Hypoglycemia in infants with hypoxic-ischemic encephalopathy is associated with additional brain injury and worse neurodevelopmental outcome
Open accessAbstract
OBJECTIVE: To determine the incidence of hypoglycemia among infants with hypoxic-ischemic encephalopathy (HIE) who received therapeutic hypothermia, and to assess whether infants with hypoglycemia had more brain injury on magnetic resonance imaging (MRI) or differences in neurodevelopmental outcome. STUDY DESIGN: Single-center, retrospective cohort study including infants cooled for HIE. Hypoglycemia (blood glucose <36.0 mg/dL <2 hours and <46.8 mg/dL ≥2 hours after birth) was analyzed in the period before brain MRI. Brain injury was graded using a validated score. Motor and neurocognitive outcomes were assessed at 2 years for all survivors, and 5.5 years for a subset who had reached this age. RESULTS: Of 223 infants analyzed, 79 (35.4%) had hypoglycemia. MRI was performed in 187 infants. Infants with hypoglycemia (n = 65) had higher brain injury scores (P = .018). After adjustment for HIE severity, hypoglycemia remained associated with higher injury scores (3.6 points higher; 95% CI, 0.8-6.4). Hyperglycemia did not affect MRI scores. In survivors at 2 years (n = 154) and 5.5 years (n = 102), a univariable analysis showed lower 2-year motor scores and lower motor and cognitive scores at preschool age in infants with hypoglycemia. After adjustment for HIE severity, infants with hypoglycemia had 9 points lower IQs (P = .023) and higher odds of adverse outcomes at preschool age (3.6; 95% CI, 1.4-9.0). CONCLUSIONS: More than one-third of infants cooled for HIE had hypoglycemia. These infants had a higher degree of brain injury on MRI and lower cognitive function at preschool age. Strategies to avoid hypoglycemia should be optimized in this setting.
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Emerging evidence highlights that factors such as hypocapnia, hyperoxia, extreme fluctuations in blood pressure and glucose are associated with worse outcomes in neonates with HIE.
“Emerging evidence highlights that factors such as hypocapnia, hyperoxia, extreme fluctuations in blood pressure and glucose are associated with worse outcomes in this population (1, 4–8).”
From Lab values in neonates with hypoxic ischemic encephalopathy over time during and after therapeutic hypothermia (2026) · cites this paper as [7]
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A korai laboratóriumi vizsgálatok jelentősége hűtött asphyxiás újszülöttek kezelésében
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“Therefore, it is very important to screen out early prognostic risk factors by combining imaging and clinical characteristics (Landais, 2015; Kapoor et al., 2020; Van Kempen et al., 2020; Parmentier et al., 2022).”
BackgroundChild and Parent Perspectives on Daily Functioning after Perinatal Brain Injury
Baak, L. M., Parmentier, C. E. J., Wagenaar, N., Buijsen, F.-S. N., de Joode, A. A. M. V. W., Gorter, J. W., Benders, M. J. N. L., Groenendaal, F., de Vries, L. S., Nijboer, C. H. A., et al. (2025) · The Journal of Pediatrics Clinical Practice · doi:10.1016/j.jpedcp.2025.200172 · Cited by 1 · see citing works
Glucose-to-lactate ratio in infants with hypoxic-ischemic encephalopathy treated with hypothermia
Dani, C., Remaschi, G., Benelli, E., Cecchi, A., Lunardi, C., Fazi, C., Bianchi, A., Scola, E., Fainardi, E., Miele, V., et al. (2025) · Early Human Development · doi:10.1016/j.earlhumdev.2025.106458 · Cited by 1 · see citing works
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Infantile Epileptic Spasms Syndrome Due to Neonatal Hypoglycemic Brain Injury: A Retrospective Audit
Gupta, S., & Passi, G. R. (2025) · Indian Pediatrics · doi:10.1007/s13312-025-00038-0 · Cited by 1 · see citing works
“The additive risks of NHBI and HIE are documented in cooling studies in neonates [9].”
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Hypoxic Ischemic Encephalopathy: Hearing Impairment and Related Risk Factors
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“%) compared with other studies [37], and the incidence was not higher in infants with HL than in those with normal hearing.”
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2025 Korean Guidelines for Cardiopulmonary Resuscitation: Part 9. Neonatal resuscitation
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- Authors
- Parmentier, C. E. J., de Vries, L. S., van der Aa, N. E., Eijsermans, M. J. C., Harteman, J. C., Lequin, M. H., Swanenburg de Veye, H. F. N., Koopman-Esseboom, C., & Groenendaal, F.
- Affiliations
- Utrecht University (NL)
- Corresponding author
- Groenendaal, Floris
- Venue
- The Journal of Pediatrics
- Publisher
- Elsevier BV
- Published
- 2022-06
- Volume
- 245
- Pages
- 30-38.e1
- ISSN
- 0022-3476 (ISSN-L)
- OpenAlex
- W4210424482
- Cited by
- 45
- References
- 46
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 12 · 2023: 11 · 2022: 3
- FWCI
- 10.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Pediatrics (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Infant Development and Preterm Care
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal Health and Biochemistry
- Keywords
- hypoglycemia, hypoxic-ischemic encephalopathy, neonatal hypothermia, therapeutic hypothermia, brain injury, neurodevelopmental outcomes, hyperglycemia, neuropsychological outcomes, motor outcome, blood glucose, brain MRI
- MeSH terms
- Brain Injuries, Child, Preschool, Humans, Hypoglycemia, Hypothermia, Induced, Infant, Magnetic Resonance Imaging, Retrospective Studies, Hypoxia-Ischemia, Brain
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