Medical Affairs

Department of Pediatrics

Clinical Practice Guideline

HYPOCALCEMIA IN CHILDREN

Document # PEDS-ENDO # 002

Date CPG Formulated Date last CPG Reviewed

December 2007Feb 2012

Next Review Date Jan 2014

I- Introduction:

In humans, 99 % of the total body calcium is stored in the bones in the form of hydroxyapatite. The remaining 1% is distributed between the extra-cellular and intra-cellular compartments. Serum calcium exists in three forms; 50% ionized, 40% protein bound, and 10% anion bound (phosphate, citrate, carbonate, etc.). In addition to its important role in bone mineralization, calcium facilitates several other functions such as:

Muscles contraction and relaxation Nerves conduction Cellular membranes integrity Blood coagulation

II- Calcium homeostasis: Normocalcemia state is maintained by balancing calcium intake (adequate nutritional calcium content and normal calcium absorption), and calcium excretion. This balance is achieved through the interactive effects of the calcium sensing receptors (CaSR), PTH, and vitamin D. CaSR detects the early changes in the level of serum ionized calcium and as a result to that, it suppresses or stimulates PTH secretion when calcium level increases or decreases, respectively. PTH increases calcium level by different mechanisms:

Stimulates 1-alpha hydroxylase in the kidney which activates 25-OH vitamin D to 1,25 (OH)2 vitamin D. Active vitamin D stimulates intestinal calcium absorption.

Increases renal calcium re-absorption (and phosphorus excretion). Increases bone resorption.

III- Clinical presentation: Hypocalcemia, especially in the mild form, might be asymptomatic, but commonly, it presents with one or more of the following symptoms:

Fatigue/irritability, poor feeding Muscle cramping, spasm, or tetany Peri-oral tingling, Numbness of the fingers or toes Positive Chvostek and/or Trousseau signs. Apnea, Seizure.

IV- Causes of hypocalcemia:

1- Decreased calcium absorption: Nutritional calcium deficiency. Vitamin D deficiency Steroids Hyperphosphatemia Intestinal malabsorption

2- Increased calcium excretion: Deficiency of or resistance to PTH. Loop diuretics.

3- Increase calcium deposition in the bones (hungry bones syndrome).

V- Causes of neonatal hypocalcemia: Neonatal hypocalcemia is classified, per the timing of onset, into early (the first 72 hours after birth) and late (after 3 days of birth):

I- Early neonatal hypocalcemia:

The most common causes are prematurity, low birth weight and neonatal stress and asphyxia, but it can also be secondary to maternal disorders such as diabetes mellitus and hyperpatahyroidism.

II- Late neonatal hypocalcemia:

Hypocalcemia in this age group can be secondary to hypoparathyroidism, hypomagnesemia, vitamin D deficiency, or increased phosphorus intake, such as that associated with formula feeding, which can be exacerbated by the limited renal excretion of phosphate. Due to the subtle clinical presentation, serum calcium should be checked in any infant with risk factor/s or clinical symptoms suggestive of hypocalcemia:

1- Premature infants. 2- Infants of diabetic mother. 3- Maternal history of hyperparathyroidism or other calcium disorders, this should include

prolonged maternal treatment with MgSO4. 4- Severe perinatal asphyxia 5- Neonatal seizure/tetany 6- Congenital bone deformities.

VI. Diagnosis of Hypocalcemia: It is crucial when assessing patient with hypocalcemia to draw labs before the correcting treatment, if possible, and to look at the relevant variables all together. The figure below

summarized the causes of hypocalcemia in relation to the PTH level:

Calcium-PTH Normogram. From Parathyroid.com

VII. Diagnostic Algorhithm:

PTH: Parathyroid hormone. 1: Primary PHP: Pseudohypoparathyroidism 2: Secondary

*Ionized calcium should be assessed in the light of acid-base status (calcium binding is suppressed during acidosis and increases during alkalosis). * Corrected calcium (mg/dL) = measured total calcium (mg/dL) + 0.8 (4-measured albumin g/dL) * Consider doing renal US for nephrocalcinosis if urine Ca/Cr ratio is high. * Karyotyping (for 22q11 mutations) and CXR to assess thymic shadow if DiGeorge is suspected.

Hypocalcemia

PTH Normal or PTH

Check (before correcting Ca level):-Phos. -Urine Ca/Cr.

-Alk. P. - 25 (OH)D -Mg -PTH

Phos 2 Hyperparathyroidism

Phos Urine Ca/Cr

Vitamin D deficiencyVitamin D Resistance

PHP?

1 Hypoparathyroidism

Phos (neonates)

Mg

-Detailed H&P

Meds (Steroids, diuretics)

GNAS 1 mutation

VI. Treatment:

Patient should be NPO if presents with seizure. Acute management:

o IV calcium gluconate 10% at 10-20 mg/kg elemental calcium (1-2ml/kg) over 10-20 minutes WITH CARDIAC MONITORING.

o IV calcium infusion at 50mg/kg/day of elemental calcium o Calcitriol 0.5 mcg daily o Check calcium level (ionized is preferred) every 6 hours o Check IV site every 30 minutes for tissue necrosis o NEVER USE the scalp veins for calcium infusion.

Maintenance treatment: o Switch from IV to oral calcium when ionized calcium is 1.0 mmol/L, or

corrected calcium is 2.0 mmol/L. o Oral calcium can be given as clacium globionate (elemental calcium is 6.5%,

oral syrup contains 23 mg of elemental calcium in each 1 ml) or carbonate (40% elemental), starting between 50-100mg/kg/day elemental calcium.

o Patient on formula feeding should be switched to a low phosphate formula if they have hyperphosphatemia on presentation.

o Calcium monitoring can be done 1-2/day once on oral supplementation. o Calcitriol can be switched to ergocalciferol or cholecalciferol if no underlying

kidney or liver disease. o Patient can be discharged home as soon as PO is well-tolerated, and corrected

calcium is maintained >2.0 mmol/L.

References:

1- Kovacs CS, Kronenberg HM : Maternal-fetal calcium and bone metabolism during pregnancy,

puerperium and lactation. Endoecr Rev 18:832, 1997

2- Barnes-Powell LL. Infants of diabetic mothers: the effects of hyperglycemia on the fetus and neonate. Neonatal Netw. Sep-Oct 2007;26(5):283-90.

3- Williams Textbook of Endocrinology, 12th Edition

Approval:

Name Signature Date

Head of the Department: Dr. Aiman Rahmani

Other involved Dept Head/Division Chief

Dr. Walid Kaplan

Dr. Suha Hadi

A/Chief Medical Officer & division Chief

Dr.Walid Kaplan

Reviewed By Johns Hopkins Member:Yes No

Johns Hopkins Member

Calcium

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