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Preterm infant nutrition: considerations for infants at risk of refeeding syndrome

Abstract

Refeeding syndrome (RS) in preterm infants is a scenario of fetal malnutrition, primarily resulting from placental insufficiency, followed by a postnatal physiologic adaptation and response to an imbalance of nutrients provided parenterally. Growth restriction and small gestational age status are common findings in infants at risk of developing RS. Adverse clinical outcomes associated with RS may be severe and life-threatening. The biochemical abnormalities that occur in RS may be mitigated through careful monitoring and adaptation of the clinical management of parenteral and enteral nutrition. This perspective reviews the physiology and metabolism in infants with RS and provides suggested approaches to their clinical monitoring and nutritional management.

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Evdokia Dimitriadis, Daniel L. Rolnik, … Ellen Menkhorst

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Data sharing is not applicable to this perspective as no datasets were generated or analyzed for its development.

References

  1. Sharma D, Shastri S, Sharma P. Intrauterine growth restriction: antenatal and postnatal aspects. Clin Med Insights Pediatr. 2016;10:67–83.

    Article  Google Scholar 

  2. ACOG Practice bulletin no. 134: fetal growth restriction. Obstet Gynecol. 2013;121:1122–33.

  3. Boateng AA, Sriram K, Meguid MM, Crook M. Refeeding syndrome: treatment considerations based on collective analysis of literature case reports. Nutrition. 2010;26:156–67.

    Article  Google Scholar 

  4. Huang X, Anderle P, Hostettler L, Baumann MU, Surbek DV, Ontsouka EC, et al. Identification of placental nutrient transporters associated with intrauterine growth restriction and pre-eclampsia. BMC Genom. 2018;19:173.

    Article  Google Scholar 

  5. Gaccioli F, Lager S. Placental nutrient transport and intrauterine growth restriction. Front Physiol. 2016;7:40.

    Article  Google Scholar 

  6. Cormack BE, Jiang Y, Harding JE, Crowther CA, Bloomfield FH, Pro VTG. Neonatal refeeding syndrome and clinical outcome in extremely low-birth-weight babies: secondary cohort analysis from the ProVIDe trial. J Parenter Enter Nutr. 2021;45:65–78.

    Article  CAS  Google Scholar 

  7. da Silva JSV, Seres DS, Sabino K, Adams SC, Berdahl GJ, Citty SW, et al. ASPEN consensus recommendations for refeeding syndrome. Nutr Clin Pract. 2020;35:178–95.

    Article  Google Scholar 

  8. Ross JR, Finch C, Ebeling M, Taylor SN. Refeeding syndrome in very-low-birth-weight intrauterine growth-restricted neonates. J Perinatol. 2013;33:717–20.

    Article  CAS  Google Scholar 

  9. Igarashi A, Okuno T, Ohta G, Tokuriki S, Ohshima Y. Risk factors for the development of refeeding syndrome-like hypophosphatemia in very low birth weight infants. Dis Markers. 2017;2017:9748031.

    Article  Google Scholar 

  10. Parramon-Teixido CJ, Gomez-Ganda L, Garcia-Palop B, Lines-Palazon M, Blanco-Grau A, Montoro-Ronsano JB, et al. The influence of parenteral protein intake on electrolyte disturbances in premature infants. Pediatrics. 2021;95:139–46.

    Google Scholar 

  11. Bustos Lozano G, Soriano-Ramos M, Pinilla Martin MT, Chumillas Calzada S, Garcia Soria CE, Pallas-Alonso CR. Early hypophosphatemia in high-risk preterm infants: efficacy and safety of sodium glycerophosphate from first day on parenteral nutrition. J Parenter Enter Nutr. 2019;43:419–25.

    Article  CAS  Google Scholar 

  12. Bradford CV, Cober MP, Miller JL. Refeeding syndrome in the neonatal intensive care unit. J Pediatr Pharm Ther. 2021;26:771–82.

    Google Scholar 

  13. 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;61:491–8.

    Article  CAS  Google Scholar 

  14. Bonsante F, Iacobelli S, Latorre G, Rigo J, De Felice C, Robillard PY, et al. Initial amino acid intake influences phosphorus and calcium homeostasis in preterm infants—it is time to change the composition of the early parenteral nutrition. PLoS One. 2013;8:e72880.

    Article  CAS  Google Scholar 

  15. Chaudhary V, Gohil J SP. Hypophosphatemia in refeeding syndrome in intrauterine growth restricted IUGR neonates who are receiving nutrition: a prospective observational study. Asian J Pediatr Res. 2020;3:23–9.

    Article  Google Scholar 

  16. Dreyfus L, Fischer Fumeaux CJ, Remontet L, Essomo Megnier Mbo Owono MC, Laborie S, Maucort-Boulch D, et al. Low phosphatemia in extremely low birth weight neonates: a risk factor for hyperglycemia? Clin Nutr. 2016;35:1059–65.

    Article  CAS  Google Scholar 

  17. Hakan N, Aydin M, Dilli D, Zenciroglu A, Okumus N. Transient hyperinsulinemia may be responsible for electrolyte abnormalities of refeeding syndrome seen in very low birth weight infants with intrauterine growth-restriction. J Perinatol. 2014;34:247.

    Article  CAS  Google Scholar 

  18. Pezzati M, Barni S, Chiti G, Danesi G, Rubaltelli FF. Prolonged hyperinsulinemic hypoglycemia in a small for date preterm. Minerva Pediatr. 2003;55:79–82.

    CAS  Google Scholar 

  19. Mizumoto H, Mikami M, Oda H, Hata D. Refeeding syndrome in a small-for-dates micro-preemie receiving early parenteral nutrition. Pediatr Int. 2012;54:715–7.

    Article  Google Scholar 

  20. Yakubovich D, Strauss T, Ohana D, Taran C, Snapiri O, Karol DL, et al. Factors associated with early phosphate levels in preterm infants. Eur J Pediatr. 2020;179:1529–36.

    Article  CAS  Google Scholar 

  21. Moltu SJ, Strommen K, Blakstad EW, Almaas AN, Westerberg AC, Braekke K, et al. Enhanced feeding in very-low-birth-weight infants may cause electrolyte disturbances and septicemia—a randomized, controlled trial. Clin Nutr. 2013;32:207–12.

    Article  CAS  Google Scholar 

  22. Mannarino CN, Chaouki AS, de Regnier RA, Robinson DT. Hypophosphatemia in prematurity leading to complete heart block: a case report. J Parenter Enteral Nutr. 2022;46:1203–6.

  23. Beune IM, Bloomfield FH, Ganzevoort W, Embleton ND, Rozance PJ, van Wassenaer-Leemhuis AG, et al. Consensus based definition of growth restriction in the newborn. J Pediatr. 2018;196:71–6 e1.

    Article  Google Scholar 

  24. Boullata JI, Mirtallo JM, Sacks GS, Salman G, Gura K, Canada T, et al. Parenteral nutrition compatibility and stability: a comprehensive review. J Parenter Enter Nutr. 2022;46:273–99.

    Article  Google Scholar 

  25. Hair AB, Chetta KE, Bruno AM, Hawthorne KM, Abrams SA. Delayed Introduction of Parenteral Phosphorus Is Associated with Hypercalcemia in Extremely Preterm Infants. J Nutr. 2016;146:1212–6.

    Article  CAS  Google Scholar 

  26. Bombell S, McGuire W. Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst Rev. 2008:CD001970.

  27. Malcolm G, Ellwood D, Devonald K, Beilby R, Henderson-Smart D. Absent or reversed end diastolic flow velocity in the umbilical artery and necrotising enterocolitis. Arch Dis Child. 1991;66:805–7. 7 Spec No

    Article  CAS  Google Scholar 

  28. Dorling J, Kempley S, Leaf A. Feeding growth restricted preterm infants with abnormal antenatal Doppler results. Arch Dis Child Fetal Neonatal Ed. 2005;90:F359–63.

    Article  CAS  Google Scholar 

  29. Manogura AC, Turan O, Kush ML, Berg C, Bhide A, Turan S, et al. Predictors of necrotizing enterocolitis in preterm growth-restricted neonates. Am J Obstet Gynecol. 2008;198:638 e1–5.

    Article  Google Scholar 

  30. Karagianni P, Briana DD, Mitsiakos G, Elias A, Theodoridis T, Chatziioannidis E, et al. Early versus delayed minimal enteral feeding and risk for necrotizing enterocolitis in preterm growth-restricted infants with abnormal antenatal Doppler results. Am J Perinatol. 2010;27:367–73.

    Article  Google Scholar 

  31. Leaf A, Dorling J, Kempley S, McCormick K, Mannix P, Linsell L, et al. Early or delayed enteral feeding for preterm growth-restricted infants: a randomized trial. Pediatrics. 2012;129:e1260–8.

    Article  Google Scholar 

  32. Dorling J, Abbott J, Berrington J, Bosiak B, Bowler U, Boyle E, et al. Controlled trial of two incremental milk-feeding rates in preterm infants. N Engl J Med. 2019;381:1434–43.

    Article  Google Scholar 

  33. Miller J, Tonkin E, Damarell RA, McPhee AJ, Suganuma M, Suganuma H, et al. A systematic review and meta-analysis of human milk feeding and morbidity in very low birth weight infants. Nutrients. 2018;10:707.

  34. Pajak A, Krolak-Olejnik B, Szafranska A. Early hypophosphatemia in very low birth weight preterm infants. Adv Clin Exp Med. 2018;27:841–7.

    Article  Google Scholar 

  35. 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;25:317–21.

    Article  CAS  Google Scholar 

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Authors

Contributions

DTR, SNT, and FM contributed equally to the design and writing for this manuscript. DTR, SNT, and FM contributed to the conception and design, equally contributed to the drafting of the manuscript, and critically revised the manuscript. DTR, SNT, and FM gave final approval of this manuscript and agree to be accountable for all aspects of this work ensuring integrity and accuracy.

Corresponding author

Correspondence to Daniel T. Robinson.

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Competing interests

DTR received compensation for serving as a member of the Data Safety Monitoring Board for a clinical investigation sponsored by Fresenius Kabi in the past 12 months. DTR and SNT serve as institutional principal investigators, with no salary funding, for a consortium database sponsored by Mead Johnson Nutrition. SNT has received an honorarium from Astarte Medical and serves as institutional principal investigator, with no salary funding, to conduct studies sponsored by Ferring Pharmaceuticals, Pfizer, and Prolacta Bioscience. FM receives research funding from Mead Johnson Nutrition.

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Robinson, D.T., Taylor, S.N. & Moya, F. Preterm infant nutrition: considerations for infants at risk of refeeding syndrome. J Perinatol 43, 120–123 (2023). https://doi.org/10.1038/s41372-022-01531-1

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