Effects of Fat-soluble Vitamins Supplementation on Common Complications and Neural Development in Very Low Birth Weight Infants

Study Overview
=================
Brief Summary
-----------------
Vitamins A, D, and E play important roles in humans, such as vision function, immune function, bone metabolism, cell growth and differentiation and oxidation resistance. Deficiencies in these vitamins will result in a high prevalence of cardiovascular disease, infection, bone diseases, etc. Preterm infants, especially very low birth weight infants, are at risk of vitamin deficiency. Intravenous perfusion is the most common and widely used method to supply vitamins for the specific population in early life. However, the current dose of vitamin supplied by intravenous perfusion whether can meet the need of growth and development is not sure and the appropriate dose for preterm infants is still uncertain. The purpose of this study is to investigate whether current dose of fat-soluble vitamin supplementation is enough for very low birth weight infants, the safety of high dose of fat-soluble vitamin supplementation, and compare the differences of prevalence of common complications, such as bronchopulmonary dysplasia, patent ductus arteriosus, sepsis, anemia, and neural development between these two groups.

Official Title
-----------------
Effects of Fat-soluble Vitamins Supplementation in Early Life on Common Complications and Neural Development in Very Low Birth Weight Infants

Conditions
-----------------
Vitamin A Deficiency, Vitamin D Deficiency, Vitamin E Deficiency, Very Low Birth Weight Infants, Bronchopulmonary Dysplasia, Anemia, Sepsis

Intervention / Treatment
-----------------
* Drug: High dose of fat-Soluble Vitamin
* Drug: Conventional dose of fat-Soluble Vitamin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: admitted to the neonatal intensive care unit (NICU) within 24 hours after birth gestational age younger than 34 weeks birth weight less than 1500 gram informed consent was obtained from the infants' parents or guardians Exclusion Criteria: congenital malformation chromosomal disease, genetic metabolic diseases the infants or his/mother has abnormal thyroid function or parathyroid gland function neonatal necrotizing enterocolitis, diarrhea intracranial hemorrhage of 3 degrees or above pulmonary hemorrhage liver enzymes elevated by more than 2 times, cholestasis death or discharge against medical advice refuse to take part in the study

Ages Eligible for Study
-----------------
Maximum Age: 24 Hours

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High dose of fat-soluble vitamins<br>Fat-soluble vitamins is administered 0.5 piece/kg (equals to 1150 U/kg vitamin A，200 U/kg vitamin D, 3.2 U/kg vitamin E) intravenously every day until the baby achieve full enteral feeding (120 ml/kg), starting with the first dose within 24 hours after birth. | Drug: High dose of fat-Soluble Vitamin<br>* Supplementation of 5 times current dose of fat-soluble vitamins by intravenous perfusion<br>|
| Active Comparator: Conventional dose of fat-soluble vitamins<br>Fat-soluble vitamins is administered 0.1 piece/kg (equals to 230 U/kg vitamin A，40 U/kg vitamin D, 0.64 U/kg vitamin E) intravenously every day until the baby achieve full enteral feeding (120 ml/kg), starting with the first dose within 24 hours after birth. | Drug: Conventional dose of fat-Soluble Vitamin<br>* Supplementation of the current dose of fat-soluble vitamins by intravenous perfusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vitamin levels | Change from baseline level of vitamin A, vitamin D, and vitamin E at 4 6 weeks | within 72 hours after birth, 4 6 weeks old | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complications | The prevalence of bronchopulmonary dysplasia, patent ductus arteriosus, sepsis, anemia, intracranial hemorrhage, extrauterine growth retardation, etc. | corrected age of 36 weeks | 
| Neural development | White matter disease of the preterm infant, was semiquantitatively assessed from MRI at term-equivalent age based on an established scoring method. | corrected age of 40 weeks | 
| Gene polymorphism in vitamin deficiency preterm infants | Association of rs4588 polymorphism in vitamin D receptor gene and rs10766197 polymorphism in the cytochrome P450 family 2 subfamily R member 1 gene with baseline level of vitamin D and change in vitamin D level after 4 6 weeks' supplementation | within 72 hours after birth, 4 6 weeks old |