Therapeutic hypothermia for neonatal encephalopathy: a report from the first 3 years of the Baby Cooling Registry of Japan

Tsuda, Kennosuke; Mukai, Takeo; Iwata, Sachiko; Shibasaki, Jun; Tokuhisa, Takuya; Ioroi, Tomoaki; Sano, Hiroyuki; Yutaka, Nanae; Takahashi, Akihito; Takeuchi, Akihito; Tamura, Toshiki; Araki, Yuko; Sobajima, Hisanori; Tamura, Masanori; Hosono, Shigeharu; Nabetani, Makoto; Iwata, Osuke

doi:10.1038/srep39508

Cited by 29 publications

(27 citation statements)

References 26 publications

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“…This is comparable to studies done elsewhere (11,36). This similarity could be due to similarities in the NICU protocols on feeding.…”

Section: Duration Of Hospital Staysupporting

confidence: 87%

Short term outcomes of newborn infants with Hypoxic Ischaemic Encephalopathy treated with therapeutic hypothermia in a low resource setting: A retrospective cohort study

Damoi¹,

Sebunya²,

Kirabira³

2020

Preprint

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Background Hypoxic Ischemic Encephalopathy (HIE) remains a significant cause of death and neuro-developmental deficits among children, especially in resource limited settings. Therapeutic hypothermia which is the mainstay of treatment for moderate to severe hypoxic ischaemic encephalopathy in developed countries, is not widely practiced in low resource settings and the available data is limited. We aimed to determine the short term outcomes and factors associated with survival among newborn infants with moderate to severe hypoxic ischaemic encephalopathy treated with therapeutic hypothermia at St. Francis Hospital, Nsambya. Methods Retrospective cohort study of 81 newborn infants with moderate to severe HIE who were 36 weeks and above that were cooled from June 2016 to February 2019, at St. Francis Hospital, Nsambya, Kampala, Uganda. Data on maternal and infant characteristics, clinical outcomes were extracted from the HIE registry and HIE follow up forms. Descriptive analysis was done to get the patient characteristics. Survival analysis was done to compare outcome among the groups of infants with significant factors at bivariate analysis. Multiple cox proportional hazards regression analysis was done to determine the factors independently associated with survival. Results The proportion of newborn infants who survived was 68/81(84%), (95%: CI: 0.74, 0.91).The factors associated with survival were a Thompson score of 7 to10 at initiation of cooling(HR: 0.07, 95% CI: 0.01, 0.94) and at 24 hours of cooling(HR:0.03, 95%CI: 0.004, 0.21), being born within the hospital providing therapeutic hypothermia (HR: 0.26, 95% CI: 0.07, 0.94) and not needing mechanical ventilator (HR: 0.03, 95% CI: 0.01, 0.14) or inotropic support.(HR: 0.13, 95%CI: 0.04, 0.38). The median time to attainment of full cup feeds was 6 days, with the majority 43/68(63%) attaining full feeds from 5 to 8 days. The median time to discharge was 7 days, and the median time to death was 3 days. The median Thompson score at discharge was 1 and at death was 16 Conclusion The survival rate of cooled infants in our setting at 84% is comparably high. The majority of infants have normal neurology at discharge.

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“…This is comparable to studies done elsewhere (11,36). This similarity could be due to similarities in the NICU protocols on feeding.…”

Section: Duration Of Hospital Staysupporting

confidence: 87%

Short term outcomes of newborn infants with Hypoxic Ischaemic Encephalopathy treated with therapeutic hypothermia in a low resource setting: A retrospective cohort study

Damoi¹,

Sebunya²,

Kirabira³

2020

Preprint

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“…Recently, the Baby Cooling Registry of Japan Collaboration Team reported data collected from 485 HIE infants who received therapeutic hypothermia from 2012 to 2014 32 . The basic characteristics of each of the study participants are similar, although the severity of HIE was slightly milder in the present study ( Table 5).…”

Section: Discussionmentioning

confidence: 99%

Autologous cord blood cell therapy for neonatal hypoxic-ischaemic encephalopathy: a pilot study for feasibility and safety

Tsuji

Sawada

Watabe

et al. 2020

Sci Rep

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Neonatal hypoxic-ischaemic encephalopathy (HIE) is a serious condition; many survivors develop neurological impairments, including cerebral palsy and intellectual disability. Preclinical studies show that the systemic administration of umbilical cord blood cells (UCBCs) is beneficial for neonatal HIE. We conducted a single-arm clinical study to examine the feasibility and safety of intravenous infusion of autologous UCBCs for newborns with HIE. When a neonate was born with severe asphyxia, the UCB was collected, volume-reduced, and divided into three doses. The processed UCB was infused at 12-24, 36-48, and 60-72 hours after the birth. The designed enrolment was six newborns. All six newborns received UCBC therapy strictly adhering to the study protocol together with therapeutic hypothermia. the physiological parameters and peripheral blood parameters did not change much between preand postinfusion. There were no serious adverse events that might be related to cell therapy. At 30 days of age, the six infants survived without circulatory or respiratory support. At 18 months of age, neurofunctional development was normal without any impairment in four infants and delayed with cerebral palsy in two infants. This pilot study shows that autologous UCBC therapy is feasible and safe. Acute brain dysfunction may occur unexpectedly during and immediately after birth. Brain dysfunction noted immediately after birth, from any cause, is collectively termed neonatal encephalopathy 1. The signs and symptoms of neonatal encephalopathy include altered levels of consciousness, weak muscle tone, impaired feeding, respiratory distress, and seizures. In many infants with neonatal encephalopathy, the pivotal pathophysiology is an insufficient supply of blood flow and oxygen to the brain in the ante-, intra-, or very immediate postpartum period. In these cases, neonatal encephalopathy is named hypoxic-ischaemic encephalopathy (HIE) 2. Mild hypothermia is the only therapy proven effective for term newborns with HIE 3,4. Even if infants with HIE receive therapeutic hypothermia, 40-44% die or survive with severe neurological impairments, including cerebral palsy and intellectual disability 3,4. The therapeutic time window is within 6 hours after birth for hypothermia to be effective 3,5,6. Hence, it is an urgent task to develop a novel therapy for HIE, especially a therapy with a long therapeutic time window 7. Cell-based therapy has attracted much attention because of not only its regenerative property but also its long therapeutic time window 8. Preclinical studies with animal models with neonatal encephalopathy show that cell therapies initiated hours or days after the injury are beneficial. Although a variety of cell therapies have been

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“…A rapid improvement in the national provision of evidencebased TH has been achieved. Our strong interventions in accordance with the international consensus guidelines might be effective in shifting empirical approaches to evidence-based practice (67).…”

Section: Framework Of Protective Therapy For Neonatal Hie In Japanmentioning

confidence: 95%

“…To examine the clinical use of TH, we analyzed the data collected during the first 3 years (2012-2014) of the Baby Cooling Registry of Japan (67). Of 485 cooled neonates, 96.5% were at ≥ 36 weeks gestation; 99.4% weighed ≥ 1,800 g. In addition, 96.7% required resuscitation for 410 min.…”

Section: Framework Of Protective Therapy For Neonatal Hie In Japanmentioning

confidence: 99%

Future perspectives of cell therapy for neonatal hypoxic–ischemic encephalopathy

2017

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Neonatal ischemic brain injury causes permanent motor-deficit cerebral palsy. Hypoxic-ischemic encephalopathy (HIE) is a very serious condition that can result in death and disability. In 1997, we reported that irreversible neuronal cell damage is induced by the elevation of intracellular Ca ion concentration that has occurred in sequence after excess accumulation of the excitatory neurotransmitter glutamate during ischemia. We also reported that hypothermia was effective in treating ischemic brain damage in rats by suppressing energy loss and raising intracellular Ca ion concentration. Following the 2010 revised International Liaison Committee on Resuscitation guideline, our group developed the Guideline for the treatment of Hypothermia in Japan, and we started online case registry in January 2012. However, therapeutic hypothermia must be initiated within the first 6 h after birth. By contrast, cell therapy may have a much longer therapeutic time window because it might reduce apoptosis/oxidative stress and enhance the regenerative process. In 2014, we administered autologous umbilical cord blood stem cell (UCBC) therapy for neonatal HIE, for the first time in Japan. We enrolled five full-term newborns with moderate-to-severe HIE. Our autologous UCBC therapy is leading to new protocols for the prevention of ischemic brain damage.

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Therapeutic hypothermia for neonatal encephalopathy: a report from the first 3 years of the Baby Cooling Registry of Japan

Cited by 29 publications

References 26 publications

Short term outcomes of newborn infants with Hypoxic Ischaemic Encephalopathy treated with therapeutic hypothermia in a low resource setting: A retrospective cohort study

Short term outcomes of newborn infants with Hypoxic Ischaemic Encephalopathy treated with therapeutic hypothermia in a low resource setting: A retrospective cohort study

Autologous cord blood cell therapy for neonatal hypoxic-ischaemic encephalopathy: a pilot study for feasibility and safety

Future perspectives of cell therapy for neonatal hypoxic–ischemic encephalopathy

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