Hyponatremia, Premature
Conditions
Keywords
Preterm infant, Sodium, Hyponatremia
Brief summary
Hyponatremia is a common complication among preterm infants, renal losses of sodium contribute to the development of hyponatremia in preterm newborns. Sodium imbalances impact in newborns outcome. There is controversy about the time of initiation and the requirements of sodium in premature infants. Hypothesis: early (24 hours of life) sodium supplementation (5mEq/kg/day) prevents the develop of hyponatremia in preterm infants.
Detailed description
This study is a randomized controlled trial in infants less than 35 weeks gestation admitted to the Newborn Intensive Care Unit at Children Hospital in Saltillo Coahuila Mexico. Infants receive at 24 hours of life; sodium (5mEq/kg/day) versus less than 1mEq/kg/day. Weight, serum and urine sodium, serum chloride, serum and urine creatinine, serum chloride, bicarbonate and glucose are monitored daily during the first 3 days of life. Patients are assessed for hyponatremia, hypernatremia, weight change, sepsis, necrotizing enterocolitis and intraventricular hemorrhage.
Interventions
DRUGSodium < 1mEq/kg/day
Sodium administration enteral and/or parenteral less than 1mEq/kg/day started on day of life 1
DRUGSodium 5mEq/kg/day
Sodium administration enteral and/or parenteral 5mEq/kg/day started on day of life 1
Sponsors
Hospital del Niño Dr. Federico Gomez Santos
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
No minimum to 24 Hours
Healthy volunteers
No
Inclusion criteria
* Preterm infants \<35 Weeks gestation
Exclusion criteria
* Urinary malformations * Congenital abdominal wall defect * Intestinal atresia / obstruction * Congenital heart defect
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hyponatremia | 72 hours | serum sodium \<130mEq/L |
| Hypernatremia | 72 hours | serum sodium \>150mEq/L |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weight Change | Initial weight (baseline) vs 72 hours | The difference between current weight and initial weight |
| Number of Participants With Late-onset Sepsis | Patients will be followed during hospitalization, an expected average of 3 months of age | Positive blood culture and/or 5 days of continuous antimicrobial therapy |
| % Weight Change | Initial weight (baseline) vs 72 hours | The difference between initial weight and 72hrs weight, expressed in percentage of birth weight. |
| Number of Participants With Intraventricular Hemorrhage | Patients will be followed during hospitalization, an expected average of 3 months of age | Bleeding into the brain´s ventricular system (intracranial ultrasound). |
| Mortality | Patients will be followed during hospitalization, an expected average of 3 months of age | Death during hospitalization. |
| Number of Participants With Necrotizing Enterocolitis | Patients will be followed during hospitalization, an expected average of 3 months of age | Number of patients with Bell stage II or greater necrotizing enterocolitis Bell's Staging: Stage II A: Gastrointestinal signs: Increasing gastric aspirates, mild abdominal distention, fecal occult blood, absent bowel sounds. Systemic signs: Temperature instability, apnea, bradycardia, lethargy. Radiological findings: Intestinal dilatation, ileus, pneumatosis intestinalis. Stage II B: Gastrointestinal signs: As stage IIA plus abdominal tenderness. Systemic signs: As stage IIA plus metabolic acidosis and thrombocytopenia. Radiological findings: As stage IIA plus portal vein gas and ascites. Stage III A: Gastrointestinal signs: As stage IIB plus marked abdominal tenderness and generalised peritonitis. Systemic signs: As stage IIB plus hypotension and severe apnea. Radiological findings: As stage IIB Stage III B: Gastrointestinal signs: As stage IIIA As stage IIIA As stage IIIA plus pneumoperitoneum |
| Change in Serum Sodium | Initial serum sodium (baseline) vs 72 hours | The difference between current serum sodium and initial serum sodium |
Countries
Mexico
Participant flow
Recruitment details
Recruitment period: March 30, 2018 - February 28, 2020 Inclusion Criteria: * Preterm infants \<35 Weeks gestation, less than 24 hrs of age. Exclusion Criteria: * Urinary malformations * Congenital abdominal wall defect * Intestinal atresia / obstruction * Congenital heart defect Location: Neonatology (Pediatric Hospital)
Participants by arm
| Arm | Count |
|---|---|
| Sodium < 1mEq/kg/Day Sodium administration enteral and/or parenteral less than 1mEq/kg/day started on day of life one
Sodium \< 1mEq/kg/day: Sodium administration enteral and/or parenteral less than 1mEq/kg/day started on day of life 1 | 23 |
| Sodium 5mEq/kg/Day Sodium administration enteral and/or parenteral 5mEq/kg/day started on day of life one
Sodium 5mEq/kg/day: Sodium administration enteral and/or parenteral 5mEq/kg/day started on day of life 1 | 19 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Guardian declined consent | 1 | 2 |
| Overall Study | No laboratory available | 2 | 2 |
| Overall Study | Protocol Violation | 1 | 2 |
Baseline characteristics
| Characteristic | Sodium < 1mEq/kg/Day | Sodium 5mEq/kg/Day | Total |
|---|---|---|---|
| Age, Continuous | 32 Weeks STANDARD_DEVIATION 2.067 | 32.05 Weeks STANDARD_DEVIATION 2.46 | 32.02 Weeks STANDARD_DEVIATION 2.225 |
| Birth weight | 1551.08 Grams STANDARD_DEVIATION 447.73 | 1609.47 Grams STANDARD_DEVIATION 394.92 | 1577.50 Grams STANDARD_DEVIATION 420.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 19 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Length of hospital stay | 28.43 Days STANDARD_DEVIATION 16.28 | 24.07 Days STANDARD_DEVIATION 18.39 | 26.40 Days STANDARD_DEVIATION 17.13 |
| Region of Enrollment Mexico | 23 participants | 19 participants | 42 participants |
| Sex: Female, Male Female | 12 Participants | 8 Participants | 20 Participants |
| Sex: Female, Male Male | 11 Participants | 11 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 23 | 2 / 19 |
| other Total, other adverse events | 0 / 23 | 0 / 19 |
| serious Total, serious adverse events | 0 / 23 | 0 / 19 |
Outcome results
Primary
Hypernatremia
serum sodium \>150mEq/L
Time frame: 72 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sodium < 1mEq/kg/Day | Hypernatremia | 1 Participants |
| Sodium 5mEq/kg/Day | Hypernatremia | 1 Participants |
p-value: 0.8995% CI: [0.081, 18.09]Chi-squared
Primary
Hyponatremia
serum sodium \<130mEq/L
Time frame: 72 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sodium < 1mEq/kg/Day | Hyponatremia | 6 Participants |
| Sodium 5mEq/kg/Day | Hyponatremia | 1 Participants |
p-value: 0.7195% CI: [0.026, 1.533]Chi-squared
Secondary
Change in Serum Sodium
The difference between current serum sodium and initial serum sodium
Time frame: Initial serum sodium (baseline) vs 72 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium < 1mEq/kg/Day | Change in Serum Sodium | 1.921 mEq/L | Standard Deviation 7.7 |
| Sodium 5mEq/kg/Day | Change in Serum Sodium | 5.71 mEq/L | Standard Deviation 7.05 |
p-value: 0.10795% CI: [-8.43, 0.858]t-test, 2 sided
p-value: 0.10795% CI: [-8.43, 0.85]ANOVA
Secondary
Mortality
Death during hospitalization.
Time frame: Patients will be followed during hospitalization, an expected average of 3 months of age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sodium < 1mEq/kg/Day | Mortality | 5 Participants |
| Sodium 5mEq/kg/Day | Mortality | 2 Participants |
p-value: 0.33Chi-squared
p-value: 0.57Regression, Cox
Secondary
Number of Participants With Intraventricular Hemorrhage
Bleeding into the brain´s ventricular system (intracranial ultrasound).
Time frame: Patients will be followed during hospitalization, an expected average of 3 months of age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sodium < 1mEq/kg/Day | Number of Participants With Intraventricular Hemorrhage | 6 Participants |
| Sodium 5mEq/kg/Day | Number of Participants With Intraventricular Hemorrhage | 4 Participants |
p-value: 0.795% CI: [0.266, 2.448]Chi-squared
Secondary
Number of Participants With Late-onset Sepsis
Positive blood culture and/or 5 days of continuous antimicrobial therapy
Time frame: Patients will be followed during hospitalization, an expected average of 3 months of age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sodium < 1mEq/kg/Day | Number of Participants With Late-onset Sepsis | 8 Participants |
| Sodium 5mEq/kg/Day | Number of Participants With Late-onset Sepsis | 5 Participants |
p-value: 0.5595% CI: [0.296, 1.932]Chi-squared
Secondary
Number of Participants With Necrotizing Enterocolitis
Number of patients with Bell stage II or greater necrotizing enterocolitis Bell's Staging: Stage II A: Gastrointestinal signs: Increasing gastric aspirates, mild abdominal distention, fecal occult blood, absent bowel sounds. Systemic signs: Temperature instability, apnea, bradycardia, lethargy. Radiological findings: Intestinal dilatation, ileus, pneumatosis intestinalis. Stage II B: Gastrointestinal signs: As stage IIA plus abdominal tenderness. Systemic signs: As stage IIA plus metabolic acidosis and thrombocytopenia. Radiological findings: As stage IIA plus portal vein gas and ascites. Stage III A: Gastrointestinal signs: As stage IIB plus marked abdominal tenderness and generalised peritonitis. Systemic signs: As stage IIB plus hypotension and severe apnea. Radiological findings: As stage IIB Stage III B: Gastrointestinal signs: As stage IIIA As stage IIIA As stage IIIA plus pneumoperitoneum
Time frame: Patients will be followed during hospitalization, an expected average of 3 months of age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sodium < 1mEq/kg/Day | Number of Participants With Necrotizing Enterocolitis | 2 Participants |
| Sodium 5mEq/kg/Day | Number of Participants With Necrotizing Enterocolitis | 2 Participants |
p-value: 0.8495% CI: [0.169, 7.096]Chi-squared
Secondary
% Weight Change
The difference between initial weight and 72hrs weight, expressed in percentage of birth weight.
Time frame: Initial weight (baseline) vs 72 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium < 1mEq/kg/Day | % Weight Change | -9.206 % of birth weight | Standard Deviation 4.305 |
| Sodium 5mEq/kg/Day | % Weight Change | -6.345 % of birth weight | Standard Deviation 3.951 |
p-value: 0.03295% CI: [-5.461, -0.261]t-test, 2 sided
p-value: 0.03295% CI: [-5.461, -0.261]ANOVA
Secondary
Weight Change
The difference between current weight and initial weight
Time frame: Initial weight (baseline) vs 72 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium < 1mEq/kg/Day | Weight Change | -135.43 Grams | Standard Deviation 57.46 |
| Sodium 5mEq/kg/Day | Weight Change | -96.05 Grams | Standard Deviation 53.11 |
p-value: 0.02895% CI: [-74.18, -4.57]t-test, 2 sided
p-value: 0.02895% CI: [-74.18, -4.57]ANOVA