Reference ranges of blood glucose values in healthy term neonates in their first days of life: a systematic review and meta-analysis

Abstract

Neonatal hypoglycaemia is the most common metabolic disorder in the first days of life. Pathological hypoglycaemia, characterized by persistent or recurrent low glucose levels, can lead to brain injury, resulting in long-term adverse neurodevelopmental outcomes. It can be challenging to differentiate between physiological and pathological hypoglycaemia. This systematic review and meta-analysis aims to define time-stratified reference blood glucose values in healthy term neonates within the first 72 h of life. We searched PubMed, EMBASE and Web of Science to identify original studies reporting glucose values within 72 h post-delivery in healthy term neonates. Glucose patterns were analyzed by random-effect models, and a normalcy curve was generated by meta-regression. Thirty-nine studies (8538 neonates) were included. Random-effects forest plots revealed dynamic glucose trends. The meta-regression analysis generated a normalcy curve that revealed a rapid decrease in glucose levels to a median of 3.1 mmol/L within 2 h, followed by fluctuations around 3.2 mmol/L for up to 12 h, and stabilized glucose levels at 3.6 mmol/L between 36 and 72 h. The 10th percentiles are 2.1 mmol/L, 2.3 mmol/L, and 2.6 mmol/L at 0-2, 12, and 24 h, respectively.

Conclusion: We observed a time-dependent change in neonatal glucose in the first 72 h after birth. The nadir was reached after 2 h, and glucose values gradually increased thereafter. A dynamic interpretation based on percentiles, with the 10th percentile as the lower limit of normal, may better capture variability in neonatal glucose regulation and allow for more personalized glucose management.

What is known: • Neonates experience a transient, physiological drop in glucose after birth. • Defining cut-offs is challenging due to limited data on normal glucose transitions and the difficulty of distinguishing physiological from pathological hypoglycaemia.

What is new: • We present a normalcy curve of blood glucose levels in the first 72 h of life of healthy term neonates with the 10th percentile as lower limit of normal. • We suggest that a personalized approach to glucose monitoring, with time-specific dynamic interpretation, could optimize neonatal glucose monitoring.

Keywords: Blood glucose; Hypoglycaemia; Infant; Newborn.