MOnitored supplementation of VItamin D in preterm infants (MOSVID trial): Study protocol for a randomised controlled trial

Abstract

Background: The pivotal role of vitamin D (vit D) in skeletal health is well known. Neonatal vit D storage at birth is dependent on maternal levels, and newborns receive 50-70% of their mother's 25-hydroxyvitamin D [25(OH)D]. Deficiency of vit D can lead to prematurity bone disease, with an incidence of up to 55% in infants weighing<1000g. The aim of this study is to assess the effectiveness of monitored supplementation of vit D in a population of preterm infants. Methods/design: Preterm infants born at 24-32 weeks of gestation will be recruited within the first 7days of life. Depending on the type of feeding, and after reaching partial enteral feeding or at 7days of life, vit D supplementation will consist of 500IU and an additional 150-300IU/kg included in human milk fortifiers (if fed exclusively with breast milk) or 190IU/kg in milk formulas. Subjects will be randomised to either monitored (with an option of dose modification based on 25(OH)D levels as per protocol) or standard therapy up to 52weeks of post-conceptional age (PCA). The primary outcome measure will be the number of neonates with deficiency or excess levels of 25(OH)D at 40 ±2weeks of PCA. Additional 25(OH)D levels will be measured at birth, at 4 and 8weeks of age, and/or at 35 and 52 ±2weeks of PCA. Secondary objectives will include the incidence of osteopenia, nephrocalcinosis and nephrolithiasis. Serum parameters of calcium phosphorus metabolism will also be measured. Discussion: Despite multiple years of research and numerous publications, there is still a lack of consensus in regard to how much vit D infants should receive and how long they should receive it. Because 80% of calcium and phosphorus placental transfer occurs between 24 and 40weeks of gestation, preterm infants are especially prone to adverse effects of vit D insufficiency. However, both inadequate and excessive amounts of vit D may be unsafe and lead to serious health issues. The results of our study may shed new light on these concerns and contribute to optimising vit D supplementation. Trial registration: ClinicalTrials.gov, NCT03087149. Registered on 15 March 2017.