An Evidence-Based Approach to
Transfusion of the Preterm Infant
Disclosure
I am on the speakers bureau for:
Ikari
and
Fisher Paykell
Anemia of Prematurity
1. ANEMIA
 Definitions
 Clinical burden and effects
 Risk : benefit ratio
2. REDUCING TRANSFUSION
Placental transfusion
Minimizing iatrogenic anemia
Erythropoietin
3. WHAT HEMOGLOBIN TRIGGERS TO USE?
Randomized Trial Data
Hemoglobin and reticulocytes during first year of life
Lundstrom
1977
Saarnen and
Siimes 1978
Cited by:
Dallman PR
1981
“Rapid
developmental
changes and
complex
interactions
for oxygen
delivery
(prevent)
developing
clear cut
criteria for
transfusion.
Consequently
clinical
practices vary
widely.’’
International survey of transfusion practices for extremely
premature infants. Guillén U Sem Perinatol 2012;36:244
Risk : benefit ratio of transfusions
Higher hemoglobin may improve
 oxygen transport
 cardiac output
 weight gain
 apnea
BUT may increase
 infections - donor related
 iron stores
 necrotising enterocolitis
 children & adults - death rates
 complications from “old blood”
Pre Tx 97-113 g/l
Pre Tx 97-113 g/l
Pre Tx Hgb<97
Pre Tx 113-129 g/l
Pre Tx Hgb<97
Pre Tx 113-129 g/l
(J Pediatr 2014;164:475-80).
Intra-hospital death to day 28 in 1077
infants with BW < 1500 g
Transfused
Non-Transfused
Red Blood cell transfusions are independently associated with intrahospital mortality in VLBW: J Pediatrics 2011; 159; 371
Do transfusions cause NEC?
Kirpalani H, Zupancic JA. Sem Perinatol 2012 36:269;
Whyte R, Kirpalani H. Low vs high haemoglobin threshold for blood transfusion in very low
birth weight infants. Cochrane Database Syst Rev. 2011:CD000512
RCT Data
More NEC with
restrictive transfusions
Favours
Restrictive
Favours
Liberal
Do transfusions cause NEC?
Kirpalani H, Zupancic JA. Sem Perinatol 2012 36:269
Observational Studies
OR of 7.5 is
implausibly high
More NEC with liberal
transfusions
Favours
Liberal
Favours
Restrictive
Anemia of Prematurity
1. ANEMIA
 Definitions
 Clinical burden and effects
 Risk : benefit ratio
2. REDUCING TRANSFUSION
Placental transfusion
Minimizing iatrogenic anemia
Erythropoietin
3. WHAT HEMOGLOBIN TRIGGERS TO USE?
Randomized Trial Data
Effects of placental transfusion in ELBW: long and short-term outcomes
Ghavam S, Batra D, Mercer J, Kugelman A, Hosono S, Oh W, Rabe H, Kirpalani H.
Transfusion. 2014;54:1192
Phlebotomy overdraw in the neonatal intensive care nursery.
Lin JC, et al: Pediatrics. 2000;106(2) .
Early Erythropoietin. Ohlsson A, Aher SM. Cochrane 2014 4:CD004863.
OUTCOME:Transfusions
614 Infants
862 Infants
RR 1.48 (1.02, 2.13)
RR 0.79 (0.73, 0.84)
Favours
ROP > Stage 3
EPO Control
Favours
EPO Control
Anemia of Prematurity
1. ANEMIA
- Definitions
- Clinical burden and effects
- Risk : benefit ratio
2. REDUCING TRANSFUSION
- Placental Transfusion
- Minimizing iatrogenic anemia
- Erythropoietin
3. WHAT HEMOGLOBIN TRIGGERS TO USE?
- Randomized Trial Data
Comparison of Trial Design
Iowa Trial
Restrictive
Participating
centers
Liberal
PINT Trial
Restrictive
Liberal
1
10
100
451
Treatment
allocation
Randomized
Randomized
Stratification
Birth weight
Birth weight, center
No. of subjects
Mean BW (g)
954
958
771
769
Mean GA (wk)
28
28
26
26
PICOT Iowa
Population
<32 wks GA
Intervention
Comparison
Outcomes
Time frame
Liberal Hgb Tx
Restrictive Hgb Tx
No. of RBC Tx
36 wks PMA
PRIMARY OUTCOME IOWA
Number of Transfusions
Low Hgb
High Hgb
3.3 + 2.9
5.2 + 4.5
p = 0.025
ADDITIONAL OUTCOMES IN IOWA STUDY
J Pediatr 2006:149; 301
PICOT PINT
Population
Intervention
Comparison
Outcomes
Time frame
<1000 g BW
Liberal Hgb Tx
Restrictive Hgb Tx
Intact Survival
36 wks PMA
 < 1000 g BW
 < 48 hours age
 < 31 wks GA
TRANSFUSION THRESHOLDS
Respiratory support
Yes
No
Age
High Low
High Low
Week one
135 115
120 100
Week two
120 100
100
85
≥ Week
three
100
85
75
85
PRIMARY OUTCOME PINT
Death, BPD, severe ROP, Brain Injury
Low Hgb
High Hgb
165/223
(74%)
159/228
(70%)
OR = 1.3
95% CI 0.8-2.0 p = 0.26
PINT-Outcome Study (PINT-OS)
Primary Outcome & a-priori components
0.1
1
Composite
10
OR
100
p=0.09
1.45 (0.94, 2.21)
1.18 (0.72,1.93)
Death
1.32 (0.53, 3.27)
Cerebral Palsy
Cognitive Delay <70
p=0.06
1.74 (0.98, 3.11)
Blindness
2.16 (0.19, 24.1)
Deafness
1.45 (0.32, 6.58)
Favors Low
Favors High
PINT-Outcome Study (PINT-OS)
Post-Hoc Secondary Analysis
0.1
1
Composite
10
100
p=0.013
Death
Cerebral Palsy
Cognitive Delay <85
p=0.016
Blindness
Deafness
Favors Low
Favors High
OR
1.71
1.12, 2.61
1.18
0.72 , 1.93
1.32
0.53 , 3.27
1.81
1.12,2.93
2.16
0.19 , 24.1
1.45
0.32 , 6.58
RCT era: Risk : benefit ratio of transfusions
Higher hemoglobin may improve
 oxygen transport
 cardiac output
 weight gain - Not true
 apnea
- Not true
 NEC
?
 Neurocognitive outcomes ?
BUT may increase or unknown
 Infections - donor related
 iron stores
 death rates - unlikely
WHEN SHOULD WE TRANSFUSE?
NICHD – NEONATAL RESEARCH NETWORK
Transfusions For
Prematures (TOP)
Does a Liberal Red Blood Cell
Transfusion Strategy Improve
Neurologically-Intact Survival of
ELBW Infants as Compared to a
Restrictive Strategy? Clinicaltrials.gov
NCT01702805
1. Low thresholds of PINT and Iowa
studies were comparable
2. It is reasonable to maintain infants
above these lower thresholds
3. The high threshold was
higher in Iowa than in PINT
4. The benefit of higher thresholds
remains uncertain
16th Century dissection