Skeletal mineralization of the fetus is due to active calcium transport from the mother across the placenta. At term, the fetus is hypercalcemic relative to the mother and may have suppressed PTH levels. Over the first 4 days of life, PTH levels fall and rise to normal adult levels by 2 weeks after birth.
In the first 24-48 days of life, “early” neonatal hypocalcemia may occur. It is more common in premature infants, infants of diabetic mothers, and infants who have suffered asphyxia. The proportional drop in ionized calcium may be less than the drop in total calcium, so those symptoms may not be manifest. Hypocalcemia in premature infants is not unusual, but the reason is not understood. One proposal is that an exaggerated rise in calcitonin occurs that provokes hypercalcemia. Other hypotheses include the fact that PTH secretion may be impaired in the premature infant. Infants of diabetic mothers have an exaggerated postnatal drop in circulating calcium levels, and strict maternal glycemic control during pregnancy reduces the incidence of hypocalcemia in these infants.
Between 5 and 10 days of life, "late" neonatal hypocalcemia may result in tetany and seizures. This disorder is more common in full-term infants than in premature infants. One risk factor is hyperphosphatemia due to administration of cow's milk, which may reflect an inability of the immature kidney to secrete phosphate. Magnesium deficiency may also masquerade as hypocalcemia in an infant. Congenital defects of intestinal magnesium absorption or renal tubular absorption can occur resulting in severe hypocalcemia.
Hyperparathyroidism during pregnancy is unusual but can result in hypocalcemia in a newborn child. Atrophy of the fetal parathyroid glands can occur during intrauterine life due to the increased calcium delivery to the fetus. The infant's parathyroid glands are not able to respond to the hypocalcemic stimulus after birth and maintain normal serum calcium levels.
A typically benign autosomal dominant disorder, familial hypocalciuric hypercalcemia (FHH), can paradoxically produce neonatal hypocalcemia. FHH is usually due to heterozygous inactivating mutations in the CaSR. There is a report of an infant with late onset life-threatening hypocalcemia secondary to relative hypoparathyroidism. The hypoparathyroidism was thought to be due to fetal parathyroid suppression secondary to high maternal calcium levels in a mother with FHH due to a heterozygous CaSR mutation.