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Supplemental Content: Figure Legends and Tables

Supplemental Table 1: Logistic regression model of propensity for compliance

Supplemental Figure 1: Butterfly plot comparing the distribution of propensities for 687 subjects with compliant (Hemoglobin < 7 g/dL, N=349) versus non-compliant (Hemoglobin ≥ 7 g/dL, N=348)

transfusion. Subjects receiving a non-compliant transfusion who had predicted propensity for compliance of < 0.25 (n = 10) were excluded from further analyses because there were no comparable subjects receiving a compliant transfusion.

Supplemental Table 2: Comparison of compliant and non-compliant transfusions and balance assessment in the original and weighted cohorts. Compliant is defined as all red blood cell transfusions for hemoglobin < 7 g/dL in hemodynamically stable patient without cardiac disease. Noncompliant is defined as all red blood cell transfusions for hemoglobin > 7 g/dL in hemodynamically stable patient without cardiac disease.

Supplemental Table 3: Outcomes in the unweighted cohort

Supplemental Table 1: Logistic regression model of propensity for compliance Pre-transfusion Hb < 7 g/dL

Odds ratio (95% CI) P value

Female 1.30 (0.95, 1.78) 0.101

Age 0.687

Infant 1.09 (0.75, 1.59)

Child Reference

Adolescent 0.85 (0.52, 1.39)

Site 0.264

A Reference

B 0.65 (0.17, 2.46)

C 0.41 (0.11, 1.42)

D 1.20 (0.38, 3.83)

E 0.84 (0.19, 3.65)

F 0.70 (0.22, 2.18)

G 0.98 (0.30, 3.13)

H 0.84 (0.19, 3.61)

I 0.76 (0.25, 2.28)

J 0.42 (0.11, 1.50)

K 0.90 (0.26, 3.12)

L 0.70 (0.22, 2.14)

M 0.42 (0.14, 1.28)

N 0.73 (0.23, 2.29)

O 0.81 (0.22, 2.95)

P 2.00 (0.52, 8.30)

Q 2.20 (0.65, 7.81)

R 1.14 (0.39, 3.34)

S 0.50 (0.17, 1.42)

T 0.74 (0.21, 2.62)

U 0.73 (0.20, 2.57)

V 0.60 (0.20, 1.75)

W 0.95 (0.31, 2.94)

X 0.37 (0.11, 1.14)

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Y 1.26 (0.32, 5.08)

Z 0.82 (0.24, 2.79)

Type of PICU admission 0.093

General, medical Reference

Surgical, non-cardiac 0.61 (0.39, 0.95)

Trauma 0.92 (0.53, 1.62)

MODS at randomization 0.80 (0.54, 1.18) 0.268

PRISM III score at randomization 1.02 (0.98, 1.06) 0.401

PELOD-2 score at randomization 0.93 (0.86, 0.99) 0.033

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Supplemental Figure 1: Butterfly plot comparing the distribution of propensities for 687 subjects with compliant (Hemoglobin < 7 g/dL, N=349) versus non-compliant (Hemoglobin ≥ 7 g/dL, N=348)

transfusion. Subjects receiving a non-compliant transfusion who had predicted propensity for compliance of < 0.25 (n = 10) were excluded from further analyses because there were no comparable subjects receiving a compliant transfusion.

Supplemental Table 2: Comparison of compliant and non-compliant transfusions and balance assessment in the original and weighted cohorts. Compliant is defined as all red blood cell transfusions for hemoglobin < 7 g/dL in hemodynamically stable patient without cardiac disease.

Noncompliant is defined as all red blood cell transfusions for hemoglobin > 7 g/dL in hemodynamically stable patient without cardiac disease.

Original Cohort Weighted Cohort

Baseline

Variables Compliant RBC Transfusion Group (N=349)

Non- Compliant RBC Transfusion Group (N=338)

Absolute Standard Differenc e

Compliant RBC Transfusion Group

Non- Compliant RBC Transfusio n Group

Absolute Standard Difference Age, N (%)

Infant 111 (32) 109 (32) <0.01 113 (32) 108 (32) 0.01

Child 191 (55) 181 (54) 0.02 189 (54) 184 (55) <0.01

Adolescent 47 (13) 48 (14) 0.02 47 (13) 46 (14) <0.01

Female, N (%) 181 (52) 152 (45) 0.14 168 (48) 166 (49) 0.02

Site, N (%)

A 12 (3) 9 (3) 0.05 10 (3) 10 (3) <0.01

B 7 (2) 9 (3) 0.04 9 (3) 8 (2) <0.01

C 8 (2) 13 (4) 0.09 11 (3) 10 (3) <0.01

D 18 (5) 12 (4) 0.08 15 (4) 15 (5) <0.01

E 6 (2) 6 (2) <0.01 6 (2) 6 (2) <0.01

F 14 (4) 16 (5) 0.04 15 (4) 14 (4) <0.01

G 16 (5) 13 (4) 0.04 14 (4) 14 (4) <0.01

H 6 (2) 6 (2) <0.01 7 (2) 6 (2) <0.01

I 18 (5) 18 (5) <0.01 19 (5) 18 (5) <0.01

J 7 (2) 11 (3) 0.08 10 (3) 8 (2) 0.02

K 11 (3) 10 (3) 0.01 10 (3) 10 (3) <0.01

L 15 (4) 17 (5) 0.03 16 (5) 16 (5) <0.01

M 14 (4) 21 (6) 0.10 17 (5) 16 (5) <0.01

N 15 (4) 16 (5) 0.02 16 (5) 16 (5) <0.01

O 9 (3) 9 (3) <0.01 9 (3) 9 (3) <0.01

P 14 (4) 5 (1) 0.16 9 (3) 8 (2) 0.02

Q 21 (6) 7 (2) 0.20 14 (4) 16 (5) 0.03

R 26 (7) 18 (5) 0.09 22 (6) 22 (6) <0.01

S 20 (6) 31 (9) 0.13 25 (7) 25 (7) <0.01

T 10 (3) 10 (3) <0.01 10 (3) 10 (3) <0.01

U 10 (3) 10 (3) <0.01 11 (3) 10 (3) <0.01

V 19 (5) 23 (7) 0.06 21 (6) 21 (6) <0.01

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W 19 (5) 14 (4) 0.06 17 (5) 16 (5) <0.01

X 11 (3) 18 (5) 0.11 16 (5) 13 (4) 0.04

Y 10 (3) 6 (2) 0.07 8 (2) 8 (2) <0.01

Z 13 (4) 10 (3) 0.04 11 (3) 11 (3) <0.01

Type of PICU admission, N (%) General,

medical

260 (74) 238 (70) 0.09 253 (73) 246 (73) <0.01

Surgical,

non-cardiac 57 (16) 69 (20) 0.11 64 (18) 61 (18) <0.01

Trauma 32 (9) 31 (9) <0.01 32 (9) 31 (9) <0.01

MODS at randomization, N (%)

96 (28) 115 (34) 0.14 108 (31) 101 (30) 0.02

PRISM III score at randomization, mean±SD

5.5 ± 5.01 5.7 ± 5.15 0.04 5.5 ± 5.11 5.5 ± 5.16 0.01

PELOD-2 score at randomization, mean±SD

4.8 ± 2.77 5.2 ± 3.05 0.16 5.0 ± 2.86 4.9 ± 3.03 0.04

RBC: red blood cell; PICU: pediatric intensive care unit; MODS: multi-organ system dysfunction; PRISM III: Pediatric Risk of Mortality III; SD: standard deviation; PELOD-2: Pediatric Logistic Organ Dysfunction 2

Supplemental Table 3: Outcomes in the unweighted cohort

Outcome Non-Compliant RBC

Transfusion Group (N=338)

Compliant RBC Transfusion Group (N=349)

Overall (N=687)

NPMODS 59 (17.5%) 52 (14.9%) 111 (16.2%)

Worst PELOD-2 score

Median (Q1, Q3) 5.0 (2.0, 7.0) 4.0 (2.0, 6.0) 4.0 (2.0, 7.0)

Mean (SD) 5.3 (4.93) 4.5 (4.58) 4.9 (4.77)

28-day mortality 7 (2.1%) 8 (2.4%) 15 (2.2%)

ICU mortality 9 (2.7%) 10 (2.9%) 19 (2.8%)

ICU-free days

Median (Q1, Q3) 20.4 (13.0, 24.8) 23.1 (17.9, 25.8) 21.8 (15.3, 25.5)

Mean (SD) 17.7 (8.65) 20.2 (7.93) 19.0 (8.38)

Ventilator-free days

Median (Q1, Q3) 24.3 (18.7, 27.8) 27.2 (22.1, 28.0) 25.9 (20.4, 28.0)

Mean (SD) 21.3 (8.22) 23.6 (7.33) 22.4 (7.86)

Sepsis 84 (31.3%) 87 (29.3%) 171 (30.3%)

ARDS 23 (8.6%) 19 (6.4%) 42 (7.4%)

Nosocomial infection 9 (2.7%) 11 (3.2%) 20 (2.9%)

Number of transfusions after randomization

Median (Q1, Q3) 1.0 (1.0, 2.0) 1.0 (1.0, 2.0) 1.0 (1.0, 2.0)

Mean (SD) 1.9 (2.67) 1.8 (2.03) 1.9 (2.37)

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