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

UNLABELLED: 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.