Academy of Diagnostics & Laboratory Medicine - Scientific Short

What Glucose Level Should Be Used to Diagnose Hypoglycemia in Newborns?

William E. Winter

​On February 9, 2012, the following question was posted on AACC's chemistry list-serv: "Would like to know what others are using for critical low value for Glucose." Part of the discussion addressed neonatal hypoglycemia. Below is my contribution to that discussion.

The definition of hypoglycemia in newborns remains controversial.

Dr. Charles Stanley from the University of Pennsylvania is an expert in the field of neonatal hypoglycemia. In a recent review Dr. Stanley wrote: "…there is no evidence that the physiologic requirements for glucose in neonates are different from older children and adults. This has led many to suggest that maintenance of blood glucose above 60 mg/dL ought to be the therapeutic goal when treating neonatal hypoglycemia. For purposes of clinical diagnosis of hypoglycemia in neonates, a plasma glucose level below 50 mg/dL has been suggested as a reasonable criterion." (Stanley CA. Hypoglycemia in the neonate. Pediatr Endocrinol Rev. 2006 Dec;4 Suppl 1:76-81.)

A recent NIH-sponsored workshop failed to arrive at a specific definition of hypoglycemia (Hay WW Jr, Raju TN, Higgins RD, Kalhan SC, Devaskar SU. Knowledge gaps and research needs for understanding and treating neonatal hypoglycemia: workshop report from Eunice Kennedy Shriver National Institute of Child Health and Human Development. J Pediatr. 2009 Nov;155(5):612-7). The paper included the following observation that is cogent for labs: "There is a great inconsistency in the sources and sampling methods of blood (capillary, venous, arterial) and the methods used for subsequent analyses, including processing techniques, thus affecting establishing ‘‘normal’’ values on the basis of existing literature. There are no noninvasive methods for measuring concentrations of glucose and other energy substrates (intermittently or continuously)…."

Dr. Marvin Cornblath, a noted senior expert in the field hypoglycemia, is quoted in the above review and this quote bears our review: "Unfortunately, untoward long-term outcomes in infants with one or two low blood glucose levels have become the grounds for litigation and for alleged malpractice, even though the causative relationship between the two is tenuous at best. The definition of clinically significant hypoglycemia remains one of the most confused and contentious issues in contemporary neonatology." (Cornblath M, Hawdon JM, Williams AF, et al. Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics 2000;105:1141-5.).

Until more definitive information is available, my conclusion is that a slightly higher definition (e.g., <50 mg/dL) for the diagnosis of hypoglycemia (versus <40 mg/dL or <45 mg/dL) may be safer for the infant.

What do other clinical chemists think about this question?

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Fellows of the Academy use the designation of FADLM. This designation is equivalent to FACB and FAACC, the previous designations used by fellows of the National Academy of Clinical Biochemistry and AACC Academy. Those groups were rebranded as Academy of Diagnostics & Laboratory Medicine in 2023.