Physiologic Approach to Sodium Supplementation in Premature Infants (Salt to Grow)

Postnatal growth failure occurs in up to 50% of very low birth weight (VLBW, <1500 grams at birth) infants as assessed by discharge weight. This study will evaluate if a sodium supplementation algorithm guided by spot urine sodium measurements can improve postnatal growth.

Study Overview

• Status: Completed
• Conditions: Postnatal Growth Disorder
• Intervention / Treatment: Drug: Sodium supplementation guided by urine sodium concentration algorithm

Detailed Description

Postnatal growth failure is a significant morbidity in very low birth weight (VLBW, <1500 grams at birth) infants. Efforts to promote growth and optimize nutritional support have included earlier initiation of parenteral nutrition and increased caloric and protein administration. While these advances in nutritional practices have resulted in improved growth, up to 50% of VLBW infants continue to experience postnatal growth failure (defined as discharge weight <10th percentile by Fenton growth charts) and over 25% experience severe postnatal growth failure (<3rd percentile). Current nutritional recommendations for sodium provision to preterm infants is 3-5 mEq/kg/d and fails to take into account the degree of renal immaturity present in extremely preterm infants. The investigators hypothesize that the sodium supplementation algorithm will improve in-hospital somatic growth (weight, length, and head circumference) between 2 weeks of postnatal age and 36 weeks postmenstrual age over current sodium replacement practices. The algorithm will be evaluated in a prospective, pragmatic, randomized trial. Infants in the sodium supplementation algorithm group will have a spot urine sodium concentration determined every two weeks beginning on the 14th postnatal day and continuing until 36 weeks postmenstrual age with sodium supplementation provided according to the algorithm.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Indiana University Health North
    • Indianapolis, Indiana, United States, 46202
      • Sidney and Lois Eskenazi Hospital
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children at IU Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week to 2 weeks (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Infants with gestational age 25 0/7 - 29 6/7 at birth
2. Birth weight ≥ 500 grams
3. Admitted within the 1st week of life
4. < 17 days of age at time of enrollment

Exclusion Criteria:

1. Infants admitted after the 1st week of life
2. Major congenital anomalies
3. Structural genitourinary abnormality
4. Renal dysfunction (serum creatinine > 1.0 mg/dl or an increase of ≥ 0.3 mg/dl between the 2 most recent consecutive measurements) immediately prior to the initiation of study procedures.
5. Diuretic use less than 48 hours prior to initiation of study procedures
6. Infant with an ostomy (infants receiving an ostomy after study entry will be withdrawn)
7. Infant with a diagnosis or suspicion of diabetes insipidus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Standard of care sodium supplementation as directed by the medical care team
Active Comparator: Sodium supplementation algorithm; Beginning on the 14th -16th postnatal day and continuing until 36 weeks postmenstrual age, infants randomized to the algorithm will have a spot urine sodium concentration determined every two weeks and sodium supplementation provided according to the algorithm.	Drug: Sodium supplementation guided by urine sodium concentration algorithm; 4 mEq/kg/d sodium added the first time urine [Na] below threshold; for each subsequent time urine [Na] below threshold, add additional 2 mEq/kg/d.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Somatic Growth (Weight)	Evaluated by the change in Z-score (standard score) provides a measure of how many standard deviations above or below the population mean the infant weight is. A Z-score of 0 represents the population mean. A positive z-score would indicate better growth.	between 2 weeks of age and 36 weeks post-menstrual age or transfer from the NICU (whichever occurs first).
Change in Somatic Growth (Length)	Evaluated by the change in Z-score (standard score) provides a measure of how many standard deviations above or below the population mean the infant length is. A Z-score of 0 represents the population mean. A positive z-score would indicate better growth.	between 2 weeks of age and 36 weeks post-menstrual age or transfer from the NICU (whichever occurs first).
Change in Somatic Growth (Head Circumference)	Evaluated by the change in Z-score (standard score) provides a measure of how many standard deviations above or below the population mean the infant head circumference is. A Z-score of 0 represents the population mean. A positive z-score would indicate better growth.	between 2 weeks of age and 36 weeks post-menstrual age or transfer from the NICU (whichever occurs first).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Somatic Growth (Weight) at Discharge/Transfer	Evaluated by the change in Z-score (standard score) provides a measure of how many standard deviations above or below the population mean the infant weight is. A Z-score of 0 represents the population mean. A positive z-score would indicate better growth.	between 2 weeks of age and discharge/transfer from hospital, up to 44 weeks post-menstrual age (whichever occurs first).
Change in Somatic Growth (Weight) at Discharge/Transfer	evaluated by the change in kilograms	between 2 weeks of age and discharge/transfer from hospital, up to 44 weeks post-menstrual age (whichever occurs first).
Change in Somatic Growth (Length) at Discharge/Transfer	Evaluated by the change in Z-score (standard score) provides a measure of how many standard deviations above or below the population mean the infant length is. A Z-score of 0 represents the population mean. A positive z-score would indicate better growth.	between 2 weeks of age and discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first)
Change in Somatic Growth (Head Circumference) at Discharge/Transfer	Evaluated by the change in Z-score (standard score) provides a measure of how many standard deviations above or below the population mean the infant head circumference is. A Z-score of 0 represents the population mean. A positive z-score would indicate better growth.	between 2 weeks of age and discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first)
Received Diuretic Therapy	number of participants who received diuretic therapy	between 2 weeks of age and discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first)
Duration of Mechanical Ventilation	days on assisted ventilation	from birth to discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first)
Need for Supplemental Oxygen at Discharge	supplemental oxygen requirement	assessed at discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first)
Incidence and Severity of Bronchopulmonary Dysplasia (BPD)	Jenson definition of bronchopulmonary dysplasia (BPD), rated 0 - 3; with 0 being no BPD and higher numbers being more severe disease	determined at 36 weeks post-menstrual age
Retinopathy of Prematurity ≥ Stage 3	Number of participants with Retinopathy of prematurity ≥ Stage 3 as diagnosed by examination of an Ophthalmologist finding abnormal retinal blood vessel growth with ridge formation or retinal detachment.	assessed at discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first)
Total Body Water	Calculated by the doubly labeled water method in ml/kg	determined during participants 32nd post-menstrual week of life
Energy Expenditure	Calculated using the doubly labeled water method	determined during the participants 32nd post-menstrual week of life

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: Thrasher Research Fund
• Investigators: Principal Investigator: Gregory M Sokol, MD, Indiana University; Principal Investigator: Jeffrey L Segar, MD, Medical College Wisconsin

Publications and helpful links

General Publications

• Segar DE, Segar EK, Harshman LA, Dagle JM, Carlson SJ, Segar JL. Physiological Approach to Sodium Supplementation in Preterm Infants. Am J Perinatol. 2018 Aug;35(10):994-1000. doi: 10.1055/s-0038-1632366. Epub 2018 Feb 27.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): July 22, 2023
• Study Completion (Actual): August 15, 2023

Study Registration Dates

• First Submitted: March 18, 2019
• First Submitted That Met QC Criteria: March 21, 2019
• First Posted (Actual): March 26, 2019

Study Record Updates

• Last Update Posted (Estimated): November 22, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Growth and development; Postnatal Growth Disorder
• Additional Relevant MeSH Terms: Pathologic Processes; Growth Disorders
• Other Study ID Numbers: 1902815407

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No