This is a field that stagnated in darkness for a while, “But, soft! what light through yonder window breaks? It is the east, and science is the sun” (with apologies to Romeo).
Recent research has shown that
1. In healthy term babies, plasma glucose concentrations frequently fall to levels which cause symptoms in adults
2. Infants who are considered at risk of low glucose concentrations are only slightly more likely to fall to those levels than those who are not so identified.
3. Most term and preterm babies do not have any clinical or metabolic signs that these low concentrations are causing them a problem.
4. Many term and preterm babies do not produce ketones in response to hypoglycemia, whether or not they are hyperinsulinaemic.
4. Screening for short-lived, asymptomatic low glucose concentrations requires blood sampling in about 50% of term and late preterm babies. But, as mentioned, the remaining 50% are at almost the same risk.
5. Low plasma glucose concentrations will often respond to oral glucose gel administration without having recourse to intravenous therapy. But infants who receive treatment also have their breastfeeding impacted and may be separated from their mothers, even if IV therapy is avoided.
6. Waiting to determine if the plasma glucose falls to below 2.0 mM/L before treating, compared to treating immediately at a plasma glucose of 2.6 mM/L, dramatically reduces the number of babies treated, and does not have an adverse impact on developmental scores at 34 months. While having less impact on breastfeeding.
What do do with all this new information? It seems to me that we should :
1. Redefine who needs screening and when. The data summarized above suggests that we should either screen every newborn infant or none of them. I am not comfortable with either idea! If we never screen then very severe prolonged hypoglycaemia without symptoms will never be diagnosed. If we screen everyone then we inflict pain on an awful lot of babies, we will have to ensure reliable methods are rapidly available and protocols in place to minimize harm, and a great proportion of those who receive intervention will not have needed it. Even if we use a low threshold, confirmed as safe by HypoEXIT, of 2.0 mM/L for plasma glucose or 1.7 mM/L for blood glucose, that will include somewhere between 10% and 30% of term and late preterm infants. I am sure that 10 to 30% of newborn infants do not have significant adverse impacts of low blood glucose.
Should we only screen the most severely growth-restricted infants? Only those who are truly growth restricted rather than the normal small baby? Only those from diabetic pregnancies, or those with poorly controlled diabetes, or those from diabetic mothers who are obese?
2. Redefine who needs treating and when. Even if we use a threshold of plasma glucose of 2.0 mM/L then between 10% and 32% of babies will be treated. I am sure that the large majority of those babies do not gain any benefit from their treatment, and may indeed be harmed.
3. Redefine the purpose of screening. There is very little indication that having 1, 2, or 3 plasma glucose concentrations between 1.5 and 2.6 mM/L (for example) has an adverse impact on newborn infants. So, in order to decide on #1 and #2, I think we should focus screening efforts on the detection of babies who are at risk of prolonged or repeated severe hypoglycaemia. The purpose of screening should be to detect hypoglycaemia which increases the chances of adverse outcomes, what are the characteristics of such infants? Can we identify them by history, or examination, or a single blood test with a full metabolic profile performed at 6 hours of age (for example)?
In the meantime, the developing evidence suggests to me :
Screening asymptomatic infants in the first 48 hours of life is of questionable value, regardless of risk factors.
During the first 48 hours plasma glucose < 1.5 mM/L is very unusual.
After 72 hours of age a plasma glucose <2.0 mM/L is very unusual.
Perhaps the best way to address the issues would be to perform a trial of universal screening before the second feed, to only intervene or retest if <1.5 mM/L (blood sugar equivalent of 1.3 mM/L) and compare the outcomes to a randomized group screened and treated according to current practice (choose which one).