Sodium supplementation algorithm to promote growth in infants who are preterm: randomized clinical trial

Authors: LUBERIO, BRIANNA - Indiana University School Of Medicine; SOKOL, GREGORY - Indiana University School Of Medicine; RAKOW, HANNAH - Indiana University School Of Medicine; MOSESSO, KELLY - Indiana University School Of Medicine; HOLE, VALERIE - Medical College Of Georgia; WONG, WILLIAM - Children'S Nutrition Research Center (CNRC); CHACKO, SHAJI - Children'S Nutrition Research Center (CNRC); SEGAR, JEFFREY - Medical College Of Wisconsin

Submitted to: Pediatrics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/22/2025
Publication Date: 2/20/2026
Citation: Luberio, B.M., Sokol, G.M., Rakow, H., Mosesso, K., Hole, V., Wong, W.W., Chacko, S.K., Segar, J.L. 2026. Sodium supplementation algorithm to promote growth in infants who are preterm: randomized clinical trial. Pediatrics. 2(1):1-10. https://doi.org/10.1542/pedsos.2025-001089.
DOI: https://doi.org/10.1542/pedsos.2025-001089

Interpretive Summary: Very preterm babies often grow poorly after birth, even with high-calorie nutrition. One reason may be low sodium levels, because these infants lose large amounts of sodium in urine and may not get enough from milk or formula. The objective of this study was to evaluate the effectiveness of using urine concentration to guide sodium supplementation in preterm infants to promote more rapid weight gain. In this randomized study, doctors used urine sodium tests to decide which infants should receive extra sodium. The scientists at CNRC found that infants given sodium this way gained weight faster early on, but by near-term age their overall growth was similar to those receiving standard care. Importantly, extra sodium did not increase fluid buildup or medical complications. Overall, the findings suggest many preterm infants may need more sodium to support healthy early growth, and supplementation at appropriate levels appears safe.

Technical Abstract: Evaluate the effectiveness of an algorithm using urine sodium (Na) concentration to guide dietary Na supplementation compared with standard care to promote growth in infants who are preterm. A randomized trial was conducted in 4 neonatal units in Indianapolis, Indiana, involving infants between 250/7 to 296/7 weeks gestation with birthweight > 500 g. Study arms consisted of standard care or use of algorithm beginning at 14 to 17 days postnatal age. The primary outcomes were somatic growth (weight, length, and head circumference) measured by change in Zscore between aged 2 weeks and 36 weeks postmenstrual age (PMA). Secondary outcomes included total body water and body composition. Of 260 eligible infants, 90 were consented and randomized, with 45 allocated to each arm and 43 in each arm completing the study. Thirty-eight (88%) infants randomized to the study algorithm had a low urine Na that qualified for Na supplementation (4 mEq/kg/d). Infants assigned the algorithm received more Na (5.75 +/- 0.96 mEq/kg/d) than infants assigned the standard care (3.62 +/- 1.25 mEq/kg/d); caloric intake did not differ. Change in weight Z-score from study entry until 36 weeks PMA was not statistically different between groups (0.16 +/- 0.41 vs 0.04 +/- 0.63, algorithm vs control; P = .16). Infants assigned the algorithm displayed a significantly more rapid increase in weight between weeks 0 to 7 of the study than infants assigned the standard care. Total body water and fat-free mass did not differ at 32 weeks PMA. Na supplementation guided by urine Na concentration did not significantly improve weight gain in infants 250/7 to 296/7 weeks gestation at 36 weeks PMA.