Kennosuke Tsuda1,2, Jun Shibasaki3, Tetsuya Isayama4, Akihito Takeuchi5, Takeo Mukai6, Tomoaki Ioroi7, Akihito Takahashi8, Hiroyuki Sano9, Nanae Yutaka9, Sachiko Iwata2, Makoto Nabetani9, Hisanori Sobajima10, Shigeharu Hosono11, Masanori Tamura12, Osuke Iwata13. 1. Department of Pediatrics, Japanese Red Cross Nagoya Daini Hospital, Aichi, Japan. 2. Center for Human Development and Family Science, Department of Neonatology and Pediatrics, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan. 3. Department of Neonatology, Kanagawa Children's Medical Center, Kanagawa, Japan. 4. Division of Neonatology, Center of Maternal-Fetal Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan. 5. Division of Neonatology, National Hospital Organization Okayama Medical Center, Okayama, Japan. 6. Department of Pediatrics, The University of Tokyo Hospital, Tokyo, Japan. 7. Department of Pediatrics, Perinatal Medical Center, Himeji Red Cross Hospital, Hyogo, Japan. 8. Department of Pediatrics, Kurashiki Central Hospital, Okayama, Japan. 9. Department of Pediatrics, Yodogawa Christian Hospital, Osaka, Japan. 10. Division of Neonatology, Center for Maternal, Fetal and Neonatal Medicine, Saitama Medical Center, Saitama Medical University, Saitama, Japan. 11. Division of Neonatology, Department of Perinatal and Neonatal Medicine, Jichi Medical University Saitama Medical Center, Saitama, Japan. 12. Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan. 13. Center for Human Development and Family Science, Department of Neonatology and Pediatrics, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan. o.iwata@med.nagoya-cu.ac.jp.
Abstract
BACKGROUND: Therapeutic hypothermia is a standard of care for neonatal encephalopathy; however, approximately one in two newborn infants fails to respond to this treatment. Recent studies have suggested potential relationships between body temperature, heart rate and the outcome of cooled infants. METHODS: The clinical data of 756 infants registered to the Baby Cooling Registry of Japan between January 2012 and December 2016 were analysed to assess the relationship between body temperature, heart rate and adverse outcomes (death or severe impairment at 18 months corrected age). RESULTS: A lower body temperature at admission was associated with adverse outcomes in the univariate analysis (P < 0.001), the significance of which was lost when adjusted for the severity of encephalopathy and other covariates. A higher body temperature during cooling and higher heart rate before and during cooling were associated with adverse outcomes in both univariate (all P < 0.001) and multivariate (P = 0.012, P < 0.001 and P < 0.001, respectively) analyses. CONCLUSIONS: Severe hypoxia-ischaemia might be a common causative of faster heart rates before and during cooling and low body temperature before cooling, whereas causal relationships between slightly higher temperatures during cooling and adverse outcomes need to be elucidated in future studies. IMPACT: In a large cohort of encephalopathic newborn infants, dual roles of body temperature to the outcome were shown; adverse outcomes were associated with a lower body temperature at admission and higher body temperature during cooling. A higher heart rate before and during cooling were associated with adverse outcomes. Severe hypoxia-ischaemia might be a common causative of faster heart rates before and during cooling and low body temperature before cooling. The exact mechanism underlying the relationship between slightly higher body temperature during cooling and adverse outcomes remains unknown, which needs to be elucidated in future studies.
BACKGROUND: Therapeutic hypothermia is a standard of care for neonatal encephalopathy; however, approximately one in two newborn infants fails to respond to this treatment. Recent studies have suggested potential relationships between body temperature, heart rate and the outcome of cooled infants. METHODS: The clinical data of 756 infants registered to the Baby Cooling Registry of Japan between January 2012 and December 2016 were analysed to assess the relationship between body temperature, heart rate and adverse outcomes (death or severe impairment at 18 months corrected age). RESULTS: A lower body temperature at admission was associated with adverse outcomes in the univariate analysis (P < 0.001), the significance of which was lost when adjusted for the severity of encephalopathy and other covariates. A higher body temperature during cooling and higher heart rate before and during cooling were associated with adverse outcomes in both univariate (all P < 0.001) and multivariate (P = 0.012, P < 0.001 and P < 0.001, respectively) analyses. CONCLUSIONS: Severe hypoxia-ischaemia might be a common causative of faster heart rates before and during cooling and low body temperature before cooling, whereas causal relationships between slightly higher temperatures during cooling and adverse outcomes need to be elucidated in future studies. IMPACT: In a large cohort of encephalopathic newborn infants, dual roles of body temperature to the outcome were shown; adverse outcomes were associated with a lower body temperature at admission and higher body temperature during cooling. A higher heart rate before and during cooling were associated with adverse outcomes. Severe hypoxia-ischaemia might be a common causative of faster heart rates before and during cooling and low body temperature before cooling. The exact mechanism underlying the relationship between slightly higher body temperature during cooling and adverse outcomes remains unknown, which needs to be elucidated in future studies.
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