The Sugar Babies trial was the subject of a post earlier this year as the largest trial to date examining the effects of using dextrose gel to treat hypoglycemia. For an analysis of the use of gel in this situation please see the original post Glucose Gel For Neonatal Hypoglycemia: Can We Afford Not To Use It?
In summary though, the trial involved 118 infants who received 40% dextrose gel vs 119 who received a placebo gel. All of the infants in this study were selected based on risk factors for hypoglycemia (IDM, IUGR, LBW, LGA, near term) and were all 35 weeks or greater. Each infant had to be less than 48 hours of age when enrolled. Infants received 0.5 mL/kg 40% dextrose gel (200 mg/kg). This was designed to deliver the same amount of sugar as would be given with a D10W bolus of 2 mL/kg. In order to receive the treatment the blood glucose had to be < 2.6 mmol/L so equivalent to our own standards in Canada and the US. Treatment failure, which was the primary outcome was defined as a blood glucose < 2.6 mmol/L despite two treatments with gel. The studies most important findings were a reduction in NICU admission and greater breastfeeding rates at 2 weeks of age (due to avoidance of formula feeding to keep the glucose stable).
But Is It Safe?
With any new strategy though, questions arise regarding safety of the product in the long term. As one reader commented after the original post, could the red dye be harmful in some way or perhaps some other constituent of the gel? The authors of the original study have now published the follow-up paper entitled Outcome at 2 Years after Dextrose Gel Treatment for Neonatal Hypoglycemia: Follow-Up of a Randomized Trial. The findings were a little concerning to me in that there was a high rate of neurosensory impairment in both arms (sham and glucose gel) with the following findings. None of the differences were significant however.
Looking at these results you could be dismayed that the glucose gel did not show any benefit compared to standard therapies for hypoglycemia but if you look at the original study one could equally ask why would we have expected it to?
Should The Results Surprise Us?
All of the newborns in either arm had an episode of hypoglycemia recorded in order to qualify for entry into the study. The glucose gel was effective compared to placebo in reducing admissions and increasing breastfeeding rates (which one might think would improve outcomes) but we don't know what the drop off rate in breastfeeding was after 2 weeks. What I can say though is that if there were significant adverse side effects with the glucose gel I would have expected to see some differences in outcome favouring the placebo group which did not occur.
An additional issue is we know that the placebo group had more treatment failures meaning they would have had more newborns in the original study with a second low glucose. Would this favour a worse outcome in the placebo group? If so does the equivalence in groups suggest that the dextrose gel might worsen outcomes?
Unfortunately, what this study is really missing is some indication of how low and how long the blood sugars remained under 2.6 mmol/L in both arms of the study. We know the mean low glucoses were similar but what about duration and range? While the rates of mild, moderate and severe impairment are the same we don't know how severe the hypoglycemia was which if unbalanced between the groups could actually lead to very different conclusions here. For example, let's say the glucose gel group had an over representation of infants with 3 or more episodes of hypoglycemia compared to the placebo arm. The fact that the outcomes are equivalent would suggest that the glucose gel is in fact protective.
What Can We Say?
I suspect that while glucose gel is effective, to truly assess harm across many different aspects of development we will need larger sample sizes. We also have to take the results of this study with a grain of salt as so many that have come before it have seen outcomes at school age reveal different findings than when assessed at 2 years of age as in this study. From my standpoint though I will continue to advocate for the use of glucose gel as the reduction in NICU admissions and enhancement of breastfeeding rates especially if sustained are well worth the efforts to implement this strategy if you aren't using it already.