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J. Pediatr. (Rio J.) vol.82 no.5 Porto Alegre Sept./Oct. 2006
Sodium intake in very low birth weight infants: is more always better?
MD, Professor of Pediatrics, Neonatology, Department of Neonatology, Children's National Medical Center, Washington, DC, USA
The problem of sodium balance in low birth weight infants
In this issue of Jornal de Pediatria, Tanaka et al. publish results of their detailed study to assess the influence of fortification of banked human breast milk feeding on urinary fractional excretion of sodium, specific gravity and osmolality.1 To our knowledge, no study in very low birth weight infants to date has examined strict sodium balance in this premature population first achieving postnatal growth with enteric feeding of human breast milk. The authors assume, and I think correctly, that human breast milk is the best nutritional resource for feeding premature human babies.
However, some controversy still exists regarding the efficacy of human milk fortifier [in this study, FM85 (Nestle) at 5 g per 100 mL of breast milk providing an additional supply of 1 g of protein, 3.4 g of carbohydrates, 20 mg of sodium, 75 mg of calcium and 45 mg of phosphorus]. While bone mineral content may be increased to values comparable to those in term infants with fortification, follow-up at 44 weeks postconceptional age was not affected by previous mineral supplementation.2 Indeed Tanaka et al. state in their discussion, the parameters evaluated are basically restricted to calcium, phosphorus, alkaline phosphatase and urea. Rarely is serum sodium evaluated. And their own data do not demonstrate significantly enhanced growth rates resulting from breast milk fortification, nor did they propose to evaluate bone mineralization as the result of breast milk fortification.
Rather, the authors raise their "concern with the potential adverse effects of diet on the renal function of preterms , since the point of renal maturity is at around 34 weeks' gestational age, and it is premature infants younger than this who require fortified breast milk. The renal function of premature infants is faced by a variety of limitations, the most significant of w hich are: glomerular tubular balance dysfunction, characterized by a low glomerular filtration rate and an even more accentuated reduction in tubular reabsorption capacity, elevated fractional sodium excretion (FENa) and limited urinary concentration capacity."3,4
Sodium balance during fetal life and with premature birth
During fetal growth, urine volume formation is relatively low due to a low GFR associated with high renal vascular resistance in utero.5 Fractional reabsorption of filtered sodium increases with maturity so that urine is hypotonic relative to plasma by mid-gestation. Urine formation again decreases towards term (past 34 weeks' gestation) as the distal tubules become more responsive to fetal arginine vasopressin.6 This coincides with the transport of large quantities of sodium chloride and obligate water into the fetus from the mother ensuring a positive water and electrolyte balance for growth.6,7 However, studies in fetal lamb preparations suggest that the by mid-gestation the fetus will respond to extracellular volume expansion with modulation of these high rates of proximal and distal tubular reabsorption.8
Term infants continue to demonstrate positive sodium balance over a wide range of sodium intakes.7 This characteristic of neonatal renal function is favorable during active growth and may be maintained by high circulating levels of aldosterone.6 This functional hyperaldosteronism is probably a result of a blunted negative feedback control on renin production.9 Despite its functional advantages for the healthy growing infant, the renal bias toward sodium reabsorption may limit the infant's ability to enhance sodium and water excretion during acute extracellular compartment loading.10,11
Premature infants have other difficulties with sodium balance. In contrast to the term infant, their basal excretion of sodium is high (reflected by a high fractional excretion of sodium at earlier gestational ages). With only a slight increase in GFR from in utero levels before 34 weeks' gestation, a relatively large percent of the filtered sodium chloride is excreted due to the less mature tubular response to aldosterone and diminished adrenal production of aldosterone in response to renin-angiotensin stimulation. Thus, the premature infant early in life is susceptible to both sodium wasting resulting in body water contraction, and an inability to accommodate salt and water volume expansion due to the limited GFR.10
Salt restriction versus salt maintenance in low birth weight infants
Costarino et al. conducted a randomized controlled trial of sodium restriction versus maintenance sodium administration during the first five days of life in infants born with less than 1,000 grams and less than 28 weeks' gestation.12 Infants were randomly assigned to receive either no maintenance sodium additive, or sodium replenishment at 3-4 mEq/kg/day added to maintenance fluids beginning on day 2 of life. Two of 9 infants in the sodium restricted group became hyponatremic with serum sodium concentrations less than 130 mEq/L, while two of eight infants in the sodium replenishment group became hypernatremic with serum sodium greater than 150 mEq/L. Daily assessments of serum sodium concentrations were significantly and consistently higher in the sodium supplemented infants.12 In Tanaka's study, infants were older, entering a growth phase, and did not demonstrate disturbances in reported serum sodium concentrations.
Sodium output in the urine remained the same for restricted infants early in the (Costarino) study,12 but began to increase after day 4 in infants in the supplemented group. Sodium balance was nearly zero in the sodium supplemented group (intake matched urinary excretion), but remained negative in the sodium restricted group up to -6 mEq/kg/day. Fluid intakes prescribed independently of prescribed sodium intakes were similar in both groups of babies between 90 and 130 mL/kg/day. However, volume intake exceeded 130 mL/kg/day after 3 days in the supplemented infants, higher than the salt restricted babies who only received approximately 90 mL/kg/day. Urine output was fixed at 2-4 mL/kg/h (about 50-100 mL/kg/day) throughout the study in both groups, and was not dependent on either the volume of fluid administered or the amount of sodium intake prescribed. Tanaka et al. did not render calculations of actual sodium balance, and instead reported spot urine fractional excretions of sodium (one of the best indicators of renal tubule function in premature neonates), and measured urine osmolality and specific gravity as clinical indicators of solute loading. This editorial reviewer agrees these are reassuringly normal in the authors' study of pooled human breast milk with fortification in still very immature kidneys at < 34 weeks postconceptional age and followed in a longitudinal fashion over 3 critical time intervals.
Survival (in the Costarino study) was similar in both groups, and the occurrences of intraventricular hemorrhage and patent ductus arteriosus were also similar.12 There was a trend, however, towards infants developing bronchopulmonary dysplasia in the high sodium/high fluid intake group: 7 of 7 infants versus 4 of 8 infants in the low sodium/low fluid intake group.
Hartnoll et al. observed that the increased risk of continuing oxygen requirement in extremely low birth weight infants is more likely to be a direct consequence of persistent expansion of the extracellular compartment and increased pulmonary interstitial fluid, resulting from sodium intake. This adds further weight to the authors' view that the timing of routine sodium supplementation should be delayed until the onset of postnatal extracellular volume contraction, marked clinically by weight loss.13
Neither the Costarino nor the Hartnoll study addressed sodium supplementation and renal salt handling in growing well premature babies, whereas Tanaka et al. address this significant question.1 Apparently infants in Tanaka's study were well, and free of significant pulmonary disease. Therefore, sodium fortification would not have adversely affected their pulmonary function. In short we agree with the authors' conclusion, "No adverse effects on the renal function of these preterms were detected as a result of being fed fortified donor human milk."1
1. Tanaka A, Rugolo LM, Miranda AF, Trindade CE. Fractional sodium excretion, urinary osmolality and specific gravity in preterm infants fed with fortified donor human milk. J Pediatr (Rio J). 2006;82:335-40.
2. Ernst JA, Gross SJ. Types and methods of feeding for infants. In: Polin RA, Fox WW, editors. Fetal and neonatal physiology. 2nd ed. Philadelphia: WB Saunders; 1992. p. 263.
3. Norero C, Maturana A. Fisiología renal en el recién-nacido. Rev Chil Pediatr. 1994;65:234-40.
4. Feld LG, Corey HE. Renal transport of sodium during early development. In: Polin RA, Fox WW, Abman SH, editors. Fetal and neonatal physiology. 3rd ed. Pennsylvania: WB Saunders; 2004. p. 1267-77.
5. Rudolph AM, Heyman MA, Teramo KA, Barrett CT, Raiha NC. Studies on the circulation of the previable human fetus. Pediatr Res. 1971;5:452-65.
6. Aperia A, Elinder G. Distal tubular sodium reabsorption in the developing rat kidney. Am J Physiol. 1981;240:F487-91.
7. Aperia A, Broberger O, Thodenius K, Zetterstrom R. Renal response to an oral sodium load in newborn full-term infants. Acta Pediatr Scand. 1972;61:670-6.
8. Robillard JE, Sessions C, Kennedey RL, Hamel-Robillard L, Smith FG Jr. Interrelationship between glomerular filtration rate and renal transport of sodium and chloride during fetal life. Am J Obstet Gynecol. 1977;128:727-34.
9. Goldsmith DI, Drukker A, Blaufox MD, Edelman CM Jr., Spitzer A. Hemodynamic and excretory responses of the neonatal canine kidney to acute volume expansion. Am J Physiol. 1979;237:F392-97.
10. Aperia A, Zetterstrom R. Renal control of fluid homeostasis in the newborn infant. Clin Perinatol. 1982;9:523-33.
11. Drukker A, Goldsmith DI, Spitzer A, Edelman CM Jr., Blaufox MD. The renin-angiotensin system in newborn dogs: developmental patterns and response to acute saline loading. Pediatr Res. 1980;14(4 Pt 1):304-7.
12. Costarino AT Jr., Gruskay JA, Corcoran L, Polin RA, Baumgart S. Sodium restriction versus daily maintenance replacement in very low birth weight premature neonates: a randomized blind therapeutic trial. J Pediatr. 1992;120:99-106. Comment in: J Pediatr. 1992;121:663-4.
13. Hartnoll G, Betremieux P, Modi N. Randomised controlled trial of postnatal sodium supplementation on body composition in 25 to 30 week gestational age infants. Arch Dis Child Fetal Neonatal Ed. 2000;82:F24-8.
A sobrevida (no estudo de Costarino) foi semelhante em ambos os grupo, e a ocorrência de hemorragia intraventricular e persistência do duto arteriovenoso também foi semelhante12. Contudo, observou-se uma tendência ao desenvolvimento de displasia broncopulmonar no grupo com ingestão elevada de sódio/fluido: 7 de 7 bebês versus 4 de 8 bebês no grupo com baixa ingestão de sódio/fluido.