Hypocalcemia in Children

Introduction to Hypocalcemia in Children

Hypocalcemia is defined as a serum calcium level below the lower limit of the normal range, which in children is typically <8.8 mg/dL (2.2 mmol/L) for total calcium or <1.12 mmol/L (4.48 mg/dL) for ionized calcium. It is a relatively common electrolyte disturbance in pediatric patients, particularly in neonates and critically ill children.

Calcium plays a crucial role in various physiological processes, including neuromuscular function, bone mineralization, cardiac contractility, and blood coagulation. The regulation of calcium homeostasis involves complex interactions between the parathyroid glands, kidneys, intestines, and bone, mediated by hormones such as parathyroid hormone (PTH), vitamin D, and calcitonin.

Hypocalcemia can result from various conditions affecting calcium metabolism, absorption, or excretion. The clinical manifestations can range from asymptomatic to life-threatening, depending on the severity and acuity of the calcium deficit. Understanding the underlying causes, recognizing the clinical signs, and implementing appropriate management strategies are essential for healthcare providers caring for pediatric patients with hypocalcemia.

Etiology of Hypocalcemia in Children

The causes of hypocalcemia in children can be categorized based on age of onset and underlying mechanisms:

Neonatal Hypocalcemia:

  • Early-onset (<72 hours):
    • Prematurity
    • Intrauterine growth restriction
    • Maternal diabetes mellitus
    • Perinatal asphyxia
  • Late-onset (>72 hours):
    • Cow's milk feeding
    • Vitamin D deficiency
    • Hypoparathyroidism (congenital or acquired)
    • Hypomagnesemia

Hypocalcemia in Infants and Children:

  • Vitamin D deficiency or resistance
  • Hypoparathyroidism:
    • Congenital (e.g., DiGeorge syndrome)
    • Acquired (e.g., post-thyroidectomy, autoimmune)
  • Pseudohypoparathyroidism
  • Chronic kidney disease
  • Acute pancreatitis
  • Hypomagnesemia
  • Medication-induced (e.g., bisphosphonates, loop diuretics)
  • Tumor lysis syndrome
  • Sepsis
  • Hungry bone syndrome (post-parathyroidectomy)

It's important to note that the etiology of hypocalcemia can be multifactorial, and a thorough evaluation is necessary to identify all contributing factors.

Clinical Presentation of Hypocalcemia in Children

The clinical manifestations of hypocalcemia in children can vary widely, depending on the severity, rate of onset, and chronicity of the condition. Symptoms may range from subtle to life-threatening:

Neuromuscular and Neurological Symptoms:

  • Tetany: Muscle cramps, spasms, and paresthesias
  • Laryngospasm and stridor
  • Seizures (especially in neonates)
  • Irritability and agitation
  • Chvostek's sign: Facial muscle twitching when tapping the facial nerve
  • Trousseau's sign: Carpopedal spasm induced by inflating a blood pressure cuff

Cardiovascular Manifestations:

  • Prolonged QT interval on ECG
  • Arrhythmias
  • Heart failure (in severe cases)

Respiratory Symptoms:

  • Apnea (particularly in neonates)
  • Bronchospasm

Musculoskeletal Manifestations:

  • Osteomalacia or rickets (in chronic hypocalcemia)
  • Delayed tooth eruption
  • Dental enamel hypoplasia

Other Symptoms:

  • Failure to thrive
  • Lethargy
  • Poor feeding (in infants)
  • Dry, scaly skin
  • Candidiasis (in hypoparathyroidism)

It's important to note that neonates and young infants may present with nonspecific symptoms, such as jitteriness, lethargy, or poor feeding. Chronic hypocalcemia may be asymptomatic or present with more subtle signs, such as cognitive impairment or cataracts. A high index of suspicion is required for timely diagnosis, especially in high-risk populations.

Diagnosis of Hypocalcemia in Children

The diagnosis of hypocalcemia in children involves a combination of clinical assessment, laboratory tests, and imaging studies:

Laboratory Investigations:

  • Serum calcium: Total and ionized calcium levels
  • Serum phosphorus
  • Serum albumin (to calculate corrected calcium)
  • Serum magnesium
  • Parathyroid hormone (PTH) level
  • 25-hydroxyvitamin D level
  • 1,25-dihydroxyvitamin D level (in select cases)
  • Renal function tests: BUN, creatinine
  • Urinary calcium excretion and calcium/creatinine ratio
  • Alkaline phosphatase

Imaging Studies:

  • Wrist and knee X-rays: To evaluate for rickets in chronic cases
  • Renal ultrasound: To assess for nephrocalcinosis in certain conditions
  • Brain CT or MRI: In cases of suspected intracranial calcifications

Additional Tests (based on suspected etiology):

  • Genetic testing: For suspected congenital disorders (e.g., DiGeorge syndrome, familial hypoparathyroidism)
  • ECG: To assess for prolonged QT interval
  • Parathyroid imaging: In cases of suspected hypoparathyroidism

Diagnostic Approach:

  1. Confirm hypocalcemia with total and ionized calcium levels
  2. Assess the severity and presence of symptoms
  3. Evaluate PTH levels to differentiate between hypoparathyroidism and secondary causes
  4. Check vitamin D status
  5. Assess magnesium levels, as hypomagnesemia can cause functional hypoparathyroidism
  6. Consider underlying conditions based on clinical presentation and initial laboratory findings
  7. Perform additional targeted testing based on suspected etiology

The diagnostic approach should be tailored to the individual patient, considering their age, clinical presentation, and initial laboratory findings. A systematic evaluation is crucial to identify the underlying cause and guide appropriate management.

Treatment of Hypocalcemia in Children

The management of hypocalcemia in children depends on the severity of the condition, the presence of symptoms, and the underlying cause. Treatment strategies can be divided into acute management and long-term treatment:

Acute Management:

  1. Symptomatic or Severe Hypocalcemia:
    • Intravenous calcium:
      • Calcium gluconate 10%: 1-2 mL/kg (maximum 20 mL) over 10-20 minutes
      • Follow with continuous infusion: 50-75 mg/kg/day
    • Monitor cardiac rhythm during administration
    • Avoid extravasation due to risk of tissue necrosis
  2. Asymptomatic or Mild Hypocalcemia:
    • Oral calcium supplementation:
      • Elemental calcium: 30-75 mg/kg/day divided in 3-4 doses
  3. Magnesium Replacement (if hypomagnesemia is present):
    • Intravenous magnesium sulfate: 25-50 mg/kg/dose (maximum 2 g)

Long-term Management:

  • Treatment of the underlying cause
  • Oral calcium supplementation:
    • Elemental calcium: 30-75 mg/kg/day divided in 3-4 doses
  • Vitamin D supplementation:
    • Cholecalciferol (Vitamin D3): 1000-2000 IU/day
    • Calcitriol (1,25-dihydroxyvitamin D): 0.25-1 mcg/day in divided doses
  • Dietary counseling to ensure adequate calcium intake
  • In hypoparathyroidism:
    • Recombinant human PTH (if available and indicated)
  • Regular monitoring of serum calcium, phosphorus, magnesium, and vitamin D levels
  • Monitoring of urinary calcium excretion to avoid hypercalciuria

Special Considerations:

  • Neonatal hypocalcemia:
    • May require higher doses of calcium and vitamin D
    • Consider early feeding with human milk or low-phosphate formula
  • Hypoparathyroidism:
    • May require lifelong calcium and vitamin D supplementation
    • Close monitoring to avoid overtreatment and hypercalciuria
  • Vitamin D deficiency:
    • May require higher initial doses of vitamin D for repletion

Treatment should be individualized based on the patient's age, severity of hypocalcemia, underlying cause, and response to therapy. Close monitoring and multidisciplinary care involving pediatric endocrinologists, nephrologists, and other specialists as needed are essential for optimal outcomes.

Complications of Hypocalcemia in Children

Untreated or poorly managed hypocalcemia can lead to various complications affecting multiple organ systems:

Acute Complications:

  • Neurological:
    • Seizures
    • Tetany
    • Laryngospasm
    • Altered mental status
  • Cardiovascular:
    • Arrhythmias (due to prolonged QT interval)
    • Heart failure (in severe cases)
  • Respiratory:
    • Apnea (especially in neonates)
    • Bronchospasm

Chronic Complications:

  • Skeletal:
    • Rickets or osteomalacia
    • Osteoporosis
    • Dental abnormalities (enamel hypoplasia, delayed tooth eruption)
  • Neurological:
    • Cognitive impairment
    • Basal ganglia calcifications
    • Parkinsonism (in severe, longstanding cases)
  • Ocular:
    • Cataracts (especially in hypoparathyroidism)
    • Papilledema
  • Dermatological:
    • Dry, scaly skin
    • Chronic mucocutaneous candidiasis (in hypoparathyroidism)
  • Growth and Development:
    • Growth retardation
    • Developmental delays
  • Psychological:
    • Anxiety
    • Depression
    • Irritability

Complications of Treatment:

  • Hypercalciuria (due to excessive calcium supplementation)
  • Nephrocalcinosis or nephrolithiasis
  • Iatrogenic hypercalcemia
  • Soft tissue calcifications
  • Vitamin D toxicity (if oversupplemented)

Long-term Sequelae:

  • Reduced bone mineral density and increased fracture risk
  • Chronic kidney disease (due to nephrocalcinosis or recurrent stone formation)
  • Impaired quality of life
  • Cognitive and behavioral issues

The severity and type of complications depend on the duration and degree of hypocalcemia, as well as the underlying cause. Early recognition and appropriate management are crucial to prevent these potentially serious complications. Regular monitoring and follow-up are essential, especially in children, to ensure normal growth and development and to address any complications promptly.

In cases of chronic hypocalcemia, such as in hypoparathyroidism, a multidisciplinary approach involving endocrinologists, nephrologists, neurologists, and other specialists may be necessary to manage the various aspects of the condition and its complications effectively.



Hypocalcemia in Children
  1. What is the definition of hypocalcemia in children?
    Hypocalcemia is defined as a total serum calcium level below 8.8 mg/dL (2.2 mmol/L) in children.
  2. What are the most common causes of hypocalcemia in neonates?
    The most common causes in neonates are prematurity, maternal diabetes, and perinatal asphyxia.
  3. Which vitamin deficiency is closely associated with hypocalcemia?
    Vitamin D deficiency is closely associated with hypocalcemia in children.
  4. What is the role of parathyroid hormone (PTH) in calcium regulation?
    PTH increases serum calcium levels by promoting bone resorption, increasing renal calcium reabsorption, and enhancing vitamin D activation.
  5. What are the clinical manifestations of acute hypocalcemia in children?
    Clinical manifestations include neuromuscular irritability, tetany, seizures, and in severe cases, laryngospasm and cardiac arrhythmias.
  6. How is Chvostek's sign elicited and what does it indicate?
    Chvostek's sign is elicited by tapping the facial nerve in front of the ear, causing facial muscle twitching. It indicates neuromuscular irritability due to hypocalcemia.
  7. What is Trousseau's sign and how is it performed?
    Trousseau's sign is performed by inflating a blood pressure cuff above systolic pressure for 3 minutes. A positive sign is carpopedal spasm, indicating hypocalcemia.
  8. Which laboratory tests are essential for diagnosing hypocalcemia?
    Essential tests include serum total and ionized calcium, phosphorus, magnesium, PTH, and 25-hydroxyvitamin D levels.
  9. How does hypomagnesemia contribute to hypocalcemia?
    Hypomagnesemia can cause functional hypoparathyroidism and end-organ resistance to PTH, leading to hypocalcemia.
  10. What is the primary treatment for severe, symptomatic hypocalcemia?
    The primary treatment is intravenous calcium gluconate administration.
  11. How is the dose of elemental calcium calculated for IV administration?
    The dose is typically 0.5-1 mg/kg of elemental calcium, given slowly over 5-10 minutes.
  12. What precautions should be taken when administering IV calcium?
    Precautions include slow administration, cardiac monitoring, and avoiding extravasation to prevent tissue necrosis.
  13. How does chronic hypocalcemia affect bone health in children?
    Chronic hypocalcemia can lead to rickets, osteomalacia, and impaired bone mineralization.
  14. What is the role of calcitriol in treating hypocalcemia?
    Calcitriol, the active form of vitamin D, enhances intestinal calcium absorption and is used in treating hypocalcemia, especially in cases of vitamin D deficiency or resistance.
  15. How does hypoparathyroidism cause hypocalcemia?
    Hypoparathyroidism leads to decreased PTH secretion, resulting in reduced calcium mobilization from bone, decreased renal calcium reabsorption, and reduced vitamin D activation.
  16. What genetic condition is associated with hypocalcemia and facial dysmorphism?
    DiGeorge syndrome (22q11.2 deletion syndrome) is associated with hypocalcemia due to hypoparathyroidism and characteristic facial features.
  17. How does hyperphosphatemia contribute to hypocalcemia?
    Hyperphosphatemia can cause hypocalcemia by forming calcium-phosphate complexes and reducing ionized calcium levels.
  18. What is the significance of measuring ionized calcium versus total calcium?
    Ionized calcium measurement is more accurate in assessing true calcium status, especially in patients with abnormal protein levels or acid-base disturbances.
  19. How does alkalosis affect calcium levels?
    Alkalosis increases calcium binding to proteins, reducing ionized calcium levels and potentially causing symptomatic hypocalcemia.
  20. What is the appropriate oral calcium supplementation dose for children with chronic hypocalcemia?
    The typical dose is 30-75 mg/kg/day of elemental calcium, divided into 2-4 doses.
  21. How does loop diuretic use contribute to hypocalcemia?
    Loop diuretics increase urinary calcium excretion, potentially leading to hypocalcemia, especially with prolonged use.
  22. What is the role of phosphate binders in managing hypocalcemia in children with chronic kidney disease?
    Phosphate binders help control serum phosphate levels, indirectly improving calcium levels and reducing the risk of secondary hyperparathyroidism.
  23. How does sepsis contribute to hypocalcemia in critically ill children?
    Sepsis can cause hypocalcemia through various mechanisms, including vitamin D deficiency, hypomagnesemia, and altered PTH function.
  24. What is the relationship between hypocalcemia and seizures in children?
    Hypocalcemia can lower the seizure threshold and cause seizures, particularly in neonates and young infants.
  25. How does pancreatitis lead to hypocalcemia?
    Pancreatitis can cause hypocalcemia through saponification of calcium in areas of fat necrosis and release of glucagon, which inhibits bone resorption.
  26. What is the significance of QT interval prolongation in hypocalcemia?
    QT interval prolongation on ECG is a sign of severe hypocalcemia and increases the risk of cardiac arrhythmias.
  27. How does vitamin D deficiency rickets present in children?
    Vitamin D deficiency rickets presents with bowing of long bones, widening of wrists and ankles, delayed fontanelle closure, and in severe cases, hypocalcemic seizures.
  28. What is the role of calcium-sensing receptors in calcium homeostasis?
    Calcium-sensing receptors in the parathyroid glands and kidneys detect changes in serum calcium levels and regulate PTH secretion and renal calcium handling.
  29. How does total parenteral nutrition (TPN) contribute to hypocalcemia in hospitalized children?
    Inadequate calcium and vitamin D supplementation in TPN, coupled with potential citrate excess from blood products, can lead to hypocalcemia.
  30. What is the appropriate management of hypocalcemia in a child with hypoparathyroidism?
    Management includes calcium supplementation, active vitamin D analogs (calcitriol), and regular monitoring of serum calcium, phosphorus, and urinary calcium excretion.


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