Oral glucose solution for the treatment of persistent asymptomatic neonatal hypoglycemia: a randomized, double-blind, placebo-controlled trial

Abstract To evaluate the efficacy of 50% dextrose solution (D50W) for treating persistent asymptomatic postnatal hypoglycemia in at-risk late preterm and term neonates and the effect on intravenous (IV) dextrose therapy. A multicenter, randomized, double-blind, placebo-controlled trial conducted at two high-risk nurseries in Bangkok, Thailand. At-risk neonates ≥ 34 weeks’ gestation with persistent asymptomatic hypoglycemia, defined as a blood glucose level that remained below the postnatal, age-dependent protocol threshold 30 min after the first feeding, were randomized to receive either buccal D50W (200 mg/kg, 0.4 mL/kg; OG group) or placebo, followed by enteral feeding. The primary outcome was the proportion of infants requiring IV dextrose. Secondary outcomes included changes in blood glucose (BG) levels and hyperglycemia. Four-hundred infants were enrolled (OG: n = 205; placebo: n = 195). Median birthweight was comparable between groups. Pre-treatment BG levels were similar (OG 37.0 [33.0, 39.0] mg/dL vs. placebo 37.0 [33.0, 39.0] mg/dL; p = 0.47). The proportion requiring IV dextrose was lower in the OG group but did not differ significantly (4.9% vs. 8.7%; p = 0.18). Median BG increment post-treatment was significantly greater in the OG group than in the placebo group (28.0 [18.0,40.0] vs. 22.5 [14.0, 35.0] mg/dL; p < 0.01). Hyperglycemia did not occur in either group. Linear mixed-effects analysis demonstrated that D50W significantly increased BG concentrations, whereas increasing postnatal age and small- or large-for-gestational-age status were associated with smaller BG responses. Conclusions : Buccal D50W administration did not significantly reduce the need for IV dextrose therapy in asymptomatic neonates with hypoglycemia, although it resulted in a greater increase in BG levels than placebo. Further studies are needed to determine its clinical role in the management of neonatal hypoglycemia. What is Known:• Oral 40% dextrose gel is recommended for asymptomatic neonatal hypoglycemia but is unavailable in many under-resourced healthcare settings.• Intravenous dextrose is effective but may disrupt mother-infant contact and breastfeeding. What is New:• Buccal 50% dextrose increased blood glucose more than placebo but did not reduce IV dextrose use.• No episodes of hyperglycemia, choking, vomiting, or mucosal irritation were observed in either group during routine clinical monitoring. Trial registration : Thai Clinical Trials Registry (TCTR), TCTR20181204005, registered on December 4, 2018. https://www.thaiclinicaltrials.org/show/TCTR20181204005