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Neonatal Hypocalcemia

By

Kevin C. Dysart

, MD, Nemours/Alfred I. duPont Hospital for Children

Last full review/revision Mar 2021| Content last modified Mar 2021
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Hypocalcemia is a total serum calcium 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 calcium 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 calcium supplementation.

Etiology of Neonatal Hypocalcemia

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 DiGeorge Syndrome DiGeorge syndrome is thymic and parathyroid hypoplasia or aplasia leading to T-cell immunodeficiency and hypoparathyroidism. Infants with DiGeorge syndrome have low-set ears, midline facial... read more ) with agenesis or dysgenesis of the parathyroid glands have both early and late (prolonged) hypocalcemia.

Early-onset hypocalcemia

Risk factors for early-onset hypocalcemia include prematurity, being small for gestational age Small-for-Gestational-Age (SGA) Infant Infants whose weight is the 10th percentile for gestational age are classified as small for gestational age. Complications include perinatal asphyxia, meconium aspiration, polycythemia, and... read more , maternal diabetes Diabetes Mellitus in Pregnancy Pregnancy aggravates preexisting type 1 (insulin-dependent) and type 2 (non–insulin-dependent) diabetes but does not appear to exacerbate diabetic retinopathy, nephropathy, or neuropathy (1)... read more , and perinatal asphyxia. Mechanisms vary. Normally, parathyroid hormone helps maintain normal calcium levels when the constant infusion of ionized calcium across the placenta is interrupted at birth. A transient, relative hypoparathyroidism may cause hypocalcemia in preterm neonates Premature Infants An infant born before 37 weeks gestation is considered premature. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing read more 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 calcium levels during pregnancy. Perinatal asphyxia may also increase serum calcitonin, which inhibits calcium release from bone and results in hypocalcemia. In other neonates, the normal phosphaturic renal response to parathyroid hormone is absent; the elevated phosphate 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 phosphate load; elevated serum phosphate leads to hypocalcemia.

Symptoms and Signs of Neonatal Hypocalcemia

Symptoms and signs of neonatal hypocalcemia rarely occur unless total serum calcium is < 7 mg/dL (< 1.75 mmol/L) or the ionized calcium 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 of Neonatal Hypocalcemia

  • Total or ionized serum calcium level

Diagnosis of neonatal hypocalcemia is by measurement of total or ionized serum calcium; ionized calcium is the more physiologic measurement, because it does not require correction for protein concentration and pH. Prolongation of the corrected QT interval (QTc) on ECG also suggests hypocalcemia.

Treatment of Neonatal Hypocalcemia

  • Early onset: IV 10% calcium gluconate

  • Late onset: Oral calcitriol or calcium

Early-onset hypocalcemia ordinarily resolves in a few days, and asymptomatic neonates with serum calcium levels > 7 mg/dL (1.75 mmol/L) or ionized calcium > 3.5 mg/dL (0.88 mmol/L) rarely require treatment. Those term infants with levels < 7 mg/dL (1.75 mmol/L) and preterm infants with calcium < 6 mg/dL (< 1.5 mmol/L) should be treated with 200 mg/kg of 10% calcium gluconate by slow IV infusion over 30 minutes. 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 calcium solution is irritating and may cause local tissue damage or necrosis. Manifestations of calcium infiltration include skin redness, calcification, and necrosis or slough; there can be radial nerve damage at the wrist.

After acute correction of hypocalcemia, calcium gluconate may be mixed in the maintenance IV infusion and given continuously. Starting with 400 mg/kg/day of calcium 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 calcium gluconate, if needed, by adding the 10% calcium gluconate solution into the day’s formula. Supplementation is usually required for only a few days.

Late-onset hypocalcemia treatment is addition of calcitriol or additional calcium to infant formula until normal calcium levels are maintained; a low-mineral formula (including low phosphate) as for infants with impaired renal function may be helpful. Oral calcium preparations have a high sucrose content, which may lead to diarrhea in preterm infants.

Key Points

  • Neonatal hypocalcemia usually occurs within the first 2 days of life and is most often caused by prematurity, being small for gestational age, maternal diabetes or hyperparathyroidism, and perinatal asphyxia.

  • Neonates may have hypotonia, tachycardia, tachypnea, apnea, poor feeding, jitteriness, tetany, and/or seizures.

  • Diagnose by measuring total or ionized serum calcium level; measure glucose level to rule out hypoglycemia.

  • Treat early-onset hypocalcemia with IV 10% calcium gluconate, followed by several days of oral calcium supplementation.

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