Neonatal Hypocalcemia

Background

• Neonatal hypocalcemia is a serum calcium level below the lower limit of normal during the newborn period, typically defined as the first 28 days of life.
• Common cutoffs are:
  • in term neonates - total calcium < 8 mg/dL (2 mmol/L) or ionized calcium < 4.8 mg/dL (1.2 mmol/L)
  • in preterm neonates - total calcium < 7 mg/dL (1.75 mmol/L) or ionized calcium < 4 mg/dL (1 mmol/L)
• Clinical presentation
  • Neonatal hypocalcemia may be asymptomatic and detected on screening of at-risk infants or on blood testing for other reasons.
  • Symptoms, if present, may range from mild to life-threatening. Common findings include jitteriness, tetany, vomiting, seizures, apnea, stridor, wheezing, and prolonged QT interval.
• Neonatal hypocalcemia can present soon after birth, or later in the neonatal period, and may be transient or persistent.
  • Hypocalcemia presenting in the first 48 or 72 hours of life is considered early-onset neonatal hypocalcemia, and is usually related to pregnancy, delivery, or early postnatal management.
    • It is often associated with prematurity, intrauterine growth restriction, perinatal stress/asphyxia, and maternal diabetes.
    • It is usually asymptomatic, and often resolves with brief calcium therapy.
  • Late-onset neonatal hypocalcemia is less common, and is often due to a genetic disorder, maternal factors, or iatrogenic causes. It is usually symptomatic, and may be transient, prolonged, or permanent, depending on the underlying cause.
• Causes of neonatal hypocalcemia include high phosphorous-containing formula, hypoparathyroidism, vitamin D disorders, hypomagnesemia, renal insufficiency, and pseudohypoparathyroidism. Iatrogenic causes include medications, phototherapy, blood transfusions, and other interventions during the neonatal period.

Evaluation

• Perform a thorough history and physical exam.
• Measure serum calcium to confirm hypocalcemia.
  • Ionized serum calcium is preferred.
  • If using total calcium, consider measuring albumin and correcting total calcium for hypoalbuminemia.
• Perform additional testing to determine the underlying cause if hypocalcemia persists despite adequate calcium therapy, and consider additional testing in any infant with late-onset neonatal hypocalcemia.
  • Consider the following additional blood tests:
    • parathyroid hormone (PTH)
    • phosphate
    • blood urea nitrogen (BUN)
    • creatinine
    • magnesium
    • alkaline phosphatase
    • vitamin D (25-hydroxyvitamin D, 1,25-dihydroxyvitamin D)
  • Consider maternal blood testing if the etiology of an identified cause is unclear.
  • Consider further testing based on blood test results, for example
    • urine creatinine, calcium, and magnesium levels
    • imaging
    • electrocardiogram (ECG)
    • genetic testing

Management

• Start calcium therapy.
  • Initial treatment
    • For symptomatic neonatal hypocalcemia:
      • give 2 mL/kg of 10% calcium gluconate diluted 1:1 with 5% dextrose by slow IV bolus under cardiac monitoring
      • follow bolus with 80 mg/kg/day of elemental calcium (8 mL/kg/day of 10% calcium gluconate) by continuous IV infusion for 48 hours
      • for treatment-refractory hypocalcemia associated with hypomagnesemia, give 0.2 mL/kg of 50% magnesium sulfate by deep intramuscular injection for 2 doses 12 hours apart, followed by oral magnesium supplementation
    • For asymptomatic neonatal hypocalcemia:
      • give 80 mg/kg/day of elemental calcium IV (continuous infusion preferred) or orally (if tolerating feeds) for 48 hours
  • If serum calcium is normal at 48 hours, continue calcium therapy at 40 mg/kg/day of elemental calcium for 24 hours.
  • If above therapy fails to achieve or maintain normal calcium level, perform additional testing to identify the underlying cause.
• Provide additional treatment as needed based on the underlying cause.
  • For hypoparathyroidism and pseudohypoparathyroidism:
    • give oral calcium and vitamin D supplementation
    • synthetic PTH may be considered if calcium and vitamin D supplementation fails to maintain normocalcemia without hypercalciuria
  • For hypomagnesemia, give oral magnesium supplementation.
  • For vitamin D disorders, give oral vitamin D supplementation.
    • Use ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) for vitamin D deficiency.
    • Use calcitriol or alfacalcidol for disorders of vitamin D metabolism or vitamin D resistance.