Hypoxic-ischemic encephalopathy (HIE) is one of the most significant causes of neurodevelopmental
problems in American children, with high rates of death and major disability. The understanding of the
impacts of glucose in these newborns has been limited to date by intermittent testing. The NOGIN
study (Neurological Outcome of Glycemia in Neonatal Encephalopathy), using continuous glucose
monitoring, has demonstrated that hyperglycemia occurs in more than 50% of HIE. While
hypoglycemia was expected to be associated with brain injury, the surprising discovery has been that
hyperglycemia, and not hypoglycemia, is associated with worse immediate brain function, brain injury
on MRI, and motor and cognitive function at 18-month follow-up, despite adjusting for HIE severity.
Standardized questionnaires also suggest increased risk for behavioural diagnoses. With the high
incidence of hyperglycemia in neonatal encephalopathy and the strong evidence suggesting major
additive impacts on long- term outcomes, it is now critical to clarify (1) how the findings of posterior-
predominant brain injury translate to difficulties in cortical visual processing and (2) how the early
findings of cognitive and behavioural concerns translate to later diagnoses by early school age.
The overall objective for this study is to determine how hyperglycemia, in the context of neonatal
encephalopathy, independently predicts outcomes by early school age. The specific aims include:
1. Assess how hypo- and hyperglycemia in neonatal encephalopathy impact cortical visual processing
by early school age.
2. Assess how hypo- and hyperglycemia in neonatal encephalopathy impact cognitive, language,
social, and behavioral function by early school age.
The NOGIN study, a prospective cohort study originally aiming to determine what degree of low
glucose results in hypoglycemic brain injury, with enrolment to complete in the next few months. The
first subject turns 5 years old in September 2019. To achieve the current research objectives, children
will be asked to return at 5 years of age for neuropsychological assessment (including WPPSI-IV,
NEPSY-II, MCHAT, CBCL) and magnetoencephalography (vision tasks, resting brain network
circuitry) to understand how specific levels of hyperglycemia translate to ongoing long-term deficits.
By correlating specific levels of hyperglycemia in HIE in neonates with the degree of
neurodevelopmental impairment, this study will help to target the management and control of
hyperglycemia to decrease brain injury and improve outcomes for these newborns. The data
generated will also help with early identification of newborns at greatest risk for adverse outcomes,
enabling more targeted early adjunctive therapies to improve outcomes after HIE.