The objective of the study is to compare supplementation with vitamin D at 800 IU/day to usual care for the first 28 days after birth with respect to 25 (OH) vitamin D levels and indicators of likely or plausible effects of vitamin D supplementation on the function or structure of the lung, bones, immune system, and brain in extremely premature (EP) infants who are \<28 weeks gestational age (GA) or \<1000 grams of birth weight (BW). The study results will be analyzed as intention to treat Bayesian analyses (Frequentist analyses will also be performed).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
180
Placebo is normal saline, given in the first 28 days after birth, prepared to have the same volume and appearance as vitamin D, which is a clear odorless solution.
800 IU/day Vitamin D supplementation until 400 IU/day are provided as part of usual care (started when infants receive full feedings of about 120-160 mL/kg/day). At that point the intervention becomes a supplement of 400 IU/day above that given with usual care. In this way all infants in the intervention group receive 800 IU/day of vitamin D total supplementation in the first 28 days after birth with feedings.
The University of Texas Health Science Center at Houston
Houston, Texas, United States
25-hydroxyvitamin D (25[OH]D) level
Time frame: about 28 days after birth
Type of respiratory support required at 36 weeks postmenstrual age
Data will be reported categorically as: * Number of participants who survive without respiratory support * Number of participants who survive with nasal cannula at ≤ 2 liters (L)/minute * Number of participants who survive with nasal cannula \>2 L/minute or noninvasive positive airway pressure * Number of participants who survive with invasive mechanical ventilation * Number of participants who die
Time frame: 36 weeks postmenstrual age (or at the time of discharge home if earlier)
25-hydroxyvitamin D (25[OH]D) level
Time frame: 36 weeks after birth
Length of Hospital stay
Time frame: from time of birth to time of discharge (about 0 to 60 weeks after birth)
Number of participants who are still on respiratory support
Respiratory support includes supplemental oxygen and positive pressure ventilation.
Time frame: 22 to 26 months corrected age
Number of days of supplemental oxygen
Time frame: from time of birth to time of discharge (about 0 to 60 weeks after birth)
Number of days of mechanical ventilation
Time frame: from time of birth to time of discharge (about 0 to 60 weeks after birth)
Number of days of positive pressure support
Time frame: from time of birth to time of discharge (about 0 to 60 weeks after birth)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Care will be unaffected and provided based on the judgment of the attending neonatal faculty and NICU policies and routine practices. When the infant receives about 120 to 160 mL/kg/day of fortified milk at 24 kcal/ounce, the infant will receive supplementation with 400 IU/day of vitamin D as usual care.
Number of participants who receive steroid treatment to decrease respiratory support
Time frame: from baseline to 36 weeks postmenstrual age
Number of participants with pulmonary hypertension
Time frame: 36 weeks postmenstrual age
Number of participants with recurrent wheezing
Assessed using the validated International Study of Asthma and Allergies modified asthma scale, which is defined as having more than two episodes (with or without a documented respiratory tract infection) in the 6 months before the 2-year-old visit
Time frame: 2 years
Weight as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator
Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.
Time frame: 28 days of life
Weight as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator
Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.
Time frame: 36 weeks postmenstrual age
Weight as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator
Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.
Time frame: 2 years
Length as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator
Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.
Time frame: 28 days of life
Length as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator
Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.
Time frame: 36 weeks postmenstrual age
Length as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator
Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.
Time frame: 2 years
Head circumference as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator
Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.
Time frame: 28 days of life
Head circumference as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator
Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.
Time frame: 36 weeks postmenstrual age
Head circumference as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator
Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.
Time frame: 2 years
Number of participants with any fractures
Time frame: from baseline to 36 weeks postmenstrual age
Number of participants with hospital-acquired sepsis
Time frame: from day 3 after birth to the time of discharge (which is 0 to 60 weeks after birth)
Calcium level
Time frame: 0 to 36 weeks postmenstrual age
Phosphorus level
Time frame: 0 to 36 weeks postmenstrual age
Alkaline phosphatase level
Time frame: 0 to 36 weeks postmenstrual age
Neurodevelopment as assessed by the Bayley-IV Scales of Infant and Toddler Development
Score ranges from 40 to 160, with a higher score indicating a better outcome.
Time frame: 2 years
Number of participants with neurodevelopmental impairment (NDI)
Time frame: 2 years
Number of participants who die or have a morbidity
Morbidities include retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), neurodevelopmental impairment (NDI), necrotizing enterocolitis (NEC), and patent ductus arteriosus (PDA).
Time frame: 36 weeks postmenstrual age
Vitamin D status as indicated by serum concentration of 24,25(OH)2D3 as assessed by Liquid Chromatography with tandem mass spectrometry (LC-MS/MS)
Time frame: about 28 days after birth
Vitamin D status as indicated by serum concentration of 24,25(OH)2D3 as assessed by LC-MS/MS
Time frame: 36 weeks postmenstrual age
Vitamin D status as indicated by serum concentration of 3-epi-25(OH)D3 as assessed by LC-MS/MS
Time frame: about 28 days after birth
Vitamin D status as indicated by serum concentration of 3-epi-25(OH)D3 as assessed by LC-MS/MS
Time frame: 36 weeks postmenstrual age
Vitamin D status as indicated by serum concentration of 25(OH)D3 as assessed by LC-MS/MS
Time frame: about 28 days after birth
Vitamin D status as indicated by serum concentration of 25(OH)D3 as assessed by LC-MS/MS
Time frame: 36 weeks postmenstrual age
Pre-discharge health system costs
Facility costs will be extracted from the hospital's cost-accounting systems. Costs associated with physician services during the birth admission will be estimated using CPT-based claims data and Relative Value Units (RVUs) from the Medicare Fee Schedule. The cost of oral vitamin D will be determined using the average wholesale price listed in the Micromedex RedBook
Time frame: From time of birth to time of discharge (about 0 to 60 weeks after birth)
Cost-effectiveness in preventing days of respiratory support
Incremental health system costs per prevented day of respiratory support
Time frame: From time of birth to time of discharge (about 0 to 60 weeks after birth)
Cost-effectiveness in increasing survival without BPD
Incremental health system costs per prevented day of respiratory support
Time frame: From time of birth to time of discharge (about 0 to 60 weeks after birth)