Use of Oral 40% Destrogel to Prevent Hypoglycaemia in Late-term Births and SGA or LGA Term Newborns
Phase: NA
Conditions: Hypoglycaemia Neonatal
Sponsor: Fondazione Poliambulanza Istituto Ospedaliero

Title Form 
 
 
 
 
“Use of oral 40% destrogel to prevent hypoglycaemia in late-term births and SGA or 
LGA term newborns” 
 
 
Date: 3/12/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
1
Study Protocol 
 
 
 
Principal Investigator:  
 
Dr. Giuseppe De Bernardo 
  
Head of S.S. Neonatal Intensive Care  
Department of Mother and Child Health  
Poliambulanza Foundation of Brescia  
 
Co - principal investigators:  
 
Dr. Rosario Ippolito 
 
Physician in specialist training of the University of Pavia 
 
Dr. Maurizio Giordano  
 
Statistic  
Department of Clinical Medicine and Surgery  
University of Naples, Federico II  
 
 
 
 
 
 
 
 
 
 
 

 
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Title of the study 
USE OF ORAL 40% DESTROGEL TO PREVENT HYPOGLYCAEMIA IN LATE-TERM 
BIRTHS AND SGA OR LGA TERM NEWBORNS 
 
Rational study 
Neonatal hypoglycemia understood as a reduction in plasma glucose can result in 
long-term neurological damage. Hypoglycemia is one of the most frequent metabolic 
alterations of the newborn. About 30% of all newborns are at risk of hypoglycemia. 
The neonatal population at risk is mainly children of diabetic mothers, born 
prematurely, late preterm (34-36,6 weeks of gestational age), born at term (37-42 
weeks of gestational age) with low body weight for gestational age ( SGA, <10o 
percentile) or with high body weight for gestational age (LGA, >90o percentile) (1, 2, 
3). The 50% of these infants have hypoglycemia in the first 48 years. It is still 
controversial today to assign the threshold value below which it is possible to define a 
condition of neonatal hypoglycemia. In 2011, the American Academy of Pediatrics 
provided practical guidance for screening and subsequent management of neonatal 
hypoglycemia in infants at risk. The chosen threshold was 45 mg/dl but they also stated 
that few studies have shown that the asymptomatic hypoglycaemia condition 
protracted for a few hours is associated with long-term neurological damage. Studies 
showing the correlation between plasma blood sugar concentration and long-term 
neurological adverse events were also influenced by the variable definition of 
hypoglycemia, the duration of hypoglycemia, the lack of studies case-control and 
sample size. The other chosen threshold to diagnose hypoglycemia was 47 mg/dl, 
however without rigorous scientific evidence (4). Subsequently in 2015 and 2017, two 
scientific evidence showed that maintaining blood sugar values above 47 mg/dl in the 
first 48 hours of life in infants at risk of hypoglycemia and in follow-up, did not associate 
with an increase in incidence of neurosensory type of alteration, at the age of 2 and 
4.5 years of life respectively (2,5). Furthermore, these papers established the 
conditions of severe hypoglycemia for plasma glucose values <36 mg/dl and of 
recurrent hypoglycemia if at least three hypoglycemia episodes were recorded (<47 
mg/dl) (5). The pathophysiological mechanisms underlying neonatal hypoglycemia 
were: the reduced glycogen storage in the liver of the preterm newborn, the reduced 
availability of amino acids for gluconeogenesis and the inadequate lipid storage as a 
source of fatty acids that are more evident in preterm. Regarding the causes of 
persistent hypoglycemia, specified as a hypoglycemia that persists more than 48 hours 
of life, we must consider: the inappropriate insulin secretion, hypopituitarism, cortisol 
deficiency, growth hormone deficiency, congenital errors of glucose metabolism, 
glycogen and fatty acids. Neonatal hypoglycemia can be completely asymptomatic or 
can manifest with neurogenic/adrenergic signs and symptoms. These are 
characterized by sweating, pallor, cyanosis, temperature instability, irritability, 
starvation, tremors, tachycardia and emesis. Neuroglycopenic signs and symptoms 
are characterized by apnea, hypotonia, hypovalid suction, seizures, coma and exitus 
(1). 

 
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Serious monitoring of neonatal blood glucose is indicated in patients at risk of 
hypoglycemia. Glycaemic monitoring in the newborn at risk should be started not 
before of the two hours of life, in fact it is seen that at birth the neonatal blood glucose 
values are very low because they are conditioned by the metabolic activity of the foetus 
in the intrauterine phase, while later these values rise again until arrive at similar values 
 to the adult within 48-72 hours (1). Monitoring is performed by glucometer, capillary 
EGA or blood sampling performed in patients at risk of painful stress (6). In recent 
years, various research groups have been evaluating the possibility of arriving at non-
pharmacological prophylaxis of hypoglycemia. In particular, the Hegarty group has set 
up a protocol that uses dextrose gel at 40% in the risk categories that could reduce 
the number of hypoglycemia cases and consequently of painful procedures (7). Body 
temperature and the state of metabolic and/or respiratory acidosis are among the main 
factors that influence blood sugar levels in the first 48 hours of life (8,9). There are 
currently no strategies to prevent hypoglycemia. The treatment, in cases of 
asymptomatic hypoglycemia, is an early administration of milk in formula while in cases 
of symptomatic hypoglycemia infusion of 10% intravenous glucose is foreseen or early 
feeding by treatment with breast milk or in formula (10-14). However, the 
administration of milk formulated in the first hours of life causes a reduction in 
breastfeeding (10). In severe cases with glycaemia <36 mg/dl, it is practiced 
intravenous infusion of 10% glucose or dextrose (5). The 40% dextrose in gel 
administered orally can be a valid preventive measure in all newborns at risk of 
hypoglycemia, sons of a diabetic mother, SGA and LGA and improve the probability 
of successful breast attachment (7,12-16). Dextrose 40% in gel is administered by 
massaging 
into 
the 
buccal 
mucosa 
to 
have 
an 
optimal 
effect. 
In 2013 Harris et al. (14) conducted a study to evaluate the failure rate in the treatment 
of hypoglycaemia in a sample of 242 newborns assigned in the 1:1 ratio to case or 
control group. The cases were treated with 40% dextrose in gel with a concentration 
of 200 mg/kg while the controls with a placebo solution. Newborns of both groups were 
encouraged to feed but if the feeding was insufficient it was administered breast milk 
or formula milk through a syringe. Blood glucose was detected 30 minutes after gel 
administration but if hypoglycaemia was persistent, it was administered up to 6 doses 
of gel during the 48 hours of life. Treated group showed a failure rate in reversion of 
lower hypoglycaemia compared to controls (14% vs 24%, RR = 0.57 (0.33-0.98), p = 
0.04). In 2016 Weston et al. (13) reviewed the scientific literature with the aim of 
evaluating the efficacy of 40% dextrose in gel in preventing hypoglycaemia and in 
reducing the long-term damage associated with neurodevelopment. Two trials 
including 312 infants were included. It was found that the administration of the gel 
reduced the mother-child separation (RR= 0.54, 95% CI = 0.31-0.93) and the 
probability of exclusive breastfeeding after discharge was increased (RR 1.10, 95% CI 
from 1.01 to 1.18).  

 
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No side effects related to gel administration were detected by investigators, and the 
group of gel-treated infants showed an increase in blood glucose of 7.2 mg/dl 
compared to the placebo group. Hegarty et al (7) conducted a clinical trial in which 416 
newborns were randomized and assigned to one of 4 types of treatment: dextrose 40% 
in gel in a single-dose  (200 mg/kg) or double-dose (400 mg/kg ) 1 hour after birth or 
followed by 3 additional doses of dextrose (200 mg/kg) in the first 12 hours. Blood 
glucose was measured at 2 hours from birth then every 2-4 hours for the first 12 hours 
of life. The incidence of hypoglycaemia was lower in the treated than in the control 
group treated with a placebo solution (41% vs 52%, RR = 0.79 (0.64-0.98), p = 0.03). 
The group of newborns treated with a single administration of gel at a concentration of 
200 mg/kg showed a greater reduction in the incidence of hypoglycaemia compared 
to the other types of treatment (38% vs 56%, RR = 0.66 (0.47-0.99), p=0.04). 
Treatment with 40% dextrose in gel also led to a reduction in admissions to NICU due 
to hypoglycaemia compared to the control group (2% vs 13%, RR = 0.12 (0.02-0.90), 
p = 0.04) and to the number of newborns treated with milk in formula (Mean Difference 
= -6.00 (-11.58-0.41), p=0.036). Scientific Safety Evidence: No side effects related to 
the use of 40% dextrose in gel were recorded in all the studies performed. In 2015, the 
guidelines published by the University of Auckland, New Zealand, stated that the use 
of dextrose in gel does not change the incidence of neurosensitive disability at 2 years 
of correct age, moreover, events like crisis convulsive or dead have not been described 
after the administration of this gel (15). Moreover, from the analysis of the literature by 
various scientific search engines including Pubmed, Scholar and others, using as 
keywords: newborn, hypoglycaemia and dextrose gel, until the moment of writing this 
synopsis, no work has been detected as far as regards the side effects in the use of 
dextrose gel. 
 
 
Justification of the 
non-commercial nature 
of the study 
The present study involves the administration of a nutriment supplement based on 
dextrose. It falls within the typology of a spontaneous/non-commercial pilot study. It 
arises from the need of the health care providers to identify a product that can 
decrease the severity of the incidence of hypoglycaemia related to the perinatal period, 
limiting the suffering for newborns and families and at the same time reducing the costs 
charged to SSN deriving from standard pharmacological and rehabilitative therapies 
in the short and medium-long term. 
The Destrogel 40% product was chosen because ORSANA ITALIA Srl proved to be 
available for the supply of the same, also signing a declaration that the scientific results 
of the research will remain available to the scientific community and that the 
management of the protection activities intellectual property on any inventions deriving 
from the research will take place according to the provisions of current legislation and 
in particular of art. 65 of Legislative Decree 10 February 2005, n. 30 “Industrial 
Property Code. Therefore, the results of the research will remain available to the 
Scientific Community and will not be used for profit or commercial purposes. 

 
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Registration status and 
marketing of the 
product in the studio 
 
Health Ministry registry non-drug products. 
The product is present in the food register for special medical purposes of the 
FARMADATI Italia website (https://www.farmadati.it/) and classified with the 
following code: 974921607. The product has been notified for marketing in Italy 
pursuant to DPR 57/2002 and intended for the dietetic treatment of 
hypoglycemia. 
Ingredients: Water, Dextrose, Food Pectin 
Description: Destrogel 40% is food for special medical purposes. It looks like a clear 
gel, slightly yellow, with a sweet taste. 
Field of use: 
Destrogel 40% is indicated in the case of increased need or reduced intake with the 
diet of its components in all the different age groups. 
Destrogel 40% may be useful, in particular, in the prevention of hypoglycemia in 
newborns who have 1 or more risk factors. 
Objectives of the study 
 
• 
Primary objective: To assess whether a single administration of Destrogel 
40% micronutrient can reduce the incidence of hypoglycaemia in late term 
newborns and in SGA and LGA term infants (gestational age: 37-42 weeks). 
• 
Secondary objective: To evaluate whether the administration of the 40% 
micronutrient Destrogel is able to decrease the incidence of the use of formula 
milk and the intravenous administration of 10% glucose solution in late term 
infants and in SGA and LGA term newborns (gestational age: 37-42 weeks), 
reducing artificial breastfeeding in favour of breastfeeding and also reducing 
the pain of the newborn during the execution of peripheral venous access for 
the administration of hypoglycaemia therapy. 
 
 
Study design 
 
Pilot study, non-commercial, with a product for special medical purposes, controlled 
(vs. standard therapy), randomized with a 1: 1 ratio, open. 
 
 
Study population and 
number 
 
Late preterm, full-term newborns, SGA and LGA (<10th and> 90th centiles of body 
weight).  
 
1. Inclusion Criteria 
 Mothers:  
-Favourable for breastfeeding  
-BMI between 19-24  
 
Newborns: 
-Late preterm (gestational age: 34-36 weeks)  
-Term neonates (gestational age: 37-42 weeks), with body weight <10th 

 
6
centile (SGA) or> 90 ° centile according to Bertino's neonatal anthropometric 
evaluation 
-Born from eutocic childbirth 
-Rooming-in 
-Body temperature between 36.5-37.5 ° C 2. 
 
2. Exclusion criteria 
Mothers:  
-Lack of informed consent  
-Diabetic mother  
-Taking medicines during pregnancy (beta blockers, tolbutamide) 
 
Newborns: 
- Major congenital malformations  
- Blood sugar <47 mg / dl 
- Body temperature <36.5 ° C or> 37.5 ° C  
- NICU admissions  
- Milk intake in formula  
- Intravenous infusion of 10% glucose solution  
- Metabolic and respiratory acidosis (pH: 7.28 - 7.38)  
 
Number of patients to be enrolled 
Enrolment of a total of 172 newborns is planned, divided into 4 groups: 
Group A: 43 newborns at risk of hypoglycaemia to which a placebo solution 
will be administered (0.5 ml / kg) 
Group B: 43 newborns at risk of hypoglycaemia to which a placebo solution 
will be administered (1 ml / kg)  
Group C: 43 newborns at risk of hypoglycaemia to which a solution of 
dextrose 40% in gel will be administered (0.5 ml / Kg)  
Group D: 43 newborns at risk of hypoglycaemia to which a solution of 
dextrose 40% in gel will be administered (1 ml / Kg). 
Randomization 
 
After enrolment, patients will be randomly divided into groups A, B, C, D, using 
statistical software. 
Number of centres 
 
Monocentric pilot experimentation. The center will be the Poliambulanza Foundation 
Hospital Institute, Department of Mother and Child Health. 
Sample Size 
The sample size will be calculated through G * Power 3.1.9.2 for Windows. The 
incidence of neonatal hypoglycaemia in the neonatal population is 30% and of these 
50% develop hypoglycaemia. Hegarty et al (7) tried to show that the use of 40% 

 
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dextrose in gel could reduce the rate of hypoglycaemia to 25%, but only achieving a 
reduction to 41%. We believe that in this study the children of a diabetic mother were 
a considerable confounding factor and could mask the beneficial effects of dextrose 
on the sample of late preterm and SGA-born and LGA-born infants. To demonstrate 
this, we have excluded the children of a diabetic mother from the analysis to reduce 
the rate of hypoglycaemia from 50% to 25% by administering 40% dextrose in gel. 
Placing α = 0.05, β = 0.1, Power = 0.90, Odds Ratio = 0.334, R2 = 0.25, allocation rate 
= 1: 1, distribution X = binomial, the number of samples required is 172. In each group 
therefore will be allocated 43 babies. This is the minimum number that can be 
recruited. We will take into consideration any disclaimers during the study (parents can 
ask not to continue the treatment at any time) which goes beyond the statistical 
calculations. Therefore, if necessary, we will recruit a sufficient number of infants to 
reach the minimum number that can be recruited according to the protocol design. 
 
Treatment and 
Posology 
Administered products: 
Dextrose group: Destrogel 40% 
Active ingredient: Dextrose 
Excipients: Water, Food Pectin. 
Placebo Group: 
Composition: Water, Food Pectin. 
Placebo Group: 
• Group A: newborns at risk of hypoglycaemia who will be given a placebo gel solution 
(0.5 ml/kg equivalent) 
• Group B: newborns at risk of hypoglycaemia who will be given a placebo gel solution 
(1 ml/kg equivalent) 
Dextrose Group: 
• Group C: newborns at risk of hypoglycaemia to which a solution of dextrose 40% in 
gel will be administered (0.5 ml/kg equivalent to 200 mg/kg) 
• Group D: newborns at risk of hypoglycaemia to which a solution of dextrose 40% in 
gel will be administered (1 ml/Kg equivalent to 400 mg/Kg). 
Route of 
administration 
In the categories at risk of hypoglycaemia the gel will be administered by massaging it 
into the buccal mucosa. 
 
Duration of the 
administration period 
The administration will be carried out 1 hour after birth. 
 
Duration of the study 
Duration of the observation period of the enrolled patient 
From birth up to 48 hours of life 
Total duration of the study: 

 
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The study will last one year: the first 11 months will be assigned to enrol clients in the 
centres concerned. In this period the planned laboratory investigations will also be 
present. The last month will be used for the study and analysis of the results obtained. 
Procedure 
 
Method: 
At birth, newborns who fall within the inclusion parameters will be randomly recruited 
and divided into 4 groups (A, B, C, D). 
 
The medical staff will be informed of the progress of the study. 
 
Eligible parents will be informed about the nature and purpose of the study in order to 
obtain informed consent to participate in the study. 
 
In the categories at risk of hypoglycaemia, the administration of the gel, which will be 
massaged into the buccal mucosa, will be performed 1 hour after birth. Glycaemic 
monitoring will be carried out at 2, 4, 6, 12 and 48 hours of life as required by the 
department protocol. The detection of blood glucose and blood gas values will be 
carried out through a capillary heel extraction already foreseen by the department 
procedures. The sample will be analysed with "ABL90 Flex". Each detection will be 
preceded by the measurement of body temperature via the skin (Covidien Filacada). 
Newborns will be exclusively breastfed after the administration of the gel and during 
the first 48 hours of life. All data will be collected by the data collection form. The 
newborns who present blood glucose values <47 mg/dl will be treated with formula 
milk (formula 1 milk) or 5% intravenous infusion of glucose according to the protocol 
of the department. 
 
Evaluation parameters: 
 
Effectiveness 
Reduction of the incidence of hypoglycaemia in neonates at risk 
 
Tolerability 
Any side effects that may be observed by the doctor will be recorded on the data 
collection form. 
Basal Visit 
 
At birth, as required by neonatal protocols, newborns will undergo medical 
examinations. 
Control Visit 
From the delivery room the babies will be transferred to the nursery where they will be 
subjected daily to several check-up. 
 
Follow-up 
As required by the neonatological protocols. 
 

 
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Statistical Analysis 
Statistical analysis will be performed by IBM SPSS Statistics for Windows, version 20.0 
(Armonk, NY: IBM Corp.). The normal distribution of data will be evaluated by Shapiro-
Wilk test. The homogeneity of the groups will be analysed by ANOVA test or chi-square 
test, respectively if the variables are continuous or discrete. If the data do not present 
a normal distribution, they will be analysed by Kruskal-Wallis test. The multiple logistic 
regression test (corrected for the risk factors for hypoglycaemia: sex and age) will 
finally be used to estimate the odds of hypoglycaemia between the placebo or dextrose 
40% gel groups. Secondary outcomes will also be studied with the multiple logistic 
regression test.  
 
 
References 
 
1. Thompson-Branch 
A, Havranek 
T (2017). 
Neonatal 
Hypoglycemia. 
Pediatrics 
Rev. 2017 
Apr;38(4):147-157. doi: 10.1542/pir.2016-0063. 
 
2. McKinlay CJ, Alsweiler JM, Ansell JM, Anstice NS, Chase JG, Gamble GD, Harris DL, Jacobs 
RJ, Jiang Y, Paudel N, Signal M, Thompson B, Wouldes TA, Yu TY, Harding JE; CHYLD Study Group 
(2015) Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years. N Engl J Med. 2015 Oct 
15;373(16):1507-18. doi: 10.1056/NEJMoa1504909 
 
3. Engle WA, Kominiarek MA (2008). Late preterm infants, early term infants, and timing of elective 
deliveries. Clin Perinatol. (2008) Jun;35(2):325- 41, vi. doi: 10.1016/j.clp.2008.03.003 
 
4. Committee on Fetus and Newborn, Adamkin DH. Postnatal glucose homeostasis in late-preterm and 
term infants. Pediatrics (2011) Mar;127(3):575-9. doi: 10.1542/peds.2010-3851. Epub 2011 Feb 28 
 
5. McKinlay CJD, Alsweiler JM, Anstice NS, Burakevych N, Chakraborty A et al. Association 
of Neonatal Glycemia With Neurodevelopmental Outcomes at 4.5 Years. JAMA Pediatr. 2017 Oct 
1;171(10):972-983 
 
6. Lago P, Frigo AC, Baraldi E, Pozzato R, Courtois E, Rambaud J, Anand KJ, Carbajal R (2017). 
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7. Hegarty JE, Harding JE, Gamble GD,Crowther CA, Edlin R, Alsweiler JM (2016). Prophylactic Oral 
Dextrose Gel for Newborn Babies at Risk of Neonatal Hypoglycaemia: A Randomised Controlled 
Dose-Finding Trial (the Pre-hPOD Study). PLoS Med 13(10): e1002155 
 
8. Raylene P. The sacred hour: uninterrupted skin-to-skin contact immediately after birth. Newborn & 
Infant Nursing Reviews 2013; 13:67–72 

 
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9. Futatani T, Shimao A, Ina S, Higashiyama H, Fujita S, Ueno K, Igarashi N, Hatasaki K. 
Capillary Blood Ketone Levels as 
an Indicator of Inadequate Breast Milk Intake in 
the Early 
Neonatal Period. J Pediatr 2017; 191:76-81. 
 
10. Spatz DL (2018) Helping Mothers Reach Personal Breastfeeding Goals. Nurs Clin North Am. 2018 
Jun;53(2):253-261. doi: 10.1016/j.cnur.2018.01.011. 
 
11. Chertok IR, Raz I, Shoham I, Haddad H, Wiznitzer A. Effects of early breastfeeding on neonatal 
glucose levels of term infants born to women with gestational diabetes. J Hum Nutr Diet. 2009; 
22(2):166–9 
 
12. Raenee L. Barb er, Amy E. Ekin, Pushparani Sivakumar, Kay Howard and Therese A. O’SullivanInt. 
Glucose Gel as a Potential Alternative Treatment to Infant Formula for Neonatal Hypoglycaemia in 
Australia J. Environ. Res. Public Health 2018, 15, 876 
 
13. Weston PJ, Harris DL, Battin M, Brown J, Hegarty JE, Harding JE. Oral dextrose gel for the treatment 
of hypoglycaemia in newborn infants (Review). Cochrane Database of Systematic Reviews 2016, 
Issue 5. Art. No.: CD011027 
 
14. Deborah L Harris, Philip J Weston, Matthew Signal, J Geoff rey Chase, Jane E Harding. Dextrose gel 
for neonatal hypoglycaemia (the Sugar Babies Study): a randomised, double-blind, placebo-controlled 
trial. The Lancet · September 2013 
 
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Department of Paediatrics: Child and Youth Health, University of Auckland, Auckland, New Zealand 
 
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Rates. Biomed J Sci &Tech Res 4(4) 2018.BJSTR.MS.ID.0001090 
 
 
 
 
 
 
 
 
 
 
 
 

 
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SIGNATURE OF APPROVALS 
 
 
 
 
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       SIGNATURE                                                                               DATE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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