The Efficacy and Safety of Early Vitamin AD Supplementation in Very Preterm Infants

Study Overview
=================
Brief Summary
-----------------
Bronchopulmonary dysplasia (BPD) is the most prevalent longterm morbidity among surviving extremely preterm infants and has a multifactorial etiology. BPD is associated with later risk of reactive airways disease, such as asthma, post neonatal mortality and adverse neurodevelopmental outcomes.Retinopathy of prematurity (ROP) is a common retinal neovascular disorder and a major cause of vision impairment or blindness in preterm infants, even with aggressed current standard care.Accumulating epidemiologic evidence suggests that vitamin D (VD) deficiency or insufficiency is associated with respiratory disease and metabolic bone disease in premature children.Vitamin A (VA) plays an integral part in lung growth and differentiation. VA is an essential micronutrient for normal visual function. Our prospective double-blinded randomized controlled trial will include infants born at <32 weeks' gestation and admitted to six tertiary NICUs in China. Infants in the intervention (vitamin AD drops) group will receive the daily dose VA at 1500 IU/day with VD 500 IU/day, added to their enteral feeds in drop form as soon as minimal feeding was introduced, and continued to 28 days or discharge. Infants in the control group will receive an equivalent volume of a placebo solution. Following informed consent, enrolled infants will be randomly allocated to the control or VAD group. The primary outcome is bronchopulmonary dysplasia (BPD) , ROP, or metabolic bone disease and the secondary outcomes are mortality; NEC ≥ stage 2; ; late-onset sepsis; weight gain, change in weight, increase in length, increase in head circumference; time to full enteral feeds; and number and type of critical incident reports.

Official Title
-----------------
The Department of Neonatology, Zhengzhou Children's Hospital

Conditions
-----------------
Efficacy and Safety

Intervention / Treatment
-----------------
* Other: Vitamin AD
* Other: Control


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: gestational age<32 weeks, <96 hours of age Exclusion Criteria: genetic metabolic diseases; congenital major abnormalities; congenital non-bacterial infection with overt signs at birth; terminal stage of illness (pH < 7.0 or hypoxia with bradycardia>2 h); ≥ grade III intracranial hemorrhage; lacking parental consent.

Ages Eligible for Study
-----------------
Minimum Age: 1 Hour
Maximum Age: 96 Hours

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin AD<br>In Vitamin AD group, the very preterm infants will receive the daily vitamin AD with vitamin A at1500 IU/day and vitamin D at 500 IU/day in drop form added to their enteral feeds when minimal feeding is introduced, and continue to 28 days or discharge. In this group ,the patient also will receive standard intravenous multivitamin preparation (1 ml/kg/d, containing VA 230 IU/kg/d, VD 80 IU/kg/d) within daily on parenteral nutrition until fed 120ml/kg. | Other: Vitamin AD<br>* In Vitamin AD group, the very preterm infants will receive the daily vitamin AD with vitamin A at 1500 IU/day and vitamin D at 500 IU/day in drop form added to their enteral feeds when minimal feeding is introduced, and continue to 28 days or discharge. In this group ,the patient also will receive standard intravenous multivitamin preparation (1 ml/kg/d,containing VA 230 IU/kg/d, VD 80 IU/kg/d) within daily on parenteral nutrition until fed 120ml/kg.<br>|
| Placebo Comparator: Control<br>In this group ,the patient will only receive standard intravenous multivitamin preparation (1 ml/kg/d,containing VA 230 IU/kg/d,VD 80 IU/kg/d ) within daily on parenteral nutrition until fed 120ml/kg. | Other: Control<br>* In this group ,the patient will only receive standard intravenous multivitamin preparation (1 ml/kg/d,containing VA 230 IU/kg/d, VD 80 IU/kg/d) within daily on parenteral nutrition until fed 120ml/kg.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rates of bronchopulmonary dysplasia | The rates of bronchopulmonary dysplasia with early vitamin AD supplementation | 1 year | 
| rates of retinopathy of prematurity | The rates of retinopathy of prematurity with early vitamin AD supplementation | 1 year | 
| Metaboloc bone disease | The rates of Metaboloc bone disease of prematurity with early vitamin AD supplementation | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rates of Necrotizing enterocolitis | The rates of Necrotizing enterocolitis with early vitamin AD supplementation | 1 year |