The study hypothesis states that giving early enteral Vitamin D supplementation to preterm infants will decrease respiratory morbidity in extremely preterm infants.
After informed consent obtained, infants will be randomized using computer-generated stratified randomization codes by the pharmacy. Clinicians, researcher, and primary caregivers will be masked. Subjects will be randomly assigned to one of the treatment arms or to a placebo concurrent control. Early vitamin D supplementation/placebo will be initiated within the first 7 days after birth. Premature infants will be randomized to receive one of the 3 fixed doses of vitamin D: either placebo (zero dose), 200 IU/day, or 800 IU/day. The supplementation will be started within 72 hours of enteral feeds being initiated and will continue until postnatal day 28. After this period of supplementation, routine supplementation will be conducted in all groups. Remnant cord blood samples will be analyzed for vitamin D levels (serum hydroxyvitamin D \[25(OH)D\]. Two circulating vitamin D concentrations (25(OH)D concentrations) will be measured on postnatal days 14 and 28. Urine samples will be collected weekly, to determine calcium excretion if high serum calcium concentrations are found. Supplementation will be discontinued and infant will exit the study if surgical necrotizing enterocolitis/bowel perforation is diagnosed, if 25 (OH)D concentrations \>60ng/mL (\>150nmol/L; potentially toxic) are detected or, if infant NPO for greater than 24 hours. If infant made briefly NPO (\<24h) for feeding intolerance, suspected sepsis, hypotension,hemodynamically significant PDA, or respiratory difficulties, enteral vitamin D will not be discontinued. All infants will be followed to discharge for primary, secondary outcomes as well as adverse events.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
100
200 IU/day given orally once per day as one of 4 doses of 0.5ml each given every 6 hours. Other 3 doses will be placebo (sterile water). Duration of 28 postnatal days
800 IU/day given orally per day as 4 doses of 200 IU/0.5ml each every 6 hours. Duration of 28 postnatal days
Sterile water 0.5ml given orally every 6 hours. Duration of 28 postnatal days
University of Alabama at Birmingham
Birmingham, Alabama, United States
Total number of days alive and off respiratory support in the first 28 days
The total number of days alive and off respiratory support. Respiratory support is defined as need of supplemental oxygen and/or positive pressure ventilation to maintain normal target oxygen saturations (88-95%).
Time frame: 28 days
Serum vitamin D concentration
Serum vitamin D levels determined by enzyme immunoassay obtained from whole blood (remnant sample or obtained during clinical blood draw)
Time frame: Day after birth 28
Number of sepsis episodes treated with antibiotics for at least 5 days
Number of episodes of culture proven or clinically suspected sepsis episodes treated with antibiotics for at least 5 days
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 4 months
Sepsis
Culture proven or culture negative clinically treated course consistent with sepsis
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 4 months
Need for supplemental oxygen at 36 weeks of corrected age (Physiologic definition)
A physiologic oxygen challenge test will be administered to infants from 36.0 weeks gestation to 37.0 weeks gestation to determine a need for supplemental oxygen to keep saturation levels between 88-95%.
Time frame: 36 weeks gestational age corrected
Duration of mechanical ventilation after randomization
Counted as number of days on which an infant is on mechanical ventilation for any part of a calendar day
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 4 months
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Days alive and off mechanical ventilation in the first 28 days after birth
Counted as days alive without mechanical ventilation for any part of a day
Time frame: 28 days
Number of re-intubation events
Counted as number of reintubations for purposes of respiratory support
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 4 months
Death
Cardiorespiratory failure
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 4 months
Surgical necrotizing enterocolitis or intestinal perforation
Radiographic documentation of pneumatosis or intestinal perforation or treatment course for clinical necrotizing enterocolitis per Bell's stage greater than 1.
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 4 months
25(OH)D concentrations >60ng/ml (150 nmol/L)
Vitamin D measurement per blood obtained either centrally or by heel stick.
Time frame: 14 postnatal (+/- 2 days)
25(OH)D concentrations >60ng/ml (150 nmol/L)
Vitamin D measurement per blood obtained either centrally or by heel stick.
Time frame: 28 days postnatal age (+/- 3 days)
Serum calcium level
Serum calcium measurement per blood obtained either centrally or by heel stick, performed for clinical care. High serum calcium level is greater than 3 mmol/l of total calcium or total calcium of \>12 mg/dL, or ionized calcium \>2 mml/L.
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 4 months
Urine calcium level
Calcium measurement per urine, random sampling. High level (\>95%tile) urine calcium to creatinine ratio is \>3.8 mmol/mmol.
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 4 months
Meningitis
Culture proven or culture negative clinically treated course consistent with meningitis
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 4 months