The time of initiation of therapeutic hypothermia and the course of hypoxic-ischemic encephalopathy in term newborns


  • K.Yu. Sokolova State Institution “Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine”, Dnіpro, Ukraine



newborns, hypoxic-ischemic encephalopathy, therapeutic hypothermia


Background. The current algorithm for therapeutic hypothermia in full-term infants with hypoxic-ischemic encephalopathy requires the initiation of hypothermia within the first six hours of life. But the question remains unsolved about the possible benefits of early initiation of hypothermia (within the first hour of life), taking into account the different models of the procedure. The aim of our work was to investigate the relationship between the time of initiation of the phase of passive cooling of therapeutic hypothermia and the short-term effects of hypoxic-ischemic encephalopathy. Materials and methods. Analysis of manifestations of hypoxic-ischemic encephalopathy was performed depending on the time of hypothermia initiation: in the first hour of life or during the first 2–6 hours of life. Results. The study included 129 full-term infants with asphyxia at birth, who underwent therapeutic hypothermia (a model of systemic hypothermia using simple means of cooling). Among infants with an early initiation of cooling, the course of hypoxic-ischemic encephalopathy was unfavourable in 27.7 % (23/83) of cases. Among newborns with later initiation of hypothermia, 36.1 % (13/46) of children had an adverse course of hypoxic-ischemic encephalopathy. No significant changes were found between the groups with different time of initiation of passive cooling in terms of the frequency of destructive hypoxic-ischemic brain lesions and fatal cases due to the development of post-ischemic brain edema and multiple organ failure (p = 0.551). Significant differences were observed between the groups in terms of the core body temperature at the time of hospitalization in the neonatal hospital (33.17 ± 0.11 °C vs. 33.85 ± 0.18 °C), the age at reaching the target temperature (4.64 ± 0.65 hours vs. 7.52 ± 1.35 hours), duration of hospitalization in neonatal department (27.3 ± 1.4 days vs. 33.8 ± 2.7 days, p = 0.020). Conclusions. No significant differences were found in the short-term effects of hypoxic-ischemic lesions depending on the initiation of passive cooling within the first 6 hours of life. However, infants, who were passively cooled during the first hour of life, had lower core body temperatures at the time of hospitalization and reached the target cooling temperature faster.


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Lee AC, Kozuki N, Blencowe H, et al. Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatr Res. 2013;74 Suppl 1(Suppl 1):50–72. doi:10.1038/pr.2013.206.

Lawn JE, Blencowe H, Oza S, et al. Every Newborn: progress, priorities, and potential beyond survival. Lancet. 2014;384(9938):189–205. doi:10.1016/S0140-6736(14)60496-7.

Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013;(1):CD003311. doi:10.1002/14651858.CD003311.pub3.

Enweronu-Laryea C, Martinello KA, Rose M, et al. Core temperature after birth in babies with neonatal encephalopathy in a sub-Saharan African hospital setting. J Physiol. 2019;597(15):4013–4024. doi:10.1113/JP277820.

El-Dib M, Inder TE, Chalak LF, Massaro AN, Thoresen M, Gunn AJ. Should therapeutic hypothermia be offered to babies with mild neonatal encephalopathy in the first 6 h after birth?. Pediatr Res. 2019;85(4):442–448. doi:10.1038/s41390-019-0291-1.

Chiang MC, Jong YJ, Lin CH. Therapeutic hypothermia for neonates with hypoxic ischemic encephalopathy. Pediatr Neonatol. 2017;58(6):475–483. doi:10.1016/j.pedneo.2016.11.001.

Mietzsch U, Radhakrishnan R, Boyle FA, Juul S, Wood TR. Active cooling temperature required to achieve therapeutic hypothermia correlates with short-term outcome in neonatal hypoxic-ischaemic encephalopathy. J Physiol. 2020;598(2):415–424. doi:10.1113/JP278790.

Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353(15):1574–1584. doi:10.1056/NEJMcps050929.

Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005;365(9460):663–670. doi:10.1016/S0140-6736(05)17946-X.

Azzopardi DV, Strohm B, Edwards AD, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy [published correction appears in N Engl J Med. 2010 Mar 18;362(11):1056]. N Engl J Med. 2009;361(14):1349–1358. doi:10.1056/NEJMoa0900854.

Simbruner G, Mittal RA, Rohlmann F, Muche R; Trial Participants. Systemic hypothermia after neonatal encephalopathy: outcomes of RCT. Pediatrics. 2010;126(4):e771–e778. doi:10.1542/peds.2009-2441.

Jacobs SE, Morley CJ, Inder TE, et al. Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial. Arch Pediatr Adolesc Med. 2011;165(8):692–700. doi:10.1001/archpediatrics.2011.43.

Lemyre B, Chau V. Hypothermia for newborns with hypoxic-ischemic encephalopathy. Paediatr Child Health. 2018;23(4):285–291. doi:10.1093/pch/pxy028.

Guillot M, Philippe M, Miller E, et al. Influence of timing of initiation of therapeutic hypothermia on brain MRI and neurodevelopment at 18 months in infants with HIE: a retrospective cohort study. BMJ Paediatr Open. 2019;3(1):e000442. doi:10.1136/bmjpo-2019-000442.

Roelfsema V, Bennet L, George S, et al. Window of opportunity of cerebral hypothermia for postischemic white matter injury in the near-term fetal sheep. J Cereb Blood Flow Metab. 2004;24(8):877–886. doi:10.1097/01.WCB.0000123904.17746.92.

Sabir H, Scull-Brown E, Liu X, Thoresen M. Immediate hypothermia is not neuroprotective after severe hypoxia-ischemia and is deleterious when delayed by 12 hours in neonatal rats. Stroke. 2012;43(12):3364–3370. doi:10.1161/STROKEAHA.112.674481.

Lemyre B, Ly L, Chau V, et al. Initiation of passive cooling at referring centre is most predictive of achieving early therapeutic hypothermia in asphyxiated newborns. Paediatr Child Health. 2017;22(5):264–268. doi:10.1093/pch/pxx062.

Thoresen M, Tooley J, Liu X, et al. Time is brain: starting therapeutic hypothermia within three hours after birth improves motor outcome in asphyxiated newborns. Neonatology. 2013;104(3):228–233. doi:10.1159/000353948.

Enweronu-Laryea C, Martinello KA, Rose M, et al. Core temperature after birth in babies with neonatal encephalopathy in a sub-Saharan African hospital setting. J Physiol. 2019 Aug;597(15):4013–4024. doi:10.1113/JP277820.

Shellhaas RA, Chang T, Tsuchida T, et al. The American Clinical Neurophysiology Society's Guideline on Continuous Electroencephalography Monitoring in Neonates. J Clin Neurophysiol. 2011;28(6):611–617. doi:10.1097/WNP.0b013e31823e96d7.

Surkov DM, Mokhulska OM. Temperature control during the therapeutic hypothermia period in neonates with hypoxicischemic encephalopathy. Actual Problems of Pediatry, Obstetrics and Gynecology. 2019;(1):26–32. doi:10.11603/24116-4944.2019.1.10177. (in Ukrainian).

Laponog SP. Features of the course of temperature changes in newborns with severe asphyxia during a session of craniocerebral hypothermia. Medicni perspektivi. 2011;16(2):35– 42. (in Ukrainian).



How to Cite

Sokolova, K. (2021). The time of initiation of therapeutic hypothermia and the course of hypoxic-ischemic encephalopathy in term newborns. CHILD`S HEALTH, 15(1), 36–41.




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