Efficacy of therapeutic hypothermia on mild neonatal hypoxic-ischemic encephalopathy: a prospective randomized controlled study

HUANG Jie; DING Ya-Ling; GAO Liang; ZHU Yao; LIN Ya-Yin; LIN Xin-Zhu

doi:10.7499/j.issn.1008-8830.2401031

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Chinese Journal of Contemporary Pediatrics ›› 2024, Vol. 26 ›› Issue (8) : 803-810. DOI: 10.7499/j.issn.1008-8830.2401031

CLINICAL RESEARCH

Efficacy of therapeutic hypothermia on mild neonatal hypoxic-ischemic encephalopathy: a prospective randomized controlled study

HUANG Jie, DING Ya-Ling, GAO Liang, ZHU Yao, LIN Ya-Yin, LIN Xin-Zhu

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Abstract

Objective To investigate the efficacy of therapeutic hypothermia on mild neonatal hypoxic-ischemic encephalopathy (HIE). Methods A prospective study was performed on 153 neonates with mild HIE who were born from September 2019 to September 2023. These neonates were randomly divided into two groups: therapeutic hypothermia (n=77) and non-therapeutic hypothermia group (n=76). The short-term clinical efficacy of the two groups were compared. Barkovich scoring system was used to analyze the severity of brain injury shown on magnetic resonance imaging (MRI) between the two groups. Results There were no significant differences in gestational age, gender, birth weight, mode of birth, and Apgar score between the therapeutic hypothermia and non-therapeutic hypothermia groups (P>0.05). There were no significant differences in the incidence rates of sepsis, arrhythmia, persistent pulmonary hypertension and pulmonary hemorrhage and the duration of mechanical ventilation within the first 72 hours after birth between the two groups. The therapeutic hypothermia group had longer prothrombin time within the first 72 hours after birth and a longer hospital stay (P<0.05). Compared with the non-therapeutic hypothermia group, the therapeutic hypothermia group had lower incidence rates of MRI abnormalities (30% vs 57%), moderate to severe brain injury on MRI (5% vs 28%), and watershed injury (27% vs 51%) (P<0.05), as well as lower medium watershed injury score (0 vs 1) (P<0.05). Conclusions Therapeutic hypothermia can reduce the incidence rates of MRI abnormalities and watershed injury, without obvious adverse effects, in neonates with mild HIE, suggesting that therapeutic hypothermia may be beneficial in neuroprotection in these neonates.

Key words

Hypoxic-ischemic encephalopathy / Therapeutic hypothermia / Brain magnetic resonance imaging / Brain injury / Neonate

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HUANG Jie, DING Ya-Ling, GAO Liang, ZHU Yao, LIN Ya-Yin, LIN Xin-Zhu. Efficacy of therapeutic hypothermia on mild neonatal hypoxic-ischemic encephalopathy: a prospective randomized controlled study[J]. Chinese Journal of Contemporary Pediatrics. 2024, 26(8): 803-810 https://doi.org/10.7499/j.issn.1008-8830.2401031

References

1 Papazian O. Neonatal hypoxic-ischemic encephalopathy[J]. Medicina (B Aires), 2018, 78 (Suppl 2): 36-41. PMID: 30199363.
2 Sun YJ, Zhang ZY, Fan B, et al. Neuroprotection by therapeutic hypothermia[J]. Front Neurosci, 2019, 13: 586. PMID: 31244597. PMCID: PMC6579927. DOI: 10.3389/fnins.2019.00586.
3 曹长青, 李宇宁, 杨学梅, 等. 亚低温治疗新生儿缺氧缺血性脑病远期临床效果的Meta分析[J]. 中国当代儿科杂志, 2015, 17(2): 122-127. PMID: 25760834. DOI: 10.7499/j.issn.1008-8830.2015.02.003.
4 中华医学会儿科学分会新生儿学组, 中华儿科杂志编辑委员会. 亚低温治疗新生儿缺氧缺血性脑病专家共识（2022）[J]. 中华儿科杂志, 2022, 60(10): 983-989. PMID: 36207843. DOI: 10.3760/cma.j.cn112140-20220418-00344.
5 Kasdorf E, Laptook A, Azzopardi D, et al. Improving infant outcome with a 10 min Apgar of 0[J]. Arch Dis Child Fetal Neonatal Ed, 2015, 100(2): F102-F105. PMID: 25342246. DOI: 10.1136/archdischild-2014-306687.
6 Conway JM, Walsh BH, Boylan GB, et al. Mild hypoxic ischaemic encephalopathy and long term neurodevelopmental outcome: a systematic review[J]. Early Hum Dev, 2018, 120: 80-87. PMID: 29496329. DOI: 10.1016/j.earlhumdev.2018.02.007.
7 Finder M, Boylan GB, Twomey D, et al. Two-year neurodevelopmental outcomes after mild hypoxic ischemic encephalopathy in the era of therapeutic hypothermia[J]. JAMA Pediatr, 2020, 174(1): 48-55. PMID: 31710357. PMCID: PMC6865301. DOI: 10.1001/jamapediatrics.2019.4011.
8 Goswami IR, Whyte H, Wintermark P, et al. Characteristics and short-term outcomes of neonates with mild hypoxic-ischemic encephalopathy treated with hypothermia[J]. J Perinatol, 2020, 40(2): 275-283. PMID: 31723237. DOI: 10.1038/s41372-019-0551-2.
9 McDouall A, Wassink G, Bennet L, et al. Challenges in developing therapeutic strategies for mild neonatal encephalopathy[J]. Neural Regen Res, 2022, 17(2): 277-282. PMID: 34269188. PMCID: PMC8464003. DOI: 10.4103/1673-5374.317963.
10 Prempunpong C, Chalak LF, Garfinkle J, et al. Prospective research on infants with mild encephalopathy: the PRIME study[J]. J Perinatol, 2018, 38(1): 80-85. PMID: 29095433. PMCID: PMC8592379. DOI: 10.1038/jp.2017.164.
11 王颖雯, 王睁, 程国强, 等. 轻度新生儿缺氧缺血性脑病神经系统发育结局的系统评价/Meta分析[J]. 中国循证儿科杂志, 2022, 17(2): 90-97. DOI: 10.3969/j.issn.1673-5501.2022.02.002.
12 中华医学会儿科学分会新生儿学组. 新生儿缺氧缺血性脑病诊断标准[J]. 中国当代儿科杂志, 2005, 7(2): 97-98. DOI: 10.3969/j.issn.1008-8830.2005.02.001.
13 Walsh BH, Neil J, Morey J, et al. The frequency and severity of magnetic resonance imaging abnormalities in infants with mild neonatal encephalopathy[J]. J Pediatr, 2017, 187: 26-33.e1. PMID: 28479101. PMCID: PMC5533615. DOI: 10.1016/j.jpeds.2017.03.065.
14 中华医学会儿科学分会围产专业委员会. 新生儿振幅整合脑电图临床应用专家共识[J]. 中华新生儿科杂志, 2019, 34(1): 3-7. DOI: 10.3760/cma.j.issn.2096-2932.2019.01.002.
15 Barkovich AJ, Hajnal BL, Vigneron D, et al. Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems[J]. AJNR Am J Neuroradiol, 1998, 19(1): 143-149. PMID: 9432172. PMCID: PMC8337350.
16 中国医师协会新生儿科医师分会. 新生儿缺氧缺血性脑病磁共振诊断与损伤类型的分类建议[J]. 中国当代儿科杂志, 2017, 19(12): 1225-1233. PMID: 29237520. PMCID: PMC7389802. DOI: 10.7499/j.issn.1008-8830.2017.12.001.
17 Bonifacio SL, Glass HC, Vanderpluym J, et al. Perinatal events and early magnetic resonance imaging in therapeutic hypothermia[J]. J Pediatr, 2011, 158(3): 360-365. PMID: 20965514. PMCID: PMC3035732. DOI: 10.1016/j.jpeds.2010.09.003.
18 Skranes JH, Cowan FM, Stiris T, et al. Brain imaging in cooled encephalopathic neonates does not differ between four and 11 days after birth[J]. Acta Paediatr, 2015, 104(8): 752-758. PMID: 25824694. DOI: 10.1111/apa.13016.
19 Zhou WH, Cheng GQ, Shao XM, et al. Selective head cooling with mild systemic hypothermia after neonatal hypoxic-ischemic encephalopathy: a multicenter randomized controlled trial in China[J]. J Pediatr, 2010, 157(3): 367-372.e3. PMID: 20488453. DOI: 10.1016/j.jpeds.2010.03.030.
20 Gagne-Loranger M, Sheppard M, Ali N, et al. Newborns referred for therapeutic hypothermia: association between initial degree of encephalopathy and severity of brain injury (what about the newborns with mild encephalopathy on admission?)[J]. Am J Perinatol, 2016, 33(2): 195-202. PMID: 26352683. DOI: 10.1055/s-0035-1563712.
21 Wang Z, Zhang D, Zhang P, et al. Safety and efficacy of therapeutic hypothermia in neonates with mild hypoxic-ischemic encephalopathy[J]. BMC Pediatr, 2023, 23(1): 530. PMID: 37884911. PMCID: PMC10601291. DOI: 10.1186/s12887-023-04365-8.
22 Wisnowski JL, Wintermark P, Bonifacio SL, et al. Neuroimaging in the term newborn with neonatal encephalopathy[J]. Semin Fetal Neonatal Med, 2021, 26(5): 101304. PMID: 34736808. PMCID: PMC9135955. DOI: 10.1016/j.siny.2021.101304.
23 Montaldo P, Lally PJ, Oliveira V, et al. Therapeutic hypothermia initiated within 6 hours of birth is associated with reduced brain injury on MR biomarkers in mild hypoxic-ischaemic encephalopathy: a non-randomised cohort study[J]. Arch Dis Child Fetal Neonatal Ed, 2019, 104(5): F515-F520. PMID: 30425113. PMCID: PMC6788875. DOI: 10.1136/archdischild-2018-316040.
24 Rao R, Mietzsch U, DiGeronimo R, et al. Utilization of therapeutic hypothermia and neurological injury in neonates with mild hypoxic-ischemic encephalopathy: a report from children's hospital neonatal consortium[J]. Am J Perinatol, 2022, 39(3): 319-328. PMID: 32892328. DOI: 10.1055/s-0040-1716341.
25 Koo E, Sheldon RA, Lee BS, et al. Effects of therapeutic hypothermia on white matter injury from murine neonatal hypoxia-ischemia[J]. Pediatr Res, 2017, 82(3): 518-526. PMID: 28561815. PMCID: PMC5570671. DOI: 10.1038/pr.2017.75.
26 Bach AM, Fang AY, Bonifacio S, et al. Early magnetic resonance imaging predicts 30-month outcomes after therapeutic hypothermia for neonatal encephalopathy[J]. J Pediatr, 2021, 238: 94-101.e1. PMID: 34237346. DOI: 10.1016/j.jpeds.2021.07.003.
27 Al Amrani F, Marcovitz J, Sanon PN, et al. Prediction of outcome in asphyxiated newborns treated with hypothermia: is a MRI scoring system described before the cooling era still useful?[J]. Eur J Paediatr Neurol, 2018, 22(3): 387-395. PMID: 29439909. DOI: 10.1016/j.ejpn.2018.01.017.
28 Barkovich AJ, Miller SP, Bartha A, et al. MR imaging, MR spectroscopy, and diffusion tensor imaging of sequential studies in neonates with encephalopathy[J]. AJNR Am J Neuroradiol, 2006, 27(3): 533-547. PMID: 16551990. PMCID: PMC7976955.
29 Saw CL, Rakshasbhuvankar A, Rao S, et al. Current practice of therapeutic hypothermia for mild hypoxic ischemic encephalopathy[J]. J Child Neurol, 2019, 34(7): 402-409. PMID: 30898007. DOI: 10.1177/0883073819828625.
30 Yieh L, Lee H, Lu T, et al. Neonates with mild hypoxic-ischaemic encephalopathy receiving supportive care versus therapeutic hypothermia in California[J]. Arch Dis Child Fetal Neonatal Ed, 2022, 107(3): 324-328. PMID: 34462319. DOI: 10.1136/archdischild-2021-322250.
31 Oliveira V, Singhvi DP, Montaldo P, et al. Therapeutic hypothermia in mild neonatal encephalopathy: a national survey of practice in the UK[J]. Arch Dis Child Fetal Neonatal Ed, 2018, 103(4): F388-F390. PMID: 28942433. DOI: 10.1136/archdischild-2017-313320.
32 El-Dib M, Inder TE, Chalak LF, et al. Should therapeutic hypothermia be offered to babies with mild neonatal encephalopathy in the first 6 h after birth?[J]. Pediatr Res, 2019, 85(4): 442-448. PMID: 30733613. DOI: 10.1038/s41390-019-0291-1.
33 Chawla S, Bates SV, Shankaran S. Is it time for a randomized controlled trial of hypothermia for mild hypoxic-ischemic encephalopathy?[J]. J Pediatr, 2020, 220: 241-244. PMID: 31952851. PMCID: PMC8462395. DOI: 10.1016/j.jpeds.2019.11.030.