Neonatal Hypomagnesaemia

Neonatal hypomagnesaemia is a serum magnesium under 0.6 mmol/L (1.5 mg/dL). It often coexists with hypocalcaemia and causes hypocalcaemia that does not respond to calcium alone.

It is uncommon. It appears in the first week of life in infants of mothers with diabetes or magnesium deficiency, in growth restricted infants and after exchange transfusion.

Other causes are intestinal malabsorption, renal magnesium wasting, hypoparathyroidism, polyuria, drugs (aminoglycosides, loop diuretics, amphotericin, proton pump inhibitors) and refeeding. Hypomagnesaemia with secondary hypocalcaemia from TRPM6 variants presents at 2 to 8 weeks of age with seizures.

Pathophysiology.

Magnesium is needed for the release of parathyroid hormone and for its action at the bone and kidney. Magnesium deficiency causes functional hypoparathyroidism and hypocalcaemia that resists calcium.

Low magnesium also raises neuromuscular and neuronal excitability, leading to tremor, tetany and seizures, and can cause arrhythmia and hypokalaemia.

• Jitteriness, tremor, hyperreflexia, tetany, apnoea and seizures that do not respond to calcium or anticonvulsants.
• Arrhythmia with prolonged QT interval and ST changes.
• Poor feeding and vomiting.

Red flags.

• Seizures with normal glucose and normal calcium.
• Hypocalcaemia resistant to calcium treatment.
• Onset at 2 to 8 weeks with seizures and hypocalcaemia, suggesting TRPM6 disease.

• Serum magnesium, ionised calcium, phosphate, potassium, creatinine, parathyroid hormone and glucose.
• Urine magnesium to creatinine ratio: low in gut losses, high in renal wasting.
• ECG for QT interval. Maternal magnesium and glucose in early disease.
• Genetic testing for TRPM6 when onset is late and magnesium is persistently low.

Differential diagnosis. Hypocalcaemia, hypoglycaemia, hypoxic injury, infection, hypomagnesaemia from renal tubulopathy and other causes of neonatal seizures.

Acute treatment.

• Magnesium sulphate 50% 0.1 mL/kg (50 mg/kg, 0.2 mmol/kg) by IV infusion over 30 to 60 minutes with ECG monitoring. Repeat every 12 hours until magnesium is over 0.7 mmol/L. Dilute to 10% or less for infusion.
• Treat hypocalcaemia as well with calcium gluconate 10% 1 to 2 mL/kg IV slowly over 10 to 30 minutes.
• Monitor reflexes, respiratory rate, blood pressure and urine output to detect overdose. If hypermagnesaemia causes bradycardia or apnoea, give calcium gluconate 10% 1 to 2 mL/kg IV slowly and support ventilation.

Maintenance.

• Oral magnesium 0.2 to 0.4 mmol/kg/day in 3 or 4 divided doses for dietary deficiency or malabsorption, reducing the dose if diarrhoea develops.
• TRPM6 disease: lifelong high dose oral magnesium, usually 0.4 to 0.8 mmol/kg/day in 3 or 4 divided doses, titrated to serum magnesium and tolerance.
• Correct potassium and treat the cause.

Monitoring. Magnesium, calcium and potassium every 12 to 24 hours during treatment, then at each dose change.

Referral and escalation. Refer to paediatric endocrinology or nephrology for persistent or recurrent hypomagnesaemia or a suspected genetic cause.

Special groups. In renal impairment, reduce the magnesium dose and monitor levels closely to avoid hypermagnesaemia.