• Term or preterm babies birth weight ≥1500 g: total serum calcium <2 mmol/L or ionised fraction <1.1 mmo/L
• Preterm baby, birth weight <1500 g: total serum calcium <1.75 mmol/L or ionised fraction <1 mmol/L

• Early onset occurs in first 2–3 days of life and is usually asymptomatic
• Late onset develops after first 2–3 days of life and typically occurs at the end of the first week
• Most babies are asymptomatic and identified on screening
• Characteristic sign is increased neuromuscular irritability including:
  • jitteriness and irritability 
  • generalised/focal seizures
  • non-specific symptoms e.g.:
    • poor feeding
    • lethargy
    • apnoea
  • prolonged QTc on ECG
  • rare presentations: 
    • stridor
    • bronchospasm
    • pylorospasm

• Early onset:
  • prematurity 
  • intrauterine growth restriction
  • babies of diabetic mother
  • hypoxic ischaemic encephalopathy 
  • hypomagnesaemia 
  • hypoparathyroidism 
  • syndromes e.g. DiGeorge syndrome 
  • maternal hyperparathyroidism 
• Late onset:
  • high phosphate load – cow’s milk, renal failure 
  • hypomagnesaemia
  • parenteral nutrition
  • exchange transfusion
  • alkalosis
  • maternal hypercalcemia
  • maternal vitamin D deficiency
  • transient hypoparathyroidism
  • syndromes and genetic mutations e.g. DiGeorge and Kenny-Caffey syndromes

• Serum calcium
  • only monitor if risk factors, most babies with hypocalcaemia are asymptomatic
  • well preterm baby with birth weight >1500 g and well term babies of diabetic mothers receiving milk feedings on day 1 of life do not need testing routinely 
  • ionised calcium preferred 
  • if using total calcium, measure albumin and correct for hypoalbuminemia
• Phosphate
• Magnesium 
• Persistent hypocalcaemia or severe hypocalcaemia despite adequate calcium therapy: 
  • 25-hydroxyvitamin D level 
  • renal function tests
  • liver function test 
  • alkaline phosphatase 
  • parathyroid hormone level 
  • urinary calcium:creatinine ratio
  • ECG for prolonged QTc interval
  • if pseudohyperparathyroidism suspected, X-ray hand 
  • chest X-ray for thymic shadow
  • if hypoparathyroidism suspected, renal ultrasound 
  • if DiGeorge syndrome suspected, echocardiography 
  • genetic test for gene mutations or suspected syndrome e.g. DiGeorge syndrome

See Flowchart: Diagnostic approach to neonatal hypocalcaemia

Asymptomatic babies

• Most babies with early onset hypocalcaemia recover with nutritional support; so early feeding provides adequate calcium
• Babies requiring IV fluid: add calcium gluconate 10% 0.46 mmol/kg/day (= 2 mL/kg/day) to IV fluid and give as continuous infusion 
  • baby tolerating oral feeds: give 0.25 mmol/kg oral 6-hrly 

Symptomatic hypocalcaemia

• If seizures, prolonged QT interval, apnoea, unstable, hypotension or poor feeding give IV calcium gluconate 10% 0.11 mmol/kg (= 0.5 mL/kg) over 5–10 min followed by maintenance
  • dilute with sodium chloride 0.9% or glucose 5% 4 mL to each 1 mL calcium gluconate 10% to give a concentration of 45 micromol/mL. Can be given undiluted via central line in an emergency
  • doses up to 0.46 mmol/kg (= 2 mL/kg calcium gluconate 10%) have been used 
  • maximum rate of administration 22 micromol/kg/hr
• Stable baby or following acute treatment 
  • oral calcium dose 0.25 mmol/kg 6-hrly
  • if enteral feeds not tolerated add calcium gluconate 10% 0.5 mmol/kg/day to IV fluid as above
• If symptomatic hypocalcaemia: hypomagnesaemia – magnesium sulphate 100 mg/kg IV/ deep IM 12-hrly for 2–3 doses 
• Vitamin D deficiency give 1000–2000 units daily and adjust dose according to response
• Hyperphosphataemia
  • high calcium, low phosphate diet
  • human milk is preferable, if not available, use formula with low phosphate 60/40 and oral calcium 

IV calcium precautions and considerations

• Extravasation can cause skin and subcutaneous tissue necrosis (see Extravasation guideline). Monitor IV site closely
• Continuous infusion preferred to bolus, but use bolus for initial management in symptomatic hypocalcaemia
• Bolus IV calcium can cause dysrhythmias – administer slowly over 5–10 min with cardiac monitoring
• Calcium can be given via UVC provided catheter tip is in vena cava 
  • inadvertent administration into portal vein can cause hepatic necrosis
• Do not mix calcium solutions with those containing phosphorus or bicarbonate as this can cause precipitation

• Monitor bone profile and phosphate levels according to clinical need
• If calcium normal after 48 hr treatment, halve maintenance dose 
• If calcium fails to normalise investigate for underlying cause 
• For extreme preterm babies with late onset hypocalcaemia [see Metabolic bone disease (MBD) guideline]
• Hyperphosphataemia – calcium and phosphate normalise in 3–5 days. Stop calcium after 1 week and switch to normal formula in 2–4 weeks

Flowchart: Diagnostic approach to neonatal hypocalcaemia