Oral dextrose gel for prevention of low blood glucose levels in newborn babies

Review question

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?

Key messages

- Current evidence is based on two studies in 2548 at-risk babies in high income countries with outcome assessments in newborns, at two years and six to seven years of age.

- Oral dextrose gel is safe and effective in reducing low blood glucose levels in newborn babies at risk of low blood glucose levels.

- It is uncertain whether oral dextrose gel increases or decreases disability at two years or older.

Why are low blood glucose levels important?

Low blood sugar (glucose) levels are important because they are common and are associated with brain injury in newborn babies. Up to 39 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.

How could dextrose gel prevent low blood glucose levels?

Oral dextrose (sugar) gel can be rubbed on the inside of a baby's mouth, where the sugar can be absorbed and thus potentially help prevent low glucose levels.

What did we want to find out?

We wanted to understand whether babies given oral dextrose gel after birth are less likely to:

- have low blood sugar levels

- have major disability at two years or older

We also wanted to know if oral dextrose gel had any unwanted effects such as vomiting or choking.

What did we do?

We searched for studies that investigated whether oral dextrose gel, compared to another treatment or no treatment, was safe and effective in preventing low blood sugar levels and major disability later in childhood. We also looked at additional clinically important outcomes.

What did we find?

We found two studies, both in high-income countries, including a total of 2548 at-risk infants. Both studies assessed the health outcomes of participating children at two years of age, and one also assessed them at six to seven years of age. From reviewing these studies, we are confident that preventative oral dextrose gel reduces the risk of low blood glucose levels in newborn infants at risk. However, we are uncertain whether oral dextrose gel alters the risk of major disability at two years or older, as one study in 360 children showed disability was possibly reduced, while the other study in 2149 children showed it was possibly increased.

Evidence from two studies suggests that infants given oral dextrose gel are not at a higher risk of adverse effects (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. Oral dextrose gel also probably reduces the need for treatment for low blood sugar levels. It may have little to no effect on separation from the mother for treatment of hypoglycaemia, but we have little confidence in this finding because of variation between the two studies. No data were available on exclusive breastfeeding after discharge.

What are the limitations of the evidence?

The two studies were conducted in high-income countries only, and the findings may not be applicable to other settings. The findings may also not be applicable to preterm infants or other preparations of dextrose gel. Where we were not confident in the evidence was generally because there were only two studies that did not allow us to be certain about the results. Also, there may have been too few events (e.g. adverse effects) to make a conclusion with certainty.

How up-to-date is this evidence?

This review updates our previous review, published in 2021. The evidence is up-to-date to April 2023.

Authors' conclusions: 

Prophylactic oral dextrose gel reduces the risk of neonatal hypoglycaemia in at-risk infants and probably reduces the risk of treatment for hypoglycaemia without adverse effects. It may make little to no difference to the risk of major neurological disability at two years, but the confidence intervals include the possibility of substantial benefit or harm. Evidence at six to seven years is limited to a single small study.

In view of its limited short-term benefits, prophylactic oral dextrose gel should not be incorporated into routine practice until additional information is available about the balance of risks and harms for later neurological disability. Additional large follow-up studies at two years of age or older are required. Future research should also be undertaken in other high-income countries, 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.

Read the full abstract...
Background: 

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 often 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 2021.

Objectives: 

To assess the effectiveness and safety of oral dextrose gel in preventing hypoglycaemia before first hospital discharge and reducing long-term neurodevelopmental impairment in newborn infants at risk of hypoglycaemia.

Search strategy: 

We searched CENTRAL, MEDLINE, Embase and Epistemonikos in April 2023. We also searched clinical trials databases and the reference lists of retrieved articles.

Selection criteria: 

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. We included newborn infants at risk of hypoglycaemia, including infants of mothers with diabetes (all types), high or low birthweight, and born preterm (< 37 weeks), age from birth to 24 hours, who had not yet been diagnosed with hypoglycaemia.

Data collection and analysis: 

Two review authors independently extracted data and assessed the 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.

Main results: 

We included two studies conducted in high-income countries comparing oral dextrose gel versus placebo in 2548 infants at risk of neonatal hypoglycaemia. Both of these studies were included in the previous version of this review, but new follow-up data were available for both. We judged these two studies to be at low risk of bias in 13/14 domains, 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). Evidence from two studies showed that there may be little to no difference in the risk of major neurological disability at two years of age after oral dextrose gel (RR 1.00, 95% CI 0.59 to 1.68; 1554 children; low-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 probably 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 effects 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 intervention or other therapies.

No data were available on exclusive breastfeeding after discharge.