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Severe Biochemical Disturbances after Introduction of a New Regional Parenteral Nutrition Formulation Matching Current ESPGHAN Recommendations

Presented at the Neonatal Society 2015 Spring Meeting.

Mulla S1, Cowey S1, Close R1, Pullan S1, Howe R1, Radbone L2, Clarke P1

1 Neonatal Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
2 East of England Neonatal Operational Delivery Network, UK

Background: Enhanced early postnatal nutrient supply to very low birth weight infants is associated with improved growth velocity, white matter maturation and head growth (1). Current ESPGHAN guidelines recommend a maximum amino acid content of 4.0 g/kg/day and a Ca2+:PO4 ratio within the range 1.3-1.7:1 for preterm parenteral nutrition (PN). In January 2013 East of England regional NICUs introduced a new PN formulation that essentially accorded with these latest ESPGHAN recommendations. Our aqueous bag contained 3.3 g amino acids, 1.7 mmol Ca2+, and 1.1 mmol PO4 per 100 mL and, including lipid, achieved a first-week Ca2+:PO4ratio in the range 1.4-1.3:1. During 2013 several regional NICUs, including our own, reported cases of severe hypercalcaemia and/or hyposphataemia in preterm infants during the first postnatal week. Our hypotheses were that these electrolyte disturbances were due to the ‘refeeding syndrome’ (2,3), and that increasing the PO4 content to match Ca2+ in an equimolar ratio would prevent these abnormalities. We report our audit of first-week biochemistry in preterm babies who received the new PN formulation in epochs before and after provision of increased phosphate supplementation.

Methods: We retrospectively reviewed casenotes, PN charts, and serum biochemistry of all preterm infants in our NICU, who received the new regional PN formulation in two discrete ~6-month epochs before (Phase 1) and after (Phase 2) the date of ad hoc-increased PO4supplementation (December 2nd 2013). The PN recipe was otherwise unchanged across epochs. We assessed the incidence and severity of biochemical derangements occurring with PN delivery in the first postnatal week. We pre-defined severe hypercalcaemia as serum Ca2+ >3.0 mmol/L, hypophosphataemia as PO4 <1.5 mmol/L, and severe hypophosphataemia as PO4 <1.0 mmol/L. We analysed by intention to treat.

Results: Data for 102 infants were reviewed. There were no significant differences in baseline characteristics or amino acid intakes between the two epochs. The table shows median (range) first-week serum Ca2+ and PO4 concentrations in the phases and numbers of infants with deranged biochemistry.

Severe Biochemical Disturbances after Introduction of a New Regional Parenteral Nutrition Formulation Matching Current ESPGHAN Recommendations

Conclusion: Introduction of the latest ESPGHAN-recommended intakes for amino acids with the recommended Ca2+:PO4 ratio for preterm PN led to severe hypercalcaemia and hypophosphataemia in most preterm babies in our NICU. Extra phosphate supplementation to achieve an equimolar Ca2+:PO4 ratio significantly reduced the incidence and severity of these biochemical disturbances, while maintaining the recommended amino acid, Ca2+ and PO4intakes. Our audit findings have assisted a revised regional PN formulation and may inform future ESPGHAN recommendations.

Corresponding author: shavetamulla@gmail.com

References
1. Strømmen K, et al. Neonatology. 2015; 107: 68-75
2. Moltu SJ, et al. Clin Nutr. 2013; 32: 207-12
3. Bonsante F, et al. PLoS One. 2013; 8: e72880

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