Definition of Pediatric Hypoglycemia and Critical Samples
Pediatric hypoglycemia is defined as blood glucose <70 mg/dL (3.9 mmol/L), with increasing severity below 54 mg/dL (3.0 mmol/L), and critical samples should be obtained during hypoglycemic episodes to diagnose the underlying etiology. 1
Hypoglycemia Classification in Pediatrics
The American Diabetes Association defines hypoglycemia in three levels:
Level 1 Hypoglycemia: Blood glucose <70 mg/dL (3.9 mmol/L) but >54 mg/dL (3.0 mmol/L)
- This is the threshold for neuroendocrine responses to falling glucose
- Considered clinically important regardless of symptoms
Level 2 Hypoglycemia: Blood glucose <54 mg/dL (3.0 mmol/L)
- Threshold at which neuroglycopenic symptoms begin
- Requires immediate action to resolve
Level 3 Hypoglycemia: Severe event characterized by altered mental and/or physical functioning
- Requires assistance from another person for recovery
- Defined by clinical presentation rather than specific glucose value 1
Age-Specific Considerations
For neonates and very young infants, different thresholds apply:
- Neonatal hypoglycemia: Blood glucose <45 mg/dL in symptomatic newborns or persistent values <36 mg/dL in repeated measurements 2
- Intervention thresholds:
- Symptomatic infants: <47 mg/dL
- Asymptomatic infants: <45 mg/dL
- Preterm infants: <36 mg/dL
- Any infant (single measurement): <18 mg/dL 2
Critical Samples to Obtain During Hypoglycemia
When hypoglycemia is detected, obtaining a "critical sample" before treatment is essential for diagnosis:
Essential Laboratory Tests:
- Blood glucose (confirm with laboratory method, not just bedside glucometer)
- Insulin level (to identify hyperinsulinism)
- Cortisol (to rule out adrenal insufficiency)
- Growth hormone (to identify growth hormone deficiency)
- Ketone bodies (urine and serum) - absence suggests hyperinsulinism 3
Additional Critical Samples:
- C-peptide (elevated in endogenous hyperinsulinism)
- Free fatty acids (suppressed in hyperinsulinism)
- Lactate and pyruvate (for metabolic disorders)
- Ammonia (for metabolic disorders)
- Acylcarnitine profile (for fatty acid oxidation disorders)
- Amino acids (plasma) (for metabolic disorders)
- Organic acids (urine) (for metabolic disorders)
Timing of Sample Collection
The critical samples must be obtained:
- During the hypoglycemic episode
- Before administering treatment (especially glucose)
- Samples should be properly processed and stored immediately 4, 3
Clinical Approach to Hypoglycemia
Immediate Management:
- Confirm hypoglycemia with laboratory testing
- Collect critical samples before treatment when possible
- Treat hypoglycemia promptly:
- Oral glucose/feeding if patient is alert
- IV dextrose if severe or patient unable to take oral glucose
- Glucagon may be used in emergency situations 5
Risk Factors to Identify:
- Diabetes with insulin therapy
- Prolonged fasting
- Gastroenteritis or infections causing poor intake
- Metabolic disorders (rare but serious)
- Endocrine disorders (hypopituitarism, adrenal insufficiency)
- Congenital hyperinsulinism 6
Important Clinical Considerations
Severe and prolonged hypoglycemia (especially <18-20 mg/dL for >1-2 hours) can cause neurological injury 7
Recurrent hypoglycemia requires thorough investigation to identify underlying cause
Blood glucose monitoring should be performed using blood gas analyzers with glucose modules for most accurate results in infants 2
Symptoms of hypoglycemia may be nonspecific in children and include:
- Altered consciousness
- Seizures
- Lethargy
- Poor feeding
- Irritability 6
The absence of ketones during hypoglycemia is a red flag for hyperinsulinism or fatty acid oxidation disorders and requires urgent investigation 3, 8
Remember that obtaining critical samples during the hypoglycemic episode is crucial for diagnosis, as many abnormalities will normalize once euglycemia is restored.