Neonatal Hypoglycemia
In a newborn, glucose levels rapidly fall to a low point in the 1st 2 hours of life which is usually transient (as the source of maternal glucose is removed) and the infant achieves homeostasis. This transition is usually smooth but there are certain high-risk infants who are at risk of hypoglycemia.
High risk infants:
Infants with increased utilization of glucose (Hyperinsulinism):
- Infants of Diabetic mothers
- Erythroblastosis fetalis
- Beckwith Wiedman syndrome
- Nesidioblastosis or islet cell adenoma.
Infants with decreased glucose stores/production:
- Premature infants
- Intra-uterine growth retardation (IUGR)
- Inadequate caloric intake
Increased utilization of glucose/stressed infants:
- Sepsis
- Asphyxia
- Respiratory distress
- Hypothermia
- Polycythemia
- Shock
Inborn errors of metabolism in infants:
- Glycogen storage disorders
- Galactosemia
- Organic acidemias
Endocrinal deficiencies in infants:
- Adrenal insufficiency
- Congenital hypopituitarism
Major Causes of Hypoglycemia in an Infant
Transient hypoglycemia in neonates
- Small for gestational age
- Premature babies
- Hypothermia
- Hypoxia
- Neonates with perinatal asphyxia -Infants of a diabetic mother
- Infants with erythroblastosis fetalis
- Neonates born to mother with toxemia
Persistent hypoglycemia
Hyperinsulinemic states
- Nesidioblastosis
- Beta cell hyperplasia
- Beckwith -Wiedmann syndrome
Hormone deficiency
Miscellaneous
Major Causes of Hypoglycemia in an Older Infant & Child
Hyperinsulinemic states
- Islet cell adenomas
- Islet cell dysmaturation syndrome
Nesidioblastosis
Enzyme deficiency
- Isolated growth hormone deficiency
- Addison's disease
- ACTH deficiency
Substrate limited
- Ketotic hypoglycemia
- Glycogen storage disorder
- Fatty acid oxidation defects
Inborn Errors of Metabolism
- Maple Syrup Urine Disease (MSUD)
- Propionic Acidemia
Miscellaneous
- Acute alcohol intoxication
- Salicylate intoxication
- Fructose intolerance
- Excessive insulin administration in IDDM
- Extraneous insulin administration
- Malnutrition
- Sepsis
- Renal failure
Hyperinsulinism
Most cases present during the 1st year of life as a result of familial or non-familial nesidioblastosis or islet cell dysmaturity syndrome. Islet cell adenoma usually presents as hypoglycemia in a child 5 years or older.
The hallmark of hyper insulin states is the inability to withstand fasting. Patients have ravenous appetites, increased demand for food, and weight gain. Jitteriness and seizures are common. At the time of documented hypoglycemia, ketonemia is low or absent. There is no acidosis and S. insulin levels are usually higher than 5 to 10 mcg/ml with elevated C-peptide (In factitious hypoglycemia, due to exogenous administration of insulin, C-peptide is not elevated). Also, S. insulin levels may be more than 100 mcg/ml). Hyperinsulinism is confirmed by fasting for several hours under close supervision and collecting blood samples for testing. MRI or high-resolution ultrasonography may be helpful in locating a pancreatic adenoma. Surgery is the treatment of choice.
Ketotic Hypoglycemia
It is the most common cause of childhood hypoglycemia. It usually presents between the age of 18 months and 5 years and remits spontaneously by 8 to 9 years of age. Hypoglycemia usually occurs during illness when food intake is limited. Diagnosis is confirmed by fasting for several hours under close supervision and collecting blood samples for testing. At the time of hypoglycemia, there is associated with ketonemia & ketonuria. S.alanine levels are reduced. Treatment consists of frequent feedings of a high-protein, high carbohydrate diet. During periods of illness, parents should check the child's urine for the presence of ketones, as it appears several hours before hypoglycemia. If urine ketones are positive, liquids with high carbohydrate content should be given to the child.
Glycogen Storage Disorder
Glycogen synthetase deficiency (GSD Type 0) presents as early morning hypoglycemia. There is associated ketonemia but no hepatomegaly. The clinical picture is similar to ketotic hypoglycemia. Prolonged hyperglycemia after glucose administration with an increase in serum lactate should indicate the deficiency. Hypoglycemia is unresponsive to glucagon administration as liver glycogen content is decreased.
Von Gierke's disease (GSD Type I): The kidneys and liver glycogen content are increased and the liver and kidneys are enlarged. Patients may have a "doll's face", stunted growth, and normal mental development. Along with hypoglycemia, there is lactic acidosis, hyperlipidemia, and hyperuricemia. IV glucagon (post-prandial) does not raise blood glucose. Continuous nighttime feeding by tube is required.
GSD Type III: Patients have hepatomegaly. However, the kidneys are not enlarged (as in GSD type I). Serum concentrations of uric acid, lactate, ketones, and lipids are normal. IV glucagon (postprandial) raises the blood glucose level.
Fatty Acid Oxidation Defects
Hypoglycemia is associated with hypoketonemia. Patients usually present in the 2nd year of life and hypoglycemia is associated with encephalopathy mimicking Reye's syndrome. Diagnosis is established by evaluating plasma for organic acids and urine for dicarboxylic acid and enzyme studies from liver biopsy tissue or cultured fibroblasts.
Diagnosis in Newborns
Most infants with transient hypoglycemia have no symptoms. The symptoms, when present are non-specific and include jitteriness, lethargy, cyanosis, apnea, seizures, and poor feeding. Hence, a blood sugar of less than 35 mg% in any infants is considered significant hypoglycemia. However, for all practical purposes, the therapy is initiated if the level falls below 40 mg%. Hence, all infants at risk for hypoglycemia should be screened with reagent strips with the first 2 hours of life. The interval between subsequent measurements of glucose levels depends on clinical judgment. If reagent strips show low glucose levels then blood sugar levels should be determined by collecting blood in a fluoride bulb.
Further Workup
When hypoglycemia lasts over 1 week, evaluate some of the rare causes of hypoglycemia. The following measurements should be considered.
Blood Insulin
Serum Growth hormone
Serum Cortisol
Serum ACTH
Serum Thyroxine
Serum Glucagon
Urinary & plasma amino acids
Urine reducing substances & ketones
Treatment
In neonates with persistent hypoglycemia due to hyperinsulinism
: subtotal pancreatectomy may be needed.
For treatment of acute neonatal or infantile hypoglycemia
: IV glucose - 2 ml/kg of D10w followed by continuous infusion at 6 - 8 mg/kg/min.
For persistent infantile hypoglycemia
: IV glucose infusion may be even up to 8 - 15 mg/kg/min. Glucagon - 0.03 - 0.1 mg/kg/dose IV/IM for patients without initial IV access. Glucagon has no effects in status of starvation, adrenal insufficiency or chronic hypoglycemia.
Other therapies for non-responding hypoglycemia in neonates
:
- IV Hydrocortisone- 5 mg/kg/24 hrs in 3 divided doses
- Oral Diazoxide - 10 - 25 mg/kg/24 hrs in 4 divided doses. Side effects - hirsutism, edema, nausea, electrolyte disturbance, hypoglycemia.
- Octreotide (Long acting somatostatin analog) - 20 - 50 mcg SC every 6 - 12 hrs. Side effects - poor growth, vomiting, diarrhea and hepatic dysfunction.
Complications
Prolonged hypoglycemia is associated with neurological damage. IV glucose can cause hypoglycemia leading to hyperosmolarity, osmotic diuresis, and dehydration.