Table 3.
Hospital Course and Statusat Discharge for Neonates in the Hypothermia Groupsa
| Duration of Cooling | Depth of Cooling | |||||||
|---|---|---|---|---|---|---|---|---|
| Neonates, No. (%) | P Valueb | Adjusted RR (95% CI) |
Neonates, No. (%) | P Valueb | Adjusted RR (95% CI) |
|||
| 72 h (n = 185) |
120 h (n = 179) |
33.5°C (n = 191) |
32.0°C (n = 173) |
|||||
| During Study Intervention | ||||||||
| Arrhythmia requiring therapyc | 2 (1) | 8 (4) | .16 | 3.12 (0.65–15.0) |
2 (1) | 8 (5) | .11 | 5.75 (0.68–48.7) |
| Acidosis lasting >3 hc | 2 (1) | 5 (3) | .85 | 0.87 (0.22–3.45) |
3 (2) | 4 (2) | .98 | 0.98 (0.23–4.14) |
| Major bleedingc | 5 (3) | 2 (1) | .04 | 0.25 (0.07–0.91) |
4 (2) | 3 (2) | .77 | 0.82 (0.22–3.04) |
| Death after initiation of cooling | ||||||||
| Within 72 h | 5 (3) | 9 (5) | .38 | 1.66 (0.53–5.24) |
4 (2) | 10 (6) | .07 | 2.33 (0.92–5.86) |
| Within 120 h | 11 (6) | 16 (9) | .31 | 1.36 (0.75–2.48) |
10 (5) | 17 (10) | .21 | 1.59 (0.77–3.30) |
| Skin erythema, cyanosis, sclerema, subcutaneous fat necrosisc | 6 (3) | 10 (6) | .42 | 1.34 (0.66–2.71) |
8 (4) | 8 (5) | .66 | 0.78 (0.26–2.36) |
| During Hospital Coursed | ||||||||
| Hypotension | 63 (34) | 55 (31) | .28 | 0.86 (0.66–1.13) |
58 (30) | 60 (35) | .43 | 1.13 (0.83–1.53) |
| Inotropic agentsc,e | 87 (47) | 93 (52) | .25 | 0.84 (0.63–1.13) |
88 (46) | 92 (53) | .32 | 1.13 (0.89–1.43) |
| Blood transfusionsc,e | 54 (29) | 63 (35) | .15 | 0.70 (0.44–1.14) |
57 (30) | 60 (35) | .11 | 1.31 (0.94–1.82) |
| Platelet transfusionsc,e | 44 (24) | 53 (30) | .21 | 0.85 (0.65–1.10) |
48 (25) | 49 (28) | .39 | 1.12 (0.87–1.43) |
| Persistent pulmonary hypertension | 47 (25) | 60 (34) | .13 | 1.23 (0.94–1.61) |
48 (25) | 59 (34) | .06 | 1.33 (0.98–1.79) |
| Inhaled nitric oxide therapy | 45 (24) | 60 (34) | .07 | 1.30 (0.97–1.72) |
46 (24) | 59 (34) | .03 | 1.36 (1.04–1.77) |
| ECMO | 10 (5) | 12 (7) | .52 | 1.26 (0.62–2.55) |
7 (4) | 15 (9) | .005 | 2.37 (1.30–4.30) |
| Documented seizures | 93 (50) | 84 (47) | .29 | 0.90 (0.75–1.09) |
94 (49) | 83 (48) | .49 | 0.94 (0.77–1.13) |
| Arrhythmia | 2 (1) | 12 (7) | .02 | 6.11 (1.26–29.5) |
5 (3) | 9 (5) | .21 | 1.82 (0.72–4.62) |
| Sustained heart rate <50 beats/minc | 10 (11) | 12 (15) | .88 | 1.06 (0.48–2.37) |
1 (1) | 21 (23) | .0007 | 6.93 (2.25–21.3) |
| Oliguria | 49 (26) | 46 (26) | .90 | 0.97 (0.66–1.44) |
48 (25) | 47 (27) | .88 | 1.04 (0.65–1.66) |
| Anuria | 5 (3) | 16 (9) | .01 | 3.24 (1.29–8.12) |
8 (4) | 13 (8) | .18 | 1.56 (0.82–2.98) |
| Hepatic dysfunctionf | 38 (21) | 52 (29) | .06 | 1.35 (0.99–1.85) |
45 (24) | 45 (26) | .70 | 1.06 (0.80–1.40) |
| Infection | ||||||||
| Positive culture during interventionc | 0 (0) | 4 (2) | .06g | 1 (1) | 3 (2) | .26h | 3.67 (0.38–35.3) |
|
| Septicemia after rewarming | 5 (3) | 8 (4) | .19 | 1.61 (0.79–3.28) |
5 (3) | 8 (5) | .06 | 1.74 (0.98–3.09) |
| Disseminated intravascular coagulopathy | 25 (14) | 29 (16) | .46 | 1.16 (0.78–1.72) |
29 (15) | 25 (14) | .67 | 0.90 (0.57–1.44) |
| Blood glucose <30 mg/dL | 30 (16) | 20 (11) | .20 | 0.68 (0.37–1.23) |
24 (13) | 26 (15) | .71 | 1.13 (0.60–2.11) |
| Blood calcium <8 mmol/L | 45 (24) | 45 (25) | .90 | 0.98 (0.74–1.30) |
49 (26) | 41 (24) | .75 | 0.93 (0.62–1.41) |
| Skin changes | 12 (6) | 16 (9) | .40 | 1.37 (0.66–2.86) |
12 (6) | 16 (9) | .29 | 1.46 (0.72–2.95) |
| Days of ventilationi | ||||||||
| Mean (SD) | 5.9 (7.3) | 6.8 (8.0) | .06 | 6.1 (7.6) | 6.6 (7.8) | .74 | ||
| Median (IQR) | 4 (1–8) | 5 (2–10) | 1.78 (0.97–3.27) |
3 (1–9) | 4 (1–10) | 1.09 (0.67–1.77) |
||
| Days receiving oxygeni | ||||||||
| Mean (SD) | 7.6 (8.2) | 9.2 (10.1) | .58 | 8.0 (9.7) | 8.8 (8.5) | .02 | ||
| Median (IQR) | 5 (2–10) | 6 (2–14) | 1.12 (0.75–1.66) |
5 (1–12) | 7 (2–13) | 1.29 (1.04–1.59) |
||
| Gastric fundoplication | 4 | 1 | 4 | 1 | ||||
| Gastrostomy | 13 | 11 | 18 | 6 | ||||
| Tracheostomy | 1 | 3 | 3 | 1 | ||||
| NICU death | 20 (11) | 29 (16) | .12 | 1.37 (0.92–2.04) |
22 (12) | 27 (16) | .47 | 1.24 (0.69–2.25) |
| Among survivors | ||||||||
| Length of stay, di | ||||||||
| Mean (SD) | 21.6 (15.3) | 26.4 (34.1) | .002 | 22.0 (15.7) | 26.0 (34.2) | .21 | ||
| Median (IQR) | 17 (11–27) | 20 (14–27) | 1.19 (1.07–1.33) |
17 (11–26) | 20 (13–28) | 1.11 (0.94–1.32) |
||
| Discharged with home therapy | 66 (40) | 52 (35) | .18 | 0.85 (0.68–1.08) |
57 (34) | 61 (42) | .24 | 1.16 (0.90–1.50) |
| Ventilator | 0 (0) | 0 (0) | 0 (0) | 0 (0) | ||||
| Oxygen | 6 (9) | 3 (6) | .51 | 0.56 (0.10–3.16) |
7 (12) | 2 (3) | .40 | 0.36 (0.03–4.03) |
| Gavage tube | 18 (27) | 16 (31) | .56 | 1.11 (0.78–1.59) |
16 (28) | 18 (30) | .69 | 1.09 (0.71–1.68) |
| Gastrostomy tube | 16 (24) | 10 (19) | .15 | 0.70 (0.42–1.14) |
18 (32) | 8 (13) | .07 | 0.49 (0.22–1.05) |
| Anticonvulsant medication | 41 (62) | 30 (58) | .73 | 0.95 (0.73–1.25) |
38 (67) | 33 (54) | .23 | 0.84 (0.63–1.12) |
Abbreviations: ECMO, extracorporeal membrane oxygenation; GEE, generalized estimating equations; HIE, hypoxic ischemic encephalopathy; IQR, interquartile range; NICU, neonatal intensive care unit; RR, relative risk.
Percentages are based on the number of mothers or neonates for whom data were available. Missing data for Table 3: hypotension (2 missing), bradycardia (190 missing; n = 174), septicemia (1 missing), hypocalcemia (1 missing), length of hospital stay (3 missing among 315 survivors), discharged with home therapy (2 missing among 315 survivors).
Unless otherwise noted, all P values are from GEE models for binary data, using a log link, adjusted for level of HIE and intracenter correlation.
These P values are from Poisson regression for the total number of events during intervention period, with offset for differential exposure times (72 h vs 120 h). These are adjusted for level of HIE and intracenter correlation in a GEE model.
The hospital course was defined as the period between birth and death or discharge.
Administration of inotropic agents, blood transfusions, and platelet transfusion were recorded during study intervention.
Hepatic dysfunction was defined as an aspartate aminotransferase level above 200 IU and an alanine aminotransferase level above 100 IU.
GEE model did not converge when accounting for intracenter correlation; P value given is adjusted for level of HIE only.
Unadjusted P value from the Fisher exact test for any positive culture during intervention; the adjusted model did not converge.
These P values are linear regression after log-transformation. These are adjusted for level of HIE and intracenter correlation in a GEE model.