Short-term and long-term effects of vitamin D supplementation for preterm infants: a systematic review and meta-analysis

Meta-analysis conducted to evaluate the effectiveness of high-dose (>=800 IU/day) and low-dose (<800 IU/day) vitamin D supplementation on preterm infants. Study quality was evaluated using the Revised Cochrane risk-of-bias tool 2 for randomized trials. 21 studies included 1130 infants. Regarding short-term (before 40 weeks' postmenstrual age [PMA] or at discharge) outcomes, high-dose vitamin D supplementation was associated with increased serum 25-hydroxyvitamin D (25[OH]D) levels (mean difference 15.62 [13.35-17.88]) and growth velocities, as well as decreased vitamin D deficiency (VDD), skeletal hypomineralization, and mortality. In the subgroup analysis of high-dose supplementation stratified by dosage, 800 IU/day significantly increased serum 25(OH)D levels (mean difference 13.99 [9.03-18.95]) and reduced the risk of VDD (risk difference -0.21 [-0.32 to -0.10]) compared to 400 IU/day, without increasing the risk of vitamin D excess. The long-term outcomes assessed after 40 weeks' PMA or at follow-up visits showed no significant differences in vitamin D status or neurodevelopmental outcomes between the high-dose and low-dose groups. The certainty of the evidence ranges from moderate to very low. High-dose vitamin D supplementation improved short-term outcomes by increasing serum 25(OH)D levels, promoting growth, and reducing mortality. Among the high-dose regimens, 800 IU/day appeared to be the most appropriate dose.