There were 856 neonates weighing ≥ 1 800g diagnosed with intrapartum asphyxia from 2015 to 2019 from 96 784 live births, giving an incidence of asphyxia at 8.8/1000 live births. Two hundred and fifty-eight (30.1%) were assessed to have normal neurological examination or mild HIE, and three (0.4%) did not have records regarding their neurological examination, thus a total of 595 neonates had moderate to severe encephalopathy. Four hundred and forty-six (52.3%) were diagnosed with moderate and 149/853 (17.5%) with severe encephalopathy. The incidence of moderate and severe encephalopathy was 4.6/1000 and 1.5/1000 live births respectively. Amongst the 595 with moderate to severe encephalopathy, three did not have information regarding whether they were cooled or not and thus, 592 were considered for further analysis. Of the 592 patients with information on cooling, 399 (67%) were cooled (Fig. 1).
Over the 5-year study period, the proportion of neonates that were cooled amongst those with moderate to severe encephalopathy ranged from 61.2–74.6%, with the first two years having the highest proportion of cooled neonates (Table 1). Table 2 lists the reasons why neonates who were eligible for cooling were not cooled. Amongst the 193 neonates who were not cooled, reasons for not cooling them were not documented in 67 (34.7%). Amongst the 126 with known reasons for not cooling, the common reasons were that the neonate was moribund (54.0%), unavailability of equipment (cooling machine) (11.1%), diagnosis of persistent pulmonary hypertension (9.5%), late presentation (> 6 hours postnatal age at arrival or diagnosis (8.7%), improvement in HIE severity (8.7%) and gestational age < 36 weeks (7.2%).
Table 1
Proportion of neonates with moderate to severe asphyxia managed with induced hypothermia over a 5-year period
Year | Number of Neonates with Moderate to Severe Asphyxia | Proportion Managed with Induced Hypothermia n (%) |
2015 | 114 | 85 (74.6) |
2016 | 159 | 111 (69.8) |
2017 | 133 | 88 (66.2) |
2018 | 98 | 60 (61.2) |
2019 | 88 | 55 (62.5) |
Total | 592 | 399 (67.4%) |
Table 2
Reasons for not offering induced hypothermia to neonates with moderate to severe asphyxia (n = 126)*
Reasons for not Cooling | 2015 | 2016 | 2017 | 2018 | 2019 | Total |
Gestational Age < 36 weeks | 2 (11.1) | 4 (10.0) | 0 | 2 (6.5) | 1 (4.5) | 9 (7.2) |
Postnatal Age > 6 hours at presentation | 1 (5.6) | 3 (7.5) | 1 (6.7) | 1 (3.2) | 5 (22.8) | 11 (8.7) |
Congenital abnormalities | 0 | 0 | 0 | 0 | 1 (4.5) | 1 (0.8) |
Improvement in Encephalopathy Severity | 2 (11.1) | 5 (12.5) | 2 (13.3) | 0 | 2 (9.1) | 11 (8.7) |
Persistent Pulmonary Hypertension of Newborn | 0 | 6(15.0) | 2 (13.3 | 4 (12.9) | 0 (0) | 12 (9.5) |
All Available Cooling Machines in Use | 2 (11.1) | 6 (15.0) | 1 (6.7) | 3 (9.7) | 2 (9.1) | 14 (11.1) |
Moribund | 11 (61.1) | 16 (40.0) | 9 (60.0) | 21 (67.7) | 11 (50.0) | 68 (54.0) |
Total | 18 | 40 | 15 | 31 | 22 | 126 |
*-reason for not cooling were not recorded in 67 neonates |
In comparing neonates who were cooled to those who were not cooled, those who were not cooled were more likely to be of lower birth weight (3 058 vs 2 961grams, p < 0.001), lower gestational age (38.1 vs 38.7 weeks, p < 0.001), had lower 5-minute Apgar scores (3 vs 5, p < 0.001), took longer to achieve spontaneous respiration (14 vs 7 minutes, p < 0.001), had a lower pH (6.90 vs 7.05, p < 0.001), and had a higher Thompson score (14 vs 11, p < 0.001) (Table 3). Proportionately, there were also more with severe encephalopathy in the non-cooled compared to the cooled group (56.5 vs 10%, p < 0.001).
Table 3
Univariate analysis comparing characteristics of neonates with moderate to severe encephalopathy between cooled and not cooled groups
| Cooled n = 399 | Not Cooled n = 193 | p-value |
Birth weight categories | | | < 0.001 |
≥ 2500 grams | 348/399 (87.2) | 148/193 (76.7) | |
< 2500 grams | 51/399 (12.8) | 45/193 (23.3) | |
Mean birth weight, in grams | 3058 ± 508 | 2961 ± 565 | 0.036 |
Gestational age categories | | | 0.003 |
≥ 38 weeks | 312/397 (78.6) | 127/189 (67.2) | |
< 38 weeks | 85/397 (21.4) | 62/189 (32.8) | |
Mean gestational age, in weeks | 38.1 ± 2.5 | 38.7 ± 2.2 | 0.006 |
Sex, male | 247/397 (62.2) | 118/193 (61.1) | 0.801 |
Apgar score at 5 minute | | | < 0.001 |
≥ 4 | 331/392 (84.4) | 88/183 (48.1) | |
0–3 | 61/392 (15.6) | 95/183 (51.9) | |
Median Apgar score at 5 minutes | 5 (4–6) | 3 (2–6) | < 0.001 |
Time to First Breath | | | < 0.002 |
< 20 minutes | 257/303 (84.8) | 67/110 (60.9)52.8) | |
≥ 20 minutes | 46/303 (15.2) | 4359 (39.1)47.2) | |
Median | 7 (3–13) | 14 (5–40) | < 0.001 |
Sarnat staging | | | < 0.001 |
Stage 2 (moderate encephalopathy) | 359 (90.0) | 84 (43.5) | |
Stage 3 (severe encephalopathy) | 40 (10.0) | 109 (56.5) | |
Thompson score | | | < 0.001 |
≤ 10 | 185/384 (48.2) | 43/148 (29.0) | |
> 10 | 199/384 (51.8) | 105/148 (71.0) | |
Median Thompson score | 11 (9–13) | 14 (10–16) | < 0.001 |
Blood gas, pH | | | < 0.001 |
≥ 7.00 | 253/398 (63.6) | 63/179 (32.2 | |
< 7.00 | 145//398 (36.4) | 116/179(64.8) | |
Median pH | 7.05 (6.90–7.16) | 6.90 (6.70–7.10) | < 0.001 |
Blood gas, Base deficit (mmols/L) | | | 0.173 |
≤ 16.0 | 104/391 (26.6) | 48/177 (27.1) | |
> 16.0 | 287/391 (73.4) | 129/177 (72.9) | |
Median base deficit | 19.9 (16.0–24.0) | 22.3 (16.0-27.1) | 0.001 |
Five neonates (1.2%) in the cooled group had missing information on outcome at discharge. Amongst those with known outcome overall, 170/587 (29.0%) neonates diagnosed with moderate to severe encephalopathy had died at hospital discharge. There were 67/394 (17.0%) deaths in the cooled and 103/193 (53.4%) deaths in the non-cooled neonates. This difference was found to be significant upon Chi-squared analysis following Yates correction (p < 0.05).
On univariate analysis factors associated with mortality in the cooled neonates included gestational age < 38 weeks (OR 1.82, 95% CI 1.00-3.31), time to first breath > 20 minutes (OR 2.64, 95% CI 1.25–5.58), severe encephalopathy (OR 5.77, 95% CI 2.81–11.8), and a Thompson score > 10 (OR- 2.11, 95% CI 1.20–3.71). None of these factors were noted to be significantly associated with mortality on multivariate analysis (Table 4).
Table 4
Factors associated with mortality amongst neonates with moderate to severe encephalopathy who were cooled
| Non-survivors n = 67 | Survivors n = 327 | Univariate analysis | Multivariate analysis |
| | | OR (95% CI) | p-value | aOR (95% CI) | p-value |
Birth weight categories | | | | | N/A | |
≥ 2500 grams | 56 (83.6) | 291 (89.0) | 1 | | | |
< 2500 grams | 11 (16.4) | 36 (11.0) | 0.63 (0.30–1.31) | 0.213 | | |
Gestational age categories | | | | | | |
≥ 38 weeks | 46 (69.7) | 217 (66.4) | 1 | | 1 | |
< 38 weeks | 20 (30.3) | 63 (19.3) | 1.82 (1.00-3.31) | 0.045 | 1.47 (0.70–3.11) | 0.307 |
Sex | | | | | N/A | |
Female | 27 (40.3) | 122 (37.5) | 1 | | | |
Male | 40 (59.7) | 203 (62.5) | 0.89 (0.52–1.52) | 0.672 | | |
Apgar score at 5 minute | | | | | N/A | |
≥ 4 | 52/66 (78.8) | 275/321 (85.7) | 1 | | | |
0–3 | 14/66 (21.2) | 46/321 (14.3) | 1.61 (0.82–3.15) | 0.16 | | |
Time to First Breath | | | | | | |
< 20 minutes | 35/48 (72.9) | 220/251 (87.6) | 1 | | 1 | |
≥ 20 minutes | 13/48 (27.1) | 31/251 (12.4) | 2.64 (1.25–5.58) | 0.008 | 1.86 (0.74–4.63) | 0.184 |
Sarnat staging | | | | | | |
Stage 2 (moderate encephalopathy) | 48/67 (71.6) | 306/327 (93.6) | 1 | | 1 | |
Stage 3 (severe encephalopathy) | 19/67 (28.4) | 21/327 (6.42) | 5.77 (2.81–11.8) | 0.001 | 2.04 (0.74–5.67 | 0.17 |
Thompson score | | | | | | |
≤10 | 22/65 (33.8) | 163/314 (51.9) | 1 | | 1 | |
> 10 | 43/65 (66.2) | 151/314 (48.1) | 2.11 (1.20–3.71) | 0.008 | 1.52 (0.75–3.08) | 0.248 |
Blood gas, pH | | | | | | |
≥ 7.00 | 36/67 (53.7) | 214/326 (65.6) | 1 | | 1 | |
< 7.00 | 31/67 (46.3) | 112/326 (34.4) | 1.65 (0.96–2.81) | 0.065 | 1.01 (0.51-2.00) | 0.981 |
Blood gas, base deficit (mmols/L) | | | | | N/A | |
≤16 | 17/66 (25.8) | 85/320 (26.6) | 1 | | | |
> 16 | 49/66 (74.2) | 235/320 (73.4) | 1.04 (0.57–1.91) | 0.893 | | |
Amongst the non-cooled neonates, factors associated with mortality on univariate analysis were 5-minute Apgar score < 3 (OR 11.2, 95% CI 4.94–25.6), time to first breath > 20 minutes (OR 6.65, 95% CI 2.77-16.0), severe encephalopathy (OR 25.9, 95% 9.17-73.0), a Thompson score > 10 (OR 19.2, 95% CI 4.69–78.8), a pH < 7.00 (OR 7.57, 95% CI 3.18-18.0), and a high base deficit (OR 4.90, 95% CI 2.22–10.8). On multivariate analysis, the only factor that was associated with mortality was severe encephalopathy (OR 51.5, 95% CI 5.86–453; Table 5).
Table 5
Factors associated with mortality amongst neonates with moderate to severe encephalopathy who were not cooled
| Non-survivors n = 103 | Survivors n = 90 | Univariate analysis | Multivariate analysis |
| | | OR (95% CI) | p-value | OR (95% CI) | p-value |
Birth weight categories | | | | | | |
≥ 2500 grams | 76/103 (73.8) | 72/90 (80.0) | 1 | | N/A | N/A |
< 2500 grams | 27/103 (26.2) | 18/90 (20.0) | 1.42 (0.72–2.81) | 0.31 | | |
Gestational age categories | | | | | | |
≥ 38 weeks | 65/100 (65.0) | 27/89 (69.7) | 1 | | N/A | N/A |
< 38 weeks | 35/100 (35.0) | 62/89 (30.3) | 1.24 (0.67–2.28) | 0.497 | | |
Sex | | | | | | |
Female | 35/103 (34.0) | 40/90 (44.4) | 1 | | N/A | N/A |
Male | 68/103 (66.0) | 50/90 (55.6) | 1.55 (0.86–2.80) | 0.138 | | |
Apgar score at 5 minute | | | | | | |
≥ 4 | 22/97 (22.7) | 66/86 (76.7) | 1 | | 1 | |
0–3 | 75/97 (77.3) | 20/86 (23.3) | 11.2 (4.94–25.6) | < 0.001 | 0.94 (0.66–1.35) | 0.752 |
Time to First Breath | | | | | | |
< 20 minutes | 19/62 (30.6) | 47/63 (74.6) | 1 | | 1 | |
≥ 20 minutes | 43/62 (69.4) | 16/63 (25.4) | 6.65 (2.77-16.0) | < 0.001 | 0.48 (0.08–2.76) | 0.413 |
Sarnat staging | | | | | | |
Stage 2 (moderate encephalopathy) | 13/103 (12.6) | 71/90 (78.9) | 1 | | 1 | |
Stage 3 (severe encephalopathy) | 90/103 (97.4) | 19/90 (21.1) | 25.9 (9.17-73.0) | < 0.001 | 51.5 (5.86–453) | < 0.001 |
Thompson score | | | | | | |
≤ 10 | 3/65 (4.6) | 40/83 (48.2) | 1 | | 1 | |
> 10 | 62/65 (95.4) | 43/83 (51.8) | 19.2 (4.69–78.8) | < 0.001 | 1.21 (0.12–11.9) | 0.871 |
Arterial blood gas, pH | | | | | | |
≥ 7.00 | 11/92 (12.0) | 36/71 (58.7) | 1 | | 1 | |
< 7.00 | 81/92 (88.0) | 35/71 (49.3) | 7.57 (3.18-18.0) | < 0.001 | 3.40 (0.45–25.5) | 0.234 |
Arterial blood gas, base deficit (mmols/L) | | | | | | |
≤ 16 | 12/92 (13.0) | 36/85 (42.4) | 1 | | 1 | |
> 16 | 80/92 (87.0) | 49/85 (57.6) | 4.90 (2.22–10.8) | < 0.001 | 0.59 (0.09–3.91) | 0.586 |
Similar findings were found when comparing non-survivors to survivors with all neonates included irrespective of cooling status (entire cohort), severe encephalopathy was the only factor associated with mortality on multivariate analysis (OR 5.91, 95% CI 2.61–13.39; p < 0.001) (Table 6).
Table 6
Factors associated with mortality amongst all neonates with moderate to severe encephalopathy
| Non-survivors n = 170 | Survivors n = 417 | Univariate analysis | Multivariate analysis |
| | | OR (95% CI) | p-value | OR (95% CI) | p-value |
Birth weight categories | | | | | | |
≥ 2500 grams | 132/170 (77.6) | 363/ 417 (87.0) | 1 | | 1 | |
< 2500 grams | 38/170 (22.4) | 54/ 417 (13.0) | 1.94 (1.22–3.08) | 0.004 | 1.01 (0.40–2.57) | 0.978 |
Gestational age categories | | | | | | |
≥ 38 weeks | 111/166 (66.9) | 326/ 416 (78.4) | 1 | | 1 | |
< 38 weeks | 55/166 (33.2) | 90/ 416 (21.6) | 1.79 (1.20–2.68) | 0.004 | 0.94 (0.82–1.09) | 0.817 |
Sex | | | | | | |
Female | 62/170 (36.5) | 162/415 (39.0) | 1 | | N/A | N/A |
Male | 108/170 (63.5) | 253/415 (61.0) | 1.12 (0.77–1.61) | 0.562 | | |
Apgar score at 5 minute | | | | | | |
≥ 4 | 29/161 (18.0) | 139/409 (34.0) | 1 | | 1 | |
0–3 | 132/161 (82.0) | 270/409 (66.0) | 2.34 (1.48–3.70) | < 0.001 | 0.91 (0.76–1.08) | 0.225 |
Time to First Breath | | | | | | |
< 20 minutes | 94/150 (49.1) | 267/314 (85.0) | 1 | | 1 | |
≥ 20 minutes | 56/150 (50.9) | 47/314 (15.0) | 5.89 (3.49–9.94) | < 0.001 | 1.40 (0.63–3.07) | 0.415 |
Sarnat staging | | | | | | |
Stage 2 (moderate encephalopathy) | 61/170 (35.9) | 377/417 (90.4) | 1 | | 1 | |
Stage 3 (severe encephalopathy) | 109/170 (64.1) | 40/417 (9.6) | 16.8 (9.72–29.2) | < 0.001 | 5.91 (2.61–13.39) | < 0.001 |
Thompson score | | | | | | |
≤ 10 | 25/130 (19.2) | 203/397 (51.1) | 1 | | 1 | |
> 10 | 105/130 (80.8) | 194/397 (48.9) | 4.39 (2.67–7.23) | < 0.001 | 1.48 (0.74–2.92) | 0.222 |
Arterial blood gas, pH | | | | | | |
≥ 7.00 | 49/161 (30.4) | 264/411 (64.2) | 1 | | 1 | |
< 7.00 | 112/161 (69.6) | 147/411 (35.8) | 4.10 (2.72–6.20) | < 0.001 | 1.44 (0.73–2.87) | 0.294 |
Arterial blood gas, base deficit (mmols/L) | | | | | | |
≤ 16 | 29/158 (18.4) | 121/405 (29.9) | 1 | | 1 | |
> 16 | 129/158 (81.6) | 284/405 (70.1) | 1.89 (1.20-3.00) | < 0.001 | 0.64 (0.30–1.34) | 0.238 |
Received Cooling | | | | | | |
Yes | 67/170 (39.4) | 327/417 (78.4) | 1 | | 1 | |
No | 103/170 (60.6) | 90/417 (21.6) | 5.59 (3.68–8.48) | < 0.001 | 0.74 (0.38–1.44) | 0.380 |