Sodium Supplementation and Growth in Very Low Birth Weight Infants

Study Overview
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Brief Summary
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Adequate growth during the neonatal period is critical for optimal long term outcomes. Despite maximal calorie intake, sixty percent of very low birth weight infants still fail to thrive suggesting that factors other than total calorie intake are important in ensuring consistent weight gain. Several reports have indicated a positive sodium balance is critical in ensuring good weight gain in very low birth weight infants, however these infants are susceptible to low serum sodium concentrations. Urine sodium values are sometimes used to diagnosis of hyponatremia or negative sodium balance after the first two weeks of life, but there is no evidence for this practice in preterm neonates. Our central hypothesis is that early supplementation with sodium will ensure positive sodium balance in very low birth weight infants and will result in optimal weight gain and enhanced long term outcomes. Secondarily we hypothesize that low sodium concentrations in the urine will not correlate with low serum sodium values.

Detailed Description
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This is a randomized, blinded, placebo-controlled trial in infants born at less than 32 weeks gestation, who are admitted to the Newborn Intensive Care Unit at University of Cincinnati Medical Center, Cincinnati, Ohio. Infants are randomized to receive either 4 meq/kg/day supplemental sodium or an equal amount of sterile water on days of life 7-35. Institutional data from 2008 revealed that a sample size of 56 infants completing the study will detect a 15% difference in the primary outcome of weight gain with 80% power and an alpha error of 0.05. Allowing that 33% drop-out rate (infants may be transferred to another hospital, expire, or be discharged prior to day of life 35), we choose to randomize 75 infants. Calorie intake, serum sodium, weight gain, urine sodium were monitored weekly till 35 days of life or discharge. Infants were assessed for common morbidities associated with prematurity including bronchopulmonary dysplasia, systemic hypertension, late-onset sepsis, necrotizing enterocolitis and retinopathy of prematurity.

Official Title
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Impact of Early Postnatal Sodium Supplementation on Weight Gain in Very Low Birth Weight Infants

Conditions
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Extreme Immaturity

Intervention / Treatment
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* Drug: Sodium chloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: infants born at less than 32 weeks postmenstrual age Exclusion Criteria: infants with major malformations deemed incompatible with life disease states characterized by edema renal failure, defined as an increase in serum creatinine by 0.5 mg/dl/day or urine output less than 0.5 ml/kg/hour

Ages Eligible for Study
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Minimum Age: 7 Days
Maximum Age: 8 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sodium chloride<br>Sodium chloride 1 meq/kg (0.4 ml/kg of 2.5meq/ml formulation for injection)q6hrs on days of life 7-35. Intervention was given enterally if feedings were at least 100 ml/kg/day; otherwise medication was diluted in equal amounts of dextrose 5% water and administered intravenously. | Drug: Sodium chloride<br> <br> |
| Placebo Comparator: sterile water<br>Sterile water, 0.4 ml/kg q6hrs on days of life 7-35. Placebo is given enterally when infant is tolerating at least 100 ml/kg/day; otherwise the product is diluted in equal amounts of dextrose 5% water and administered intravenously. | Drug: Placebo<br>* sterile water, 0.4 ml/kg every 6 hours on days of life 7-35.<br>* Other names: Sterile Water;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight Gain at Six Weeks of Age | Average weight gain in g/kg/day and also as a % birthweight over the first six weeks of the study will be compared between the two study arms | Six weeks of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Length at Six Weeks of Age | The percentage of infants maintaining birth percentile at six weeks between the two study arms will be analyzed | six weeks of age | 
| Head Circumference | The percentage of infants maintaining birth percentile for head circumference will be compared between the two groups. | six weeks of age | 
| Mean Systolic Blood Pressure | Systolic blood pressures at 36 weeks post-conceptual age will be compared between the two groups | 36 weeks post-conceptual age | 
| Chronic Diuretic Therapy | The incidence of chronic diuretic therapy will be compared between the two groups | patients will be followed during birth hospital stay; an expected average of 3 months of age | 
| Late-onset Sepsis | The incidence of late-onset sepsis, defined as positive blood culture for credible pathogen and/or 5 days of continuous antimicrobial therapy after the first week of life will be compared between the two groups. | patients will be followed during birth hospitalization; an expected average of 3 months of age | 
| Necrotizing Enterocolitis | The incidence of Bell stage II or greater necrotizing enterocolitis after the second week of life will be compared between the two groups | patients will be followed during birth hospitalization; an expected average of 3 months of age | 
| Chronic Lung Disease | The incidence of chronic lung disease, defined as respiratory support at 36 weeks postmenstrual age will be compared between the two groups | 36 weeks post-mentrual age | 
| Mortality | The incidence of death during birth hospitalization will be compared between the two study arms | patients will be followed during birth hospitalization; an expected 3 months of age | 
| Patent Ductus Arteriosus | prolonged Patent Ductus Arteriosus after the second week of life | After the second week of life | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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weight, anthropometrics, nutrition