CommentaryKnowledge Gaps and Research Needs for Understanding and Treating Neonatal Hypoglycemia: Workshop Report from Eunice Kennedy Shriver National Institute of Child Health and Human Development
Section snippets
Objectives of the Workshop
The objectives of the workshop were to identify major gaps in knowledge related to neonatal hypoglycemia and not to develop a “consensus” on either its definition or treatment. The participants were asked to propose a research agenda that, if successfully completed, might help address key issues on this topic, such as how to define clinically significant hypoglycemia; how to monitor glucose concentrations in newborn infants; how best to prevent and treat neonatal hypoglycemia; and how to
Fetal and Neonatal Glucose Metabolism
The fetus depends entirely on maternal supply and placental transfer of glucose, amino acids, free fatty acids, ketones, and glycerol for its energy needs. The normal lower limit of fetal glucose concentration remains around 3 mmol/L (54 mg/dL) over most of gestation, particularly after 20 weeks.29, 30 There is no fetal glucose production under normal conditions; in most cases, gluconeogenesis appears only after birth, although it has been produced in animal models with prolonged periods (days
Brain and Glucose Metabolism
Glucose supply to all cell types in the brain is regulated by the plasma glucose concentration and the glucose transporter 1 (GLUT1) and 3 (GLUT3) proteins. GLUT1 is expressed in the blood-brain barrier endothelial cells, astrocytes, oligodendrocytes, and choroid plexus, and GLUT3 primarily in neurons and their synaptic membranes.42, 43 GLUT 1 expression in the neonatal cerebral cortex44 and GLUT 3 expression in the cerebellum equal those in adults.45
Neuronal glucose use rate is high, and whole
Defining Clinically Significant Hypoglycemia
With current knowledge, one cannot identify any specific concentration or range of plasma glucose concentrations that defines “significant hypoglycemia” as a pathologic entity. The so-called operational threshold values are useful guidelines for clinicians to take appropriate actions. However, the recommendations are not based on evidence of significant morbidity if no actions are taken. Similarly, there is no evidence that outcomes improve if actions are taken at the operational threshold
Treatment Issues
There are no evidence-based guidelines that can be used for treating all newborn infants with low plasma glucose concentrations. Published guidelines of “operational thresholds” do not define “dangerous” values of glucose concentration. They only indicate that glucose concentrations are below an arbitrarily defined threshold that is based on statistical evaluations of cross-sectional data. These values are at or below the threshold value the caregiver may opt to take some action. Such actions
Education
Health care professionals at all levels need to be educated about glucose metabolism in the newborn infant. Such education must emphasize the need for continued research to define the characteristics of low plasma glucose, its prevention and treatment, and its actual effects on neuronal injury and later developmental outcome. Parents and the public also need to be educated about the broader aspects and major gaps in knowledge about this condition.
The clinical, logistical, and ethical
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Editor's Note: The National Institutes of Health organizes focused workshops on topics that are in need of new clinical approaches or research. This article summarizes a workshop on neonatal hypoglycemia.
—Alan H. Jobe, MD, PhD
Funded by NICHD and NIH Office of Rare Diseases. Additional funding was received by The March of Dimes Foundation to the general NICHD gift fund. The American Academy of Pediatrics sponsored the travels of six speakers (none is the author) to this meeting. The study sponsors and co-funders were not involved on the conference agenda, discussions of materials, and interpretation of the presentations, the writing of the report, and the decision to submit the report for publications. The opinions expressed in this article are those of the author alone. They are not necessarily those of the US Department of Health and Human Services or of the National Institutes of Health, or of the co-sponsors. The authors declare no potential conflicts.