administration of a platelet transfusion is often based upon this parameter. Accurate measurement of platelet function in small volumes of adult blood samples by flow cytometry is well established and we propose that the use of the same technology could provide complementary information to guide the administration of platelet transfusions in premature neonates. METHODS: In 28 neonates born at 27-41 weeks gestation, platelet function after stimulation agonists was measured using fibrinogen binding and P-selectin expression (a marker of degranulation). RESULTS: Platelets of neonates with gestation of ≤36 weeks (n = 20) showed reduced fibrinogen binding and degranulation with ADP, and reduced degranulation with CRP-XL. Degranulation Scores of 7837 ± 5548, 22,408 ± 5301 and 53,131 ± 12,102 (mean ± SEM) identified significant differences between three groups: <29, 29-36 and >36 weeks gestation). Fibrinogen binding and degranulation responses to ADP were significantly reduced in suspected septic neonates (n = 6) and the Fibrinogen Binding scores clearly separated the septic and healthy group (88.2 ± 10.3 vs 38.6 ± 12.2, P = 0.03). CONCLUSIONS: Flow cytometric measurement of platelet function identified clinically different neonatal groups and may eventually contribute to assessment of neonates requiring platelet transfusion.

Biomarkers of hepatic injury and function in neonatal hypoxic ischemic encephalopathy and with therapeutic hypothermia.

Therapeutic hypothermia (TH) is now provided as standard care to infants with moderate-severe hypoxic ischemic encephalopathy (HIE). The role of TH in limiting neuronal injury is well recognized, but its effect on hepatic injury which occurs frequently in neonatal HIE is not known. Our objective was to characterize biomarkers of liver injury and function in the setting of neonatal HIE and to describe whether HIE severity and provision of TH influence these hepatic biomarkers. We performed a multicenter retrospective study and compared hepatic biomarkers obtained during the first postnatal week, according to the severity of HIE and whether treated with TH. Of a total of 361 infants with HIE, 223 (62%) received TH and 138 (38%) were managed at normal temperature. Most hepatic biomarkers and C-reactive protein (CRP) were significantly associated with the severity of HIE (p < 0.001). Infants treated with TH had lower peak alanine aminotransferase (ALT) concentrations (p = 0.025) and a delay in reaching peak CRP concentration (p < 0.001). CONCLUSION: We observed a significant association between the clinical grade of HIE and biomarkers of liver metabolism and function. Therapeutic hypothermia was associated with delayed CRP responses and with lower ALT concentrations and so may have the potential to modulate hepatic injury. What is Known: • Ischemic hepatic injury occurs frequently as a part of multiorgan dysfunction in infants with hypoxic ischemic encephalopathy (HIE). • The neuroprotective role of therapeutic hypothermia in management of infants with HIE is well recognized, but the potential hepato-protective effects of hypothermia are unclear. What is New/What this study adds: • Therapeutic hypothermia was associated with lower alanine aminotransferase and albumin concentrations and a delayed C-reactive protein (CRP) response and so may have the potential to modulate hepatic injury. • An elevated CRP concentration during the first postnatal week may be regarded as an expected finding in moderate and severe HIE and, in the overwhelming majority of cases, occurs secondary to hepatic hypoxia-ischemia in the absence of blood culture-positive sepsis.

Characteristics of babies who unexpectedly survive long term after withdrawal of intensive care.

AIM: Occasional babies survive long term after withdrawal of intensive care despite a poor prognosis. We aimed to review in detail the clinical cases, characteristics, and outcomes of neonates with unexpected protracted survival following planned withdrawal of intensive cardiorespiratory support. METHODS: We reviewed infants who unexpectedly survived for more than one week following planned withdrawal of intensive care in two tertiary-level NICUs over a seven-year period. RESULTS: We identified eight long-term survivors (six term, two preterm) between 2007 and 2013. All had a clinical diagnosis of grade 3 hypoxic-ischaemic encephalopathy and severely abnormal electroencephalography and neuroimaging prior to intensive care withdrawal. Intensive care was withdrawn at five days postnatal age (range: two to nine days), but the possibility of protracted survival was discussed beforehand in only two cases. Three infants died before three months of age. Five infants remain alive, currently aged from 2.0 to 6.5 years, and all have significant neurodevelopmental problems. CONCLUSION: Unexpected long-term survival after neonatal intensive care withdrawal occurs occasionally but unpredictably. Significant neurodevelopmental adversity was invariable in those surviving beyond infancy. Ventilator dependency along with severely abnormal electroencephalography and neuroimaging is still compatible with long-term survival. The possibility of protracted survival should be discussed routinely with parents before intensive care withdrawal.

GATA1-mutant clones are frequent and often unsuspected in babies with Down syndrome: identification of a population at risk of leukemia.

Transient abnormal myelopoiesis (TAM), a preleukemic disorder unique to neonates with Down syndrome (DS), may transform to childhood acute myeloid leukemia (ML-DS). Acquired GATA1 mutations are present in both TAM and ML-DS. Current definitions of TAM specify neither the percentage of blasts nor the role of GATA1 mutation analysis. To define TAM, we prospectively analyzed clinical findings, blood counts and smears, and GATA1 mutation status in 200 DS neonates. All DS neonates had multiple blood count and smear abnormalities. Surprisingly, 195 of 200 (97.5%) had circulating blasts. GATA1 mutations were detected by Sanger sequencing/denaturing high performance liquid chromatography (Ss/DHPLC) in 17 of 200 (8.5%), all with blasts >10%. Furthermore low-abundance GATA1 mutant clones were detected by targeted next-generation resequencing (NGS) in 18 of 88 (20.4%; sensitivity ∼0.3%) DS neonates without Ss/DHPLC-detectable GATA1 mutations. No clinical or hematologic features distinguished these 18 neonates. We suggest the term "silent TAM" for neonates with DS with GATA1 mutations detectable only by NGS. To identify all babies at risk of ML-DS, we suggest GATA1 mutation and blood count and smear analyses should be performed in DS neonates. Ss/DPHLC can be used for initial screening, but where GATA1 mutations are undetectable by Ss/DHPLC, NGS-based methods can identify neonates with small GATA1 mutant clones.

Skin colonisation at the catheter exit site is strongly associated with catheter colonisation and catheter-related sepsis.

AIM: The commonest mode of catheter colonisation is via the extraluminal route with skin bacteria. Catheter-related sepsis causes significant mortality and morbidity in neonates. Our aim was to study the relationships between culture-positive catheter exit site skin swabs, percutaneous central venous catheter segments and blood to determine the magnitude of associations between exit site skin colonisation, catheter colonisation and catheter-related sepsis. METHODS: In a prospective study, an exit site skin swab and three formerly in vivo catheter segments (proximal, middle and tip) were taken for culture at catheter removal. In those neonates who were clinically unwell at catheter removal, a peripheral blood culture was also collected. Univariate and multivariate analyses were used to study associations. RESULTS: Skin swabs were culture positive in 39 (21%) of 187 catheter removals. With a culture-positive skin swab, the risk of associated catheter colonisation was nearly eight times higher (OR: 7.84, 95% CI: 3.59-17.15) and the risk of definite catheter-related sepsis with the same organism was nearly 10 times higher (OR 9.86, 95% CI: 3.13-31.00). CONCLUSION: Culture-positive skin swabs from the catheter exit site were strongly associated with catheter colonisation and with definite catheter-related sepsis with the same organism. These data provide further evidence supporting catheter colonisation via the extraluminal route and highlight the importance of optimising skin disinfection before catheter insertion.

Newborn face mask ventilation training using a standardised intervention and respiratory function monitor: a before and after manikin study.

OBJECTIVE: The International Liaison Committee on Resuscitation has recommended improvements in training for neonatal resuscitation, highlighting the potential role of respiratory function monitors (RFMs). Our objective was to determine whether a manikin-based, standardised face mask ventilation training intervention using an RFM with a simple visual display reduced face mask leak. DESIGN: Multicentre, before and after study. Participants and instructors were blinded to the RFM display during both assessment periods. PARTICIPANTS: Healthcare professionals working or training in a hospital providing maternity and neonatal services. INTERVENTION: All participants underwent a training intervention on positive pressure ventilation using a modified, leak-free manikin and RFM. The intervention consisted of a demonstration of optimal face mask ventilation technique, training in RFM interpretation with corrective strategies for common scenarios and a period of deliberate practice. Each participant performed 30 s of positive pressure ventilation blinded to the RFM display before and after training. MAIN OUTCOME MEASURES: The primary outcome was face mask leak (%) measured after training. Secondary outcome measures included expired tidal volume, inflating pressures and ventilation rate. Adjustments made to technique during training were an important qualitative outcome. RESULTS: Four hundred and fourteen participants were recruited over a 13-month period from April 2022, and 412 underwent analysis. Median (IQR) face mask leak before training was 31% (10-69%) compared with 10% (6-18%) after training (p<0.0001). Improvements were noted across all other ventilation parameters. CONCLUSION: Standardised face mask ventilation training using an RFM with simple visual feedback led to a significant reduction in leak.

How we decide when a neonate needs a transfusion.

The decision to transfuse a neonate can be approached by addressing a series of questions that cover the cause of anaemia, alternatives to transfusion, the need for transfusion and the risks. Recent clinical trials of red cell transfusions have started to inform evidence-based transfusion practice, but have raised uncertainties about neurological outcomes when policies advocating use of fewer red cell transfusions at lower haemoglobin concentration (Hb) thresholds were tested. Red cell transfusions should be considered when the Hb <120 g/l for premature neonates requiring mechanical ventilation support, with lower thresholds applying for oxygen-dependent neonates not requiring ventilation or for late anaemia (Hb <70-100 g/l, depending on gestational and post-natal age). There is no recent high quality evidence to inform thresholds for prophylactic platelet transfusions in stable non-bleeding premature neonates with platelet count levels of 50 × 10(9) /l, although common practice has become more restrictive, using lower safe thresholds for platelet transfusion between 20 and 30 × 10(9) /l. A more appropriate transfusion strategy for fresh frozen plasma (FFP) in neonates is one that emphasizes the therapeutic use of FFP in the face of bleeding, rather than prophylactic use in stable non-bleeding neonates who often have mild to moderate apparent abnormalities of standard coagulation tests, after allowing for appropriate reference ranges.

Nasal high-flow therapy to Optimise Stability during Intubation: the NOSI pilot trial.

OBJECTIVE: In adult patients with acute respiratory failure, nasal high-flow (NHF) therapy at the time of intubation can decrease the duration of hypoxia. The objective of this pilot study was to calculate duration of peripheral oxygen saturation below 75% during single and multiple intubation attempts in order to inform development of a larger definitive trial. DESIGN AND SETTING: This double-blinded randomised controlled pilot trial was conducted at a single, tertiary neonatal centre from October 2020 to October 2021. PARTICIPANTS: Infants undergoing oral intubation in neonatal intensive care were included. Infants with upper airway anomalies were excluded. INTERVENTIONS: Infants were randomly assigned (1:1) to have NHF 6 L/min, FiO2 1.0 or NHF 0 L/min (control) applied during intubation, stratified by gestational age (<34 weeks vs ≥34 weeks). MAIN OUTCOME MEASURES: The primary outcome was duration of hypoxaemia of <75% up to the time of successful intubation, RESULTS: 43 infants were enrolled (26 <34 weeks and 17 ≥34 weeks) with 50 intubation episodes. In infants <34 weeks' gestation, median duration of SpO2 of <75% was 29 s (0-126 s) vs 43 s (0-132 s) (p=0.78, intervention vs control). Median duration of SpO2 of <75% in babies ≥34 weeks' gestation was 0 (0-32 s) vs 0 (0-20 s) (p=0.9, intervention vs control). CONCLUSION: This pilot study showed that it is feasible to provide NHF during intubation attempts. No significant differences were noted in duration of oxygen saturation of <75% between groups; however, this trial was not powered to detect a difference. A larger, higher-powered blinded study is warranted.

Safety and feasibility of platelet transfusion through long catheters in the neonatal intensive care unit: an in vitro study.

OBJECTIVE: To assess the safety and feasibility of platelet transfusion through small-bore long lines used in the neonatal intensive care unit (NICU), including double-lumen umbilical venous catheters (UVCs) and 24 G and 28 G peripherally inserted central catheters (PICCs). DESIGN: Prospective in vitro controlled study. SETTING: Blood transfusion service laboratory. METHODS: In vitro platelet transfusions were set up as per NICU practice. Transfusion line pressure was monitored. Post-transfusion swirling, presence of aggregates, pH analysis and automated cell count in vitro activation response by flow cytometry assessing CD62P expression were assessed. MAIN OUTCOME MEASURES: All transfusions completed successfully. The rate of infusion was reduced in 5 of 16 transfusions through 28 G lines due to 'pressure high' alarms. There was no difference in swirling values or transfusion aggregate formation, CD62P expression levels, platelet count, platelet distribution width, mean platelet volume, plateletcrit or platelet to large cell ratio across transfusions post-transfusion. CONCLUSIONS: This study showed that in vitro platelet transfusion performed through 24 G and 28 G neonatal PICC lines and double-lumen UVCs is non-inferior to 24 G short cannulas, using outcome measures of platelet clumping, platelet activation and line occlusion. This suggests that where available these lines can be used if necessary for platelet transfusion.

Two-year outcomes following a randomised platelet transfusion trial in preterm infants.

OBJECTIVE: Assess mortality and neurodevelopmental outcomes at 2 years of corrected age in children who participated in the PlaNeT-2/MATISSE (Platelets for Neonatal Transfusion - 2/Management of Thrombocytopenia in Special Subgroup) study, which reported that a higher platelet transfusion threshold was associated with significantly increased mortality or major bleeding compared to a lower one. DESIGN: Randomised clinical trial, enrolling from June 2011 to August 2017. Follow-up was complete by January 2020. Caregivers were not blinded; however, outcome assessors were blinded to treatment group. SETTING: 43 level II/III/IV neonatal intensive care units (NICUs) across UK, Netherlands and Ireland. PATIENTS: 660 infants born at less than 34 weeks' gestation with platelet counts less than 50×109/L. INTERVENTIONS: Infants were randomised to undergo a platelet transfusion at platelet count thresholds of 50×109/L (higher threshold group) or 25×109/L (lower threshold group). MAIN OUTCOMES MEASURES: Our prespecified long-term follow-up outcome was a composite of death or neurodevelopmental impairment (developmental delay, cerebral palsy, seizure disorder, profound hearing or vision loss) at 2 years of corrected age. RESULTS: Follow-up data were available for 601 of 653 (92%) eligible participants. Of the 296 infants assigned to the higher threshold group, 147 (50%) died or survived with neurodevelopmental impairment, as compared with 120 (39%) of 305 infants assigned to the lower threshold group (OR 1.54, 95% CI 1.09 to 2.17, p=0.017). CONCLUSIONS: Infants randomised to a higher platelet transfusion threshold of 50×109/L compared with 25×109/L had a higher rate of death or significant neurodevelopmental impairment at a corrected age of 2 years. This further supports evidence of harm caused by high prophylactic platelet transfusion thresholds in preterm infants. TRIAL REGISTRATION NUMBER: ISRCTN87736839.

The safety and efficacy of red cell transfusions in neonates: a systematic review of randomized controlled trials.

Premature neonates commonly receive red blood cell (RBC) transfusions. This study systematically identified and appraised randomized controlled trials (RCTs) where the intervention was 'transfusion of red blood cells' from searches of multiple databases. Primary review outcomes were mortality, neurodevelopmental and respiratory endpoints. Two reviewers extracted data and assigned overall quality. Twenty-seven RCTs were identified and grouped into four predefined categories: trials comparing RBC transfusion versus no transfusion/placebo (n = 3); different thresholds for transfusion (n = 6); differing doses or administration schedule (n = 4), or different types or products of RBC (n = 14). In the threshold group of trials, enrolling 679 neonates, no significant differences in mortality (relative risk 1·22, 95% confidence interval 0·84-1·75) or chronic lung disease were found. Only two trials assessed neurodevelopment outcomes, both within the threshold group, but with differing results. The largest subgroup of RCTs by number evaluated different media for storage of red cells (n = 7), enrolling 221 neonates. The methodological quality of many RCTs was poor. The design of future RCTs can be informed by the lessons from this review. Many trials failed to report on outcomes that would be considered of primary importance to clinicians. Consistent reporting of adverse events is required, and endpoints need to include neurodevelopmental outcomes.