Background
Methods
Study population
Definition of neonatal variables
Neurodevelopmental assessment
Outcome definitions
Statistical analysis
Results
Study population
BSID-II (n = 684) | No BSID-II (n = 160) | ||
---|---|---|---|
N (%) | N (%) | p-value§
| |
Median (IQR) | Median (IQR) | ||
Inborn | 654 (96%) | 144 (90%) | 0.005 |
Male gender | 362 (53%) | 89 (56%) | 0.54 |
Gestational age [weeks] | 26.7 (25.9-27.3) | 27 (26.1-27.6) | 0.007 |
Birth weight [gram] | 855 (730–990) | 940 (800–1100) | <0.001 |
SGA | 52 (8%) | 7 (5%) | 0.15 |
Singleton | 487 (71%) | 121 (76%) | 0.26 |
Antenatal corticosteroids (completed) | 441 (69%) | 99 (65%) | 0.29 |
Caesarean delivery | 552 (81%) | 117 (73%) | 0.028 |
SES score | 6 (4–8) | 6 (4–8) | 0.72 |
Umbilical artery pH | 7.31 (7.25-7.35) | 7.30 (7.23-7.34) | 0.17 |
PDA | 311 (46%) | 62 (39%) | 0.12 |
PDA ligation | 55 (8%) | 15 (9%) | 0.58 |
Mechanical ventilation | 505 (79%) | 109 (73%) | 0.14 |
Mechanical ventilation [days] | 4 (1–10) | 4 (0–8) | 0.20 |
Bronchopulmonary dysplasia | 139 (21%) | 18 (11%) | 0.008 |
IVH > 2 | 46 (7%) | 8 (5%) | 0.42 |
Major brain injury | 61 (9%) | 10 (6%) | 0.27 |
ROP stage 3 or higher | 35 (5%) | 8 (6%) | 0.77 |
Proven sepsis | 171 (25%) | 32 (20%) | 0.18 |
Necrotizing enterocolitis | 18 (3%) | 2 (1%) | 0.30 |
Outcome prediction at time of birth
Gestational age | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
240/7 to 246/7
| 250/7 to 256/7
| 260/7 to 266/7
| 270/7 to 276/7
|
Total
| ||||||
N | % | N | % | N | % | N | % |
N
| % | |
Favourable outcome
| 28 | 13 | 76 | 28 | 140 | 40 | 196 | 45 |
440
|
35
|
Moderate ND
| 18 | 9 | 36 | 13 | 51 | 15 | 61 | 14 |
166
|
13
|
Severe ND
| 11 | 5 | 18 | 7 | 21 | 6 | 28 | 6 |
78
|
6
|
Died after delivery room
| 61 | 29 | 90 | 33 | 76 | 22 | 65 | 15 |
292
|
23
|
Died in delivery room
| 87 | 41 | 28 | 10 | 8 | 2 | 7 | 2 |
130
|
10
|
Survived, no FU
| 5 | 2 | 23 | 8 | 50 | 14 | 82 | 19 | 160 | 13 |
Total | 210 | 100 | 271 | 100 | 346 | 100 | 439 | 100 | 1266 | 100 |
Birth weight
| ||||||||||
< 500g
|
500-749g
|
750-999g
|
> 999g
|
Total
| ||||||
N
|
%
|
N
|
%
|
N
|
%
|
N
|
%
|
N
|
%
| |
Favourable outcome
| 4 | 9 | 110 | 27 | 211 | 40 | 115 | 42 | 440 | 35 |
Moderate ND
| 5 | 11 | 44 | 11 | 82 | 15 | 35 | 13 | 166 | 13 |
Severe ND
| 1 | 2 | 25 | 6 | 36 | 7 | 16 | 6 | 78 | 6 |
Died after delivery room
| 22 | 49 | 119 | 29 | 112 | 21 | 39 | 14 | 292 | 23 |
Died in delivery room
| 12 | 27 | 83 | 20 | 25 | 5 | 3 | 1 | 123 | 10 |
Survived, no FU
| 1 | 2 | 29 | 7 | 65 | 12 | 65 | 24 | 160 | 13 |
Total
|
45
|
100
|
410
|
100
|
531
|
100
|
273
|
100
|
1259
|
100
|
Sex
| ||||||||||
female
|
male
|
Total
| ||||||||
N
|
%
|
N
|
%
|
N
|
%
| |||||
Favourable outcome
| 218 | 37 | 222 | 33 |
440
|
35
| ||||
Moderate ND
| 75 | 13 | 91 | 13 |
166
|
13
| ||||
Severe ND
| 29 | 5 | 49 | 7 |
78
|
6
| ||||
Died after delivery room
| 128 | 22 | 164 | 24 |
292
|
23
| ||||
Died in delivery room
| 64 | 11 | 65 | 10 |
129
|
10
| ||||
Survived, no FU
| 71 | 12 | 89 | 13 | 160 | 13 | ||||
Total | 585 | 100 | 680 | 100 | 1265 | 100 | ||||
Antenatal corticosteroids
| ||||||||||
incomplete/none
|
completed
|
Total
| ||||||||
N
|
%
|
N
|
%
|
N
|
%
| |||||
Favourable outcome
| 140 | 28 | 296 | 41 | 436 | 35 | ||||
Moderate ND
| 53 | 10 | 113 | 16 | 166 | 13 | ||||
Severe ND
| 24 | 5 | 53 | 7 | 77 | 6 | ||||
Died after delivery room
| 139 | 27 | 150 | 21 | 289 | 23 | ||||
Died in delivery room
| 95 | 19 | 16 | 2 | 111 | 9 | ||||
Survived, no FU
| 58 | 11 | 99 | 14 | 157 | 13 | ||||
Total
|
509
|
100
|
727
|
100
|
1236
|
10
|
MORTALITY | Univariate model† | Multivariate model‡ | ||
---|---|---|---|---|
OR (95%-CI) | p-value | OR (95%-CI) | p-value | |
Gestational age (weeks) | 0.39 (0.34 - 0.44) | <0.001 | 0.40 (0.35 - 0.47) | <0.001 |
BW z-score
| 0.64 (0.56 - 0.74) | <0.001 | NA | |
BW z-score < −2
| 6.99 (3.09 - 15.85) | <0.001 | 11.68 (4.73 - 28.86) | <0.001 |
BW z-score −2 to −1
| 2.10 (1.46 - 3.03) | <0.001 | 2.71 (11.78 - 4.12) | <0.001 |
Male sex
| 1.06 (0.82 - 1.35) | 0.67 | 1.15 (0.86 - 1.54) | 0.33 |
Outborn
| 0.80 (0.45 - 1.45) | 0.47 | NA | |
Antenatal corticosteroids
| 0.34 (0.26 - 0.44) | <0.001 | 0.46 (0.34 - 0.62) | <0.001 |
Caesarean delivery
| 0.49 (0.37 - 0.65) | <0.001 | NA | |
Multiple pregnancy
| 1.02 (0.77 - 1.34) | 0.90 | 1.27 (0.91 - 1.78) | 0.16 |
ADVERSE OUTCOME
|
Univariate model†
|
Multivariate model‡
| ||
OR
(95%-CI)
|
p-value
|
OR
(95%-CI)
|
p-value
| |
Gestational age (weeks) | 0.47 (0.41 - 0.53) | <0.001 | 0.49 (0.42 - 0.56) | <0.001 |
BW z-score
| 0.71 (0.62 - 0.88) | <0.001 | NA | |
BW z-score < −2
| 5.36 (2.22 - 12.90) | <0.001 | 7.90 (3.08 - 20.25) | <0.001 |
BW z-score −2 to −1
| 1.91 (1.32 - 2.78) | <0.001 | 2.35 (1.59 - 3.55) | <0.001 |
Male sex
| 1.20 (0.94 - 1.54) | 0.15 | 1.34 (1.01 - 1.77) | 0.042 |
Outborn
| 0.98 (0.53 - 1.81) | 0.95 | NA | |
Antenatal corticosteroids
| 0.40 (0.31 - 0.53) | <0.001 | 0.51 (0.38 - 0.69) | <0.001 |
Caesarean delivery
| 0.53 (0.39 - 0.70) | <0.001 | NA | |
Multiple pregnancy
| 0.96 (0.73 - 1.27) | 0.80 | 1.19 (0.87 - 1.64) | 0.28 |
UNFAVOURABLE OUTCOME
|
Univariate model†
|
Multivariate model‡
| ||
OR
(95%-CI)
|
p-value
|
OR
(95%-CI)
|
p-value
| |
Gestational age (weeks) | 0.52 (0.45 - 0.59) | <0.001 | 0.54 (0.47 - 0.61) | <0.001 |
BW z-score
| 0.73 (0.63 - 0.85) | <0.001 | NA | |
BW z-score < −2
| 12.05 (2.82 - 51.48) | <0.001 | 16.91 (3.84 - 74.47) | <0.001 |
BW z-score −2 to −1
| 1.59 (1.08 - 2.33) | 0.019 | 1.82 (1.20 - 2.74) | 0.004 |
Male sex
| 1.24 (0.96 - 1.59) | 0.09 | 1.35 (1.02 - 1.77) | 0.033 |
Outborn
| 1.30 (0.68 - 2.49) | 0.42 | NA | |
Antenatal corticosteroids
| 0.48 (0.36 - 0.63) | <0.001 | 0.57 (0.43 - 0.77) | <0.001 |
Caesarean delivery
| 0.69 (0.51 - 0.93) | <0.001 | NA | |
Multiple pregnancy
| 1.05 (0.79 - 1.38) | 0.76 | 1.31 (0.96 - 1.78) | 0.087 |
MORTALITY | Univariate model† | Multivariate model‡ | ||
---|---|---|---|---|
OR (95%-CI) | p-value | OR (95%-CI) | p-value | |
Gestational age (weeks) | 0.47 (0.41 - 0.55) | <0.001 | 0.46 (0.39 - 0.54) | <0.001 |
BW z-score
| 0.66 (0.56 - 0.77) | <0.001 | NA | |
BW z-score < −2
| 6.92 (2.89 - 16.59) | <0.001 | 10.09 (4.01 - 25.40) | <0.001 |
BW z-score −2 to −1
| 2.02 (1.35 - 3.02) | <0.001 | 2.52 (1.63 - 3.90) | <0.001 |
Male sex
| 1.13 (0.86 - 1.49) | 0.38 | 1.16 (0.86 - 1.57) | 0.33 |
Outborn
| 1.15 (0.64 - 2.06) | 0.65 | NA | |
Antenatal corticosteroids
| 0.52 (0.39 - 0.70) | <0.001 | 0.55 (0.41 - 0.76) | <0.001 |
Caesarean delivery
| 0.77 (0.55 - 1.06) | 0.1 | NA | |
Multiple pregnancy
| 0.94 (0.69 - 1.29) | 0.72 | 1.28 (0.90 - 1.81) | 1.17 |
ADVERSE OUTCOME
|
Univariate model†
|
Multivariate model‡
| ||
OR
(95%-CI)
|
p-value
|
OR
(95%-CI)
|
p-value
| |
Gestational age (weeks) | 0.56 (0.49 - 0.65) | <0.001 | 0.55 (0.47 - 0.64) | <0.001 |
BW z-score
| 0.73 (0.62 - 0.85) | <0.001 | NA | |
BW z-score < −2
| 4.99 (1.98 - 12.56) | <0.001 | 6.74 (2.58 - 17.60) | <0.001 |
BW z-score −2 to −1
| 1.82 (1.22 - 2.72) | 0.003 | 2.20 (1.44 - 3.36) | <0.001 |
Male sex
| 1.29 (0.98 - 1.69) | 0.066 | 1.35 (1.01 - 1.80) | 0.041 |
Outborn
| 1.34 (0.73 - 2.47) | 0.34 | NA | |
Antenatal corticosteroids
| 0.58 (0.44 - 0.78) | <0.001 | 0.61 (0.45 - 0.83) | 0.002 |
Caesarean delivery
| 0.79 (0.57 - 1.09) | 0.15 | NA | |
Multiple pregnancy
| 0.91 (0.67 - 1.23) | 0.55 | 1.17 (0.85 - 1.63) | 0.34 |
UNFAVOURABLE OUTCOME
|
Univariate model†
|
Multivariate model‡
| ||
OR (95%-CI) |
p-value
|
OR
(95%-CI)
|
p-value
| |
Gestational age (weeks) | 0.60 (0.52 - 0.68) | <0.001 | 0.59 (0.51 - 0.68) | <0.001 |
BW z-score
| 0.75 (0.64 - 0.87) | <0.001 | NA | |
BW z-score < −2
| 11.32 (2.60 - 49.16) | 0.001 | 15.24 (3.43 - 67.71) | <0.001 |
BW z-score −2 to −1
| 1.47 (0.96 - 2.19) | 0.059 | 1.69 (1.12 - 2.57) | 0.013 |
Male sex
| 1.30 (1.00 - 1.67) | 0.049 | 1.35 (1.02 - 1.78) | 0.033 |
Outborn
| 1.65 (0.87 - 3.15) | 0.13 | NA | |
Antenatal corticosteroids
| 0.64 (0.48 - 0.86) | 0.002 | 0.66 (0.49 - 0.89) | 0.006 |
Caesarean delivery
| 0.96 (0.70 - 1.33) | 0.82 | NA | |
Multiple pregnancy
| 1.01 (0.76 - 1.35) | 0.94 | 1.29 (0.94 - 1.76) | 0.11 |
Outcome prediction at 360/7weeks PMA
ADVERSE OUTCOME (severe ND or death after 360/7 weeks PMA versus favourable outcome or moderate ND) | ||||
---|---|---|---|---|
Univariate model† | Multivariate model‡ | |||
OR (95%-CI) | p-value | OR (95%-CI) | p-value | |
Gestational age (weeks) | 0.81 (0.65 - 1.02) | 0.077 | 1.00 (0.76 - 1.32) | 0.98 |
BW z-score
| 0.85 (0.64 - 1.13) | 0.271 | NA | |
BW z-score < −2
| 1.19 (0.14 - 10.2) | 0.88 | 0.70 (0.08 - 6.33) | 0.75 |
BW z-score −2 to −1
| 1.33 (0.68 - 2.62) | 0.41 | 1.22 (0.56 - 2.67) | 0.62 |
Male sex
| 1.60 (1.00 - 2.54) | 0.049 | 1.35 (0.79 - 2.24) | 0.27 |
Antenatal corticosteroids
| 1.17 (0.70 - 1.96) | 0.55 | 0.86 (0.49 - 1.51) | 0.61 |
Multiple pregnancy
| 0.96 (0.58 - 1.60) | 0.88 | 1.34 (0.77 - 2.36) | 0.3 |
PDA
| 1.52 (0.95 - 2.43) | 0.083 | 1.29 (0.77 - 2.17) | 0.33 |
NEC
| 5.45 (2.25 - 13.22) | <0.001 | 1.94 (0.58 - 6.50) | 0.28 |
Sepsis
| 1.47 (1.10 - 1.95) | 0.008 | 1.20 (0.87 - 1.65) | 0.27 |
Duration of ventilation (days) | 1.04 (1.02 - 1.06) | <0.001 | NA | |
Mechanical ventilation
| 3.50 (1.55 - 7.93) | 0.003 | NA | |
BPD
| 3.09 (1.89 - 5.03) | <0.001 | 2.81 (1.59 - 4.96) | <0.001 |
IVH ≥3
| 1.84 (0.86 - 3.93) | 0.11 | NA | |
Cystic PVL
| 2.07 (1.40 - 3.05) | <0.001 | NA | |
Major brain injury
| 2.72 (1.45 - 5.10) | 0.002 | 2.64 (1.28 - 5.43) | 0.008 |
ROP ≥3
| 2.73 (1.21 - 6.14) | 0.015 | 2.56 (1.05 - 6.26) | 0.039 |
SES class
| 0.74 (0.53 - 1.03) | 0.078 | 0.74 (0.51 - 1.06) | 0.096 |
UNFAVOURABLE OUTCOME (moderate or severe ND or death after 36
0/7
weeks PMA versus favourable outcome) | ||||
Univariate model†
|
Multivariate model‡
| |||
OR (95%-CI) |
p-value
|
OR (95%-CI) |
p-value
| |
Gestational age (weeks) | 0.76 (0.65 - 0.90) | 0.001 | 0.90 (0.74 - 1.10) | 0.31 |
BW z-score
| 0.85 (0.70 - 1.04) | 0.11 | NA | |
BW z-score < −2
| 6.52 (1.26 - 33.79) | 0.025 | 5.29 (0.91 - 30.84) | 0.064 |
BW z-score −2 to −1
| 1.04 (0.63 - 1.73) | 0.88 | 0.95 (0.54 - 1.68) | 0.86 |
Male sex
| 1.35 (0.98 - 1.86) | 0.063 | 1.16 (0.81 - 1.65) | 0.42 |
Antenatal corticosteroids
| 0.97 (0.68 - 1.38) | 0.85 | 0.73 (0.49 - 1.09) | 0.12 |
Multiple pregnancy
| 1.11 (0.78 - 1.58) | 0.58 | 1.31 (0.88 - 1.96) | 0.18 |
PDA
| 1.17 (0.84 - 1.63) | 0.35 | 1.05 (0.73 - 1.53) | 0.78 |
NEC
| 2.34 (0.99 - 5.52) | 0.052 | 1.22 (0.43 - 3.49) | 0.71 |
Sepsis
| 1.26 (1.03 - 1.54) | 0.026 | 1.10 (0.87 - 1.38) | 0.42 |
Duration of ventilation (days) | 1.03 (1.02 - 1.05) | <0.001 | NA | |
Mechanical ventilation
| 1.23 (0.81 - 1.87) | 0.32 | NA | |
BPD
| 2.26 (1.53 - 3.33) | <0.001 | 1.92 (1.24 - 2.99) | 0.004 |
IVH ≥3
| 1.35 (0.74 - 2.48) | 0.33 | NA | |
Cystic PVL
| 1.43 (1.04 - 1.98) | 0.03 | NA | |
Major brain injury
| 1.68 (0.99 - 2.86) | 0.054 | 1.74 (0.95 - 3.18) | 0.07 |
ROP ≥3
| 5.03 (2.33 - 10.86) | <0.001 | 4.88 (2.07 - 11.52) | <0.001 |
SES class
| 0.76 (0.61 - 0.96) | 0.022 | 0.74 (0.58 - 0.95) | 0.018 |