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Neonatal hypocalcemia

Steven A Abrams, MD
Section Editors
Joseph A Garcia-Prats, MD
Joseph I Wolfsdorf, MB, BCh
Deputy Editor
Melanie S Kim, MD


Hypocalcemia is a common metabolic problem in newborns.

The diagnosis, clinical manifestations, and treatment of neonatal hypocalcemia are reviewed here. Calcium (Ca) requirements and the etiology of hypocalcemia after the neonatal period are discussed elsewhere. (See "Management of neonatal bone health" and "Etiology of hypocalcemia in infants and children".)


During pregnancy, calcium is transferred actively from the maternal circulation to the fetus by a transplacental Ca pump regulated by parathyroid hormone-related peptide (PTHrP) [1]. The majority of fetal Ca accretion occurs in the third trimester. This process results in higher plasma Ca concentrations in the fetus than in the mother and leads to fetal hypercalcemia, with total and ionized Ca concentrations of 10 to 11 mg/dL (2.5 to 2.75 mmol/L) and 6 mg/dL (1.5 mmol/L), respectively, in umbilical cord blood at term [2].

After the abrupt cessation of placental transfer of Ca at birth, total serum Ca concentration falls to 8 to 9 mg/dL (2 to 2.25 mmol/L) and ionized Ca to as low as 4.4 to 5.4 mg/dL (1.1 to 1.35 mmol/L) at 24 hours [3,4]. Serum Ca concentration subsequently rises, reaching levels seen in older children and adults by two weeks of age [5].


Within the plasma, calcium (Ca) circulates in different forms. Approximately 40 percent is bound to serum proteins, principally albumin; 10 percent is complexed with citrate, bicarbonate, sulfate, or phosphate; and 50 percent exists as the physiologically important ionized (or free) calcium [6]. The ionized Ca concentration is tightly regulated by parathyroid hormone and vitamin D.


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Literature review current through: Apr 2016. | This topic last updated: Apr 15, 2014.
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  1. Kovacs CS, Lanske B, Hunzelman JL, et al. Parathyroid hormone-related peptide (PTHrP) regulates fetal-placental calcium transport through a receptor distinct from the PTH/PTHrP receptor. Proc Natl Acad Sci U S A 1996; 93:15233.
  2. Rubin LP, Posillico JT, Anast CS, Brown EM. Circulating levels of biologically active and immunoreactive intact parathyroid hormone in human newborns. Pediatr Res 1991; 29:201.
  3. Loughead JL, Mimouni F, Tsang RC. Serum ionized calcium concentrations in normal neonates. Am J Dis Child 1988; 142:516.
  4. Wandrup J, Kroner J, Pryds O, Kastrup KW. Age-related reference values for ionized calcium in the first week of life in premature and full-term neonates. Scand J Clin Lab Invest 1988; 48:255.
  5. Rubin LP. Disorders of calcium and phosporus metabolism. In: Avery's Diseases of the Newborn, 7th ed, Taeusch HW, Ballard RA (Eds), WB Saunders, Philadelphia 1998. p.1189.
  6. Marx SJ, Bourdeau JE. Calcium metabolism. In: Clinical Disorders of Fluid and Electrolyte Metabolism, 4th ed, Maxwell MH, Kleeman CR, Narins RG (Eds), McGraw-Hill, New York 1987.
  7. Oberleithner H, Greger R, Lang F. The effect of respiratory and metabolic acid-base changes on ionized calcium concentration: in vivo and in vitro experiments in man and rat. Eur J Clin Invest 1982; 12:451.
  8. Husain SM, Veligati N, Sims DG, et al. Measurement of ionised calcium concentration in neonates. Arch Dis Child 1993; 69:77.
  9. Tsang RC, Light IJ, Sutherland JM, Kleinman LI. Possible pathogenetic factors in neonatal hypocalcemia of prematurity. The role of gestation, hyperphosphatemia, hypomagnesemia, urinary calcium loss, and parathormone responsiveness. J Pediatr 1973; 82:423.
  10. Venkataraman PS, Tsang RC, Steichen JJ, et al. Early neonatal hypocalcemia in extremely preterm infants. High incidence, early onset, and refractoriness to supraphysiologic doses of calcitriol. Am J Dis Child 1986; 140:1004.
  11. Rosenn B, Miodovnik M, Tsang R. Common clinical manifestations of maternal diabetes in newborn infants: implications for the practicing pediatrician. Pediatr Ann 1996; 25:215.
  12. Mimouni F, Tsang RC, Hertzberg VS, Miodovnik M. Polycythemia, hypomagnesemia, and hypocalcemia in infants of diabetic mothers. Am J Dis Child 1986; 140:798.
  13. Tsang RC, Chen I, Friedman MA, et al. Parathyroid function in infants of diabetic mothers. J Pediatr 1975; 86:399.
  14. Tsang RC, Chen I, Hayes W, et al. Neonatal hypocalcemia in infants with birth asphyxia. J Pediatr 1974; 84:428.
  15. Venkataraman PS, Tsang RC, Chen IW, Sperling MA. Pathogenesis of early neonatal hypocalcemia: studies of serum calcitonin, gastrin, and plasma glucagon. J Pediatr 1987; 110:599.
  16. Spinillo A, Capuzzo E, Egbe TO, et al. Pregnancies complicated by idiopathic intrauterine growth retardation. Severity of growth failure, neonatal morbidity and two-year infant neurodevelopmental outcome. J Reprod Med 1995; 40:209.
  17. Kramer MS, Olivier M, McLean FH, et al. Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome. Pediatrics 1990; 86:707.
  18. Thomas TC, Smith JM, White PC, Adhikari S. Transient neonatal hypocalcemia: presentation and outcomes. Pediatrics 2012; 129:e1461.
  19. Müller W, Peter HH, Wilken M, et al. The DiGeorge syndrome. I. Clinical evaluation and course of partial and complete forms of the syndrome. Eur J Pediatr 1988; 147:496.
  20. Müller W, Peter HH, Kallfelz HC, et al. The DiGeorge sequence. II. Immunologic findings in partial and complete forms of the disorder. Eur J Pediatr 1989; 149:96.
  21. Wilson DI, Burn J, Scambler P, Goodship J. DiGeorge syndrome: part of CATCH 22. J Med Genet 1993; 30:852.
  22. Chiruvolu A, Engle WD, Sendelbach D, et al. Serum calcium values in term and late-preterm neonates receiving gentamicin. Pediatr Nephrol 2008; 23:569.
  23. Camadoo L, Tibbott R, Isaza F. Maternal vitamin D deficiency associated with neonatal hypocalcaemic convulsions. Nutr J 2007; 6:23.
  24. Teaema FH, Al Ansari K. Nineteen cases of symptomatic neonatal hypocalcemia secondary to vitamin D deficiency: a 2-year study. J Trop Pediatr 2010; 56:108.
  25. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 2011; 96:53.
  26. Venkataraman PS, Tsang RC, Greer FR, et al. Late infantile tetany and secondary hyperparathyroidism in infants fed humanized cow milk formula. Longitudinal follow-up. Am J Dis Child 1985; 139:664.
  27. Walton DM, Thomas DC, Aly HZ, Short BL. Morbid hypocalcemia associated with phosphate enema in a six-week-old infant. Pediatrics 2000; 106:E37.
  28. Hakanson DO, Bergstrom WH. Phototherapy-induced hypocalcemia in newborn rats: prevention by melatonin. Science 1981; 214:807.
  29. Foldenauer A, Vossbeck S, Pohlandt F. Neonatal hypocalcaemia associated with rotavirus diarrhoea. Eur J Pediatr 1998; 157:838.
  30. Venkataraman PS, Wilson DA, Sheldon RE, et al. Effect of hypocalcemia on cardiac function in very-low-birth-weight preterm neonates: studies of blood ionized calcium, echocardiography, and cardiac effect of intravenous calcium therapy. Pediatrics 1985; 76:543.
  31. Newfield RS. Recombinant PTH for initial management of neonatal hypocalcemia. N Engl J Med 2007; 356:1687.
  32. Mimouni F, Tsang RC. Neonatal hypocalcemia: to treat or not to treat? (A review). J Am Coll Nutr 1994; 13:408.