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Hypoglycaemia in the neonate

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Background

Hypoglycaemia is important because it is a common, readily diagnosed and readily treated problem. If untreated, it may cause permanent brain damage. 

Definition

Serum glucose <2.6mM. This is based on the following:

  • Glucose levels within the 'normal' range are not necessarily optimal.
  • There is no physiological reason why brain glucose requirements should differ between term and preterm infants, or between the first and subsequent days of life.
  • The aim is to define a level which is safe for all babies, rather than is adequate for most.
  • Altered electrophysiological measurements and poor long-term neurological outcome have been reported in infants with recurrent serum glucose levels <2.6mM.

Causes of Hypoglycaemia

  1. Transient neonatal hypoglycaemia.
    Due to inadequate substrate stores and/or inability to mobilise these e.g. prematurity, intrauterine growth retardation, perinatal asphyxia, delayed or inadequate feeding.
    Due to increased glucose requirements e.g. birth asphyxia, sepsis, congenital heart disease, hypothermia, neurological problems (periventricular haemorrhage, convulsions).
  2. Hyperinsulinism
    Maternal diabetes
    Erythroblastosis (e.g. severe Rhesus disease)
    Leucine sensitivity
    Islet cell hyperplasia or hyperfunction
    Insulinoma
    Beckwith-Wiedemann Syndrome
    Maternal anti-diabetic drugs
    Neonatal Hyperinsulinaemic Hypoglycaemia (nesidioblastosis)
  3. Endocrine Causes
    Panhypopituitarism
    Hypothyroidism
    Growth hormone deficiency
    ACTH unresponsiveness
  4. Inborn Errors of Metabolism
    Carbohydrate metabolism
      - Galactosaemia
      - Glycogen Storage Disease Type I (Von Gierke's), also III and VI
      - Fructose Intolerance
    Amino Acid metabolism
      - Maple Syrup Urine Disease
      - Proprionicacidaemia
      - Methylmalonicacidaemia
      - Hereditary Tyrosinaemia
  5. Other Problems
    Abrupt cessation of glucose infusion
    Exchange transfusion without glucose replacement
    Drugs (e.g. THAM, maternal β-blockers)

Symptoms

These are a poor guide to hypoglycaemia. Half of hypoglycaemic infants are asymptomatic, and half of infants with symptoms are not hypoglycaemic.

Hypoglycaemia should therefore be treated regardless of the presence of symptoms. Possible symptoms include:

Signs of neuroglycopaenia
• Abnormal cry
• Lethargy, apathy, floppiness (hypotonia)
• Poor feeding
• Jitteriness
• Apnoea
• Convulsions

Other signs occur occasionally:

Due to catecholamine response - unusual in neonates except those with hyperinsulinaemia
• Pallor
• Sweating
• Tachycardia
Effects of hypoglycaemia on heart. Common following severe asphyxia
• Bradycardia
• Hypotension
• Heart failure
• Cardiac arrest

Diagnosis

Monitor at-risk infants

  • All infants <10th centile or >95th centile
  • If centile charts are not available, all term infants with a birthweight < 2.8kg or >4.5kg
  • Infants with clinical exam findings of significant growth restriction (i.e. evidence of late placental insufficiency and loss of sub-cutaneous fat stores at birth)
  • Infants of diabetic mothers
  • Preterm infants (<37 weeks gestation)
  • Stressed infants - i.e. those with birth asphyxia, sepsis, haemolytic disease, respiratory distress or congenital heart disease
  • Infants with symptoms of hypoglycaemia e.g. jitteriness, poor feeding
  • Infants with possible Septo-Optic Dysplasia e.g. midline brain abnormality seen antenatally (Absent Cavum Septum Pellucidum)

Venn diagram

Figure 1. Incidence of neonatal hypoglycaemia in babies with different combinations of risk factors. Taken from Harris et al1

When to monitor

Measure blood glucose between 60 - 120 mins of age, then 3 hourly before feeds.

How to monitor

All blood glucose measurements should be analysed by a glucose oxidase method e.g. iSTAT, gas machine or lab analysis. Point of care monitors e.g. Accucheck, are not sufficiently accurate to measure blood glucose concentrations in babies at risk of neonatal hypoglycaemia.

How long to monitor

If feeding well - at least 12 hours (i.e. 3 normal blood glucose measurements)
Any recorded hypoglycaemia - at least 12 hours after last low level

Consider monitoring for longer or recommencing monitoring if there are new clinical concerns, and request paediatric review.

Notify the neonatal paediatric service if the blood glucose is < 2.0 mM at any stage.

Management Algorithm

click on algorithm to open a pdf printable version

Hypoglycaemia management algorithm

  1. Continue monitoring blood glucose concentrations until three consecutive blood glucose concentrations have been > 2.6mM
  2. Notify the neonatal paediatric service if the blood glucose is <2.0 mM at any stage.

Investigations (recurrent, persistent or severe hypoglycaemia)

At the time of low blood glucose (ie measure the glucose at the same time):

Insulin (most important investigation) 0.5ml in Paed Micor-PST tube  (Green Top) 4 x Green micro-containers
Cortisol 0.5ml in Paed Micor-PST tube (Green Top)
Growth Hormone 0.5ml in Paed Micor-PST tube (Green Top)
Ketones 0.5ml in Paed Micor-PST tube (Green Top)
Free Fatty acids 1ml blood in EDTA tube, sent to the laboratory on ice (is analysed in Christchurch, 3 week turnaround)
2 x Mauve micro-containers

Can Be Done at Any Time:

Ammonia 0.5ml blood in mauve top (EDTA) tube on ICE. Send immediately!  Notify laboratory - 22000

Treatment

Delivery Suite, Post Natal Ward or PACU (This summarises the above flow chart)

  1. All at risk infants (see above) should receive milk feedings (either breastfeed or formula - maternal preference) or intravenous glucose as soon as feasible, and always within the first 2 hours of life.
    If glucose between 1.2-2.5mM on first testing (1-2 hours)
    - rub 0.5 ml/kg of 40% dextrose gel into buccal mucosa
    - then feed the baby (breastfeed or formula; maternal preference)
    - recheck glucose 30min after dextrose gel.
  2. If glucose between 1.2-2.5mM on subsequent testing
    - rub 0.5 ml/kg of 40% dextrose gel into buccal mucosa
    - then feed the baby (breastfeed or formula; maternal preference)
    - recheck glucose 30min after dextrose gel.
  3. If glucose between 2.0-2.5mM on subsequent testing
    - feed the baby a bottle of formula or EBM 12 ml/kg (90 ml/kg/day)
    - recheck glucose in 1 hour
  4. If glucose below 1.2mM at any stage; below 2.0mM despite two doses of oral dextrose gel; below 2.6mM despite two doses of oral dextrose gel and a bottle of formula/EBM; or if feeds not tolerated, admit the baby to NICU.
  5. If the glucose is <2.0mM at any stage notify the neonatal paediatric service.
  6. Dextrose gel must be prescribed on a medication chart either by a midwife, nurse specialist - neonatal advanced practice, or medical practitioner.

NICU

  1. Start IV Glucose 10% at 60ml/kg/day (=4.2mg/kg/min glucose)
  2. Consider a bolus of 1-2ml/kg 10% Glucose IV
  3. Recheck glucose within 1 hour

Recurrent or persistent hypoglycaemia not responding to above measures - increase IV glucose concentration or volume e.g. 12.5 or 15% glucose and continue feeding if tolerated.

In an emergency, particularly if there is difficulty in starting intravenous glucose infusion,  glucagon 200 microgram/kg intramuscularly will stabilise blood glucose in most babies for one to two hours. The dose can be repeated, but subsequent doses are much less likely to be effective. (Glucagon mobilises glycogen stores. After the first dose, stores will probably be depleted).

Continuing therapy

Continue to monitor glucoses while IV glucose is being gradually reduced. Rapid reductions in glucose infusion are likely to cause rebound hypoglycaemia.

For persistent or severe hypoglycaemia (requiring more than 10mg/kg/min of glucose or lasting longer than 1 week) see Severe Hypoglycaemia below

Severe Hypoglycaemia

Persistent or severe hypoglycaemia (requiring more than 10mg/kg/min of glucose or lasting longer than 1 week) may require further investigation and management, e.g. with glucagon, diazoxide, steroids or surgery. Consider discussing with Paediatric Endocrine Service.

References

  1. Harris D, Weston P, Harding J. Incidence of neonatal hypoglycaemia in babies identified as being at risk. J Pediatr. 2012;161:787-91.
  2. Hay Jr W, Faju T, 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;155(5):612-7.
  3. Koh THHG, Aynsley-Green A, Tarbit M, Eyre JA. Nerual dysfunction during hypoglycemia. Arch Dis Child. 1988;63:1353-8.
  4. Lucas A, Morley R, Cole TJ. Adverse neurodevelopmental outcome of moderate neonatal hypoglycaemia. BMJ. 1988;297(6659):1304-8.
  5. Harris D, Weston P, Battin M, Harding JE. Dextrose Gel for Treating Neonatal Hypoglycemia:A Randomized Placebo-Controlled Trial (The Sugar Babies Study). Lancet, 2013, published online 25 September.
  6. Alsweiler, J. M., Harding, J. E., Crowther, C., & Woodall, S. M. (2015). Oral dextrose gel to treat neonatal hypoglycaemia: Clinical Practice Guidelines. Prepared by the "The Oral Dextrose Gel to Treat Neonatal Hypoglycaemia Clinical Practice Guidelines" Panel (pp. 73 pages). http://hdl.handle.net/2292/26266.
  7. Koh THHG, Eyre JA, Aynsley-Green A; Neonatal hypoglycaemia - the controversy regarding definition. Arch Dis Child 1988; 63:1386-1398
  8. LaFranchi S; Hypoglycaemia of infancy and childhood. Pediatric Clin N Amer 1987; 34(4): 961-80.
  9. Lubchenco LO, Bard H; Incidence of hypoglycemia in newborn infants classified by birth weight and gestational age. Pediatrics 1971; 47: 831-8.
  10. Senior B, Sadeghi-Nejad A; Hypoglycemia: A pathophysiologic approach. Acta Paediatr Scand Suppl 1989; 352: 1-27.
  11. Glaser B, Thornton P, Otonkoski T, Junien C. Genetics of neonatal hyperinsulinism. Arch Dis Child Fetal Neonatal Ed 2000; 82:F79-F86.
  12. Shepherd RM, Cosgrove KE, O'Brien RE, et al. Hyperinsulinism of infancy: towards an understanding of unregulated insulin release. Arch Dis Child Fetal Neonatal Ed 2000; 82:F87-F97.
  13. Aynsley-Green A, Hussain K, Hall J, et al. Practical management of hyperinsulinism in infancy. Arch Dis Child Fetal Neonatal Ed 2000; 82:F98-F107.
  14. Rahier J, Guiot Y, Sempoux C. Persistent hyperinsulinaemic hypoglycaemia of infancy: a heterogenous syndrome unrelated to nesidioblastosis. Arch Dis Child Fetal Neonatal Ed 2000; 82:F108-F112.

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Document Control

  • Date last published: 03 December 2018
  • Document type: Clinical Guideline
  • Services responsible: Neonatology
  • Owner: Newborn Services Clinical Practice Committee
  • Editor: Sarah Bellhouse
  • Review frequency: 2 years