Controversies in Neonatal Hypoglycemia

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Background

Over two decades ago, Cornblath and colleagues (Pediatrics 2000;105) wrote “the definition of clinically significant hypoglycemia remains one of the most confused and contentious issues in contemporary neonatology”. Today, this comment remains true. Why has the definition not been clarified or evidence-based guidelines for screening and management not been established? Neonatal hypoglycemia is the most common neonatal metabolic disturbance affecting up to 15% of term healthy newborns and up to 50% of at-risk newborns. While prolonged/severe neonatal hypoglycemia is associated with adverse neurodevelopment, it is unclear, due to a lack of prospective long-term studies, whether transient neonatal hypoglycemia is a normal physiological process or associated with long-term cognitive/neurological problems. Based on these concerns, various international organizations have provided different recommendations on which newborns to screen and the specific glucose concentration thresholds to treat. Screening is usually performed using point-of-care glucometers; when concentrations are abnormal, additional specimens are sent to the laboratory for confirmation, often leading to multiple painful needlesticks. Furthermore, when initial treatments (early feeding, dextrose gel) fail to normalize glucose concentrations, subsequent transfer to the NICU leads to more pain and separation from the mother, negatively impacting maternal-fetal bonding and successful breastfeeding. This occurs, however, despite the absence of evidence that treatment of neonatal hypoglycemia actually improves outcomes.

The goal of this project is to identify many of the controversies surrounding neonatal hypoglycemia according to field experts, to develop evidence-based guidelines and a consensus where evidence is lacking. A randomized and controlled multicenter trial design to assess long-term cognitive/neurodevelopmental outcomes of neonatal hypoglycemia would be recommended to a) develop evidence in relation to whom to screen, b) determine the glucose concentration treatment thresholds and specific treatments to use, c) determine whether transient neonatal hypoglycemia has long-term adverse consequences, and d) determine whether treatment of transient neonatal hypoglycemia improves outcomes.

Scope and information for authors: The editors would welcome original research, reviews, and systematic reviews that address controversies and accepted practices, and provide evidence-based recommendations regarding the care of newborns with transient neonatal hypoglycemia.

Themes:

1. What is the glucose concentration (i.e. definition) that determines physiologic vs. pathologic hypoglycemia? Should alternative fuel concentrations be added to the diagnosis?

2. What glucose concentration threshold should be used to treat hypoglycemia? Should the approach be age (hours)-based?

3. Should universal newborn glucose screening be recommended for all newborns?

4. Which growth curves should be used to determine SGA/LGA status? Should weight cutoffs of <2.5 kg and >4 kg (or >4.5 kg) be used instead of growth charts?

5. While prophylactic dextrose gel decreases hypoglycemia but has no influence on the outcome, is that reason sufficient to use prophylactic dextrose gel? Is it cost-effective?

6. Does early feeding actually influence glucose homeostasis?

7. American Academy of Pediatrics (AAP) or Pediatric Endocrine Society (PES) guidelines? Or local guidelines? Are the AAP and PES guidelines based on glucose concentrations using older glucose analyzers?

8. Since the introduction of the PES guidelines (with higher glucose concentration cutoffs), have more children with congenital hyperinsulinism been diagnosed during the initial newborn hospitalization?

9. Is there a benefit (fewer needlesticks, cost-effective) to using lab-quality analyzers vs. point-of-care devices in Newborn Nurseries?

10. Does giving lower glucose infusion rates by a graded approach, based on the degree of hypoglycemia, lead to lower hyperinsulinemic responses and decrease length of stay? Does a rapid rise in glucose concentration lead to more adverse neurodevelopment?

11. Should continuous glucose monitoring be used? Does it lead to fewer needlesticks? Are concentrations accurate and precise? Is it cost-effective?

12. Management of neonatal hypoglycemia in low-resource settings.

13. Is transient neonatal hypoglycemia simply a proxy for disturbed metabolic adaptation from fetal to newborn life? Does the treatment of transient neonatal hypoglycemia actually improve outcome, or does it, perhaps, cause harm? Do all the screening (needlesticks), treatments, and transfers of newborns from Newborn Nurseries to NICUs result in unnecessary painful, costly, and bonding-disrupting actions? Do these protocols and procedures benefit the minority of newborns with congenital hyperinsulinism, identifying them early, before severe brain injury occurs?

Keywords: neonatal, hypoglycemia, newborn, glucose, screening, neurodevelopment

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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