Persistent or refractory hypoglycaemia in the neonate : a guideline for management

Initial discussion should be undertaken with the attending Neonatal Consultant.
Full clinical history and examination of the neonate should be carried out to include:

• History:
• Maternal history of ingestion of medications which can induce hypoglycaemia, for example labetalol
• Maternal history of diabetes
• Feeding patterns since birth and relationship with hypoglycaemia
• Family history of consanguinity and sudden infant death
• History of prolonged jaundice
• Birth weight centile (<10^th centile)
• Preterm (<37 weeks)
• Severe illness e.g. sepsis, hypoxia, rhesus disease
• Examination (Robinson et al., 2009)
• Small penis, midface abnormalities with or without prolonged jaundice suggestive of panhypopituitarism
• Macrosomia – hyperinsulinism, infants of diabetic mothers
• Ambiguous genitalia or virilisation or a pigmented scrotum in a Caucasian infant – congenital adrenal hyperplasia
• Progressive liver enlargement in the first week of life – disorders of gluconeogenesis or glycogen storage disease
• Hypotension – cortisol deficiency
• Abnormal ear lobes, macroglossia, hemi-hypertrophy, umbilical hernia – Beckwith-Wiedemann syndrome

Refractory hypoglycaemia (requiring >8mg/kg/min Glucose to maintain normoglycaemia) in the first few days after birth will usually be caused by hyperinsulinism.  For such babies, the investigations outlined in bold in the table below should be prioritised.  These investigations should be carried out at the time of hypoglycaemia.

Babies with persistent hypoglycaemia (more than 2 days), or with atypical presentation  (babies with no clear cause for the hypoglycaemia such as maternal diabetes or beta blockers),  should be discussed with the Neonatal Consultant on call and consideration given to  undertaking the extended list of investigations as below.
Note that some investigations may be hard to interpret in the first few days after birth due to  normal physiological hormonal changes after delivery.

If you wish to discuss which investigations are needed, discuss with the Endocrine Consultant on Call at the Royal Hospital for Children, Glasgow.

In total, you should take 2 lithium heparin blood bottles, a grey top fluoride/oxalate bottle, a blood spot card and a urine sample during hypoglycaemia and send them to Biochemistry.

These tests are performed in different laboratories throughout Glasgow. If you wish to discuss how these tests should be sent, please discuss with the On Call Biochemist.

Table 1. Investigations required for neonates with refractory or persistent hypoglycaemia at time of hypoglycaemia

Whilst investigating possible underlying causes, treatment should continue as per the WoS guidelines entitled ‘Hypoglycaemia: term infants’ or 'Hypoglycaemia preterm infants'.  If an underlying cause is identified, advice should be sought from the endocrine/metabolic team.

The aim of treatment is to maintain BM>3.0 mmol/l in the first 48h and 3.5 mmol/l thereafter, this reduces the risk of hypoglycaemia and subsequent neurological impairment.

If concerns re ongoing hypoglycaemia, blood sugars should be monitored at least 4-6 hourly, ideally pre-feed. Closer monitoring will be required after any change in therapy, particularly if reduction in glucose delivery. Blood sugars should be taken using the blood gas analyser machine, as bedside BM monitors are not accurate with glucose levels <3mmol/l. There should be early consideration of central access for the neonate.

*If unable to keep Glucose >3.0 mmol/l in the first 48h or >3.5 mmol/l thereafter, consider escalation of therapy and discussion with endocrine/metabolic team.

Drugs which may be recommended by the Metabolic/Endocrine service:

For doses please see relevant pharmacy monographs

Preparation for discharge

All patients who have required medication to treat refractory hypoglycaemia should have a ‘Fasting Challenge’ performed prior to discharge to ensure they would tolerate a missed feed in the community. During this challenge, one of the usual 3 hourly feeds should be omitted and glucose should be monitored hourly after the scheduled omitted meal until 6 hours post feed. The following observations should also be noted on an hourly basis:

• Level of consciousness (responsive and can be roused)
• Tone (normal)
• Temperature (36.5-37.5 degrees Celsius)
• Respiration (consistently >30, <60)
• Colour (pink)

If this is satisfactory, the baby can be safely discharged. The parents should however be advised that they must feed their infant at a minimum of every 3 hours. The parents should also be advised of the symptoms to watch for which may signify hypoglycaemia (jitteriness, lethargy, high pitched cry) and to seek medical advice if they have any concerns.

NB – if the blood glucose falls below 2.6mmol/l , the baby should be fed and the fasting test abandoned.  Regular 3hly feeds should be recommenced and the test repeated after an interval (interval to be determined by the medical team).

Neonatal Hypoglycaemia Results Sheet (pdf)

Example care plan for discharge of babies who have refractory hypoglycaemia (pdf)
 (please discuss with endocrine team)