Details of studies meeting the eligibility criteria
| Study | N* | GA | Evidence of asphyxia | Neurological exam | Intervention | Device | Age at follow up | Definition of adverse outcome |
| Jacobs et al 12 | 40 | >35 | A/S <5 or resuscitation at 10 min; Cord pH <7.0; BD >12. | Modified Sarnat staging. | Whole body cooling (33.0°C–34.0°C) for 72 hours. | Ice packs. | 24 months. | Mortality or major sensorineural disability (Bayley II Psychomotor or mental development index <2 SD, cerebral palsy, blindness or deafness) at 2 years of age. |
| Zhou et al 13 | 39 | ≥37 | A/S <6 or need for resuscitation at 5 min; Cord pH <7.0 or BD >16. | Modified Sarnat staging. | Selective head cooling (rectal temperature 34.5°C–35.0°C) for 72 hours. | Cooling cap. | 18 months. | Gesell Child Development Age Scale (Gross Motor Function Classification System level 3–5 or DQ <70). |
| Thayyil et al 5 | 19 | ≥36 | A/S <6 or need for resuscitation at 5 min. | Thompson encephalopathy score. | Whole body cooling (33.0°C–34.0°C) for 72 hours. | Phase change material. | 42 months. | Cerebral palsy, visual or hearing impairment, composite motor score <82 or composite cognitive score <85 on Bayley III. |
| Battin et al 14 | 11 | >37 | A/S <6 at 5 min; Cord pH <7. | Clinical encephalopathy (lethargy/stupor, hypotonia, abnormal reflexes including absent/weak suck). | Selective head cooling either: minimally cooled (36.5°C–36.0°C) or mildly cooled (35.9°C–35.5°C) for 72 hours. | Cooling cap. | 18 months. | Death, cerebral palsy, Bayley scores >2 SDs from the norm, blindness or hearing impairment requiring amplification, at 2 years of age. |
| Gluckman et al 6 | 8 | ≥36 | A/S <6 or resuscitation at 10 min; pH <7 or BD >16; abnormal aEEG. | Modified Sarnat staging. | Selective head cooling (34.5±0.5°C) for 72 hours. | Cooling cap. | 18 months. | Severe neurodevelopmental disability was defined as (1) gross motor function classification levels 3–5 (non-ambulatory, sits with support applied to lower back or limited or no self-mobility), (2) Bayley Mental Developmental Index of 70 or (3) bilateral cortical visual impairment; at 18 months of age. |
| Lin et al 15† | 14 | ≥37 | A/S <6 at 5 min; pH <7 or BD >15. | Decreased muscle tone, lethargy, coma or seizures. | Selective head cooling with rectal temperature 34.5°C–35.0°C for 72 hours. | Cooling cap. | 10 days. | Neonatal Behavioural Neurological Assessment score at 7–10 days of life, CT scan grading at 5–7 postnatal days. No long-term follow-up available. |
| Eicher et al 16‡ | 2 | ≥36 | Cord gas pH <7.0 or BD >13, initial infant gas pH <7.1, Apgar score 5 at 10 min or continued resuscitation after 5 min. | Any two of: posturing, seizures, autonomic dysfunction or increased/decreased abnormalities of tone, reflexes or state of consciousness. | Whole body cooling (33.0°C–34.0°C) for 48 hours. | Blanketrol. | 12 months. | Severely abnormal was defined as >2 SDs from mean, moderately abnormal as >1 and ≤2 SD on neurodevelopmental tests of motor function (Bayley Psychomotor Development Index, Vineland gross motor) and cognitive function (Bayley II). |
*Number of babies with mild encephalopathy.
†Not included in the meta-analysis as the authors did not provide the data on babies with mild encephalopathy.
‡Two babies with mild encephalopathy recruited: one withdrew from the study and other lost to follow-up (data provided by the corresponding author). Hence, not included in the meta-analysis.
aEEG, amplitude integrated electroencephalography; A/S, Apgar score; BD, base deficit; DQ, developmental quotient; GA: gestational age.