Vitamin A to prevent bronchopulmonary dysplasia in very-low-birth-weight infants: has the dose been too low? The NICHD Neonatal Research Network.
OBJECTIVE
Inconsistent effects of vitamin A supplementation on prevention of bronchopulmonary dysplasia have been reported. Meta-analysis of these reports resulted in a relative risk of 0.69-1.02 for death or bronchopulmonary dysplasia associated with vitamin A supplementation. Effective dosage regimens or serum retinol concentrations have not been determined in previous reports. The purpose of this pilot study was to define a vitamin A regimen that produces serum retinol concentrations of 25-55 micrograms/dl.


METHODS
In this three-phase study, 91 infants (mean birth weight 799-864 g) were enrolled. Vitamin A was administered three times/week for 4 weeks at an average daily dose of 986-2143 IU/day. Physical examinations were performed and serum retinol specimens were collected weekly to assess clinical signs of toxicity.


RESULTS
The majority of serum retinol concentrations remained < 25 micrograms/dl until an intramuscular vitamin A dose of 5000 IU/dose three times/week was used. No clinical signs of toxicity were associated with the higher dosage and higher serum concentrations of vitamin A.


CONCLUSIONS
A large clinical trial of vitamin A supplementation with 5000 IU/dose three times/week (25-114% more than the dose used in the three published clinical trials) is needed to assess whether vitamin A supplementation safely reduces the risk of bronchopulmonary dysplasia in very-low-birth-weight infants.
Kennedy
K A
KA
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063, USA.
Stoll
B J
BJ
Ehrenkranz
R A
RA
Oh
W
W
Wright
L L
LL
Stevenson
D K
DK
Lemons
J A
JA
Sowell
A
A
Mele
L
L
Tyson
J E
JE
Verter
J
J
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D001997:Bronchopulmonary Dysplasia / Q000517:prevention & control*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004952:Esters / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D015201:Meta-Analysis as Topic; D010865:Pilot Projects; D012177:Retinol-Binding Proteins / Q000378:metabolism; D015996:Survival Rate; D014801:Vitamin A / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood
D000305:Adrenal Cortex Hormones; D004952:Esters; D012177:Retinol-Binding Proteins; D014801:Vitamin A