hPOD

The aim of hPOD (hypoglycaemia Prevention with Oral Dextrose) is to determine whether oral dextrose gel, given to babies at risk of hypoglycaemia shortly after birth, will prevent neonatal hypoglycaemia and, therefore, admission to the newborn intensive care unit or special care baby unit (NICU/SCBU). The aim of the follow-up study is to determine if the gel is safe in the long term, and whether it helps protect babies’ brains.

Hypoglycaemia (low blood sugar) is the commonest metabolic disorder of the newborn, and the only known common preventable cause of brain damage in newborn babies. Up to 15% of newborn babies will have low blood glucose concentrations, and the rate is around 50% in babies who have additional risk factors: those born small, large, preterm, or to a mother with diabetes. Neonatal hypoglycaemia can cause brain damage and death, and its treatment commonly requires admission to the newborn intensive care unit or special care baby unit (NICU/SCBU), separating mothers and babies and interfering with the establishment of breast-feeding, thus incurring high social and financial cost.

A previous study (the Sugar Babies Study) demonstrated that treatment of neonatal hypoglycaemia with oral dextrose gel was more effective than feeding alone in reversing hypoglycaemia, and reduced both the rate of NICU admission for hypoglycaemia and the rate of formula feeding at two weeks of age.

Importantly, the gel is cheap, well tolerated, simple and safe to administer, and was acceptable to families and caregivers. hPOD and the follow-up study are determining whether oral dextrose gel is effective in preventing hypoglycaemia and admission to NICU/SCBU, and so preventing many of the adverse effects associated with this common problem.

1. Dosage Trial (pre-hPOD)
   The first stage of this research was a trial to determine the dose of dextrose gel that should be used for the hPOD trial. This was a randomised, placebo-controlled trial, comparing two doses (0.5 ml/kg or 1.0 ml/kg) of 40% dextrose gel with an identical appearing placebo gel, given either once only or an additional three times before feeds in the first 12 hours. The most effective, acceptable and safe dose of dextrose gel that prevents neonatal hypoglycaemia was found to be a single dose of 40% dextrose gel at 0.5ml/kg. Completed: November 2014
   
   
2. Multicentre Trial (hPOD)
   This is a multicentre, randomised, placebo controlled trial to determine if dextrose gel is more effective than an identically appearing placebo to prevent admission to a newborn intensive care unit or special care baby unit (NICU/SCBU). The study gel was given once at one hour of age, followed by a breastfeed. Completed: May 2019
   
   
3. Follow-up at Two Years
   Children recruited to the pre-hPOD and hPOD studies in New Zealand are assessed at two years of age using play-based tasks to determine if dextrose gel had any effect on children’s growth, development, behaviour and health. Completed:  July 2021
   
   
4. Follow-up at Six Years
   Children recruited to the pre-hPOD and hPOD studies in New Zealand are being assessed at six years of age to determine if dextrose gel had any effect on children’s growth, development, early learning and health. This assessment programme is called NIEOS. In progress.

The pre-hPOD Dosage Trial showed that giving any dose of dextrose gel to babies at risk helped reduce the risk of them developing hypoglycaemia. There were no adverse effects, and families and carers found the gel acceptable. The most effective dose of gel (0.5ml/kg at 1 hour of age) was chosen for use in the hPOD Trial.

The hPOD Trial showed that babies who received the dextrose gel were less likely to develop hypoglycaemia. However, this did not reduce the chances of them needing to go to a neonatal unit. This may be because babies who are at risk of hypoglycaemia are also at risk of having other problems that need extra care. There were no side effects of the dextrose gel, and the gel did not affect breastfeeding.

Follow-up at Two Years of the smaller group of children who took part in pre-hPOD showed that there were no differences in development, behaviour, growth or health between the children who received dextrose gel and those who received placebo gel. Children who received the dextrose gel had slightly fewer difficulties with executive function (skills for memory, attention, problem solving and planning), but this difference was not big enough to be considered significant in children of this age. 

In the larger group of children who took part in the hPOD trial, there were also no differences in development, behaviour, growth or health between children who received dextrose gel and those who received placebo gel. However, children who received dextrose gel had slightly lower scores on thinking (cognitive) and movement (motor) tests. The reasons why these findings are different from those of the pre-hPOD cohort are not clear. We are therefore assessing these children again at school age (the NIEOS study) to see if any differences persist.

The problem we are addressing is common and becoming ever more so: the rate of maternal diabetes in New Zealand, for example, has quadrupled from 2% in 1991 to 8% in 2010, and is most common in Māori and Pasifika mothers. This novel study is the first to investigate whether neonatal hypoglycaemia can be prevented by a simple, cheap and painless intervention.

A summary of the findings so far published as an authoritative Cochrane Review concludes that giving preventative oral dextrose gel reduces the risk of hypoglycaemia and need for treatment, and has little effect on later development. However, further follow-up beyond two years of age is important.

Distinguished Professor Jane Harding  
Dr Jane Alsweiler
Professor Caroline Crowther      
Dr Richard Edlin
Greg Gamble   
Dr Jo Hegarty
Dr Chris McKinlay

• Pre-hPOD (Hegarty JE, Harding JE, Gamble GD, Crowther CA, Edlin R, Alsweiler JM. Prophylactic oral dextrose gel for newborn babies at risk of neonatal hypoglycaemia: A randomised controlled dose-finding trial (the pre-hPOD study). PLOS Medicine 13 (10): e1002155, 2016. doi:10.1371/journal.pmed.1002155)
• hPOD  (Harding JE, Hegarty JE, Crowther CA, Edlin RP, Gamble GD, Alsweiler JM.  Neonatal hypoglycemia prevention with oral dextrose gel (hPOD): A multicentre double blind randomized controlled trial.  PLoS Medicine 18: e1003411, 2021.  https://doi.org/10.1371/journal.pmed.1003411)
• Pre-hPOD follow-up at two years (Griffith R, Hegarty JE, Alsweiler JM, Gamble GD, May R, McKinlay CJD, Thompson B, Wouldes TA, Harding JE for the hPOD Study Group. Two-year outcomes after dextrose gel prophylaxis for neonatal hypoglycaemia.  Archives of Disease in Childhood Fetal and Neonatal Edition 206: F278-285, 2021.  doi:10.1136/archdischild-2020-320305.)
• hPOD follow-up at two years (Edwards T, Alsweiler JM, Crowther CA, Edlin R, Gamble GD, Hegarty JE, Lin L, McKinlay CJD, Rogers JA, Thompson B, Wouldes TA, Harding JE. Prophylactic oral dextrose gel and neurosensory impairment at 2-year follow-up of participants in the hPOD randomized trial. JAMA 327: 1149-57, 2022. doi:10.1001/jama.2022.2363)
• Cochrane Review (Roberts L, Lin, L, Alsweiler J, Edwards T, Liu G, Harding JE.Oral dextrose gel to prevent hypoglycaemia in at-risk neonates. Cochrane Database of Systematic Reviews 11:CD012152, 2023. doi: 10.1002/14651858.CD012152.pub4).

Trial-related enquiries may be emailed to the Principal Investigator, Distinguished Professor Jane Harding, email j.harding@auckland.ac.nz