Neonatal Hypoglycemia

Excerpt

Hypoglycemia is the most common metabolic disturbance occurring in the neonatal period. Screening at-risk infants and the management of low blood glucose levels in the first hours to days of life is a frequent issue in the care of the newborn infant. Yet, a clear definition of neonatal hypoglycemia is lacking. Current screening guidelines and management algorithms are based on limited evidence, relying more on expert opinion to guide recommendations.

Despite a better understanding of early glucose homeostasis and transitional hypoglycemia in the first 48 hours of life, gaps in our knowledge persist. Observations have shown that healthy infants experience transient hypoglycemia as a part of the normal adaption to extrauterine life, with a decline in blood glucose concentrations to values as low as 20 to 25 mg/dL in the first two hours of life. However, because we do not routinely measure blood glucose concentrations in healthy infants without risk factors for hypoglycemia, it is difficult to define 'normal' levels of blood glucose in the first 48 hours of life. As Harding et al. question: "even if healthy infants experience low glucose concentrations, can we extend these values to infants at risk of impaired metabolic adaption?" And how low is too low?

A 1988 multicenter nutritional study by Lucas et al. suggested a blood glucose concentration <47 mg/dL as the critical threshold associated with adverse neurodevelopmental outcomes. The study looked at blood glucose levels in 661 preterm infants with a birth weight of <1850 grams enrolled in a nutritional study investigating early feeding strategies and cognitive outcomes. Investigators found that the number of days of blood glucose concentrations <47 mg/dL associated with lower motor and mental developmental scores on the Bayley Scales of Infant Development at 18 months corrected age. Infants that experienced hypoglycemia (glucose <47 mg/dL) on 5 or greater days had 3 to 5 times increased risk of neurodevelopmental impairment. The authors concluded that "even moderate hypoglycemia is associated with a considerable increase in adverse neurodevelopmental sequelae" and called for a reevaluation of the then current practice trends. As a result, this value of '47 mg/dL' became widely accepted as the standard numerical value to define neonatal hypoglycemia for all infants, even healthy, term, appropriate for gestational age infants.

It is clear that extremely low blood glucose concentrations in neonates can cause apnea, irritability, lethargy, seizures, and brain damage ; and that prolonged or symptomatic hypoglycemia may correlate with long-term neurodevelopmental deficits. However, the long-term significance of early, asymptomatic and transiently low glucose levels remain not well established. And the evidence to support a clear numerical value of blood glucose that is associated with brain injury or reliably predicts adverse neurodevelopmental outcomes is lacking. Even Lucas et al. acknowledged that 'the association between [blood glucose concentrations <47 mg/dL] and poor neurodevelopmental outcomes might not be causal and might reflect a failure to adjust for confounding factors.'