Best Practice Guideline article
Measurement of glucose levels in the newborn

https://doi.org/10.1016/j.earlhumdev.2010.05.005Get rights and content

Abstract

Accurate measurement of blood glucose levels in the newborn is important as hypoglycaemia and hyperglycaemia are common treatable conditions and there is evidence linking both with detrimental clinical outcomes. Point of care (POC) glucose testing provides rapid results with small sample volumes and therefore clinical care can be modified quickly if needed. However the common thresholds for the diagnosis of hypoglycaemia in the newborn (blood glucose < 2.0 mmol/l or < 2.6 mmol/l) and hyperglycaemia (blood glucose > 10 mmol/l) are at the limits of accuracy for many POC glucose analysers. Therefore although useful for screening, such devices cannot be relied upon for accurate diagnosis of hypoglycaemia. Stand alone local laboratory devices or glucose biosensors incorporated into blood gas analysers help to balance the benefits of POC testing with the accuracy of laboratory analyses. However these clinical methods all rely on intermittent blood sampling and there may be many hours between measurements, when both hypoglycaemia and hyperglycaemia may be undetected clinically. Less invasive and continuous methods of glucose monitoring are under development. Continuous glucose monitoring provides detailed information regarding glucose levels and has led to improvements in the care of patients with diabetes mellitus. These devices also have the potential to help provide improved glucose monitoring and management in the high risk neonate.

Introduction

The accurate measurement of blood glucose in the newborn is clinically important as hypoglycaemia and hyperglycaemia are not always associated with overt clinical signs [1], although both extremes have been associated with poor clinical outcomes [2], [3]. As interventions are available to maintain glucose levels within a ‘normal range’ it is important that glucose levels can be measured efficiently and accurately so that any necessary clinical interventions can be made. Accuracy of measurement is dependent on many factors related to the sample itself and device used for analyses. There is a wide range of devices and different methodologies available for measurement of glucose and it is important that devices are validated for use in the newborn before being used for clinical care. One of the particular difficulties in the newborn is that the blood glucose (BG) levels at the thresholds for changes in clinical management are at levels that are at the limits of the accuracy for many glucose analysers. New methods such as continuous subcutaneous glucose monitoring are increasingly being used to help improve glucose control in patients with diabetes mellitus and may in the future provide the opportunity to improve glucose management in the newborn.

Section snippets

Why measure glucose levels?

Hypoglycaemia can be detected after birth in a healthy population of term neonates, as part of physiological adaptation [4], and therefore routine testing of all babies is not indicated. The fasting newborn produces lactate and ketones which can be used as alternative fuels in the neonatal period having a glucose sparing effect. However infants who are unable to produce alternative fuels due to limited fat and glycogen reserves or impaired counter regulation are at risk from hypoglycaemia. In

How should glucose levels be measured?

Balancing efficiency and accuracy are the factors that influence decisions regarding the choice of method for measuring glucose levels. In infants requiring intensive care BG levels may change quickly and they therefore require frequent glucose measurements. Therefore minimal sample volumes must be used to avoid the need for frequent blood transfusions, and rapid results are required so that changes in clinical care can be made in a timely fashion. However this has to be balanced by the

Current clinical methods for measuring glucose levels

The first line in glucose measurement in most clinical settings is a point of care glucose meter. Point of care testing can provide rapid results (in as little as 3 s) using small sample volumes (as small as 0.3 μl). This is potentially helpful in providing efficient clinical care and has been shown to reduce the need for blood transfusions [17]. There have been dramatic developments in point of care devices for measurement of glucose over the last 40 years. The first dry reagent blood glucose

Continuous glucose monitoring

Current clinical methods for measuring glucose in the newborn rely on blood sampling to provide single one off measures. Developments in continuous subcutaneous glucose monitoring can now provide detailed information on glucose levels throughout the 24-hour period. Continuous glucose monitoring has demonstrated that glucose levels can fluctuate widely particularly in infants requiring intensive care and may result in undetected periods of both hypoglycaemia and hyperglycaemia [31] (Fig. 1).

Non invasive devices

Attempts have also been made to develop non invasive techniques to measure glucose levels to prevent the need for frequent blood sampling. Such methodologies include optical sensors or transdermal devices but attempts have generally been unsuccessful. Optical sensors measure the characteristics of reflected light that are changed as a result of an interaction with glucose. Spectrophotometry is based on specific absorption in different spectral ranges with glucose concentration derived

Summary

The ability to measure glucose levels in the newborn is a critical part of good clinical care. Glucose monitoring devices need to give accurate results particularly at levels that would affect clinical care. However devices also need to be practical to use and maintain by neonatal staff and cost efficient. There is a wide range of methodologies and devices available for measurement of glucose but it is important that devices are validated for use in the newborn before being used for clinical

Key guidelines

  • Accurate measurement of glucose levels in the newborn at risk of hyperglycaemia or hypoglycaemia is important.

  • Accuracy of any measurement is affected by both preanalytical and analytical errors.

  • POC devices although useful for screening cannot be relied upon for the diagnosis of hypoglycaemia.

  • Laboratory analyses although considered the gold standard will give inaccurately low levels if there is a delay in samples being analysed.

  • Optimal glucose levels in the newborn are not known.

  • Any new

Research directions

  • What are optimal glucose levels for the newborn both term and preterm?

  • What are the optimal interventions to achieve these targets?

  • Validation of the use of continuous glucose monitoring as part of clinical care

  • Development of improved methods for non invasive continuous glucose monitoring in the newborn

References (32)

  • E. Hey

    Hyperglycaemia and the very preterm baby

    Semin Fetal Neonatal Med

    (2005 Aug)
  • P.A. Kavsak et al.

    Challenges of implementing point-of-care testing (POCT) glucose meters in a pediatric acute care setting

    Clin Biochem

    (2004 Sep)
  • M. Cornblath et al.

    Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds

    Pediatrics

    (2000 May)
  • A. Lucas et al.

    Adverse neurodevelopmental outcome of moderate neonatal hypoglycaemia

    BMJ

    (Nov 19 1988)
  • S.P. Hays et al.

    Hyperglycemia is a risk factor for early death and morbidity in extremely low birth-weight infants

    Pediatrics

    (2006 Nov)
  • J.M. Hawdon et al.

    Aynsley-Green A. Patterns of metabolic adaptation for preterm and term infants in the first neonatal week

    Arch Dis Child

    (Apr 1992)
  • G. Van den Berghe et al.

    Intensive insulin therapy in critically ill patients

    NEJM

    (2001)
  • L.S. Kao et al.

    Hyperglycemia and morbidity and mortality in extremely low birth weight infants

    J Perinatol

    (Aug 24 2006)
  • K. Beardsall et al.

    Early insulin therapy in very-low-birth-weight infants

    N Engl J Med

    (2008 Oct 30)
  • M. Egi et al.

    Variability of blood glucose concentration and short-term mortality in critically ill patients

    Anesthesiology

    (2006 Aug)
  • C. Balion et al.

    Screening for hypoglycemia at the bedside in the neonatal intensive care unit (NICU) with the Abbott PCx glucose meter

    BMC Pediatr

    (2006)
  • Z. Tang et al.

    Effects of different hematocrit levels on glucose measurements with handheld meters for point-of-care testing

    Arch Pathol Lab Med

    (2000 Aug)
  • M. Kaplan et al.

    Screening for hypoglycemia with plasma in neonatal blood of high hematocrit value

    Crit Care Med

    (1989 Mar)
  • J.M. Bland et al.

    Statistical methods for assessing agreement between two methods of clinical measurement

    Lancet

    (1986 Feb 8)
  • W.L. Clarke et al.

    Evaluating clinical accuracy of systems for self-monitoring of blood glucose

    Diab Care

    (Sep-Oct 1987)
  • D.G. Altman et al.

    Diagnostic tests. 1: sensitivity and specificity

    Bmj

    (Jun 11 1994)
  • Cited by (48)

    • The Term Newborn: Hypoglycemia

      2021, Clinics in Perinatology
    • The impact of continuous blood glucose monitoring on glucose stability in the preterm infant; A systematic review

      2020, Journal of Neonatal Nursing
      Citation Excerpt :

      Glucose instability remains one of the most common challenges in neonatal medicine (Mola-Schenzle et al., 2014; Tin, 2014; Tiberi et al., 2016). It is believed that their developing brain is exceptionally vulnerable to fluctuations in blood glucose levels (Alexandrou et al., 2010; Beardsall, 2010). Glucose instability especially in the pre term infant can be detrimental and has a positive association with an increase in morbidity and mortality (McKinlay et al., 2015; Galderisi et al., 2017).

    • Pathophysiology and Management of Disorders of Carbohydrate Metabolism and Neonatal Diabetes

      2020, Maternal-Fetal and Neonatal Endocrinology: Physiology, Pathophysiology, and Clinical Management
    View all citing articles on Scopus
    View full text