What is hypoglycemia? part 2

The new statement from the CPS, and many others, don’t discuss which measurement that we are really interested in, is it blood glucose, or plasma glucose? The different data sources are discussed as if they were all measuring the same thing.

But this is where it gets a bit confusing. Whole blood glucose is lower than plasma glucose, by about 15%, depending on hematocrit. Even more confusing, some laboratories will convert glucose measurements even when they perform whole blood glucose, and report the results as if they were a plasma glucose. Most glucose reagent strips actually measure whole blood glucose, but pretend they are measuring plasma glucose and apply a conversion factor. So what you see on the screen is what was measured multiplied by 1.15 (or something similar)

Some studies, such as the excellent study from Auckland on the incidence of low blood sugars among at-risk infants (Harris DL, et al. Incidence of neonatal hypoglycemia in babies identified as at risk. J Pediatr. 2012;161(5):787-91) used a whole-blood glucose oxidase method, and defined hypoglycaemia as a whole blood glucose < 2.6 mmol/L. The other studies that I referenced from the same group, such as the McKinlay study, used the same reliable method, and were measuring whole blood glucose.

The study by Lucas that I mentioned in part 1, in contrast, studied plasma glucose concentrations, so the preterm babies that he found to have increased long term risks, with multiple days of plasma glucose < 2.6 mmol/L, had the equivalent of multiple days of blood glucose < 2.26 mmol/L.

The study by Duvanel in contrast used bedside reagent strips for most measures, and only performed blood glucose measurements if the bedside test was <2.0 mmol/L.

This is more than a detail; a plasma glucose of 2.6 is equivalent to a blood glucose concentration, of about 2.26 mmol/L. So using one or the other will have a major impact on how many babies are treated and re-tested.

The recent Swedish guidelines for hypoglycaemia monitoring and intervention (Wackernagel D, et al. Swedish national guideline for prevention and treatment of neonatal hypoglycaemia in newborn infants with gestational age >/= 35 weeks. Acta Paediatr. 2020) Discuss exclusively plasma glucose concentrations, this is the algorithm they suggest, which prescribes glucose gel application at a plasma glucose of <2.6, which is about 2.26 mmol/L for blood glucose.

Although this is a small difference, between plasma and blood glucose, in the ranges we are discussing, it means that tens of thousands more babies will be treated if we use a threshold of 2.6 mmol/L of blood glucose (for example) compared to the number who need treating at a threshold of 2.6 mmol/L of plasma glucose.

The criteria used for determining who is at risk also needs to be reconsidered.

All SGA babies are not growth restricted, many of them are just constitutionally small, and probably not at increased risk compared to AGA babies who are not growth restricted. How to identify these babies is challenging, but probably a baby with symmetrical growth over the third trimester following the same percentile throughout, and with normal antenatal dopplers in a normotensive mother is at very low risk of being growth restricted.

By the same reasoning, some babies over the 10th %le are growth restricted, they started out growing on a higher percentile and fell because of placental dysfunction, and have lower glycogen stores than their peers, and are at increased risk of early transitional low glucose.

At the other end of the spectrum, LGA infants who are not infants of diabetic mothers, but just constitutionally large are probably not at increased risk either, and, if we have a completely normal glucose loading test during pregnancy, could they be taken out of the screened groups? One registry study, which uses discharge diagnoses, found that less than 2% of LGA infants of non-diabetic mothers had hypoglycemia (referred to as a blood glucose < 2.6 mmol/L). On the other hand mild glucose intolerance, while not satisfying definitions for gestational diabetes, might increase the risk for neonatal hypoglycemia (not defined in this study). Some other studies show less hypoglycemia among LGA infants who are not infants of diabetic mothers, but continue to show over 5% incidence of hypoglycaemia, however, they might include mothers with mild glucose intolerance, so it isn’t really clear what is the risk for LGA infants of mothers with completely normal glucose tolerance.

The UK guidelines have taken all this to heart and only recommend screening for babies who are <2 percentile for birth weight or are clinically wasted, or infants of diabetic mothers. They do discuss plasma and blood glucose, but seem to think that blood gas machines report “plasma glucose equivalents”, which ours don’t.

The guidelines from the experts in Auckland, in contrast, refer to hypoglycemia as being “a serum glucose <2.6mM” (serum and plasma glucose being very similar), but the rest of their guideline refers to blood glucose. They recommend screening all infants <10th centile or >95th centile, and infants of diabetic mothers and preterm babies.

If you are getting confused by now you are not alone! Just try comparing the US guidelines from the AAP to the US guidelines from the Pediatric Endocrine Society, which are endorsed by the AAP.

“Oh! for an RCT of fire!” (Apologies to Will Shakespeare)

About keithbarrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
This entry was posted in Neonatal Research and tagged , . Bookmark the permalink.

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