Vitamin A Supplementation for Extremely-Low-Birth-Weight Infants

Study Overview
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Brief Summary
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This multi-site, randomized trial was conducted to determine the safety and effectiveness of a higher dose of vitamin A and determine if this would increase the rate of survival without bronchopulmonary dysplasia (BPD) and reduce the risk of sepsis. Infants with birth weights from 401-1000g and who were on mechanical ventilation or supplemental oxygen at 24-96 hours of age were enrolled. Subjects were randomized to either the Vitamin A or a control group. Infants in the Vitamin A group were given a dose of 5000 IU (0.1 ml) intramuscularly on Mondays, Wednesdays, and Fridays for four weeks. Control infants received a sham procedure rather than placebo injections.

Detailed Description
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Infants with extremely low birth weights (≤1,000 g) have low plasma and tissue concentrations of vitamin A, and vitamin A deficiency may predispose these infants to chronic lung disease. A meta-analysis of clinical trials of vitamin A supplementation for preterm infants revealed a 17% increase in the rate of survival without chronic lung disease, which approached statistical significance. This multi-site, randomized trial was conducted to determine the safety and effectiveness of a higher dose of vitamin A than that used in previous trials in extremely-low-birth-weight (ELBW) infants. We hypothesized that vitamin A supplementation would increase the rate of survival without bronchopulmonary dysplasia and reduce the risk of sepsis. Infants with birth weights from 401-1000g and who received mechanical ventilation or supplemental oxygen at 24-96 hours of age were enrolled. Subjects were randomized to either the vitamin A or a control group. Infants in the Vitamin A group were given a dose of 5000 IU (0.1 ml) intramuscularly on Mondays, Wednesdays, and Fridays for four weeks. Control infants received a sham procedure rather than placebo injections. Serum vitamin A was measured in a central laboratory at base line and at 28 days in the first 300 infants. On study day 28 (two to three days after the last treatment and immediately after a blood sample was collected), the relative dose-response was evaluated.

Official Title
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Randomized Trial of Vitamin A Supplementation for Extremely-Low-Birth-Weight

Conditions
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Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Bronchopulmonary Dysplasia, Respiration, Artificial, Respiratory Distress Syndrome, Newborn, Sepsis

Intervention / Treatment
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* Drug: Vitamin A
* Other: Sham Procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants wtih birth weights from 401-1,000g Receiving mechanical ventilation or supplemental oxygen at 24-96 hours of age Exclusion Criteria: Major congenital anomalies Congenital nonbacterial infection Infants diagnosed with a terminal illness (as indicated by a pH below 6.80 or by the presence of hypoxia with bradycardia for more than two hours) Infants who were to receive vitamin A in a parenteral fat emulsion or in doses exceeding recommendations for multivitamin preparations

Ages Eligible for Study
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Minimum Age: 24 Hours
Maximum Age: 96 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Vitamin A group. | Drug: Vitamin A<br>* 5,000 IU (0.1 ml) was given on Mondays, Wednesdays, and Fridays for four weeks.<br>|
| Sham Comparator: Control<br>Sham procedure Control group. | Other: Sham Procedure<br>* Control infants received a sham procedure rather than placebo injections.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic lung disease or death | Chronic lung disease was defined as the need for oxygen at 36 weeks' postmenstrual age. | 36 weeks' postmenstrual age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sepsis | Sepsis was defined on the basis of a positive blood culture and treatment with antibiotics for at least five days (unless the infant died within five days). | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Prematurity, Vitamin A, Chronic Lung Disease