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Erschienen in: Indian Journal of Pediatrics 3/2024

18.05.2023 | Original Article

Comparison of Different Adjuvant Therapies for Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review and Network Meta-Analysis

verfasst von: Qiang Fei, Dandan Wang, Tianming Yuan

Erschienen in: Indian Journal of Pediatrics | Ausgabe 3/2024

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Abstract

Objectives

Neonatal hypoxic-ischemic encephalopathy is a major cause of perinatal death and neurodevelopmental impairment (NDI). Hypothermia (HT) is the standard of care; however, additional neuroprotective agents are required to improve prognosis. The authors searched for all drugs in combination with HT and compared their effects using a network meta-analysis.

Methods

The authors searched PubMed, Embase, and Cochrane Library until September 24, 2022 for articles assessing mortality, NDI, seizures, and abnormal brain imaging findings in neonates with hypoxic-ischemic encephalopathy. Direct pairwise comparisons and a network meta-analysis was performed under random effects.

Results

Thirteen randomized clinical trials enroled 902 newborns treated with six combination therapies: erythropoietin magnesium sulfate, melatonin (MT), topiramate, xenon, and darbepoetin alfa. The results of all comparisons were not statistically significant, except for NDI, HT vs. MT+HT: odds ratio = 6.67, 95% confidence interval = 1.14–38.83; however, the overall evidence quality was low for the small sample size.

Conclusions

Currently, no combination therapy can reduce mortality, seizures, or abnormal brain imaging findings in neonatal hypoxic-ischemic encephalopathy. According to low quality evidence, HT combined with MT may reduce NDI.
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Literatur
1.
Zurück zum Zitat Tagin MA, Woolcott CG, Vincer MJ, Whyte RK, Stinson DA. Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. Arch Pediatr Adolesc Med. 2012;166:558–66.CrossRefPubMed Tagin MA, Woolcott CG, Vincer MJ, Whyte RK, Stinson DA. Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. Arch Pediatr Adolesc Med. 2012;166:558–66.CrossRefPubMed
2.
Zurück zum Zitat Liu L, Oza S, Hogan D, et al. Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet. 2015;385:430–40.CrossRefPubMed Liu L, Oza S, Hogan D, et al. Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet. 2015;385:430–40.CrossRefPubMed
3.
Zurück zum Zitat Azzopardi DV, Strohm B, Edwards AD, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009;361:1349–58.CrossRefPubMed Azzopardi DV, Strohm B, Edwards AD, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009;361:1349–58.CrossRefPubMed
4.
Zurück zum Zitat Victor S, Rocha-Ferreira E, Rahim A, Hagberg H, Edwards D. New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy. Eur J Pediatr. 2022;181:875–87.CrossRefPubMed Victor S, Rocha-Ferreira E, Rahim A, Hagberg H, Edwards D. New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy. Eur J Pediatr. 2022;181:875–87.CrossRefPubMed
5.
Zurück zum Zitat Nair J, Kumar VHS. Current and emerging therapies in the management of hypoxic ischemic encephalopathy in neonates. Children (Basel). 2018;5:99.PubMed Nair J, Kumar VHS. Current and emerging therapies in the management of hypoxic ischemic encephalopathy in neonates. Children (Basel). 2018;5:99.PubMed
6.
Zurück zum Zitat Wachtel EV, Verma S, Mally PV. Update on the current management of newborns with neonatal encephalopathy. Curr Probl Pediatr Adolesc Health Care. 2019;49:100636.CrossRefPubMed Wachtel EV, Verma S, Mally PV. Update on the current management of newborns with neonatal encephalopathy. Curr Probl Pediatr Adolesc Health Care. 2019;49:100636.CrossRefPubMed
7.
Zurück zum Zitat Rouse B, Chaimani A, Li T. Network meta-analysis: An introduction for clinicians. Intern Emerg Med. 2017;12:103–11.CrossRefPubMed Rouse B, Chaimani A, Li T. Network meta-analysis: An introduction for clinicians. Intern Emerg Med. 2017;12:103–11.CrossRefPubMed
8.
Zurück zum Zitat Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162:777–84.CrossRefPubMed Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162:777–84.CrossRefPubMed
9.
Zurück zum Zitat Higgins JP, Altman DG, Gøtzsche PC, et al. The cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.CrossRefPubMedPubMedCentral Higgins JP, Altman DG, Gøtzsche PC, et al. The cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Lv HY, Wu SJ, Wang QL, et al. Effect of erythropoietin combined with hypothermia on serum tau protein levels and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy. Neural Regen Res. 2017;12:1655–63.CrossRefPubMedPubMedCentral Lv HY, Wu SJ, Wang QL, et al. Effect of erythropoietin combined with hypothermia on serum tau protein levels and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy. Neural Regen Res. 2017;12:1655–63.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Wu YW, Mathur AM, Chang T, et al. High-dose erythropoietin and hypothermia for hypoxic-Ischemic encephalopathy: A phase II trial. Pediatrics. 2016;137:e20160191.CrossRefPubMed Wu YW, Mathur AM, Chang T, et al. High-dose erythropoietin and hypothermia for hypoxic-Ischemic encephalopathy: A phase II trial. Pediatrics. 2016;137:e20160191.CrossRefPubMed
12.
Zurück zum Zitat Wu YW, Comstock BA, Gonzalez FF, et al. Trial of erythropoietin for hypoxic-ischemic encephalopathy in newborns. N Engl J Med. 2022;387:148–59.CrossRefPubMedPubMedCentral Wu YW, Comstock BA, Gonzalez FF, et al. Trial of erythropoietin for hypoxic-ischemic encephalopathy in newborns. N Engl J Med. 2022;387:148–59.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Rahman SU, Canpolat FE, Oncel MY, et al. Multicenter randomized controlled trial of therapeutic hypothermia plus magnesium sulfate versus therapeutic hypothermia plus placebo in the management of term and near-term infants with hypoxic ischemic encephalopathy (The Mag Cool study): A pilot study. J Clin Neonatol. 2015;4:158–63.CrossRef Rahman SU, Canpolat FE, Oncel MY, et al. Multicenter randomized controlled trial of therapeutic hypothermia plus magnesium sulfate versus therapeutic hypothermia plus placebo in the management of term and near-term infants with hypoxic ischemic encephalopathy (The Mag Cool study): A pilot study. J Clin Neonatol. 2015;4:158–63.CrossRef
14.
Zurück zum Zitat Abdel-Aziz SM, Rahman MSMA, Shoreit AH, Din MEE, Hamed EA, Gad EF. Outcome of infants with hypoxic-ischemic encephalopathy treated by whole body cooling and magnesium sulfate. J Child Sci. 2021;11:e280–6.CrossRef Abdel-Aziz SM, Rahman MSMA, Shoreit AH, Din MEE, Hamed EA, Gad EF. Outcome of infants with hypoxic-ischemic encephalopathy treated by whole body cooling and magnesium sulfate. J Child Sci. 2021;11:e280–6.CrossRef
16.
Zurück zum Zitat Aly H, Elmahdy H, El-Dib M, et al. Melatonin use for neuroprotection in perinatal asphyxia: A randomized controlled pilot study. J Perinatol. 2015;35:186–91.CrossRefPubMed Aly H, Elmahdy H, El-Dib M, et al. Melatonin use for neuroprotection in perinatal asphyxia: A randomized controlled pilot study. J Perinatol. 2015;35:186–91.CrossRefPubMed
17.
Zurück zum Zitat Jerez-Calero A, Salvatierra-Cuenca MT, Benitez-Feliponi Á, et al. Hypothermia plus melatonin in asphyctic newborns: A Randomized-Controlled Pilot Study. Pediatr Crit Care Med. 2020;21:647–55.CrossRefPubMed Jerez-Calero A, Salvatierra-Cuenca MT, Benitez-Feliponi Á, et al. Hypothermia plus melatonin in asphyctic newborns: A Randomized-Controlled Pilot Study. Pediatr Crit Care Med. 2020;21:647–55.CrossRefPubMed
18.
Zurück zum Zitat Nuñez-Ramiro A, Benavente-Fernández I, Valverde E, et al. Topiramate plus cooling for hypoxic-ischemic encephalopathy: A randomized, controlled, multicenter, double-blinded trial. Neonatology. 2019;116:76–84.CrossRefPubMed Nuñez-Ramiro A, Benavente-Fernández I, Valverde E, et al. Topiramate plus cooling for hypoxic-ischemic encephalopathy: A randomized, controlled, multicenter, double-blinded trial. Neonatology. 2019;116:76–84.CrossRefPubMed
19.
Zurück zum Zitat Filippi L, Fiorini P, Catarzi S, et al. Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI): a feasibility study. J Matern Fetal Neonatal Med. 2018;31:973–80.CrossRefPubMed Filippi L, Fiorini P, Catarzi S, et al. Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI): a feasibility study. J Matern Fetal Neonatal Med. 2018;31:973–80.CrossRefPubMed
20.
Zurück zum Zitat Azzopardi D, Robertson NJ, Bainbridge A, et al. Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): A proof-of-concept, open-label, randomised controlled trial. Lancet Neurol. 2016;15:145–53.CrossRefPubMedPubMedCentral Azzopardi D, Robertson NJ, Bainbridge A, et al. Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): A proof-of-concept, open-label, randomised controlled trial. Lancet Neurol. 2016;15:145–53.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Azzopardi D, Chew AT, Deierl A, et al. Prospective qualification of early cerebral biomarkers in a randomised trial of treatment with xenon combined with moderate hypothermia after birth asphyxia. EBioMedicine. 2019;47:484–91.CrossRefPubMedPubMedCentral Azzopardi D, Chew AT, Deierl A, et al. Prospective qualification of early cerebral biomarkers in a randomised trial of treatment with xenon combined with moderate hypothermia after birth asphyxia. EBioMedicine. 2019;47:484–91.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Baserga MC, Beachy JC, Roberts JK, et al. Darbepoetin administration to neonates undergoing cooling for encephalopathy: a safety and pharmacokinetic trial. Pediatr Res. 2015;78:315–22.CrossRefPubMedPubMedCentral Baserga MC, Beachy JC, Roberts JK, et al. Darbepoetin administration to neonates undergoing cooling for encephalopathy: a safety and pharmacokinetic trial. Pediatr Res. 2015;78:315–22.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Juul S. Recombinant erythropoietin as a neuroprotective treatment: in vitro and in vivo models. Clin Perinatol. 2004;31:129–42.CrossRefPubMed Juul S. Recombinant erythropoietin as a neuroprotective treatment: in vitro and in vivo models. Clin Perinatol. 2004;31:129–42.CrossRefPubMed
24.
Zurück zum Zitat Lee CYZ, Chakranon P, Lee SWH. Comparative efficacy and safety of neuroprotective therapies for neonates with hypoxic ischemic encephalopathy: A network meta-analysis. Front Pharmacol. 2019;10:1221.CrossRefPubMedPubMedCentral Lee CYZ, Chakranon P, Lee SWH. Comparative efficacy and safety of neuroprotective therapies for neonates with hypoxic ischemic encephalopathy: A network meta-analysis. Front Pharmacol. 2019;10:1221.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Liu TS, Yin ZH, Yang ZH, Wan LN. The effects of monotherapy with erythropoietin in neonatal hypoxic-ischemic encephalopathy on neurobehavioral development: A systematic review and meta-analysis. Eur Rev Med Pharmacol Sci. 2021;25:2318–26.PubMed Liu TS, Yin ZH, Yang ZH, Wan LN. The effects of monotherapy with erythropoietin in neonatal hypoxic-ischemic encephalopathy on neurobehavioral development: A systematic review and meta-analysis. Eur Rev Med Pharmacol Sci. 2021;25:2318–26.PubMed
26.
Zurück zum Zitat Robertson NJ, Lingam I, Meehan C, et al. High-dose melatonin and ethanol excipient combined with therapeutic hypothermia in a newborn piglet asphyxia model. Sci Rep. 2020;10:3898.ADSCrossRefPubMedPubMedCentral Robertson NJ, Lingam I, Meehan C, et al. High-dose melatonin and ethanol excipient combined with therapeutic hypothermia in a newborn piglet asphyxia model. Sci Rep. 2020;10:3898.ADSCrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Zhao Z, Lu C, Li T, et al. The protective effect of melatonin on brain ischemia and reperfusion in rats and humans: In vivo assessment and a randomized controlled trial. J Pineal Res. 2018;65:e12521.CrossRefPubMed Zhao Z, Lu C, Li T, et al. The protective effect of melatonin on brain ischemia and reperfusion in rats and humans: In vivo assessment and a randomized controlled trial. J Pineal Res. 2018;65:e12521.CrossRefPubMed
29.
Zurück zum Zitat Ramos E, Patino P, Reiter RJ, et al. Ischemic brain injury: New insights on the protective role of melatonin. Free Radic Biol Med. 2017;104:32–53.CrossRefPubMed Ramos E, Patino P, Reiter RJ, et al. Ischemic brain injury: New insights on the protective role of melatonin. Free Radic Biol Med. 2017;104:32–53.CrossRefPubMed
30.
Zurück zum Zitat Dixon BJ, Reis C, Ho WM, Tang J, Zhang JH. Neuroprotective strategies after neonatal hypoxic ischemic encephalopathy. Int J Mol Sci. 2015;16:22368–401.CrossRefPubMedPubMedCentral Dixon BJ, Reis C, Ho WM, Tang J, Zhang JH. Neuroprotective strategies after neonatal hypoxic ischemic encephalopathy. Int J Mol Sci. 2015;16:22368–401.CrossRefPubMedPubMedCentral
Metadaten
Titel
Comparison of Different Adjuvant Therapies for Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review and Network Meta-Analysis
verfasst von
Qiang Fei
Dandan Wang
Tianming Yuan
Publikationsdatum
18.05.2023
Verlag
Springer India
Erschienen in
Indian Journal of Pediatrics / Ausgabe 3/2024
Print ISSN: 0019-5456
Elektronische ISSN: 0973-7693
DOI
https://doi.org/10.1007/s12098-023-04563-3

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