Postnatal Growth Disorder
Conditions
Keywords
Postnatal Growth Disorder, Growth and development
Brief summary
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.
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.
Interventions
DRUGSodium 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.
Sponsors
Thrasher Research Fund
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Masking description
Data entered as group A and B.
Eligibility
Sex/Gender
ALL
Age
7 Days to 16 Days
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Somatic Growth (Weight) | between 2 weeks of age and 36 weeks post-menstrual age or transfer from the NICU (whichever occurs first). | 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. |
| Change in Somatic Growth (Length) | between 2 weeks of age and 36 weeks post-menstrual age or transfer from the NICU (whichever occurs first). | 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. |
| Change in Somatic Growth (Head Circumference) | between 2 weeks of age and 36 weeks post-menstrual age or transfer from the NICU (whichever occurs first). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Received Diuretic Therapy | between 2 weeks of age and discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first) | number of participants who received diuretic therapy |
| Duration of Mechanical Ventilation | from birth to discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first) | days on assisted ventilation |
| Need for Supplemental Oxygen at Discharge | assessed at discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first) | supplemental oxygen requirement |
| Change in Somatic Growth (Weight) at Discharge/Transfer | between 2 weeks of age and discharge/transfer from hospital, up to 44 weeks post-menstrual age (whichever occurs first). | 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. |
| Retinopathy of Prematurity ≥ Stage 3 | assessed at discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first) | 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. |
| Total Body Water | determined during participants 32nd post-menstrual week of life | Calculated by the doubly labeled water method in ml/kg |
| Energy Expenditure | determined during the participants 32nd post-menstrual week of life | Calculated using the doubly labeled water method |
| Incidence and Severity of Bronchopulmonary Dysplasia (BPD) | determined at 36 weeks post-menstrual age | Jenson definition of bronchopulmonary dysplasia (BPD), rated 0 - 3; with 0 being no BPD and higher numbers being more severe disease |
| Change in Somatic Growth (Length) at Discharge/Transfer | between 2 weeks of age and discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first) | 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. |
| Change in Somatic Growth (Head Circumference) at Discharge/Transfer | between 2 weeks of age and discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first) | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from 3 level III NICUs and 1 level IV NICU within an academic health care system between July 2019 and August 2023.
Pre-assignment details
Of the 385 infants screened for eligibility, 260 met inclusion/exclusion criteria, and 90 provided informed consent.
Participants by arm
| Arm | Count |
|---|---|
| Control Standard of care sodium supplementation as directed by the medical care team | 43 |
| 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.
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. | 43 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | met exclusion criteria | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Sodium Supplementation Algorithm | Control |
|---|---|---|---|
| Age at Randomization | 14.34 Days STANDARD_DEVIATION 1.22 | 14.33 Days STANDARD_DEVIATION 1.23 | 14.35 Days STANDARD_DEVIATION 1.23 |
| Age, Continuous | 27.93 weeks STANDARD_DEVIATION 1.4 | 27.87 weeks STANDARD_DEVIATION 1.36 | 28.00 weeks STANDARD_DEVIATION 1.44 |
| Apgar Score at 1 minute | 4.64 scores on a scale STANDARD_DEVIATION 2.2 | 4.77 scores on a scale STANDARD_DEVIATION 2.11 | 4.51 scores on a scale STANDARD_DEVIATION 2.29 |
| Apgar Score at 5 minutes | 6.55 scores on a scale STANDARD_DEVIATION 1.86 | 6.56 scores on a scale STANDARD_DEVIATION 1.59 | 6.53 scores on a scale STANDARD_DEVIATION 2.11 |
| Birth Head Circumference | 25.43 cm STANDARD_DEVIATION 1.98 | 25.16 cm STANDARD_DEVIATION 2.12 | 25.70 cm STANDARD_DEVIATION 1.82 |
| Birth Head Circumference z-score | 0.05 Z-score STANDARD_DEVIATION 1.1 | -0.16 Z-score STANDARD_DEVIATION 1.18 | 0.25 Z-score STANDARD_DEVIATION 0.99 |
| Birth Length | 36.17 cm STANDARD_DEVIATION 3.02 | 36.29 cm STANDARD_DEVIATION 3.03 | 36.05 cm STANDARD_DEVIATION 3.04 |
| Birth Length z-score | -0.03 Z-score STANDARD_DEVIATION 1.39 | -0.11 Z-score STANDARD_DEVIATION 1.63 | 0.04 Z-score STANDARD_DEVIATION 1.1 |
| Birth Weight | 1.13 kilograms STANDARD_DEVIATION 0.26 | 1.13 kilograms STANDARD_DEVIATION 0.28 | 1.14 kilograms STANDARD_DEVIATION 0.24 |
| Birth Weight z-score | 0.35 Z-score STANDARD_DEVIATION 0.94 | 0.24 Z-score STANDARD_DEVIATION 0.96 | 0.45 Z-score STANDARD_DEVIATION 0.93 |
| Cesarian Delivery | 65 Participants | 31 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 72 Participants | 38 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Inborn | 81 Participants | 41 Participants | 40 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 11 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 56 Participants | 30 Participants | 26 Participants |
| Received Antenatal glucocorticoids | 74 Participants | 40 Participants | 34 Participants |
| Region of Enrollment United States | 86 Participants | 43 Participants | 43 Participants |
| Sex: Female, Male Female | 48 Participants | 24 Participants | 24 Participants |
| Sex: Female, Male Male | 38 Participants | 19 Participants | 19 Participants |
| Singleton | 68 Participants | 38 Participants | 30 Participants |
| Small for Gestational Age (< 3rd percentile) | 4 participants | 2 participants | 2 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 43 |
| other Total, other adverse events | 5 / 43 | 9 / 43 |
| serious Total, serious adverse events | 3 / 43 | 2 / 43 |
Outcome results
Primary
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.
Time frame: between 2 weeks of age and 36 weeks post-menstrual age or transfer from the NICU (whichever occurs first).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Change in Somatic Growth (Head Circumference) | 0.60 score on a scale | Standard Deviation 0.88 |
| Sodium Supplementation Algorithm | Change in Somatic Growth (Head Circumference) | 0.54 score on a scale | Standard Deviation 0.57 |
p-value: 0.956Kruskal-Wallis
Primary
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.
Time frame: between 2 weeks of age and 36 weeks post-menstrual age or transfer from the NICU (whichever occurs first).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Change in Somatic Growth (Length) | -0.34 score on a scale | Standard Deviation 0.66 |
| Sodium Supplementation Algorithm | Change in Somatic Growth (Length) | -0.48 score on a scale | Standard Deviation 0.48 |
p-value: 0.242Kruskal-Wallis
Primary
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.
Time frame: between 2 weeks of age and 36 weeks post-menstrual age or transfer from the NICU (whichever occurs first).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Change in Somatic Growth (Weight) | 0.04 score on a scale | Standard Deviation 0.63 |
| Sodium Supplementation Algorithm | Change in Somatic Growth (Weight) | 0.16 score on a scale | Standard Deviation 0.41 |
p-value: 0.162Kruskal-Wallis
Secondary
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.
Time frame: between 2 weeks of age and discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Change in Somatic Growth (Head Circumference) at Discharge/Transfer | 1.03 score on a scale | Standard Deviation 1.07 |
| Sodium Supplementation Algorithm | Change in Somatic Growth (Head Circumference) at Discharge/Transfer | 2.07 score on a scale | Standard Deviation 7.39 |
p-value: 0.979Kruskal-Wallis
Secondary
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.
Time frame: between 2 weeks of age and discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Change in Somatic Growth (Length) at Discharge/Transfer | -0.39 score on a scale | Standard Deviation 0.96 |
| Sodium Supplementation Algorithm | Change in Somatic Growth (Length) at Discharge/Transfer | 0.92 score on a scale | Standard Deviation 8.56 |
p-value: 0.746Kruskal-Wallis
Secondary
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.
Time frame: between 2 weeks of age and discharge/transfer from hospital, up to 44 weeks post-menstrual age (whichever occurs first).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Change in Somatic Growth (Weight) at Discharge/Transfer | 0.04 score on a scale | Standard Deviation 0.8 |
| Sodium Supplementation Algorithm | Change in Somatic Growth (Weight) at Discharge/Transfer | 0.24 score on a scale | Standard Deviation 0.76 |
p-value: 0.132Kruskal-Wallis
Secondary
Change in Somatic Growth (Weight) at Discharge/Transfer
evaluated by the change in kilograms
Time frame: between 2 weeks of age and discharge/transfer from hospital, up to 44 weeks post-menstrual age (whichever occurs first).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Change in Somatic Growth (Weight) at Discharge/Transfer | 2.00 kilograms | Standard Deviation 0.76 |
| Sodium Supplementation Algorithm | Change in Somatic Growth (Weight) at Discharge/Transfer | 2.14 kilograms | Standard Deviation 0.82 |
p-value: 0.445Kruskal-Wallis
Secondary
Duration of Mechanical Ventilation
days on assisted ventilation
Time frame: from birth to discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Duration of Mechanical Ventilation | 12.60 Days | Standard Deviation 44.38 |
| Sodium Supplementation Algorithm | Duration of Mechanical Ventilation | 8.74 Days | Standard Deviation 16.08 |
p-value: 0.94Kruskal-Wallis
Secondary
Energy Expenditure
Calculated using the doubly labeled water method
Time frame: determined during the participants 32nd post-menstrual week of life
Population: Samples were not collected for 2 Control participants and 1 Sodium supplementation algorithm participant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Energy Expenditure | 61.6 kcal/kg/d | Standard Deviation 9.6 |
| Sodium Supplementation Algorithm | Energy Expenditure | 65.4 kcal/kg/d | Standard Deviation 9.8 |
p-value: 0.095Kruskal-Wallis
Secondary
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
Time frame: determined at 36 weeks post-menstrual age
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control | Incidence and Severity of Bronchopulmonary Dysplasia (BPD) | Grade 0 | 16 Participants |
| Control | Incidence and Severity of Bronchopulmonary Dysplasia (BPD) | Grade 1 | 11 Participants |
| Control | Incidence and Severity of Bronchopulmonary Dysplasia (BPD) | Grade 2 | 12 Participants |
| Control | Incidence and Severity of Bronchopulmonary Dysplasia (BPD) | Grade 3 | 4 Participants |
| Sodium Supplementation Algorithm | Incidence and Severity of Bronchopulmonary Dysplasia (BPD) | Grade 3 | 2 Participants |
| Sodium Supplementation Algorithm | Incidence and Severity of Bronchopulmonary Dysplasia (BPD) | Grade 0 | 15 Participants |
| Sodium Supplementation Algorithm | Incidence and Severity of Bronchopulmonary Dysplasia (BPD) | Grade 2 | 16 Participants |
| Sodium Supplementation Algorithm | Incidence and Severity of Bronchopulmonary Dysplasia (BPD) | Grade 1 | 10 Participants |
p-value: 0.738Fisher Exact
Secondary
Need for Supplemental Oxygen at Discharge
supplemental oxygen requirement
Time frame: assessed at discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Need for Supplemental Oxygen at Discharge | 7 Participants |
| Sodium Supplementation Algorithm | Need for Supplemental Oxygen at Discharge | 13 Participants |
p-value: 0.126Chi-squared
Secondary
Received Diuretic Therapy
number of participants who received diuretic therapy
Time frame: between 2 weeks of age and discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Received Diuretic Therapy | 7 Participants |
| Sodium Supplementation Algorithm | Received Diuretic Therapy | 11 Participants |
p-value: 0.289Chi-squared
Secondary
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.
Time frame: assessed at discharge/transfer from the NICU or 44 weeks post-menstrual age (whichever occurs first)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Retinopathy of Prematurity ≥ Stage 3 | 4 Participants |
| Sodium Supplementation Algorithm | Retinopathy of Prematurity ≥ Stage 3 | 2 Participants |
p-value: 0.676Fisher Exact
Secondary
Total Body Water
Calculated by the doubly labeled water method in ml/kg
Time frame: determined during participants 32nd post-menstrual week of life
Population: Samples not collected for 6 Control participants and 4 Sodium supplementation algorithm participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Total Body Water | 755.5 ml/kg of water | Standard Deviation 41.4 |
| Sodium Supplementation Algorithm | Total Body Water | 756.2 ml/kg of water | Standard Deviation 41.6 |
p-value: 0.996Kruskal-Wallis