Chapter 10 - Glucose and perinatal brain injury: Questions and controversies

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Neonatal hypoglycemia is the most common biochemical abnormality of the newborn, affecting 5%–15% of all infants and 50% of those with risk factors. Although severe hypoglycemia has been incontrovertibly linked with brain injury and impairment, the glucose thresholds below which injury occurs have not been clearly established, and in fact, may differ based on various host factors. In the absence of clear evidence of a causative link between mild or asymptomatic neonatal hypoglycemia and brain injury, committees have recommended that infants who are at high risk based on maternal or fetal physiology are screened and treated if their blood glucose drops below “operational thresholds,” or concentration of blood glucose at which clinicians should consider intervention. These thresholds have been determined based on consensus opinion, incorporating a combination of norms in healthy infants, neuroglycopenic thresholds, and associations between early glycemia and later development from observational studies. In this chapter, we will review key metabolic transitions that occur soon after birth that, when dysregulated, can result in neonatal hypoglycemia, summarize mechanisms that underlie the association between neonatal hypoglycemia and later outcomes, and review the animal and human studies that have investigated the link between hypoglycemia and neurodevelopment. We will also summarize current glycemic assessment modalities and prevention and treatment recommendations. Throughout, we will highlight unanswered questions and areas of controversy that urgently require further inquiry.