ObjectivesThrombocytopenia is a frequent problem in neonatal sepsis and is among the most predictive, independent risk factors for sepsis-associated mortality. This study aims to clarify the occurrence, severity and duration of thrombocytopenia in neonatal sepsis.Study designA cohort study was carried out among all neonates with proven culture positive sepsis that were admitted to a tertiary NICU between 2006 and 2015 (n = 460). The occurrence, severity and duration of thrombocytopenia were recorded, as well as major bleedings and potential risk factors for mortality in neonatal sepsis.ResultsSepsis was diagnosed in 460 of 6551 neonates (7%). Severe thrombocytopenia (platelets ≤50*109/L) occurred in 20% (92/460) of septic neonates. The median time for platelets to rise >100*109 was 6.0 days (interquartile range 4.0–7.0). On multivariate analysis, maternal hypertension, intravascular thrombosis and Gram negative (as opposed to Gram positive) sepsis were independently associated with thrombocytopenia in neonatal sepsis. In severe thrombocytopenia, 10% (9/92) suffered a severe IVH, compared to 5% (20/356) in neonates with platelets >50*109/L (p = 0.125). 10% (9/92) suffered a pulmonary hemorrhage, compared to 2% (9/368) in neonates with platelets >50*109/L (p = 0.001). On multivariate analysis, thrombocytopenia and Gram negative (as opposed to Gram positive) sepsis were independently associated with neonatal mortality.ConclusionsThrombocytopenia is independently associated with maternal hypertension, intravascular thrombosis and Gram negative sepsis. Thrombocytopenia in neonatal sepsis increases the risk of mortality nearly four-fold, with another six-fold increase in mortality in case of Gram negative sepsis.

This meta-analysis examines loneliness in children and adolescents with chronic physical conditions as compared with their peers. Multilevel meta-analyses were performed on 43 studies (69 samples), published between 1987 and 2015. A total of 2,518 individuals with chronic physical conditions and 1,463 control peers were included in the analyses. Children and adolescents with chronic conditions are, on average, somewhat lonelier than their peers without such conditions. Moreover, the link between chronic conditions and loneliness varied according to the recruitment procedure used for participant selection. Stronger links were found for studies that recruited from patient organizations as compared with clinical registers. Findings support the link between loneliness and chronic conditions. To take into account the heterogeneity within patient groups, we advocate an alternative approach that cuts across diagnostic boundaries and focuses on illness-related variables such as illness duration and visibility of the condition.

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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 NCT87736839.

The aim of this study was to evaluate changes in the use of fresh-frozen plasma (FFP) transfusions and the use of clotting tests in preterm neonates in our center over the past two decades. In this retrospective cohort analysis, we included all consecutive neonates with a gestational age at birth between 24 + 0 and 31 + 6 weeks admitted to our neonatal intensive care unit (NICU) between 2004 and 2019. We divided all included neonates into three consecutive time epochs according to date of birth: January 2004 to April 2009, May 2009 to August 2014 and September 2014 to December 2019. The main outcomes were the use of FFP transfusion, coagulation testing and the indications for FFP transfusion. The percentage of preterm neonates receiving FFP transfusion decreased from 5.7% (47/824) to 3.7% (30/901) to 2.0% (17/852) from the first epoch to the last epoch (p < 0.001). Additionally, the rate of neonates undergoing coagulation testing decreased from 24.3% (200/824) to 14.5% (131/901) to 8% (68/852) over the epochs (p < 0.001). Most FFP transfusions were prescribed prophylactically based on prolongation of activated partial thromboplastin time (aPTT) or prothrombin time (PT) (56%). In conclusion, both the use of FFP transfusions and the use of coagulation tests decreased significantly over the years. The majority of the FFP transfusions were administrated prophylactically for abnormal coagulation tests.

BackgroundPreterm infants commonly receive red blood cell (RBC), platelet and fresh frozen plasma (FFP) transfusions. The aim of this Neonatal Transfusion Network survey was to describe current transfusion practices in Europe and to compare our findings to three recent randomised controlled trials to understand how clinical practice relates to the trial data.MethodsFrom October to December 2020, we performed an online survey among 597 neonatal intensive care units (NICUs) caring for infants with a gestational age (GA) of <32 weeks in 18 European countries.ResultsResponses from 343 NICUs (response rate: 57%) are presented and showed substantial variation in clinical practice. For RBC transfusions, 70% of NICUs transfused at thresholds above the restrictive thresholds tested in the recent trials and 22% below the restrictive thresholds. For platelet transfusions, 57% of NICUs transfused at platelet count thresholds above 25×109/L in non-bleeding infants of GA of <28 weeks, while the 25×109/L threshold was associated with a lower risk of harm in a recent trial. FFP transfusions were administered for coagulopathy without active bleeding in 39% and for hypotension in 25% of NICUs. Transfusion volume, duration and rate varied by factors up to several folds between NICUs.ConclusionsTransfusion thresholds and aspects of administration vary widely across European NICUs. In general, transfusion thresholds used tend to be more liberal compared with data from recent trials supporting the use of more restrictive thresholds. Further research is needed to identify the barriers and enablers to incorporation of recent trial findings into neonatal transfusion practice.

Introduction Limited evidence supports the widely used practice of administering platelet transfusions to prevent major bleeding in preterm thrombocytopenic neonates. Only 1 randomized controlled trial addressed this issue, but used thresholds higher than those currently used in clinical practice. In order to assess the impact of platelet transfusions on bleeding risk, the primary objective of this study was to develop a prediction model for bleeding. Platelet transfusion was included as variable in this model. In these secondary analyses, we further explored the impact of platelet transfusions on bleeding risk. Materials and methods In this multicenter cohort study, neonates with a gestational age (GA) &lt;34 weeks at birth, admitted to a neonatal intensive care unit (NICU) who developed a platelet count &lt;50x109/L were included. The main study endpoint was major bleeding, defined as intraventricular hemorrhage (IVH) grade 3, IVH with parenchymal involvement, other types of intracranial hemorrhage visible on ultrasound scans, pulmonary hemorrhage or any other type of bleeding requiring immediate interventions. The prediction model was developed using landmarking, in which multiple cox models at regular time-points were combined into 1 supermodel. To further explore the impact of platelet transfusions on bleeding risk, we performed 3 sensitivity analyses by selecting specific transfusions (instead of all transfusions). Sensitivity analysis 1 : transfusions according to protocol, defined as transfusions for platelet counts &gt;20x109/L only allowed in case of GA&lt;32 weeks and &lt;1500 grams and presence of NEC, sepsis, or treatment with mechanical ventilation, or in case of invasive procedures. Sensitivity analysis 2: transfusions with fair increments, defined as platelet count ≥50x109/L within 24 hours. Sensitivity analysis 3: transfusion dose 11 ml/kg or higher. Results A total of 640 neonates were included with a median gestational age of 28 weeks. 70 neonates developed a major bleed. IUGR, postnatal age, platelet count and mechanical ventilation were independent predictors of bleeding. The model allowed calculation of two bleeding risks for individual neonates: one in case of platelet transfusion and one in case of no platelet transfusion. 1361 platelet transfusions were administered to 449 of 640 (70%) neonates, of which 87 were hyperconcentrates. The hazard ratio for transfusion in the original model was 1.0, indicating no predictive power. Sensitivity analysis 1: 704 (52%) transfusions were given according to protocol. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.5, but the p-value remained &gt; 0.05.Sensitivity analysis 2: 764 (56%) of transfusions resulted in a count &gt;50x109/L within 24 hours. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.25, but the p-value remained &gt;0.05. 115 (8%) transfusions did not have a follow up platelet count within 24 hours. Sensitivity analysis 3: of the non-hyperconcentrated platelet transfusions, 517 of 1274 (41%) transfusions were ≥ 11 ml/kg. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.1, with a p-value of 0.05. Conclusion With this tool, absolute risk of bleeding in individual preterm thrombocytopenic neonates can be calculated. Additionally, risk of bleeding can be assessed for 2 scenarios: with and without platelet transfusion. This can help clinicians in deciding whether or not to transfuse a patient. In the primary model, platelet transfusion was not a predictor for bleeding risk. However, the findings of the sensitivity analyses suggest that transfusions with a dose &gt; 11ml/kg may have a more profound effect on bleeding risk. Disclosures No relevant conflicts of interest to declare.