These guidelines apply to most babies on the neonatal unit. There are separate guidelines for postnatal ward care.

Use the following guideline only for babies born <37/40 if admitted to the neonatal unit.

Use only blood gas analyser or lab blood sugar results to initiate major changes in treatment.

Who to test

Infants admitted into the NNU are at risk of both hypo- and hyperglycaemia and therefore blood sugar testing should be considered in the following infants.

At risk of hypoglycaemia			At risk of hyperglycaemia
Decreased stores	Increased utilisation	Other
Infants <1.8 kg	Infants of diabetic mothers	Maternal drugs – beta agonists	Infants with ELBW
Infants with IUGR (<2nd centile-see WHO 2009 charts)	Infants with perinatal hypoxia	Iatrogenic – Infants with tissued IV	Infants receiving TPN or high glucose solutions
Infants with inborn errors of metabolism	Infants with temperatures <36.4o		Infants experiencing  stress/painful situations
	Infants with respiratory distress
	Infants with polycythemia
	Infants with blood group incompatibility haemolytic disease
	Infants with seizures
	Infants with sepsis

Frequency of taking blood for glucose estimation depends on the risk status. All infants receiving intensive care or on i.v. fluids should have a ‘sugar’ taken on admission and at least once per shift. Where there is an acute event, for example tissued IVI or seizure, a blood sugar must be done after the event and within 1 hour.       

Timing of tests

Initial screening

• Do not test the blood sugar routinely on admission of babies with other problems to the neonatal unit. In these babies, the first blood sugar should be done 1 hour after the first feed or 1 hour after starting iv fluids
• In babies admitted for treatment with iv glucose because of hypoglycaemia the blood sugar should be checked 1 hour after treatment is started
• Do an immediate blood sugar only if the baby’s symptoms might be caused by hypoglycaemia (fits, other severe neurological presentations of unknown cause)

Subsequent testing

• If blood sugars have been previously normal and stable and there has been no recent treatment change, test once per shift 
• If blood sugars have been unstable, test 3 hourly (before feeds if receiving milk) 
• Retest 1 hour after any treatment change (ideally within an hour of previous sample)

Symptomatic hypoglycaemia

If the baby is thought to have symptoms because of hypoglycaemia of any degree, i.v. treatment should be given urgently (2.5ml/kg 10% glucose bolus, then 10% glucose infusion).  

Do further investigations at time of symptoms (see below).  Collect bloods before giving any glucose.

Once the blood sugar is normalised, wean as with other babies.

Asymptomatic hypoglycaemia

Intervene if blood sugar is 2.0 - 2.6mmol/l on 2 occasions or < 2.0mmol/l on 1 occasion

Baby on full enteral feeds

• If there are concerns about toleration and there is significant hypoglycaemia, occasionally iv fluids may have to be started
• Otherwise give an early milk feed (it may be appropriate to give a larger than usual volume, eg 2 hours’ volume in hourly fed baby) and increase frequency and/or total daily intake
• Otherwise healthy term babies with hypoglycaemia may have glucose fortified feeds as the next step (avoid this in preterm infants because of the risk of NEC)

Baby on enteral and iv fluids

• Check the iv line
• If blood sugar < 1.0mmol/l give a bolus of 10% glucose, then increase glucose infusion
• If blood sugar >1.0mmol/l increase glucose infusion -either increase total volume or concentration (if the baby is on other iv fluids consider reconstituting drugs to reduce the proportion they contribute to daily fluids rather than increasing total daily fluid intake)

Weaning

When a baby with problematic hypoglycaemia or an infant of a diabetic mother on intravenous fluids is well enough to receive milk feeds follow these guidelines. (If there has been no such problem, go to alternative guidelines, weaning glucose).

At any stage in the weaning process infants should be receiving some enteral feed.

Baby not sucking

Continue at least 1ml/hr of milk (provided no contraindications) as extra to prescribed fluids in babies on I.V. treatment (this can be given hourly NG)

Baby wanting to suck

Allow to breast/ bottle feed in addition if  hungry (unless specific contraindication). If the baby is well, there is no need to include this in the total daily fluids until the baby is taking regular oral feeds and iv fluids are being weaned.

Weaning from 10% glucose

First convert 10% glucose to hourly measured enteral feeds (by NG tube/cup/bottle/syringe) by increasing milk by 1ml every 3-4 hours and reducing glucose appropriately. If babies want to suck more than the prescribed volume, then that should be allowed. Blood glucose should be checked 1 hour after treatment changes. When blood glucose is satisfactory and the baby is on full enteral feeds, go to 2 and 3 hourly feeds quite quickly (as quickly as 24 hours if toleration is good).

Weaning from i.v. glucose >10% concentration

First wean the concentration of iv glucose to 10% (increase 10% glucose infusion rate and decrease 20% glucose infusion rate by 1ml/hr every 4 hours). Once onto 10% glucose convert to enteral feeds as outlined above.

Weaning unsuccessful: go back a step and wean more slowly.

Investigation: Consider investigating for endocrine/metabolic causes of hypoglycaemia if weaning is difficult.

Severe or prolonged hypoglycaemia

Indications for investigation

N.B. Always ensure that drip is working if hypoglycaemia occurs in a baby on i.v. glucose.

Suspicious patterns of hypoglycaemia (this should not be applied to infants of diabetic mothers):

• Hypoglycaemia recurring in the first 48 hours in a term infant, despite standard regimen of 10% glucose
• Severe recurrent hypoglycaemia (blood glucose <1 mmol/l on more than 2 occasions) in the first 48 hours
• Severe hypoglycaemia (blood glucose <2 mmol/l on one occasion) occurring after 48 hours of age, provided this is not related to weaning
• Symptomatic hypoglycaemia at any time
• High glucose requirement (>8 mg/kg/min). To calculate the infusion rates using 2 different glucose concentrations, use the calculator.

Hypoglycaemia with other problems:

• Hypoglycaemia requiring treatment at any stage, and prolonged jaundice -add plasma cortisol measurement to prolonged jaundice screen
• Hypoglycaemia associated with hyponatraemia or hypernatraemia in a term infant
• Hypoglycaemia associated with micropenis
• Hypoglycaemia associated with absent corpus collosum, midline defect (including cleft palate) or hypertelorism

Investigations

• Discuss the infant with a senior member of staff on NNU
• Discuss with Biochemistry RIE (Duty Biochemist during working hours).  See notes below.
• Send the investigations at the time of an episode of hypoglycaemia, before giving any glucose.

Blood for:

• glucose, taken at the same time as other tests
• insulin
• cortisol
• growth hormone
• ß-hydroxybutyrate
• free fatty acids
• amino acids

Put urine bag on at once for

• urinalysis (ketones)
• amino and organic acids

Note

• When a hypoglycaemia screen is performed, the specimen for insulin levels will be frozen and stored.  It is important that RIE Biochemistry is aware that the sample is being taken.
• RIE will send frozen insulin samples to WGH on Tuesday am to catch the weekly run on Wednesday am.
• If a result is needed urgently (within 48 hours) then you should contact the Biochemst at RIE (26880), during normal working hours, who will arrange both the analysis with WGH and transport of the specimen to WGH.  The decision to ask for an urgent sample must be made by a Consultant, preferably after discussion with Dr Midgley or one of the Endocrinologists from RHSC.
• The lab will not analyse insulin, cortisol ß-hydroxybutyrate or growth hormone if the blood sugar was not low at the time.
• Investigations are cascaded - free fatty acids will and ß-hydroxybutyrate will not be analysed if the insulin level is high.  Similarly gross ketosis without dicarboxylic acids on organic acid profile makes free fatty acid analysis unnecessary.  Free fatty acid/ß-hydroxybutyrate ratio is very useful if for some reason no urine sample is collected.
• Investigations for potential panhypopituitarism will often be cascaded - e.g. blood will be stored if possible for later ACTH if cortisol inappropriately low.

Hyperinsulinism

Clinical Presentation

• Severe persistent hypoglycaemia, usually apparent on day 1.
• Glucose requirement >8mg/kg/min.
• May be large infant (PHHI), or stigmata of Beckwith Wiedeman syndrome or predisposing factor for transient hyperinsulinism (maternal diabetes, SGA, severe rhesus disease)

Differential diagnosis

• Transient hyperinsulinism
• Persistent hyperinsulinism of infancy (PHHI)

Investigations

Samples during hypoglycaemia blood for:

• Insulin, C-peptide,
• ketone bodies ß-hydroxybutyrate
• free fatty acids,
• amino acids, lactate, ammonia
• cortisol
• growth hormone
• urine for amino and organic acids, ketones and acyl carnitine

Management

• Insert central (eg silastic venous) line for security of glucose infusion.
• Glucagon 0.5mg i.m. can be used for emergencies, i.e. tissued drip, but will cause rebound increase in insulin secretion thereafter.
• If blood glucose requirement >12mg/kg/min may need drugs to suppress insulin secretion.
• If persistently in the 15-20 mg/kg/min range will definitely need drug therapy

If the infant is tolerating oral feeds (but beware that the protein load of milk may stimulate insulin secretion)

• Use diazoxide (5-20mg/kg/day divided into 3 doses, suggest start at 5-10mg/kg/day).  Diazoxide can also be given I.V (with alternative diuretic).
• Always use with Chlorothiazide. Chlorothiazide helps counteract the fluid retention caused by diazoxide and also has additional effects on suppression of insulin secretion.
• Avoid excessive fluid intake during diazoxide therapy. 
• Must monitor BP (intermittently will do) on diazoxide therapy. 
• Side effects: fluid retention, hypertrichosis (chronic use), hyperuricaemia, hypotension, rarely leucopenia, thrombocytopenia.

If not tolerating feeds, or not controlled by diazoxide/chlorothiazide 

• Use Somatostatin (octreotide) 5-20 micrograms/kg/day as a continuous infusion either I.V. or s.c. (start on low dose as causes vasoconctriction in the gut) usually accompanied by I.V. glucagon infusion 1-10 micrograms/kg/hour
• Must be under ECG monitoring (somatostatin).
• Somatostatin also suppresses GH, TSH, ACTH, can cause steatorrhea, cholelithiasis, abdominal distension.
• Glucagon infusion can cause hypokalaemia, vomiting, increased myocardial contractility, and increases growth hormone.

If neither diazoxide or octreotice effective or diazoxide having some effect, but not sufficient to wean off drip consider:

• Nifedipine 0.25-2.5 mg/kg/day divided into 8 hourly regime, start at lowest dose and work up as blood pressure tolerates.
• In practice almost impossible to administer <1mg.
• If no arterial line, then measure BP before and at 15 minute intervals after each dose, continuing for at least an hour.

Infant not controlled by drug therapy

The infant will require surgery (removal of part of pancreas) if unable to wean from I.V. glucose onto feeds, or if requiring >20mg/kg/day diazoxide. Recent data shows that a significant number of cases (40%) are due to focal hyperplasia of the islet cells, where resection of the affected portion can be undertaken, but location of the lesion requires selective pancreatic venous sampling. This is important as there is a high risk of pancreatic failure (diabetes, with or without exocrine deficiency) later in childhood following subtotal pancreatectomy. In the UK selective venous sampling is only done intra-operatively, and only at Great Ormond Street.

Long term

Genetics.

• Send sample for DNA extraction, stating that the infant has hyperinsulinism, and mark it for the attention of Dr. Wayne Lam.
• Refer to Dr. Lam for investigation of family.
• Counselling - May be autosomal recessive

Home management

• Monitoring blood glucose at home by parents
• Not infrequently require tube feeds
• Use of cornstarch to increase feed interval
• Hypostop and injection of glucagon for emergency use
• Flow chart for parents on action for low blood sugar readings