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VOLUME 2 , ISSUE 2 ( April-June, 2023 ) > List of Articles


Sodium and Growth in Preterm Infants: A Review

Benjamin R Araya, Alisha A Ziegler, Connie C Grobe, Justin L Grobe, Jeffrey L Segar

Keywords : Growth, Human, Postnatal, Premature, Preterm, Review, Sodium

Citation Information : Araya BR, Ziegler AA, Grobe CC, Grobe JL, Segar JL. Sodium and Growth in Preterm Infants: A Review. 2023; 2 (2):142-147.

DOI: 10.5005/jp-journals-11002-0060

License: CC BY-NC 4.0

Published Online: 05-07-2023

Copyright Statement:  Copyright © 2023; The Author(s).


Aim: This article is intended to review the relationship between sodium homeostasis and growth, outline reasons why preterm infants may become sodium deficient, and share data from our group and others regarding the potential benefits of dietary sodium supplementation. Background: Despite tremendous efforts over the past 20 years to optimize neonatal nutrition, postnatal growth failure in preterm infants remains a significant problem. Compelling associations have been identified between in-hospital growth failure and cardiometabolic and neurodevelopmental disorders, heightening the need to further identify the optimal nutritional needs of preterm infants. Results: The impact of sodium deficiency may have on somatic growth is poorly studied and reported upon within the human literature. In contrast, animal studies dating back almost 100 years highlight the nutritional importance of dietary sodium. Sodium homeostasis during early postnatal life is understudied and underappreciated by neonatologists. Conclusion: Insufficient sodium intake during early life is likely a critical yet underappreciated contributor to growth failure. Total body sodium depletion may be an important risk factor driving complications of premature birth. Clinical significance: Increased awareness of sodium homeostasis in preterm infants may improve outcomes in this population. Sodium intake recommendations are provided based on the interpretation of currently available literature.

  1. El Rafei R, Maier RF, Jarreau PH, et al. Postnatal growth restriction and neurodevelopment at 5 years of age: A European extremely preterm birth cohort study. Arch Dis Child Fetal Neonatal Ed 2023;fetal-neonatal-2022-324988. DOI: 10.1136/archdischild-2022-324988.
  2. Martínez-Jiménez MD, Gómez-García FJ, Gil-Campos M, et al. Comorbidities in childhood associated with extrauterine growth restriction in preterm infants: A scoping review. Eur J Pediatr 2020;179(8):1255–1265. DOI: 10.1007/s00431-020-03613-8.
  3. Mitchell HH, Carman GG. Does the addition of sodium chloride increase the value of a corn ration for growing animals? J Biol Chem 1926;68(1):165–181. Available from
  4. Koo WW, Gupta JM. Breast milk sodium. Arch Dis Child 1982;57(7):500–502. DOI: 10.1136/adc.57.7.500.
  5. Gates A, Marin T, De Leo G, et al. Nutrient composition of preterm mother's milk and factors that influence nutrient content. Am J Clin Nutr 2021;114(5):1719–1728. DOI: 10.1093/ajcn/nqab226.
  6. Perrin MT, Friend LL, Sisk PM. Fortified donor human milk frequently does not meet sodium recommendations for the preterm infant. J Pediatr 2022;244:219–223.e1. DOI: 10.1016/j.jpeds.2022.01.029.
  7. Segar JL, Grobe CC, Grobe JL. Fetal storage of osmotically inactive sodium. Am J Physiol Regul Integr Comp Physiol 2020;318(3):R512–R514. DOI: 10.1152/ajpregu.00336.2019.
  8. Schafflhuber M, Volpi N, Dahlmann A, et al. Mobilization of osmotically inactive Na+ by growth and by dietary salt restriction in rats. Am J Physiol Renal Physiol 2007;292(5):F1490–F1500. DOI: 10.1152/ajprenal.00300.2006.
  9. Gattineni J, Baum M. Developmental changes in renal tubular transport – An overview. Pediatr Nephrol 2015;30(12):2085–2098. DOI: 10.1007/s00467-013-2666-6.
  10. Bueva A, Guignard JP. Renal function in preterm neonates. Pediatr Res 1994;36(5):572–577. DOI: 10.1186/s40348-016-0068-0.
  11. Siegel SR, Oh W. Renal function as a marker of human fetal maturation. Acta Paediatr Scand 1976;65(4):481–485. DOI: 10.1111/j.1651-2227.1976.tb04917.x.
  12. Gubhaju L, Sutherland MR, Horne RS, et al. Assessment of renal functional maturation and injury in preterm neonates during the first month of life. Am J Physiol Renal Physiol 2014;307(2):F149–F158. DOI: 10.1152/ajprenal.00439.2013.
  13. Segar DE, Segar EK, Harshman LA, et al. Physiological approach to sodium supplementation in preterm infants. Am J Perinatol 2018;35(10):994–1000. DOI: 10.1055/s-0038-1632366.
  14. Segar JL, Grobe CC, Grobe JL. Maturational changes in sodium metabolism in periviable infants. Pediatr Nephrol 2021;36(11):3693–3698. DOI: 10.1007/s00467-021-05119-3.
  15. Martinerie L, Pussard E, Foix-L’Hélias L, et al. Physiological partial aldosterone resistance in human newborns. Pediatr Res 2009;66(3):323–328. DOI: 10.1203/PDR.0b013e3181b1bbec.
  16. Martinerie L, Pussard E, Yousef N, et al. Aldosterone-signaling defect exacerbates sodium wasting in very preterm neonates: The premaldo study. J Clin Endocrinol Metab 2015;100(11):4074–4081. DOI: 10.1210/jc.2015-2272.
  17. Sulyok E. Letter to the editor: Comments on “aldosterone-signaling defect exacerbates sodium wasting in very preterm neonates: The premaldo study” by Martinerie L., et al. J Clin Endocrinol Metab 2016;101(5):L54–L55. DOI: 10.1210/jc.2016-1193.
  18. Tulassay T, Rascher W, Seyberth HW, et al. Role of atrial natriuretic peptide in sodium homeostasis in premature infants. J Pediatr 1986;109(6):1023–1027. DOI: 10.1016/s0022-3476(86)80293-1.
  19. Shaffer SG, Geer PG, Goetz KL. Elevated atrial natriuretic factor in neonates with respiratory distress syndrome. J Pediatr 1986;109(6):1028–1033. DOI: 10.1016/s0022-3476(86)80294-3.
  20. Rascher W, Bald M, Kreis J, et al. Atrial natriuretic peptide in infants and children. Horm Res 1987;28(1):58–63. DOI: 10.1159/000180926.
  21. Stephenson TJ, Broughton Pipkin F, Hetmanski D, et al. Atrial natriuretic peptide in the preterm newborn. Biol Neonate 1994;66(1):22–32. DOI: 10.1159/000244086.
  22. Wassner SJ. Altered growth and protein turnover in rats fed sodium-deficient diets. Pediatr Res 1989;26(6):608–613. DOI: 10.1203/00006450-198912000-00019.
  23. Wassner SJ. The effect of sodium repletion on growth and protein turnover in sodium-depleted rats. Pediatr Nephrol 1991;5(4):501–504. DOI: 10.1007/BF01453690.
  24. Fine BP, Ty A, Lestrange N, et al. Sodium deprivation growth failure in the rat: Alterations in tissue composition and fluid spaces. J Nutr 1987;117(9):1623–1628. DOI: 10.1093/jn/117.9.1623.
  25. Haycock GB. The influence of sodium on growth in infancy. Pediatr Nephrol 1993;7(6):871–875. DOI: 10.1007/BF01213376.
  26. Mendoza SA. The Na+-H+ antiport is a mediator of cell proliferation. Acta Paediatr Scand 1987;76(4):545–547. DOI: 10.1111/j.1651-2227.1987.tb10518.x.
  27. Segar JL, Grobe CC, Balapattabi K, et al. Dissociable effects of dietary sodium in early life upon somatic growth, fluid homeostasis, and spatial memory in mice of both sexes. Am J Physiol Regul Integr Comp Physiol 2021;320(4):R438–R451. DOI: 10.1152/ajpregu.00281.2020.
  28. Ziegler AA, Grobe CC, Reho JJ, et al. Low sodium supply in early life causes growth restriction and programs long-term changes in energy homeostasis. FASEB J 2022;36(S1) R2377. Available from:
  29. Vanpée M, Herin P, Broberger U, et al. Sodium supplementation optimizes weight gain in preterm infants. Acta Paediatr 1995;84(11):1312–1314. DOI: 10.1111/j.1651-2227.1995.tb13556.x.
  30. Al-Dahhan J, Haycock GB, Nichol B, et al. Sodium homeostasis in term and preterm neonates. III. Effect of salt supplementation. Arch Dis Child 1984;59(10):945–950. DOI: 10.1136/adc.59.10.945.
  31. Isemann B, Mueller EW, Narendran V, et al. Impact of early sodium supplementation on hyponatremia and growth in premature infants: A randomized controlled trial. JPEN J Parenter Enteral Nutr 2016;40(3):342–349. DOI: 10.1177/0148607114558303.
  32. Monnikendam CS, Mu TS, Aden JK, et al. Dysnatremia in extremely low birth weight infants is associated with multiple adverse outcomes. J Perinatol 2019;39(6):842–847. DOI: 10.1038/s41372-019-0359-0.
  33. Dalton J, Dechert RE, Sarkar S. Assessment of association between rapid fluctuations in serum sodium and intraventricular hemorrhage in hypernatremic preterm infants. Am J Perinatol 2015;32(8):795–802. DOI: 10.1055/s-0034-1396691.
  34. Howell HB, Lin M, Zaccario M, et al. The impact of hypernatremia in preterm infants on neurodevelopmental outcome at 18 months of corrected age. Am J Perinatol 2022;39(5):532–538. DOI: 10.1055/s-0040-1716845.
  35. Gervais AS, Luu TM, Viennet A, et al. Neurodevelopmental consequences of early plasma sodium changes in very preterm infants. Pediatr Res 2022;92(5):1350–1356. DOI: 10.1038/s41390-022-02164-y.
  36. Al-Dahhan J, Jannoun L, Haycock GB. Effect of salt supplementation of newborn premature infants on neurodevelopmental outcome at 10–13 years of age. Arch Dis Child Fetal Neonatal Ed 2002;86(2):F120–F123. DOI: 10.1136/fn.86.2.f120.
  37. Kim YJ, Lee JA, Oh S, et al. Risk factors for late-onset hyponatremia and its influence on neonatal outcomes in preterm infants. J Korean Med Sci 2015;30(4):456–462. DOI: 10.3346/jkms.2015.30.4.456.
  38. Park JS, Jeong SA, Cho JY, et al. Risk factors and effects of severe late-onset hyponatremia on long-term growth of prematurely born infants. Pediatr Gastroenterol Hepatol Nutr 2020;23(5):472–483. DOI: 10.5223/pghn.2020.23.5.472.
  39. Wilck N, Balogh A, Markó L, et al. The role of sodium in modulating immune cell function. Nat Rev Nephrol 2019;15(9):546–558. DOI: 10.1038/s41581-019-0167-y.
  40. Jobin K, Müller DN, Jantsch J, et al. Sodium and its manifold impact on our immune system. Trends Immunol 2021;42(6):469–479. DOI: 10.1016/
  41. Jantsch J, Schatz V, Friedrich D, et al. Cutaneous Na+ storage strengthens the antimicrobial barrier function of the skin and boosts macrophage-driven host defense. Cell Metab 2015;21(3):493–501. DOI: 10.1016/j.cmet.2015.02.003.
  42. Evans RDR, Antonelou M, Sathiananthamoorthy S, et al. Inherited salt-losing tubulopathies are associated with immunodeficiency due to impaired IL-17 responses. Nat Commun 2020;11(1):4368. DOI:
  43. Tan C, Sehgal K, Sehgal K, et al. Diuretic use in infants with developing or established chronic lung disease: A practice looking for evidence. J Paediatr Child Health 2020;56(8):1189–1193. DOI: 10.1111/jpc.14877.
  44. Embleton ND, Moltu SJ, Lapillonne A, et al. Enteral nutrition in preterm infants (2022): A position paper from the espghan committee on nutrition and invited experts. J Pediatr Gastroenterol Nutr 2023;76(2):248–268. DOI: 10.1097/MPG.0000000000003642.
  45. Kleinman RE, Frank RG, eds. Pediatric nutrition: Policy of the American Academy of Pediatrics. 8th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2020. Available from:
  46. Bischoff AR, Tomlinson C, Belik J. Sodium intake requirements for preterm neonates: Review and recommendations. J Pediatr Gastroenterol Nutr 2016;63(6):e123–e129. DOI: 10.1097/MPG.0000000000001294.
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