Hyperglycemia associated with acute brain injury in neonatal encephalopathy

Tam, Emily; Kamino, Daphne; Shatil, Anwar S.; Chau, Vann; Moore, Aideen M.; Brant, Rollin; Widjaja, Elysa

doi:10.1016/j.nicl.2021.102835

Cited by 17 publications

(9 citation statements)

References 48 publications

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“…Consequently, this study determined that a glucose threshold of 10.1 mmol/L during the first 48 HOL has good predictive ability for brain injury, suggesting that maintaining glucose levels below 10.1 mmol/L could potentially lead to a reduction in brain injury after NE. Of note, we recently reported widespread changes in brain microstructure associated with higher maximum glucose during the first day of life in this same cohort, 13 further highlighting the importance of managing hyperglycemia and monitoring the sequelae of brain injury in these regions. Additionally, the current study found that during the first 48 HOL, severity of hyperglycemia was inversely related to duration of exposure for predicting the presence of basal ganglia and watershed injury patterns, suggesting that both severity and duration of hyperglycemia should be considered when developing glucose management strategies.…”

Section: Discussionmentioning

confidence: 53%

“… 3 , 6 , 7 Moreover, in the context of HIE, hyperglycemia might result from a reduced net metabolism of severely damaged tissues or a prolonged rise in stress hormones, and may be further prolonged by therapeutic hypothermia. 8 , 9 Both hypoglycemia and hyperglycemia are potential candidate modifiable risk factors since they are prevalent in NE, and in the era of therapeutic hypothermia, have been associated with unfavourable neurophysiological changes in the neonatal period, 10 , 11 brain injury on neonatal MRI, 12 , 13 and adverse developmental outcomes at preschool age. 4 , 6 , 14 …”

Section: Introductionmentioning

confidence: 99%

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Severity and duration of dysglycemia and brain injury among patients with neonatal encephalopathy

Kamino¹,

Widjaja²,

Brant³

et al. 2023

eClinicalMedicine

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Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Severity and duration of dysglycemia and brain injury among patients with neonatal encephalopathy

Kamino¹,

Widjaja²,

Brant³

et al. 2023

eClinicalMedicine

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“…Clinical data were collected from the patient's medical records and stored in research electronic data capture. 35…”

Section: Methodsmentioning

confidence: 99%

“…Clinical data were collected from the patient's medical records and stored in research electronic data capture. 35 The severity of clinical encephalopathy in the first day of life was quantified using an encephalopathy score known to be associated with outcome, 22 scored 0-6 with 1 point given for abnormalities in each category of feeding, alertness, tone, respiratory status, reflexes, and seizure activity. In addition, the overall severity of encephalopathy for the duration of acute illness was categorized using the Sarnat staging criteria to further categorize the cohort.…”

Section: Study Design and Populationmentioning

confidence: 99%

Seizure Burden and Neurologic Outcomes After Neonatal Encephalopathy

et al. 2023

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Background and Objectives:Seizures are common during neonatal encephalopathy, but the contribution of seizure burden to outcomes remains controversial. This study aims to examine the relationship between electrographic seizure burden and neurological outcomes after neonatal encephalopathy.Methods:This prospective cohort study recruited newborns ≥36 weeks PMA around 6 hours of life between August 2014 to November 2019 from a Neonatal Intensive Care Unit. Participants underwent continuous electroencephalography for at least 48 hours, brain MRI within 3-5 days of life, and structured follow-up at 18 months. Electrographic seizures were identified by board-certified neurophysiologists, and quantified as total seizure burden and maximum hourly seizure burden. A medication exposure score was calculated based on all anti-seizure medications given during NICU admission. Brain MRI injury severity was classified based on basal ganglia and watershed scores. Developmental outcomes were measured using the Bayley Scales of Infant Development, 3rdEdition. Multivariable regression analyses were performed, adjusting for significant potential confounders.Results:Of 108 enrolled subjects, 98 subjects had cEEG and MRI data collected, of which 5 were lost to follow-up, and 6 died before age 18 months. All subjects with moderate-severe encephalopathy completed therapeutic hypothermia. cEEG-confirmed neonatal seizures occurred in 21(24%) newborns, with a total seizure burden mean of 12.5 ± 36.4 minutes, and a maximum hourly seizure burden mean of 4 ± 10 min/hr. After adjusting for MRI brain injury severity and medication exposure, total seizure burden was significantly associated with lower cognitive (-0.21, 95%CI -0.33 – -0.08, p=0.002) and language (-0.25, 95%CI -0.39 – -0.11, p=0.001) scores at 18 months. Total seizure burden of 60 minutes was associated with 15-point decline in language scores, and 70 minutes for cognitive scores. However, seizure burden was not significantly associated with epilepsy, neuromotor score, or cerebral palsy (p>0.1).Discussion:Higher seizure burden during neonatal encephalopathy was independently associated with worse cognitive and language scores at 18 months, even after adjusting for exposure to anti-seizure medications and severity of brain injury. These observations support the hypothesis that neonatal seizures occurring during neonatal encephalopathy independently contribute to long-term outcomes.

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“…Neonates with hypoxic ischaemic encephalopathy (HIE) are also at risk of hypoglycaemia which may compound ischaemic injury. Masked CGM has been used in this cohort and shown associations between dysglycaemia and worse neurodevelopmental outcomes ( 16 , 28 – 30 ). Implementation of CGM use as part of clinical decision making in HIE has not been explored, and needs to be preceded by validation of sensor accuracy during cooling.…”

Section: What Types Of Neonates May Benefit?mentioning

confidence: 99%

Should continuous glucose monitoring be used to manage neonates at risk of hypoglycaemia?

2023

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The National Institute for Clinical Excellence (NICE) now recommends that continuous glucose monitoring (CGM) be offered to adults and children with diabetes who are at risk from hypoglycaemia. Hypoglycaemia is common in the neonatal period, and is a preventable cause of poor neurodevelopmental outcome, but is CGM helpful in the management of neonates at risk of hypoglycaemia? Neonatal studies have shown that CGM can detect clinically silent hypoglycaemia, which has been associated with reduced executive and visual function in early childhood. Intervention trials have further shown CGM can support the targeting of glucose levels in high-risk extremely preterm neonates. In spite of significant advances in technology, including smaller sensors, better accuracy and factory calibration, further progress and adoption into clinical practice has been limited as current devices are not designed nor have regulatory approval for the specific needs of the newborn. The use of CGM has the potential to support clinical management, and prevention of hypoglycaemia but must be set within its current limitations. The data CGM provides however also provides an important opportunity to improve our understanding of potential risks of hypoglycaemia and the impact of clinical interventions to prevent it.

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Hyperglycemia associated with acute brain injury in neonatal encephalopathy

Cited by 17 publications

References 48 publications

Severity and duration of dysglycemia and brain injury among patients with neonatal encephalopathy

Severity and duration of dysglycemia and brain injury among patients with neonatal encephalopathy

Seizure Burden and Neurologic Outcomes After Neonatal Encephalopathy

Should continuous glucose monitoring be used to manage neonates at risk of hypoglycaemia?

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