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Frequency of red blood cell transfusions in preterm neonates in Brazil: A systematic review and meta-analysis
Valete, C. O. S., Angelica Luiz Ferreira, E., Montenegro, C. P., Pilati, M. C. A., Rodrigues Wilde, M. O. D., Witkowski, S. M.
Vox sanguinis. 2023
Abstract
BACKGROUND AND OBJECTIVES Red blood cell transfusions are frequent in preterm neonates. The proportion of preterm neonates transfused in Brazil remains unknown. We systematically reviewed the literature to estimate the frequency of red blood cell transfusions in preterm neonates in Brazil. MATERIALS AND METHODS The LILACS, EMBASE, Cochrane, SciELO, MEDLINE (PubMed), Web of Science, Scopus, BDTD and 27 national university institutional databases were searched for studies that analysed red blood cell transfusion in preterm neonates in Brazil without period restriction. The Preferred Reporting Items in Systematic Reviews and Meta-Analyses guidelines were followed, and the GRADE methodology was applied. A random-effects model along with the restricted maximum likelihood method was used, and the Freeman-Tukey transformed proportion was used to estimate effect size. RESULTS Nine studies, representing 6548 preterm neonates, were included in the qualitative and quantitative analyses. The mean gestational age ranged from 26.0 to 31.6 weeks. Most of the studies were from the Southeast region. The pooled estimated frequency of red blood cell transfusions was 58.0% (95% confidence interval = 52.0%-64.0%, p < 0.001) with low certainty. There was statistically significant heterogeneity among studies (I(2) = 92.5%, p < 0.001). CONCLUSION In this current meta-analysis of the evidence available, which included moderate and extremely preterm neonates, the observed frequency of red blood cell transfusions in preterm neonates in Brazil was 58.0% and this estimate can help health programming. Some Brazilian regions were not included in this study, and further research is needed to provide a more representative overview of Brazil.
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Anemia and Red Blood Cell Transfusions, Cerebral Oxygenation, Brain Injury and Development, and Neurodevelopmental Outcome in Preterm Infants: A Systematic Review
Kalteren WS, Verhagen EA, Mintzer JP, Bos AF, Kooi EMW
Frontiers in pediatrics. 2021;9:644462
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Editor's Choice
Abstract
Background: Anemia remains a common comorbidity of preterm infants in the neonatal intensive care unit (NICU). Left untreated, severe anemia may adversely affect organ function due to inadequate oxygen supply to meet oxygen requirements, resulting in hypoxic tissue injury, including cerebral tissue. To prevent hypoxic tissue injury, anemia is generally treated with packed red blood cell (RBC) transfusions. Previously published data raise concerns about the impact of anemia on cerebral oxygen delivery and, therefore, on neurodevelopmental outcome (NDO). Objective: To provide a systematic overview of the impact of anemia and RBC transfusions during NICU admission on cerebral oxygenation, measured using near-infrared spectroscopy (NIRS), brain injury and development, and NDO in preterm infants. Data Sources: PubMed, Embase, reference lists. Study Selection: We conducted 3 different searches for English literature between 2000 and 2020; 1 for anemia, RBC transfusions, and cerebral oxygenation, 1 for anemia, RBC transfusions, and brain injury and development, and 1 for anemia, RBC transfusions, and NDO. Data Extraction: Two authors independently screened sources and extracted data. Quality of case-control studies or cohort studies, and RCTs was assessed using either the Newcastle-Ottawa Quality Assessment Scale or the Van Tulder Scale, respectively. Results: Anemia results in decreased oxygen-carrying capacity, worsening the burden of cerebral hypoxia in preterm infants. RBC transfusions increase cerebral oxygenation. Improved brain development may be supported by avoidance of cerebral hypoxia, although restrictive RBC transfusion strategies were associated with better long-term neurodevelopmental outcomes. Conclusions: This review demonstrated that anemia and RBC transfusions were associated with cerebral oxygenation, brain injury and development and NDO in preterm infants. Individualized care regarding RBC transfusions during NICU admission, with attention to cerebral tissue oxygen saturation, seems reasonable and needs further investigation to improve both short-term effects and long-term neurodevelopment of preterm infants.
PICO Summary
Population
Preterm infants in neonatal intensive care unit (NICU), (38 studies).
Intervention
Systematic overview of the impact of anaemia and red blood cell (RBC) transfusions during NICU admission on cerebral oxygenation and neurodevelopmental outcome in preterm infants.
Comparison
Outcome
Anaemia resulted in decreased oxygen-carrying capacity, worsening the burden of cerebral hypoxia in preterm infants. RBC transfusions increased cerebral oxygenation. Improved brain development may be supported by avoidance of cerebral hypoxia, although restrictive RBC transfusion strategies were associated with better long-term neurodevelopmental outcomes.
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Restrictive versus liberal transfusion thresholds in very low birth weight infants: A systematic review with meta-analysis
Wang P, Wang X, Deng H, Li L, Chong W, Hai Y, Zhang Y
PloS one. 2021;16(8):e0256810
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Editor's Choice
Abstract
BACKGROUND To assess the efficacy and safety of restrictive versus liberal red blood cell transfusion thresholds in very low birth weight infants. METHODS We searched MEDLINE, EMBASE, and Cochrane database without any language restrictions. The last search was conducted in August 15, 2020. All randomized controlled trials comparing the use of restrictive versus liberal red blood cell transfusion thresholds in very low birth weight (VLBW) infants were selected. Pooled risk ratio (RR) for dichotomous variable with 95% confidence intervals were assessed by a random-effects model. The primary outcome was all-cause mortality. RESULTS Overall, this meta-analysis included 6 randomized controlled trials comprising 3,483 participants. Restrictive transfusion does not increase the risk of all-cause mortality (RR, 0.99; 95% CI, 0.84 to 1.17; I2 = 0%; high-quality evidence), and does not increase the composite outcome of death or neurodevelopmental impairment (RR, 1.01, 95% CI, 0.93-1.09; I2 = 7%; high-quality evidence) or other serious adverse events. Results were similar in subgroup analyses of all-cause mortality by weight of infants, gestational age, male infants, and transfusion volume. CONCLUSIONS In very low birth weight infants, a restrictive threshold for red blood cell transfusion was not associated with increased risk of all-cause mortality, in either short term or long term.
PICO Summary
Population
Very low birth weight infants (6 studies, n= 3,483).
Intervention
Restrictive red blood cell transfusion threshold.
Comparison
Liberal red blood cell transfusion threshold.
Outcome
Restrictive transfusion did not increase the risk of all-cause mortality (RR, 0.99; I2 = 0%; high-quality evidence), and did not increase the composite outcome of death or neurodevelopmental impairment (RR, 1.01; I2 = 7%; high-quality evidence) or other serious adverse events. Results were similar in subgroup analyses of all-cause mortality by weight of infants, gestational age, male infants, and transfusion volume.
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Regional Oxygenation and Perfusion Monitoring to Optimize Neonatal Packed Red Blood Cell Transfusion Practices: A Systematic Review
Jani P, Balegarvirupakshappa K, Moore JE, Badawi N, Tracy M
Transfusion medicine reviews. 2021
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Editor's Choice
Abstract
Contemporary packed red blood cell transfusion practices in anaemic preterm infants are primarily based on measurement of hemoglobin or haematocrit. In neonatal intensive care units, most preterm infants receive at least 1 packed red cell transfusion as standard treatment for anaemia of prematurity. Clinicians are faced with a common question "at what threshold should anaemic preterm infants receive packed red blood cell transfusion?". While evidence from interventional trials offers a range of haemoglobin levels to clinicians on thresholds to initiate red cell transfusion, it does not offer identification of exact haemoglobin level at which regional oxygenation and perfusion gets compromised. Assessment of regional oxygenation using near infrared spectroscopy and perfusion using ultrasound could offer a personalized transfusion medicine approach to optimize transfusion practices. We conducted a systematic review of the literature to identify the role of both regional oxygenation and/or ultrasound-based perfusion monitoring as a potential trigger to initiate packed red blood cell transfusion in anaemic preterm infants. MEDLINE, Embase, Maternity and Infant Care database were searched up to March 2021. Publications identified were screened and relevant data was extracted. Changes to regional oxygenation and/or perfusion monitoring before and after packed red blood cell transfusion were the primary outcomes. 44 out of 755 studies met the inclusion criteria and were included in the final analysis. Most were prospective, observational studies in stable preterm infants. Overall, studies reported an improvement in regional oxygenation and/or ultrasound-based perfusion after packed red blood cell transfusion. These changes were more consistently observed when hemoglobin <9.6g/dL or hematocrit was <0.30. Significant variation was found for patient characteristics, postnatal age at the time of monitoring, criteria for diagnosis of anaemia, and period of monitoring as well as regional oxygenation monitoring methodology. Regional oxygenation and/or perfusion monitoring can identify at-risk anaemic preterm infants and are promising tools to individualize packed red blood cell transfusion practices. However, there is lack of evidence for incorporating this monitoring, in their present form, into standard clinical practice. Additionally, consistency in reporting of study methodology should be improved.
PICO Summary
Population
Anaemic preterm infants (44 studies).
Intervention
Systematic review to identify the role of both regional oxygenation and/or ultrasound-based perfusion monitoring as a potential trigger to initiate packed red blood cell transfusion.
Comparison
Outcome
Overall, studies reported an improvement in regional oxygenation and/or ultrasound-based perfusion after packed red blood cell transfusion. These changes were more consistently observed when haemoglobin <9.6g/dL or haematocrit was <0.30. Significant variation was found for patient characteristics, postnatal age at the time of monitoring, criteria for diagnosis of anaemia, and period of monitoring as well as regional oxygenation monitoring methodology.
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Effect of red blood cell transfusion on the development of retinopathy of prematurity: A systematic review and meta-analysis
Zhu Z, Hua X, Yu Y, Zhu P, Hong K, Ke Y
PLoS One. 2020;15(6):e0234266
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Editor's Choice
Abstract
BACKGROUND The effect of red blood cell (RBC) transfusion on retinopathy of prematurity (ROP) is difficult to establish, because ROP may also be influenced by other factors. Therefore, we carried out a systematic review and meta-analysis to explore the relationship between RBC transfusion and the development of ROP. METHODS The PubMed, Embase, Cochrane Library and Web of Science databases were searched from their inception to September 1, 2019. Observational studies that reported the relationship between RBC transfusion and ROP after adjusting for other potential risk factors were included. The combined result was analyzed by a random effect model. Heterogeneity and publication bias were tested, and sensitivity analysis was performed. RESULTS Of the 2628 identified records, 18 studies including 15072 preterm infants and 5620 cases of ROP were included. A random effect model was used and revealed that RBC transfusion was significantly associated with ROP (pooled OR = 1.50, 95% CI: 1.27-1.76), with moderate heterogeneity among the included studies (I2 = 44.2%). Subgroup analysis indicated that RBC transfusion was more closely related to ROP in the group with a gestational age (GA) ≤32 weeks (OR = 1.77, 95% CI: 1.29-2.43) but not in the groups with a GA ≤34 weeks (OR = 1.36, 95% CI: 0.85-2.18) or a GA <37 weeks (OR = 1.25, 95% CI: 0.86-1.82). No obvious publication bias was found based on the funnel plot and Egger's test. Removing any single study did not significantly alter the combined result in the sensitivity analysis. CONCLUSIONS Our study revealed that RBC transfusion is an independent risk factor for the development of ROP, especially in younger preterm infants. However, there seemed to be no evidence to support an effect of RBC transfusion on ROP in older groups. Further studies addressing this issue in older preterm neonates are warranted.
PICO Summary
Population
Preterm infants (18 studies, n= 15072).
Intervention
Received red blood cell (RBC) transfusion.
Comparison
Did not receive RBC.
Outcome
A random effect model revealed that RBC transfusion was significantly associated with retinopathy of prematurity (ROP), with moderate heterogeneity among the included studies (I2= 44.2%). Subgroup analysis indicated that RBC transfusion was more closely related to ROP in the group with a gestational age (GA) </=32 weeks but not in the groups with a GA </=34 weeks or a GA <37 weeks.
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Umbilical cord blood as a source for red-blood-cell transfusion in neonatology: a systematic review
Bianchi M, Papacci P, Valentini CG, Barbagallo O, Vento G, Teofili L
Vox Sanguinis. 2018;113((8):):713-725
Abstract
The prevention and treatment of anaemia in newborn patients made tremendous progress in the last decades. However, red-blood-cell (RBC) transfusions remain unavoidable in many neonates candidate to surgery and especially in preterm infants. In particular, anaemia occurring in neonates born at extremely low gestational age is actually severe and frequently requires transfusions. Several approaches have been explored to prevent or even to reduce the threshold and the frequency of RBC transfusions. Among these, umbilical cord blood (UCB) collection and processing to obtain RBC components for autologous or allogeneic transfusion have been extensively investigated. In this systematic review, we revised the literature concerning the use of UCB for either autologous or allogeneic transfusion purposes and we illustrated the rationale for a transfusion therapy tailored to extremely preterm neonates, based on RBC concentrates from allogeneic UCB donations.
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Withholding feeds and transfusion-associated necrotizing enterocolitis in preterm infants: a systematic review
Jasani B, Rao S, Patole S
Advances in Nutrition (Bethesda, Md.). 2017;8((5)):764-769.
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Abstract
Limited evidence exists to support the withholding of feeds during packed red blood cell (PRBC) transfusion to reduce the incidence of transfusion-associated necrotizing enterocolitis (TANEC) in preterm infants. The aim of the manuscript was to systematically review studies reporting the effect of implementing a policy of withholding feeds on the incidence of TANEC in preterm infants. The following databases were searched for relevant studies published between the databases' inception and December 2016: PubMed, Embase, the Cochrane Central Register of Controlled Trials, the Cumulative Index of Nursing and Allied Health Literature, and Pediatric Academic Societies Abstract Archive. Other relevant sources were also searched. There were no restrictions on study design. Studies reporting on the incidence of TANEC (stage ≥2 necrotizing enterocolitis within 48-72 h) after implementation of a policy of withholding feeds in the peritransfusion period in preterm infants were included. This meta-analysis used a random-effects model with assessment of quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. There were no randomized controlled trials (RCTs). Pooled results from 7 non-RCTs (n = 7492) showed that withholding feeds during PRBC transfusion significantly reduced the incidence of TANEC (RR: 0.47; 95% CI: 0.28, 0.80; P = 0.005; I2 = 11%). The overall quality of evidence was moderate on GRADE analysis. These findings suggest that withholding feeds during the peritransfusion period may reduce the risk of TANEC in preterm infants. Adequately powered RCTs are needed to confirm these findings.
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Transfusion-associated necrotizing enterocolitis re-evaluated: a systematic review and meta-analysis
Rai SE, Sidhu AK, Krishnan RJ
Journal of Perinatal Medicine. 2017;46((6):):665-676
Abstract
CONTEXT Significant controversy exists surrounding the possible association between recent packed red blood cell (PRBC) transfusion and the subsequent development of necrotizing enterocolitis (NEC) in infants. Previous studies and meta-analyses reporting a statistically significant association led to a practice change to withhold enteral feeds in the peri-transfusion period in many centers in an effort to prevent NEC; however, results from more recent studies do not support the existence of an association and, thus, question the validity of this practice change. OBJECTIVE This study aimed to perform a systematic review and meta-analysis to determine whether exposure to recent PRBC transfusion (defined as within 48 h) is associated with the subsequent development of NEC stage ≥II (Bell's criteria) in infants. METHODS Medline, Embase, CINAHL, and the Cochrane Library were searched from inception to October 7, 2015. A gray literature search was also performed. Studies comparing the risk of NEC in infants exposed and unexposed to recent PRBC transfusion were included. Thirteen studies met eligibility criteria, and 10 (n=15,675 infants) were included in the meta-analysis. Three authors independently extracted data, and meta-analysis was performed using a random effects model. RESULTS We found a statistically significant 45% reduction in the unadjusted odds of NEC in infants exposed to a recent PRBC transfusion (odds ratio=0.55, 95% confidence interval=0.31-0.98). CONCLUSION Our results show a protective effect of recent PRBC transfusion on the subsequent development of NEC. The practice of withholding enteral feeds during the peri-transfusion period should be re-evaluated in light of these results.
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Transfusion-associated necrotizing enterocolitis in preterm infants: an updated meta-analysis of observational data
Garg P, Pinotti R, Lal CV, Salas AA
Journal of Perinatal Medicine. 2017;46((6):):677-685
Abstract
BACKGROUND The number of observational studies that report an association between packed red blood cell (PRBC) transfusions and necrotizing enterocolitis (NEC) has increased. The primary objective of this study was to evaluate the association between PRBC transfusions and NEC in observational studies. METHODS Medline, Embase and Cochrane Library databases as well as the Pediatrics Academic Societies abstract archives were systematically searched to identify observational studies that investigated the association between PRBC transfusions and NEC. Key search terms included premature infant, blood transfusion and necrotizing enterocolitis. The generic inverse variance method with a random-effects model was used to meta-analyze selected studies. Odds ratios (ORs) and confidence intervals (CIs) were calculated. RESULTS A meta-analysis of 17 observational studies that reported the association between PRBC transfusions and NEC was performed. The meta-analysis revealed no evidence of an association between PRBC transfusions and a higher risk of NEC (OR: 0.96; 95% CI: 0.53-1.71; P=0.88). The effect estimates that suggested an association between PRBC transfusion and NEC in matched case-control studies (OR: 1.20; 95% CI: 0.58-2.47; P=0.63) differed from those reported in cohort studies (OR: 0.51; 95% CI: 0.34-0.75; P=<0.01). CONCLUSIONS This updated meta-analysis of predominantly low-to-moderate quality observational studies suggests that there is no significant association between PRBC transfusions and NEC. A higher quality of evidence on this topic is needed.
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10.
Washed versus unwashed red blood cells for transfusion for the prevention of morbidity and mortality in preterm infants
Keir AK, Wilkinson D, Andersen C, Stark MJ
The Cochrane Database of Systematic Reviews. 2016;((1)):CD011484.
Abstract
BACKGROUND Infants born very preterm often receive multiple red blood cell (RBC) transfusions during their initial hospitalisation. However, there is an increasing awareness of potential adverse effects of RBC transfusions in this vulnerable patient population. Modification of RBCs prior to transfusion, through washing with 0.9% saline, may reduce these adverse effects and reduce the rate of significant morbidity and mortality for preterm infants and improve outcomes for this high-risk group. OBJECTIVES To determine whether pre-transfusion washing of RBCs prevents morbidity and mortality in preterm infants. SEARCH METHODS We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), MEDLINE via PubMed (31 July 2015), EMBASE (31 July 2015), and CINAHL (31 July 2015). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA Randomised, cluster randomised, and quasi-randomised controlled trials including preterm infants (less than 32 weeks gestation) or very low birth weight infants (less than 1500 g), or both, who received one or more washed packed RBC transfusions. DATA COLLECTION AND ANALYSIS Two review authors independently assessed the eligibility of the trials. We identified four studies from the initial search. After further review of the full-text studies, we found one study meeting the selection criteria. MAIN RESULTS We included a single study enrolling a total of 21 infants for analysis in this review and reported on all-cause mortality during hospital stay, length of initial neonatal intensive care unit (NICU) stay (days), and duration of mechanical ventilation (days). There was no significant difference in mortality between the washed versus the unwashed RBCs for transfusion groups (risk ratio 1.63, 95% confidence interval (CI) 0.28 to 9.36; risk difference 0.10, 95% CI -0.26 to 0.45). There was no significant difference in the length of initial NICU stay between the washed versus the unwashed RBCs for transfusion groups (mean difference (MD) 25 days, 95% CI -21.15 to 71.15) or the duration of mechanical ventilation between the washed versus the unwashed RBCs for transfusion groups (MD 9.60 days, 95% CI -1.90 to 21.10). AUTHORS' CONCLUSIONS We identified a single small study. The results from this study show a high level of uncertainty, as the confidence intervals are consistent with both a large improvement or a serious harm caused by the intervention. Consequently, there is insufficient evidence to support or refute the use of washed RBCs to prevent the development of significant neonatal morbidities or mortality. Further clinical trials are required to assess the potential effects of pre-transfusion washing of RBCs for preterm or very low birth weight infants, or both, on short- and long-term outcomes.