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Even though as many as 25% of newborns are screened for "low blood sugar", there is no agreement what constitute neonatal hypoglycemia (NH). Study objective was to propose an evidence-based "working definition" of NH. Methods: We reviewed the clinically relevant English language literature on NH using the evidence-based-medicine-approach. Articles classified as grade A (randomized, controlled, large sample), B (randomized, small) and C (cohort with historical controls, time and case series, and prospective trials), were analyzed. We focused on the following: 1. Physiologic responses to low blood glucose levels, 2. Developmental outcomes of infants who had low blood glucose levels, and 3. Lower glucose limits of serial blood glucose levels (GL) in newborns during the first postnatal days. Results: Only grade C studies were analyzed since Grade A and B studies had never been published. 1. Physiologic data: Whole blood GL of < 45 mg/dl (day 1-3) were associated with abnormal brainstem-evoked potentials in term infants and with increased epinephrine plasma levels and cerebral blood flow (day 1) in preterm infants. 2. Developmental data: Plasma GL between 30-45 mg/dl (in ≥ 5 separate days) were associated with decreased mental and developmental outcomes, and increased incidence of cerebral palsy in preterm infants. Whole blood GL of < 20 mg/dl (day 1-4) were associated with decreased IQ and head circumference in preterm infants. 3. Glucose limits: The 5th percentile for serum GL in healthy term infants were 33-39, and 46-48 mg/dl at the ages of ≤ 24, and 25-48 hrs, respectively. The lower limit of 95% confidence interval for plasma GL in healthy term infants were approximately 45, 50 and 60 mg/dl at the ages of 24, 25-72 and > 72 hrs, respectively. Based on the above data, the proposed definition for neonatal hypoglycemia is: (Table)
Alkalay, A., Klein, A., Nagel, R. et al. Neonatal Hypoglycemia: A Need for a New Definition?.
Pediatr Res45, 276 (1999). https://doi.org/10.1203/00006450-199904020-01639
