Effect of vitamin D administration on sepsis score and C-reactive protein (CRP) levels in preterm infants with neonatal sepsis: a randomized controlled trial

BACKGROUND: Neonatal sepsis remains a leading cause of mortality in preterm infants. While Vitamin D possesses immunomodulatory properties, evidence for its adjuvant role in sepsis is limited. This study evaluated the efficacy of two Vitamin D doses (400 IU vs. 800 IU) on clinical sepsis scores and C-reactive protein (CRP) levels. METHODS: An open-label, randomized controlled trial was conducted in Indonesia (August-December 2025) involving preterm infants (28-36 weeks) with sepsis. Patients were randomized into three groups for 7 days: (1) Controls (antibiotics only, nil per os [NPO]), (2) Vitamin D 400 IU/day, and (3) Vitamin D 800 IU/day. The open-label design was necessary due to the difference in feeding status (enteral vs. NPO). Outcomes included changes in the modified Töllner score, Sepsis Prediction Score (SPS), and serum CRP. Analysis was performed using ANCOVA and UNIANOVA, with laboratory analysts blinded to group allocation to strengthen the internal validity. RESULTS: A total of 78 neonates were enrolled and randomized. After exclusions (n = 17), the final analysis included 61 neonates (Control: n = 23; 400 IU: n = 19; 800 IU: n = 19) with largely comparable baseline characteristics. Baseline Vitamin D deficiency was prevalent (73.7%). Both intervention groups showed significantly greater improvements in modified Töllner score and SPS compared to controls (p < 0.001), with no significant difference between the 400 IU and 800 IU doses (p = 1.000). Although CRP levels stabilized in the intervention groups and gained a significant increase in controls, adjusted inter-group differences at day 7 were not significant (p = 0.421). Mortality was higher in the control group (48.6%) compared to the intervention groups (p < 0.001); however, this is likely influenced by the greater baseline severity and cardiovascular instability inherent to their NPO status. Reported adverse events (Grade 1) did not require protocol cessation. CONCLUSION: Vitamin D administration (400 and 800 IU/day) significantly improves sepsis scores in preterm infants with comparable clinical effectiveness between doses, supporting its potential as an effective adjuvant therapy in neonatal sepsis. TRIAL REGISTRATION: ClinicalTrials.gov NCT07245277. Registered 22 September 2025 - Retrospectively registered.