Red blood cell (RBC) transfusions in the neonate

INTRODUCTION — Transfusion of red blood cells (RBCs) can be lifesaving in patients with severe anemia. However, RBC transfusion has risks, including volume overload, transmission of infectious agents, transfusion reactions, and various immunologic consequences.

The rationale and indications for RBC transfusion in neonates, as well as selection of RBC products and their administration will be reviewed here. Other aspects of transfusion in neonates, infants, and children are discussed in separate topic reviews:

●(See "Anemia of prematurity (AOP)".)

●(See "Alloimmune hemolytic disease of the newborn: Postnatal diagnosis and management".)

●(See "Red blood cell transfusion in infants and children: Indications".)

●(See "Red blood cell transfusion in infants and children: Selection of blood products".)

●(See "Red blood cell transfusion in infants and children: Administration and complications".)

●(See "Pretransfusion testing for red blood cell transfusion".)

GENERAL PRINCIPLES

Rationale for transfusion — The principal rationale for RBC transfusion in neonates is to prevent or reverse tissue hypoxia due to reduced oxygen availability. Symptoms of anemia (eg, increased heart rate, apnea, need for increased respiratory support, poor weight gain, acidosis) occur when the RBC mass is not adequate to meet the oxygen demands of tissues. An RBC transfusion provides an immediate increase in oxygen delivery to tissues and is an effective and rapid intervention to treat severe symptomatic anemia. Optimal transfusion practice aims to avoid unnecessary transfusions while ensuring that a transfusion isn't withheld from neonates who would truly benefit from it. However, based on the available data, it is not possible to precisely define a minimum hemoglobin (Hgb) or hematocrit (Hct) level required for sufficient oxygen delivery in neonates. Nevertheless, clinical trials have demonstrated that using more a restrictive threshold for transfusion does not increase morbidity and mortality compared with using a more liberal threshold [1-5]. (See 'Restrictive versus liberal strategy' below.)

Risks — Although rare, transfusions have well-established risks, which are discussed in detail separately [6,7]:

●Transfusion-transmitted infections (see "Epidemiology and transmission of hepatitis C virus infection" and "Blood donor screening: Medical history", section on 'Screening for infectious risks' and "Blood donor screening: Laboratory testing", section on 'Infectious disease screening and surveillance')

●Immune-mediated transfusion reactions (see "Immunologic transfusion reactions")

●Graft-versus-host disease (see "Transfusion-associated graft-versus-host disease")

●Transfusion related acute lung injury (TRALI) (see "Transfusion-related acute lung injury (TRALI)")

●Transfusion associated circulatory overload (TACO) (see "Transfusion-associated circulatory overload (TACO)")

●Toxic effects of anticoagulants or preservatives (see "Red blood cell transfusion in infants and children: Administration and complications" and "Red blood cell transfusion in infants and children: Administration and complications", section on 'Metabolic toxicity')

In addition, observational studies suggest that neonatal RBC transfusions are associated with increased risk of mortality and the following adverse outcomes [8-18]. However, a causal relationship has not been firmly established. These associations may be due, at least in part, to selection bias (ie, sicker neonates are more likely to receive transfusions).

●Neurodevelopmental impairment (see "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors")

●Venous thromboembolism (see "Neonatal thrombosis: Clinical features and diagnosis")

●Necrotizing enterocolitis (see "Neonatal necrotizing enterocolitis: Pathology and pathogenesis", section on 'Anemia and red blood cell transfusion')

●Extension of intraventricular hemorrhage (IVH) (see "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis")

●Retinopathy of prematurity (see "Retinopathy of prematurity (ROP): Risk factors, classification, and screening", section on 'Risk factors')

●Bronchopulmonary dysplasia (see "Bronchopulmonary dysplasia (BPD): Clinical features and diagnosis")

These findings underscore the need to carefully weigh the decision to transfuse, particularly in nonemergency situations.

Restrictive versus liberal strategy — For most neonates, we recommend a restrictive transfusion strategy (ie, giving fewer transfusions and transfusing at a lower Hgb level) over a liberal transfusion strategy (ie, giving more transfusions, transfusing at a higher Hgb level). Our approach is based on Hgb/Hct levels and the clinical status of the infant (table 1). (See 'Transfusion thresholds' below.)

This practice is supported by multicenter clinical trials involving preterm infants in which restrictive transfusion thresholds reduced transfusions without increasing mortality or serious morbidity [1-5]. The two largest trials were the TOP trial (Transfusion of Prematures) and the ETTNO trial (Effects of liberal versus restrictive Transfusion Thresholds on survival and Neurocognitive Outcomes) [4,5]. In both trials, neurodevelopmental outcomes were similar between restrictive and liberal transfusion groups. Further details of these trials are provided separately. (See "Anemia of prematurity (AOP)", section on 'Transfusion'.)

Additional support comes from trials in older infants and children, which also reported similar outcomes between restrictive and liberal transfusion groups. These data are discussed separately. (See "Red blood cell transfusion in infants and children: Indications", section on 'Critical illness'.)

PREVALENCE OF TRANSFUSION — The overall prevalence of transfusion across all neonates is approximately 0.4 to 0.5 percent (4 to 5 per 1000 live births) [19,20]. Among neonates admitted to the neonatal intensive care unit (NICU), approximately 15 to 20 percent receive at least one transfusion [21,22]. The prevalence varies by gestational age (GA), with the highest prevalence among extremely preterm (EPT) and extremely low birth weight (ELBW) neonates. For preterm neonates ≤32 weeks GA, the prevalence is approximately 20 percent. For EPT and ELBW neonates, the prevalence is approximately 60 to 75 percent [4,21,22]. The prevalence is lower among ELBW infants treated with erythropoiesis stimulating agents, as discussed separately. (See "Anemia of prematurity (AOP)", section on 'Erythropoiesis stimulating agents (ESAs)'.)

The prevalence of transfusion in preterm neonates has decreased over time due to the shift towards more restrictive transfusion practices. In a multicenter retrospective study conducted over nine years, rates of RBC transfusion among preterm neonates ≤30 weeks GA declined from 62 percent in the study's earlier era (2004 to 2006) to 53 percent in the later era (2010 to 2012) [22]. The decline was most notable among neonates born at 26 to 29 weeks GA.

INDICATIONS FOR TRANSFUSION — Common reasons for RBC transfusion in neonates include perinatal blood loss, anemia of prematurity, and iatrogenic withdrawal of blood for laboratory testing. The following sections review criteria for determining the need for transfusion in different clinical circumstances.

Transfusion thresholds — For most neonates, we recommend using a restrictive transfusion strategy (ie, transfusing at a lower hemoglobin (Hgb) level) rather than a liberal strategy (transfusing at a higher Hgb level). However, clinicians should not use the Hgb/hematocrit (Hct) alone as the sole basis for decision-making. Other factors to consider include the neonate's postnatal age, cardiopulmonary status, degree of symptoms, acuity of anemia, whether there is ongoing blood loss, and whether the infant has other underlying conditions.

At our institution, the thresholds we use to trigger transfusion are based chiefly upon the Hgb/Hct level, gestational age (GA), postnatal age, and clinical status (table 1). These thresholds are appropriate for most term and preterm neonates cared for in the neonatal intensive care unit (NICU). However, they do not apply to neonates with cyanotic congenital heart disease, severe alloimmune hemolytic disease (ie, requiring exchange transfusion), acute severe or ongoing blood loss, severe persistent pulmonary hypertension of the newborn (PPHN), or those requiring extracorporeal membrane oxygenation (ECMO) [23]. (See 'Special circumstances' below.)

The rationale and supporting evidence for restrictive transfusion practice are briefly summarized above and discussed in greater detail separately. (See 'Restrictive versus liberal strategy' above and "Anemia of prematurity (AOP)", section on 'Transfusion'.)

Neonates with clinical instability — This includes neonates with cardiac, respiratory, or hemodynamic instability and those who are undergoing major surgery. Within this topic, clinical instability is defined as any of the following:

●Need for invasive mechanical ventilation

●Need for inotropic/vasopressor support

●Need for continuous positive airway pressure or other non-invasive positive pressure ventilation support with fraction of inspired oxygen >0.4

●Acute sepsis or necrotizing enterocolitis with hemodynamic instability

●>6 nurse-documented apneas requiring intervention within 24 hours

●Undergoing major surgery (within or up to 48 hours after surgery)

For infants with one or more of these indicators of clinical instability, we suggest the following transfusion thresholds (table 1):

●Preterm neonates <35 weeks GA:

•0 to 7 days old – Hgb <11 g/dL (Hct <32 percent)

•8 to 14 days old – Hgb <10 g/dL (Hct <29 percent)

•≥15 days old – Hgb <8g/dL (Hct <24 percent)

●Neonates ≥35 weeks GA:

•0 to 7 days old – Hgb <11 g/dL (Hct <32 percent)

•≥8 days old – Hgb <7 g/dL (Hct <21 percent)

A Hgb threshold of <7 g/dL (Hct <21 percent) is appropriate for most neonates ≥35 weeks gestation who are >7 days old provided they are not small for gestational age (in which case the preterm thresholds listed above should be used). The Hgb <7 g/dL threshold applies to hemodynamically stabilized critically ill neonates (ie, not hypotensive and not requiring escalating inotropic/vasopressor support) [24,25]. A higher threshold may be warranted in neonates with severe or progressive shock and/or severe hypoxemia. In addition, separate thresholds are used for neonates with any of the conditions listed below. (See 'Special circumstances' below.)

Stable neonates — For stable neonates (ie, without any of the conditions or circumstances listed above), we suggest the following transfusion thresholds (table 1):

●Preterm neonates <35 weeks GA:

•0 to 7 days old – Hgb <10 g/dL (Hct <29 percent)

•8 to 14 days old – Hgb <8 g/dL (Hct <24 percent)

•≥15 days old – Hgb <7 g/dL (Hct <21 percent)

For preterm neonates with anemia of prematurity who otherwise appear well and are asymptomatic but who continue to have significant anemia (ie, Hct <21 percent or Hgb <7 g/dL) at four to six weeks after birth, measuring the reticulocyte count can help guide decisions regarding RBC transfusion. If the absolute reticulocyte is ≥100,000/microL (≥2 percent), RBC transfusion may not be necessary.

●Term and late preterm neonates ≥35 weeks GA:

•0 to 7 days old – Hgb <10 g/dL (Hct <29 percent)

•≥8 days old – Hgb <7 g/dL (Hct <21 percent)

Special circumstances — The thresholds in the table (table 1) are appropriate for most term and preterm neonates cared for in the NICU. However, they do not apply to neonates with acute severe or ongoing blood loss, severe alloimmune hemolytic disease of newborn (ie, requiring exchange transfusion), cyanotic congenital heart disease (CHD), severe PPHN requiring ECMO [23].

Antenatal/perinatal blood loss — Infants born to mothers with hemorrhage that occurs before or during delivery (eg, fetomaternal hemorrhage, placenta previa, placental abruption) may be severely anemic at birth and may require urgent transfusion. These issues are discussed separately. (See "Acute placental abruption: Pathophysiology, clinical features, diagnosis, and consequences", section on 'Consequences' and "Spontaneous massive fetomaternal hemorrhage", section on 'Fetal/neonatal'.)

Neonates with long-standing in-utero anemia (eg, twin-twin transfusion, chronic fetomaternal hemorrhage) may have elevated circulating blood volume and evidence of high-output heart failure. Such patients may tolerate partial exchange transfusion better than simple transfusion.

Acute blood loss — For neonates with significant acute blood loss, the decision to transfuse is based largely on the estimated blood loss rather than a specific Hgb/Hct threshold. Transfusion is generally warranted if blood loss is estimated to be >10 to 20 percent of the neonate's total blood volume or if there are persistent and concerning signs attributable to anemia (eg, persistent acidosis, tachycardia) after adequate volume expansion with crystalloid.

The amount of blood loss can be estimated as follows:

●Estimated volume of blood loss (mL)

•External bleeding – For neonates with external blood loss (eg, intraoperative or postoperative bleeding), blood loss is estimated by measuring the weight of blood-soaked bandages, gauze, and blankets and subtracting the dry weight of these items.

•Internal bleeding – Internal blood loss is more difficult to estimate; some calculations have been proposed for specific clinical scenarios. For example, blood loss due to a subgaleal hemorrhage can be estimated at 38 mL for every 1 cm increase in head circumference.

●Percent blood loss = estimated blood loss (mL) ÷ total blood volume (ie, 80 mL/kg)

Alloimmune hemolytic disease of the newborn — Alloimmune hemolytic disease of the newborn (HDN) is a condition in which the red blood cells of the fetus or newborn are destroyed by maternally derived alloantibodies. These antibodies arise in the mother as a direct result of a blood group incompatibility, generally from previous transfusions or pregnancies. Some neonates with HDN may require exchange transfusion to manage severe hyperbilirubinemia. Management of HDN is discussed in detail separately. (See "Alloimmune hemolytic disease of the newborn: Postnatal diagnosis and management", section on 'Postnatal management'.)

Neonates undergoing surgery — At our institution, the transfusion thresholds used in the perioperative setting (within or up to 48 hours after surgery) are the same as for clinically unstable neonates, even if the neonate is asymptomatic (table 1). (See 'Neonates with clinical instability' above.)

Perioperative transfusion may also be required if surgical bleeding is significant (eg, blood loss exceeding 20 percent of total blood volume). The approach is the same as for neonates with acute blood loss from other sources, as described above. (See 'Acute blood loss' above.)

Congenital heart disease — Details regarding RBC transfusion in infants undergoing surgical repair of congenital heart disease are provided separately. (See "Red blood cell transfusion in infants and children: Indications", section on 'Congenital heart disease surgery'.)

Persistent pulmonary hypertension of the newborn — For neonates with severe hypoxemia in the setting of PPHN, the threshold used to trigger RBC transfusion is higher than in the general NICU population, as discussed separately. (See "Persistent pulmonary hypertension of the newborn (PPHN): Management and outcome", section on 'Transfusion'.)

SELECTION OF RBC PRODUCTS — Important considerations in selecting an RBC product for neonates are discussed here. Other details about RBC products (eg, storage duration, preservative solution, hematocrit of a unit of RBCs) are provided in a separate topic. (See "Red blood cell transfusion in infants and children: Selection of blood products".)

Cytomegalovirus-safe RBCs for all neonates — All neonates who require transfusion should receive "cytomegalovirus (CMV)-safe" (also called "CMV-reduced risk") blood products. This refers to RBC units that are leukoreduced and/or CMV-seronegative. Leukoreduction removes nearly all white blood cells (WBCs) from blood products at the time of collection by highly efficient filters [26]. Both leukoreduction and CMV-negative products are effective in reducing the risk of CMV transmission; combining both strategies essentially eliminates the risk of transfusion-related CMV infection [27,28].

It is standard practice at most institutions to use leukoreduced RBCs for all neonatal transfusions [27,29]. The practice of using CMV-seronegative blood for neonatal transfusion varies from center to center. In settings where the seropositivity for CMV is high, there may be insufficient CMV-seronegative donors to fill the need for CMV-safe blood products. Thus, leukoreduction alone may be used in many centers. Additional details are provided separately. (See "Red blood cell transfusion in infants and children: Selection of blood products", section on 'Cytomegalovirus-reduced-risk products' and "Overview of cytomegalovirus infections in children", section on 'Prevention of neonatal transmission'.)

Note that leukoreduction and irradiation are not the same thing. Irradiation alone does not provide a CMV-safe product. Conversely, though leukoreduction greatly reduces the number of WBCs, the few remaining WBCs are capable of replication and can cause transfusion-associated graft-versus-host disease (TA-GVHD) in susceptible individuals. Thus, leukoreduction alone is insufficient to prevent TA-GVHD. (See 'Indications for irradiated RBCs' below.)

Indications for irradiated RBCs — Irradiated RBCs are used in patients at risk for TA-GVHD, including patients with acquired or congenital immunodeficiency. Many institutions, including ours, routinely use irradiated RBC units for all neonatal transfusions, particularly preterm neonates [30].

Irradiated RBC units are exposed to gamma or x-ray radiation at a standard dose prior to transfusion. This dose of radiation stops proliferation of foreign lymphocytes and eliminates the risk of TA-GVHD; however, it is not sufficient to kill viruses. Thus, irradiation does not provide a CMV-safe product and does not eliminate the need for either leukoreduction or CMV-seronegative blood products if a CMV-safe product is required. Other indications for irradiated RBCs are discussed in a separate topic review. (See "Red blood cell transfusion in infants and children: Selection of blood products", section on 'Irradiated red blood cells'.)

Use of O-negative blood — In emergency situations, neonates requiring transfusion can be issued group O, RhD-negative RBCs. This mostly occurs when there is no time for blood typing and screening for antibodies as can occur in the delivery room.

For nonemergency transfusions, there is time for testing of the infant's blood for ABO and RhD type and screening for unexpected RBC antibodies using plasma or serum from the infant or mother for compatible RBCs. Some centers use group O, RhD-negative RBCs for all neonatal transfusions to simplify blood banking procedures.

Additional details of emergency release of blood, use of Group O, RhD-negative RBCs, and pretransfusion testing are provided separately. (See "Red blood cell transfusion in infants and children: Selection of blood products", section on 'Emergency release of blood' and "Red blood cell transfusion in infants and children: Selection of blood products", section on 'Newborns and young infants' and "Pretransfusion testing for red blood cell transfusion", section on 'Serologic testing (type and screen)'.)

Alloimmune hemolytic disease of the newborn — Neonates with alloimmune hemolytic disease sometimes require transfusion, which may consist of double-volume exchange transfusion (if the neonate has severe hyperbilirubinemia) or less commonly a simple transfusion. In either circumstance, additional considerations are necessary when selecting RBCs for transfusion, as summarized in the table (table 2) and discussed in detail separately. (See "Alloimmune hemolytic disease of the newborn: Postnatal diagnosis and management", section on 'Transfusion'.)

ADMINISTRATION — The following sections review specific aspects of administering RBC transfusions in neonates. Additional details regarding administration of RBC transfusion more broadly (eg, issues related to informed consent, practices for ensuring correct patient identification, compatible fluids, and details of exchange transfusion) are provided separately. (See "Red blood cell transfusion in infants and children: Administration and complications" and "Unconjugated hyperbilirubinemia in term and late preterm newborns: Escalation of care".)

●Volume & infusion duration – RBC transfusions generally are given in aliquots of 10 to 20 mL/kg, over two to four hours. We typically use 20 mL/kg volumes. In some circumstances, such as hemodynamic instability or hypovolemia due to blood loss, a smaller volume (10 mL/kg) is given more rapidly (over one to two hours).

The optimal volume for neonatal RBC transfusion is uncertain, and there are few data comparing different approaches. A systematic review identified two trials (89 neonates) comparing higher transfusion volume (20 mL/kg) with lower volume (10 mL/kg) [2]. There were no apparent differences in mortality or other clinical outcomes between the two groups. However, the trials were too small to reach a definitive conclusion.

●Special techniques for ELBW and VLBW infants – In extremely low birth weight (ELBW) and very low birth weight (VLBW) neonates, the total volume for a single transfusion may be as low as 5 to 10 mL of blood. Special equipment can maximize the use of a single unit from a donor and allow for serial transfusions to an individual neonate from the same donor. This includes the following two systems:

•Small bags may come as part of a transfusion set (referred to as satellite packs) in which four or six aliquots can be made from a single red cell unit. If the blood bank has a sterile connecting device, the small bags can be connected to the large blood unit, and an appropriate amount can be withdrawn at any time.

•A syringe set in which the syringe is sterilely connected to the original unit may also be used for small-volume transfusions. Blood is drawn through a filter into a syringe, and can be used within four hours without further filtration. Such systems have been shown to be safe and can increase the number of transfusions from a single unit [31].

With both systems, the original expiration date of the unit is maintained if the sampling device remains connected to the original unit in a sterile manner. This period may be up to six weeks for use of a single unit in a nutrient solution such as Adsol (AS-1) and Nutricel (AS-2). However, irradiated RBC units have a shelf life of only 28 days. If a single unit is designated for a premature infant and is used until its expiration date, as many as 13 individual transfusions can be made from a single donor unit, which markedly decreases donor exposure [32].

STRATEGIES TO REDUCE RBC TRANSFUSION

●Delayed cord clamping – Delayed clamping of the umbilical cord may reduce RBC transfusions, especially in preterm neonates. This issue is discussed separately. (See "Labor and delivery: Management of the normal third stage after vaginal birth", section on 'Early versus delayed cord clamping'.)

●Iron supplementation – Optimal nutrition, including iron supplementation, is important for all neonates, particularly those requiring neonatal intensive care unit (NICU) care. Neonates in the NICU often receive iron supplementation to replace iron lost through hemorrhage or phlebotomy. (See "Iron deficiency in infants and children <12 years: Screening, prevention, clinical manifestations, and diagnosis", section on 'Recommendations for iron supplementation'.)

Iron supplementation should be continued even in neonates who have received RBC transfusions. This is because the iron provided from an RBC transfusion (which is approximately 8 mg/kg of iron for a 10 mL/kg aliquot of packed RBCs) isn't available until the transfused RBCs reach the end of their lifespan.

Extremely low birth weight (ELBW) neonates who are treated with erythropoiesis stimulating agents (ESAs) generally require more iron supplementation, as summarized in the table (table 3) and discussed separately. (See "Anemia of prematurity (AOP)", section on 'Additional iron supplementation'.)

●Limiting blood loss from phlebotomy – In neonates requiring NICU care, iatrogenic blood loss for laboratory testing is an important contributor to development of anemia, particularly in ELBW neonates [33,34]. There is a strong correlation between the amount of blood lost from phlebotomy and the number of transfusions ELBW neonates require, regardless of whether restrictive transfusion thresholds are used. (See "Anemia of prematurity (AOP)", section on 'Blood loss from phlebotomy'.)

Strategies to minimize blood loss from phlebotomy include using microtechniques (such as using point-of-care devices that can analyze small blood samples) and limiting blood sampling to essential testing.

●Use of cord blood – Initial laboratory tests can be obtained using fetal blood remaining in the placenta and umbilical vessels (cord blood). Use of cord blood for initial blood tests decreases initial phlebotomy losses and may reduce the need for transfusion, particularly in preterm very low birth weight (VLBW; <1500 g) neonates. In one study, this method was successful for obtaining initial blood samples in 95 percent (91 of 96) VLBW neonates [35]. Compared with matched controls in whom initial blood tests drawn from the neonate, the use of cord blood for initial laboratory evaluation was associated with higher hematocrit (Hct) at 12 to 24 hours and lower rates of transfusion in the first week after birth. Additional details of cord blood sampling for initial laboratory testing are provided separately. (See "Labor and delivery: Management of the normal third stage after vaginal birth", section on 'Cord blood'.)

Cord blood has also been suggested as a form of autologous blood donation. However, most birthing hospitals are not prepared for collecting and storing neonatal cord blood. Even with a program in place to collect and process umbilical cord blood, one study found that autologous blood was only available in one-third of neonates who required transfusion [36]. Another limitation is that delayed cord clamping significantly reduces the volume of cells available for cord blood donation and may prevent adequate collection. Collection of cord blood for autologous transfusion is distinct from collection and banking cord blood for hematopoietic stem cell transplant, which is discussed separately. (See "Collection and storage of umbilical cord blood for hematopoietic cell transplantation".)

●ESAs – Erythropoietin and darbepoetin have been studied as a strategy for reducing transfusion in preterm neonates, particularly ELBW neonates. Use of either medication increases the red cell mass, decreases the need for transfusion, and reduces donor exposures. However, use of ESAs varies by institution. At the author's center, we use darbepoetin routinely in all ELBW infants and selectively in more mature neonates who are at risk for significant anemia (eg, those requiring frequent blood draws or who are undergoing surgery). Other centers do not routinely use ESAs in these patients. Additional details regarding ESAs, including dosing guidance (table 3) and discussion of the supporting evidence, are provided separately. (See "Anemia of prematurity (AOP)", section on 'Erythropoiesis stimulating agents (ESAs)'.)

ESAs are also sometimes used in the management of alloimmune hemolytic disease of the newborn, as discussed separately. (See "Alloimmune hemolytic disease of the newborn: Postnatal diagnosis and management", section on 'Erythropoiesis stimulating agents'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Transfusion and patient blood management".)

SUMMARY AND RECOMMENDATIONS

●Rationale for transfusion – The principal rationale for red blood cell (RBC) transfusion in neonates is to prevent or reverse tissue hypoxia from reduced oxygen carrying capacity. Optimal transfusion practice aims to avoid unnecessary transfusions while ensuring that transfusion isn't withheld from neonates who would truly benefit from it. (See 'Rationale for transfusion' above.)

Overall, <1 percent of newborns require RBC transfusion. However, approximately 15 to 20 percent of neonates admitted to the neonatal intensive care unit (NICU) receive at least one transfusion. Common reasons for RBC transfusion in neonates include anemia of prematurity, alloimmune hemolytic disease, perinatal blood loss, and iatrogenic withdrawal of blood for laboratory testing. (See 'Prevalence of transfusion' above.)

●Risks – Transfusion has rare but established risks, including transfusion-transmitted infections, immune-mediated transfusion reactions, graft-versus-host disease, and toxic effects of anticoagulants or preservatives. (See "Red blood cell transfusion in infants and children: Administration and complications", section on 'Complications'.)

In addition, observational studies suggest that exposure to RBC transfusions is associated with adverse neonatal outcomes including intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, and neurodevelopment impairment; however, causality has not been established. (See 'Risks' above.)

●Restrictive transfusion thresholds – For most neonates with anemia, we recommend a restrictive rather than a liberal transfusion strategy (Grade 1B). The thresholds we use are based upon gestational and postnatal age, hemoglobin (Hgb) or hematocrit (Hct) levels, and the clinical status of the infant, as summarized in the table (table 1). Clinical trials in different populations have consistently shown that a restrictive transfusion practice reduces exposure to transfusions without increasing mortality or serious morbidity. (See 'Transfusion thresholds' above and "Anemia of prematurity (AOP)", section on 'Transfusion' and "Red blood cell transfusion in infants and children: Indications", section on 'Restrictive versus liberal strategy'.)

●Special circumstances – The thresholds in the table (table 1) are appropriate for most term and preterm neonates cared for in the NICU. However, they do not apply to neonates with the following conditions or circumstances:

•Alloimmune hemolytic disease of the newborn (see "Alloimmune hemolytic disease of the newborn: Postnatal diagnosis and management")

•Acute severe or ongoing blood loss (see 'Antenatal/perinatal blood loss' above and 'Acute blood loss' above)

•Cyanotic congenital heart disease (see "Red blood cell transfusion in infants and children: Indications", section on 'Congenital heart disease surgery')

•Severe persistent pulmonary hypertension of the newborn (PPHN) (see "Persistent pulmonary hypertension of the newborn (PPHN): Management and outcome", section on 'Transfusion')

•Extracorporeal membrane oxygenation (ECMO)

●Selection of RBC products – For all neonatal RBC transfusions, we suggest an irradiated and cytomegalovirus (CMV)-safe (leukoreduced and/or CMV seronegative) product (Grade 2C). (See 'Selection of RBC products' above.)

●Administration – RBC transfusions generally are given in aliquots of 10 to 20 mL/kg, over two to four hours. Special equipment in the blood bank can maximize the use of a single unit of blood and reduce donor exposure. (See 'Administration' above.)

●Strategies to reduce RBC transfusion – Strategies aimed at reducing the need for RBC transfusion in neonates include the following interventions, which are discussed in separate topic reviews (see 'Strategies to reduce RBC transfusion' above):

•Delayed cord clamping (see "Labor and delivery: Management of the normal third stage after vaginal birth", section on 'Early versus delayed cord clamping')

•Providing optimal nutrition, including iron supplementation (see "Iron deficiency in infants and children <12 years: Screening, prevention, clinical manifestations, and diagnosis", section on 'Recommendations for iron supplementation')

•Minimizing blood loss from phlebotomy (see "Anemia of prematurity (AOP)", section on 'Blood loss from phlebotomy')

•Using cord blood for initial laboratory tests (see "Labor and delivery: Management of the normal third stage after vaginal birth", section on 'Cord blood')

•Using erythropoiesis stimulating agents in at-risk neonates (see "Anemia of prematurity (AOP)", section on 'Erythropoiesis stimulating agents (ESAs)')