Very Preterm and Extremely Preterm Birth
Conditions
Keywords
growth, body composition, sodium monitoring
Brief summary
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?
Detailed 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.
Interventions
DIAGNOSTIC_TESTUrine sodium testing
The investigators will utilize urine sodium testing every two weeks in conjunction with serum sodium testing to determine if sodium supplementation is indicated.
DIAGNOSTIC_TESTSerum sodium testing
The investigators will use serum sodium testing to determine if sodium supplementation or adjustments to sodium supplementation need to be made.
DIETARY_SUPPLEMENTMilk fortification
The investigators will provide milk fortification using either a bovine-based or a human-milk-based fortifier (per unit protocol), based on growth trajectories.
Sponsors
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
0 Days to 14 Days
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Body composition by point-of-care ultrasound | Enrollment to study completion, on average 4-10 weeks | Evaluate muscle and subcutaneous fat accretion from enrollment to 36 weeks posmtnestrual age. The study team will perform biceps and rectus femoris cross-sectional area measurements using point-of-care ultrasound every 2 weeks. We will perform arm and mid-thigh subcutaneous fat measurements using point-of-care ultrasound every 2 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body composition using air-displacement plethysmography | At study completion, on average 4-10 weeks | We will conduct air-displacement plethysmography when the infant is off of oxygen at 36 weeks postmenstrual age or prior to discharge, whichever comes earlier. |
Countries
United States
Contacts
CONTACTJohn Feltner, MS
CONTACTDebbie Ng, MPH
PRINCIPAL_INVESTIGATORKatie Strobel, MD, MSCR
University of Washington
Outcome results
None listed