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Neonatal Hypocalcemia

by Nicholas Jospe, MD

Hypocalcemia is a serum total Ca concentration < 8 mg/dL (< 2 mmol/L) in term infants or < 7 mg/dL (< 1.75 mmol/L) in preterm infants. It is also defined as an ionized Ca level < 3.0 to 4.4 mg/dL (< 0.75 to 1.10 mmol/L), depending on the method (type of electrode) used. Signs are primarily neurologic and include hypotonia, apnea, and tetany. Treatment is IV or oral Ca supplementation.

Etiology

Neonatal hypocalcemia occurs in 2 forms:

  • Early onset (in the first 2 days of life)

  • Late onset (> 3 days), which is rare

Some infants with congenital hypoparathyroidism (eg, caused by DiGeorge syndrome with agenesis or dysgenesis of the parathyroid glands [see DiGeorge Syndrome]) have both early and late (prolonged) hypocalcemia.

Early-onset hypocalcemia

Risk factors for early-onset hypocalcemia include prematurity, being small for gestational age, maternal diabetes, and perinatal asphyxia. Mechanisms vary. Normally, parathyroid hormone helps maintain normal Ca levels when the constant infusion of ionized Ca across the placenta is interrupted at birth. A transient, relative hypoparathyroidism may cause hypocalcemia in preterm and some small-for-gestational-age neonates, who have parathyroid glands that do not yet function adequately, and in infants of mothers with diabetes or hyperparathyroidism, because these women have higher-than-normal ionized Ca levels during pregnancy. Perinatal asphyxia may also increase serum calcitonin, which inhibits Ca release from bone and results in hypocalcemia. In other neonates, the normal phosphaturic renal response to parathyroid hormone is absent; the elevated phosphate (PO 4 ) level leads to hypocalcemia.

Late-onset hypocalcemia

The cause of late-onset hypocalcemia is usually ingestion of cow’s milk or formula with a too-high PO 4 load; elevated serum PO 4 leads to hypocalcemia.

Symptoms and Signs

Symptoms and signs rarely occur unless total serum Ca is < 7 mg/dL (< 1.75 mmol/L) or the ionized Ca is < 3.0 mg/dL (< 0.75 mmol/L). Signs include hypotonia, tachycardia, tachypnea, apnea, poor feeding, jitteriness, tetany, and seizures. Similar symptoms may occur with hypoglycemia and opioid withdrawal.

Diagnosis

  • Total or ionized serum Ca level

Diagnosis is by measurement of serum total or ionized Ca; ionized Ca is the more physiologic measurement, because it obviates concerns about protein concentration and pH. Prolongation of the corrected QT interval (QT c ) on ECG also suggests hypocalcemia.

Treatment

  • Early onset: IV 10% Ca gluconate

  • Late onset: Oral calcitriol or Ca

Early-onset hypocalcemia ordinarily resolves in a few days, and asymptomatic neonates with serum Ca levels > 7 mg/dL or ionized Ca > 3.5 mg/dL rarely require treatment. Those term infants with levels < 7 mg/dL and preterm infants with Ca < 6 mg/dL (< 1.5 mmol/L) should be treated with 2 mL/kg of 10% Ca gluconate (200 mg/kg) by slow IV infusion over 30 min. Too-rapid infusion can cause bradycardia, so heart rate should be monitored during the infusion. The IV site should also be watched closely because tissue infiltration by a Ca solution is irritating and may cause local tissue damage or necrosis. Manifestations of Ca infiltration include skin redness, calcification, and necrosis or slough; there can be radial nerve damage at the wrist.

After acute correction of hypocalcemia, Ca gluconate may be mixed in the maintenance IV infusion and given continuously. Starting with 400 mg/kg/day of Ca gluconate, the dose may be increased gradually to 800 mg/kg/day, if needed, to prevent a recurrence. When oral feedings are begun, the formula may be supplemented with the same daily dose of Ca gluconate, if needed, by adding the 10% Ca gluconate solution into the day’s formula. Supplementation is usually required for only a few days.

Treatment of late-onset hypocalcemia is addition of calcitriol or additional Ca to infant formula to provide a 4:1 molar ratio of Ca:PO 4 until normal Ca levels are maintained. Oral Ca preparations have a high sucrose content, which may lead to diarrhea in preterm infants.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • MIACALCIN
  • ROCALTROL

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