Hypoglycemia is difficult to define in neonates but is generally considered a serum glucose concentration < 40 mg/dL (< 2.2 mmol/L) in symptomatic term neonates, < 45 mg/dL (< 2.5 mmol/L) in asymptomatic term neonates between 24 hours and 48 hours of life, or < 30 mg/dL (<
(See also general discussion of hypoglycemia.)
Etiology of Neonatal Hypoglycemia
Neonatal hypoglycemia may be transient or persistent.
Transient neonatal hypoglycemia
Causes of transient hypoglycemia are
Inadequate substrate (eg, glycogen)
Immature enzyme function leading to deficient glycogen stores
Transient hyperinsulinism
Deficiency of glycogen stores at birth is common among preterm infants who have a very low birth weight, infants who are small for gestational age because of placental insufficiency, and infants who have perinatal asphyxia. Anaerobic glycolysis consumes glycogen stores in these infants, and hypoglycemia may develop at any time in the first few hours or days, especially if there is a prolonged interval between feedings or if nutritional intake is poor. A sustained input of exogenous glucose is therefore important to prevent hypoglycemia.
Hyperinsulinism most often occurs in infants of mothers with diabetes and is inversely related to the degree of maternal control of diabetes. When a mother has diabetes, her fetus is exposed to increased levels of glucose because of the elevated maternal blood glucose levels. The fetus responds by producing increased levels of insulin. When the umbilical cord is cut, the infusion of glucose to the neonate ceases, and it may take hours or even days for the neonate to decrease its insulin production. Hyperinsulinism also commonly occurs in physiologically stressed infants who are small for gestational age. In both cases, the hyperinsulinism is transient.
Hypoglycemia may also occur if an IV infusion of dextrose is abruptly interrupted.
Finally, hypoglycemia can be due to malposition of an umbilical catheter or sepsis.
Persistent neonatal hypoglycemia
Causes of persistent hypoglycemia include
Hyperinsulinism
Defective counter-regulatory hormone release (growth hormone, corticosteroids, glucagon, catecholamines)
Inherited disorders of metabolism (eg, glycogen storage diseases, disorders of gluconeogenesis, fatty acid oxidation disorders)
Although most hyperinsulinism is transient, less common and longer lasting causes include congenital hyperinsulinism (genetic conditions transmitted in both autosomal dominant and recessive fashion), severe hemolytic disease of the neonate, and Beckwith-Wiedemann syndrome (in which islet cell hyperplasia accompanies features of macroglossia and umbilical hernia). Hyperinsulinemia characteristically results in a rapid fall in serum glucose in the first 1 to 2 hours after birth when the continuous supply of glucose from the placenta is interrupted.
Blood glucose levels depend multiple interacting factors. Although insulin is the primary factor, glucose levels also depend on growth hormone, cortisol, and thyroid hormone levels. Any condition that interferes with the appropriate secretion of these hormones can lead to hypoglycemia.
Symptoms and Signs of Neonatal Hypoglycemia
Many infants remain asymptomatic.
Prolonged or severe hypoglycemia causes both adrenergic and neuroglycopenic signs. Adrenergic signs include diaphoresis, tachycardia, lethargy or weakness, and shakiness. Neuroglycopenic signs include seizure, coma, cyanotic episodes, apnea, bradycardia or respiratory distress, and hypothermia. Listlessness, poor feeding, hypotonia, and tachypnea may occur.
Diagnosis of Neonatal Hypoglycemia
Bedside glucose check
All signs are nonspecific and also occur in neonates who have asphyxia, sepsis or hypocalcemia, or opioid withdrawal. Therefore, at-risk neonates with or without these signs require an immediate bedside blood glucose check from a capillary sample. Abnormally low levels are confirmed by a venous sample.
Treatment of Neonatal Hypoglycemia
Enteral feeding
Most high-risk neonates are treated preventively (1). For example, infants of women with diabetes who have been using insulin are often started at birth on a 10% D/W infusion IV or given oral glucose, as are those who are sick, are extremely preterm, or have respiratory distress. Other at-risk neonates who are not sick should be started on early, frequent formula feedings to provide carbohydrates.
Any neonate whose glucose falls to ≤ 50 mg/dL (≤dextrose infusion should always be tapered because sudden discontinuation can cause hypoglycemia.
If hypoglycemia is refractory to treatment, other causes (eg, sepsis) and possibly an endocrine evaluation for persistent hyperinsulinism and disorders of defective gluconeogenesis or glycogenolysis should be considered.
Prognosis depends on the underlying condition.
Treatment reference
1. Harding JE, Alsweiler JM, Edwards TE, McKinlay CJ. Neonatal hypoglycaemia. BMJ Med. 2024;3(1):e000544. Published 2024 Apr 9. doi:10.1136/bmjmed-2023-000544
Key Points
Small and/or preterm infants often have low glycogen stores and become hypoglycemic unless they are fed early and often.
Infants of mothers with diabetes have hyperinsulinemia caused by high maternal glucose levels; they may develop transient hypoglycemia after birth, when maternal glucose is withdrawn.
Signs include diaphoresis, tachycardia, lethargy, poor feeding, hypothermia, seizures, and coma.
Give preventive treatment (using oral or IV glucose) to infants of mothers with diabetes, extremely preterm infants, and infants with respiratory distress.
If glucose falls to ≤ 50 mg/dL (≤ 2.75 mmol/L), promptly give enteral feeding or an IV infusion of 10% to 12.5% D/W, 2 mL/kg over 10 minutes; follow this bolus with supplemental IV or enteral glucose and closely monitor glucose levels.
