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Severe hypercalcaemia and hypophosphataemia with an optimised preterm parenteral nutrition formulation in two epochs of differing phosphate supplementation
  1. Shaveta Mulla1,
  2. Susan Stirling2,
  3. Sarah Cowey1,
  4. Rosie Close1,
  5. Sara Pullan1,
  6. Rosalind Howe1,
  7. Lynne Radbone3,
  8. Paul Clarke1
  1. 1 Neonatal Intensive Care Unit, Jenny Lind Children’s Hospital, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
  2. 2 Norwich Clinical Trials Unit, Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK
  3. 3 East of England Neonatal Operational Delivery Network, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  1. Correspondence to Dr Paul Clarke, Consultant Neonatologist, Neonatal Intensive Care Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich NR4 7UY, UK; paul.clarke{at}


Objective To compare in two epochs of differing phosphate provision serum calcium, phosphate, potassium, and sodium concentrations and the frequency of abnormality of these electrolytes and of sepsis in preterm infants who received an optimised higher amino acid-content formulation.

Design and setting Retrospective cohort study at a single tertiary-level neonatal unit.

Patients Preterm infants given parenteral nutrition (PN) in the first postnatal week during two discrete 6-month epochs in 2013–2014.

Interventions In epoch 1 the Ca2+:PO4 molar ratio of the PN formulation was ~1.3–1.5:1 (1.7 mmol Ca2+ and 1.1 mmol PO4 per 100 mL aqueous phase) and in epoch 2 was 1.0:1 via extra phosphate supplementation (1.7 mmol Ca2+ and 1.7 mmol PO4 per 100 mL).

Main outcome measures Peak calcium and nadir phosphate and potassium concentrations, and proportions with severe hypercalcaemia (Ca2+ >3.0 mmol/L), hypophosphataemia (PO4<1.5 mmol/L), and hypokalaemia (K+ <3.5 mmol/L) within the first postnatal week.

Results In epoch 2, peak calcium concentrations were lower than in epoch 1 (geometric means: 2.83 mmol/L vs 3.09 mmol/L, p value<0.0001), fewer babies were severely hypercalcaemic (10/49, 20%, vs 31/51, 61%, p value<0.0001); nadir plasma phosphate concentrations were higher (means: 1.54 mmol/L vs 1.32 mmol/L, p value=0.006), and there were fewer cases of hypophosphataemia (17/49, 35% vs 31/51, 61%, p value=0.009) and hypokalaemia (12/49, 25% vs 23/51, 45%, p value=0.03).

Conclusions Reverting from a PN Ca2+:PO4 molar ratio of 1.3–1.5:1 to a ratio of 1.0:1 was associated with a lower incidence and severity of hypophosphataemia and hypercalcaemia. For preterm infants given higher concentrations of amino acids (≥2.5 g/kg/day) from postnatal day 1, an equimolar Ca2+:PO4 ratio may be preferable during the first postnatal week.

  • complications
  • hyperalimentation
  • phosphate
  • amino acids
  • protein

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  • These data were presented orally in abstract form at the Spring meeting of the Neonatal Society, March 2015, and at the jENS Congress, Budapest, September 2015.

  • Contributors PC conceived the idea for this project. SM, SC, RC and RH undertook the data collection. LR and SP provided intellectual input. SS provided statistical expertise and analysed the data. PC and SM wrote the first manuscript draft and PC wrote the final draft. All authors contributed to manuscript revisions and approved the final version. PC is guarantor.

  • Competing interests PC served as an independent member of the Trial Steering Committee for the NEON study.

  • Ethics approval This study was undertaken as a clinical audit and service evaluation. Formal ethics approval was not required under the contemporaneous NRES guidance.

  • Provenance and peer review Not commissioned; externally peer reviewed.