Should metabolites other than glucose be measured?

Ketones, lactate, and insulin concentrations should not be measured routinely in addition to glucose for the diagnosis and monitoring of neonatal hypoglycaemia in the first 72 hours. [Conditional recommendation]

Consider measuring glucose, beta-hydroxybutyrate, and insulin concentrations in babies with hypoglycaemia that persists beyond 72 hours to help distinguish between those with congenital hyperinsulinemia and those with other causes.

Measuring ketones, lactate or insulin may help uncover uncommon causes of hypoglycaemia but requires additional blood tests, thus causing additional distress to the baby and whānau and incurring additional costs.

Since most neonatal hypoglycaemia is transitional, testing before 72 hours may show concerning findings (e.g. detectable insulin concentrations at the time of low glucose concentrations) that will resolve spontaneously and therefore should not alter management for most babies.

Preliminary evidence suggests that measuring ketones at approximately 72 hours may help distinguish the cause of the hypoglycaemia.

If hyperinsulinism is suspected and there are no risk factors for hypoglycaemia, insulin concentrations might be measured earlier. However, there was uncertainty about whether testing before 72 hours makes a difference even for congenital hyperinsulinism.

The overall consensus was that 72 hours is an appropriate time to consider measuring other metabolites, as testing earlier is unlikely to be useful.

Consider measuring insulin before 72 hours if hypoglycaemia is severe (<1.5 mmol/L) and the baby does not have risk factors for hypoglycaemia or has other concerning clinical features. Additionally, consider paediatric endocrinology/metabolic referral for severe hypoglycaemia (<1.5 mmol/L) within the first 72 hours.

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The additional blood tests may not be available at all healthcare facilities, which could potentially worsen inequities for those with limited access. However, it is possible to collect the samples at any facility and have them analysed at a different location, helping to reduce some of the access barriers.