Table 3. Primary and Secondary End Points.
| End points | Liberal transfusion threshold | Restrictive transfusion threshold | Absolute difference, % (95% CI)a | Odds ratio or adjusted difference in least-square means (95% CI)b | P valuec |
|---|---|---|---|---|---|
| Primary end point | |||||
| Death or neurodevelopmental impairment by 24 mo, No./total (%)d | 200/450 (44.4) | 205/478 (42.9) | 1.6 (−4.8 to 7.9) | 1.05 (0.80 to 1.39) | .72 |
| Secondary end points | |||||
| Death by 24 mo, No./total (%) | 38/460 (8.3) | 44/491 (9.0) | −0.7 (−4.3 to 2.9) | 0.91 (0.58 to 1.45)e | .70 |
| Cognitive deficit, No./total (%)f | 154/410 (37.6) | 148/430 (34.4) | 3.1 (−3.3 to 9.6) | 1.12 (0.83 to 1.51) | .47 |
| Cognitive deficit defined by Bayley 2 MDI score, No./total (%)f | |||||
| <85 | 143/378 (37.8) | 139/387 (35.9) | 1.9 (−4.9 to 8.8) | 1.09 (0.81 to 1.46)e | .58 |
| <70 | 71/378 (18.8) | 62/387 (16.0) | 2.8 (−2.6 to 8.1) | 1.21 (0.83 to 1.76)e | .31 |
| Bayley 2 MDI score, mean (SD)f | 92.6 (16.5) [n = 336] | 92.4 (17.5) [n = 360] | 0.2 (−2.4 to 2.7) | 0.4 (−2.1 to 2.9)g | .75 |
| Cerebral palsy, No./total (%) | 18/419 (4.3) | 25/443 (5.6) | −1.3 (−4.2 to 1.5) | 0.75 (0.40 to 1.40)e | .37 |
| Bayley 2 PDI score, mean (SD)f | 89.3 (15.1) [n = 315] | 89.2 (15.4) [n = 312] | 0.0 (−2.4 to 2.4) | 0.1 (−2.0 to 2.2)g | .92 |
| GMFCS score I-V, No./total (%)h | 34/416 (8.2) | 42/440 (9.5) | −1.4 (−5.2 to 2.4) | 0.84 (0.53 to 1.36)e | .48 |
| Severe visual impairment, No./total (%)i | 10/417 (2.4) | 12/443 (2.7) | −0.3 (−2.4 to 1.8) | 0.88 (0.61 to 2.07)e | .77 |
| Severe hearing impairment, No./total (%)j | 4/418 (1.0) | 6/443 (1.4) | −0.4 (−1.8 to 1.0) | 0.70 (0.20 to 2.51)e | .59 |
| Length of hospital stay, mean (SD), d | 93 (41) [n = 489] | 92 (38) [n = 510] | 0.7 (−4.2 to 5.6) | −0.0 (−4.7 to 4.7)g | 1.00 |
| Duration of support, postnatal age, mean (SD), dk | |||||
| At end of invasive ventilatory supportl | 23 (28) [n = 298] | 23 (26) [n = 321] | 0.1 (−4.2 to 4.3) | 0.0 (−4.1 to 4.1)g | 1.00 |
| At last positive pressure respiratory supportl | 53 (31) [n = 451] | 53 (29) [n = 475] | 0.5 (−3.3 to 4.6) | −0.1 (−3.4 to 3.1)g | .94 |
| At last supplemental oxygen | 52 (33) [n = 371] | 50 (33) [n = 378] | 2.7 (−2.1 to 7.4) | 1.6 (−2.5 to 5.8)g | .44 |
| At last caffeine administration | 69 (26) [n = 417] | 70 (26) [n = 425] | −1.0 (−4.6 to 2.5) | −2.0 (−5.1 to 1.1)g | .20 |
| At end of gavage feeding | 75 (25) [n = 422] | 77 (27) [n = 441] | −1.6 (−5.1 to 1.8) | −2.6 (−5.5 to 0.4)g | .09 |
Abbreviations: Bayley 2, Bayley Scales of Infant Development second edition; GMFCS, Gross Motor Function Classification System; MDI, Mental Developmental Index; PDI, Psychomotor Developmental Index.
Absolute differences were calculated post hoc for binary and continuous end points, without adjustment for center or birth weight stratum.
Odds ratios were calculated by logistic regression with the factors of treatment, center, and birth weight stratum (400-749 g or 750-999 g). Standardized residuals as well as the results of the Hosmer-Lemeshow goodness-of-fit test and contingency coefficient c are provided in eTable 7 in the Supplement. Reduced models (with a factor of treatment only) were fitted if iterations did not converge. Differences in least-square means were calculated for continuous variables by analysis of variance with the factors of treatment, center, and birth weight stratum (400-749 g or 750-999 g). Normal probability plots are provided in eTable 7.
P values were calculated by logistic regression for binary end points and by analysis of variance for continuous end points.
Neurodevelopmental impairment was defined as any of the following: cognitive deficit defined as a Bayley 2 MDI score <85 or similar indications of cognitive deficit, cerebral palsy, or severe visual or hearing impairment.
Logistic regression with a factor of treatment only.
Both the MDI and PDI scores are standardized to a mean of 100 (SD, 15) with a range from 50 to 150. For cognitive deficit as a component of the primary outcome, other cognitive assessments were taken into account if no Bayley test was available, as described in the Methods section of the text. Data for the rows with MDI scores <85 and <70 and PDI scores <85 are based on infants with attempted Bayley 2 testing only (including infants whose raw scores were so low that MDI/PDI was <50). Analyses of the MDI and PDI as continuous variables are based on complete Bayley 2 data only.
Adjusted difference in least-square means.
GMFCS scores of I, II, III, IV, and V indicate increasing degrees of gross motor function impairment, whereas 0 indicates that there is no deficit. GMFCS score was defined as a “further end point,” not as a secondary end point, in the study protocol. The presentation of the GMFCS data herein deviates from the statistical analysis plan, which foresaw presentation as median (interquartile range), due to the low rate of GMFCS scores >0.
Defined as best corrected visual acuity <6/60.
Defined as need for hearing aid or cochlear implant.
Analyses of the duration of various forms of support are limited to infants who received that therapeutic intervention (eg, 158 infants in the liberal threshold group and 155 infants in the restrictive threshold group never received invasive ventilatory support through an endotracheal tube, so duration of invasive ventilation is reported in only 298 and 321 infants) and discontinued the intervention before the day of discharge home.
Because nonparametric analyses would not have enabled adjustment for center and birth weight stratum, mean (SD) and results of analysis of variance are reported.