Continuous glucose monitoring (CGM) in very low birth weight newborns needing parenteral nutrition: validation and glycemic percentiles.

Very low birth weight (VLBW) neonates are at high risk of glycemic disorders. Neonates requiring intensive care have impaired glucose control and a wide fluctuation in blood glucose levels. Their developing brain is likely to be more susceptible to these metabolic insults. Hypoglycemia is associated with poor neurodevelopmental outcome [1‐3] and hyperglycemia is correlated with increased mortality and morbidity in preterm infants [4]. Plasma glucose level detection represents the gold standard to diagnose these metabolic disorders, however, this method produces only punctual values and does not allow a real-time (RT) monitoring of glycaemia and its trends. This could explain the great deal of controversy over the values of normoglycemia in neonatal population and the paucity of proper diagnoses [5, 6]. Specifically, there is no consensus on the definition of “significant hypoglycemia” (blood glucose values requiring a medical treatment), and on the threshold of glucose concentration and the time needed to cause neurological damage [7, 8]. Continuous glucose monitoring (CGM) can be used to investigate glucose homeostasis during the neonatal period and some studies showed its use is safe and reliable [8‐10]. Moreover, it is demonstrated that CGM can detect a significantly higher number of hypo/hyperglycemia episodes as compared to intermittent blood glucose measurement. A better management of glucose administration [11] can be obtained with a RT visualization of glycemic values in the new generation CGM system (CGMS) [12‐14]. Recently, however, some authors expressed concerns about using CGM in the clinical setting [15]. In fact, they showed that the calibration methods of new generations CGM sensors are designed for higher glucose concentrations of children and adults, and not for neonates. Therefore, the routine usage of a CGMS with its specific sensor, could be proposed only after validation studies conducted in a neonatological setting. This study was conducted using RT Medtronic’s CGMS, a system previously tested by our research group in a population of neonates at risk of dysglycemia with a median gestational age (GA) of 32 weeks. Not many dysglicemic episodes were detected, but the CGMS demonstrated reliable in the normoglycemic range [12]. Only VLBW neonates fed by parenteral nutrition were included in this study, with the aim of testing the reliability of the Medtronic’s CGMS in this specific new setting. Babies had a lower mean gestational age and birth weight than in the previous study, and both hyper- and hypoglycemic episodes were detected during the study period. We also aimed at describing the distribution of glycemic values in the studied population. Such data is currently lacking in the scientific literature [16] for VLBW infant requiring parenteral nutrition, but it could be very useful to allow a proper modulation of the glucose infusion, thus preventing dysglycemic episodes, to reduce and optimize the need of insulin therapy, and hopefully to lead to the definition of a new protocol for a strict glycemic control in randomized controlled trials.

Twenty-three infants were enrolled, 9 males and 14 females, with a median birth weight (BW) of 860 g (range 500–1092 g) and a median gestational age of 28 weeks (range 23–30 weeks). Other population details are summarized in Table 2.

The sensor was well tolerated with an average (DS) duration of 112,7 (31,7) h. We collected 299 pairs of CGMV vs GTX measurements.

Figure 1 reports the Bland Altman Analyses for glucose measurements. The mean (95% CI) difference was 1,4 (− 33,5 to 36,3) mg/dl.

Figure 2 reports the MCEG: 83,6% of measurements fall in region A, 15,4% of measurements fall in region B, and 1,0% of measurements in region D, without any value in region C or E. It is to be mentioned that glucose values obtained during the study did not fall under the lower limit detected by CGMS.

Seventy-four episodes of hypoglycemia and and 33 of hyperglycemia were detected; mean (DS) durations were 44 (48) and 96 min (130); 15 hypo- and 3 hyperglicemic CGMV turned out to be inaccurate at the blood sample analysis performed with point of care glucometer. 31,329 CGMV were obtained and analyzed.

Tables 3 and 4 present distribution and percentiles of glycemic values of the studied population.

CGM has a great potential for optimizing glycaemic control [21] and there is growing interest in using CGM devices in neonatal intensive care. However, as remarked in a recent review [15], CGM has a clear role in adult and child care but there are some concerns about its use in neonatology. This study evaluated feasibility and safety of the Medtronic’s CGMS in VLBW fed by parenteral nutrition. This CGMS proved to be safe to use in this population and it was well tolerated after the sensor’s insertion. Moreover, it didn’t interfere with nursing care and it showed an unexpected satisfaction by the neonatal staff. Furthermore, MCEG demonstrated the accuracy of the tool tested in the studied population. However, the data presented here show that this CGMS was inaccurate in some episodes of both hyper- and hypoglycemia, although all such inaccuracies by CGMV evidenced by GTX, fell in B region of MCEG, thus not leading to an inappropriate treatment. Some authors have published previous studies focused on CGM in neonates, suggesting the CGM as a useful instrument to be used in neonates requiring intensive care and in VLBW [9, 10, 22]. However, in all these studies both an old sensor and an old (not RT) continuous glucose monitoring system were used. More recently, the usefulness and reliability of RT-GCM was demonstrated in babies born at 32 weeks gestation who were at risk of hypoglycemia [23]. Moreover, a randomized controlled trial focused on VLBW babies, describes the CGM as a more effective tool in detecting and treating hypoglycemic episodes when compared to standard methods [11]. New glucose infusion protocols [13, 24], based on real time visualization of glycemic values, are incoming and will be proposed for newborns at high risk of hyper- or hypoglycemia. The main strengths of our study are the focus on a selected population at high risk of disglycemia and the use of a new generation sensor and a RT-CGM device. We also described the distribution of glycemic values of the studied population. At our knowledge it is the first time such an analysis has been performed. This distribution is very interesting, as in the future new glucose infusion rate protocols, based on the CGM usage, may be designed to tailor patient-based nutritional intake. Glycemic percentiles’ generation could allow to overcome the current limits of the “significant hypoglycemia” definition, correlating it to the glycemic trend rather than to punctual values. The main limitation of our study is the small size of the population. However, the observational design allowed to assess the efficacy and safety of the CGMS in this specific population. In conclusion, our results suggest that the presented CGM system with its sensor can be used, being both safe and accurate, in the management of glucose infusion and insulin therapy in VLBW neonates in total parenteral nutrition during the first week of life.

Medtronic’s CGMS is safe and reliable in VLBW neonates fed by parenteral nutrition and is well tolerated after the sensor’s insertion. It doesn’t interfere with nursing care, as shown by the good satisfaction by the neonatal staff. Collecting glycemic values allowed to generate glycemic percentiles that could be useful to tailor patient-based glucose intakes. The data presented here are promising but a larger population of VLBW is needed in a randomized controlled clinical trial setting to properly define the place in therapy of CGMS.