Glycemia and Neonatal Encephalopathy: Outcomes in the LyTONEPAL (Long-Term Outcome of Neonatal Hypoxic EncePhALopathy in the Era of Neuroprotective Treatment With Hypothermia) Cohort
Abstract
Objectives To assess in newborns with neonatal encephalopathy (NE), presumptively related to a peripartum hypoxic-ischemic event, the frequency of dysglycemia and its association with neonatal adverse outcomes. Study design We conducted a secondary analysis of LyTONEPAL (Long-Term Outcome of Neonatal hypoxic En-cePhALopathy in the era of neuroprotective treatment with hypothermia), a population-based cohort study including 545 patients with moderate-to-severe NE. Newborns were categorized by the glycemia values assessed by routine clinical care during the first 3 days of life: normoglycemic (all glycemia measurements ranged from 2.2 to 8.3 mmol/L), hyperglycemic (at least 1 measurement >8.3 mmol/L), hypoglycemic (at least 1 measurement <2.2 mmol/L), or with glycemic lability (measurements included at least 1 episode of hypoglycemia and 1 episode of hyperglycemia). The primary adverse outcome was a composite outcome defined by death and/or brain lesions on magnetic resonance imaging, regardless of severity or location. Results In total, 199 newborns were categorized as normoglycemic (36.5%), 74 hypoglycemic (13.6%), 213 hyperglycemic (39.1%), and 59 (10.8%) with glycemic lability, based on the 2593 glycemia measurements collected. The primary adverse outcome was observed in 77 (45.8%) normoglycemic newborns, 37 (59.7%) with hypoglycemia, 137 (67.5%) with hyperglycemia, and 40 (70.2%) with glycemic lability (P < .01). With the normoglycemic group as the reference, the aORs and 95% 95% CIs for the adverse outcome were significantly greater for the group with hyperglycemia (aOR 1.81; 95% CI 1.06-3.11). Conclusions Dysglycemia affects nearly two-thirds of newborns with NE and is independently associated with a greater risk of mortality and/or brain lesions on magnetic resonance imaging. (J Pediatr 2023;-:1-8). Trial registration NCT02676063 A meta-analysis has demonstrated the effectiveness of therapeutic hypothermia in reducing the risk of death and neurologic damage in newborns with neonatal encephalopathy (NE), presumptively related to a hypoxic-ischemic peripartum event, 1 and led to its widespread use in developed countries. 2,3 Nevertheless, a large proportion-approximately 46%-of treated patients will die or develop moderate or severe disabilities. 1 Among the mechanisms of neuroprotection, those preventing secondary cerebral insults of systemic origin could improve outcomes, 4,5 as described for other patients with brain injuries with hypotension, hypertension, 6 and inadequate metabolic homeostasis. 7 Hypoglycemia is reported to exacerbate asphyxia-induced neonatal brain damage in animal studies as well as in preclinical and clinical studies in humans. 8,9 Results about the effects of hyperglycemia on clinical outcomes conflict. 10-12 All of these findings, nonetheless, come from trials and single-center studies and require further confirmation before changes in the routine management of patients treated for NE can be recommended. The LyTONEPAL (Long-Term Outcome of Neonatal hypoxic EncePhALopathy in the era of neuroprotective treatment with hypothermia) cohort study 13 is a large prospective, nationwide, population-based cohort in France including newborns with NE in routine care and full access to therapeutic hypothermia. 14 We
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BibTeX
@article{guellec2026glycemia,
title = {{Glycemia and Neonatal Encephalopathy: Outcomes in the LyTONEPAL (Long-Term Outcome of Neonatal Hypoxic EncePhALopathy in the Era of Neuroprotective Treatment With Hypothermia) Cohort}},
author = {Isabelle Guellec and Pierre-Yves Ancel and Jonathan Beck and Gauthier Loron and Marie Chevallier and Véronique Pierrat and Gilles Kayem and Antoine Vilotitch and Olivier Baud and Anne Ego and Thierry Debillon},
journal = {The Journal of Pediatrics},
year = {2026},
month = oct,
doi = {10.1016/j.jpeds.2023.02.003},
url = {https://hal.science/hal-05762650v1},
note = {CC BY-ND 4.0},
}
RIS
TY - JOUR
TI - Glycemia and Neonatal Encephalopathy: Outcomes in the LyTONEPAL (Long-Term Outcome of Neonatal Hypoxic EncePhALopathy in the Era of Neuroprotective Treatment With Hypothermia) Cohort
AU - Isabelle Guellec
AU - Pierre-Yves Ancel
AU - Jonathan Beck
AU - Gauthier Loron
AU - Marie Chevallier
AU - Véronique Pierrat
AU - Gilles Kayem
AU - Antoine Vilotitch
AU - Olivier Baud
AU - Anne Ego
AU - Thierry Debillon
PY - 2026
DA - 2026/10/02
JO - The Journal of Pediatrics
DO - 10.1016/j.jpeds.2023.02.003
UR - https://hal.science/hal-05762650v1
AB - Objectives To assess in newborns with neonatal encephalopathy (NE), presumptively related to a peripartum hypoxic-ischemic event, the frequency of dysglycemia and its association with neonatal adverse outcomes. Study design We conducted a secondary analysis of LyTONEPAL (Long-Term Outcome of Neonatal hypoxic En-cePhALopathy in the era of neuroprotective treatment with hypothermia), a population-based cohort study including 545 patients with moderate-to-severe NE. Newborns were categorized by the glycemia values assessed by routine clinical care during the first 3 days of life: normoglycemic (all glycemia measurements ranged from 2.2 to 8.3 mmol/L), hyperglycemic (at least 1 measurement >8.3 mmol/L), hypoglycemic (at least 1 measurement <2.2 mmol/L), or with glycemic lability (measurements included at least 1 episode of hypoglycemia and 1 episode of hyperglycemia). The primary adverse outcome was a composite outcome defined by death and/or brain lesions on magnetic resonance imaging, regardless of severity or location. Results In total, 199 newborns were categorized as normoglycemic (36.5%), 74 hypoglycemic (13.6%), 213 hyperglycemic (39.1%), and 59 (10.8%) with glycemic lability, based on the 2593 glycemia measurements collected. The primary adverse outcome was observed in 77 (45.8%) normoglycemic newborns, 37 (59.7%) with hypoglycemia, 137 (67.5%) with hyperglycemia, and 40 (70.2%) with glycemic lability (P < .01). With the normoglycemic group as the reference, the aORs and 95% 95% CIs for the adverse outcome were significantly greater for the group with hyperglycemia (aOR 1.81; 95% CI 1.06-3.11). Conclusions Dysglycemia affects nearly two-thirds of newborns with NE and is independently associated with a greater risk of mortality and/or brain lesions on magnetic resonance imaging. (J Pediatr 2023;-:1-8). Trial registration NCT02676063 A meta-analysis has demonstrated the effectiveness of therapeutic hypothermia in reducing the risk of death and neurologic damage in newborns with neonatal encephalopathy (NE), presumptively related to a hypoxic-ischemic peripartum event, 1 and led to its widespread use in developed countries. 2,3 Nevertheless, a large proportion-approximately 46%-of treated patients will die or develop moderate or severe disabilities. 1 Among the mechanisms of neuroprotection, those preventing secondary cerebral insults of systemic origin could improve outcomes, 4,5 as described for other patients with brain injuries with hypotension, hypertension, 6 and inadequate metabolic homeostasis. 7 Hypoglycemia is reported to exacerbate asphyxia-induced neonatal brain damage in animal studies as well as in preclinical and clinical studies in humans. 8,9 Results about the effects of hyperglycemia on clinical outcomes conflict. 10-12 All of these findings, nonetheless, come from trials and single-center studies and require further confirmation before changes in the routine management of patients treated for NE can be recommended. The LyTONEPAL (Long-Term Outcome of Neonatal hypoxic EncePhALopathy in the era of neuroprotective treatment with hypothermia) cohort study 13 is a large prospective, nationwide, population-based cohort in France including newborns with NE in routine care and full access to therapeutic hypothermia. 14 We
SN - 0022-3476
SN - 1097-6833
ER -