From the Guidelines
Hypercalcemia in neonates requires prompt recognition and management, and the initial approach involves identifying and treating the underlying cause while implementing supportive measures, with treatment typically beginning with hydration using intravenous normal saline at 1.5-2 times maintenance fluid requirements to promote calcium excretion, as recommended by the most recent guidelines 1.
Causes and Prevalence
Hypercalcemia can occur in neonates due to various causes, including iatrogenic factors, maternal hypoparathyroidism, Williams syndrome, subcutaneous fat necrosis, and certain endocrine disorders. According to a study published in Pediatrics in 2020, the prevalence of hypercalcemia in children with Williams syndrome is estimated to be around 15-40% 1.
Management
The management of hypercalcemia in neonates involves a step-wise approach, starting with:
- Hydration using intravenous normal saline at 1.5-2 times maintenance fluid requirements to promote calcium excretion
- If hypercalcemia persists, furosemide at 1-2 mg/kg/dose every 6-12 hours can be administered to enhance calcium excretion, but electrolytes must be closely monitored, as noted in a study published in the American Journal of Respiratory and Critical Care Medicine in 2003 1
- For moderate to severe cases (calcium >14 mg/dL or symptomatic), calcitonin may be used at 4-8 IU/kg every 6-12 hours subcutaneously or intramuscularly
- In severe or refractory cases, bisphosphonates like pamidronate (0.5-1 mg/kg as a single dose) may be considered, though experience in neonates is limited
- Glucocorticoids can be effective for certain etiologies, particularly vitamin D intoxication or granulomatous diseases, using prednisolone 1-2 mg/kg/day
Monitoring and Long-term Management
Monitoring should include regular calcium, phosphorus, and electrolyte measurements, cardiac monitoring for arrhythmias, and assessment of renal function. Dietary calcium restriction may be necessary in formula-fed infants. Long-term management depends on the underlying cause, with some conditions requiring ongoing treatment and monitoring, as recommended by the American Academy of Pediatrics in 2020 1. Some key points to consider in the management of hypercalcemia in neonates include:
- Regular monitoring of calcium levels and renal function
- Avoiding multivitamin preparations containing vitamin D in early childhood
- Using vitamin D supplementation with caution in older children and adults
- Referral to a pediatric nephrologist and/or pediatric endocrinologist for management of persistent hypercalcemia, hypercalciuria, or nephrocalcinosis.
From the Research
Hypercalcemia in Neonates
- Hypercalcemia is a condition characterized by elevated calcium levels in the blood, which can be caused by various factors, including genetic disorders, maternal hypocalcaemia, and dietary factors 2.
- Neonatal hypercalcemia can present with a range of symptoms, including failure to thrive, poor feeding, constipation, polyuria, irritability, lethargy, seizures, and hypotonia 2.
- The causes of neonatal hypercalcemia can be classified into high or low PTH disorders, with disorders associated with high serum PTH including neonatal severe hyperparathyroidism, familial hypocalciuric hypercalcaemia, and Jansen's metaphyseal chondrodysplasia 2.
- Conditions associated with low serum PTH include idiopathic infantile hypercalcaemia, Williams-Beuren syndrome, and inborn errors of metabolism, including hypophosphatasia 2.
- Severe hypercalcemia can occur in very premature infants due to hypophosphatemia, which can be caused by intrauterine malnutrition, sepsis, and early high-energy parenteral nutrition (PN) 3.
- Treatment of hypercalcemia in neonates depends on the underlying cause, with options including hydration, furosemide, glucocorticoids, and bisphosphonates such as pamidronate 4, 5.
- In cases of hypophosphatemic hypercalcemia, infusion of phosphate (PO4) is necessary to manage the condition, with strict monitoring of calcium and phosphate concentrations 3.
Diagnosis and Treatment
- Diagnosis of hypercalcemia in neonates requires an evaluation of potential causes, assessment of physical features, and biochemical measurements, including total and ionized serum calcium, serum phosphate, creatinine, and albumin, intact parathyroid hormone (PTH), vitamin D metabolites, and urinary calcium, phosphate, and creatinine 2.
- Treatment of hypercalcemia in neonates should be individualized based on the underlying cause and severity of the condition, with the goal of reducing serum calcium levels and improving symptoms 6, 4, 5, 2, 3.
- In some cases, treatment may involve a combination of medications, including bisphosphonates, glucocorticoids, and phosphate supplements, as well as supportive care such as hydration and monitoring of electrolyte levels 6, 4, 5, 2, 3.