Extreme Immaturity
Conditions
Keywords
anthropometrics, weight, nutrition
Brief summary
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
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.
Interventions
DRUGSodium chloride
DRUGPlacebo
sterile water, 0.4 ml/kg every 6 hours on days of life 7-35.
Sponsors
University of Cincinnati
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
7 Days to 8 Days
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weight Gain at Six Weeks of Age | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Head Circumference | six weeks of age | The percentage of infants maintaining birth percentile for head circumference will be compared between the two groups. |
| Mean Systolic Blood Pressure | 36 weeks post-conceptual age | Systolic blood pressures at 36 weeks post-conceptual age will be compared between the two groups |
| Chronic Diuretic Therapy | patients will be followed during birth hospital stay; an expected average of 3 months of age | The incidence of chronic diuretic therapy will be compared between the two groups |
| Late-onset Sepsis | patients will be followed during birth hospitalization; an expected average of 3 months of age | 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. |
| Body Length at Six Weeks of Age | six weeks of age | The percentage of infants maintaining birth percentile at six weeks between the two study arms will be analyzed |
| Chronic Lung Disease | 36 weeks post-mentrual age | The incidence of chronic lung disease, defined as respiratory support at 36 weeks postmenstrual age will be compared between the two groups |
| Mortality | patients will be followed during birth hospitalization; an expected 3 months of age | The incidence of death during birth hospitalization will be compared between the two study arms |
| Patent Ductus Arteriosus | After the second week of life | prolonged Patent Ductus Arteriosus after the second week of life |
| Necrotizing Enterocolitis | patients will be followed during birth hospitalization; an expected average of 3 months of age | The incidence of Bell stage II or greater necrotizing enterocolitis after the second week of life will be compared between the two groups |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sodium Chloride 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.
Sodium chloride | 27 |
| Sterile Water 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.
Placebo: sterile water, 0.4 ml/kg every 6 hours on days of life 7-35. | 26 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 3 |
| Overall Study | discharged from hospital | 7 | 5 |
| Overall Study | Protocol Violation | 3 | 0 |
| Overall Study | transferred to quaternary hospital | 2 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Sodium Chloride | Sterile Water | Total |
|---|---|---|---|
| Age, Continuous | 28.4 weeks | 29.3 weeks | 28.5 weeks |
| Body length at birth in centimeters | 35.8 centimeters | 34.9 centimeters | 35.4 centimeters |
| Head circumference at birth in centimeters | 25.1 centimeters | 24.6 centimeters | 24.9 centimeters |
| Maternal Milk as Primary Diet | 17 participants | 14 participants | 31 participants |
| Modified CRIB score | 1 units on a scale | 2 units on a scale | 1 units on a scale |
| Sex: Female, Male Female | 14 Participants | 15 Participants | 29 Participants |
| Sex: Female, Male Male | 13 Participants | 11 Participants | 24 Participants |
| Weight at birth in grams | 1080 grams | 1021 grams | 1051 grams |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 27 | 0 / 26 |
| serious Total, serious adverse events | 0 / 27 | 0 / 26 |
Outcome results
Primary
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
Time frame: Six weeks of age
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intervention | Weight Gain at Six Weeks of Age | 26.9 g/kg/day |
| Placebo | Weight Gain at Six Weeks of Age | 22.4 g/kg/day |
Secondary
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
Time frame: six weeks of age
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention | Body Length at Six Weeks of Age | 14 percentage |
| Placebo | Body Length at Six Weeks of Age | 15 percentage |
Secondary
Chronic Diuretic Therapy
The incidence of chronic diuretic therapy will be compared between the two groups
Time frame: patients will be followed during birth hospital stay; an expected average of 3 months of age
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention | Chronic Diuretic Therapy | 4 participants |
| Placebo | Chronic Diuretic Therapy | 3 participants |
Secondary
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
Time frame: 36 weeks post-mentrual age
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention | Chronic Lung Disease | 9 participants |
| Placebo | Chronic Lung Disease | 5 participants |
Secondary
Head Circumference
The percentage of infants maintaining birth percentile for head circumference will be compared between the two groups.
Time frame: six weeks of age
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention | Head Circumference | 14 percent |
| Placebo | Head Circumference | 15 percent |
Secondary
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.
Time frame: patients will be followed during birth hospitalization; an expected average of 3 months of age
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention | Late-onset Sepsis | 2 participants |
| Placebo | Late-onset Sepsis | 12 participants |
Secondary
Mean Systolic Blood Pressure
Systolic blood pressures at 36 weeks post-conceptual age will be compared between the two groups
Time frame: 36 weeks post-conceptual age
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention | Mean Systolic Blood Pressure | 84.4 mmHg |
| Placebo | Mean Systolic Blood Pressure | 81.8 mmHg |
Secondary
Mortality
The incidence of death during birth hospitalization will be compared between the two study arms
Time frame: patients will be followed during birth hospitalization; an expected 3 months of age
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention | Mortality | 0 participants |
| Placebo | Mortality | 4 participants |
Secondary
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
Time frame: patients will be followed during birth hospitalization; an expected average of 3 months of age
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention | Necrotizing Enterocolitis | 0 participants |
| Placebo | Necrotizing Enterocolitis | 4 participants |
Secondary
Patent Ductus Arteriosus
prolonged Patent Ductus Arteriosus after the second week of life
Time frame: After the second week of life
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention | Patent Ductus Arteriosus | 7 participants |
| Placebo | Patent Ductus Arteriosus | 9 participants |