Background
Hypocalcemia is a laboratory and clinical abnormality that is observed with relative frequency, especially in neonatal pediatric patients. Laboratory hypocalcemia is often asymptomatic, and its treatment in neonates is controversial. However, children with hypocalcemia in pediatric intensive care units (PICUs) have mortality rates higher than those of children with normal calcium levels. (See Prognosis, Clinical, Workup, and Treatment.)
The definition of hypocalcemia is based on both gestational and postnatal age in neonates and is different for children. Calcium data are presented as both mg/dL and mmol/L (1 mg/dL = 0.25 mmol/L)
In children, hypocalcemia is defined as a total serum calcium concentration less than 2.1 mmol/L (8.5 mg/dL).
In term infants, hypocalcemia is defined as total serum calcium concentration less than 2 mmol/L (8 mg/dL) or ionized fraction of less than 1.1 mmol/L (4.4 mg/dL)
In preterm infants, hypocalcemia is defined as total serum calcium concentration less than 1.75 mmol/L (7 mg/dL) is defined as hypocalcemia in infants weighing less than 1500 g birthweight. Symptomatology often manifests when the ionized calcium level falls below 0.8-0.9 mmol/L.
Calcium metabolism and function
Calcium is the most abundant mineral in the body. Of the body’s total calcium, 99% is stored in bone, and serum levels constitute less than 1%.
Various factors regulate the homeostasis of calcium and maintain serum calcium within a narrow range. These include parathormone (PTH), vitamin D, hepatic and renal function (for conversion of vitamin D to active metabolites), and serum phosphate and magnesium levels. (See Etiology and Workup)
Serum calcium is present in two forms: the free (ionized) and the bound form. Only about 50% of circulating calcium is present in the physiologically free form. The rest is either bound to proteins (40%) or complexed (10%) with bicarbonate, citrate, and phosphate. The ionized calcium level varies based on the level of serum albumin, blood pH, serum phosphate, magnesium, and bicarbonate levels, the administration of transfused blood containing citrate and free fatty acid content in total parenteral nutrition. The normal range for ionized calcium is 1-1.25 mmol/L (4-5 mg/dL).
The concentration of calcium in the serum is critical to many important biologic functions, including the following:
Calcium messenger system by which extracellular messengers regulate cell function
Activation of several cellular enzyme cascades
Smooth muscle and myocardial contraction
Nerve impulse conduction
Secretory activity of exocrine glands
Calcium physiology during pregnancy and Lactation
The fetus requires approximately 30gm calcium to mineralize its skeleton and to maintain normal physiologic processes. The newborn requires more than this amount during the first few months of life from breastmilk. The unique adaptations of the mother’s body allow her to meet the baby’s calcium demands without adverse long-term consequences to the maternal skeleton. The bulk of the calcium transmitted to the fetus during the third trimester is derived from the maternal intestinal absorption. Intestinal absorption of calcium doubles in pregnancy. Serum calcitriol level doubles or triples and stays elevated in pregnancy despite falling PTH level. It is instead increased, as 1-hydroxylase is upregulated by PTH-related Protein (PTHrP), prolactin and placental lactogen. The rise in PTHrP allows for the rise in calcium while protecting the maternal skeleton.
There is an average daily loss of 210 mg of calcium during lactation. Unlike during pregnancy, elevated PTHrP and low estradiol result in temporary demineralization of maternal skeleton to meet the calcium needs of the breastfeeding infant. These bone density losses are significantly reversed within twelve months of weaning.