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

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 < 1000 g. 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 7 days of life. Depending on the type of feeding, and after reaching partial enteral feeding or at 7 days of life, vit D supplementation will consist of 500 IU and an additional 150-300 IU/kg included in human milk fortifiers (if fed exclusively with breast milk) or 190 IU/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 52 weeks 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 ±2 weeks of PCA. Additional 25(OH)D levels will be measured at birth, at 4 and 8 weeks of age, and/or at 35 and 52 ±2 weeks 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 40 weeks 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.

MONITORED SUPPLEMENTATION OF VITAMIN D IN PRETERM NEONATES--A PRIMARY REPORT.

AIM: To evaluate vitamin D (vitD) monitored therapy effectiveness and safety in preterm neonates. PATIENTS AND METHODS: Our observational study was carried out in 80 neonates born before 33 weeks' gestational age (GA) hospitalized in the Clinical Department of Neonatology and Neonatal and Intensive Care Department Medical University of Warsaw from July 2013 to July 2014. Daily vitamin D oral supplementation was provided from 1 to 3 weeks of age at the dose of 500-1000 IU/24 h. The dosage was modified according of 25-hydroxyvitamin-D blood serum concentration. Both blood serum 25(OH) D concentration and calcium-phosphate metabolism were assessed at 4 weeks of age, at 34-37 weeks' post-conceptual age (on discharge) and at 39-41 weeks PCA. RESULTS: Mean serum 25(OH)D level was 40 ng/ml at 4 weeks of age, 61 ng/ml at 34-37 weeks PCA, and 53 ng/ml at 39-41 weeks PCA. Higher concentrations were observed in ELBW neonates. Deficiency was noted most often at the first measurement. 52.5% of neonates received 500IU vitD before discharge, 19% had stopped supplementation due to overdosing. High dose vitD supplementation was provided in 34% cases. Disturbance of calcium-phosphate metabolism due to vitD deficiency was observed in one patient. Hypervitaminosis was associated with higher calcium-creatinine ratio. Very high individual heterogeneity of 25(OH)D concentration changes were observed (from 70 ng/ml/4 weeks decrease to 92 ng/ml/4 weeks increase). CONCLUSIONS: Supplementation of vitamin D in preterm neonates needs monitoring. A safe time interval to monitor vitamin D supplementation seems to be 1 month. The schedule of the therapy requires further studies.