Monitored vs Standard Supplementation of Vitamin D in Preterm Infants

Vitamin D Deficiency Clinical Trial

— MOSVID  

Official title:

Supplementation of Vitamin D in Preterm Infants- Monitored Therapy vs Standard Therapy. A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03087149
• Other study ID #: VitD-2016
• Status: Completed
• Phase: N/A
• Start date: May 1, 2017
• Est. completion date: March 31, 2020

Study information

• Verified date: February 2021
• Source: Princess Anna Mazowiecka Hospital, Warsaw, Poland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine wheather the monitored vitamin D (vit D) therapy is safer and more effective than standard therapy in pretrem infants.

Description:

Vitamin D (vit D) deficiency is a risk factor of osteopenia of prematurity, which leads to rickets or decreased bone mass mineral density. Recently multiple studies have been published on vit D adjust biological functions. Dosage, safety and effectiveness of vitD supplementation in preterm infants still remains a controversial topic. We hypothesize that monitored supplementation of vit D is more effective and safer than standard therapy 500IU in preterm infants. The study will be carried out in 138 preterm infants, born at 24-32 week of gestational age (GA) at the Princess Anne's Hospital in Warsaw, Poland. We will determine if monitored supplementation of vit D decreases the incidence of vit D deficiency and/or overdosing at 40 week (GA). For secondary objective we shall assess if monitored therapy reduces the incidence of vit D deficiency and/or overdosing at 35, 52 week (GA), prevalence of osteopenia, low bone mass, nephrocalcinosis and nephrolithiasis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: March 31, 2020
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 7 Days

Eligibility

Inclusion Criteria:

• Preterm infants born between 24 and 32 weeks of gestation (estimated by ultrasound)

• In born or admitted to the unit within 48hours from birth.

• Randomization within 7 days from birth.

• Parental consent.

• Mothers willing to return for follow up visits.

Exclusion Criteria:

• Preterm delivery >=33 weeks of gestation or term delivery (estimated by ultrasound).

• Major congenital abnormalities.

• Participation in another trial.

• Severe illness at birth deemed incompatible with survival.

• Congenital HIV infection.

• Total parenteral nutrition > 14 days.

• Cholestasis

Related Conditions & MeSH terms

• Bone Diseases, Metabolic
• Drug Overdose
• Kidney Calculi
• Nephrolithiasis
• Osteopenia
• Vitamin D Deficiency

Intervention

Dietary Supplement:
• monitored vit D supplementation
The vit D supplementation dose start from dose 500IU from 7th day of age and is modified based on vit D measurement at 4 week of age for infants born <30 GA, at 8 week of age for infants born <26 GA at 35+/-2 weeks PMA(postmenstrual age), +/-at 40+/-2 weeks PMA according to the protocol.
• standard vit D supplementation
The vitamin D supplementation dose is 500IU from 7th day of age.

Locations

Country	Name	City	State
Poland	Princess Anna Mazowiecka Hospital	Warsaw

Sponsors (2)

Lead Sponsor	Collaborator
Princess Anna Mazowiecka Hospital, Warsaw, Poland	Medical University of Warsaw

Country where clinical trial is conducted

Poland, 

References & Publications (24)

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. Review. — View Citation

Agostoni C, Buonocore G, Carnielli VP, De Curtis M, Darmaun D, Decsi T, Domellöf M, Embleton ND, Fusch C, Genzel-Boroviczeny O, Goulet O, Kalhan SC, Kolacek S, Koletzko B, Lapillonne A, Mihatsch W, Moreno L, Neu J, Poindexter B, Puntis J, Putet G, Rigo J, Riskin A, Salle B, Sauer P, Shamir R, Szajewska H, Thureen P, Turck D, van Goudoever JB, Ziegler EE; ESPGHAN Committee on Nutrition. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2010 Jan;50(1):85-91. doi: 10.1097/MPG.0b013e3181adaee0. — View Citation

Backström MC, Kouri T, Kuusela AL, Sievänen H, Koivisto AM, Ikonen RS, Mäki M. Bone isoenzyme of serum alkaline phosphatase and serum inorganic phosphate in metabolic bone disease of prematurity. Acta Paediatr. 2000 Jul;89(7):867-73. — View Citation

Backström MC, Mäki R, Kuusela AL, Sievänen H, Koivisto AM, Ikonen RS, Kouri T, Mäki M. Randomised controlled trial of vitamin D supplementation on bone density and biochemical indices in preterm infants. Arch Dis Child Fetal Neonatal Ed. 1999 May;80(3):F161-6. — View Citation

Çetinkaya M, Çekmez F, Erener-Ercan T, Buyukkale G, Demirhan A, Aydemir G, Aydin FN. Maternal/neonatal vitamin D deficiency: a risk factor for bronchopulmonary dysplasia in preterms? J Perinatol. 2015 Oct;35(10):813-7. doi: 10.1038/jp.2015.88. Epub 2015 Jul 30. — View Citation

Cizmeci MN, Kanburoglu MK, Akelma AZ, Ayyildiz A, Kutukoglu I, Malli DD, Tatli MM. Cord-blood 25-hydroxyvitamin D levels and risk of early-onset neonatal sepsis: a case-control study from a tertiary care center in Turkey. Eur J Pediatr. 2015 Jun;174(6):809-15. doi: 10.1007/s00431-014-2469-1. Epub 2014 Dec 12. — View Citation

Dinlen N, Zenciroglu A, Beken S, Dursun A, Dilli D, Okumus N. Association of vitamin D deficiency with acute lower respiratory tract infections in newborns. J Matern Fetal Neonatal Med. 2016 Mar;29(6):928-32. doi: 10.3109/14767058.2015.1023710. Epub 2015 Mar 19. — View Citation

Fort P, Salas AA, Nicola T, Craig CM, Carlo WA, Ambalavanan N. A Comparison of 3 Vitamin D Dosing Regimens in Extremely Preterm Infants: A Randomized Controlled Trial. J Pediatr. 2016 Jul;174:132-138.e1. doi: 10.1016/j.jpeds.2016.03.028. Epub 2016 Apr 11. — View Citation

Gernand AD, Simhan HN, Caritis S, Bodnar LM. Maternal vitamin D status and small-for-gestational-age offspring in women at high risk for preeclampsia. Obstet Gynecol. 2014 Jan;123(1):40-48. doi: 10.1097/AOG.0000000000000049. — View Citation

Grant CC, Kaur S, Waymouth E, Mitchell EA, Scragg R, Ekeroma A, Stewart A, Crane J, Trenholme A, Camargo CA Jr. Reduced primary care respiratory infection visits following pregnancy and infancy vitamin D supplementation: a randomised controlled trial. Acta Paediatr. 2015 Apr;104(4):396-404. doi: 10.1111/apa.12819. Epub 2014 Oct 21. — View Citation

Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res. 2011 Oct;26(10):2341-57. doi: 10.1002/jbmr.463. Erratum in: J Bone Miner Res. 2011 Dec; 26(12):3001. — View Citation

Javaid MK, Crozier SR, Harvey NC, Gale CR, Dennison EM, Boucher BJ, Arden NK, Godfrey KM, Cooper C; Princess Anne Hospital Study Group. Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study. Lancet. 2006 Jan 7;367(9504):36-43. Erratum in: Lancet. 2006 May 6;367(9521):1486. — View Citation

Monangi N, Slaughter JL, Dawodu A, Smith C, Akinbi HT. Vitamin D status of early preterm infants and the effects of vitamin D intake during hospital stay. Arch Dis Child Fetal Neonatal Ed. 2014 Mar;99(2):F166-8. doi: 10.1136/archdischild-2013-303999. Epub 2013 Jul 13. — View Citation

Nemet D, Dolfin T, Wolach B, Eliakim A. Quantitative ultrasound measurements of bone speed of sound in premature infants. Eur J Pediatr. 2001 Dec;160(12):736-40. — View Citation

Pinto K, Collins CT, Gibson RA, Andersen CC. Vitamin D in preterm infants: A prospective observational study. J Paediatr Child Health. 2015 Jul;51(7):679-81. doi: 10.1111/jpc.12847. Epub 2015 Feb 12. — View Citation

Pludowski P, Holick MF, Pilz S, Wagner CL, Hollis BW, Grant WB, Shoenfeld Y, Lerchbaum E, Llewellyn DJ, Kienreich K, Soni M. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence. Autoimmun Rev. 2013 Aug;12(10):976-89. doi: 10.1016/j.autrev.2013.02.004. Epub 2013 Mar 28. Review. — View Citation

Pludowski P, Karczmarewicz E, Bayer M, Carter G, Chlebna-Sokól D, Czech-Kowalska J, Debski R, Decsi T, Dobrzanska A, Franek E, Gluszko P, Grant WB, Holick MF, Yankovskaya L, Konstantynowicz J, Ksiazyk JB, Ksiezopolska-Orlowska K, Lewinski A, Litwin M, Lohner S, Lorenc RS, Lukaszkiewicz J, Marcinowska-Suchowierska E, Milewicz A, Misiorowski W, Nowicki M, Povoroznyuk V, Rozentryt P, Rudenka E, Shoenfeld Y, Socha P, Solnica B, Szalecki M, Talalaj M, Varbiro S, Zmijewski MA. Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe - recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency. Endokrynol Pol. 2013;64(4):319-27. — View Citation

Rack B, Lochmüller EM, Janni W, Lipowsky G, Engelsberger I, Friese K, Küster H. Ultrasound for the assessment of bone quality in preterm and term infants. J Perinatol. 2012 Mar;32(3):218-26. doi: 10.1038/jp.2011.82. Epub 2011 Jun 16. — View Citation

Rigo J, Pieltain C, Salle B, Senterre J. Enteral calcium, phosphate and vitamin D requirements and bone mineralization in preterm infants. Acta Paediatr. 2007 Jul;96(7):969-74. Review. — View Citation

Vogiatzi MG, Jacobson-Dickman E, DeBoer MD; Drugs, and Therapeutics Committee of The Pediatric Endocrine Society. Vitamin D supplementation and risk of toxicity in pediatrics: a review of current literature. J Clin Endocrinol Metab. 2014 Apr;99(4):1132-41. doi: 10.1210/jc.2013-3655. Epub 2014 Jan 23. Review. — View Citation

Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Hart PH, Kusel MM. Maternal vitamin D levels and the autism phenotype among offspring. J Autism Dev Disord. 2013 Jul;43(7):1495-504. doi: 10.1007/s10803-012-1676-8. — View Citation

Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Kusel MM, Hart PH. Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development. Pediatrics. 2012 Mar;129(3):485-93. doi: 10.1542/peds.2011-2644. Epub 2012 Feb 13. — View Citation

Zerofsky M, Ryder M, Bhatia S, Stephensen CB, King J, Fung EB. Effects of early vitamin D deficiency rickets on bone and dental health, growth and immunity. Matern Child Nutr. 2016 Oct;12(4):898-907. doi: 10.1111/mcn.12187. Epub 2015 Apr 7. — View Citation

Zhu K, Whitehouse AJ, Hart PH, Kusel M, Mountain J, Lye S, Pennell C, Walsh JP. Maternal vitamin D status during pregnancy and bone mass in offspring at 20 years of age: a prospective cohort study. J Bone Miner Res. 2014;29(5):1088-95. doi: 10.1002/jbmr.2138. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants with vitamin D- acceptable range	25-hydroxyvitamin D serum level between 30ng/ml (75nmol/l ) and 80ng/ml (200nmol/l )	at 35, 40, 52 (+/-2 weeks) PMA (postmenstrual age)
Other	Number of Participants with vitamin D- optimal range	25-hydroxyvitamin D serum level between 30ng/ml (75nmol/l ) and 50ng/ml (125nmol/l )	at 35, 40, 52 (+/-2 weeks) PMA (postmenstrual age)
Other	Avarage of vitamin D level	25-hydroxyvitamin D serum level	at 35, 40, 52 (+/-2 weeks) PMA (postmenstrual age)
Primary	Number of Participants with D- deficiency or access	25-hydroxyvitamin D serum level below 20ng/ml (50nmol/l ) or above 100ng/ml (250nmol/l )	at 40 (+/-2 weeks) PMA (postmenstrual age)
Primary	Number of Participants with D- deficiency or access	25-hydroxyvitamin D serum level below 20ng/ml (50nmol/l ) or above 100ng/ml (250nmol/l )	at 4 weeks of age
Primary	Number of Participants with D- deficiency or access	25-hydroxyvitamin D serum level below 20ng/ml (50nmol/l ) or above 100ng/ml (250nmol/l )	At 35 (+/-2 weeks) PMA (postmenstrual age)
Primary	Number of Participants with D- deficiency or access	25-hydroxyvitamin D serum level below 20ng/ml (50nmol/l ) or above 100ng/ml (250nmol/l )	At 52 (+/-2 weeks) PMA (postmenstrual age)
Secondary	Number of Participants with biochemical markers of osteopenia	ALP>500IU and serum phosphate level <1,8mmol/l or ALP>900IU	at 35, 40, 52 (+/-2 weeks) PMA (postmenstrual age)
Secondary	average of bone mass	measurement of speed of sound [SOS] in meters per second in the axial transmission mode with a small ultrasound probe along the mid tibia by Sunlight Omnisence 7000 Premier using CRB Probe	at 35, 40 (+/-2 weeks) PMA
Secondary	Number of Participants with hypercalcemia	serum calcium level above 2,75mmol/l	at 35, 40, 52 (+/-2 weeks) PMA (postmenstrual age)
Secondary	Number of Participants with hypercalcuria	urine calcium:creatinine ratio >3,8mmol/mmol for 0-4 week of age; >3,5mmol/mmol for 5-8 week of age; >2,8mmol/mmol for 9-12 week of age; >2,5mmol/mmol for 13-18 week of age; >2,2mmol/mmol for >19 week of age	at 35, 40, 52 (+/-2 weeks) PMA
Secondary	Number of Participants with nephrocalcinosis	nephrocalcinosis detected in ultrasonography examination of kidneys	at 35, 52 (+/-2 weeks) PMA

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