Calcium (ca),Phosphorus( P) and 25-hydroxyvitamin D(25OHD)] in Infants Born ≤ 32 PMA Gestational Weeks (GA) (Ca-P)

The Impact of the Dose of Vitamin D (vitD) on the Metabolism of ca, p and Concentrations of 25OHD, Bone Status and Development of Premature Infants up to 2 Years of Age. Prospective, Randomized, Clinical Study

It has not yet been established the optimal dose of vit. D for preterm infants in Poland. It is not known what dose of vit. D will provide the correct concentration of vit. D and the optimal development of the skeleton of the premature.

The study will try to determine the optimal supplementation of vitamin D and the supply of Ca and P for normal growth and development of a child born prematurely.

In addition, the investigators will evaluate any risk factors for deficiency and excess of vitamin D and the consequences of its deficiency and overdose. Simultaneously the study would make possible the determination of an optimal schedule for controlling the Ca-P levels in the group of the youngest infants born prematurely. In addition, the study will assess the relationship between maternal and newborn vitamin D resources right after birth, and the incidence of vitamin D deficiency in infants born prematurely. Preterm infants will be randomized in 3 groups assigned to different doses of vit. D. The study will investigate the metabolism of calcium, phosphorus, the health of bones and development of the premature babies till the age of 2.

Study Overview

• Status: Unknown
• Conditions: Infant, Premature, Diseases
• Intervention / Treatment: Dietary supplement: Cholecalciferol 400; Dietary supplement: Cholecalciferol 800; Drug: Cholecalciferol 1200

Detailed Description

The participants of the study will be prematures, born ≤32 GA, hospitalized in the Department of Neonatology, in the neonatal intensive care unit. Hospitalized patients who meet the inclusion criteria will be randomized in 3 groups assigned to different doses of vit. D (400, 800 or 1200 units(UNT) of vitamin D).

At defined age points of postnatal life, parameters of calcium and phosphorus metabolism and vitamin D level will be tested, along with the health of bones, health status and development.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Poland
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 00-416
      • Recruiting
      • SPSK im. prof. W.Orłowskiego CMKP Neonatology Departament

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 7 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• gestational age ≤32 weeks at birth
• hospitalization in the department no later than at the age of 7 days (for infants born outside the center)
• No birth defects or diseases permanently affecting the ability to accept enteral feeding
• Anticipated possibility of continuous monitoring of the course of treatment in hospital until discharge
• Consent of Parents / legal guardians for the participation in the study.

Exclusion criteria

• gestational age> 32 weeks at birth
• the beginning of hospitalization in the department later than the age of 7 days (for infants born outside the center)
• presence of congenital defects or diseases permanently affecting the ability to accept enteral feeding (e.g.oesophageal atresia, anal atresia, congenital umbilical hernia, gastroschisis, syndromes genetically determined)
• significant interruption (> 1 week) of the hospitalization in the center
• lack of consent of the Parents / legal guardians to participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lower dose; cholecalciferol 400UNT, oral solution	Dietary supplement: Cholecalciferol 400; dose 400 UNT/day for 12 months; Other Names: vit D
Active Comparator: Middle dose; cholecalciferol 800UNT, oral solution	Dietary supplement: Cholecalciferol 800; dose 800 UNT/day for 12 months; Other Names: vit D
Experimental: Higher dose; cholecalciferol 1200UNT, oral solution,	Drug: Cholecalciferol 1200; dose 1200 UNT/day for 12 months; Other Names: vit D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum 25OHD levels in cord blood in Polish preterm infants	assessment of 25OH D levels in children deficiency: <10ng/ml, insufficient level: 10-30ng/ml, sufficient level: 30-50ng/ml	day of labour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of supplementation of Vit. D during pregnancy on 25OHD serum level in Polish mothers	assessment of 25OH D levels in mothers deficiency: <10ng/ml, insufficient level: 10-30ng/ml, sufficient level: 30-50ng/ml	day of labour
Impact of dosage of Vit D3 (400/800/1200 UNT per day) on serum 25OH D levels in preterm children	assessment of serum 25OH D levels in children deficiency: <10ng/ml, insufficient level: 10-30ng/ml, sufficient level: 30-50ng/ml; high level > 60ng/ml, toxic level > 100ng/ml	4,8,12 weeks of life,1 and 2 years of age
Impact of dosage of Vit D3 (400/800/1200 UNT /per day) on Ca serum levels	assessment of Ca serum levels in children	4,8,12 weeks of life,1 and 2 years of age
Impact of dosage of Vit D3 (400/800/1200 UNT /per day) on P serum levels	assessment of P serum levels in children	4,8,12 weeks of life,1 and 2 years of age
Impact of dosage of Vit D3 (400/800/1200 UNT /per day) on urinary Ca excretion	assessment of urinary calcium/creatinine index	4,8,12 weeks of life,1 and 2 years of age
Impact of dosage of Vit D3 (400/800/1200 UNT /per day) on urinary P excretion	assessment of urinary P/creatinine index (mg/mg)	4,8,12 weeks of life,1 and 2 years of age
impact of total annual Vit D3 dose and bone calcification in children	assessment of bone status :Densitometry (DEXA)	average of 1 and 2 years of age
correlation of cord blood 25OHD level and GA	birth <24 GA, 24-28GA, 28-32GA	1st day of life
impact of cord blood 25OHD level on birth weight	assessment of percentile of birth weight (Fenton 2013) hypotrophy <3p, eutrophy 3-97p, hypertrophy >97p	1st day of life of age

Collaborators and Investigators

• Sponsor: Centre of Postgraduate Medical Education
• Investigators: Principal Investigator: Magdalena Zarlenga, MD, Mc postgraduate SPSK im prof.W.Orłowskiego Warszawa; Study Chair: Maria Wilińska, DSc, Mc postgraduate SPSK im prof.W.Orłowskiego Warszawa; Principal Investigator: Ewa Głuszczak-Idziakowska, PhD, Mc postgraduate SPSK im prof.W.Orłowskiego Warszawa

Publications and helpful links

General Publications

• 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.
• Bodnar LM, Klebanoff MA, Gernand AD, Platt RW, Parks WT, Catov JM, Simhan HN. Maternal vitamin D status and spontaneous preterm birth by placental histology in the US Collaborative Perinatal Project. Am J Epidemiol. 2014 Jan 15;179(2):168-76. doi: 10.1093/aje/kwt237. Epub 2013 Oct 11.
• Natarajan CK, Sankar MJ, Agarwal R, Pratap OT, Jain V, Gupta N, Gupta AK, Deorari AK, Paul VK, Sreenivas V. Trial of daily vitamin D supplementation in preterm infants. Pediatrics. 2014 Mar;133(3):e628-34. doi: 10.1542/peds.2012-3395. Epub 2014 Feb 10.
• van de Lagemaat M, Rotteveel J, Schaafsma A, van Weissenbruch MM, Lafeber HN. Higher vitamin D intake in preterm infants fed an isocaloric, protein- and mineral-enriched postdischarge formula is associated with increased bone accretion. J Nutr. 2013 Sep;143(9):1439-44. doi: 10.3945/jn.113.178111. Epub 2013 Jul 31.
• Schanler RJ, Burns PA, Abrams SA, Garza C. Bone mineralization outcomes in human milk-fed preterm infants. Pediatr Res. 1992 Jun;31(6):583-6. doi: 10.1203/00006450-199206000-00009.
• Kislal FM, Dilmen U. Effect of different doses of vitamin D on osteocalcin and deoxypyridinoline in preterm infants. Pediatr Int. 2008 Apr;50(2):204-7. doi: 10.1111/j.1442-200X.2008.02553.x.
• Christmann V, de Grauw AM, Visser R, Matthijsse RP, van Goudoever JB, van Heijst AF. Early postnatal calcium and phosphorus metabolism in preterm infants. J Pediatr Gastroenterol Nutr. 2014 Apr;58(4):398-403. doi: 10.1097/MPG.0000000000000251.
• Backstrom MC, Maki R, Kuusela AL, Sievanen H, Koivisto AM, Koskinen M, Ikonen RS, Maki M. The long-term effect of early mineral, vitamin D, and breast milk intake on bone mineral status in 9- to 11-year-old children born prematurely. J Pediatr Gastroenterol Nutr. 1999 Nov;29(5):575-82. doi: 10.1097/00005176-199911000-00019.
• Fewtrell MS, Prentice A, Jones SC, Bishop NJ, Stirling D, Buffenstein R, Lunt M, Cole TJ, Lucas A. Bone mineralization and turnover in preterm infants at 8-12 years of age: the effect of early diet. J Bone Miner Res. 1999 May;14(5):810-20. doi: 10.1359/jbmr.1999.14.5.810.
• McCarthy RA, McKenna MJ, Oyefeso O, Uduma O, Murray BF, Brady JJ, Kilbane MT, Murphy JF, Twomey A, O' Donnell CP, Murphy NP, Molloy EJ. Vitamin D nutritional status in preterm infants and response to supplementation. Br J Nutr. 2013 Jul 14;110(1):156-63. doi: 10.1017/S0007114512004722. Epub 2012 Nov 27.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: June 18, 2016
• First Submitted That Met QC Criteria: September 28, 2018
• First Posted (Actual): October 2, 2018

Study Record Updates

• Last Update Posted (Actual): October 2, 2018
• Last Update Submitted That Met QC Criteria: September 28, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: premature; osteopenia; 25OHD; Vit. D; LBW (low birth weight)
• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Infant, Premature, Diseases; Premature Birth; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 501-1-13-15-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No