Red cell and platelet transfusions in neonates: a population based study

Objectives: Reports of neonatal transfusion practices have focused predominantly on premature neonates admitted to neonatal intensive care units (NICU), however little is known about transfusion among other neonates. This study aimed to describe the use of blood products among all neonates. Design: Linked population-based birth and hospital discharge data from New South Wales (NSW), Australia was used to determine rates of blood product transfusion in the first 28 days of life. The study included all livebirths ≥23 weeks’ gestation in NSW between 2001 and 2011. Results: Between 2001-2011, 5326 of 989,491 live born neonates received a blood product transfusion (5.4 per 1000 births). Transfusion rates were 4.8 per 1000 for red cells, 1.3 per 1000 for platelets and 0.3 per 1000 for exchange transfusion. High transfusion rates were seen in neonates with prior in-utero transfusion (631/1000), congenital anomaly requiring surgery (440/1000) or haemolytic disorder (106/1000). Among transfused infants, 7% received transfusions in a hospital without a NICU. Of those transfused, 64% were born ≤32 weeks gestation (n=3384, 255/1000 births), with 96% of these receiving red cells. 36% were born >32 weeks gestation (n= 1942, 1.98/1000 births), with 76% receiving red cells and 38% receiving platelets. Conclusions: In this population based study, high transfusion rates were seen in neonates with haemolytic disorders or requiring surgery, as well as in those born preterm. Thirty-six percent of neonates who received blood products were born >32 weeks gestation and 7% were transfused in hospitals without a NICU.NHMRC, AR

Age of blood and adverse outcomes in a maternity population

BACKGROUND In recent times there has been debate around whether longer storage time of blood is associated with increased rates of adverse outcomes following transfusion. It is unclear whether results focused on cardiac or critically ill patients apply to a maternity population. This study investigates whether older blood is associated with increased morbidity and readmission in women undergoing obstetric transfusion. STUDY DESIGN AND METHODS Women giving birth in hospitals in New South Wales, Australia between July 2006‐December 2010 were included in the study population if they had received between 1‐4 red cell units during the birth admission. Information on women’s characteristics, transfusions and outcomes were obtained from 5 routinely collected datasets including blood collection, birth and hospitalisation data. Generalised propensity score methods were used to determine the effect of age of blood on rates of severe morbidity and readmission, independent of confounding factors. RESULTS Transfusion data were available for 2990 women, with a median age of blood transfused of 20 days (interquartile range 14,27 days). There were no differences in the age of blood transfused between women with and without severe morbidity (21 (14,28) vs 22 (15,30) days), and in women readmitted or not (22 (14,28) vs 22 (16,30) days). After considering potential confounding factors, no relationship was found between the age of blood transfused and rates of severe morbidity and readmission. CONCLUSION Among women receiving low volume transfusions during a birth admission, there was no evidence of increased rates of adverse outcomes following transfusion with older blood.NHMRC, Australian Red Cross, NSW Clinical Excellence Commission, AR

Preclinical Evaluation and Dosimetry of [111In]CHX-DTPA-scFv78-Fc Targeting Endosialin/Tumor Endothelial Marker 1 (TEM1)

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WHAT FACTORS CONTRIBUTE TO HOSPITAL VARIATION IN OBSTETRIC TRANSFUSION RATES?

Background & Objectives: To explore variation in red blood cell transfusion rates between hospitals, and the extent to which this can be explained. A secondary objective was to assess whether hospital transfusion rates are associated with maternal morbidity. Materials & Methods: Linked hospital discharge and birth data were used to identify births (N=279,145) in hospitals with at least 10 deliveries per annum between 2008-2010 in New South Wales, Australia. To investigate transfusion rates, a series of random effects multilevel logistic regression models were fitted, progressively adjusting for maternal, obstetric and hospital factors. Correlations between hospital transfusion and maternal, neonatal morbidity and readmission rates were assessed. Results: Overall, the transfusion rate was 1.4% (hospital range 0.6 to 2.9) across 89 hospitals. Adjusting for maternal casemix, reduced the variation between hospitals by 26%. Adjustment for obstetric interventions further reduced variation by 8% and a further 39% after adjustment for hospital type. At a hospital level, high transfusion rates were moderately correlated with maternal morbidity (0.56, p=0.01) and low Apgar scores (0.54, p=0.002), but not with readmission rates (0.18, p=0.28). Conclusion: Both casemix and practice differences contributed to the variation in transfusion rates between hospitals. The relationship between outcomes and transfusion rates was variable, however low transfusion rates were not associated with worse outcomes.Partnership Grant from the Australian National Health and Medical Research Council NHMRC (#1027262), the Australian Red Cross and the NSW Clinical Excellence Commission, NHMRC Senior Research Fellowship (#1021025). ARC Future Fellowship (#120100069)

WHAT FACTORS CONTRIBUTE TO HOSPITAL VARIATION IN OBSTETRIC TRANSFUSION RATES?

Background & Objectives: To explore variation in red blood cell transfusion rates between hospitals, and the extent to which this can be explained. A secondary objective was to assess whether hospital transfusion rates are associated with maternal morbidity. Materials & Methods: Linked hospital discharge and birth data were used to identify births (N=279,145) in hospitals with at least 10 deliveries per annum between 2008-2010 in New South Wales, Australia. To investigate transfusion rates, a series of random effects multilevel logistic regression models were fitted, progressively adjusting for maternal, obstetric and hospital factors. Correlations between hospital transfusion and maternal, neonatal morbidity and readmission rates were assessed. Results: Overall, the transfusion rate was 1.4% (hospital range 0.6 to 2.9) across 89 hospitals. Adjusting for maternal casemix, reduced the variation between hospitals by 26%. Adjustment for obstetric interventions further reduced variation by 8% and a further 39% after adjustment for hospital type. At a hospital level, high transfusion rates were moderately correlated with maternal morbidity (0.56, p=0.01) and low Apgar scores (0.54, p=0.002), but not with readmission rates (0.18, p=0.28). Conclusion: Both casemix and practice differences contributed to the variation in transfusion rates between hospitals. The relationship between outcomes and transfusion rates was variable, however low transfusion rates were not associated with worse outcomes.Partnership Grant from the Australian National Health and Medical Research Council NHMRC (#1027262), the Australian Red Cross and the NSW Clinical Excellence Commission, NHMRC Senior Research Fellowship (#1021025). ARC Future Fellowship (#120100069)

A Recombinant Blood-Stage Malaria Vaccine Reduces Plasmodium falciparum Density and Exerts Selective Pressure on Parasite Populations in a Phase 1-2b Trial in Papua New Guinea

The malaria vaccine Combination B comprises recombinant Plasmodium falciparum ring-infected erythrocyte surface antigen and 2 merozoite surface proteins (MSP1 and MSP2) formulated in oil-based adjuvant. A phase 1-2b double-blind, randomized, placebo-controlled trial in 120 children (5-9 years old) in Papua New Guinea demonstrated a 62% (95% confidence limits: 13%, 84%) reduction in parasite density in children not pretreated with sulfadoxine-pyrimethamine. Vaccinees had a lower prevalence of parasites carrying the MSP2-3D7 allelic form (corresponding to that in the vaccine) and a higher incidence of morbid episodes associated with FC27-type parasites. These results demonstrate functional activity of Combination B against P. falciparum in individuals with previous malaria exposure. The specific effects on parasites with particular msp2 genotypes suggest that the MSP2 component, at least in part, accounted for the activity. The vaccine-induced selection pressure exerted on the parasites and its consequences for morbidity strongly argue for developing vaccines comprising conserved antigens and/or multiple components covering all important allelic type

SARS Coronavirus-2 microneutralisation and commercial serological assays correlated closely for some but not all enzyme immunoassays

Serological testing for SARS-CoV-2-specific antibodies provides important research and diagnostic information relating to COVID-19 prevalence, incidence and host immune response. A greater understanding of the relationship between functionally neutralising antibodies detected using microneutralisation assays and binding antibodies detected using scalable enzyme immunoassays (EIA) is needed in order to address protective immunity post-infection or vaccination, and assess EIA suitability as a surrogate test for screening of convalescent plasma donors. We assessed whether neutralising antibody titres correlated with signal cut-off ratios in five commercially available EIAs, and one in-house assay based on expressed spike protein targets. Sera from recovered patients or convalescent plasma donors who reported laboratory-confirmed SARS-CoV-2 infection (n = 200), and negative control sera collected prior to the COVID-19 pandemic (n = 100), were assessed in parallel. Performance was assessed by calculating EIA sensitivity and specificity with reference to microneutralisation. Neutralising antibodies were detected in 166 (83%) samples. Compared with this, the most sensitive EIAs were the Cobas Elecsys Anti-SARS-CoV-2 (98%) and Vitros Immunodiagnostic Anti-SARS-CoV-2 (100%), which detect total antibody targeting the N and S1 antigens, respectively. The assay with the best quantitative relationship with microneutralisation was the Euroimmun IgG. These results suggest the marker used (total Ab vs. IgG vs. IgA) and the target antigen are important determinants of assay performance. The strong correlation between microneutralisation and some commercially available assays demonstrates their potential for clinical and research use in assessing protection following infection or vaccination, and use as a surrogate test to assess donor suitability for convalescent plasma donation

SARS-CoV-2 neutralizing antibodies : longevity, breadth, and evasion by emerging viral variants

The Severe Acute Respiratory Syndrome Coronavirus 2 (SAU ARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus–cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 reverse transcription polymerase chain reaction (RT-PCR)–confirmed Coronavirus Disease 2019 (COVID-19) individuals with detailed demographics and followed up to 7 months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of “high responders” maintained high neutralizing responses over time, representing ideal convalescent plasma donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design