Bronchopulmonary Dysplasia, Preterm Infants, Vitamin D Deficiency
Conditions
Keywords
Vitamin D, Newborn, Preterm, Supplementation, Respiratory
Brief summary
The study hypothesis states that giving early enteral Vitamin D supplementation to preterm infants will decrease respiratory morbidity in extremely preterm infants.
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTCholecalciferol
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
DIETARY_SUPPLEMENTPlacebo
Sterile water 0.5ml given orally every 6 hours. Duration of 28 postnatal days
Sponsors
Children's Health System, Alabama
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Minutes to 7 Days
Healthy volunteers
No
Inclusion criteria
* Infants admitted to the Regional Newborn ICU of the University of Alabama with gestational age between 23-27 completed weeks
Exclusion criteria
* Major congenital/chromosomal anomalies * Moribund infant with low likelihood of survival, in opinion of the clinical team
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum vitamin D concentration | Day after birth 28 | Serum vitamin D levels determined by enzyme immunoassay obtained from whole blood (remnant sample or obtained during clinical blood draw) |
| Total number of days alive and off respiratory support in the first 28 days | 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%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sepsis | Participants will be followed for the duration of hospital stay, an expected average of 4 months | Culture proven or culture negative clinically treated course consistent with sepsis |
| Need for supplemental oxygen at 36 weeks of corrected age (Physiologic definition) | 36 weeks gestational age corrected | 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%. |
| Duration of mechanical ventilation after randomization | Participants will be followed for the duration of hospital stay, an expected average of 4 months | Counted as number of days on which an infant is on mechanical ventilation for any part of a calendar day |
| Days alive and off mechanical ventilation in the first 28 days after birth | 28 days | Counted as days alive without mechanical ventilation for any part of a day |
| Number of re-intubation events | Participants will be followed for the duration of hospital stay, an expected average of 4 months | Counted as number of reintubations for purposes of respiratory support |
| Surgical necrotizing enterocolitis or intestinal perforation | Participants will be followed for the duration of hospital stay, an expected average of 4 months | Radiographic documentation of pneumatosis or intestinal perforation or treatment course for clinical necrotizing enterocolitis per Bell's stage greater than 1. |
| 25(OH)D concentrations >60ng/ml (150 nmol/L) | 14 postnatal (+/- 2 days) | Vitamin D measurement per blood obtained either centrally or by heel stick. |
| Serum calcium level | Participants will be followed for the duration of hospital stay, an expected average of 4 months | 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. |
| Urine calcium level | Participants will be followed for the duration of hospital stay, an expected average of 4 months | Calcium measurement per urine, random sampling. High level (\>95%tile) urine calcium to creatinine ratio is \>3.8 mmol/mmol. |
| Meningitis | Participants will be followed for the duration of hospital stay, an expected average of 4 months | Culture proven or culture negative clinically treated course consistent with meningitis |
| Death | Participants will be followed for the duration of hospital stay, an expected average of 4 months | Cardiorespiratory failure |
| Number of sepsis episodes treated with antibiotics for at least 5 days | Participants will be followed for the duration of hospital stay, an expected average of 4 months | Number of episodes of culture proven or clinically suspected sepsis episodes treated with antibiotics for at least 5 days |
Other
| Measure | Time frame |
|---|---|
| Death or Neurodevelopmental Impairment | Birth to 22-26 months of age |
Countries
United States
Outcome results
None listed