Neonatal hypoglycaemia can be an indication of an underlying illness or a failure to adapt physiologically to extra-uterine life. Newborns are screened for hypoglycaemia based on risk factors, starting at 1-2 hours after birth. Neonatal hypoglycaemia is common, preventable and can cause and potentiate neonatal brain injury. It is important to recognise infants at risk so hypoglycaemia can be prevented and/or treated promptly. Breastfeeding should be supported, but supplementation with expressed breastmilk; infant formula or intravenous dextrose administration may be required as part of the safe management of the infant, in consultation with the parents or primary carers.An episode of neonatal hypoglycaemia should last no longer than 2 hours without medical intervention.

Hypoglycaemia - The term hypoglycaemia refers to a low blood glucose concentration. In the neonate, hypoglycaemia is defined as a blood glucose level (BGL) <2.6mmol/L.

Blood glucose level (BGL) - Is measured by a blood glucose monitor and reagent strips. These measurements are less accurate at a lower BGL and a true blood glucose (TBG) should be sent to the laboratory or performed utilising the blood gas analyser (Istat) in the Special Care Nursery (SCN)or Maternity unit for any BGL <2.6mmol/L.

True blood glucose (TBG) - Is measured by the blood gas analyser (Istat)in SCN, Maternity unit or by laboratory analysis. TBG should be used in preference to BGL monitoring when available.

At Risk - those infants who have a higher probability of requiring medical intervention to monitor or rectify blood glucose levels.

Jitteriness - Excessive repetitive movements of one or more limbs, which are unprovoked and usually relatively fast. Jitteriness is distinguished from seizure activity by the ability to stop the movements by holding the affected area/limb in flexion. It is not a definitive sign of hypoglycaemia, as it also occurs in neonatal abstinence and in babies of mothers who were on selective serotonin reuptake inhibitors (SSRI's) during pregnancy. Hypoglycaemia should however be excluded in all babies who have symptomatic jitteriness.

Many neonates with hypoglycaemia are initially asymptomatic.

Clinical signs which suggest clinically significant hypoglycaemia are non-specific and may include:

• Jitteriness
• Hypothermia
• Poor feeding
• Irritability
• High pitched cry
• Lethargy
• Hypotonia
• Altered levels of consciousness
• Seizures
• Cyanotic episodes
• Apnoea

The following infants are considered ‘at risk’ of hypoglycaemia:

Maternal factors:

• Maternal diabetes (pre-existing and gestational), particularly if poorly controlled, irrespective of whether on insulin or not
• Maternal use of beta-blockers (e.g. labetalol)

Infant factors:

• Preterm (<37 weeks completed gestation)
• Low birth weight (LBW) (<2500g), regardless of gestation
• Small for gestational age (SGA) (<10th centile by gestation)
• Large for gestation age (>90th centile by gestation)
• Clinically wasted infant, regardless of birth weight
• Perinatal stress (severe acidosis, intrapartum asphyxia)
• Respiratory distress
• Hypothermia/cold stress
• Suspected or actual sepsis/other illness in the baby
• Rhesus iso-immunisation
• Polycythemia
• Birth asphyxia
• Suspected or known inborn errors of metabolism or endocrine disorders
• Nil orally

Table 1: Birthweight thresholds for small and large for gestational age.

Table Reference: https://thewomens.r.worldssl.net/images/uploads/downloadable-records/clinical-guidelines/hypoglycaemia-newborn-management_280720.pdf

PREVENTION

All preventative measures and care should be fully explained and implemented in consultation with the parents or primary carers of the affected infant.

Whilst these principles apply to all neonates it is important to recognise the infant at risk of hypoglycaemia and initiate strategies from birth to assist with prevention. 

Prevention strategies include:

• Antenatal expression of colostrum to have expressed milk available for early feeds (refer to guideline CPG0170 Antenatal Expression of Colostrum).
• Skin-to-skin contact at birth and an early breastfeed within the first hour, unless the baby requires immediate resuscitation or transfer to the Special Care Nursery (SCN).
• Ongoing skin-to-skin contact to aid thermoregulation and promote frequent breastfeeds.
• Educating mothers to recognise and respond to early feeding cues (these may not be present in the ‘at risk’ infant).
• Feeding frequently and regularly on demand, feeding every three hours at a minimum.
• Support breastfeeding at each feed and assessing the quality of each feed. Correct positioning and attachment must be established to ensure efficient milk transfer.
• Encouraging expressing by the mother if feeding at the breast is not achievable; expressing can be done initially by hand, later by pump, consider the 'initiate' program on medela symphony pump for earlier pump use.  The expressed breast milk (EBM) may be given to the baby, unless the baby is nil orally for another medical reason. CPG0186 Breastmilk - Expressing, storing and feeding.
• Supplementation with infant formula is only used according to Appendix 2 Neonatal Hypoglycaemia: Management of infant diagnosed with or at risk of hypoglycaemia (enteral feeding) flow chart in response to documented hypoglycaemia, or when it is the maternal feeding choice.
• The above preventative care should be discussed with and explained to parents/guardians.
  

INFANTS OF MOTHERS WHO HAVE DIABETES

The on call Paediatric Registrar/Consultant should be aware of the impending birth of an infant of a mother who has diabetes.

Infants who have been identified antenatally as at risk of complications should be discussed with the Paediatric team as part of the booking process for induction of labour/delivery and delivery should be managed in partnership between the Obstetric and Paediatric teams.  The Paediatric team may decide prior to or at birth that an infant should be managed in the SCN. Wherever feasible, mother and infant should however not be separated, i.e. the infant is managed on the postnatal ward.

The recommended admission criteria for the infant to the SCN includes:

Maternal indications:

• Poor glycaemia control during pregnancy (most recent HbA1c >7.5%)
• BGL > 8.0 mmol/L during labour
• IV glucose during labour

Infant Indications:

• Unwell (e.g. signs of respiratory distress)
• LBW (<2300g) or clinically wasted regardless of birth weight
• Additional or other medical concerns/conditions

Infants of mother’s who have diabetes (pre-existing/gestational) may be admitted to the postnatal ward if good glycemic control during pregnancy can be demonstrated and the infant does not fit the above criteria. 

This is always done in consultation with the Paediatric Team.  The infant admitted to the postnatal ward is considered “at risk” of hypoglycaemia and management includes the following:

• Feeding: Support of early, frequent and regular breastfeeding/breastmilk.  Supplementary feeds should be introduced only if milk supply is insufficient or if formula feeding is the maternal choice.
• Blood sugar monitoring and management of hypoglycaemia (BGL<2.6 mmol/L) is according to the flowcharts and should occur in a timely manner with appropriate documentation:
  • Appendix 1 Neonatal Hypoglycaemia: Management of infant diagnosed with or at “AT RISK” of hypoglycaemia (nil orally) or,  
  • Appendix 2 Neonatal Hypoglycaemia: Management of infant diagnosed with or at “AT RISK” of hypoglycaemia (enteral feeding)
• Observation: should be performed and documented on the infant’s chart prior to each feed and should include:
  • Level of consciousness
  • Tone
  • Temperature
  • Respiration
  • Colour/perfusion

INFANTS AT RISK OF HYPOGLYCAEMIA ADMITTED TO THE POSTNATAL WARD

All infants 'at risk' of hypoglycaemia admitted to the postnatal ward require the following care:

• Commence feeding within one hour of birth and then regularly, on demand, but at least 3 hourly.
• Blood glucose monitoring should occur:
• At two hours of age and before the second feed
  • If clinical signs of hypoglycaemia are present
  • Before each subsequent feed until there are 3 consecutive readings ≥ 2.6 or as requested by the Paediatric Team.
  • If any other significant risk factors for hypoglycaemia present and 3 x BSL's not >3.0mmol/L, Medical review required prior to ceasing.
  • BGL monitoring should recommence is there is a change in feeding (e.g. feeding less frequently or weaning supplementary feeding) or with clinical concern.

All asymptomatic babies with BSL < 2mmol/l as well as symptomatic babies with BSL <2.6mmol/l should have a confirmatory TBG without delay.

If an infant is hypoglycaemic (TBG<2.6 mmol/l), management should be initiated according to the flowchart Appendix 2 Neonatal Hypoglycaemia.  Management of infant diagnosed with or at risk of hypoglycaemia (enteral feeding).

Management based on first TBG:

• TBG < 1.5mmol/L or <2.6mmol/L and clinically symptomatic: Discuss with paediatric registrar and transfer to SCN for management as per Appendix 2 (Appendix 1 if Nil Orally)
• TBG 1.5mmol/L to 2.5 mmol/L: Massage glucose gel into the buccal mucosa (0.5ml/kg of 40% glucose gel) if this can be done safely AND then proceed to feed the baby as per Appendix 2, notify the paediatric medical team.
• TBG >/= 2.6mmol/Ll: Continue demand feeds with 3 hourly limit, and continue as per Appendix 2.

Continue to follow flow chart in Appendix 2 for subsequent results.  

Further management based on second BGL/TBG:

• TBG < 1.5mmol/l or <2.6mmol/L and clinically symptomatic: as above.
• TBG 1.5mmol/L to 2.5 mmol/L: Repeat glucose gel into the buccal mucosa (0.5ml/kg of 40% glucose gel) if this can be done safely AND then proceed to feed the baby:
  • TBG >/= 2.0mmol/L give 30ml/kg/day of EBM/formula
  • TBG <2.0mmol/L give 60ml/kg/day of EBM/formula
• Repeat TBG at 1 hour (MAX) of previous TBG, and notify Paediatric Medical staff if TBG <2.6mmol/L
• BSL >/=2.6mmol/l: Continue demand feeds with 3 hourly limit.  No further supplement feeds required if only required a single 30ml/kg/day top-up. Gradually phase out supplementary feeds if required a 60-90ml/kg/day, depending on BSL's and maternal breast milk supply.

In all instances:

• Glucose gel: first 2 doses can be nurse initiated on post natal ward. Further doses (up to total of 6 in 48hrs) only to be in consultation with medical staff.
• Breastfeed prior to supplementary feed, unless symptomatic. If baby is hypoglycaemic, limit duration of breastfeed to no more than 30 minutes whilst hypoglycaemic (less if feed is assessed as not being effective).
• Provide supplementary feed by syringe, finger feed, gavage, or bottle as appropriate, without delay.
• Consider 2 hourly or continuous feed if struggling to tolerate the required volume.
• Recheck BGL 60 minutes (MAX) after enteral feed if prefeed TBG < 2.6mmol/l.
• Cease BGL monitoring when 3 consecutive BGLs >/= 2.6mmol/l.
• Once infants are transferred to the postnatal ward, after initial care and stabilization for hypoglycaemia in the SCN, paediatric review prior to discharge home is suggested to ensure appropriateness for discharge and to plan follow-up, if indicated.

Administration of Glucose Gel:

• Dry inside of baby's mouth
• Twist tip of tube off and squeeze contents into a measuring cup to withdraw dose.  Tube maybe used by the same baby until discharge or contents expire (if prior to the discharge.) Label tube with Baby's identification sticker.
• Measure required dose of glucose gel with oral syringe.
• Apply small amount of gel at a time to buccal mucosa and massage gently with a clean, gloved finger.
• Do not put gel back in mouth
• Document administration on the medication charts. Two doses may be initiated in the 'once only medicines' by a Registered Nurse/Midwife thereafter ordered by a medical officer (up to 6 doses in the first 48hours) or ordered as per hospital policy.
• Continue to monitor TBG as per appropriate flow chart.
• Side effects of Glucose Gel
  • Gagging
  • Vomiting
  • Hyperglycaemia  

INFANTS 'AT RISK' OF HYPOGLYCAEMIA - ADMITTED TO THE SPECIAL CARE NURSERY

All infants 'at risk' of hypoglycaemia admitted to the SCN require the following care:

• Commence feeding within one hour of birth and then regularly every 3 hours if able to tolerate enteral feeds. If there is a contraindication to enteral feeds or no response to feeding, an IV cannula must be inserted and proceed as follows:
  • Give an IV bolus of 200-300mg/kg (2-3ml/kg of 10% Dextrose)
  • This is followed by a continuous IV infusion of 10% Dextrose at 60-80ml/kg/day (4.2-5.6mg/kg/min glucose) to prevent rebound hypoglycaemia.
  • If restriction is necessary, give more concentrated glucose solution.

Note: IV infusion of solution with >12.5% dextrose are best given through an umbilical venous catheter or central line in order to avoid complications. (However, inability to gain such access should not preclude using such higher concentrations of glucose. 

• Blood glucose monitoring should occur:
  • At half an hour of age or earlier if medically indicated (first TBG/BGL usually with insertion of IV cannula).
  • If clinical signs of hypoglycaemia are present
  • Before each subsequent feed, or 3 hourly if the infant is nil orally, until there are 3 consecutive readings ≥2.6 or as requested by the Paediatric team
  • The infant who is nil orally with intravenous therapy must have 2 consecutive readings ≥ 2.6 mmol/L measured 3 hourly and may then have 6 hourly BGL monitoring. 
  • BGL monitoring may need to be more frequent with a change in management/feeding (e.g. weaning IV dextrose or changing frequency of feeds.
  • BGL monitoring may be less frequent (12 hourly) if an infant is stable on a combination of enteral feeds and IV fluids.
• Once the blood glucose normalises, enteral feeds can be reintroduced and the infusion weaned off.
• If the infusion is no longer required, the otherwise well infant could have their blood glucose measurements taken in the postnatal ward if it is otherwise safe to do so.

Prescriptions for IV glucose

Prescription to make up a 50 mL solution of various glucose infusions are listed below:

INFUSION CONCENTRATION VOLUME OF 10%GLUCOSE

Glucagon:

• Allows mobilisation of hepatic glycogen stores
• Less likely to be useful in infants < 34 weeks (due to minimal glycogen stores) or infants >24 hours postnatal age with inadequate feeding (stores deplete within 24 hours).
• May be used as an intramuscular injection for the acute management of hypoglycaemia, or as a continuous infusion where hypoglycaemia is treatment resistant
  • In infants with adequate glucogen stores (eg: hyperinsulinaemic states) whose hypoglycaemia persists in spite of an IV infusion, administer an IM injection of glucagon (0.03 to 0.1 mg/kg).  This may be repeated after 6-12 hours.  Some infants of diabetic mothers may require up to 0.3 mg/kg to a maximum dose of 1mg (total dose, not per kilogram).
  • If hypoglycaemia recurs or persists despite IV infusion of 12.5% glucose at 120mL/kg/d (10.5 mg/kg/min), an IV glucagon infusion should be considered (1-20 micrograms/kg/hr) should be considered while arrangements are made to transfer the infant to a tertiary centre for continued treatment.

Persistent hypoglycaemia

If hypoglycaemia is persistent, the following management will be considered:

• Increase rate of IV 10% dextrose to a maximum of 120mL/kg/d within first 24 hrs of life
• Increase rate of IV 10% dextrose to a maximum of 150mL/kg/d (10mg/kg/min) after 24hrs of life
• If fluid restriction is required (e.g. with birth asphyxia), increase the concentration of the IV dextrose infusion to 12.5 or 15%.
• Concentrations >12.5% must be given via central venous access

The Paediatrician may discuss the management with PIPER, neonatal emergency transfer team.  Further management might involve a glucagon infusion or administration of hydrocortisone.  The need for central IV access will be an indication to consider transfer to a tertiary centre.

Documentation of IV glucose infusions must be in mL/kg/day and the hourly rate documented on the IV orders by the Paediatric team.

It is useful to also calculate the infant’s dextrose requirement in mg/kg/min, a glucose delivery calculator is located in NICU tools: http://www.nicutools.org/ (see appendix 3)

Persistent dextrose requirement of >10mg/kg/min suggests the need for further investigation, including blood tests whilst hypoglycaemic (<2mmol/l) see below.

Hyperinsulinism

Hyperinsulinism is suspected if:

• Hypoglycaemia persists after day 3 and/or it is not possible to wean the glucose infusion
• Glucose requirement > 10mg/kg/min
• Features of overgrowth syndrome or metabolic disorder

In these circumstances further investigation will be appropriate:

When TBG < 2.0mmol/l, collect arterial or venous blood for:

• Glucose (grey top tube) -  processed at BHS
• Insulin (yellow top tube) -  processed offsite
• Growth hormone (yellow top tube/needs to be on ice) - processed offsite
• Cortisol (yellow top) - processed offsite
• Free fatty acids (grey top tube) -  processed off site
• urine for ketones and organic acids

Also consider:

• Ammonia (purple top tube/on ice) -  processed offsite (can be done at SJOG).
• Acyl carnitine (Newborn screening card) - processed at Victorian Newborn Screening laboratory
• Lactate (grey top tube) - processed at BHS

Total pathology tubes suggested for all of above:

• 2 grey (1 for glucose and lactate and 1 for free fatty acids),
• 3 yellow (for 3 individual test done offsite, 1 on ice),
• 1 purple (for ammonia/on ice).

Note: Management should be in consultation with an endocrinologist/tertiary center.