Severe Hypercalcemia Associated with Hypophosphatemia in Very Premature Infants: a Case Report

Overview

Journal Ital J Pediatr

Publisher Biomed Central

Specialty Pediatrics

Date 2021 Jul 8

PMID 34233724

Citations 1

Authors

Nicola Improda

Francesca Mazzeo

Alessandro Rossi

Claudia Rossi

Francesco Paolo Improda

Angelo Izzo

Affiliations

Soon will be listed here.

Abstract

Background: Severe hypercalcemia is rare in newborns; even though often asymptomatic, it may have important sequelae. Hypophosphatemia can occur in infants experiencing intrauterine malnutrition, sepsis and early high-energy parenteral nutrition (PN) and can cause severe hypercalcemia through an unknown mechanism. Monitoring and supplementation of phosphate (PO4) and calcium (Ca) in the first week of life in preterm infants are still debated.

Case Presentation: We report on a female baby born at 29 weeks' gestation with intrauterine growth retardation (IUGR) experiencing sustained severe hypercalcemia (up to 24 mg/dl corrected Ca) due to hypophosphatemia while on phosphorus-free PN. Hypercalcemia did not improve after hyperhydration and furosemide but responded to infusion of PO4. Eventually, the infant experienced symptomatic hypocalcaemia (ionized Ca 3.4 mg/dl), likely exacerbated by contemporary infusion of albumin. Subsequently, a normalization of both parathyroid hormone (PTH) and alkaline phosphatase (ALP) was observed.

Conclusions: Although severe hypercalcemia is extremely rare in neonates, clinicians should be aware of the possible occurrence of this life-threatening condition in infants with or at risk to develop hypophosphatemia. Hypophosphatemic hypercalcemia can only be managed with infusion of PO4, with strict monitoring of Ca and PO4 concentrations.

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References

Rodd C, Goodyer P . Hypercalcemia of the newborn: etiology, evaluation, and management. Pediatr Nephrol. 1999; 13(6):542-7. DOI: 10.1007/s004670050654. View

Ichikawa G, Watabe Y, Suzumura H, Sairenchi T, Muto T, Arisaka O . Hypophosphatemia in small for gestational age extremely low birth weight infants receiving parenteral nutrition in the first week after birth. J Pediatr Endocrinol Metab. 2012; 25(3-4):317-21. DOI: 10.1515/jpem-2011-0485. View

Mulla S, Stirling S, Cowey S, Close R, Pullan S, Howe R . Severe hypercalcaemia and hypophosphataemia with an optimised preterm parenteral nutrition formulation in two epochs of differing phosphate supplementation. Arch Dis Child Fetal Neonatal Ed. 2017; 102(5):F451-F455. DOI: 10.1136/archdischild-2016-311107. View

Bushinsky D, Monk R . Electrolyte quintet: Calcium. Lancet. 1998; 352(9124):306-11. DOI: 10.1016/s0140-6736(97)12331-5. View

Fenton T, Lyon A, Rose M . Cord blood calcium, phosphate, magnesium, and alkaline phosphatase gestational age-specific reference intervals for preterm infants. BMC Pediatr. 2011; 11:76. PMC: 3179922. DOI: 10.1186/1471-2431-11-76. View

Ehrenkranz R . Early nutritional support and outcomes in ELBW infants. Early Hum Dev. 2010; 86 Suppl 1:21-5. DOI: 10.1016/j.earlhumdev.2010.01.014. View

Davies J, Shaw N . Investigation and management of hypercalcaemia in children. Arch Dis Child. 2012; 97(6):533-8. DOI: 10.1136/archdischild-2011-301284. View

Senterre T, Abu Zahirah I, Pieltain C, De Halleux V, Rigo J . Electrolyte and Mineral Homeostasis After Optimizing Early Macronutrient Intakes in VLBW Infants on Parenteral Nutrition. J Pediatr Gastroenterol Nutr. 2015; 61(4):491-8. DOI: 10.1097/MPG.0000000000000854. View

Reynolds A, OConnell S, Kenny L, Dempsey E . Transient neonatal hypercalcaemia secondary to excess maternal vitamin D intake: too much of a good thing. BMJ Case Rep. 2017; 2017. PMC: 5534804. DOI: 10.1136/bcr-2016-219043. View

10.

Bustos Lozano G, Soriano-Ramos M, Pinilla Martin M, Chumillas Calzada S, Garcia Soria C, Pallas-Alonso C . Early Hypophosphatemia in High-Risk Preterm Infants: Efficacy and Safety of Sodium Glycerophosphate From First Day on Parenteral Nutrition. JPEN J Parenter Enteral Nutr. 2018; 43(3):419-425. DOI: 10.1002/jpen.1426. View

11.

Lyon A, McIntosh N, Wheeler K, Brooke O . Hypercalcaemia in extremely low birthweight infants. Arch Dis Child. 1984; 59(12):1141-4. PMC: 1628893. DOI: 10.1136/adc.59.12.1141. View

12.

Guellec I, Gascoin G, Beuchee A, Boubred F, Tourneux P, Ramful D . Biological Impact of Recent Guidelines on Parenteral Nutrition in Preterm Infants. J Pediatr Gastroenterol Nutr. 2015; 61(6):605-9. DOI: 10.1097/MPG.0000000000000898. View

13.

McNeilly J, Boal R, Shaikh M, Ahmed S . Frequency and aetiology of hypercalcaemia. Arch Dis Child. 2016; 101(4):344-7. DOI: 10.1136/archdischild-2015-309029. View

14.

Imel E, Econs M . Approach to the hypophosphatemic patient. J Clin Endocrinol Metab. 2012; 97(3):696-706. PMC: 3319220. DOI: 10.1210/jc.2011-1319. View

15.

Marinella M . The refeeding syndrome and hypophosphatemia. Nutr Rev. 2003; 61(9):320-3. DOI: 10.1301/nr.2003.sept.320-323. View

16.

Christmann V, de Grauw A, Visser R, Matthijsse R, van Goudoever J, van Heijst A . Early postnatal calcium and phosphorus metabolism in preterm infants. J Pediatr Gastroenterol Nutr. 2013; 58(4):398-403. DOI: 10.1097/MPG.0000000000000251. View

17.

Lietman S, Germain-Lee E, Levine M . Hypercalcemia in children and adolescents. Curr Opin Pediatr. 2010; 22(4):508-15. PMC: 2967024. DOI: 10.1097/MOP.0b013e32833b7c23. View

18.

Mizumoto H, Mikami M, Oda H, Hata D . Refeeding syndrome in a small-for-dates micro-preemie receiving early parenteral nutrition. Pediatr Int. 2012; 54(5):715-7. DOI: 10.1111/j.1442-200X.2012.03590.x. View

19.

Hearing S . Refeeding syndrome. BMJ. 2004; 328(7445):908-9. PMC: 390152. DOI: 10.1136/bmj.328.7445.908. View

20.

Brener Dik P, Galletti M, Fernandez Jonusas S, Alonso G, Mariani G, Fustinana C . Early hypophosphatemia in preterm infants receiving aggressive parenteral nutrition. J Perinatol. 2015; 35(9):712-5. DOI: 10.1038/jp.2015.54. View