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

Overview

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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Other
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: January 1, 2025

Interventions

  • Dietary Supplement: Placebo
    • 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 Supplement: 800 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. 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.
  • Other: Usual Care
    • Co-interventions will be unaffected and provided based on the judgment of the attending neonatal faculty and NICU policies and routine practices

Arms, Groups and Cohorts

  • Active Comparator: Usual care plus placebo
    • 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.
  • Experimental: Usual care plus vitamin D supplementation
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • 25-hydroxyvitamin D (25[OH]D) level
    • Time Frame: about 28 days after birth

Secondary Measures

  • 25-hydroxyvitamin D (25[OH]D) level
    • Time Frame: 36 weeks after birth
  • Type of respiratory support required at 36 weeks postmenstrual age
    • Time Frame: 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
  • 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
    • Time Frame: 22 to 26 months corrected age
    • Respiratory support includes supplemental oxygen and positive pressure ventilation.
  • 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)
  • 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 wheezing
    • Time Frame: 2 years
  • Weight as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator
    • Time Frame: 28 days of life
    • Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.
  • Weight as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator
    • Time Frame: 36 weeks postmenstrual age
    • Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.
  • Weight as assessed by sex-specific Z-score on the Fenton 2013 Growth Calculator
    • Time Frame: 2 years
    • 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
    • Time Frame: 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
    • Time Frame: 36 weeks postmenstrual age
    • 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
    • Time Frame: 2 years
    • 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
    • Time Frame: 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
    • Time Frame: 36 weeks postmenstrual age
    • 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
    • Time Frame: 2 years
    • 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
    • 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 Scale of Infant and Toddler Development (Cognitive composite score)
    • Time Frame: 2 years
    • Cognitive composite score ranges from 40 to 160, with a higher score indicating a better outcome.
  • Neurodevelopment as assessed by the Bayley-IV Scale of Infant and Toddler Development (Language composite score)
    • Time Frame: 2 years
    • Language composite score ranges from 40 to 160, with a higher score indicating a better outcome.
  • Neurodevelopment as assessed by the Bayley-IV Scale of Infant and Toddler Development (Motor composite score)
    • Time Frame: 2 years
    • Motor composite score ranges from 40 to 160, with a higher score indicating a better outcome.
  • Number of participants with neurodevelopmental impairment (NDI)
    • Time Frame: 2 years
  • Number of participants who die or have a morbidity
    • Time Frame: 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)
    • 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

Participating in This Clinical Trial

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 overt 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.

Gender Eligibility: All

Minimum Age: 24 Hours

Maximum Age: 96 Hours

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • The University of Texas Health Science Center, Houston
  • Provider of Information About this Clinical Study
    • Principal Investigator: Maria del Mar Romero López, Assistant Professor – The University of Texas Health Science Center, Houston
  • Overall Official(s)
    • Sunil Jain, MD, Principal Investigator, The University of Texas Medical Branch
  • Overall Contact(s)
    • Sunil Jain, MD, 409-772-2815, skjain@utmb.edu

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