The High Initial Dose of Monitored Vitamin D Supplementation in Preterm Infants.

Official title

The High Initial Dose of Monitored Vitamin D Supplementation in Preterm Infants. A Randomized Controlled Study.

Overview

The aim of this study will be to assess the effectiveness of monitored vit D supplementation in a population of preterm infants and to identify whether the proper vit D supplementation in preterm infants can reduce the incidence of neonatal sepsis and incidence of metabolic bone disease.

Detailed description

Vitamin D deficiency can escalate prematurity bone disease in preterm infants and negatively influence their immature immunology system. Infants born at 24+0/7 weeks to 32+6/7 weeks of gestation will be considered for inclusion. Cord or vein blood samples will be obtained within 48 h after birth for 25-hydroxyvitamin D level measurements. Parathyroid hormone and interleukin-6 levels will be measured. Infants will be randomized to the monitored group (i.e., initial dose of 1000 IU/day and possible modification) or the controlled group (i.e., 250 IU/day or 500 IU/day dose, depending on weight). Supplementation will be monitored up to postconceptional age 35 weeks. The primary endpoint is the percentage of infants with deficient or suboptimal 25-hydroxyvitamin D levels at 28±2 days of age. 25-Hydroxyvitamin D levels will be measured at postconceptional age 35±2 weeks. Secondary objectives include the incidence of sepsis, osteopenia, hyperparathyroidism, and elevated interleukin-6 concentration. The aim of this study will be to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants and to determine whether a high initial dose of monitored vitamin D supplementation in preterm infants can reduce the incidence of neonatal sepsis and incidence of metabolic bone disease.

Interventions

• Dietary supplement cholecalciferol/ Devikap
  Infants in the monitored group will receive an initial dose of 1000 IU of vit D. An additional 160 IU/kg of vit D is included in parenteral nutrition, as well as 150-300 IU/kg in enteral nutrition, depending on the amount and source of enteral feeding (i.e., human milk fortifiers or milk formula). At 28±2 days of age, blood samples will be obtained for 25(OH)D concentration measurement, followed by measurements every 4 weeks and/or 35±1 weeks of PCA. In the monitored group, vit D doses will be a
• Dietary supplement cholecalciferol/ Devikap
  Infants in the controlled group will receive 250 IU for very low birth weight infants and 500 IU for infants weighing above 1000 g. An additional 160 IU/kg of vit D is included in parenteral nutrition, as well as 150-300 IU/kg in enteral nutrition, depending on the amount and source of enteral feeding (i.e., human milk fortifiers or milk formula). Infants assigned to the standard therapy group will undergo the same blood sample collection procedure as the monitored group, but without any alterat

Primary outcome measures

• The number of infants with deficient or suboptimal 25(OH)D levels. [Time frame: at 28±2 days of age, after that every 4 weeks (number of measurements depends on gestation age at birth) and/ or at 35±1 weeks of postconceptional age]

Secondary outcome measures (6)

• The number of infants with neonatal late-onset sepsis. [Time frame: after 3 days of age]
• The number of infants with biochemical markers of metabolic bone disease. [Time frame: at 35±1 weeks of postconceptional age]
• The number of infants with hyperparathyroidism. [Time frame: at birth, at 28±2 days of life, and at 35±1 weeks of postconceptional age]
• The number of infants with high interleukin-6 levels. [Time frame: at birth, at 28±2 days of life, and at 35±1 weeks of postconceptional age]
• The number of infants with nephrocalcinosis and nephrolithiasis. [Time frame: at 28±2 days of life and at 35±1 weeks of postconceptional age]
• The number of infants with potentially toxic 25(OH)D levels. [Time frame: at 28±2 days of age, after that every 4 weeks (number of measurements depends on gestation age at birth) and/ or at 35±1 weeks of postconceptional age]

Eligibility criteria

Inclusion criteria

• preterm infants with a gestational age of 24+0/7 to 32+6/7 born at our clinic
• preterm infants with a gestational age of 24+0/7 to 32+6/7 outborn and admitted to our intensive care unit within 48h after delivery
• written informed consent form caregivers for the mother and the child to participate in the study

Exclusion criteria

• infants born at >32 weeks of gestation
• infants with major congenital abnormalities or other severe congenital malformations
• infants with genetic disorders (diagnosed before and after birth) deemed incompatible with survival
• infants with diagnosed cholestasis
• the absence of written informed consent and challenges in communication with caregivers

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Poland · 1 center

• Princess Anna Mazowiecka Hospital — Warsaw

Publications

• Lips P, van Schoor NM. The effect of vitamin D on bone and osteoporosis. Best Pract Res Clin Endocrinol Metab. 2011 Aug;25(4):585-91. doi: 10.1016/j.beem.2011.05.002. PMID 21872800
• Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81. doi: 10.1056/NEJMra070553. No abstract available. PMID 17634462
• Shaker JL, Deftos L. Calcium and Phosphate Homeostasis. 2023 May 17. In: Feingold KR, Adler RA, Ahmed SF, Anawalt B, Blackman MR, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hamilton E, Hofland J, Jan de Beur S, Kalra S, Kaltsas G, Kapoor N, Kim M, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrere B, Levy M, McGee EA, McLachlan R, Muzumdar R, Purnell J, Rey R, Sahay R, Sh PMID 25905252
• Khundmiri SJ, Murray RD, Lederer E. PTH and Vitamin D. Compr Physiol. 2016 Mar 15;6(2):561-601. doi: 10.1002/cphy.c140071. PMID 27065162
• Thorsen SU, Pipper CB, Skogstrand K, Pociot F, Svensson J. 25-Hydroxyvitamin D and Peripheral Immune Mediators: Results from Two Nationwide Danish Pediatric Cohorts. Nutrients. 2017 Apr 6;9(4):365. doi: 10.3390/nu9040365. PMID 28383493
• Pinto MRC, Machado MMT, de Azevedo DV, Correia LL, Leite AJM, Rocha HAL. Osteopenia of prematurity and associated nutritional factors: case-control study. BMC Pediatr. 2022 Sep 1;22(1):519. doi: 10.1186/s12887-022-03581-y. PMID 36050673
• Pludowski P, Kos-Kudla B, Walczak M, Fal A, Zozulinska-Ziolkiewicz D, Sieroszewski P, Peregud-Pogorzelski J, Lauterbach R, Targowski T, Lewinski A, Spaczynski R, Wielgos M, Pinkas J, Jackowska T, Helwich E, Mazur A, Ruchala M, Zygmunt A, Szalecki M, Bossowski A, Czech-Kowalska J, Wojcik M, Pyrzak B, Zmijewski MA, Abramowicz P, Konstantynowicz J, Marcinowska-Suchowierska E, Bleizgys A, Karras SN, G PMID 36771403
• Taylor SN, Wagner CL, Hollis BW. Vitamin D supplementation during lactation to support infant and mother. J Am Coll Nutr. 2008 Dec;27(6):690-701. doi: 10.1080/07315724.2008.10719746. PMID 19155428

Identifiers

NCT: NCT06199102 · VitD-2023

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗