HYPOGLYCEMIA IN INFANTS AND CHILDREN

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Despite extensive literature on the subject, hypoglycemia in infants and children remains a puzzling yet urgent diagnostic and therapeutic challenge. When the patient presents with vague symptoms, pediatricians may find it hard to determine whether an extensive work-up is indicated, such as a diagnostic fast. In children, conditions that cause hypoglycemia are often complex, diverse, and unique; therefore, evaluation and management of the hypoglycemic child requires a substantial knowledge of all physiologic mechanisms that maintain euglycemia. This article reviews the different aspects of glucose homeostasis in infants and children, the various causes of hypoglycemia, and the adverse effect of low blood glucose on the central nervous system. It also attempts to give a practical approach to the management and treatment of hypoglycemic disorders in childhood.

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GLUCOSE HOMEOSTASIS IN INFANTS AND CHILDREN

The exact regulation of glucose homeostasis in newborns and young infants is not well-established. Most conclusions are drawn from studies performed in experimental animals. Although children and adults may have similar substrate and hormonal control of glucose metabolism, glucose homeostasis in newborns has some different features.

When the pregnant woman receives adequate nutrition, gluconeogenesis and ketogenesis in the fetus are virtually absent.45 The precise timing of the induction of the

DEFINITION OF HYPOGLYCEMIA

Cornblath and Schwartz defined hypoglycemia in the 1960s as a blood glucose level of 20 mg/dL in preterm infants, 30 mg/dL in term infants during the first 3 days of life, and 40 mg/dL in older infants.31 When these studies were carried out, early feeding was commonly discouraged. More recent studies have shown that, except during the first postnatal hours, a blood glucose level lower than 40 mg/dL is uncommon in both premature and full-term infants fed immediately after birth.110, 128 Some

SIGNS AND SYMPTOMS

Signs and symptoms of hypoglycemia are nonspecific in the neonate. Clinical manifestations include lethargy, hypotonia, irritability, feeding difficulties, cyanosis, tachypnea, apnea, hypothermia, seizures, and coma. A similar presentation may be seen in several other disorders, including septicemia, brain injury, severe respiratory distress, and congenital heart disease. Infants who are at a higher risk for hypoglycemia need to be closely monitored because serious sequelae may develop when

ADVERSE SIDE EFFECTS

Glucose is an essential substrate for neuronal metabolism. In animal models, severe and sustained hypoglycemia leads to major structural damage, including neural necrosis with loss of dendrites. Neural damage is most likely caused by the activation of receptors for excitatory amino acids, mainly the N-methyl- D-aspartate (NMDA) receptor.7 Prolonged excitation of NMDA receptors causes cell depolarization with subsequent cell swelling and activation of lipases and proteases. A subtle decrease in

DIAGNOSTIC APPROACH

A methodical approach is required when the diagnosis of hypoglycemia is suspected. A careful medical history and a thorough physical examination give important clues to the diagnosis. Hypoglycemia that is triggered by certain components of the diet may be indicative of an inborn error of metabolism such as galactosemia, maple syrup urine disease, and fructose intolerance. Marked obesity at birth suggests some forms of hyperinsulinism. Cholestasis and micropenis occur in the setting of

TREATMENT

The goal of treatment is to normalize blood glucose concentrations by providing adequate glucose enterally or parenterally. In patients with hyperinsulinemia, subcutaneous glucagon (0.03 mg/kg) can reverse the hypoglycemia. Prevention of hypoglycemia is dependent on its cause. If hypoglycemia develops with increased fasting, uncooked cornstarch is often useful (see section on glycogen storage disease).

HYPOGLYCEMIC DISORDERS

Several classifications of hypoglycemic disorders have been proposed depending on the age and clinical characteristics103 of the patient or based on the pathophysiology of hypoglycemia (increased glucose use or decreased glucose production).55 For the purpose of this review, hypoglycemic disorders are listed without any specific reference to glucose metabolism (Table 1).

CONCLUSION

Childhood hypoglycemia remains a challenging but fascinating subject. Conditions that cause hypoglycemia should be promptly recognized and treated. Delaying therapy may lead to neuronal damage, especially in premature and young infants.

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    Address reprint requests to W. F. Schwenk, MD, Division of Pediatric Endocrinology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905

    *

    Section of Pediatric Endocrinology, Mayo Medical School, Rochester, Minnesota

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