Prophylactic Dextrose Gel for Neonatal Hypoglycemia and Neurocognitive Function at 6 to 7 Years of Age

Importance: Effective, safe, and infant-friendly interventions are needed to prevent transitional neonatal hypoglycemia, neonatal unit admissions, and neurological sequelae. Objective: To determine if prophylactic buccal dextrose gel at 1 hour of age in at-risk late preterm and term infants improves neurocognitive function at 6 to 7 years of age, without adverse effects on general health and well-being. Design, Setting, and Participants: This study focused on school-age follow-up of children in the Hypoglycaemia Prevention With Oral Dextrose (hPOD) multicenter, double-blind, 2-arm, parallel, placebo-controlled trial. Participants were recruited at birth across 9 hospitals in New Zealand. Follow-up was conducted primarily at the children's schools. Children in the hPOD Trial were born at 35 weeks' or more gestation and weighed 2.2 kg or more with 1 or more risk factors for transitional neonatal hypoglycemia: preterm, maternal diabetes, small or large for gestational age, or birth weight less than 2.5 kg or more than 4.5 kg. The assessments for this study (data collection) were performed from April 2021 to July 2025. The primary database extraction was on July 24, 2025. Data analysis was completed in October 2025. Interventions: A 0.2-g/kg dose of buccal or placebo (hydroxymethylcellulose, 2%) at 1 hour of age. Main Outcome and Measures: The primary outcome for this follow-up study was neurocognitive impairment at 6 to 7 years of age, defined as a standard score more than 1 SD below the normative mean on 1 or more of 7 items from the National Institutes of Health Toolbox. Eleven main exploratory outcomes included components of the primary outcome, low numeracy, visual perception, emotional-behavioral difficulty (Strengths and Difficulties Questionnaire), low physical or psychosocial functioning (Child Health Questionnaire), and overweight/obesity. Results: There were 532 of 652 (252 female and 280 male [82%]) eligible children assessed in the dextrose gel group and 535 of 642 (271 female and 264 male [83%]) in the placebo group. The proportion with neurocognitive impairment was similar between groups (dextrose gel, 59%, vs placebo, 57%; adjusted risk difference [aRD], 3%; 95% CI, -3% to 9%; P = .36). Of exploratory outcomes, children who received dextrose gel, compared with placebo, were more likely to have emotional-behavioral difficulty (24% vs 18%; aRD, 7%; 95% CI, 1%-12%) and low psychosocial function (17% vs 12%; aRD, 6%; 95% CI, 1%-10%). Other outcomes were similar between groups. Conclusions and Relevance: In this follow-up study, a single dose of dextrose gel to prevent hypoglycemia, compared with placebo, had little to no effect on the risk of neurocognitive impairment at early school age, but could have adverse effects on psychological well-being. The current evidence does not support the routine use of dextrose gel for the prevention of neonatal transitional hypoglycemia. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12614001263684.