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

NCT06199102 | Not Yet Recruiting DMC

• 1 other identifier: VitD-2023
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Vitamin D Deficiency; Osteopenia of Prematurity; Nephrolithiasis; Metabolic Bone Disease; Late-Onset Neonatal Sepsis

Keywords

vitamin D; preterm infants; osteopenia of prematurity; late-onset sepsis; metabolic bone disease

Outcome Measures

Primary Outcomes (1)

• The number of infants with deficient or suboptimal 25(OH)D levels.

  25-hydroxyvitamin D serum level below 30ng/ml

  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 Outcomes (6)

• The number of infants with neonatal late-onset sepsis.

  after 3 days of age

• The number of infants with biochemical markers of metabolic bone disease.

  at 35±1 weeks of postconceptional age

• The number of infants with hyperparathyroidism.

  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.

  at birth, at 28±2 days of life, and at 35±1 weeks of postconceptional age

• The number of infants with nephrocalcinosis and nephrolithiasis.

  at 28±2 days of life and at 35±1 weeks of postconceptional age

Study Arms (2)

monitored group

EXPERIMENTAL

Infants in the monitored group will receive an initial dose of 1000 IU of vit D (cholecalciferol/ Devikap; Polpharma, Starogard Gdański, Poland).

Dietary Supplement: cholecalciferol/ Devikap

controlled group

ACTIVE COMPARATOR

Infants in the controlled group will receive 250 IU (cholecalciferol/ Devikap; Polpharma, Starogard Gdański, Poland) for very low birth weight infants and 500 IU (cholecalciferol/ Devikap; Polpharma, Starogard Gdański, Poland) for infants weighing above 1000 g.

Dietary Supplement: cholecalciferol/ Devikap

Interventions

cholecalciferol/ Devikap DIETARY_SUPPLEMENT

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 appropriately modified, based on 25(OH)D levels, using the scheme described in the Polish recommendation. The intake from the diet will be calculated from the second month of life.

monitored group

Eligibility Criteria

• Age: 1 Day - 2 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Princess Anna Mazowiecka Hospital, Warsaw, Poland: lead
• Medical University of Warsaw: collaborator

Study Sites (1)

Princess Anna Mazowiecka Hospital

Warsaw, 00-315, Poland

Location

Related Publications (26)

• 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 BACKGROUND

• 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 BACKGROUND

• 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, Shah AS, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from http://www.ncbi.nlm.nih.gov/books/NBK279023/

  PMID: 25905252 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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, Grant WB, Carlberg C, Pilz S, Holick MF, Misiorowski W. Guidelines for Preventing and Treating Vitamin D Deficiency: A 2023 Update in Poland. Nutrients. 2023 Jan 30;15(3):695. doi: 10.3390/nu15030695.

  PMID: 36771403 BACKGROUND

• 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 BACKGROUND

• Rigo J, De Curtis M, Pieltain C, Picaud JC, Salle BL, Senterre J. Bone mineral metabolism in the micropremie. Clin Perinatol. 2000 Mar;27(1):147-70. doi: 10.1016/s0095-5108(05)70011-7.

  PMID: 10690569 BACKGROUND

• Abrams SA; Committee on Nutrition. Calcium and vitamin d requirements of enterally fed preterm infants. Pediatrics. 2013 May;131(5):e1676-83. doi: 10.1542/peds.2013-0420. Epub 2013 Apr 29.

  PMID: 23629620 BACKGROUND

• Embleton ND, Jennifer Moltu S, Lapillonne A, van den Akker CHP, Carnielli V, Fusch C, Gerasimidis K, van Goudoever JB, Haiden N, Iacobelli S, Johnson MJ, Meyer S, Mihatsch W, de Pipaon MS, Rigo J, Zachariassen G, Bronsky J, Indrio F, Koglmeier J, de Koning B, Norsa L, Verduci E, Domellof M. Enteral Nutrition in Preterm Infants (2022): A Position Paper From the ESPGHAN Committee on Nutrition and Invited Experts. J Pediatr Gastroenterol Nutr. 2023 Feb 1;76(2):248-268. doi: 10.1097/MPG.0000000000003642. Epub 2022 Oct 28.

  PMID: 36705703 BACKGROUND

• Kolodziejczyk-Nowotarska A, Bokiniec R, Seliga-Siwecka J. Monitored Supplementation of Vitamin D in Preterm Infants: A Randomized Controlled Trial. Nutrients. 2021 Sep 28;13(10):3442. doi: 10.3390/nu13103442.

  PMID: 34684442 BACKGROUND

• Walker VP, Modlin RL. The vitamin D connection to pediatric infections and immune function. Pediatr Res. 2009 May;65(5 Pt 2):106R-113R. doi: 10.1203/PDR.0b013e31819dba91.

  PMID: 19190532 BACKGROUND

• Dong Y, Speer CP. Late-onset neonatal sepsis: recent developments. Arch Dis Child Fetal Neonatal Ed. 2015 May;100(3):F257-63. doi: 10.1136/archdischild-2014-306213. Epub 2014 Nov 25.

  PMID: 25425653 BACKGROUND

• Aranow C. Vitamin D and the immune system. J Investig Med. 2011 Aug;59(6):881-6. doi: 10.2310/JIM.0b013e31821b8755.

  PMID: 21527855 BACKGROUND

• Workneh Bitew Z, Worku T, Alemu A. Effects of vitamin D on neonatal sepsis: A systematic review and meta-analysis. Food Sci Nutr. 2020 Nov 10;9(1):375-388. doi: 10.1002/fsn3.2003. eCollection 2021 Jan.

  PMID: 33473300 BACKGROUND

• Haque KN. Definitions of bloodstream infection in the newborn. Pediatr Crit Care Med. 2005 May;6(3 Suppl):S45-9. doi: 10.1097/01.PCC.0000161946.73305.0A.

  PMID: 15857558 BACKGROUND

• Bohnhorst B, Lange M, Bartels DB, Bejo L, Hoy L, Peter C. Procalcitonin and valuable clinical symptoms in the early detection of neonatal late-onset bacterial infection. Acta Paediatr. 2012 Jan;101(1):19-25. doi: 10.1111/j.1651-2227.2011.02438.x. Epub 2011 Aug 29.

  PMID: 21824193 BACKGROUND

• Mercy J, Dillon B, Morris J, Emmerson AJ, Mughal MZ. Relationship of tibial speed of sound and lower limb length to nutrient intake in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2007 Sep;92(5):F381-5. doi: 10.1136/adc.2006.105742. Epub 2007 Mar 16.

  PMID: 17369280 BACKGROUND

• Rustico SE, Calabria AC, Garber SJ. Metabolic bone disease of prematurity. J Clin Transl Endocrinol. 2014 Jul 4;1(3):85-91. doi: 10.1016/j.jcte.2014.06.004. eCollection 2014 Sep.

  PMID: 29159088 BACKGROUND

• Shahkar L, Keshtkar A, Mirfazeli A, Ahani A, Roshandel G. The role of IL-6 for predicting neonatal sepsis: a systematic review and meta-analysis. Iran J Pediatr. 2011 Dec;21(4):411-7.

  PMID: 23056824 BACKGROUND

• Eichberger J, Resch B. Reliability of Interleukin-6 Alone and in Combination for Diagnosis of Early Onset Neonatal Sepsis: Systematic Review. Front Pediatr. 2022 Mar 23;10:840778. doi: 10.3389/fped.2022.840778. eCollection 2022.

  PMID: 35402358 BACKGROUND

• Prinsen JH, Baranski E, Posch H, Tober K, Gerstmeyer A. Interleukin-6 as diagnostic marker for neonatal sepsis: determination of Access IL-6 cutoff for newborns. Clin Lab. 2008;54(5-6):179-83.

  PMID: 18780664 BACKGROUND

• Barrueto F Jr, Wang-Flores HH, Howland MA, Hoffman RS, Nelson LS. Acute vitamin D intoxication in a child. Pediatrics. 2005 Sep;116(3):e453-6. doi: 10.1542/peds.2004-2580.

  PMID: 16140692 BACKGROUND

• Al-Kandari A, Sadeq H, Alfattal R, AlRashid M, Alsaeid M. Vitamin D Intoxication and Nephrocalcinosis in a Young Breastfed Infant. Case Rep Endocrinol. 2021 Jul 30;2021:3286274. doi: 10.1155/2021/3286274. eCollection 2021.

  PMID: 34373793 BACKGROUND

• Staub E, Wiedmer N, Staub LP, Nelle M, von Vigier RO. Monitoring of urinary calcium and phosphorus excretion in preterm infants: comparison of 2 methods. J Pediatr Gastroenterol Nutr. 2014 Apr;58(4):404-8. doi: 10.1097/MPG.0000000000000244.

  PMID: 24253368 BACKGROUND

MeSH Terms

Conditions

Vitamin D Deficiency; Bone Diseases, Metabolic; Nephrolithiasis; Neonatal Sepsis

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urolithiasis; Male Urogenital Diseases; Sepsis; Infections; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Renata Bokiniec, MD, PhD

  renata.bokiniec@wum.edu.pl

  STUDY CHAIR

Central Study Contacts

Dominika M Paw, MD

CONTACT

22 596 61 36; dominika.paw@wum.edu.pl

Alicja J Kołodziejczyk-Nowotarska, MD, PhD

CONTACT

alicja.kolodziejczyk-nowotarska@wum.edu.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: December 27, 2023
• First Posted: January 10, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 10, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share

Locations

PL (1)