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. 2020 Feb 11;2020(2):CD004863. doi: 10.1002/14651858.CD004863.pub6

1. Transfusion guidelines.

Reference Indications
Arif 2005 Infants with Hgb concentrations < 7 g/dL and with a reticulocyte count lower than < 100,000/µL or Hgb concentrations < 8 g/dL having bradycardia, tachypnoea, or apnoea, or who were not able to gain weight despite adequate calorie intake, were chosen as candidates for blood transfusion.
Avent 2002 Infants received blood transfusions if they met the following criteria:
 1. Hgb of 10 g/dL and 1 of the following: (i) an oxygen requirement greater than 30%; (ii) less than 1250 grams body weight
 2. Hgb < 8 g/dL and 1 of the following: (i) 3 or more episodes of apnoea (respiration absent for 20 seconds) or bradycardia (heart rate < 100 beats/min) in a 24‐hour period not due to other causes and not responsive to methylxanthine treatment; (ii) fractional inspired oxygen concentrations increasing by > 10% per week; and (iii) tachycardia (> 170 beats/min) or tachypnoea (> 70 breaths/min) sustained over a 24‐hour period associated with acute cardiac decompression
Carnielli 1992 Infants were transfused during the first week of life with packed erythrocytes if the Hct level was < 42% or 36%, depending on whether or not the patient was receiving supplemental oxygen. After the first week of life, indications for transfusions were Hct < 36% for oxygen‐dependent patients and 32% if breathing room air. Anaemia was the only indication for giving packed erythrocytes to all infants.
Carnielli 1998 Infants received transfusions of packed cells during the first week of life if their peripheral Hct (heel stick) was < 42% or 36%, depending on whether or not the patient was receiving supplemental oxygen.
 After the first week of life, indications for transfusion were Hct < 36% for oxygen‐dependent patients and 32% if in room air. Hct concentrations for red blood cell transfusions for blood obtained from venipuncture or arterial samples were 4% lower than the above mentioned values (38% and 32% for oxygen‐dependent and non‐oxygen‐dependent patients in the first week, and 0.32 and 0.28 thereafter). All infants received dedicated units of red blood cells.
Chang 1998 Transfusion guidelines not provided
El‐Ganzoury 2014 Transfusion guidelines not provided
Fauchère 2008 Transfusion guidelines not provided
Fauchère 2015 Transfusion guidelines not provided
Haiden 2005 Infants were transfused at Hct < 20%:
 1. if asymptomatic with reticulocytes < 100,000/µL
 
 Infants were transfused at Hct < 30%:
 1. if receiving < 35% supplemental hood oxygen
 2. if on CPAP or mechanical ventilation with mean air way pressure < 6 cmH2O
 3. if significant apnoea and bradycardia are noted (> 9 episodes in 12 hours or 2 episodes in 24 hours requiring bag and mask ventilation) while receiving therapeutic doses of methylxanthines
 4. if heart rate > 180 beats/min or respiratory rate > 80 breaths/min persists for 24 hours
 5. if weight gain < 10 g/d is observed over 4 days while receiving > 100 kcal/kg/d
 6. if undergoing surgery
 
 Transfuse for Hct < 35%
 1. if receiving > 35% supplemental hood oxygen
 2. if intubated on CPAP or mechanical ventilation with mean airway pressure > 6 to 8 cmH2O
 Do not transfuse:
 1. to replace blood removed for laboratory tests alone
 2. for low Hct alone
He 2008 Transfusion guidelines are not reported in the English abstract of this study. We have requested the full text in Chinese from trial authors.
Khatami 2008 "Guidelines for red‐cell transfusions were based on the relatively strict existing policy in the nursery which was used to administer transfusions during the study period".
Kremenopoulos 1997A Transfusions were ordered by the clinicians caring for each infant without consulting the investigators, based on general guidelines for erythrocyte transfusions. According to these guidelines, neonates who were well received transfusions if their hematocrit was < 30% during the third week, < 25% during the fourth week, and < 23% after the first month of life, combined with signs referable to their anaemia, such as poor weight gain, episodes of persistent bradycardia or tachycardia, and apnoea. Neonates with severe respiratory disease (bronchopulmonary dysplasia), particularly those requiring oxygen and/or ventilator support, were given transfusions to maintain their hematocrit level at > 40%.
Kremenopoulos 1997B See Kremenopoulos 1997A,
Lauterbach 1995 Transfusion was given when the Hct level reached 28% and if clinical symptoms of tachypnoea, tachycardia, and bradycardia were present at Hct of 0.32.
Lima‐Rogel 1998 According to criteria published by Klaus and Fanaroff (see text for more info)
Maier 1994 Infants who were receiving ventilation or who were less than 2 weeks old and had signs of anaemia were given transfusions if their Hct fell below 40%, their Hgb concentration fell below 14 g/dL (8.7 mmol/L), or blood samples totaling at least 9 mL/kg had been obtained from them since their previous transfusion.
 Spontaneously breathing infants, more than 2 weeks old, whose FiO2 was < 0.40, were given transfusions if they had signs of anaemia and their Hct fell below 32% and their Hgb concentration below 11 g/dL (6.8 mmol/L); if they had signs of anaemia, corresponding cutoff values were 27% and 9 g/dL (5.6 mmol/L).
Maier 2002 Infants with artificial ventilation or > 40% of inspired oxygen were not transfused unless Hct dropped below 0.40.
 Spontaneously breathing infants were not transfused unless Hct dropped below 0.35 during the first 2 weeks of life, 0.30 during the third to fourth weeks, and 0.25 thereafter. Transfusion was allowed when life‐threatening anaemia or hypovolaemia was assumed by the treating neonatologist, or surgery was planned. Twelve of the 14 centres used satellite packs of the original red cell pack to reduce donor exposure.
Meister 1997 Infants more than 2 weeks old who had been breathing spontaneously and whose FiO2 was less than 0.40 were given transfusions if they had signs of anaemia and their Hct fell below 11 g/dL (6.8 mmol/L); if they had no signs of anaemia, corresponding cutoff values were 27% and 9 g/dL (5.6 mmol/L).
Meyer 2003 Indications for transfusions were:
 1. Hct of 36% to 40% and critically ill with requirement for oxygen > 45% via CPAP; ventilation (mean airway pressure > 10 cmH2O); severe sepsis; active bleeding
 2. Hct of 31% to 35% and requirement for oxygen (up to 45%) via CPAP; ventilation (mean airway pressure 7 to 10 cmH2O)
 3. Hct of 21% to 30% and gain less than 10 g/d averaged over 1 week; experienced at least 10 to 12 apneic or bradycardic episodes in 12 hours or 2 or more such episodes requiring bag and mask ventilation within a 24‐hour period, not owing to other causes and not responsive to methylxanthine treatment; had a sustained tachycardia (> 170 beats/min) or tachypnoea (> 70/min) per 24 hours and not attributable to other causes; developed cardiac decompensation secondary to a clinically apparent patent ductus arteriosus; positive‐pressure ventilation on low settings (mean airway pressure < 7 cmH2O) or nasal CPAP; those requiring surgery
 4. Hct 20% and reticulocyte count < 100 × 109/L
Obladen 1991 Indications for transfusion of packed red cells:
 1. If venous Hct < 42%, Hgb < 14 g/dL or > 9 mL/kg blood sampled since last transfusion transfuse if infant is ventilated or requires FiO2 > 0.40
 2. If age 1 to 2 weeks and symptoms of anaemia (apneic spells, distended abdomen, failure to thrive), transfuse if venous Hct < 36%, Hgb < 12 g/dL, or > 9 mL/kg blood sampled since last transfusion.
 3. If age 3 to 5 weeks and symptoms of anaemia (apneic spells, distended abdomen, failure to thrive), transfuse if venous Hct < 30%, Hgb < 10 g/dL or > 9 mL/kg blood sampled since last transfusion.
 4. If no symptoms of anaemia, transfuse at any age if venous Hct is < 27%, Hgb < 9 g/dL.
Ohls 1995 Transfusions were given during the first 3 weeks of life if Hct was < 33%, and if the infant had 1 or more symptoms thought to be due strictly to anaemia. Symptoms were defined as tachycardia (heart rate > 160 beats/min, calculated as the average of all heart rates recorded by the bedside nurse during the preceding 24‐hour period), an increasing oxygen requirement (an increase in fraction of inspired oxygen of > 0.20 during a 24‐hour period), "lethargy" as assessed by the primary caregiver, or an increase in the number of episodes of bradycardia requiring stimulation to increase the heart rate from less than 60 beats/min (an increase of such episodes by 3 or more per day). Infants in both groups whose Hct were > 33% and yet whose phlebotomy losses exceeded 10 mL/kg body weight received an infusion of 5% albumin, administered in aliquots of not less than 10 mL/kg. Infants were not given transfusions if they were free of symptoms, even if Hct fell to < 33%.
Ohls 1997 Transfusions were administered in both groups according to standardised transfusion criteria: For infants requiring mechanical ventilation, transfusions were given if Hct fell below 33%. For infants not receiving ventilatory support, transfusions were given if Hct fell below 28%, and if the infant was experiencing symptoms. Symptoms were defined as tachycardia (heart rate > 160 beats/min, calculated as the average of all heart rates recorded by the bedside nurse over the preceding 24‐hour period), an increasing oxygen requirement (an increase in FiO2 of > 0.20 over a 24‐hour period, or an elevated lactate level (> 2.5 mmol/L). In some instances, a new donor would be used each day for the newborn intensive care unit (University of Florida), and in other instances, a unit would be dedicated to a single infant for the life of the unit (University of New Mexico and University of Utah).
Ohls 2001A If Hct ≤ 35%/Hgb ≤ 11 g/dL, transfuse infants requiring moderate or significant mechanical ventilation (MAP > 8 cmH2O and FiO2 > 0.4).
 If Hct ≤ 30%/Hgb ≤ 10 g/dL, transfuse infants requiring minimal respiratory support (any mechanical ventilation or endotracheal/nasal CPAP > 6 cmH2O and FiO2 ≤ 0.4).
 If Hct ≤ 25%/Hgb ≤ 8 g/dL, transfuse infants not requiring mechanical ventilation but who are on supplemental O2 or CPAP with an FiO2 ≤ 0.4 and in whom 1 or more of the following is present: 24 hours of tachycardia (180 beats/min) or tachypnoea (>80 breaths/min), an increased oxygen requirement from the previous 48 hours, defined as 4‐fold increase in nasal cannula flow (i.e. 0.25 L/min to 1 L/min), or an increase in nasal CPAP of 20% from the previous 48 hours (i.e. 5 cm to 6 cmH2O), weight gain < 10 g/kg/d over the previous 4 days while receiving 100 kcal/kg/d, increase in episodes of apnoea and bradycardia (> 9 episodes in a 24‐hour period or 2 episodes in 24 hours requiring bag‐mask ventilation) while receiving therapeutic doses of methylxanthines, undergoing surgery.
 If Hct ≤ 25%/Hgb ≤ 7 g/dL, transfuse asymptomatic infants with absolute reticulocyte count < 100,000 cells/µL.
Ohls 2001B See Ohls 2001A.
Ohls 2013 The PRBC volume transfused was based on Hct/Hgb, respiratory support, and/or symptoms.
If Hct ≤ 30/Hgb ≤ 10 and the infant required moderate/significant ventilation (MAP > 8 cmH2O and FiO2 > 0.4), the PRBC volume to be transfused was 15 to 20 mL/kg.
 If Hct ≤ 25/Hgb ≤ 8 and the infant required minimal respiratory support (any mechanical ventilation with FiO2 ≤ 0.4, or CPAP > 6 cmH2O and FiO2≤ 0.4), the PRBC volume to be transfused was 20 mL/kg.
 If Hct was ≤ 20/Hgb ≤ 7 and the infant required supplemental oxygen or CPAP with FiO2 ≤ 0.4, and at least 1 of the following:
 1. ≥ 24 hours of tachycardia (heart rate > 180) or tachypnoea (RR > 60)
 2. doubling of the oxygen requirement from the previous 48 hours
 3. lactate ≥ 2.5 mEq/L or an acute metabolic acidosis (pH 7.20)
 4. weight gain < 10 g/kg/d over the previous 4 days while receiving ≥ 120 kcal/kg/d
 5. undergoing surgery within 24 hours
PRBC volume to be transfused was 20 mL/kg.
If Hct ≤18/Hgb ≤ 6 and the infant was asymptomatic and absolute reticulocyte count (ARC) was < 100,000 cells/µL, the PRBC volume to be transfused was 20 mL/kg.
Peltoniemi 2017 Infants with the following respiratory needs received 10 to 15 mL/kg of RBC volume based on Hct:
 1. < 0.40 mechanical ventilation, FiO2 > 0.40
 2. < 0.35 mechanical ventilation, FiO2 < 0.40, or use of nasal CPAP at the age of < 2 weeks
 3. < 0.30 supplemental oxygen, nasal CPAP, or apneas during later neonatal period
 4. < 0.25 no symptoms during later neonatal period
Qiao 2017 Transfusion guidelines not reported
Salvado 2000 Preterm infants with Hct < 20%
 Preterm infants with Hct < 30% when presenting with frequent apneas, or tachycardia > 180 beats/min, or requiring surgery
Song 2016 Blood transfusion criteria followed strict clinical criteria as used by Vázquez López 2011.
Soubasi 1993 Neonates who were well were transfused if their Hct was < 25% combined with signs referable to their anaemia, such as poor weight gain, persistent episodes of bradycardia or tachypnoea, and apnoea. Neonates with severe respiratory disease (BPD), particularly those requiring oxygen and/or ventilator support, received transfusions to maintain Hct level at > 40%.
Soubasi 1995 Infants who were receiving mechanical ventilation or who were less than 2 weeks old were given transfusion if their Hct fell below 40%. Spontaneously breathing infants more than 2 weeks old whose FiO2 was less than 0.35 were given transfusion if they had signs of anaemia and their Hct fell below 30%; if they had no signs of anaemia, transfusion was given if Hct fell below 0.25. Growing, asymptomatic infants were transfused if Hct fell below 20%. Signs of anaemia included tachycardia, (> 170 beats/min) or tachypnoea (> 70/min) sustained over a 24‐hour period or associated with acute cardiac decompression; recurrent apnoea (respirations absent for 20 seconds) or bradycardia (heart rate < 100 beats/min) in a 24‐hour period not due to other causes and not responsive to methylxanthine treatment; an increase in fractional oxygen requirement by 20% or more over a 24‐hour period; or weight gain < 10 g/d averaged over a 1‐week period while on adequate caloric intake.
Soubasi 2000 Neonates were transfused when Hct was < 20%, if they were asymptomatic, or < 30% if they were receiving O2 < 0.35 and/or unexplained breathing disorders combined with signs referable to their anaemia, such as poor weight gain, episodes of persistent bradycardia or tachycardia.
Yasmeen 2012 After discharge from hospital, any patient with Hgb level ≤ 7 g/dL was readmitted to the hospital and managed with packed red cell transfusion.
Yeo 2001 Infants who were receiving mechanical ventilation or who were less than 2 weeks old were given transfusion if their Hct fell below 40%. Spontaneously breathing infants more than 2 weeks old whose FiO2 was less than 35% were given transfusion if they had signs of anaemia and their Hct fell below 30%; if they had no signs of anaemia, transfusion was given if Hct fell below 25%. Growing, asymptomatic infants were transfused if Hct fell below 20%. Signs of anaemia included tachycardia, (> 170 beats/min) or tachypnoea (> 70/min) sustained over a 24‐hour period or associated with acute cardiac decompression; recurrent apnoea (respirations absent for 20 seconds) or bradycardia (heart rate < 100 beats/min) in a 24‐hour period not due to other causes and not responsive to methylxanthine treatment; increased fractional oxygen requirement by 20% or more over a 24‐hour period; or weight gain < 10 g/d averaged over a 1‐week period while on adequate caloric intake.

ARC: absolute reticulocyte count.
 BPD: bronchopulmonary dysplasia.
 CPAP: continuous positive airway pressure.
 FiO2: fraction of inspired oxygen.
 Hct: hematocrit.
 Hgb: haemoglobin.
 MAP: mean airway pressure.
 PRBC: packed red blood cells.
 RBC: red blood cell.
 RR: respiratory rate.