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

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
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

Conditions
-----------------
Infant, Premature, Diseases

Intervention / Treatment
-----------------
* Dietary Supplement: Cholecalciferol 400
* Dietary Supplement: Cholecalciferol 800
* Drug: Cholecalciferol 1200


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 24 Weeks
Maximum Age: 32 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lower dose<br>cholecalciferol 400UNT, oral solution | Dietary Supplement: Cholecalciferol 400<br>* dose 400 UNT/day for 12 months<br>* Other names: vit D;|
| Active Comparator: Middle dose<br>cholecalciferol 800UNT, oral solution | Dietary Supplement: Cholecalciferol 800<br>* dose 800 UNT/day for 12 months<br>* Other names: vit D;|
| Experimental: Higher dose<br>cholecalciferol 1200UNT, oral solution, | Drug: Cholecalciferol 1200<br>* dose 1200 UNT/day for 12 months<br>* 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
premature, osteopenia, Vit. D, LBW (low birth weight), 25OHD