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Effect of Early Erythropoietin on Retinopathy of Prematurity: A Stratified Meta-Analysis
Fischer, H. S., Reibel, N. J., Bührer, C., Dame, C.
Neonatology. 2023;:1-11
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Editor's Choice
Abstract
BACKGROUND Recombinant human erythropoietin (rhEPO) lost its role in minimizing red blood cell transfusion in very preterm infants after it had been associated with severe retinopathy of prematurity (ROP). Previous systematic reviews did not stratify ROP by gestation and birth weight (BW). OBJECTIVES The aim of this study was to investigate the effect of early prophylactic rhEPO on ROP in a stratified meta-analysis of randomized controlled trials (RCTs). METHODS The databases EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched in January 2022 and complemented by citation searching. RCTs comparing early rhEPO treatment with no treatment or placebo were selected if they were published in a peer-reviewed journal and reported ROP outcomes. Previously unpublished data were requested from the study authors to allow stratified analyses by gestational age (GA) and BW. Data were extracted and analyzed using the standard methods of the Cochrane Neonatal Review Group. Pre-specified outcomes were "ROP stage ≥3" (primary outcome) and "any ROP." RESULTS Fourteen RCTs, comprising 2,040 infants of <29 weeks of GA, were included for meta-analysis. Data syntheses showed no effects of rhEPO on ROP stage ≥3 or on any ROP, neither in infants of <29 weeks GA, nor in infants of <1,000 g BW, nor in any GA strata. The risk ratio (95% confidence interval) for ROP stage ≥3 in infants of <29 weeks of GA was 1.13 (0.84, 1.53), p = 0.41 (quality of evidence: moderate). CONCLUSIONS The present meta-analysis detected no effects of early rhEPO on ROP in any comparison, but most stratified analyses were limited by low statistical power.
PICO Summary
Population
Infants of <29 weeks of gestational age (GA), (14 randomised controlled trials, n= 2,040).
Intervention
Early recombinant human erythropoietin (rhEPO).
Comparison
No treatment or placebo.
Outcome
Data syntheses showed no effects of rhEPO on retinopathy of prematurity (ROP) stage ≥3 or on any ROP, neither in infants of <29 weeks GA, nor in infants of <1,000 g birth weight, nor in any GA strata. The risk ratio for ROP stage ≥3 in infants of <29 weeks of GA was 1.13; 95% confidence interval [0.84, 1.53], (quality of evidence: moderate).
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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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Sustained low-dose prophylactic early erythropoietin for improvement of neurological outcomes in preterm infants: A systematic review and meta-analysis
Liang L, Yu J, Xiao L, Wang G
Journal of affective disorders. 2021;282:1187-1192
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Editor's Choice
Abstract
The aim of this meta-analysis was conducted to assess the effects of different doses of prophylactic rhEPO on neurodevelopmental outcomes and provide reference for rational drug use. The primary outcome was the number of infants with a Mental Developmental Index (MDI) <70 on the Bayley Scales of Infant Development. Five RCTs, comprising 2282 infants, were included in this meta-analysis. Overall, prophylactic rhEPO administration reduced the incidence of infants with an MDI <70, with an odds ratio (95% confidence interval) of 0.55 (0.38-0.79), P <0.05. The low-dose rhEPO subgroup was superior to the placebo subgroup, with an OR (95% CI) of 0.47 (0.25-0.87), P <0.05. However, high-dose rhEPO subgroup had no significant impact on MDI <70 in infants <28 weeks' gestational age. The definitions of the secondary outcome showed that there was no significant effect of rhEPO on cerebral palsy. For neonatal complications, although four studies showed that there were no differences in the pooled results of BPD and ICH events between rhEPO treatment and placebo, the ICH events were significantly lower in the low-dose rhEPO (OR 0.36; 95% CI 0.23-0.59). In addition, in the pooled results of NEC and ROP events, there were significant differences between the two groups (OR 0.63; 95% CI 0.43-0.93) (OR 0.80; 95% CI 0.65-0.98). And the NEC events were significantly lower in the low-dose rhEPO (OR 0.45; 95% CI 0.27-0.73). Sustained low-dose prophylactic early erythropoietin might be more superior than high-dose for improvement of neurological outcomes and several neonatal complications in preterm infants.
PICO Summary
Population
Children who were born prematurely, aged between 18-24 months corrected age (n= 2,282, 5 RCTs).
Intervention
High-dose or low-dose prophylactic erythropoietin (rhEPO).
Comparison
Placebo.
Outcome
Overall, prophylactic rhEPO administration reduced the incidence of infants with a mental development index (MDI) <70, with an odds ratio (95% confidence interval) of 0.55 (0.38-0.79). The low-dose rhEPO subgroup was superior to the placebo subgroup, with an OR (95% CI) of 0.47 (0.25-0.87). However, high-dose rhEPO subgroup had no significant impact on MDI <70 in infants <28 weeks' gestational age. There was no significant effect of rhEPO on cerebral palsy. For neonatal complications, although four studies showed that there were no differences in the pooled results of bronchopulmonary dysplasia and intracranial haemorrhage (ICH) events between rhEPO treatment and placebo, the ICH events were significantly lower in the low-dose rhEPO (OR 0.36; 95% CI 0.23-0.59). In addition, in the pooled results of necrotizing enterocolitis (NEC) and retinopathy of prematurity events, there were significant differences between the two groups (OR 0.63; 95% CI 0.43-0.93), (OR 0.80; 95% CI 0.65-0.98). And the NEC events were significantly lower in the low-dose rhEPO (OR 0.45; 95% CI 0.27-0.73).
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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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6.
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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The Role of Platelets in Premature Neonates with Intraventricular Hemorrhage: A Systematic Review and Meta-Analysis
Grevsen AK, Hviid CVB, Hansen AK, Hvas AM
Seminars in thrombosis and hemostasis. 2019
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Editor's Choice
Abstract
Intraventricular hemorrhage (IVH) affects up to 22% of extremely low birth weight neonates. Impaired coagulation might contribute to the pathogenesis of IVH. The aims of this study were to summarize the current knowledge on the role of platelet indices in premature neonates with IVH and to provide an overview of secondary hemostasis parameters as well as fibrinolysis in premature neonates with IVH. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases PubMed, Embase, Scopus, and Web of Science were searched on March 7, 2019, without time restrictions. In total, 30 studies were included. Most studies investigated the significance of platelet counts and/or mean platelet volume (MPV). The meta-analysis showed that at day 1 of life, neither platelet count nor MPV differed significantly between neonates with or without IVH (standardized mean difference [SMD]: -0.15 x 10(9)/L, 95% confidence interval [CI]: -0.37 to 0.07 and SMD: 0.22 fl, 95% CI: -0.07 to 0.51, respectively). However, platelet counts < 100 x 10(9)/L were associated with an increased risk of IVH. Secondary hemostasis parameters did not differ between neonates with and without IVH. Fibrinolysis was only sparsely investigated. In conclusion, platelet counts < 100 x 10(9)/L were associated with an increased risk of IVH in premature neonates. The impact of secondary hemostasis was only sparsely investigated but seemed to be minor, and the role of fibrinolysis in IVH in premature neonates needs further research. Whether reduced platelet function is associated with an increased risk of IVH in premature neonates remains to be investigated.
PICO Summary
Population
Extremely low birth weight neonates (30 studies).
Intervention
Platelet indices in neonates with IVH.
Comparison
Platelet indices in neonates without IVH.
Outcome
The meta-analysis showed that at day 1 of life, neither platelet count nor MPV differed significantly between neonates with or without IVH. However, platelet counts < 100 x 10(9)/L were associated with an increased risk of IVH. Secondary hemostasis parameters did not differ between neonates with and without IVH. Fibrinolysis was only sparsely investigated.
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What clinical practice strategies have been shown to decrease incidence rates of intraventricular haemorrhage in preterm infants?
Howes A, Hilditch C, Keir A
Journal of paediatrics and child health. 2019;55(10):1269-1278
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Editor's Choice
Abstract
AIM: To answer the clinical question 'In infants about to be delivered and admitted to neonatal units, what clinical practice strategies, compared to standard care, have been shown to decrease incidence rates of intraventricular haemorrhage (IVH)?' METHODS MEDLINE via Ovid (1943 to 5 January 2018), Embase via Ovid (1974 to 5 January 2018) and the Cochrane Library (5 January 2018) were searched for relevant articles. RESULTS A total of 478 articles, after the removal of duplicates, were found and screened by title and abstract. Forty full-text articles were subsequently reviewed, and 19 were included as relevant to the structured clinical question. An additional article was included based on expert advice. CONCLUSION There are various levels of research evidence for clinical practice strategies to decrease the incidence rates of IVH. Higher-quality evidence suggests that antenatal corticosteroids decrease the rates of IVH, and multiple evidence-based intervention bundles implemented in the neonatal unit are associated with decreased rates of IVH.
PICO Summary
Population
Infants at high risk of intraventricular haemorrhage (IVH) due to prematurity (20 studies).
Intervention
Clinical practice strategies to decrease (IVH) incidence rates, including: perinatal and delivery room practices, respiratory and cardiovascular management, and quality improvement strategies.
Comparison
Standard care.
Outcome
Higher-quality evidence suggested that antenatal corticosteroids decreased the rates of IVH, and multiple evidence-based intervention bundles implemented in the neonatal unit were associated with decreased rates of IVH.