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Position statement

Minimizing blood loss and need for transfusions in newborns

Posted: Nov 12, 2025

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Principal author(s)

Souvik Mitra MD PhD, Emer Finan MBBCH, Deepak Manhas MD; Canadian Paediatric Society, Fetus and Newborn Committee

Abstract

Minimizing blood loss and need for blood transfusions is a priority in the care of preterm and critically ill term newborns that can be facilitated at birth by deferring cord clamping for at least 60 seconds in both preterm and term infants. Also, using umbilical cord blood sampling for initial blood work in preterm infants, whenever feasible, and avoiding routine blood work whenever possible, help to minimize blood loss and transfusion need. In very preterm and very low birth weight infants, a restrictive red cell transfusion strategy stratified by respiratory support and postnatal age is recommended. In late preterm and term neonates who are hemodynamically unstable or in acute severe hypoxemia, blood transfusion strategies should be individualized based on clinical condition. In stable preterm infants without fetal intracranial hemorrhage or major active bleeding, a platelet transfusion threshold of <25 x 109/L should be used.

Keywords: Blood transfusion; Platelet transfusion; Preterm

Background

Very preterm (born less than 32 weeks of gestation) and critically ill term infants frequently receive blood product transfusions in the neonatal intensive care unit (NICU). Data from the Canadian Neonatal Network have established that the blood products most used in preterm infants (born <30 weeks gestational age [GA]) are packed red blood cells (PRBCs) (56%), followed by platelets (15%)[1]. Neither product is biologically inert, and administering  blood products carries short-term risks for infection, transfusion-related lung injury, and transfusion-related necrotizing enterocolitis (NEC). Further, repeated transfusions can negatively impact neurodevelopmental outcomes[2]. Therefore, every attempt should be made to minimize blood loss and blood product transfusion. When transfusions are required, they must be administered in the most evidence-based manner. The needs to decrease phlebotomy, avoid routine blood work, and minimize sample volumes in neonates are likewise urgent.

A previous Canadian Paediatric Society (CPS) statement, ‘Minimizing blood loss and the need for transfusion in very premature infants’ (2015) included a review of literature until 2014, while the statement ‘Red blood cell transfusion in newborn infants’ (2014) considered published literature until 2012, with no specific recommendations on blood transfusion thresholds for critically ill term infants[3][4]. Topics such as deferred cord clamping, minimizing blood loss, and transfusion thresholds have gained considerable high-quality research since, thereby creating sizeable evidence-to-practice gaps. This statement, therefore, systematically addresses the most important topics that may be a source of variation in clinical practice related to reducing blood loss and transfusion need in newborns.

Statement development methods

A list of priority topics on neonatal transfusion was drafted by the authoring team following discussion with the CPS Fetus and Newborn Committee. For each topic, a comprehensive electronic search was conducted on one or more of the following databases: Cochrane Central Register of Controlled Trials, MEDLINE, and Embase. Randomized controlled trials (RCTs), cohort studies, and systematic reviews were specifically sought. Searches were not restricted by language. The principles of the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) Evidence to Decision framework were used to formulate revised recommendations[5].

Priority topics on neonatal transfusion

Cord management strategy

Preterm infants

Evidence from recent RCTs has demonstrated that preterm infants randomized to deferred cord clamping (DCC) for 60 to 120 seconds have significantly lower need for blood transfusions during hospital stay (RR 0.66, 95% CI 0.50 to 0.86][6] and increased serum ferritin levels at 6 to 10 weeks postnatal age (MD 0.38, 95% CI 0.01 to 0.74)[7]. Regarding umbilical cord milking (UCM; squeezing or stripping the cord toward the newborn immediately after birth) as an alternative to DCC, one meta-analysis of five RCTs found a significant increase in severe intraventricular hemorrhage (IVH) in infants <33 weeks GA with UCM versus DCC (RR 1.95, 95% CI 1.01 to 3.76)[8].

Term infants

In term singletons, RCTs of DCC beyond 60 seconds have demonstrated significantly improved hemoglobin (Hb), iron, ferritin, and transferring saturation with lower rates of iron deficiency between 4 and 12 months of age (20 studies, RR 0.68, 95% CI 0.49 to 0.94)[9]. However, DCC beyond 60 seconds may increase risk for hyperbilirubinemia[9][10].

Recommendation: In both preterm (<37 weeks) and extremely preterm (<28 weeks) singletons, deferred cord clamping (DCC) is recommended for 60 to 120 seconds. In term singletons, DCC is recommended for at least 60 seconds. Umbilical cord milking (UCM) is not recommended in very preterm infants (<32 weeks). These recommendations align with a 2022 joint statement on umbilical cord management by the CPS and the Society of Obstetricians and Gynecologists of Canada[11].

Transfusion thresholds for blood products

PRBCs are usually transfused in two main clinical scenarios: critically ill infants with hypovolemic anemia or anemic shock, and more stable infants with normovolemic anemia.

PRBCs in very preterm infants

Despite previous recommendations from the CPS to use lower threshold of Hb concentration for PRBC transfusion, a Canadian cohort study demonstrated that there was a trend toward fewer RBC transfusions among neonates born at 26 to 29 weeks gestation while use remained unchanged or increased for neonates born at 23 to 25 weeks gestation[1]. Two more recent, large RCTs (the TOP[12] and ETTNO[13] trials), which were specifically conducted in the extremely low birth weight (ELBW) population, now provide high certainty of evidence to conclude that using a lower Hb transfusion threshold with fixed volume transfusions adjusted for age and acuity result in no difference in death or cerebral palsy in survivors at 2 years of age, while reducing the number of PRBC transfusions[12][13]. This finding was reflected in a 2024 clinical practice guideline on red blood cell thresholds in very preterm neonates, which was rigorously developed using GRADE methodology and reinforced the utility of a lower threshold stratified by required respiratory support and postnatal age[14]. A recent prospective cohort study of PRBC transfusion practices in Europe for preterm infants <32 weeks GA (n=1143) showed that transfusion thresholds were below the restrictive thresholds set by ETTNO in 44.4% and TOP in 36.4% transfusions, while they were between restrictive and liberal thresholds in 48.3% and 56.1% transfusions respectively[15].

Recommendation: In very preterm (<32 weeks GA) and very low birth weight (VLBW) infants (<1500 g birth weight), a restrictive PRBC transfusion strategy stratified by need for respiratory support and postnatal age (Table 1) is recommended.

Table 1. Packed red blood cell transfusion thresholds in very preterm or very low birth weight infants
Postnatal age Respiratory support* No/minimal respiratory support
Hemoglobin g/L (Hematocrit %)
Week 1 110 (32%) 100 (29%)
Week 2 100 (29%) 85 (25%)
Week 3 85 (25%) 70 (21%)

* Respiratory support is defined as invasive mechanical ventilation, continuous positive airway pressure, non-invasive intermittent positive pressure ventilation, or nasal cannula flow rate of 1 L/minute or greater[14].

PRBCs in late preterm and term infants

There is limited evidence from the literature on PRBC transfusion thresholds in late preterm and term infants. The TRIPICU trial (n=637, age range 3 days to 14 years) showed that a restrictive transfusion strategy (Hb threshold 70 g/L) was non-inferior to a liberal strategy (95 g/L) in hemodynamically stable critically ill children[16]. The 2023 Association for the Advancement of Blood and Biotherapies (AABB) guidelines recommend that:

  • For critically ill children and those at risk for critical illness who are hemodynamically stable and without a hemoglobinopathy, cyanotic cardiac condition, or severe hypoxemia, consider red cell transfusion when the Hb concentration is less than 70 g/L (strong recommendation, moderate-certainty evidence).
  • For hemodynamically stable children with congenital heart disease, consider a transfusion threshold based on the cardiac abnormality and stage of surgical repair: 70 g/L (biventricular repair), 90 g/L (single-ventricle palliation), or 70 to 90 g/L (uncorrected congenital heart disease) (conditional recommendation, low-certainty evidence)[17].

These recommendations largely align with the consensus recommendations developed in 2018 by the Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI), Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network[18].

It is important to note that the TAXI  panel explicitly refrained from prescribing a transfusion threshold and suggested using clinical judgement for children with acute severe hypoxemia, unstable non-hemorrhagic shock, hemodynamically stable allo- or autoimmune hemolytic anemia, and for those undergoing extracorporeal membrane oxygenation. For children with pulmonary hypertension, they noted that the benefit of transfusion above an Hb threshold of 100 g/L was uncertain. Acknowledging the lack of specific evidence in term and late preterm newborns, the following recommendation may be reasonably extrapolated from the above guidelines:

Recommendation: In late preterm and term neonates who are hemodynamically unstable or in acute severe hypoxemia, blood transfusion strategies should be individualized based on clinical condition. In stable term infants without a hemoglobinopathy or cyanotic heart disease, an Hb transfusion threshold of 70 g/L may be considered.

Volume of blood transfusion

The volume of transfusion is a function of an infant’s Hb level, desired Hb, body weight, estimated blood volume (EBV), and the Hb concentration of the donor RBC unit, and can be derived using this formula:

Transfusion volume (mL) = patient weight (kg) x EBV (mL/kg) x (desired Hb (g/L) – patient Hb (g/L)/ Hb of donor unit)[19].

In clinical practice, variation in blood banking practices and donor characteristics make it challenging to predict the expected post-transfusion Hb. On average, each 10 to 15 mL/kg PRBC transfused is expected to increase the infant’s Hb level by approximately 10 to 20 g/L[19]. Blood transfusion volumes in RCTs of preterm infants have typically ranged between 10 to 20 mL/kg (median 15 mL/kg)[14]. One small RCT (n=20) of VLBW infants showed that transfusion with 20 mL/kg significantly improved Hb levels without affecting pulmonary function[20]. However, another small (n=4) observational study of extremely preterm infants noted that those diagnosed with transfusion-related NEC received larger mean volumes of total blood (27.75 ± 8.77 mL/kg) than non-NEC infants (15.25 ± 0.5 mL/kg)[21]. A recent international survey (343 NICUs) found that RBC transfusion volumes ranged between 10 and 20 mL/kg with a median transfusion duration of 4 hours (IQR 3 to 4 h), while a recent European cohort study demonstrated that the most common transfusion volume was 15 mL/kg (63.7% transfusions) over 3 hours (54.2% transfusions) in infants <32 weeks GA[21][22].

Recommendation: PRBCs should be transfused at a volume of 10 to 20 mL/kg over 3 to 4 hours. In very preterm or low birth weight infants, consider a transfusion volume of no more than 15 mL/kg.

Platelet transfusion

Thrombocytopenia is a common problem, estimated to occur in 18% to 35% of infants in the NICU and 73% of ELBW infants[23]. Traditional transfusion thresholds in NICU settings have tended to be more liberal, largely due to concern for an increased risk of bleeding, particularly IVH in preterm infants. In the recent PlaNeT2 multi-centre trial (n=660, median GA 26.6 weeks), stable preterm infants (i.e., no fetal intracranial hemorrhage or major bleeding episode in the previous 72 hours) who were randomly assigned to receive a higher (<50 x 109/L) platelet threshold experienced significantly more death or severe bleeding (OR 1.57, 95% CI 1.06 to 2.32; p=0.02) compared with those assigned to a lower (<25 x 109/L) threshold[26]. Follow-up data from this trial also showed a higher incidence of death or adverse neurodevelopmental outcome in the higher threshold group (OR 1.54, 95% CI 1.09 to 2.17, p=0.017)[25]. These findings are further supported by a subgroup analysis of the Preterm Erythropoietin Neuroprotection (PENUT) trial[26], where the adverse outcomes of death or severe neurodevelopmental impairment were significantly higher in infants who received platelets versus those who did not (OR 2.43, 95% CI 1.24 to 4.76)[26]. Increased risk of mortality and IVH has also been noted with more transfusion and higher platelet transfusion thresholds in another large, single-centre retrospective cohort study (n=1221)[27]. Finally, a recent systematic review and meta-analysis which included 18 reports from 13 studies associated platelet transfusion with an increased incidence of death, sepsis, and NEC in preterm infants[28]. While the pathophysiology causing such adverse effects is unclear, they may result from underlying immune-mediated effects[29][30].

While thrombocytopenia occurs more commonly in preterm and ELBW infants, term infants with neonatal alloimmune thrombocytopenia (NAIT), those undergoing major invasive procedures, and those with major active bleeding are other groups with limited evidence to guide platelet transfusion thresholds.

Recommendation: In stable preterm infants (<34 weeks GA) without fetal intracranial hemorrhage or major active bleeding, a platelet transfusion threshold of <25 x 109/L should be used. For more mature preterm and term stable infants, a cut-off of <20 x 109/L may be acceptable[31][32]. For infants scheduled to undergo an invasive procedure, who are actively bleeding, or who have experienced major bleeding within the last 72 hours, a threshold between 50 x 109/L and 100 x 109/L may be acceptable[33].

Preventing blood loss: “Keeping the baby’s blood in the baby”

Studies have shown significant estimated blood loss in the NICU, ranging between 14.2 mL/kg and 98.5 mL/kg over 7 to 70 study days[32][34][35]. Blood losses resulting from medical interventions are especially pronounced in very preterm infants. A 2021 study of infants born <28 weeks GA showed a median cumulative blood loss of 24.2 mL/kg (IQR 15.8 to 30.3 mL/kg) over the first 28 days post-birth from blood sampling[36]. This amount equates to about 28.5% (IQR 18.6 to 35.6%) of an infant’s circulating blood volume. The average number of punctures per infant was 47 (IQR 26 to 56) over the first 4 weeks of life. These same infants also had a median volume of 30 mL/kg of PRBC transfused in the same period[36]. There is urgent need to decrease phlebotomy, avoid routine blood work, and minimize sample volumes in neonates[37]. Unnecessary blood work can also be costly and painful, with associated risks for long-term growth and neurodevelopment. Keeping circulating blood “inside the baby” is best practice[38] and may involve the following strategies. 

Cord blood sampling

The feasibility and safety of obtaining umbilical cord blood for initial blood work in VLBW infants (including complete blood count [CBC])[32][37][39]-[42], coagulation studies[43][44], blood culture[32][39][42][44]-[47], newborn metabolic screen[32][40], blood type and antibody screen[32][40][48] have been well established in the literature. One multi-centre RCT (n=80) comparing cord sampling with routine blood work, where 38% of enrolled infants underwent DCC, demonstrated lower transfusion needs and lower rates of severe IVH and BPD in the cord sampling group, thus demonstrating the benefit of cord blood sampling, even in infants undergoing DCC[49].

Routine blood work

There is no standard definition of ‘routine’ blood sampling for preterm infants, and because investigations are often bundled, comparing the benefits of routine versus decreased sampling is difficult. However, targeted interventions with guideline development, auditing guideline compliance, and bundling laboratory draws with non-invasive monitoring and point-of-care testing may significantly reduce laboratory testing without increasing harms[37][50]. NICUs should advocate for the use of standardized neonatal blood collection tubes by their respective clinical laboratories to minimize blood loss. For example, infant-appropriate microtainers only require a 0.3 mL blood sample for CBC and 0.4 mL for basic electrolyte panels[51].

Non-invasive monitoring

Non-invasive monitoring for bilirubin and carbon dioxide can minimize iatrogenic blood loss. Transcutaneous bilirubin measurement has replaced serum bilirubin testing in many health care centres[52][53]. Similarly, distal end-tidal carbon dioxide monitoring may avoid blood gas sampling in ventilated neonates, but validity may vary based on the GA and clinical condition of the neonate[54]. Using non-invasive methods to measure Hb are not yet sufficiently accurate to replace invasive tests[55]-[57].

Point-of-care testing

In-line blood gas and chemistry monitoring can reduce iatrogenic blood loss and need for transfusions in the first weeks of life[34]. Using a multi-parameter point-of-care (POC) blood test analyzer has been shown to decrease the need for PRBC transfusions (38.9% versus 50%, p<0.05) and their number (2.53 versus 1.57, p<0.01) in VLBW infants[58]. One RCT (n=195) of VLBW infants showed that continuous glucose monitoring via a subcutaneously implanted device could provide accurate information on trends in glucose control and guide need for blood glucose assessment[59][60].

Recommendation: In preterm infants, umbilical cord blood sampling when feasible for initial blood work and avoidance of routine blood work is recommended. Non-invasive monitoring for bilirubin and carbon dioxide may be considered.

Supplementing neonatal blood volume

Enteral/parenteral iron supplementation

A systematic review of eight RCTs (n=1093) provided moderate certainty of evidence that enteral iron supplementation, initiated at 2 to 4 mg/kg/day, improves Hb concentration and reduces anemia in human milk-fed preterm and LBW infants[61]. Also, initiating iron supplementation early, at 2 weeks of age, may improve ferritin concentration compared with later initiation (i.e., beyond 6 to 8 weeks)[61]. This evidence aligns with CPS recommendations on iron requirements in the first 2 years of life[62]. However, the evidence is insufficient to determine whether earlier supplementation reduces need for blood transfusion. A recent survey of US NICUs showed that nearly all (54/56) supplement iron routinely, with the median starting dose of 2 mg/kg/day (range 1 to 6)[61]. Nine NICUs provided parenteral iron when enteral administration was not feasible, and this supplement was administered most often in parenteral nutrition at a dose range between 1 and 7 mg/kg/week[63].

Recommendation: Preterm infants should receive enteral supplementation with iron at doses recommended in CPS guidance[60].

Erythropoiesis-stimulating agents (ESAs)

A recent large RCT of extremely preterm infants (n=941) showed that high-dose erythropoietin (EPO), initiated within 24 hours of birth, was effective in reducing the number of PRBC transfusions, cumulative transfused volume, and donor exposure. However, the trial did not find any difference in incidence of mortality or severe neurodevelopmental impairment at 2 years of age[64][65]. The 2025 Cochrane update (in press) on early ESAs in preterm infants (initiated within 8 days of birth; 37 RCTs, n=5963) showed similar results with regards to reduction in PRBC transfusion, transfusion volume, and donor exposure without increasing the risk of retinopathy of prematurity (ROP)[66]. It was also noted that early EPO may reduce moderate-to-severe neurodevelopmental impairment and severe IVH and NEC, though such effects were not evident on sensitivity analysis of high quality RCTs, thereby precluding a recommendation for routine use. One recent large RCT (n=650) evaluating once-weekly darbepoetin in extremely preterm infants demonstrated a reduction in transfusion requirements (from 79% to 60% receiving at least one transfusion) but did not show improvement in long-term neurodevelopmental outcomes[67].

A 2020 Cochrane review update on late initiation of ESAs (initiated >8 days; 31 RCTs, n=1651) suggested a probable reduction in need for and number of PRBC transfusions in preterm infants, but there was a concerning increase in all-stage (RR 1.27; 95% CI 0.99 to 1.64) and severe ROP (RR 1.73; 95% CI 0.92 to 3.24), albeit based on low-certainty evidence[68].

Recommendation: Early administration of ESAs may be considered as a strategy to minimize blood transfusions in select high-risk very preterm or low birth weight infants, based on institutional factors (e.g., local transfusion needs) and parental values and preferences. Routine prophylactic use of ESAs is not recommended.

Key recommendations

  1. In both preterm and term infants, deferred cord clamping (DCC) is recommended for at least 60 seconds.

  2. In very preterm (<32 weeks gestational age [GA]) and very low birth weight (VLBW) (<1500 g birth weight) infants, a restrictive packed red blood cell (PRBC) transfusion strategy stratified by need for respiratory support and postnatal age is recommended (Table 1).
  3. In late preterm and term neonates who are hemodynamically unstable or in acute severe hypoxemia, blood transfusion strategies should be individualized based on clinical condition.
  4. PRBCs should be transfused at a volume of 10 mL/kg to 20 mL/kg over 3 to 4 hours.
  5. In stable preterm infants (born <34 weeks GA) without fetal intracranial hemorrhage or major active bleeding, a platelet transfusion threshold of <25 x 109/L should be used.
  6. In preterm infants, using umbilical cord blood sampling (when feasible) for initial blood work (specifically complete blood count, coagulation studies, blood culture, newborn metabolic screen, blood type, and antibody screen) and avoidance of routine bloodwork are recommended.
  7. Preterm infants should receive enteral supplementation with iron at the doses recommended by the CPS statement on iron supplementation.
  8. Early erythropoiesis-stimulating agents(ESAs) may be considered to minimize blood transfusions in select high-risk very preterm or VLBW infants, based on institutional factors and parental values and preferences. Routine prophylactic use of ESAs is not recommended.

Acknowledgements

This position statement was reviewed by the Community Paediatrics Committee of the Canadian Paediatric Society.

CANADIAN PAEDIATRIC SOCIETY FETUS AND NEWBORN COMMITTEE (2024-2025)

Members: Souvik Mitra MD PhD (Chair), Michael Narvey MD (Past Chair), Sidd Thakore MD (Board Representative), Gabriel Altit MD, Nicole Radziminski MD, Emer Finan MBBCH, Mireille Guillot MD, Frances Morin MD (Resident Member)
Liaisons: William Ehman MD (College of Family Physicians of Canada), Chantal Nelson (Public Health Agency of Canada), Eric Eichenwald MD (American Academy of Pediatrics, Committee on Fetus and Newborn), Douglas Wilson MD (The Society of Obstetricians and Gynaecologists of Canada), Isabelle Milette IPSNN (Canadian Association of Neonatal Nurses), Deepak Manhas MD (CPS Neonatal-Perinatal Medicine Section)
Principal authors: Souvik Mitra MD PhD, Emer Finan MBBCH, Deepak Manhas MD

Funding
There is no funding to declare.

Potential Conflict of Interest
The authors have indicated they have no conflicts of interest.

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Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.

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