Neonatal hypocalcaemia seen transiently in the first few days of life is commonly referred to as early neonatal hypocalcaemia. This is often seen in preterm infants and has been explained as an exaggeration of the normal postnatal decrease in serum calcium levels. Early neonatal hypocalcaemia appears to occur with greater frequency in asphyxiated babies and in infants of diabetic mothers (IDM) than otherwise. The hypocalcaemia seen in IDM is probably multifactorial. Magnesium deficiency has been implicated, as well as alterations in maternal metabolism secondary to poor glucose control throughout gestation. Whether the normal postnatal increase in PTH secretion is blunted is not entirely clear.
Late neonatal hypocalcaemia occurs after 5– 7 days of life and is more characteristic of the term infant. Late neonatal hypocalcaemia often presents with seizures and is less likely to be transient in nature. Hypoparathyroidism and magnesium deficiency often present in this time frame. Hypocalcaemia in babies with congenital heart disease of many types has been reported as a relatively common finding. Hypocalcaemia related to vitamin D deficiency may pre sent at several weeks of age, however, radiographic evidence of rickets is usually not observed until over 2 months of age.
One classic situation in which prolonged neonatal hypocalcaemia occurs is in the infant of the hyperparathyroid mother. Presumably the maternal hypercalcaemia results in increased trans port of calcium from the maternal to fetal circulation. The resultant excess calcium supply to the fetus is thought to suppress para thyroid responsivity, and prolonged hypoparathyroidism results. Symptomatic hypocalcaemia and hyperphosphataemia are typical biochemical features; hypomagnesaemia may occur as well. The disorder is usually transient, but some cases have been prolonged for months. Unrecognized maternal hyperparathyroidism should be carefully investigated in children that present with the characteristic features of the disorder. Maternal familial hypocalciuric hypercalcaemia (FHH) can result in this syndrome. We have encountered similar cases due to excessive maternal ingestion of calcium- containing antacids during pregnancy, suggesting that other causes of chronic maternal hypercalcaemia can result in a similar clinical picture.
Hypocalcaemia in the newborn setting may also occur during blood transfusions using citrated blood products. Citrate complexes with ionized calcium, reducing its circulating concentration to a level where neuromuscular hyperexcitability may occur. Total serum calcium is usually not decreased. Hypocalcaemia can occur in the congenital nephrotic syndrome. Persistent hypocalcaemia may present in this time frame as well. Congenital hypoparathyroidism may be present, as in the DiGeorge syndrome. The classic triad of this chromosome 22 deletion syndrome (hypoparathyroidism, athymia, and cono- truncal defects of the heart) typically results in long- standing hypoparathyroidism, although ‘partial’ hypoparathyroidism has been described. (See next for a detailed de scription of congenital disorders of the parathyroid glands.) Severe osteopetrosis may present with hypocalcaemia secondary to impaired mobilization of calcium from bone. Typically, PTH levels are elevated in order to compensate for the hypocalcaemia engendered by defective osteoclastic bone resorption in such cases. Severe vitamin D deficiency is generally an acquired condition manifest as hypocalcaemia as early as 2 to 3 months, but low maternal stores have rarely contributed to its development in an even younger age range.
Osteopaenia of prematurity is commonly encountered in pre mature infants. Poor bone mineralization is evident on radiographs or other measures of BMD. In general, the problem is more severe in children of lower birth weight. With increasing survival of children with birth weights less than 1000 grams the severity of this problem is increasing. Classical rachitic changes of flared and frayed epiphyses, craniotabes, and a rachitic rosary may develop over the first months of life. The histologic pattern of bone is thought to be a combined lesion with components of osteomalacia and osteo porosis. This disorder is a consequence of premature withdrawal of the maternal mineral supply. The enteral route, even with maximum feeding delivery, cannot provide for the mineral demands of the skeleton as it rapidly grows and mineralizes throughout the latter weeks of gestation. The problem often occurs in the setting of normocalcaemia. In preterm infants fed solely with breast milk, a phosphate deficiency syndrome may occur, as the phosphate con tent of breast milk is considerably less than that of commonly used in cow’s milk formulas. Although breast milk phosphate is adequate for the growth of the term infant’s skeleton, human breast milk fortifiers are routinely used to increase the mineral intake of the preterm infant. One caveat regarding the use of such fortifiers: calcium intake, if excessive, can result in hypercalcaemia, as its absorption is not tightly regulated in early infancy, and the fractional absorption of calcium can be very high in a low birth weight premature infant.
Treatment of Neonatal Hypocalcaemia
Symptomatic infants are treated with calcium, but there is controversy regarding treatment of hypocalcaemic infants who are asymptomatic. The emergency treatment of neonatal hypocalcaemia consists of intravenous administration of 1 ml/ min of 10% calcium gluconate, which should not exceed 2.0 ml per kg body weight (which is equivalent to ~19 mg of elemental calcium per kilogram). This may be repeated three to four times in 24 hours. After acute symptoms have been managed, 5.0 ml/ kg of 10% calcium gluconate may be given with intravenous fluids over 24 hours. It should be emphasized that repetitive and frequent boluses of high- dose intravenous calcium only temporarily raise the serum calcium level and an enormous renal calcium load result. Thus the favoured way of longer- term management when the parenteral route is necessary employs a constant intravenous infusion, which results in a lower calcium load per unit time to the kidneys, and maintains serum calcium at a relatively steady level. Calcium supplements may be introduced orally if tolerated. In persistent cases, the load of dietary phosphate should be lessened with a formula such as Similac PM 60/ 40. When hypomagnesaemia is identified, it can be treated with 0.1– 0.2 ml/ kg of a 50% solution of magnesium sulphate (MgSO4 •7H2O).
