eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Hypocalcemia

Abhay Singhal, MD, Assistant Professor of Clinical Pediatrics, Department of Pediatrics, Division of Neonatology, Indiana University School of Medicine
Deborah E Campbell, MD, Professor of Clinical Pediatrics, Albert Einstein College of Medicine; Director, Department of Pediatrics, Division of Neonatology, Weiler Hospital Division of Montefiore Medical Center

Updated: Oct 23, 2009

Introduction

Background

Hypocalcemia is a relatively frequently observed laboratory and clinical abnormality seen especially in neonates. Laboratory hypocalcemia is often asymptomatic, and its treatment in neonates is controversial. However, children with hypocalcemia in pediatric ICUs (PICUs) have mortality rates higher than those of children with normal calcium levels. Hypocalcemia is defined as a total serum calcium concentration of less than 2.1 mmol/L (8.5 mg/dL) in children, less than 2 mmol/L (8 mg/dL) in term neonates, and less than 1.75 mmol/L (7 mg/dL) in preterm neonates.

Electrocardiogram (ECG) findings in severe hypocalcemia.

Pathophysiology

Calcium is the most abundant mineral in the body. Of the body's total calcium, 99% is in bone, and serum levels constitute less than 1%.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.

Although total serum calcium levels are often measured and reported, ionized calcium is the active and physiologically important component. Total calcium level includes both the ionized fraction and the bound fraction. The ionized calcium level is affected by the albumin level, blood pH, serum phosphate, serum magnesium, and serum bicarbonate and may be reduced by exogenous factors that may bind calcium, such as citrate from transfused blood or free fatty acids from total parenteral nutrition (TPN). At a physiologic pH of 7.4, 40% of total calcium is bound to albumin; 10% is complexed with bicarbonate, phosphate, or citrate; and the remaining 50% is free ionized calcium. 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

Hypocalcemia manifests as CNS irritability and poor muscular contractility. Low calcium levels decrease the threshold of excitation of neurons, causing them to have repetitive responses to a single stimulus. Because neuronal excitability occurs in both sensory and motor nerves, hypocalcemia produces a wide range of peripheral and CNS effects, including paresthesias, tetany (ie, contraction of hands, arms, feet, larynx, bronchioles), seizures, and even psychiatric changes in children. Tetany is not caused by increased excitability of the muscles. Muscle excitability is depressed because hypocalcemia impedes acetylcholine release at neuromuscular junctions and, therefore, inhibits muscle contraction. However, the increase in neuronal excitability overrides the inhibition of muscle contraction. Cardiac function may also be impaired because of poor muscle contractility.

Frequency

United States

The incidence of neonatal hypocalcemia varies in different studies. Hypocalcemia occurs in as many as 30% of infants with very low birth weight (<1500 g) and in as many as 89% of infants whose gestational age at birth was less than 32 weeks. A high incidence is also reported in infants of mothers with diabetes mellitus and in infants with birth asphyxia.

International

No variation is reported across national boundaries. However, late-onset hypocalcemia is more common in infants in developing countries where babies are fed cow's milk or formulas containing high amounts of phosphate than in countries where infants are fed human milk or formulas containing low amounts of phosphate.

Mortality/Morbidity

Higher mortality rates have been reported in children with hypocalcemia than in normocalcemic children in PICU settings.

Sex

No sex-based variation in incidence is known.

Age

Most pediatric patients with hypocalcemia are newborns. In older children, hypocalcemia is usually associated with critical illness, acquired hypoparathyroidism, activating mutations of the calcium-sensing receptor, or defects in vitamin D supply or metabolism.

Clinical

History

In patients with hypocalcemia, the history varies depending on age.

• Newborns
  • Possibly no symptoms
  • Lethargy
  • Poor feeding
  • Vomiting
  • Abdominal distension
• Children
  • Seizures
  • Twitching
  • Cramping
  • Laryngospasm, a rare initial manifestation

Physical

• Lethargy
• Cyanosis
• Tremulousness
• Seizures
• Apnea
• Tetany and signs of nerve irritability, such as the Chvostek sign, carpopedal spasm, the Trousseau sign, and stridor
• Abdominal distension
• Prematurity, birth asphyxia, or congenital heart disease (features associated with infants of mothers with diabetes mellitus)

Causes

Overall, one of the most common causes of hypocalcemia is renal failure, which results in hypocalcemia because of inadequate 1-hydroxylation of 25-hydroxyvitamin D and hyperphosphatemia due to diminished glomerular filtration.

Although hypocalcemia is most commonly observed among neonates, it is frequently reported in older children and adolescents, especially in PICU settings. The causes of hypocalcemia can be classified by the child's age at presentation.

• Early neonatal hypocalcemia (within 48-72 h of birth)
  • Prematurity: Possible mechanisms include poor intake, decreased responsiveness to vitamin D, increased calcitonin, and hypoalbuminemia leading to decreased total but normal ionized calcium.
  • Birth asphyxia: Delayed introduction of feeds, increased calcitonin production, increased endogenous phosphate load, and alkali therapy all may contribute to hypocalcemia.
  • Diabetes mellitus in the mother: Magnesium depletion in mothers with diabetes mellitus causes hypomagnesemic state in the fetus. This hypomagnesemia induces functional hypoparathyroidism and hypocalcemia in the infant. A high incidence of birth asphyxia and prematurity in infants of diabetic mothers are also contributing factors.
  • Intrauterine growth retardation (IUGR): Infants with IUGR may have hypocalcemia if they are also preterm or have had perinatal asphyxia.
• Late neonatal hypocalcemia (3-7 d after birth, though occasionally as late as age 6 wk)
  • Exogenous phosphate load: This is most commonly seen in developing countries. Hypocalcemia is caused by feeding with phosphate-rich formula or cow's milk. Whole cow's milk has 7 times the phosphate load of breast milk (956 vs 140 mg/L in breast milk).
  • Magnesium deficiency
  • Transient hypoparathyroidism of newborn
  • Hypoparathyroidism due to other causes
  • Gentamicin use: Data have suggested association with gentamicin use, especially with the newer every-24-hour dosing schedule.²
• Hypocalcemia in infants and children
  • Hypoparathyroidism
    • Aplasia or hypoplasia -DiGeorge syndrome; velocardiofacial syndrome; gestational diabetes mellitus, fetal exposure to retinoic acid; complex of vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, and radial and renal abnormalities (VATER); and association of coloboma, heart defects, choanal atresia, renal abnormalities, growth retardation, male genital anomalies, and ear abnormalities (CHARGE)
    • Parathormone (PTH) receptor defects - Pseudohypoparathyroidism
    • Autoimmune parathyroiditis
    • Infiltrative lesions -Hemosiderosis, Wilson disease, thalassemia
    • Activating mutations of the calcium-sensing receptor leading to inappropriately suppressed PTH secretion
    • Idiopathic causes
  • Abnormal vitamin D production or action
    • Vitamin D deficiency: Dietary insufficiency and maternal use of anticonvulsants have been reported.
    • Acquired or inherited disorders of vitamin D metabolism
    • Resistance to actions of vitamin D
    • Liver disease: Liver disease can affect 25-hydroxylation of vitamin D. Certain drugs (eg, phenytoin, carbamazepine, phenobarbital, isoniazid and rifampin) can increase the activity of P-450 enzymes, which can increase the 25-hydroxylation and also the catabolism of vitamin D.
  • Hyperphosphatemia
    • Excessive phosphate intake because of improper formula
    • Excessive phosphate intake caused by inappropriate use of phosphate-containing enemas
    • Loading in total parenteral nutrition (TPN)
    • Increased endogenous loading caused by anoxia, chemotherapy, or rhabdomyolysis
    • Renal failure
  • Others
    • Malabsorption syndromes
    • Alkalosis -Respiratory alkalosis caused by hyperventilation; metabolic alkalosis with the administration of bicarbonate, diuretics, or chelating agents, such as the high doses of citrates taken in during massive blood transfusions
    • Pancreatitis
    • Pseudohypocalcemia (ie, hypoalbuminemia)
    • Hungry bones syndrome - Rapid skeletal mineral deposition seen in infants with rickets or hypoparathyroidism after starting vitamin D therapy

Differential Diagnoses

Other Problems to Be Considered

Anoxia
Intracranial bleeding
Narcotic withdrawal
Pseudohypoparathyroidism
Rickets, osteomalacia, or rachitis (ie, vitamin D deficiency)
Hyperphosphatemia
Hypoalbuminemia
Renal failure
Metabolic disease affecting vitamin D, seizures

Workup

Laboratory Studies

The following should be assessed in patients with hypocalcemia:

• Total and ionized serum calcium levels
  • Measuring ionized calcium level is essential to differentiate true hypocalcemia from a mere decrease in total calcium concentration.
  • A decrease in total calcium can be associated with low serum albumin concentration and abnormal pH.
• Serum magnesium levels
  • Serum magnesium levels may be low in patients with hypocalcemia.
  • Hypocalcemia may not respond to calcium therapy if hypomagnesemia is not corrected.
  • Severe hypomagnesemia (0.46 mmol/L) causes hypocalcemia by impairing the secretion and action of parathormone (PTH).
• Serum electrolyte and glucose levels
  • Seizures and irritability in newborns and children can be associated with hypoglycemia and sodium abnormalities.
  • Low bicarbonate levels and acidosis may be associated with Fanconi syndrome and renal tubular acidosis.
• Phosphorus levels
  • Estimating the phosphate level is essential to establish the etiology of hypocalcemia.
  • Phosphate levels are increased in cases of exogenous and endogenous phosphate loading and renal failure.
  • Levels are usually high in patients with hypoparathyroidism.
  • Levels are low in cases of vitamin D abnormalities and rickets.
• PTH levels
  • Hormone studies are indicated if hypocalcemia persists in the presence of normal magnesium and normal or elevated phosphate levels.
  • Low PTH levels suggest hypoparathyroidism; serum calcium rises in response to PTH challenge.
  • On the converse, PTH levels are elevated in patients with vitamin D abnormalities and pseudohypoparathyroidism, and calcium levels do not rise in response to PTH challenge.
  • N -terminal fragment of PTH is the only biologically active fragment of PTH. It is difficult to measure because of its short half life of 2-5 minutes. Circulating PTH levels are determined by assaying for intact PTH peptide.
• Vitamin D metabolite (25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) levels: These may be assessed, along with hormone concentrations, to eliminate uncommon causes of hypocalcemia (eg, malabsorption, disorders of vitamin D metabolism).
• Urine calcium, magnesium, phosphorus, and creatinine levels
  • These values should be assessed in patients with suspected renal tubular defects and renal failure.
  • Urine should also be evaluated for pH, glucose, and protein.
  • In patients with renal defects, calcium excretion is high in presence of hypocalcemia.
  • A urine calcium-to-creatinine ratio of more than 0.3 on a spot sample in presence of hypocalcemia suggests inappropriate excretion.
• Serum alkaline phosphatase levels: Values are generally elevated in patients with rickets.

Imaging Studies

• Chest radiography: Evaluate for thymic shadow, which may be absent in patients with DiGeorge syndrome.
• Ankle and wrist radiography
  • Evaluate for evidence of rickets.
  • Changes appear at an early stage in the radius and ulna; the distal ends are widened, concave, and frayed.

Other Tests

• Electrocardiography
  • A prolonged QTc (>0.4 s), a prolonged ST segment, and T-wave abnormalities may be observed.
  • Measurements of specific intervals are of little value in predicting hypocalcemia.
• Malabsorption workup
• Total lymphocyte and T-cell subset analyses: Findings are decreased in patients with DiGeorge syndrome.
• Karyotyping to assess for 22q11 and 10p13 deletion.
• Maternal and family screening: This is helpful in familial forms of hypocalcemia, such as those caused by activating mutations of the calcium-sensing receptor.

Treatment

Medical Care

• General medical care in patients with hypocalcemia involves stabilization with management of the patient's airway and breathing if seizures occur.
  • Anticonvulsants are commonly administered before hypocalcemia is confirmed in a new patient.
  • Seizures usually do not respond to the usual antiseizure medications until calcium is intravenously administered.
• Treatment of an asymptomatic patient with hypocalcemia remains controversial, especially in neonates.
  • Some authorities suggest that treating such patients is unnecessary.
  • In contrast, most clinicians agree that hypocalcemia should be treated promptly in any symptomatic neonate or older child because of its serious implications for neuronal and cardiac function.
  • Intravenous treatment is usually indicated in patients having seizures, those who are critically ill, and those who are planning to have surgery.
  • Oral calcium therapy is used in asymptomatic patients and as follow-up to intravenous calcium therapy.
• In certain conditions like pancreatitis and rhabdomyolysis, full correction of hypocalcemia should be avoided. After the primary condition is resolved, these patients may develop hypercalcemia due to the release of complexed calcium.
• In cases with concurrent acidemia, hypocalcemia should be corrected first. Acidemia increases the ionized calcium levels by displacing calcium from albumin. If acidemia is corrected first, it decreases ionized calcium levels.

Consultations

• Pediatric endocrinologist
• Geneticist

Diet

• A diet high in calcium and low in phosphate is required in most instances.
• Infants drinking regular cow's milk or evaporated milk must be given humanized infant formula instead.
• Patients with renal failure should be given a low-solute low-phosphate formula, such as Similac PM 60/40.

Medication

Calcium therapy is the mainstay of treatment for hypocalcemia. Therapy with intravenous calcium is the most effective and rapid means of elevating serum calcium concentration. After hypocalcemia is controlled, follow-up treatment with oral therapy can be given. However, in patients with asymptomatic hypocalcemia, therapy with oral calcium alone may be sufficient. Vitamin D, in one of its various forms, is also indicated, depending on the metabolic abnormality present. However, the use of vitamin D formulations in newborns to prevent hypocalcemia has not been effective. The most important aspect of management is resolution of the primary cause (eg, hyperphosphatemia, hypomagnesemia).

The American Academy of Pediatrics (AAP) recently published revisions for guidelines for adequate vitamin D intake in infants, children, and adolescents.³ The revised guidelines now recommend a minimum daily intake of 400 IU of vitamin D beginning in the first few days following birth and continuing through adolescence. Symptomatic hypocalcemia may occur during periods of rapid growth with increased metabolic demands, long before any physical findings or radiologic evidence of vitamin D deficiency occur.

Although not used routinely due to suggested risk of osteosarcoma, effectiveness of recombinant parathormone (PTH) in an infant with hypocalcemia refractory to calcitriol and calcium supplementation has been reported.⁴

Calcium compounds

Calcium is the most abundant mineral in the human body. It is essential for blood coagulation and the development and/or function of bone, teeth, nerves, and muscles. Calcium also functions as an enzymatic cofactor and affects endocrine secretory function. Supplements are used to increase serum calcium concentrations in patients with hypocalcemia. Oral preparations are prescribed to reduce phosphate absorption from the intestine in patients with hyperphosphatemia.

Calcium, intravenous

Calcium gluconate 10% (100 mg/mL) IV solution contains 9.8 mg/mL (0.45 mEq/mL) elemental calcium. Calcium chloride 10% (100 mg/mL) contains 27 mg/mL (1.4 mEq/mL) elemental calcium.
Calcium chloride is more irritating to the veins and may affect pH; therefore, typically avoided in pediatric patients.

Dosing

Adult

200-1500 mg (as elemental calcium) IV over 24 h

Pediatric

10-20 mg/kg elemental calcium (1-2 mL calcium gluconate/kg) IV slowly over 5-10 min to control seizures; may be continued as IV infusion at 50-75 mg/kg/d over 24 h

Interactions

May cause arrhythmias in patients taking digoxin; precipitates in solution with sodium bicarbonate; may decrease effects of tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones; antagonizes effects of verapamil; large intakes of dietary fiber may decrease calcium absorption and levels

Contraindications

Renal calculi; hypercalcemia hypophosphatemia; ventricular fibrillation during cardiac arrest, digitalis toxicity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Use extreme care with peripheral infusion because extravasation can cause severe tissue necrosis; rapid IV infusion may cause bradycardia and hypotension; may cause liver necrosis if administered in umbilical venous catheter lodged in branch of portal vein; prolonged use of calcium chloride may lead to hyperchloremic acidosis

Calcium glubionate (Neo-Calglucon)

Calcium supplement for PO use. Available as liquid product containing glubionate salt (1800 mg/5 mL) contains 115 mg elemental calcium/5 mL.

Dosing

Adult

1-2 g/d (as elemental calcium) PO divided tid/qid

Pediatric

50-75 mg/kg/d (as elemental calcium) PO divided q6-8h

Interactions

May decrease effects of tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones; large intakes of dietary fiber may decrease calcium absorption and levels

Contraindications

Renal calculi; hypercalcemia hypophosphatemia; ventricular fibrillation during cardiac arrest, digitalis toxicity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Use with caution in small neonates because of high osmolar load; may cause diarrhea in older children

Calcium carbonate (Oyster Cal, Caltrate, Tums, Os-Cal)

Supplement for PO use. In many ways, calcium supplement of choice because provides 40% elemental calcium. Therefore, 1 g of calcium carbonate provides 400 mg of elemental calcium. Well absorbed PO and unlikely to cause diarrhea. Available as tab and liquid.

Dosing

Adult

1-2 g/d (as elemental calcium) PO divided tid/qid

Pediatric

Neonates: 30-150 mg/kg/d PO divided qid; some infant formulas contain supplemental calcium (eg, Similac PM 60/40 contains calcium-phosphorous ratio of 2:1)
Children: 20-65 mg/kg/d PO divided bid/qid

Interactions

May decrease effects of tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones; large intakes of dietary fiber may decrease calcium absorption and levels

Contraindications

Renal calculi; hypercalcemia hypophosphatemia; ventricular fibrillation during cardiac arrest, digitalis toxicity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Hypercalcemia or hypercalcuria may occur when therapeutic amounts given

Vitamin D metabolites

The active forms of vitamin D regulate calcium absorption and its uses in the body. They increase calcium levels by promoting absorption of calcium in intestines and retention in kidneys.

Calcitriol (Rocaltrol)

Active metabolic form of vitamin D (ie, 1,25-dihydroxycholecalciferol). Especially useful in liver or renal impairment because these cause inability to hydroxylate vitamin D to its active forms. Generally, the product is rapid-acting, but may act slowly in neonates (36-48 h). Preterm infants may be resistant to its actions. Also used to treat acute hypocalcemia.

Dosing

Adult

0.25 mcg PO qd initially; may increase by 0.25 mcg every 3-4 wk; typical range 0.5-2 mcg/d

Pediatric

0.01-0.05 mcg/kg/d IV initially; adjust dosage until normocalcemia attained

Interactions

Cholestyramine and colestipol decrease absorption of calcitriol; magnesium-containing antacids and thiazide diuretics can increase calcitriol effects

Contraindications

Documented hypersensitivity; hypercalcemia, hypercalciuria, malabsorption syndrome

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause hypercalciuria; give with calcium salts to attain optimum results; may add hydrochlorothiazide to regimen to control hypercalciuria

Dihydrotachysterol (DHT, Hytakerol)

Synthetic analog of vitamin D, which does not require activation by renal 1 hydroxylase for activity. Also available as liquid, which facilitates administration of variable doses in infants and young children. 1 mg equivalent to 120,000 U (ie, 3 mg) vitamin D-2.

Dosing

Adult

0.75-2.5 mg/d PO for 2-3 d initially; maintain with 0.1-2 mg/d

Pediatric

Neonates: 0.05-0.1 mg/d PO
Children: 0.5-2 mg/d PO

Interactions

None reported

Contraindications

Documented hypersensitivity; hypercalcemia; hypercalcuria; malabsorption syndrome

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause hypercalciuria; give with calcium salts to attain optimum results; may add hydrochlorothiazide to regimen to control hypercalciuria

Follow-up

Further Inpatient Care

• Most babies with hypocalcemia are preterm and have already been admitted to the neonatal ICU (NICU).
• Any newborn infant with hypocalcemia should be monitored in the NICU.
• Any child with symptomatic hypocalcemia should be admitted to the hospital unless the diagnosis is hyperventilation.

Further Outpatient Care

• Regular follow-up monitoring of serum calcium concentration and appropriate monitoring of the underlying disease (eg, parathormone [PTH] concentration in hypoparathyroidism) is necessary.
• This monitoring is important because no definitive measures are available to determine whether an infant has transient hypoparathyroidism that may last for several years or is at risk for recurrence of hypoparathyroidism and hypocalcemia; recurrence has been reported as late as adolescence.

Inpatient & Outpatient Medications

• Magnesium administration is necessary to correct any hypomagnesemia because hypocalcemia does not respond until the low magnesium level is corrected.
• Phosphate-lowering agents may be necessary if hypocalcemia is associated with hyperphosphatemia.

Deterrence/Prevention

• Late-onset hypocalcemia in neonates, which is typically caused by hyperphosphatemia, can be prevented by avoiding high-phosphate diets (eg, regular cow's milk). Ensuring adequate vitamin D stores in mothers during pregnancy also prevents late hypocalcemia.⁵
• Feeding a low-phosphate diet such as human milk or Similac PM 60/40 formula may prevent hypocalcemia in hyperphosphatemic states, such as renal failure, hypoparathyroidism, and endogenous phosphate loading. Enhancing the calcium-phosphorus ratio to 4:1 in the diet (by adding calcium supplements to a low-phosphate diet) also reduces intestinal absorption of phosphate.

Prognosis

• Most cases of early neonatal hypocalcemia resolve within 48-72 hours without any clinically significant sequelae.
• Late neonatal hypocalcemia secondary to exogenous phosphate load and magnesium deficiency also responds well to phosphate restriction and magnesium repletion.
• When caused by hypoparathyroidism, hypocalcemia requires continued therapy with vitamin D metabolites and calcium salts. The period of therapy depends on the nature of the hypoparathyroidism, which can be transient, last several weeks to months, or be permanent.

Miscellaneous

Medicolegal Pitfalls

• Intravenous infusion with calcium-containing solutions can cause severe tissue necrosis. This can cause contractures and may require skin grafting. Integrity of the intravenous site should be ascertained before administering calcium through a peripheral vein.
• Necrosis of liver can occur after calcium infusion through an umbilical vein catheter placed in a branch of the portal vein. The position of all umbilical vein catheters must be confirmed radiologically before infusing calcium-containing solutions.
• Rapid infusion of calcium-containing solutions through arterial lines can cause arterial spasm and, if administered via an umbilical artery catheter, intestinal necrosis.

Multimedia

Media file 1: Electrocardiogram (ECG) findings in severe hypocalcemia.

References

1. Gertner JM. Disorders of calcium and phosphorus homeostasis. Pediatr Clin North Am. Dec 1990;37(6):1441-65. [Medline].

2. Jackson GL, Sendelbach DM, Stehel EK, et al. Association of hypocalcemia with a change in gentamicin administration in neonates. Pediatr Nephrol. Jul 2003;18(7):653-6. [Medline].

3. [Guideline] Wagner CL, Greer FR. Prevention of rickets and vitamin d deficiency in infants, children, and adolescents. Pediatrics. Nov 2008;122(5):1142-52. [Medline].

4. Newfield RS. Recombinant PTH for initial management of neonatal hypocalcemia. N Engl J Med. Apr 19 2007;356(16):1687-8. [Medline].

5. Mulligan ML, Felton SK, Riek AE, Bernal-Mizrachi C. Implications of vitamin D deficiency in pregnancy and lactation. Am J Obstet Gynecol. Oct 19 2009;[Medline].

6. Guise TA, Mundy GR. Clinical review 69: Evaluation of hypocalcemia in children and adults. J Clin Endocrinol Metab. May 1995;80(5):1473-8. [Medline].

7. Mimouni F, Tsang RC. Neonatal hypocalcemia: to treat or not to treat? (A review). J Am Coll Nutr. Oct 1994;13(5):408-15. [Medline].

8. Reichel H, Koeffler HP, Norman AW. The role of the vitamin D endocrine system in health and disease. N Engl J Med. Apr 13 1989;320(15):980-91. [Medline].

9. Sanchez GJ, Venkataraman PS, Pryor RW, et al. Hypercalcitoninemia and hypocalcemia in acutely ill children: studies in serum calcium, blood ionized calcium, and calcium-regulating hormones. J Pediatr. Jun 1989;114(6):952-6. [Medline].

10. Singh J, Moghal N, Pearce SH, Cheetham T. The investigation of hypocalcaemia and rickets. Arch Dis Child. May 2003;88(5):403-7. [Medline].

11. Yamamoto M, Akatsu T, Nagase T, Ogata E. Comparison of hypocalcemic hypercalciuria between patients with idiopathic hypoparathyroidism and those with gain-of-function mutations in the calcium-sensing receptor: is it possible to differentiate the two disorders?. J Clin Endocrinol Metab. Dec 2000;85(12):4583-91. [Medline].

Keywords

hypocalcemia, neonatal hypocalcemia, low calcium, low ionized calcium, diabetes mellitus, hypoparathyroidism, abdominal distension, seizures, laryngospasm, prematurity, birth asphyxia, congenital heart disease, hypomagnesemia, treatment, diagnosis

Contributor Information and Disclosures

Author

Abhay Singhal, MD, Assistant Professor of Clinical Pediatrics, Department of Pediatrics, Division of Neonatology, Indiana University School of Medicine
Abhay Singhal, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Coauthor(s)

Deborah E Campbell, MD, Professor of Clinical Pediatrics, Albert Einstein College of Medicine; Director, Department of Pediatrics, Division of Neonatology, Weiler Hospital Division of Montefiore Medical Center
Deborah E Campbell, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Medical Association, National Perinatal Association, New York Academy of Medicine, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Medical Editor

Thomas A Wilson, MD, Professor of Clinical Pediatrics, Department of Pediatrics; Director of Pediatric Endocrinology, Division of Pediatric Endocrinology, Department of Pediatrics, State University of New York at Stony Brook
Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London), Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece
George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and Arkansas Children's Hospital
Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research
Disclosure: Genentech, Inc. Honoraria Speaking and teaching; Pfizer, Inc. Honoraria Consulting

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)