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Hypoglycemia is frequent in very low birth weight (VLBW) neonates and compromises their neurological outcome. The aim of this study was to compare real-time continuous glucose monitoring system (RT-CGMS) to standard methods by intermittent capillary blood glucose testing in detecting and managing hypoglycemia.Forty-eight VLBW neonates were enrolled in this prospective study. During their 3 first days of life, their glucose level was monitored either by RT-CGMS (CGM-group), or by intermittent capillary glucose testing (IGM-group) associated with a blind-CGMS to detect retrospectively missed hypoglycemia. Outcomes were the number and duration of hypoglycemic (≤ 50 mg/dl) episodes per patient detected by CGMS.Forty-three monitorings were analyzed (IGM n = 21, CGM n = 22), with a median recording time of 72 hours. In the IGM group, blind-CGMS revealed a significantly higher number of hypoglycemia episodes than capillary blood glucose testing (1.2 ± 0.4 vs 0.4 ± 0.2 episode/patient, p