Randomized Trial of Enteral Vitamin D Supplementation in Infants < 28 Weeks Gestational Age or <1000 Grams Birth Weight

Study Overview
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Brief Summary
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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).

Official Title
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Randomized Trial of Enteral Vitamin D Supplementation in Infants < 28 Weeks Gestational Age or <1000 Grams Birth Weight

Conditions
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Vitamin D Deficiency

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: 800 IU/day vitamin D supplementation with feedings in the first 28 days after birth
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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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 An 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.

Ages Eligible for Study
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Minimum Age: 24 Hours
Maximum Age: 96 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Usual care plus placebo<br>Infants will receive placebo (normal saline) in the first 28 days after birth. Co-interventions will be unaffected and provided based on the judgment of the attending neonatal faculty and NICU policies and routine practices. | Dietary Supplement: Placebo<br>* 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.<br>* Other names: Normal saline;Other: Usual Care<br>* Co-interventions will be unaffected and provided based on the judgment of the attending neonatal faculty and NICU policies and routine practices<br>|
| Experimental: Usual care plus vitamin D supplementation<br>Infants will receive cholecalciferol 800 IU/day in the first 28 days after birth, given enterally four times per day (0.5mL per dose = 200 IU) until the infant is provided 400 IU/day. At that point the study cholecalciferol will be reduced to 400 IU/day for a total supplementation of 800 IU/day. | Dietary Supplement: 800 IU/day vitamin D supplementation with feedings in the first 28 days after birth<br>* 800 IU/day Vitamin D supplementation until 400 IU/ day are provided as part of usual care. 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.<br>* Other names: Cholecalciferol;Other: Usual Care<br>* Co-interventions will be unaffected and provided based on the judgment of the attending neonatal faculty and NICU policies and routine practices<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 25-hydroxyvitamin D (25[OH]D) level |  | about 28 days after birth | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 25-hydroxyvitamin D (25[OH]D) level |  | 36 weeks 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 | 36 weeks postmenstrual age (or at the time of discharge home if earlier) | 
| 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 | Respiratory support includes supplemental oxygen and positive pressure ventilation. | 22 to 26 months corrected age | 
| 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 wheezing |  | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 2 years | 
| 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 Scale of Infant and Toddler Development (Cognitive composite score) | Cognitive composite score ranges from 40 to 160, with a higher score indicating a better outcome. | 2 years | 
| Neurodevelopment as assessed by the Bayley-IV Scale of Infant and Toddler Development (Language composite score) | Language composite score ranges from 40 to 160, with a higher score indicating a better outcome. | 2 years | 
| Neurodevelopment as assessed by the Bayley-IV Scale of Infant and Toddler Development (Motor composite score) | Motor composite score ranges from 40 to 160, with a higher score indicating a better outcome. | 2 years | 
| Number of participants with neurodevelopmental impairment (NDI) |  | 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). | 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) |  | 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 3-epi-25(OH)D3 as assessed by LC-MS/MS |  | 36 weeks postmenstrual age | 
| Vitamin D status as indicated by serum concentration of 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 |  | 36 weeks postmenstrual age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Premature infant, Vitamin D