Sodium Supplementation for Premature Birth

Overseen By Elizabeth Awe, BA

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Must not be taking: Diuretics

Disqualifiers: Non-English speaking, Congenital anomalies, Renal dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this project is to determine the direct impact of sodium supplementation in preterm infants and to see the overall improvement of their growth and health status. from this study will help us develop a better treatment for in the future.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that infants using diuretics (medications that help remove excess fluid) at the start of the study may need to wait or be re-evaluated.

What data supports the effectiveness of sodium supplementation as a treatment for premature birth?

Research shows that sodium supplementation in very low birth weight preterm infants can significantly improve growth rates, such as weight, length, and head circumference, without causing harmful sodium imbalances. This suggests that sodium supplementation may help support healthy development in premature infants. ^{1 2 3 4 5}

Is sodium supplementation safe for premature infants?

Sodium supplementation in premature infants appears to be generally safe, with studies showing no significant adverse effects like hypernatremia (high sodium levels) or renal failure. It can improve growth and biochemical status without causing undesirable side effects, although careful monitoring is necessary to avoid complications. ^{1 2 3 5 6}

How does sodium supplementation differ from other treatments for premature birth?

Sodium supplementation for premature infants is unique because it specifically addresses sodium deficiency, which is common in these infants due to high renal sodium losses. This treatment improves growth and biochemical status without causing undesirable side effects, unlike other treatments that may not target sodium balance directly. ^{1 2 5 6 7}

Research Team

Jeffrey Segar, MD

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

This trial is for preterm infants with a birth weight over 500 grams, born between 25 and less than 30 weeks of gestation, and who are younger than 14 days old at the time they join. Infants with major birth defects, kidney problems indicated by high creatinine levels, or those on diuretics can't participate unless their condition stabilizes.

Inclusion Criteria

Birthweight >500 grams

I am between 25 and 30 weeks pregnant.

I am less than 14 days old.

Exclusion Criteria

I have a structural issue with my urinary system.

I am using diuretics and can pause for the study's initial 2 weeks.

Non-English speaking parents

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Treatment

Participants are randomized into two groups: one receiving sodium supplementation based on a urine sodium concentration algorithm, and the other managed by current standards. Nutritional and health data are collected.

8 weeks

Weekly visits for sodium level assessment and data collection

Follow-up

Participants are monitored for safety and effectiveness after treatment, including microbiome diversity and weight gain.

4 weeks

Treatment Details

Interventions

• Sodium algorithm

Trial Overview The study is testing how adding sodium to the diets of premature babies affects their growth and gut bacteria. Researchers will use an algorithm to decide how much sodium these babies need. The goal is to find out if this helps them grow better.

Participant Groups

Group I: Sodium algorithm Experimental Treatment 1 Intervention

Starting at 2 weeks of age, the sodium algorithm group will be started based on their sodium levels. This will be adjusted weekly based on weight gain and sodium levels.

Group II: Control Active Control 1 Intervention

Subjects will be cared for by current protocols

Sodium algorithm is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Sodium chloride for:

• Hyponatremia correction
• Fluid resuscitation
• Electrolyte imbalance

Approved in United States as Sodium chloride for:

• Hyponatremia correction
• Fluid resuscitation
• Electrolyte imbalance

Approved in Canada as Sodium chloride for:

• Hyponatremia correction
• Fluid resuscitation
• Electrolyte imbalance

Approved in Japan as Sodium chloride for:

• Hyponatremia correction
• Fluid resuscitation
• Electrolyte imbalance

Approved in China as Sodium chloride for:

• Hyponatremia correction
• Fluid resuscitation
• Electrolyte imbalance

Approved in Switzerland as Sodium chloride for:

• Hyponatremia correction
• Fluid resuscitation
• Electrolyte imbalance

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Findings from Research

The implementation of a clinical practice algorithm for sodium supplementation in preterm infants led to a significant increase in average daily sodium intake, with 75% of infants in the 2016 cohort requiring supplementation within the first 4 weeks after birth.

Growth outcomes improved in the 2016 cohort, as indicated by a greater change in weight Z-score compared to the 2014-2015 cohort, although there was no observed impact on respiratory status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiological Approach to Sodium Supplementation in Preterm Infants. Segar, DE., Segar, EK., Harshman, LA., et al.[2019]

Sodium supplementation in 41 very low birth weight preterm infants led to significant increases in weight gain, length gain, and head circumference over a six-week period, compared to a control group of 25 infants.

Despite high renal excretion of sodium in the supplemented group, there were no cases of hypernatremia or hyponatremia, indicating that sodium supplementation is safe and may positively influence growth rates through its effects on bone and protein metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium supplementation in very low birth weight infants fed on their own mothers milk I: Effects on sodium homeostasis. Ayisi, RK., Mbiti, MJ., Musoke, RN., et al.[2013]

In a study of 17 premature infants, restricting sodium intake during the first few days of life significantly reduced the risk of hypernatremia and the need for large fluid volumes, compared to those receiving maintenance sodium.

Sodium-restricted infants had a lower incidence of bronchopulmonary dysplasia, suggesting that this approach may improve outcomes in very low birth weight babies without increasing mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium restriction versus daily maintenance replacement in very low birth weight premature neonates: a randomized, blind therapeutic trial. Costarino, AT., Gruskay, JA., Corcoran, L., et al.[2019]

In a study of 21 preterm infants, those receiving total parenteral nutrition showed a statistically significant weight gain of 3% compared to their birth weight by day 10, indicating that this feeding method may support better growth in low birth weight infants.

Sodium intake was higher in the total parenteral nutrition group (2.03 mmol/kg/day) compared to those receiving enteral feeding, which correlated with a positive sodium balance in all infants in this group by day 5, suggesting that adequate sodium intake is crucial for weight gain in preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Sodium balance in premature infants]. Prekajski, NB., Ljujić, M., Dudić, S., et al.[2013]

In a study of 72 newborn infants, it was found that premature infants (less than 33 weeks gestation) had significant renal sodium losses that exceeded their dietary intake, indicating a need for early sodium supplementation to prevent negative sodium balance.

Fluid administration for premature infants should be carefully calculated to allow for a weight loss of about 10% of body weight in the first days of life, as this helps prevent complications related to cardiovascular and gastrointestinal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Developmental physiologic aspects of volume and sodium regulation in premature and mature newborn infants]. Leititis, JU., Burghard, R., Gordjani, N., et al.[2013]

Supplementing sodium intake to 4 to 5 mmol(mEq)/kg/day in preterm infants (27 to 34 weeks gestation) led to improved weight gain and faster recovery of birth weight compared to unsupplemented infants, with positive sodium and potassium balance observed in the supplemented group.

No adverse effects such as edema or hypernatremia were reported, and the incidence of serious conditions like patent ductus arteriosus and necrotizing enterocolitis remained unchanged, indicating that sodium supplementation is safe and beneficial for growth in these vulnerable infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium homeostasis in term and preterm neonates. III. Effect of salt supplementation. Al-Dahhan, J., Haycock, GB., Nichol, B., et al.[2019]

Early sodium administration in preterm newborns (less than 35 weeks gestation) did not lead to significant differences in the development of hypo- or hyper-natremia, complications, or mortality compared to low sodium intake.

However, the high sodium intake group experienced significantly less weight loss from birth to 48 and 72 hours, suggesting that early sodium implementation may help improve weight retention and reduce related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of High Sodium Intake (5 mEq/kg/day) in Preterm Newborns ( Sánchez, C., Castillo, D., Valdés, BD., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Physiological Approach to Sodium Supplementation in Preterm Infants. [2019]

2. Kenya pubmed.ncbi.nlm.nih.gov

Sodium supplementation in very low birth weight infants fed on their own mothers milk I: Effects on sodium homeostasis. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Sodium restriction versus daily maintenance replacement in very low birth weight premature neonates: a randomized, blind therapeutic trial. [2019]

4. Serbia pubmed.ncbi.nlm.nih.gov

[Sodium balance in premature infants]. [2013]

5. Germany pubmed.ncbi.nlm.nih.gov

[Developmental physiologic aspects of volume and sodium regulation in premature and mature newborn infants]. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Sodium homeostasis in term and preterm neonates. III. Effect of salt supplementation. [2019]

7. India pubmed.ncbi.nlm.nih.gov

Effect of High Sodium Intake (5 mEq/kg/day) in Preterm Newborns ( [2023]