Skip to main content
SpringerLink
Log in

Factors associated with early phosphate levels in preterm infants

  • Original Article
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

To investigate perinatal factors and early morbidities associated with early serum phosphate (sPhos) levels in a cohort of preterm infants. Retrospective data were obtained from the medical records of a cohort of 454 infants born at < 32 weeks gestational age. Serum phosphate levels were directly associated with gestational age, body weight z-score, and Apgar scores and inversely associated with timing of enteral nutrition initiation and diet consisting of mostly breast milk. Maternal hypertension, lactate levels, early symptomatic hypotension, and total protein supplemented on days 1 to 3 were also inversely associated with sPhos. Morbidities that were found to be associated with sPhos did not persist after adjustment for confounding factors.

Conclusions: We report a novel association between early sPhos and timing and content of enteral nutrition, as well as with the early neonatal hemodynamic condition of preterm infants. This information may help identify infants at risk for low sPhos and aid in the nutritional strategy utilized in these patients. This study did not identify early morbidities associated with sPhos.

What is Known:

• High initial amino acid intake is associated with increased risk of Refeeding like syndrome and hypophosphatemia, among preterm infants.

What is New:

• Early enteral nutrition, starting within the first 72 h of life, is associated with higher serum phosphate (sPhos) compared to nothing per os (NPO).

• sPhos was not associated with early adverse neonatal outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

BW:

birth weight

GA:

gestational age

IVH:

intraventricular hemorrhage

NEC:

necrotizing enterocolitis

NICU:

neonatal intensive care units

PI-ReFeeding syndrome:

placental incompletely restored feeding syndrome

PN:

parenteral nutrition

PVL:

periventricular leukomalacia

SGA:

small for gestational age

sPhos:

serum Phosphor levels

References

  1. Skipper A (2012) Refeeding syndrome or refeeding hypophosphatemia: a systematic review of cases. Nutr Clin Pract. https://doi.org/10.1177/0884533611427916

  2. Patel U, Sriram K (2009) Acute respiratory failure due to refeeding syndrome and hypophosphatemia induced by hypocaloric enteral nutrition. Nutrition. https://doi.org/10.1016/j.nut.2008.09.011

  3. Bonsante F, Iacobelli S, Latorre G et al (2013) 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. https://doi.org/10.1371/journal.pone.0072880

  4. Antachopoulos C, Margeli A, Giannaki M, Bakoula C, Liakopoulou T, Papassotiriou I (2002) Transient hypophosphataemia associated with acute infectious disease in paediatric patients. Scand J Infect Dis. https://doi.org/10.1080/0036554021000026960

  5. Igarashi A, Okuno T, Ohta G, Tokuriki S, Ohshima Y (2017) Risk factors for the development of refeeding syndrome-like hypophosphatemia in very low birth weight infants. Dis Markers. https://doi.org/10.1155/2017/9748031

  6. Ichikawa G, Watabe Y, Suzumura H, Sairenchi T, Muto T, Arisaka O (2012) Hypophosphatemia in small for gestational age extremely low birth weight infants receiving parenteral nutrition in the first week after birth. J Pediatr Endocrinol Metab. https://doi.org/10.1515/jpem-2011-0485

  7. Ross JR, Finch C, Ebeling M, Taylor SN (2013) Refeeding syndrome in very-low-birth-weight intrauterine growth-restricted neonates. J Perinatol 33:717–720. https://doi.org/10.1038/jp.2013.28

    Article  CAS  PubMed  Google Scholar 

  8. Valentine CJ, Fernandez S, Rogers LK et al (2009) Early amino-acid administration improves preterm infant weight. J Perinatol. https://doi.org/10.1038/jp.2009.51

  9. Dinerstein A, Nieto RM, Solana CL, Perez GP, Otheguy LE, Larguia AM (2006) Early and aggressive nutritional strategy (parenteral and enteral) decreases postnatal growth failure in very low birth weight infants. J Perinatol. https://doi.org/10.1038/sj.jp.7211539

  10. Ibrahim M, Jones LJ, Lai NM, Tan K (2016) Dexmedetomidine for analgesia and sedation in newborn infants receiving mechanical ventilation. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD012361

  11. Lucas A, Morley R, Cole TJ et al (1990) Early diet in preterm babies and developmental status at 18 months. Lancet. https://doi.org/10.1016/0140-6736(90)93026-L

  12. Sakurai M, Itabashi K, Sato Y, Hibino S, Mizuno K (2008) Extrauterine growth restriction in preterm infants of gestational age ≤32 weeks. Pediatr Int. https://doi.org/10.1111/j.1442-200X.2007.02530.x

  13. Mizumoto H, Mikami M, Oda H, Hata D (2012) Refeeding syndrome in a small-for-dates micro-preemie receiving early parenteral nutrition. Pediatr Int. https://doi.org/10.1111/j.1442-200X.2012.03590.x

  14. Boubred F, Herlenius E, Bartocci M, Jonsson B, Vanpée M (2015) Extremely preterm infants who are small for gestational age have a high risk of early hypophosphatemia and hypokalemia. Acta Paediatr Int J Paediatr. https://doi.org/10.1111/apa.13093

  15. Christmann V, De Grauw AM, Visser R, Matthijsse RP, Van Goudoever JB, Van Heijst AFJ (2014) Early postnatal calcium and phosphorus metabolism in preterm infants. J Pediatr Gastroenterol Nutr. https://doi.org/10.1097/MPG.0000000000000251

  16. Moltu SJ, Strømmen K, Blakstad EW et al (2013) Enhanced feeding in very-low-birth-weight infants may cause electrolyte disturbances and septicemia - a randomized, controlled trial. Clin Nutr. https://doi.org/10.1016/j.clnu.2012.09.004

  17. Senterre T, Zahirah IA, Pieltain C, De Halleux V, Rigo J (2015) Electrolyte and mineral homeostasis after optimizing early macronutrient intakes in VLBW infants on parenteral nutrition. J Pediatr Gastroenterol Nutr. https://doi.org/10.1097/MPG.0000000000000854

  18. Boateng AA, Sriram K, Meguid MM, Crook M (2010) Refeeding syndrome: treatment considerations based on collective analysis of literature case reports. Nutrition. https://doi.org/10.1016/j.nut.2009.11.017

  19. Mulla S, Stirling S, Cowey S et al (2017) Severe hypercalcaemia and hypophosphataemia with an optimised preterm parenteral nutrition formulation in two epochs of differing phosphate supplementation. Arch Dis Child Fetal Neonatal Ed. https://doi.org/10.1136/archdischild-2016-311107

  20. Pająk A, Królak-Olejnik B, Szafrańska A (2018) Early hypophosphatemia in very low birth weight preterm infants. Adv Clin Exp Med. https://doi.org/10.17219/acem/70081

  21. Fenton TR, Kim JH (2013) A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. https://doi.org/10.1186/1471-2431-13-59

  22. Papile LA, Burstein J, Burstein R, Koffler H (1978) Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. https://doi.org/10.1016/S0022-3476(78)80282-0

  23. Kliegman RM, Walsh MC (1987) Neonatal necrotizing enterocolitis: pathogenesis, classification, and spectrum of illness. Curr Probl Pediatr. https://doi.org/10.1016/0045-9380(87)90031-4

  24. Greer FR (2016) Calcium and phosphorus and the preterm infant. Neoreviews. https://doi.org/10.1542/neo.17-4-e195

  25. Mihatsch W, Fewtrell M, Goulet O et al (2018) ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: calcium, phosphorus and magnesium. Clin Nutr. https://doi.org/10.1016/j.clnu.2018.06.950

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Schneider Children’s Medical Center, Petah Tikva, Israel

    Daniel Yakubovich & Ori Snapiri

  2. Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel

    Daniel Yakubovich, Tzipi Strauss, Dror Ohana, Ori Snapiri, Abraham Tsur & Iris Morag

  3. Department of Pediatrics, Chaim Sheba Medical Center, Ramat Gan, Israel

    Tzipi Strauss & Briggite Kochavi

  4. Department of Pediatrics, Grigore Alexandrescu Emergency Clinical Hospital for Children in Bucharest, București, Romania

    Camelia Taran

  5. Faculty of Medicine, University of Ottawa, Ottawa, Canada

    Dalia Limor Karol

  6. Department of Neonatology, Soroka Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel

    Orna Starez- Chaham

  7. Department of Obstetrics and Gynecology, Stanford University, Stanford, CA, USA

    Abraham Tsur

  8. Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Ramat Gan, Israel

    Abraham Tsur

  9. Department of Pediatrics, Shamir Medical Center, 70300, Zerifin, Israel

    Iris Morag

Authors
  1. Daniel Yakubovich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tzipi Strauss
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dror Ohana
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Camelia Taran
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ori Snapiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dalia Limor Karol
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Orna Starez- Chaham
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Briggite Kochavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Abraham Tsur
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Iris Morag
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Dr. Daniel Yakubovich made substantial contributions to the study design, data analysis, and interpretation as well as for the manuscript preparation.

Dr. Tzipi Strauss made substantial contributions to conception and design, made substantial contributions to interpretation of results, critically revised the manuscript, and gave the final approval of the version to be published.

Dr. Dror Ohana, Dr. Camelia Taran, and Dr. Ori Snapiri, made substantial contributions to study design, data collection, and interpretation of results; critically revised the manuscript; and gave final approval of the version to be published.

Ms. Dalia Limor Karol provided assistance with data acquisition, the manuscript preparation, including review of each version of the manuscript, and gave final approval of the version to be published.

Dr. Orna Starez- Chaham and Dr. Abraham Tsur made substantial contributions to study design, provided assistance with interpretation of results and manuscript preparation, and gave final approval of the version to be published.

Mrs. Brigitte Kochavi made substantial contributions to conception and design, critically revised the manuscript, and gave final approval of the version to be published.

Dr. Iris Morag is the principal investigators, made substantial contributions to conception and design, provided supervision with all aspects of the research including study design and data collection, made substantial contributions to interpretation of results, and critically revised the manuscript, final approval of the version to be published.

Corresponding author

Correspondence to Iris Morag.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

The study protocol has been approved by the institute’s committee on human research (3739-16-SMC) and this committee waived the need for consent.

Additional information

Communicated by Daniele De Luca

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 40 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yakubovich, D., Strauss, T., Ohana, D. et al. Factors associated with early phosphate levels in preterm infants. Eur J Pediatr 179, 1529–1536 (2020). https://doi.org/10.1007/s00431-020-03622-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-020-03622-7

Keywords

Search

Navigation