Safety and efficacy of packed red blood cell transfusions
at different doses in very low birth weight infants
Lea H. Mallett, PhD, Vinayak P. Govande, MD, Ashita Shetty, MD, and Madhava R. Beeram, MD
This double-blinded, randomized, crossover study evaluated the safety
and effectiveness of 20 mL/kg aliquots of packed red blood cell (PRBC)
transfusions versus 15 mL/kg aliquot transfusions in very low birth weight
(VLBW) infants with anemia. The study enrolled 22 hemodynamically
stable VLBW infants requiring PRBC transfusions, with a mean gestational
age of 25.7 ± 2.2 weeks and birth weight of 804 ± 261 g. Each infant
was randomized to receive one of two treatment sequences: 15 mL/kg
followed by 20 mL/kg or 20 mL/kg followed by 15 mL/kg. The infants
were monitored during and after transfusions, and the efficacy and safety
of the treatments were evaluated. Infants had higher posttransfusion
hemoglobin (13.2 g/dL vs 11.8 g/dL, P < 0.01) and hematocrit levels
(38.6 g/dL vs 34.4 g/dL, P < 0.01) following 20 mL/kg PRBC transfusions
when compared to 15 mL/kg transfusions. There were no differences
in the incidence of tachypnea, hepatomegaly, edema, hypoxia, necrotiz-
ing enterocolitis, or vital sign instability between groups. In conclusion,
high-volume PRBC transfusions (20 mL/kg) were associated with higher
posttransfusion hemoglobin and hematocrit levels but no adverse effects.
Higher-volume transfusions may reduce the need for multiple transfusions
and therefore the number of donors the infant is exposed to.
A
nnually, more than 60,000 infants are born in the
United States with a birth weight ≤1500 g. These very
low birth weight (VLBW) infants are at risk of seri-
ous complications, including anemia of prematurity.
Anemia of prematurity is caused by ineffective hematopoiesis
and iatrogenic blood loss through frequent phlebotomy and
is exacerbated by low iron stores. Anemia leads to inadequate
oxygen delivery to tissues and poor growth. As a result, VLBW
infants are a heavily transfused population, accounting for near-
ly three-quarters of neonatal red blood cell transfusions (1–3).
Although blood transfusions are considered essential, there
are concerns related to infection risk, the safety of directed
donations, and refusal based on religious beliefs (4). Limiting
packed red blood cell (PRBC) transfusions may reduce trans-
fusion-associated infection and iron overload (5). Transfusion
guidelines are based on expert opinion, rather than evidence,
and therefore vary among hospitals, with some units favoring
restrictive guidelines and others more liberal guidelines (6–8).
Although the traditional volume of PRBC transfusions ranges
from 10 to 20 mL/kg (9), there is still considerable debate
128
regarding the optimal volume of transfusion. In a systematic
review, only four trials, with 146 infants, compared transfusion
volumes of 10 versus 20 mL/kg (3). These studies showed no
differences in neonatal outcomes, but the number of patients in
each study was small and markedly limited the power of these
studies to detect a difference. The purpose of this study was
to evaluate the safety and effectiveness of using larger-volume
aliquots for PRBC transfusions in preterm VLBW infants.
METHODS
This study was conducted at McLane Children’s Hospital,
Baylor Scott & White Health, in Temple, Texas. VLBW infants
admitted to the neonatal intensive care unit that were expected
to require at least two PRBC transfusions after 48 hours of
life were eligible for enrollment. Patients with any of the fol-
lowing were excluded: birth weight <500 g, congenital heart
defects, or hemodynamic instability (defined as pulse >180
beats/min and capillary refill >3 sec). This was a random-
ized, double-blind, crossover study. Informed parental con-
sent was obtained for eligible patients and then each infant
was randomized, using a random number generator, to one of
the two treatment sequences: 15 mL/kg transfusion followed
by 20 mL/kg transfusion or 20 mL/kg transfusion followed by
15 mL/kg transfusion. For both treatment groups, the blood
was transfused intravenously over 3 hours.
The blood product utilized for this study consisted of
component aliquot bags with a hematocrit of 60%, stored in
Nutricel AS-3 (Haemonetics, Pittsburgh, PA), which contains
dextrose, adenine, monobasic sodium phosphate, and sodium
chloride transfused via sterile tubing. All PRBC transfusions
were cytomegalovirus negative, leukocyte reduced, O-type with
the same Rh type as the infant.
Patients were enrolled over a 24-month period (January
2000–December 2002). Clinical and demographic information,
including the Score for Neonatal Acute Physiology (SNAP-II),
From the Department of Pediatrics, McLane Children’s Hospital, Baylor Scott &
White Health/Texas A&M Health Science Center College of Medicine, Temple,
Texas.
Corresponding author: Lea H. Mallett, PhD, Department of Pediatrics, McLane
Children’s Hospital, Baylor Scott & White Health, 1901 SW H. K. Dodgen Loop,
Building 300, MS-CK-100, Temple, TX 76502 (e-mail: lmallett@sw.org).
Proc (Bayl Univ Med Cent) 2016;29(2):128–130
was collected (10). The need for transfusion was based on cur-
rent transfusion guidelines but ultimately determined by the Table 1. Demographic and clinical characteristics
attending neonatologist. Before transfusion, the following spe- by treatment group
cific parameters were assessed among both treatment groups: Treatment sequence
1) respiratory distress employing the Silverman Score (11); 2) 15, 20 mL/kg 20, 15 mL/kg
presence of edema or hepatomegaly; and 3) vital signs (heart (n = 10) (n = 12)
rate, respiratory rate, blood pressure, and oxygen saturations). Gestational age (wk, mean ± SD) 25.6 ± 2.2 26.4 ± 2.2
Vital signs were monitored hourly during and up to 6 hours
Birthweight (g, mean ± SD) 773 ± 258 830 ± 272
after transfusion. Hematocrit, hemoglobin, and red blood cell
counts were also collected 1 hour before transfusion and for Mother’s race or ethnic group
3 hours after transfusion. White 6 5
The primary outcome was posttransfusion change in he- Black 2 5
moglobin and hematocrit in infants following both PRBC Hispanic 2 2
transfusion treatment sequences. Secondary outcomes included Delivery route
vital sign instability, edema or hepatomegaly, and respiratory
Vaginal 4 4
distress. Statistical analyses were performed using SAS Version
8.2 (SAS Institute, Cary, NC). All data were compared using Routine C-section 5 7
analysis of variance for a crossover design (12). The traditional Emergency C-section 1 1
definition of a P value of 0.05 or less for statistical significance Maternal age (yr, mean ± SD) 26 ± 6 28 ± 6
was applied (13). Gravida
1 1 0
RESULTS
2 3 8
Twenty-four infants were enrolled in the study; 2 parents
withdrew consent prior to randomization, and the remain- 3 2 3
ing 22 patients were randomized into one of the two treat- 4+ 4 1
ment sequences: 15 mL/kg transfusion followed by 20 mL/kg Prenatal care 10 12
transfusion or 20 mL/kg transfusion followed by 15 mL/kg Antepartum complications 10 11
transfusion. Seven patients were discharged after receiving only Arterial line 1 1
the first transfusion and 15 patients received 2 transfusions.
Apgar scores (mean ± SD)
Demographic and clinical characteristics of study infants by
treatment group are presented in Table 1. The median number 1 min 4.8 ± 2.8 6.2 ± 2.4
of days between the first and second transfusion for all patients 5 min 7.9 ± 1.3 8.1 ±1.3
was 8 days (range, 1–22). Cord pH (mean ± SD)
As shown in Table 2, infants from both sequence groups Arterial 7.2 ± 0.1 7.3 ± 0.1
had higher posttransfusion hemoglobin (13.2 vs 11.8 g/dL,
Venous 7.3 ± 0.2 7.3 ± 0.1
P < 0.01) and hematocrit levels (38.6 vs 34.4 g/dL, P < 0.01)
following 20 mL/kg PRBC transfusions when compared to SNAP score (mean ± SD) 22.5 ± 7.3 21.6 ± 7.1
15 mL/kg transfusions. There were no significant differences SNAP indicates Score for Neonatal Acute Physiology.
in the incidence of hepatomegaly, edema, respiratory distress,
or abnormal vital signs during the 20 mL/kg transfusions com-
pared to the 15 mL/kg transfusions. One patient (5%) had hep- higher hemoglobin and hematocrit values when compared to
atomegaly following a transfusion of 15 mL/kg. Four patients 15 mL/kg transfusions. Infants tolerated the higher volumes
(18%) had edema following transfusion, one after 15 mL/kg well, with no significant differences in the incidence of re-
and three after 20 mL/kg transfusions. Necrotizing enterocoli- spiratory distress, hepatomegaly, peripheral edema, hypoxia,
tis developed in one patient (5%), who
received 20 mL/kg followed by 15 mL/kg
2 days after the two transfusions were Table 2. Pre- and posttransfusion treatment effects by dose
completed, requiring surgical interven-
tion. The infant survived to discharge. 15 mL/kg 20 mL/kg
Variable Pre Post Pre Post P value
DISCUSSION Hemoglobin (g/dL) 9.0 ± 1.2 11.8 ± 1.4 9.1 ± 1.0 13.2 ± 1.2 <.01
Our findings support the efficacy
Hematocrit (g/dL) 26.2 ± 3.4 34.4 ± 3.8 26.8 ± 2.8 38.6 ± 3.6 <.01
and safety of higher-volume (20 mL/kg)
PRBC transfusions, currently supported Red blood cells (M/μL) 2.8 ± 0.4 3.8 ± 0.4 2.8 ± 0.3 4.2 ± 0.4 <.01
by four similar studies. The larger trans- Respiratory distress (Silverman score) 2.1 ± 1.1 2.2 ± 1.0 2.2 ± 1.3 2.2 ± 1.2 .31
fusion volumes resulted in significantly

April 2016 Safety and efficacy of packed red blood cell transfusions at different doses in very low birth weight infants 129
necrotizing enterocolitis, or vital sign insatiability. These find-
ings are consistent with a previous study by Wong et al in 2005
comparing 20 mL/kg with 15 mL/kg PRBC transfusions.
The randomized crossover design and the addition of the
SNAP-II score were strengths of this study. By randomizing the
sequence and having each infant serve as his or her own con-
trol, the observed changes in hemoglobin and hematocrit were
not biased by order of transfusion or by infant idiosyncrasies.
However, our study had several limitations. First, our study had
a limited sample size, which may have impacted our ability to
detect safety signal. However, our findings add to the paucity of
data in this area. Second, our results may not be generalizable
to other centers with different transfusion practices. Finally,
the Silverman score is subject to ascertainment bias. Therefore,
further study in this area may address some of these limitations
and expand its scope.
Our findings suggest that higher-volume PRBC transfu-
sions lead to higher posttransfusion hemoglobin and hematocrit
volumes without increasing acute complications. These results
suggest a way to potentially decrease or eliminate the need for
multiple transfusions and the number of donors the infant is
exposed to, thereby decreasing risk. Prospective validation of this
practice, with larger studies, is needed to determine long-term
benefits, safety profile, and cost-effectiveness.
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