Lavoie PM, et al. Oral glucose during targeted neonatal echocardiography: is it useful? Archives of Disease in Childhood – Fetal and Neonatal Edition. 2015.

Echocardiography can sometimes disturb unstable babies. In this randomized controlled trial the investigators wanted to see if glucose helps to keep the babies stable and pain free during an echocardiogram. Specifically a functional echocardiogram performed by neonatal caregivers (not cardiologists or cardiology techs necessarily) in sick newborn infants.

I really don’t understand why this is reported only as a letter, and not a full report of an RCT. It certainly appears to be a better quality trial than many full publications that get published. Because it is a letter there is no CONSORT figure, and many CONSORT details are not in the manuscript.  This was a factorial study, randomizing 2 interventions: both glucose and wrapping the babies up (facilitated tucking). Neither intervention was effective, compared to just being careful, and gentle, using a soother, and warming the ultrasound gel.

I didn’t think, before the study, that echocardiography was painful, this study tends to confirm it, and shows that you can perform a study with very little disturbance of the baby.

The only problem I have with the study (apart from not having all the details because they didn’t publish it as a proper manuscript, such as a good description of the participants, a good description of the randomization methodology and so on) is a sentence in their discussion of the results, where they say the following: “concerns have been expressed that repeated use of oral sweeteners in itself may have long term neurodevelopmental effects particularly in preterm infants”. They give an incorrect reference to this, to a publication on a completely different issue, which was that although oral sucrose decrease PIPP scores after a heel lance, there was not an obvious effect on “pain-specific” EEG responses.

I think what the author of this letter are really referring to is this study, one of Celeste Johnston’s studies of sucrose use in the preterm infant. I’m guessing it must be this study as it is the only one,as far as I am aware, that has raised any questions at all about adverse consequences of sucrose use.

In the manuscript reporting the Johnston study, there was a secondary analysis of the data, which was inappropriately reported and has since been blown out of all proportion. In that study, 107 preterm babies were randomized to get sucrose every time they had a painful procedure during the 1^st week of life, they were compared to babies who got water (placebo). The “long term neurodevelopmental outcome” was no such thing, it was a NAPI (neurobehavioural assessment of the preterm infant) performed at discharge, or, to be more accurate, the investigators picked out 2 items of the 7 items in the NAPI, and examined babies at 32, 36, and 40 weeks post-menstrual age, they got to just over half of the babies at 40 weeks (67 of the 107 in the study).

That study showed no difference at discharge between the groups. I repeat no difference, that is, there were no “adverse” effects of sucrose on the MDV score of the NAPI. A secondary analysis, looking at the number of sucrose doses, was only performed in the sucrose group, and showed a significant correlation between results on the MDV (motor development and vigour) item of the NAPI (but not the other one that they tested, the AO, alertness and orientation) and more doses of sucrose. The authors unfortunately did not examine the effects of numbers of doses of placebo, which they clearly should have done. More sucrose means more painful procedures, which could certainly have been the potential link between the changes in NAPI scores and the sucrose doses; testing the same effect in the placebo group would have been appropriate.

What the authors did examine in the placebo group was the number of painful procedures, and they found a very strong correlation between numbers of painful procedures and the nursery neurobiologic risk score (NNBRS) a score invented by Jane Brazy several years go which has a reasonably good correlation with longer term outcomes. In the sucrose group, the babies who received more doses of sucrose had a worse NNBRS, which confirms what I was saying about the probable reason for the association on secondary analysis between sucrose doses and the subscale of the NAPI at discharge. Sucrose doesn’t affect any of the items in the NNBRS, so there is no reason whatsoever to think that the association is causative, sicker babies had more sucrose, had a higher NNBRS and a slightly different score on one item of the NAPI.

I am taking this long excursion into the results of an older study because it has been quoted many times as perhaps showing an adverse effect of sucrose on what is often referred to as “neurodevelopmental outcome”. So lets be completely clear, on secondary analysis of a small RCT, data from 2/3 of the preterm babies enrolled showed a statistically significant correlation between the number of sucrose doses given and one item of the 7 items of the NAPI at 40 weeks PMA.

This mildly interesting result, perhaps being hypothesis generating, and perhaps being worthy of a better evaluation, has been seized on as an indication of potential adverse consequences of sucrose.

It is no such thing.

There has never been any data to show an adverse neurodevelopmental effect of sucrose, all of the data available shows that it is safe.

So, it appears, is functional echocardiography.