Do feeding practices during transfusion influence the risk of developing necrotising enterocolitis in preterm infants?

Our evidence‐based review set out to answer the clinical question ‘In a preterm infant (patient) with anaemia of prematurity, do feeding practices (intervention) during blood transfusion reduce the risk of developing transfusion‐associated necrotising enterocolitis (outcome)’? We found limited evidence that withholding feeding during red blood cell transfusion in preterm infants may reduce the risk of development of transfusion‐associated necrotising enterocolitis. As clinical equipoise seemingly exists, it seems reasonable for individual units to make their own decisions regarding whether to withhold or continue enteral feeds during red blood cell transfusion until further evidence is available. The UK‐based Withholding Enteral Feeds Around Transfusion (WHEAT) trial, a nation‐wide multi‐centre ‘opt‐out’ randomised controlled study, hopefully will definitively answer our clinical question. Further research in other areas of neonatal care, using this innovative study design, is needed and it is exciting to see such a study underway.     

Red blood cell transfusion in newborn infants

Red blood cell transfusion is an important and frequent component of neonatal intensive care. The present position statement addresses the methods and indications for red blood cell transfusion of the newborn, based on a review of the current literature. The most frequent indications for blood transfusion in the newborn are the acute treatment of perinatal hemorrhagic shock and the recurrent correction of anemia of prematurity. Perinatal hemorrhagic shock requires immediate treatment with large quantities of red blood cells; the effects of massive transfusion on other blood components must be considered. Some guidelines are now available from clinical trials investigating transfusion in anemia of prematurity; however, considerable uncertainty remains. There is weak evidence that cognitive impairment may be more severe at follow-up in extremely low birth weight infants transfused at lower hemoglobin thresholds; therefore, these thresholds should be maintained by transfusion therapy. Although the risks of transfusion have declined considerably in recent years, they can be minimized further by carefully restricting neonatal blood sampling.     

The contribution of red blood cell transfusion to neonatal morbidity and mortality

Anaemia of prematurity will affect 90% of all very preterm infants, resulting in at least one red blood cell (RBC) transfusion. A significant proportion of preterm infants require multiple transfusions over the course of hospital admission. Growing evidence supports an association between transfusion exposure and adverse neonatal outcomes. In adults, transfusion‐associated sepsis, transfusion‐related acute lung injury and haemolytic reactions are the leading causes of transfusion‐related morbidity and mortality; however, these are seldom recognised in newborns. The association between transfusion and adverse outcomes remains inconclusive. However, the evidence from preclinical studies demonstrates that RBC products can directly modulate immune cell function, a pathway termed transfusion‐related immunomodulation (TRIM), which may provide a mechanism linking transfusion exposure with neonatal morbidities. Finally, we discuss the impact of TRIM on transfusion medicine, how we may address these issues and the emerging areas of research aimed at improving the safety of transfusions in this vulnerable population.     

儿童成分输血与输全血的选择

目前，临床实践中成分输血已普遍应用，全血输血仅用于少数临床场景。成分输血的优点在于疗效好、副反应小，节约血资源，便于保存运输。常用的成分输血制品种类包括红细胞、血小板、新鲜冰冻血浆及冷沉淀等。该文旨在对儿童成分输血中所涉及的各主要血液成分的选择、输注适应证、输注阈值、输注剂量、输注速度和特殊要求等临床问题进行探讨。     

Practical guide to red blood cell transfusion in paediatrics

Red cell transfusion is common in paediatric practice and indicated in haemorrhagic shock, anaemia and certain inherited haematological diseases. As with other blood products there are risks associated with their administration and improper use. Extensive national and local guidance is available in the UK in order to maintain safe transfusion practice. This article summarises the rationale behind red cell transfusion and offers a practical guide to clinical decision making in the acute hospital setting.     

A practical guide to red blood cell transfusion in children

Red cell transfusion is common in paediatric practice and indicated in haemorrhagic shock, anaemia and certain inherited haematological diseases. As with other blood products there are risks associated with their administration and improper use. Extensive guidance is available in the UK in order to maintain adequate haemovigilance and safe transfusion practice. This article summarises the rationale behind red cell transfusion and offers a practical guide to clinical decision making in the acute hospital setting.     

中国新生儿重症监护病房极早及超早产儿非红细胞血制品使用现况

目的分析2019年中国新生儿协作网(CHNN)新生儿重症监护病房住院的极早及超早产儿非红细胞血制品的使用现状及单位间差异,为探讨输注合理性与规范性提供证据。方法基于CHNN大规模极早产儿队列数据库进行横断面研究,纳入2019年生后24 h内收入CHNN 57家NICU治疗、出生胎龄<32周且接受完整治疗的6598例早产儿。收集患儿一般情况,描述不同出生胎龄、不同病情危重程度早产儿非红细胞血制品(血小板、血浆、人免疫球蛋白、白蛋白、冷沉淀和凝血酶原复合物)的使用率及次数。输注过至少1种非红细胞血制品即为输注组。采用两独立样本t检验、秩和检验或χ²检验进行输注组和非输注组组间比较。使用线性回归模型对单位间输注率和单位特征进行相关性分析。结果6598例早产儿出生胎龄为30.0(28.7,31.0)周,出生体重为(1353±312)g,女2877例(43.6%)。2816例(42.7%)早产儿为输注组,输注次数为3(1,6)次。与未输注组相比,输注组患儿出生胎龄更小(Z=17.62,P<0.01),出生体重更低(t=18.64,P<0.01),小于胎龄、多胎以及产房高级复苏比例均更高(χ²=31.06、12.82、287.52,均P<0.01),女婴比例以及本院出生比例则均更低(χ²=10.68、78.23,均P<0.01)。总研究人群中,使用率高的非红细胞血制品依次为白蛋白25.4%(1674例)、人免疫球蛋白21.5%(1417例)、血浆18.9%(1245例)。901例超早产儿中,60.4%(544例)输注过非红细胞血制品,使用次数4(2,8)次;5697例极早产儿中,39.9%(2272例)输注过非红细胞血制品,使用次数3(1,6)次。病情危重和非危重组中非红细胞血制品输注率分别达62.2%(1693/2723)和29.0%(1123/3875),输注次数分别为4(2,7)次和2(1,4)次。57家NICU中,调整与非红细胞血制品输注相关的因素后,各单位间极早及超早产儿非红细胞血制品输注率差异有统计学意义(校正χ²=153.48,P<0.01)。结论2019年中国NICU救治的极早及超早产儿中,接近半数曾接受非红细胞血制品输注,各单位非红细胞血制品使用率存在巨大差异。     

Nutrition for the micro preemie: Beyond milk

Nutritional support is a fundamental component of the care of the extremely preterm infant, including the “micro preemie” (here defined as a baby born weighing less than 500 g), but goes beyond considerations of milk as a food. This is because milk from an infant's own mother, unlike currently available substitutes, additionally provides invaluable non-nutritive benefits.Nutritional support requires suitable devices or techniques to administer nutrients enterally or intravenously, products shown to be safe in preterm populations, and efficacy demonstrated in respect of important functional outcomes. Sadly, preterm feeding remains characterised by a deficit of evidence. In this chapter, we will briefly describe the history of preterm nutrition, discuss current enteral and parenteral practice, important evidence gaps, a summary of approaches for evaluating nutritional practice, and key considerations for future endeavour. Our discussion refers to all extremely preterm infants and it not confined to the micro preemie.     

When to transfuse preterm babies

The physiological anaemia experienced by preterm babies is exacerbated by common care practices such as early clamping of the umbilical cord at birth and gradual exsanguination by phlebotomy for laboratory monitoring. The need for subsequent transfusion with red blood cells can be reduced by delaying cord clamping for 30-60 s in infants who do not require immediate resuscitation. The need for transfusions can be further reduced by limiting phlebotomy losses, providing good nutrition, and using standard guidelines for transfusion based on haemoglobin or haematocrit. What those guidelines should be is not clear. Analysis of two recent large clinical trials comparing restrictive and liberal transfusion guidelines leads to several conclusions. Restrictive transfusion guidelines may reduce the number of transfusions given, but there is no reduction in donor exposures if a single-donor transfusion programme is used. There is some evidence that more liberal transfusion guidelines may help to prevent brain injury, but information on the impact of transfusion practice on long-term outcome is lacking. Until further guidance emerges, transfusion thresholds lower than those used in the two trials should not be used, as there is no evidence that lower thresholds are safe.     

Rheological properties of blood and their possible role in the circulation and development of intracranial hemorrhage in preterm infants

Blood viscosity and other rheological properties of blood have important effects on blood circulation. In preterm infants, blood viscosity (at given hematocrit), plasma viscosity and red cell aggregation are decreased compared to term neonates and adults. In addition, the Fahraeus-Lindqvist effect (i.e., decrease in blood viscosity with decreasing vessel diameter) is more pronounced in preterm infants. This suggests that blood flow through arteries, arterioles and veins is facilitated in preterm infants. The large neonatal red cells are less filterable and less able to enter small capillaries than adult red cells. This suggests that the passage of neonatal red cells through narrow capillaries and splenic pores is impaired. The high risk of intracranial hemorrhage in small preterm infants may in part result from poor red cell aggregation, impeded passage of their large red cells through narrow cerebral capillaries and raised blood viscosity due to rapid transfusion of adult blood.     

Transfusion therapy in critically ill children

Critically ill children in pediatric intensive care units are commonly indicated for blood transfusion due to many reasons. Children are quite different from adults during growth and development, and that should be taken into consideration. It is very difficult to establish a universal transfusion guideline for critically ill children, especially preterm neonates. Treating underlying disease and targeted replacement therapy are the most effective approaches. Red blood cells are the first choice for replacement therapy in decompensated anemic patients. The critical hemoglobin concentration may be higher in critically ill children for many reasons. Whole blood is used only in the following conditions or diseases: (1) exchange transfusion; (2) after cardiopulmonary bypass; (3) extracorporeal membrane oxygenation; (4) massive transfusion, especially in multiple component deficiency. The characteristics of hemorrhagic diseases are so varied that their therapy should depend on the specific needs associated with the underlying disease. In general, platelet transfusion is not needed when a patient has platelet count greater than 10,000/mm3 and is without active bleeding, platelet functional deficiency or other risk factors such as sepsis. Patients with risk factors or age less than 4 months should be taken into special consideration, and the critical thrombocyte level will be raised. Platelet transfusion is not recommended in patients with immune-mediated thrombocytopenia or thrombocytopenia due to acceleration of platelet destruction without active bleeding or life-threatening hemorrhage. There are many kinds of plasma-derived products, and recombinant factors are commonly used for hemorrhagic patients due to coagulation factor deficiency depending on the characteristics of the diseases. The most effective way to correct disseminated intravascular coagulation (DIC) is to treat the underlying disease. Anticoagulant therapy is very important; heparin is the most common agent used for DIC but the results are usually not satisfactory. Antithrombin III, protein C, or recombinant thrombomodulin has been used successfully to treat this condition. For reducing the risk of organism transmission and adverse reactions resulting from blood transfusion, the following measures have been suggested: (1) replacement therapy using products other than blood (e.g., erythropoietin, iron preparation, granulocyte colony-stimulating factor); (2) special component replacement therapy for specific diseases; (3) autotransfusion; (4) subdividing whole packed blood products into smaller volumes to reduce donor exposure; (5) advances in virus-inactivating procedures. To avoid viral transmission, vapor-heated or pasteurized products and genetic recombinant products are recommended. Cytomegalovirus (CMV)-seronegative blood, leukoreduced and/or irradiated blood are recommended for prevention of CMV infection, graft-versus-host-disease and alloimmunization in neonate and immunocompromised patient transfusion. There is no reason to prescribe a plasma product for nutritional supplementation because of the risk of complications. The principle: complications of transfusion must be avoided, the rate of blood exposure should be reduced and the safety of the transfused agents or components should be maintained must always be kept in mind.     

Guidelines for auditing pediatric blood transfusion practices.

Although transfusion of blood products is an essential and potentially life-saving measure, not all blood transfusions are beneficial to patients. The associated risks, particularly transfusion-transmitted viral illnesses, such as hepatitis and acquired immunodeficiency syndrome, require that careful consideration be given before a decision is made to transfuse any blood product. Many institutions have established a local committee to monitor transfusion practices and audit such practices regularly. To assist in this task, the Pediatric Hemotherapy Committee of the American Association of Blood Banks has developed guidelines for the conduct of pediatric blood transfusion audits. These guidelines, summarized herein, cover transfusion of red blood cells, platelets, white blood cells, fresh-frozen plasma, albumin, and clotting concentrates. The use of cytomegalovirus low-risk and irradiated blood products is also discussed. Throughout the report, special attention is given to the transfusion needs of newborn infants.     

Red blood cell transfusions in newborn infants: Revised guidelines

In general, health care professionals taking care of high risk infants in neonatal intensive care units have become more restrictive in their use of red blood cell transfusion over the past 10 years. The present statement is intended for those caring for high risk newborn infants (preterm to one month of age). The objectives of this statement are to provide guidelines to reduce the incidence of anemia in preterm and term infants, to identify strategies to decrease the need for red blood cell transfusions and to limit donor exposure in this population. Recommendations for red blood cell transfusions are included.     

Transfusion management strategies: a survey of practicing pediatric hematology/oncology specialists

BACKGROUND: Little is known about the criteria used by pediatric oncologists for the transfusion of red blood cells and platelets to pediatric oncology patients. PROCEDURE: Data regarding red blood cell and platelet transfusion practices were collected with an internet-based survey of physician members of the American Society for Pediatric Hematology/Oncology (ASPH/O). Respondents were asked to define platelet and red blood cell transfusion thresholds in a variety of clinical scenarios, and to describe criteria for dealing with cytomegalovirus (CMV) transmission from blood products, platelet dosing strategies, and prevention of RhD alloimmunization. RESULTS: The overall response rate was 31.4% (264 of 841). Of the respondents, 76% indicated that their institution had defined criteria for acceptable transfusion practice; of these respondents, 114 (57%) indicated that there were special guidelines for pediatric oncology patients. Examination of the distribution of threshold platelet counts and hemoglobin levels that would prompt transfusion indicated a wide range of transfusion practice in commonly encountered clinical scenarios. Similar variability in practice was evident in platelet dosing strategies, CMV prevention strategies, and in the use of anti-D in RhD-negative patients who received RhD-positive platelets. CONCLUSIONS: This current survey demonstrates that transfusion practices vary widely among pediatric hematology/oncology specialists and that prospective clinical trials may be necessary to determine optimal criteria for blood product support in pediatric oncology patients.     

Blood transfusion increases radical promoting non-transferrin bound iron in preterm infants

BACKGROUND: Blood transfusion has been recognised as a risk factor for the development of retinopathy of prematurity (ROP) or chronic lung disease (CLD) in preterm infants, but the precise mechanism involved is not understood. AIM: To investigate the level of non-transferrin bound "free" iron, which has the potential to promote the generation of reactive oxygen species, and its redox status in the plasma of preterm infants immediately before and after blood transfusion. METHODS: Twenty one preterm infants with a median gestational age and birth weight of 27 weeks and 1021 g respectively were prospectively enrolled in the study. Sixteen of the 21 infants developed ROP and/or CLD. The infants were transfused with concentrated red blood cells at a median age of 32 days. The plasma concentration of total bleomycin detectable iron (BDI) was measured and also the ferrous iron (Fe(2+)) activity by bleomycin-iron complex dependent degradation of DNA. RESULTS: Even before blood transfusion, BDI was detectable in one third of the blood samples, and all but one sample had ferrous iron activity. After transfusion, both BDI and ferrous iron activity were significantly increased, in contrast with the situation in full term infants. Plasma ascorbic acid (AA) concentration was significantly decreased after blood transfusion, whereas the level of its oxidation product, dehydroascorbic acid (DHAA), and the DHAA/AA ratio were significantly increased compared with before the transfusion. The activity of plasma ferroxidase, which converts iron from the ferrous to the ferric state, was appreciably decreased in preterm infants, as expected from their very low plasma caeruloplasmin concentration. CONCLUSIONS: Plasma non-transferrin bound iron was significantly increased in preterm infants after blood transfusion and existed partly in the ferrous form, because of the low ferroxidase activity and the reduction of ferric iron (Fe(3+)) by ascorbic acid. This finding was specific to preterm infants and was not observed in full term infants after blood transfusion. Non-transferrin bound "free" iron may catalyse the generation of reactive oxygen species, which may be responsible for the clinical association of blood transfusion with ROP and CLD.     

Short-term effects of blood transfusion on blood volume and resting peripheral blood flow in preterm infants

The effects of blood transfusion on cardiac output and blood pressure are variable, but resting peripheral blood flow (RPBF) may be a sensitive indicator of changes in blood volume. The purpose of this investigation was to study the effects of red cell transfusion on blood volume (Evans blue), blood pressure, RPBF in the leg (strain-gauge plethysmography) and blood viscosity (cone-plate viscometer) in preterm infants during the first week after birth. Fourteen infants with mean ± SD birth weight of 1658 ± 429 g, gestational age 33 ± 3 weeks and postnatal age 64 ± 40 h received 18 ±4 ml/kg of packed red cells (red cells 11±2 ml/kg, plasma 7± 1 ml/kg) because their hematocrit was less than 0.45 l/l. Mean blood volume before transfusion was 88±15 ml/kg. The increase in blood volume (9 ±4 ml/kg) measured 4 to 6 h after transfusion was smaller than the transfused volume (18 ± 4 ml/kg), due to a shift of plasma to the extravascular space. The plasma shift increased with increasing pretransfusion blood volume ( r = 0.70; p = 0.007). Red cell transfusion caused an increase in RPBF by 25% ( p <0.01), whereas systolic blood pressure (BP) increased by only 12%. Peripheral resistance (R = BP/RPBF) decreased by 9% (p<0.01). Blood viscosity (±) increased by 21'% ( p <0.001) and vascular hindrance (R/±) decreased by 24% ( p < 0.001), indicating vasodilatation of limb arteries. The increase in RPBF and the decrease in hindrance were particularly pronounced in infants with high pretransfusion blood volume. We conclude that the increase in blood volume after transfusion is not proportional to the transfused volume and that RPBF increases more than systolic blood pressure with increasing blood volume. The increase in RPBF can be explained by vasodilatation of limb arteries and by increased blood pressure.     

Effects of blood transfusion on left ventricular output in premature babies

Objective:   To investigate the acute effects of red blood cell transfusion on haemodynamics in preterm babies.
Setting:   A neonatal unit in a University Hospital.
Patients:   Preterm babies whose postnatal age was less than four weeks and who required red blood cell transfusion.
Measurement:   Cardiac output and left ventricular systolic function was determined using Doppler echocardiography before, one hour and 24  h after red blood cell transfusion. Blood pressure and haematocrit were also recorded at the same time. Mixed-effects regression model was used to analyse the effect of blood transfusion on left ventricular function and cardiac output.
Results:   57 preterm babies were recruited. Univariate analysis showed that cardiac index decreased significantly 24  h after transfusion ( P <0.05). Systemic red cell transport increased by an average of 11.1% 24  h after transfusion ( P <0.05). Multivariate analysis showed that the cardiac index was negatively associated with haematocrit and the index was higher in male babies.
Conclusion:   There was a significant drop in cardiac index and an increase in systemic red cell transport 24  h after transfusion in premature babies.     

Management of infants with chronic lung disease of prematurity in China

With improved survival of very low birth weight infants in China over the last decade, chronic lung disease of prematurity (CLD) is only now becoming prevalent. As a result the management of CLD in China is only now beginning. In this paper, we describe the practice of managing these infants with as much evidence base as possible but often the management is based on other published papers in China and elsewhere and other people's personal experience. It appears that oxygen therapy is important to the survival of CLD infants but blood oxygen concentrations must be monitored closely in infants needing oxygen supplementation. We aim for a target range for oxygen saturation range of between 90%-95% to prevent retinopathy of prematurity. Although dexamethasone is effective in the treatment of CLD particularly extubation of preterm infants from mechanical ventilation, we restrict its use in severe infant due to their side effects. We have little experience of home oxygen and are only now setting up management protocols for oxygen use for CLD in both hospital and at home. We hope that the survival and outlook for these infants with CLD will improve over the next few years.     

Factors related to transfusion in very low birthweight infants treated with erythropoietin.

The need for red cell transfusions is reduced but not eliminated by recombinant human erythropoietin (rhEPO) in very low birthweight (VLBW) infants. To detect factors associated with the decision to transfuse VLBW infants during rhEPO treatment and to explain rhEPO ''non-responders'', the subgroup of those 120 VLBW infants who were treated with rhEPO 750 IU/kg per week in the second European Multicentre rhEPO Trial was evaluated. Sixty (50%) infants received at least one transfusion during erythropoietin treatment. Transfusion was frequent in infants with extremely low birthweight (79% for 750-999 g), low gestational age (70% for < or = 28 weeks), low initial haematocrit or low initial reticulocyte count (61% for haematocrit < or = 0.48 and reticulocytes < or = 9%, respectively). Considerable differences among centres were found for sampling blood loss, iron supply, and transfusion rate, which ranged from 13% to 73% and was related to the volume of diagnostic blood loss (19% vs 80% for blood loss < 1 vs > or = 1 ml/kg per day). The prognostic variables birthweight, initial haematocrit, and gestational age were found to be most predictive for transfusion. To improve rhEPO response in VLBW infants, there is a need to minimise diagnostic blood loss, to prevent iron deficiency, and to develop rational criteria for transfusion in preterm infants.     

Blood and blood component therapy in neonates

Blood component therapy is a very common intervention practiced in newborns; nearly 85% of extremely low birth weight (ELBW) babies get transfusions during their hospital stay. However, there are no set guidelines for transfusion of blood component therapy in newborns. This protocol includes available types of blood components, their methods of preparation, indications and side effects of transfusion, in relation to newborns.