625 - Is Earlier and Higher Dose Vitamin D Supplementation Better for Extremely Preterm Infants? A Randomized Trial (ViDES Trial)
Saturday, April 25, 2026
3:30pm - 5:45pm ET
Publication Number: 2610.625
Mar Romero-Lopez, UT Health. Houston, Houston, TX, United States; Mamta Naik, Children's Memorial Hermann Hospital, houston, TX, United States; Claudia Pedroza, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Chenyue Huang, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Matthew Rysavy, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Glenville Jones, Queen's University at Kingston, Kingston, ON, Canada; Martin Kaufmann, Queen's University, Kingston, ON, Canada; Elenir B. C.. Avritscher, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Ricardo A. Mosquera, University of Texas Health science Houston, Houston, TX, United States; Covi Anne Tibe, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Lindsay F. Holzapfel, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Amir M. Khan, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Jon E. Tyson, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States
Assistant Professor of Pediatrics. Division of Neonatology UT Health. Houston Houston, Texas, United States
Background: Vitamin D deficiency is common in extremely preterm infants (EPI) at birth. Low 25-hydroxyvitamin D (25(OH)D) may contribute to multiple adverse outcomes and is only slowly corrected by the usual vitamin D supplements provided in the U.S.: 400 IU/d after feedings are established. Early and higher-dose (EHD) supplementation — 800 IU/d, started when the infant is fed, as used in some European countries —may reduce these problems. Objective: To perform the largest single-center randomized trial feasible with a KL2 award in a large level IV NICU to assess the probability that serum 25(OH)D and important prespecified clinical outcomes are improved with EHD compared to usual supplementation in the U.S. for EPI. Design/Methods: EPI infants ( < 28 weeks’ gestation [GA] or < 1000 g birthweight [BW]) were stratified by BW ( < 750g vs ≥750 g) and randomized 1:1 within 96 postnatal hours to the two regimens provided with feedings for the first 28 postnatal days. Clinical staff, parents, and investigators were blinded using a small volume saline placebo. Conservative Bayesian analyses using a neutral prior were used to assess the probability of higher serum 25(OH)D by liquid chromatography–tandem mass spectrometry (primary outcome), and better in-hospital outcomes are indicated below. Results: Between September 2022 and June 2025, 180 infants were randomized (mean ± SD GA 25.1 ± 2.1 wks; BW 773 ± 210 g; baseline 25(OH)D3 18 ± 7 ng/ml). The probability of increased serum 25(OH)D3 levels with EHD vs usual supplementation at one postnatal month was >99% (mean 67 vs 32 ng/mL; levels < 30 ng/ml 2% vs 59% of infants). The probability that EHD supplementation improved survival with less severe bronchopulmonary dysplasia was 66% (OR 1.11; 95% credible interval: 0.67–1.85). The probability of benefit from EHD vs. usual supplementation was 81% for mortality (6% vs. 10%), 75% for grade 2-3 bronchopulmonary dysplasia (44% vs 49%), 90% for bacterial sepsis (18% vs 27%), 70% for necrotizing enterocolitis Bell stage ≥2b (17% vs 20%,), 88% for spontaneous intestinal perforation (9% vs 16%), and 76% for fractures (4% vs 8%). Vitamin D clinical toxicity was prospectively assessed but not identified.
Conclusion(s): In this, the largest vitamin D trial in EPI to date, EHD supplementation increased serum 25(OH)D levels at one month and was 66-90% likely to improve important clinical outcomes compared to usual vitamin D supplementation. These findings justify a definitive multicenter randomized trial to determine whether EPI should receive earlier and higher dose vitamin D supplementation.
