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

NICHD Neonatal Research Network

Status and phase

Completed

Phase 2

Phase 1

Conditions

Infant, Low Birth Weight

Respiration, Artificial

Infant, Newborn

Respiratory Distress Syndrome, Newborn

Infant, Small for Gestational Age

Bronchopulmonary Dysplasia

Infant, Premature

Sepsis

Treatments

Drug: Vitamin A

Other: Sham Procedure

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT01203488

M01RR000997 (U.S. NIH Grant/Contract)

U10HD021415 (U.S. NIH Grant/Contract)

U10HD021373 (U.S. NIH Grant/Contract)

U10HD027853 (U.S. NIH Grant/Contract)

NICHD-NRN-0015

U10HD034167 (U.S. NIH Grant/Contract)

U01HD019897 (U.S. NIH Grant/Contract)

M01RR000070 (U.S. NIH Grant/Contract)

M01RR006022 (U.S. NIH Grant/Contract)

U10HD021364 (U.S. NIH Grant/Contract)

U10HD027880 (U.S. NIH Grant/Contract)

U10HD027856 (U.S. NIH Grant/Contract)

U10HD027851 (U.S. NIH Grant/Contract)

U10HD027881 (U.S. NIH Grant/Contract)

M01RR000750 (U.S. NIH Grant/Contract)

U10HD021397 (U.S. NIH Grant/Contract)

U10HD034216 (U.S. NIH Grant/Contract)

M01RR008084 (U.S. NIH Grant/Contract)

U10HD021385 (U.S. NIH Grant/Contract)

U10HD027904 (U.S. NIH Grant/Contract)

U10HD027871 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

807 patients

Sex

All

Ages

24 to 96 hours old

Volunteers

No Healthy Volunteers

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