Neonatal hypoglycaemia is far from a rare curiosity. Up to 15% of otherwise healthy newborns experience blood glucose levels low enough to be flagged in the first hours of life, and among infants with risk factors such as prematurity, being small or large for gestational age, or maternal diabetes, the incidence can climb to roughly half. The transition from the constant glucose supply of the placenta to independent metabolic regulation is inherently precarious, and many healthy babies dip transiently while adapting to life outside the womb. The concern is what happens when the dip is prolonged or severe: prior research has linked severe neonatal hypoglycaemia to abnormal fine motor function, deficits in visual-motor integration and symptoms consistent with attention-deficit/hyperactivity disorder later in childhood. That long shadow is what drives clinicians to monitor, feed and, when necessary, treat aggressively.

Conventional management relies on early identification of at-risk infants, prompt feeding, frequent glucose checks and, for symptomatic or severe cases, intravenous dextrose. The problem is that IV dextrose is invasive, demands NICU admission, separates mother and baby, interrupts breastfeeding and generates anxiety and cost. Oral 40% dextrose gel promised a way around all of that. It is cheap, stable, easy to administer through the buccal mucosa and works within minutes without displacing a feed. The landmark Sugar Babies trial in New Zealand, published in 2013, appeared to prove the concept: at-risk late preterm and term infants treated with dextrose gel were less likely to fail treatment and less likely to be admitted to the NICU for hypoglycaemia. The much larger hPOD multicentre trial later confirmed a modest reduction in hypoglycaemia incidence but found no reduction in NICU admission, planting the first seeds of doubt.

Since then, the picture has grown murkier rather than clearer. Some recent trials reported no significant difference between dextrose gel and control in treatment success, while others suggested the gel helps maintain blood glucose in specific subgroups such as infants of diabetic mothers or late preterm babies. A previous meta-analysis had concluded that the gel significantly lowered NICU admissions, but it included fewer studies and roughly 1,000 fewer participants than the new synthesis. Motivated by that expanding but inconsistent evidence base, an international team of researchers registered a protocol with PROSPERO and set out to pool every available randomized trial of 40% dextrose gel for both prevention and treatment of neonatal hypoglycaemia, following the PRISMA 2020 reporting standards.

The search strategy was exhaustive. The team combed PubMed, Embase, Web of Science, Scopus and the Cochrane Library from inception to March 2026, retrieving 1,332 records. After deduplication, 1,285 studies were screened by title and abstract, 58 went to full-text review, and eight randomized controlled trials ultimately met the eligibility criteria. Together they enrolled 4,368 neonates, 2,256 assigned to 40% dextrose gel and 2,112 to control. The trials spanned New Zealand, Australia, India, Argentina, Italy, Ireland and the Czech Republic, and they varied enormously in design: some gave the gel prophylactically in the delivery room or at one hour of life, others used it to treat established asymptomatic hypoglycaemia; comparators ranged from placebo gel to breastfeeding alone to formula milk; and hypoglycaemia thresholds ranged from below 1.8 mmol/L to below 2.6 mmol/L or below 45 mg/dL.

The pooled results were uniformly null. Across five prevention trials involving 3,618 infants, dextrose gel did not significantly reduce the incidence of hypoglycaemia, with a pooled risk ratio of 0.92 and a 95% confidence interval of 0.76 to 1.11, accompanied by moderate heterogeneity. In three treatment trials covering 750 infants, treatment success, defined as avoiding IV dextrose, showed no significant difference, with a risk ratio of 1.10 and striking heterogeneity of 95%. Recurrent hypoglycaemia, NICU admission, breastfeeding at discharge and any formula feeding all likewise showed no statistically significant differences. The NICU result deserves particular attention: the pooled risk ratio was 0.87, but when the massive hPOD trial was excluded in sensitivity analysis, heterogeneity collapsed and the estimate became a statistically significant 24% reduction in admissions, hinting that protocol differences, such as a single prophylactic dose versus multiple doses, may determine whether the gel delivers on its promise.

The authors are careful to stress what these numbers do and do not mean. Non-significant findings, they emphasize, are not evidence of equivalence. The confidence intervals for several outcomes, particularly treatment success and NICU admission, are wide enough to encompass both clinically meaningful benefit and potential harm. For treatment success, the interval spans a possible 23% reduction to a 57% increase. Certainty of evidence, graded using the GRADE framework, ranged from moderate for breastfeeding at discharge down to very low for treatment success, reflecting serious risk of bias in one trial, substantial inconsistency and imprecision across outcomes. Publication bias assessments using Doi plots and trim-and-fill adjustments did not materially change the conclusions, but with fewer than ten studies per outcome, those methods have limited power.

Why might the gel underperform expectations? The review offers several technical explanations. Doses varied from a single 200 mg/kg dose to multi-dose regimens totalling up to 1,000 mg/kg, and timing ranged from the delivery room to two hours after birth, yet no clear dose-response or timing effect emerged. Comparators mattered too: in the Argentine trial, formula-fed controls actually achieved higher treatment success than gel-treated babies, since formula feeding is itself an effective hypoglycaemia remedy. Definitions of hypoglycaemia differed across trials, and measurement methods varied from laboratory glucose oxidase assays to bedside glucometers, introducing misclassification that biases estimates toward the null. Subgroup signals persisted, however: infants of diabetic mothers in one Indian trial showed a marked benefit, and late preterm infants in an Italian study had higher glucose levels with gel, while extremely preterm infants under 32 weeks in the GEHPPI trial showed none, with identical hypoglycaemia rates of 29% in both arms.

On the reassuring side, the gel appears harmless to breastfeeding. Despite concerns that any neonatal supplementation can delay breastfeeding initiation and shorten duration, the pooled analysis found no difference in breastfeeding at discharge or formula use, with zero heterogeneity across trials. No adverse events were reported in any of the included studies, though the authors caution that long-term neurodevelopmental safety remains untested. Clinically, the team suggests the gel’s low cost, safety profile and ease of administration still justify a role as an adjunctive therapy, particularly in resource-limited settings or while awaiting IV access, but not as a replacement for intravenous dextrose when clearly indicated, and always within standardized protocols covering dosing, monitoring and escalation.

The research agenda that follows is demanding. The authors call for dose-finding trials comparing multi-dose regimens with single-dose prophylaxis, population-specific trials stratified by the underlying mechanism of hypoglycaemia, continuous glucose monitoring to replace intermittent heel-prick checks, and long-term neurodevelopmental follow-up. Until such trials arrive, the humble sugar gel remains what it has arguably always been: a plausible, cheap and safe tool whose true value, for whom, at what dose and at what hour of life, medicine has not yet pinned down.

Subject of Research: The efficacy of 40% oral dextrose gel for preventing and treating neonatal hypoglycaemia, assessed in an updated systematic review and meta-analysis of randomized controlled trials.

Article Title: Efficacy of Oral Dextrose Gel for Neonatal Hypoglycaemia: An Updated Systematic Review and Meta‐Analysis of Randomized Controlled Trials With 4368 Patients

Article References: Al‐Enezi, R. T., Alshebeeb, F. A., Panikulam, J. R., AlKhaldi, D. B., Almutairi, R. B., Alenezi, R. T., Aljassar, A. M., Aldosari, R. B., Alkandari, F. A., Dashti, A. A., Aldhahi, K. A., Abdul‐Hafez, H. A., & Alharran, A. M. (2026). Efficacy of Oral Dextrose Gel for Neonatal Hypoglycaemia: An Updated Systematic Review and Meta‐Analysis of Randomized Controlled Trials With 4368 Patients. Endocrinology, Diabetes & Metabolism, 9(5), Article e70327. https://doi.org/10.1002/edm2.70327

Image Credits: AI Generated

DOI: 10.1002/edm2.70327

Keywords: neonatal hypoglycaemia, oral dextrose gel, systematic review, meta-analysis, randomized controlled trials, NICU admission, newborn health, breastfeeding, intravenous dextrose, GRADE evidence, neonatal intensive care, glucose monitoring