NEONATAL HYPOGLYCEMIA and CONTINUOUS GLUCOSE MONITORING: A RANDOMIZED CONTROLLED TRIAL IN PRETERM INFANTS

Background - Neonatal hypoglycemia is a common event during the first week of life and has been associated to brain injuries and poor neurodevelopment. Unfortunately it may be unrecognized for several hours from its occurrence, since it is asymptomatic/poor symptomatic in newborns (Hay WW, 2009; Cornblath, 2000; Adamkin DH, 2011; Burns et al, 2008; Wong, 2013; Duvanel et al, 1999) Despite the dramatic consequences of prolonged hypoglycemia on the neonatal brain are well known, the only tool to recognize it is represented by the capillary glycemic test performed according to risk-based protocols of Neonatal Intensive Care Units (NICUs): they consider a limited window of intervention based on 2-3 glycemic tests a day (Thomas F et al, J. Diab Science Technol. 2014).

Continuous glucose monitoring systems have offered, in the last decade, a new powerful tool to recognize more hypoglycemic events in neonates than traditional monitoring. All the works developed in neonates, to date, have been aimed to evaluate the performance of the CGM devices and have been used to record the effect of medical "intervention" in the correction of hypo or hyperglycemia (Neonatal Insulin Replacement Therapy in Europe (NIRTURE, Beardsall et al, NEJM 2008; McKinlay et al, NEJM 2015) (Harris et al J Pediatrics, 2010; Beardsall et al, Arch Dis Child Fetal Neonatal 2013). The CGM has never been used to drive medical inteventions in newborns and evaluate as independent tool to improve time-in-target for glycemia.

Previous studies demonstrated that up to 81% of the hypoglycemic episodes were not detected with blood glucose measurement (Harris et al, J Pediatrics 2010). All the published studies in neonates, to date, have used Medtronic CGM systems (Medtronic, USA). No adverse effects, associated to the implant of CGM, have been reported neither in late-preterm neither in preterm newborns.

Glycemic control in terms, and moreover, in preterm newborns still represent a challenge for physicians and the wide fluctuation (both hyperglycemia and hypoglycemia) commonly observed in such population still remains difficult to be managed with traditional blood glucose monitoring (few data/day, delay of therapeutic intervention).

Aim - The study the Investigators are going to conduct is aimed to evaluate if CGM, as driver of therapeutic decisions in preterm newborns (birthweight ≤1500g, gestational age ≤32 weeks) during the first week of life, may be able to maintain "euglycemia". Euglycemia will be defined as values within the range 72-144mg/dl (4-8mmol/L)(Harris et al J Pediatrics, 2010; Beardsall et al, Arch Dis Child Fetal Neonatal Ed 2013)