Vitamin D Deficiency
Conditions
Keywords
Premature infant, Vitamin D
Brief summary
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).
Interventions
DIETARY_SUPPLEMENTPlacebo
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.
DIETARY_SUPPLEMENT800 IU/day vitamin D supplementation with feedings in the first 28 days after birth
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.
OTHERUsual Care
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.
Sponsors
The University of Texas Health Science Center, Houston
National Center for Advancing Translational Sciences (NCATS)
The Gerber Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
24 Years to 96 Years
Healthy volunteers
No
Inclusion criteria
* Infants born at \< 28 weeks gestational age (GA) or \<1000 grams birth weight (BW) * Inborn * Informed written consent in an Institutional Review Board (IRB)-approved manner
Exclusion criteria
* GA \>32 weeks regardless of birth weight (BW) * Any major congenital anomaly * A known congenital nonbacterial infection * Prenatal diagnosis of disorders that affect vitamin D absorption (e.g, cystic fibrosis) * Such severe illness or immaturity that the attending neonatologist judges intensive care to be unjustified.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 25-hydroxyvitamin D (25[OH]D) level | about 28 days after birth | — |
| Type of respiratory support required at 36 weeks postmenstrual age | 36 weeks postmenstrual age (or at the time of discharge home if earlier) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 25-hydroxyvitamin D (25[OH]D) level | 36 weeks after birth | — |
| Length of Hospital stay | from time of birth to time of discharge (about 0 to 60 weeks after birth) | — |
| Number of participants who are still on respiratory support | 22 to 26 months corrected age | Respiratory support includes supplemental oxygen and positive pressure ventilation. |
| Number of days of supplemental oxygen | from time of birth to time of discharge (about 0 to 60 weeks after birth) | — |
| Number of days of mechanical ventilation | from time of birth to time of discharge (about 0 to 60 weeks after birth) | — |
| Number of days of positive pressure support | from time of birth to time of discharge (about 0 to 60 weeks after birth) | — |
| Number of participants who receive steroid treatment to decrease respiratory support | from baseline to 36 weeks postmenstrual age | — |
| Number of participants with pulmonary hypertension | 36 weeks postmenstrual age | — |
| Number of participants with recurrent wheezing | 2 years | 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 |
| Weight as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator | 28 days of life | Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome. |
| Length as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator | 28 days of life | Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome. |
| Head circumference as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator | 28 days of life | Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome. |
| Number of participants with any fractures | from baseline to 36 weeks postmenstrual age | — |
| Number of participants with hospital-acquired sepsis | from day 3 after birth to the time of discharge (which is 0 to 60 weeks after birth) | — |
| Calcium level | 0 to 36 weeks postmenstrual age | — |
| Phosphorus level | 0 to 36 weeks postmenstrual age | — |
| Alkaline phosphatase level | 0 to 36 weeks postmenstrual age | — |
| Neurodevelopment as assessed by the Bayley-IV Scales of Infant and Toddler Development | 2 years | Score ranges from 40 to 160, with a higher score indicating a better outcome. |
| Number of participants with neurodevelopmental impairment (NDI) | 2 years | — |
| Number of participants who die or have a morbidity | 36 weeks postmenstrual age | Morbidities include retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), neurodevelopmental impairment (NDI), necrotizing enterocolitis (NEC), and patent ductus arteriosus (PDA). |
| 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) | about 28 days after birth | — |
| Vitamin D status as indicated by serum concentration of 24,25(OH)2D3 as assessed by LC-MS/MS | 36 weeks postmenstrual age | — |
| Vitamin D status as indicated by serum concentration of 3-epi-25(OH)D3 as assessed by LC-MS/MS | about 28 days after birth | — |
| Vitamin D status as indicated by serum concentration of 25(OH)D3 as assessed by LC-MS/MS | about 28 days after birth | — |
| Pre-discharge health system costs | From time of birth to time of discharge (about 0 to 60 weeks after birth) | 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 |
| Cost-effectiveness in preventing days of respiratory support | From time of birth to time of discharge (about 0 to 60 weeks after birth) | Incremental health system costs per prevented day of respiratory support |
| Cost-effectiveness in increasing survival without BPD | From time of birth to time of discharge (about 0 to 60 weeks after birth) | Incremental health system costs per prevented day of respiratory support |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMaria del Mar Romero López, MD
The University of Texas Health Science Center, Houston
Outcome results
None listed