Sodium supplementation shows no growth benefit in very preterm infants

Data published in Pediatrics Open Science has highlighted no significant improvement in weight gain among infants born 25- through 29-weeks’ gestation at 36 weeks postmenstrual age (PMA) from sodium (Na) supplementation guided by urine Na concentrations.¹

A significant correlation has been identified between in-hospital growth and impaired neurodevelopment among infants, leading to strong concerns about sub-optimal extrauterine growth. Na intake has been highlighted as a major factor in supporting somatic growth.²

“Preterm infants are at risk for Na depletion due to large, underappreciated urine Na (U_Na) losses coupled with the low Na content of human milk and infant formula,” wrote investigators.¹

Determining Na effects

The randomized controlled trial was conducted to guide dietary Na supplementation alongside standard care (SC) to promote somatic growth among preterm infants. Participants included infants born from 25- through 29-weeks’ gestation with a birth weight of at least 500 grams admitted within 1 week after birth.

Patients with major congenital anomalies, structural genitourinary abnormalities, intestinal ostomies, or diabetes insipidus were excluded from the analysis. Participants were randomized to either a study algorithm (SA) or standard care (SC) group and stratified by gestational age at birth.

Standard infant nutrition, provided to all patients before randomization, included 2 to 3 mEq/kg/day of Na alongside parenteral nutrition. Those in the SA group underwent an initial U_Nameasurement at 14 to 17 days postpartum, followed by regular measurements every 2 weeks until 36-weeks PMA.

Na administration and size outcomes

Na was given to SC infants at the medical care team’s discretion. In the SA group, Na supplementation was provided to infants with U_Na measurements below the level outlined in the algorithm, with an initial amount of 4 mEq/kg/d chosen.

Medical records were assessed for maternal and infant demographic variables, birth history, infant comorbidities, weights, and nutrition data. Differences in somatic growth, including weight, length, and head circumference, were reported as the primary outcome. These differences were reported as changes in Z-scores between 2- and 36-weeks PMA.

The incidence and severity of bronchopulmonary dysplasia, retinopathy of prematurity, dysnatremias, duration of mechanical ventilation, need for supplemental oxygen, and use of diuretics were also reported as secondary outcomes. There were 86 participants included in the final analysis, 43 per study arm.

Urine sodium findings and nutrient intake

Weight, length, and head circumference did not significantly differ between groups at birth and at 2-weeks’ PMA. An initial U_Na below the threshold leading to Na supplementation was reported in 58% of the Na group. At weeks 3 and 6, this rate rose to 81% and 88%, respectively.

Of the SA group, 33% had their Na supplementation increased from 4 to 6 mEq/kg/day. Mean daily caloric intake did not significantly differ between groups during the first 8 weeks of the study, but the SA group had a greater daily protein intake of 4.04 ±0.41 g/kg/day vs 3.83 ± 0.51 g/kg/day in the SC group.

The mean Na intake in the SA group was 5.75 ± 0.96 mEq/kg/day vs 3.62 ± 1.25 mEq/kg/day in the SC group. No differences in human milk or formula exposure were reported between groups.

Growth outcomes over time

There were also no significant differences in the change in weight, length, or head circumference Z-scores between groups from week 2 to week 36. However, post-hoc testing indicated significantly greater body weight Z-scores among SA infants vs SC infants during the early- and mid-study periods. By 36-weeks’ PMA, this evened out to be similar between groups.

Secondary outcomes also did not significantly differ between SA and SC infants. Overall, these results indicated no increase in morbidity risks from Na supplementation among preterm infants.

“For infants failing to grow at desirable rates despite high energy and protein intakes, measurement of U_Na concentration to guide Na supplementation may assist with clinical management,” wrote investigators.

References

1. Liberio BM, Sokol GM, Takow H, et al. Sodium supplementation algorithm to promote growth in preterm infants: randomized clinical trial. Pediatrics Open Science. 2025. doi:10.1542/pedsos.2025-001089
2. 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.