Neonatal hypoglycemia still remains a challenge, due to the uncertainty in its definition and in the threshold to consider intervention . For asymptomatic at-risk neonates, management is focused on normalizing their blood glucose levels and preventing both short and long-term severe neurological sequelae. Secondary but relevant target is to reduce physical separation between mothers and newborns so enhancing bonding and breastfeeding success. The introduction of the administration of 40% dextrose gel in the protocols for hypoglycemia was targeted to control neonatal asymptomatic hypoglycemia until feeding was established, to reduce the need of glucose intravenous therapy and NICU admission, and to promote breastfeeding and maternal bonding.
We analyzed the data from two groups of newborns at-risk for hypoglycemia, managed with (Gr2, prospective study group) or without the administration of 40% dextrose gel (Gr1, historical control group).
In the last decades, the incidence of neonatal hypoglycemia in otherwise healthy infants is 5–15% [1, 13]; in our experience this data is respected, because we found an incidence of 10% (39/389) in the historical group (Gr1) and 12% (37/308) in the cohort of infants managed with the new protocol (Gr2).
Gr2 presented a reduced need of NICU admission, of iv therapy and a shorter length of hospitalization. Moreover, the rate of exclusively breastfed newborns at discharge, was higher in this group of infants when compared to the infants of the historical group (Gr1).
We found a significative different incidence of NICU admission for hypoglycemia: 48.7% (19/39) in the historical cohort of patients (Gr1) versus 10% (3/30) in the cohort of patients treated with dextrose gel at 40% (Gr2). This finding is similar to data reported in the literature. Rawat et al  demonstrated that the introduction of dextrose oral gel for the management of hypoglycemia reduced the hospitalization rate from 42–26% (p < 0.01). Similar findings were found by Scheans et al , who demonstrated that in the first year of use of dextrose gel the admission at NICU due to hypoglycemia was reduced of 73%. In other two studies performed in Australia  and USA , the Authors found a reduction of admission to NICU for the treatment of hypoglycemia of 15% and 7.7%, respectively. On the contrary, two recent studies did not demonstrate the efficacy of the dextrose gel to reduce NICU admission rates. In the former study , the Authors found a non-significant reduction from 2.5–1.5%; they tried to explain this result suggesting that the study took place in a Baby-Friendly Hospital with a low NICU admission rates already before the introduction of dextrose gel for the management of hypoglycemia. Ponnapakkam et al  explained their controversial results by pointing out that despite a high compliance with dextrose gel usage, the skin-to-skin care and the early feeding are more comfortable measures for healthcare to prevent neonatal hypoglycemia.
In our study the percentage of patients who required iv treatment was significantly reduced from 35.9–10% in the cohort of newborns managed with dextrose oral gel at 40%. Similar conclusions were reached in other studies. Rawat et al  demonstrated a reduction of iv therapy of 15.5%, Gregory et al.  showed a reduction from 8.6–5.6% after the introduction of dextrose oral gel in clinical practice and, at last, even the retrospective study of Makker et al  emphasized the significant impact of the oral treatment on the NICU admission rate and the number of iv dextrose administration. The Cochrane review of 2016  showed no significant differences in the need of iv treatment between the group of patients treated with dextrose oral gel and placebo group, but the authors underlined the low quality of the two included studies due to inaccuracy of data collection, the presence of bias and deviations on outcomes analyzed.
Our data showed that even the length of hospital stay of asymptomatic hypoglycemic newborns managed with dextrose oral gel (Gr2) was significantly shorter than newborns in Gr1. This conclusion is, of course, linked to the reduced transfer of patients at NICU and the reduced need of iv treatment. In the same way, Rawat et al  and Stewart et al  showed a significant decrease of the length of hospital stay from 7.3 ± 4.3 to 3.1 ± 1.1 days and from 5.8 to 3.8 days, respectively. Conversely, Makker et al  found no differences in the length of hospitalization between newborns managed with dextrose oral gel and iv treatment. The authors concluded that this non-randomized and not-controlled study could have some limitations regarding especially the impact of the new protocol on healthcare routine and the maximum number of doses of dextrose oral gel fixed at 4 times instead of 6 administrations as usually made in the other studies.
Although in our study we did not directly perform a cost analysis, we observed the results of similar studies in literature  and we can assume that a reduced number of NICU admission, less iv treatment and a shorter length of hospitalization, make dextrose oral gel a less costly option for the management of neonatal asymptomatic hypoglycemia.
The rate of exclusive breastfeeding at discharge was the last secondary outcome evaluated in our study. Many data from the literature [24, 25] underline the crucial role of early initiation of breastfeeding and the skin-to-skin care immediately after birth. This is crucial to increase and promote maternal bonding and breastfeeding and to achieve successful exclusive breastfeeding during hospitalization and at discharge. Our results showed a significantly increased rate of newborns exclusively breastfed in group 2: 30% (9/30) in Gr2 vs 7.7% (3/39) in Gr1. This is certainly related to the fact that it was possible, in the first hours of life, to keep mothers and newborns together thanks to the use of dextrose gel. Several others studies in literature confirmed our result. Rawat et al  and Makker et al  demonstrated an increase of exclusive breastfeeding in newborns managed with dextrose oral gel from 19–28% and from 6–19%, respectively. Weston et al in 2016  confirmed the increase in the percentage of exclusive breastfeeding at discharge in the group of newborns treated with dextrose oral gel during hospital stay. Two studies in literature showed different results. Stanzo et al  found an increase in exclusively breastfed newborns from 56.6–59.1%. This not significant result could be linked to the high rate of breastfeeding even before the introduction of management of hypoglycemia with dextrose oral gel, due to the Baby-Friendly practices. Ponnapakkam et al  showed an increase only of 3 percentage points in exclusive breastfed infants and they attributed this result to the critical issues related to the new protocol for healthcare personnel but also to the frequent rotation of the same staff.
In order to reduce this bias, before the application of the new protocol for the management of at-risk infants for hypoglycemia, in our department we performed several training sessions with doctors, nurses and residents. Although we have not assessed it directly, we can say that the administration of dextrose oral gel was tolerated by newborns, and, especially, by parents and staff. Moreover, the administration of dextrose oral gel appears safe even in the long term, as indicated by the data in literature .
One of our concerns was the possible adverse effect of dextrose gel on breastfeeding; in fact it is reported that the administration of any supplements in the neonatal period may delay the establishment of breastfeeding, and decreased its duration [27, 28]. However, our data show that newborns managed with dextrose oral gel present higher rate of exclusive breastfeeding.
Our study has several limitations. First of all, the COVID 19 pandemic forced us to interrupt the Group 2 recruitment (due to less availability of hospital staff) and this group is less numerous. Some inhomogeneities between groups are shown in Table 1: birth weight and gestational age differences, though statistically significant, do not change the clinical definition of the neonates, who remain adequate for gestational age (AGA) and term neonates. Moreover this is a comparison between a prospective group and a historical group managed with two different protocols for the management of asymptomatic hypoglycemia. The analysis of retrospective data may limit the stringency and robustness of data quality, and it was dependent on the accuracy of documentation by clinical staff. Finally, we did not evaluate the rate of breastfeeding after discharge; this data could be interesting to confirm the relevant role of dextrose gel to improve breastfeeding during the hospital stay in hypoglycemic infants.