107: Magnesium Disorders (Hypomagnesemia, Hypermagnesemia)

As noted in Chapter 85, abnormalities of magnesium (Mg⁺²) and calcium (Ca⁺²) metabolism are commonly seen in the neonatal intensive care unit. Calcium disturbances may be mirrored by magnesium, as in hypocalcemia with hypomagnesemia or hypercalcemia with hypermagnesemia. Infants of diabetic mothers (IDMs) and infants with intrauterine growth restriction (IUGR) may present with hypocalcemia, hypomagnesemia, or both. Abnormalities in serum values for Ca⁺² and Mg⁺² are of concern in any infant and warrant further investigation.

1. Definition. Normal serum levels for Mg⁺² are typically 0.6–1.0 mmol/L (1.6–2.4 mg/dL). Hypomagnesemia is usually seen as any value <0.66 mmol/L (1.6 mg/dL); however, clinical signs do not manifest until levels drop below 0.5 mmol/L (1.2 mg/dL).

2. Incidence. True overall incidence in neonates is not well documented and remains to be determined; however, neonates appear to be more predisposed than other groups of patients, and the most frequent occurrence tends to follow that of those infants with hypocalcemia.

3. Pathophysiology. Mg⁺² is a key trace element for maintaining skeletal integrity, and it acts as a catalyst for intracellular enzymes for adenosine triphosphate (ATP) activation in skeletal and myocardial contractility. It has an important role in different processes related to cell physiology, hormonal and metabolic pathways, nerve conduction, and blood coagulation. It is also integral to protein synthesis, vitamin D metabolism, parathyroid function, and calcium homeostasis.

4. Risk factors

   1. Hypocalcemia

   2. Preterm and late-preterm infants

   3. Inadequate intake of magnesium

   4. Infant of diabetic mother (IDM), reflecting maternal Mg⁺² deficiency secondary to gestational diabetes

   5. IUGR, especially if mother had preeclampsia

   6. Inherited renal wasting (eg, Gitelman syndrome, Na⁺-K-ATPase mutation, others)

   7. Hypoparathyroidism

   8. Associated hypocalciuria and nephrocalcinosis

   9. Magnesuria secondary to furosemide or gentamicin

   10. Citrated blood exchange transfusions

5. Clinical presentation

   1. Similar to hypocalcemia (see Chapter 85, Section I.E) (eg, jitteriness, apnea, feeding intolerance), and may also present as seizures.

   2. Clinical signs may be masked as hypocalcemia. If symptoms persist after adequate calcium gluconate therapy, hypomagnesemia should be considered.

6. Diagnosis. Laboratory testing to establish serum levels.

   1. Serum magnesium level. Normal values are 0.6–1.0 mmol/L (1.6–2.4 mg/dL), although it may vary minimally with gestational age. Twin gestation, multiple births, or vaginal delivery may result in lower levels of Mg⁺². It is important to note that most methods to assess Mg⁺² levels measure total Mg⁺² concentration, while only free Mg⁺² is biologically active and almost 30% is inactive bound to albumin.

   2. Total and ionized calcium levels. Usually hypomagnesemia is associated with hypocalcemia, and hypercalcemia may inhibit magnesium reabsorption in the distal loop of Henle and cause hypomagnesemia.

7. Prevention. Adequate intake of magnesium should be assured in parenteral and enteral nutrition to prevent hypomagnesemia (recommend 8–15 mg/kg/d).

8. Management. Acute hypomagnesemia should be treated with intravenous magnesium sulfate (see Chapter 148 for specific dosing guidelines). Infusion must be monitored closely for cardiac arrhythmias and hypotension. Maintenance Mg⁺² can be by parenteral nutrition solutions or by oral feeds with 5-fold dilution of Mg⁺² salt solution. Mg⁺² infusion should be used cautiously if patient has impaired renal function due to its accumulated toxicity.

9. Prognosis. Hypomagnesemia generally has good outcome if diagnosed promptly and treated adequately. The exception is a clinical presentation that includes hypomagnesemia-induced seizures with follow-up studies suggesting ≥20% incidence of neurologic abnormalities.

1. Definition. Reference levels of serum magnesium signifying hypermagnesemia vary from >1.15 mmol/L (2.3 mg/dL) to >1.5 mmol/L (3.0 mg/dL).

2. Incidence. Largely unknown, however, it occurs more frequently in infants whose mothers have been treated with magnesium sulfate. Otherwise, it occurs rarely in healthy newborns. There have been 5 trials over the past decade, which included a total of 6145 patients, to study the effects of magnesium sulfate as neuroprotection to reduce the incidence of cerebral palsy in neonates. Two published meta-analyses analyzed these trials and concluded that there is enough evidence to support the use of magnesium sulfate for reducing cerebral palsy. The American College of Obstetrics and Gynecology and Australian national guidelines have recommended the prenatal administration of magnesium sulfate as neuroprotection for preterm infants. This new trend of magnesium sulfate use may increase the incidence of hypermagnesemia in preterm infants being admitted to neonatal units.

3. Pathophysiology. Increased serum Mg⁺² levels depress the central nervous system, impair electrical conduction, and decrease skeletal muscle contractility. Antenatal magnesium sulfate administration to mothers before preterm delivery may have a neuroprotective role and decreased incidence of cerebral palsy in infants. Magnesium may serve as an N-methyl-d-aspartate (NMDA) receptor antagonist, membrane stabilizer, vasodilator, and anticonvulsive. Mg⁺² also has anticonvulsive properties (by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse) that may contribute to diminish extension of brain damage. Mg⁺² may reduce vascular instability, prevent hypoxic damage, and mitigate cytokine or excitatory amino acid damage, all of which threaten the vulnerable preterm brain.

4. Risk factors

   1. Increased maternal serum levels following magnesium sulfate therapy for pregnancy-related hypertension, preeclampsia, and neonatal neuroprotection before preterm delivery.

   2. Excessive magnesium sulfate administration to an infant with hypomagnesemia (iatrogenic medication error) or following administration of Mg⁺²-containing antacids, especially if dehydrated. Excess magnesium in total parenteral nutrition (TPN) is a cause.

5. Clinical presentation. Severity of symptoms and signs of hypermagnesemia may not correlate with serum Mg⁺² levels. Symptoms may mimic hypercalcemia.

   1. Hypotonia, hypotension, hyporeflexia, seizures

   2. Respiratory depression, hypoventilation, apnea

   3. Bradycardia, hypotension, cardiac arrest with toxic Mg⁺² levels (ie, >7.5 mmol/L)

   4. Poor suck, feeding intolerance, decreased gastrointestinal motility, increased gastric aspirates, abdominal distention, and delayed meconium passage

   5. Meconium plug syndrome, intestinal perforation

   6. Urinary retention

6. Diagnosis

   1. Laboratory studies

      1. Serum magnesium. Normal levels are 0.6–1.0 mmol/L (1.6–2.4 mg/dL).

      2. Serum calcium. Always determine both total and ionized calcium levels with Mg⁺² abnormalities.

   2. Electrocardiogram. May reveal a prolonged PR interval, increased QRS interval, prolonged QT interval, and AV block.

7. Management

   1. Identify and remove the source of excess magnesium (ie, TPN, antacids).

   2. Urinary excretion is the only mechanism for decreasing serum Mg⁺² levels.

   3. Maintain IV hydration if the patient is symptomatic.

   4. Furosemide diuresis may facilitate Mg excretion, but close monitoring of electrolytes is needed and its effect is not well studied.

   5. Monitor serum electrolytes, urine output, and acid-base status.

   6. With acute signs such as seizures or electrocardiogram (ECG) changes, give IV calcium gluconate in doses as for hypocalcemia Early-onset hypocalcemia (first week of life).

   7. Avoid aminoglycosides as they may potentiate the neuromuscular manifestations of hypermagnesemia.

   8. Respiratory support may be needed in severely affected infants (hypoventilation, apnea).

   9. Exchange transfusion has been used. Dialysis is uncommon in neonates.

8. Prognosis is good following treatment, especially if normal renal function has been preserved. In general, antenatal use of magnesium sulfate is very safe in the postnatal period. It has been successfully used in multiple trials, but in 1 recent study, increased mortality in neonates has been reported with the use of magnesium sulfate administration for neuroprotection.