Sodium and Milk Fortification Evaluation of Body Composition Among Very Preterm Infants (SAFE)

University of Washington

Status: Enrolling

Conditions: Very Preterm and Extremely Preterm Birth

Treatments: Dietary Supplement: Milk fortification; Diagnostic Test: Serum sodium testing; Diagnostic Test: Urine sodium testing

Study type: Interventional

Funder types: Other

Identifiers

NCT07562997

STUDY00023657

Details and patient eligibility

About

The goal of the trial is to learn if targeted sodium supplementation (including blood and urine sodium testing) versus standard milk fortification (including blood sodium testing) improves growth and body composition in very preterm infants?

Full description

Very preterm infants (born <32 weeks gestational age) are at high risk for postnatal growth faltering, which is associated with adverse neurodevelopmental outcomes. Despite routine use of enriched human milk fortification in the NICU, many infants fail to achieve adequate somatic and lean mass growth. Sodium depletion has been identified as a potentially modifiable contributor to this problem: renal tubular immaturity in preterm infants results in obligate urinary sodium wasting. Total body sodium depletion has been associated with poor growth in infants and poor muscle mass development in animal studies.

Current NICU practice relies primarily on serum sodium to guide supplementation; however, serum sodium is a late and insensitive marker of total body sodium depletion. Urine sodium is a more sensitive indicator of sodium balance and may identify depletion before serum levels fall. Gestational-age-specific urine sodium thresholds to guide supplementation have recently been proposed (Stalter et al., 2025), but have evaluated body composition in a prospective randomized trial.

This trial tests whether a structured, urine sodium-guided supplementation protocol based on every other week urine and serum sodium monitoring improves anthropometric growth and lean mass accrual compared to standard enriched fortification alone. The intervention runs from day of life 14 through 36 weeks postmenstrual age, with tapering through 38 weeks PMA.

Body composition assessment incorporates two complementary modalities: serial point-of-care ultrasound (POCUS) of the biceps, rectus femoris, and subcutaneous fat for longitudinal lean and fat mass tracking, and Air Displacement Plethysmography (PeaPod) at 36 weeks postmenstrual age or discharge for criterion-standard whole-body composition. Fat mass, fat-free mass, and body fat percentage will be referenced against the Norris et al. preterm normative curves.

The trial uses an open-label design with block randomization stratified by gestational age. A Data Safety and Monitoring Board will conduct oversight and interim safety reviews.

Enrollment: 150 estimated patients

Sex: All

Ages: Under 14 days old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Admitted to the University of Washington, Oregon Health and Sciences, or University of Cincinnati NICU at 14 days of age
• Born between 24w0days and 31w6d
• Achieved full enteral feeding

Exclusion criteria

• Congenital or chromosomal anomalies affecting growth
• Acute renal insufficiency (KDIGO stage 1 or higher)
• Necrotizing enterocolitis (modified Bell's stage IIA or higher)
• Anticipated NICU stay less than 30 days
• Enrollment in a concurrent interventional study that may confound study outcomes

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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150 participants in 2 patient groups

Targeted sodium supplementation

Experimental group

Description:

Every two weeks serum sodium and urine sodium testing with sodium supplementation if indicated by algorithm. Milk fortification per growth metrics.

Treatment:

Diagnostic Test: Urine sodium testing

Diagnostic Test: Serum sodium testing

Dietary Supplement: Milk fortification

Enriched Milk Fortification

Active Comparator group

Description:

Serum sodium testing every two weeks with sodium supplementation if indicated by clinical team. Milk fortification per growth metrics.

Treatment:

Diagnostic Test: Serum sodium testing

Dietary Supplement: Milk fortification