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). 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. 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. 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). 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 characterized by: sweating, pallor, cyanosis, temperature instability, irritability, starvation, tremors, tachycardia, emesis and neuroglycopenic signs and symptoms characterized by: apnea, hypotonia, hypovalid suction, seizures, up to the come and the exitus.

Serious monitoring of neonatal blood glucose is indicated in patients at risk of hypoglycemia. Glycemic 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 fetus in the intrauterine phase, while later these values rise again until arrive at similar values to the adult within 48-72 hours. Monitoring is performed by glucometer, capillary EGA or blood sampling performed in patients at risk of painful stress. 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. 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. 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. However, the administration of milk formulated in the first hours of life causes a reduction in breastfeeding. In severe cases with glycaemia \<36 mg/dl, it is practiced intravenous infusion of 10% glucose or dextrose. 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. Dextrose 40% in gel is administered by massaging it into the buccal mucosa to have an optimal effect.

In 2013 Harris et al. 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. 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).

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 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 hypoglycemia 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 hypoglycemia 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 hypoglycemia 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. Moreover, from the analysis of the literature by various scientific search engines including Pubmed, Scholar and others, using as keywords: newborn, hypoglycemia 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.