Neonatal hypocalcemia: The role of ionized calcium
Catch up on this on-demand webinar to learn about early and late-onset neonatal hypocalcemia diagnosis
19 May 2021
In this on-demand webinar, Dr. Monet Sayegh, Senior Clinical Consultant at Siemens Healthineers, reviews calcium metabolism, with a focus on early and late onset of neonatal hypocalcemia – including a case report. Both calcium and ionized calcium are discussed in detail in conjunction with the role of magnesium, serum albumin, phosphate, and blood pH in the proper diagnosis of hypocalcemia.
Read on for highlights of the live Q&A session or register to watch the webinar at any time that suits you.
Watch on demandQ: Who should be screened for hypocalcemia?
MS: Most infants with early-onset hypocalcemia are usually asymptomatic. Serum ionized calcium should be measured in infants with risk factors for hypocalcemia — now preterm infants with a gestational age of less than 32 weeks, or infants of diabetic mothers, and infants with severe prenatal asphyxia and a one-minute APGAR score of less than four. The higher the score, the better the baby is doing after birth. Normally a score of seven, eight or nine is normal, and usually gives us a sign that the newborn baby is in a good health. Those who are at risk for hypocalcemia should be screened at about 24 and 48 hours after birth.
For infants with extremely low birth weight, babies less than a thousand grams, or one kilogram, calcium levels should be measured at 12, 24 and 48 hours of birth. For preterm infants with a birth weight somewhere around 1,000 to 1,500 grams, calcium level is measured at 24 to 48 hours of birth.
Therefore, monitoring calcium levels should continue until the values return to normal and calcium intake is adequate.
Q: Is there a difference between fetal and neonatal calcium homeostasis?
MS: Calcium usually is transferred from maternal circulation to fetal circulation by active transport from the placenta in the last trimester. As a result, the calcium concentration is higher in cord blood than in maternal blood at delivery. At term pregnancy, fetal total and ionized calcium concentration is between 10 to 11 milligrams per deciliter, and 6 milligrams per deciliter, respectively, in umbilical cord blood.
Therefore, parathyroid hormone (PTH) and calcitonin cannot pass through the placental barrier. Parathyroid hormone-related peptide is the major regulator of positive calcium balance in the placenta. The post-partum serum level of calcium in newborns is associated with various factors, such as PTH secretion, or parathyroid hormone secretion, dietary calcium intake, and there's renal calcium reabsorption, skeletal calcium stores, and also the status of vitamin D.
After the infant becomes detached from the placenta in the post-partum period, serum total and ionized calcium levels decrease, reaching a physiological nadir in a healthy two-day term infant.
Q: What other roles can calcium play in the human body aside from bone mineralization?
MS: Calcium is involved in many biochemical processes in the body, including blood coagulation, intracellular signal transduction, neural transmission, muscle functions, cellular membrane integrity and functions, cellular enzymatic activities, and cell differentiation. About 99% of body calcium resides in bone tissue, and the remaining is present in the extracellular fluid. Almost half the calcium found in the extracellular fluid is in the ionized active form, whereas 10% is complexed to anions such as the phosphates, citrate, sulphate and lactate, and about 40% is bound to albumin.
Q: What factors affect serum calcium levels?
MS: Serum calcium level is affected by serum levels of phosphates such as magnesium, albumin, and bicarbonate. The change in albumin concentration does not change the blood level of ionized calcium but changes measurement of the total calcium level. In general, the plasma calcium concentration reduces by about 0.8 milligrams per deciliter for every 1 gram per deciliter reduction in plasma albumin level.
Ionized calcium, referring to the active form, is not measured directly. Calcium corrected for the measured total calcium and measured albumin should be calculated. Furthermore, the blood PH affects the level of ionized calcium. Alkalosis increases the amount of albumin-bound calcium, and decreases the level of ionized calcium, leading to symptoms of hypocalcemia. In acute respiratory alkalosis, the level of ionized calcium falls to about 0.16 milligrams per deciliter for each 0.1 unit increase in PH. Conversely, in metabolic acidosis, calcium albumin binding is reduced, while the level of ionized calcium increases.
Magnesium is also involved in the regulation of the intracellular release of the parathyroid hormone. Therefore, low magnesium may reduce the activity of the parathyroid hormone, or cause resistance to the parathyroid hormone. Long-term magnesium deficiency also inhibits the release of parathyroid hormone.
Q: Between the different forms of calcium, protein-bound and ionized, which is directly implicated or most important in the pathogenesis of hypocalcemia?
MS: In most cases, plasma calcium exists in three forms: ionized form, protein-bound, and complex with anion. The ionized calcium is mentioned several times during the presentation. This is the biologically active form of calcium and permits a more accurate assessment of calcium status. In each of these formulas, to measure the correct total calcium level, there have been potential errors that are not reflective of the actual calcemic status of the patient.
We want to make sure that clinicians, laboratorians, and healthcare providers all consider looking at ionized calcium as routine rather than as an exception.