Is oral dextrose gel effective and safe in preventing low blood glucose levels and reducing long-term disability in newborn babies at risk of low blood glucose levels?
Low blood sugar (glucose) levels are important because they are common and are associated with brain injury in newborn babies. Up to 15 of every 100 babies will have low blood glucose levels over the first few days after they are born, and as many as half of babies who are at higher risk (those born preterm, or smaller or larger than usual, or whose mothers have diabetes).
Low blood glucose levels can cause problems with academic achievement and development during childhood. Some evidence suggests that even one episode of low blood glucose or episodes that are undetected can contribute to these problems. Therefore, it would be useful to prevent low glucose levels from occurring. Additionally, treatments for low glucose levels often include formula milk or admission to the neonatal unit, leading to the separation of mother and baby. The treatments and the separation may both impair breastfeeding.
Dextrose (sugar) gel can be rubbed on the inside of a baby's mouth, where the sugar can be absorbed and help raise blood glucose levels, thus potentially helping prevent low glucose levels.
We identified two studies in high-income countries that compared oral dextrose gel with placebo (inactive) gel for preventing low blood glucose levels in 2548 at-risk infants. The evidence in this Cochrane Review is current to October 2020.
Two studies showed that preventative oral dextrose gel reduces the risk of low blood glucose levels in newborn infants at risk. A single study reporting two-year outcomes in 360 infants found that oral dextrose gel given to at-risk infants to prevent low blood glucose levels probably reduces the risk of major disability at two years of age, but additional follow-up studies are needed.
Two studies showed that oral dextrose gel probably reduces the chance of receiving any treatment for low blood glucose during initial hospital stay but makes little or no difference to the chance of receiving intravenous treatment for low glucose, or separation from the mother for treatment of low glucose levels.
Evidence from two studies suggests that infants given oral dextrose gel are not at a higher risk of adverse events (harms) such as choking or vomiting compared with infants given placebo gel, but there was no information to assess whether oral dextrose gel is safer than no treatment or other therapies. No data were available on exclusive breastfeeding after discharge.
We assessed the risk of bias in the included studies as low, meaning it is unlikely that there is a systematic error in estimating the effect of the intervention.
Future research should be undertaken in low- and middle-income countries, preterm infants, using other dextrose gel preparations and comparators other than placebo gel. There are three studies awaiting classification and one ongoing study which may alter the conclusions of the review when they are published.
Certainty of evidence
We graded the certainty of the evidence as moderate for all outcomes except risk of low blood glucose levels (assessed as high certainty) and separation from mother (assessed as low certainty).
Oral dextrose gel reduces the risk of neonatal hypoglycaemia in at-risk infants and probably reduces the risk of major neurological disability at two years of age or greater without increasing the risk of adverse events compared to placebo gel. Additional large follow-up studies at two years of age or older are required. Future research should also be undertaken in low- and middle-income countries, preterm infants, using other dextrose gel preparations, and using comparators other than placebo gel. There are three studies awaiting classification and one ongoing study which may alter the conclusions of the review when published.
Neonatal hypoglycaemia is a common condition that can be associated with brain injury. Current practice usually includes early identification of at-risk infants (e.g. infants of diabetic mothers; preterm, small- or large-for-gestational-age infants), and prophylactic measures are advised. However, these measures usually involve use of formula milk or admission to the neonatal unit. Dextrose gel is non-invasive, inexpensive and effective for treatment of neonatal hypoglycaemia. Prophylactic dextrose gel can reduce the incidence of neonatal hypoglycaemia, thus potentially reducing separation of mother and baby and supporting breastfeeding, as well as preventing brain injury.
This is an update of a previous Cochrane Review published in 2017.
To assess the effectiveness and safety of oral dextrose gel given to newborn infants at risk of hypoglycaemia in preventing hypoglycaemia and reducing long-term neurodevelopmental impairment.
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 10) in the Cochrane Library; and Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R) on 19 October 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
We included randomised controlled trials (RCTs) and quasi-RCTs comparing oral dextrose gel versus placebo, no intervention, or other therapies for the prevention of neonatal hypoglycaemia.
Two review authors independently extracted data and assessed risk of bias. We contacted investigators to obtain additional information. We used fixed-effect meta-analyses. We used the GRADE approach to assess the certainty of evidence.
We included two studies conducted in high-income countries comparing oral dextrose gel versus placebo in 2548 infants at risk of neonatal hypoglycaemia. Of these, one study was included in the previous version of this review. We judged these two studies to be at low risk of bias, and that the evidence for most outcomes was of moderate certainty.
Meta-analysis of the two studies showed that oral dextrose gel reduces the risk of hypoglycaemia (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.79 to 0.95; risk difference (RD) -0.06, 95% CI -0.10 to -0.02; 2548 infants; high certainty evidence). One study reported that oral dextrose gel probably reduces the risk of major neurological disability at two years' corrected age (RR 0.21, 95% CI 0.05 to 0.78; RD -0.05, 95% CI -0.09 to 0.00; 360 infants; moderate certainty evidence).
Meta-analysis of the two studies showed that oral dextrose gel probably reduces the risk of receipt of treatment for hypoglycaemia during initial hospital stay (RR 0.89, 95% CI 0.79 to 1.00; 2548 infants; moderate certainty evidence) but makes little or no difference to the risk of receipt of intravenous treatment for hypoglycaemia (RR 1.01, 0.68 to 1.49; 2548 infants; moderate certainty evidence). Oral dextrose gel may have little or no effect on the risk of separation from the mother for treatment of hypoglycaemia (RR 1.12, 95% CI 0.81 to 1.55; two studies, 2548 infants; low certainty evidence).
There is probably little or no difference in the risk of adverse events in infants who receive oral dextrose gel compared to placebo gel (RR 1.22, 95% CI 0.64 to 2.33; two studies, 2510 infants; moderate certainty evidence), but there are no studies comparing oral dextrose with other comparators such as no treatment, standard care or other therapies.
No data were available on exclusive breastfeeding after discharge.