OBJECTIVE: Early hypoglycaemia at the time of neonatal intensive care unit (NICU) admission is common in very/extreme preterm infants. This study aimed to determine whether buccal dextrose gel in the delivery room (DR) would improve rates of early hypoglycaemia in this population. DESIGN: Randomised, blinded, placebo-controlled trial. SETTING: Four level-3 and one level-2 neonatal units. PATIENTS: Inborn infants≤32+0 weeks gestational age (GA). INTERVENTIONS: Infants were randomised to 40% dextrose or placebo gel in the DR (≤29+0 GA: 0.5 mL gel, ≥29+1 GA: 1 mL gel). MAIN OUTCOME MEASURE: Hypoglycaemia (<1.8 mmol/L) measured at the time of first intravenous access at NICU admission. RESULTS: Between November 2020 and August 2022, the recruitment rate was slow (impacted by the requirement for antenatal consent). This fact, coupled with finite research resources, led to a decision to end recruitment early. Data analysis of 169 newborns (33% of target sample size) showed no significant difference in the frequency of the primary outcome between dextrose 24/84 (29%) and placebo 25/85 (29%) groups (OR 0.95; 95% CI 0.49 to 1.86; p=0.88). A post-hoc analysis indicated that the trial had a low (47% conditional power) chance of detecting a statistically significant benefit from the intervention (had the target sample been achieved). CONCLUSIONS: This study showed no evidence of benefit of 40% dextrose gel on rates of hypoglycaemia at NICU admission. Management of these vulnerable newborns should continue to focus on vascular access and commencement of dextrose-containing intravenous fluids as early as possible. TRIAL REGISTRATION NUMBER: NCT04353713.

Department of Neonatology University Hospital Galway Galway Ireland

Neonatology Department Motol University Hospital Prague Czech Republic

Neonatology Department Rotunda Hospital Dublin Ireland

Neonatology Department The National Maternity Hospital Dublin Ireland

Paediatrics and Newborn Medicine The Coombe Hospital Dublin Ireland

Pharmacy Department The Coombe Hospital Dublin Ireland

See more in PubMed

Burns CM, Rutherford MA, Boardman JP, et al. Patterns of cerebral injury and neurodevelopmental outcomes after symptomatic neonatal hypoglycemia. Pediatrics. 2008;122:65–74. doi: 10.1542/peds.2007-2822. PubMed DOI

Filan PM, Inder TE, Cameron FJ, et al. Neonatal hypoglycemia and occipital cerebral injury. J Pediatr. 2006;148:552–5. doi: 10.1016/j.jpeds.2005.11.015. PubMed DOI

Edwards T, Alsweiler JM, Crowther CA, et al. Prophylactic Oral Dextrose Gel and Neurosensory Impairment at 2-Year Follow-up of Participants in the hPOD Randomized Trial. JAMA. 2022;327:1149–57. doi: 10.1001/jama.2022.2363. PubMed DOI PMC

Duvanel CB, Fawer CL, Cotting J, et al. Long-term effects of neonatal hypoglycemia on brain growth and psychomotor development in small-for-gestational-age preterm infants. J Pediatr. 1999;134:492–8. doi: 10.1016/s0022-3476(99)70209-x. PubMed DOI

Kerstjens JM, Bocca-Tjeertes IF, de Winter AF, et al. Neonatal morbidities and developmental delay in moderately preterm-born children. Pediatrics. 2012;130:e265–72. doi: 10.1542/peds.2012-0079. PubMed DOI

McKinlay CJD, Alsweiler JM, Ansell JM, et al. Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years. N Engl J Med. 2015;373:1507–18. doi: 10.1056/NEJMoa1504909. PubMed DOI PMC

Shah R, Dai DWT, Alsweiler JM, et al. Association of Neonatal Hypoglycemia With Academic Performance in Mid-Childhood. JAMA. 2022;327:1158–70. doi: 10.1001/jama.2022.0992. PubMed DOI PMC

Lucas A, Morley R, Cole TJ. Adverse neurodevelopmental outcome of moderate neonatal hypoglycaemia. BMJ. 1988;297:1304–8. doi: 10.1136/bmj.297.6659.1304. PubMed DOI PMC

Kaiser JR, Bai S, Gibson N, et al. Association Between Transient Newborn Hypoglycemia and Fourth-Grade Achievement Test Proficiency: A Population-Based Study. JAMA Pediatr. 2015;169:913–21. doi: 10.1001/jamapediatrics.2015.1631. PubMed DOI

Tin W, Brunskill G, Kelly T, et al. 15-year follow-up of recurrent “hypoglycemia” in preterm infants. Pediatrics. 2012;130:e1497–503. doi: 10.1542/peds.2012-0776. PubMed DOI

Tottman AC, Alsweiler JM, Bloomfield FH, et al. Relationship between Measures of Neonatal Glycemia, Neonatal Illness, and 2-Year Outcomes in Very Preterm Infants. J Pediatr. 2017;188:115–21. doi: 10.1016/j.jpeds.2017.05.052. PubMed DOI

Goode RH, Rettiganti M, Li J, et al. Developmental Outcomes of Preterm Infants With Neonatal Hypoglycemia. Pediatrics. 2016;138:e20161424. doi: 10.1542/peds.2016-1424. PubMed DOI PMC

Hay WW. Recent observations on the regulation of fetal metabolism by glucose. J Physiol. 2006;572:17–24. doi: 10.1113/jphysiol.2006.105072. PubMed DOI PMC

Mitanchez D. Glucose regulation in preterm newborn infants. Horm Res. 2007;68:265–71. doi: 10.1159/000104174. PubMed DOI

Sharma D. Golden 60 minutes of newborn’s life: Part 1: Preterm neonate. J Matern Fetal Neonatal Med. 2017;30:2716–27. doi: 10.1080/14767058.2016.1261398. PubMed DOI

Koolen MR, van Kempen AA, Maaskant JM, et al. Incidence and risk factors for early hypoglycemia in very preterm infants: The hyporisk study. Clin Nutr ESPEN. 2023;56:67–72. doi: 10.1016/j.clnesp.2023.05.001. PubMed DOI

Mitchell NA, Grimbly C, Rosolowsky ET, et al. Incidence and Risk Factors for Hypoglycemia During Fetal-to-Neonatal Transition in Premature Infants. Front Pediatr. 2020;8:34. doi: 10.3389/fped.2020.00034. PubMed DOI PMC

Lilien LD, Pildes RS, Srinivasan G, et al. Treatment of neonatal hypoglycemia with minibolus and intraveous glucose infusion. J Pediatr. 1980;97:295–8. doi: 10.1016/s0022-3476(80)80499-9. PubMed DOI

King G, Tabery K, Hall M, et al. Delivery room glucose to reduce the risk of admission hypoglycemia in preterm infants: a systematic literature review. J Matern Fetal Neonatal Med. 2023;36:2183466. doi: 10.1080/14767058.2023.2183466. PubMed DOI

Gregory K, Turner D, Benjamin CN, et al. Incorporating dextrose gel and feeding in the treatment of neonatal hypoglycaemia. Arch Dis Child Fetal Neonatal Ed. 2020;105:45–9. doi: 10.1136/archdischild-2018-316430. PubMed DOI

Gupta K, Amboiram P, Balakrishnan U, et al. Dextrose Gel for Neonates at Risk With Asymptomatic Hypoglycemia: A Randomized Clinical Trial. Pediatrics. 2022;149:e2021050733. doi: 10.1542/peds.2021-050733. PubMed DOI

Makker K, Alissa R, Dudek C, et al. Glucose Gel in Infants at Risk for Transitional Neonatal Hypoglycemia. Am J Perinatol. 2018;35:1050–6. doi: 10.1055/s-0038-1639338. PubMed DOI

Rawat M, Chandrasekharan P, Turkovich S, et al. Oral Dextrose Gel Reduces the Need for Intravenous Dextrose Therapy in Neonatal Hypoglycemia. Bio Hub. 2016;1:1–9.:448511. doi: 10.1159/000448511. PubMed DOI PMC

Harris DL, Weston PJ, Signal M, et al. Dextrose gel for neonatal hypoglycaemia (the Sugar Babies Study): a randomised, double-blind, placebo-controlled trial. The Lancet. 2013;382:2077–83. doi: 10.1016/S0140-6736(13)61645-1. PubMed DOI

Hegarty JE, Harding JE, Gamble GD, et al. Prophylactic Oral Dextrose Gel for Newborn Babies at Risk of Neonatal Hypoglycaemia: A Randomised Controlled Dose-Finding Trial (the Pre-hPOD Study) PLoS Med. 2016;13:e1002155. doi: 10.1371/journal.pmed.1002155. PubMed DOI PMC

Harding JE, Hegarty JE, Crowther CA, et al. Evaluation of oral dextrose gel for prevention of neonatal hypoglycemia (hPOD): A multicenter, double-blind randomized controlled trial. PLoS Med. 2021;18:e1003411. doi: 10.1371/journal.pmed.1003411. PubMed DOI PMC

Coors SM, Cousin JJ, Hagan JL, et al. Prophylactic Dextrose Gel Does Not Prevent Neonatal Hypoglycemia: A Quasi-Experimental Pilot Study. J Pediatr. 2018;198:156–61. doi: 10.1016/j.jpeds.2018.02.025. PubMed DOI

Edwards T, Liu G, Battin M, et al. Oral dextrose gel for the treatment of hypoglycaemia in newborn infants. Cochrane Database Syst Rev. 2022;3:CD011027. doi: 10.1002/14651858.CD011027.pub3. PubMed DOI PMC

Roberts L, Lin L, Alsweiler J, et al. Oral dextrose gel to prevent hypoglycaemia in at-risk neonates. Cochrane Database Syst Rev. 2023;11:CD012152. doi: 10.1002/14651858.CD012152.pub4. PubMed DOI PMC

Adamkin DH. Neonatal hypoglycemia. Semin Fetal Neonatal Med. 2017;22:36–41. doi: 10.1016/j.siny.2016.08.007. PubMed DOI

British Association of Perinatal Medicine Identification and management of neonatal hypoglycaemia in the full term infant (2017) 2017. [01-Jan-2024]. https://www.bapm.org/resources/40-identification-and-management-of-neonatal-hypoglycaemia-in-the-full-term-infant-2017 Available. Accessed. PubMed

Jamovi The jamovi project (2022) 2022

American Diabetes Association Standards of medical care in diabetes--2013. Diabetes Care. 2013;36 Suppl 1:S11–66. doi: 10.2337/dc13-S011. PubMed DOI PMC

Abraham MB, Karges B, Dovc K, et al. ISPAD Clinical Practice Consensus Guidelines 2022: Assessment and management of hypoglycemia in children and adolescents with diabetes. Pediatr Diabetes. 2022;23:1322–40. doi: 10.1111/pedi.13443. PubMed DOI PMC

Carr CP, MacMillan H, Reynolds PR. Routine buccal glucose reduces admission hypoglycaemia in premature newborns: A quality improvement project. Acta Paediatr. 2022;111:1709–11. doi: 10.1111/apa.16419. PubMed DOI

Beardsall K. Measurement of glucose levels in the newborn. Early Hum Dev. 2010;86:263–7. doi: 10.1016/j.earlhumdev.2010.05.005. PubMed DOI

Rich WD, Katheria AC. Waived Consent in Perinatal/Neonatal Research-When Is It Appropriate? Front Pediatr. 2019;7:493. doi: 10.3389/fped.2019.00493. PubMed DOI PMC

See more in PubMed

ClinicalTrials.gov
NCT04353713