Table 1 Baseline and clinical characteristics, and outcome of the total and neurodevelopmental follow-up cohort
Total PEPaNIC study cohort (N = 1440) | Neurodevelopmental follow-up cohort (N = 674) | Neurodevelopmental follow-up cohort with available baseline NSE/S100B (N = 556) | |||||||
|---|---|---|---|---|---|---|---|---|---|
Patients without hypoglycemia in PICU (N = 1319) | Patients with hypoglycemia in PICU (N = 121) | P | Patients without hypoglycemia in PICU (N = 614) | Patients with hypoglycemia in PICU (N = 60) | P | Patients without hypoglycemia in PICU (N = 500) | Patients with hypoglycemia in PICU (N = 56) | P | |
Baseline characteristics | |||||||||
Age (years) | 1.8 (0.3–7.2) | 0.2 (0.02–0.5) | < 0.0001 | 1.5 (0.2–5.2) | 0.1 (0.02–0.5) | < 0.0001 | 2.0 (0.4–6.0) | 0.1 (0.02–0.5) | < 0.0001 |
Male sex | 765 (58.0%) | 65 (53.7%) | 0.39 | 353 (57.5%) | 35 (58.3%) | 0.90 | 280 (56.0%) | 34 (60.7%) | 0.57 |
Treatment center | < 0.0001 | < 0.0001 | 0.0003 | ||||||
Leuven | 656 (49.7%) | 94 (77.7%) | 346 (56.4%) | 53 (88.3%) | 344 (68.8%) | 51 (91.1%) | |||
Rotterdam | 569 (43.1%) | 24 (19.8%) | 268 (43.6%) | 7 (11.7%) | 156 (31.2%) | 5 (8.9%) | |||
Edmonton | 94 (7.1%) | 3 (2.5%) | |||||||
Randomization to Late-PN | 646 (49.0%) | 71 (58.7%) | 0.046 | 313 (51.0%) | 40 (66.7%) | 0.022 | 254 (50.8%) | 40 (71.4%) | 0.004 |
PIM3 score | − 3.6 (− 4.4 to − 2.5) | − 2.5 (− 3.6 to − 1.3) | < 0.0001 | − 3.9 (− 4.5 to − 2.8) | − 3.1 (− 3.6 to − 1.8) | < 0.0001 | − 3.9 (− 4.4 to − 2.8) | − 3.1 (− 3.6 to − 1.8) | < 0.0001 |
PIM3 probability of death | 2.7% (1.2–7.6%) | 7.8% (2.6–21.1%) | < 0.0001 | 2.0% (1.1–5.9%) | 4.3% (2.6–14.5%) | < 0.0001 | 2.1% (1.2–5.7%) | 4.4% (2.7–14.5%) | < 0.0001 |
STRONGkids risk level | 0.28 | 0.89 | 0.99 | ||||||
Medium | 1176 (89.2%) | 112 (92.6%) | 549 (89.4%) | 54 (90.0%) | 457 (91.4%) | 52 (92.9%) | |||
High | 143 (10.8%) | 9 (7.4%) | 65 (10.6%) | 6 (10.0%) | 43 (8.6%) | 4 (7.1%) | |||
Diagnostic category | < 0.0001 | < 0.0001 | 0.0002 | ||||||
Surgical–cardiac | 475 (36.0%) | 72 (59.5%) | 250 (40.7%) | 38 (63.3%) | 245 (49.0%) | 37 (66.1%) | |||
Surgical–other | 213 (16.1%) | 9 (7.4%) | 127 (20.7%) | 3 (5.0%) | 69 (13.8%) | 1 (1.8%) | |||
Neurosurgery–neurology | 215 (16.3%) | 4 (3.3%) | 97 (15.8%) | 3 (5.0%) | 86 (17.2%) | 3 (5.4%) | |||
Trauma–burn | 63 (4.8%) | 1 (0.8%) | 22 (3.6%) | 0 (0.0%) | 22 (4.4%) | 0 (0.0%) | |||
Transplantation–hematology–oncology | 38 (2.9%) | 1 (0.8%) | 16 (2.6%) | 0 (0.0%) | 12 (2.4%) | 0 (0.0%) | |||
Medical–other | 315 (23.9%) | 34 (28.1%) | 102 (16.7%) | 16 (26.7%) | 66 (13.2%) | 15 (26.8%) | |||
History of malignancy | 81 (6.1%) | 3 (2.5%) | 0.11 | 37 (6.0%) | 1 (1.7%) | 0.24 | 34 (6.8%) | 1 (1.8%) | 0.24 |
Diabetes | 2 (0.2%) | 1 (0.1%) | 0.23 | 0 (0.0%) | 0 (0.0%) | – | 0 (0.0%) | 0 (0.0%) | – |
Predefined syndrome | 220 (16.7%) | 21 (17.4%) | 0.80 | 55 (9.0%) | 6 (10.0%) | 0.81 | 51 (10.2%) | 6 (10.7%) | 0.82 |
Demographics | |||||||||
Known non-white race | – | – | 51 (8.3%) | 2 (3.3%) | 0.21 | 36 (7.2%) | 2 (3.6%) | 0.41 | |
Known non-European origin | – | – | 110 (17.9%) | 9 (15.0%) | 0.72 | 85 (17.0%) | 9 (16.1%) | 0.99 | |
Known not exclusive Dutch or English language | – | – | 144 (23.4%) | 12 (20.0%) | 0.63 | 119 (23.8%) | 11 (19.6%) | 0.62 | |
Socioeconomic status1 | |||||||||
Parental educational level | 0.33 | 0.22 | |||||||
Level 1 | – | – | 24 (3.9%) | 6 (10.0%) | 18 (3.6%) | 6 (10.7%) | |||
Level 1.5 | – | – | 47 (7.7%) | 4 (6.7%) | 39 (7.8%) | 4 (7.1%) | |||
Level 2 | – | – | 141 (23.0%) | 16 (26.7%) | 117 (23.4%) | 14 (25.0%) | |||
Level 2.5 | – | – | 105 (17.1%) | 11 (18.3%) | 82 (16.4%) | 11 (19.6%) | |||
Level 3 | – | – | 170 (27.7%) | 13 (21.7%) | 145 (29.0%) | 12 (21.4%) | |||
Level unknown | – | – | 127 (20.7%) | 10 (16.7%) | 99 (19.8%) | 9 (16.1%) | |||
Parental occupational level | 0.075 | 0.065 | |||||||
Level 1 | – | – | 4 (0.7%) | 2 (3.3%) | 4 (0.8%) | 2 (3.6%) | |||
Level 1.5 | – | – | 55 (9.0%) | 7 (11.7%) | 46 (9.2%) | 7 (12.5%) | |||
Level 2 | – | – | 92 (15.0%) | 16 (26.7%) | 85 (17.0%) | 16 (28.6%) | |||
Level 2.5 | – | – | 63 (10.3%) | 4 (6.7%) | 52 (10.4%) | 4 (7.1%) | |||
Level 3 | – | – | 108 (17.6%) | 9 (15.0%) | 93 (18.6%) | 9 (16.1%) | |||
Level 3.5 | – | – | 51 (8.3%) | 1 (1.7%) | 40 (8.0%) | 0 (0.0%) | |||
Level 4 | – | – | 93 (15.1%) | 8 (13.3%) | 76 (15.0%) | 8 (14.3%) | |||
Level unknown | – | – | 148 (24.1%) | 13 (21.7%) | 105 (21.0%) | 10 (17.9%) | |||
Known parental smoking between birth and PICU admission | – | – | 172 (28.0%) | 14 (23.3%) | 0.55 | 130 (26.0%) | 13 (23.2%) | 0.75 | |
Left-hand preference | – | – | 86 (14.0%) | 9 (15.0%) | 0.85 | 70 (14.0%) | 9 (16.1%) | 0.69 | |
Baseline biomarkers | |||||||||
NSE (ng/mL) | – | – | – | – | 9 (7–13) | 12 (8–17) | 0.001 | ||
S100B (pg/mL) | – | – | – | – | 29 (11–55) | 38 (19–63) | 0.078 | ||
In PICU characteristics2 | |||||||||
Mean morning blood glucose (mg/dL) | 107 (93–125) | 91 (84–102) | < 0.0001 | 104 (91–121) | 89 (82–99) | < 0.0001 | 104 (90–122) | 89 (82–98) | < 0.0001 |
SD of all glucose measurements in PICU (mg/dL) | 27 (18–43) | 35 (27–48) | < 0.0001 | 26 (17–41) | 32 (25–42) | 0.005 | 27 (19–42) | 31 (25–42) | 0.055 |
Length of PICU stay (days) | 3 (2–7) | 8 (4–20) | < 0.0001 | 3 (2–6) | 8 (4–19) | < 0.0001 | 3 (2–6) | 8 (5–19) | < 0.0001 |
Mortality | |||||||||
in PICU | 55 (4.2%) | 13 (10.7%) | 0.003 | – | – | – | – | ||
at 90 days | 70 (5.3%) | 17 (14.0%) | 0.0005 | – | – | – | – | ||
at 4 years | 116 (8.8%) | 21 (17.4%) | 0.005 | – | – | – | – | ||
Neurodevelopmental outcome after 4 years3 | |||||||||
Clinical neurological evaluation score4, range 0–8 | – | – | 0.6 (1.2) | 0.4 (1.0) | 0.38 | 0.5 (1.2) | 0.5 (1.0) | 0.75 | |
Executive functioning as reported by parents or caregivers, T-score4 | |||||||||
Inhibition | – | – | 49.6 (11.1) | 51.4 (12.6) | 0.34 | 49.3 (11.0) | 51.6 (12.8) | 0.25 | |
Flexibility | – | – | 49.3 (10.2) | 48.9 (9.6) | 0.81 | 49.0 (9.9) | 49.3 (9.7) | 0.80 | |
Emotional control | – | – | 48.9 (9.8) | 49.0 (11.2) | 0.66 | 48.6 (9.7) | 49.3 (11.5) | 0.89 | |
Working memory | – | – | 51.4 (11.1) | 55.7 (12.8) | 0.015 | 51.3 (11.1) | 56.3 (12.9) | 0.006 | |
Planning and organization | – | – | 49.9 (10.2) | 54.2 (12.8) | 0.012 | 49.8 (10.4) | 54.6 (12.9) | 0.008 | |
Metacognition index | – | – | 50.1 (10.9) | 54.0 (13.3) | 0.046 | 50.0 (10.9) | 54.5 (13.5) | 0.025 | |
Total score | – | – | 49.5 (11.2) | 52.4 (13.2) | 0.15 | 49.3 (11.1) | 52.8 (13.4) | 0.082 | |
Emotional and behavioral problems as reported by parents or caregivers, T-score4 | |||||||||
Internalizing problems | – | – | 51.1 (10.7) | 49.7 (11.6) | 0.33 | 51.2 (10.6) | 49.6 (11.9) | 0.30 | |
Externalizing problems | – | – | 48.6 (10.0) | 49.2 (10.0) | 0.97 | 48.7 (9.7) | 49.4 (10.1) | 0.93 | |
Total problems | – | – | 50.1 (10.6) | 49.1 (11.4) | 0.34 | 50.3 (10.2) | 49.3 (11.7) | 0.36 | |
Intelligence5 | |||||||||
Total IQ, range 45–155 | – | – | 93.3 (16.8) | 94.1 (16.1) | 0.79 | 93.6 (17.1) | 93.7 (16.6) | 0.93 | |