Effect of vitamin A supplementation on morbidity of low-birthweight neonates

Background. Low-birth-weight (LBW) infants (< 2 500 g) are at increased ris k of respiratory infection in the first few months of life and have low liv er stores of vitamin A. As retinol is essential for respiratory epithelial cell differentiation, deficiency could result in pathological changes in th e respiratory epithelium, with respiratory problems. Objective. A randomised, double-blind, placebo-controlled trial to investig ate the effect of vitamin A supplementation on the incidence and severity o f respiratory infections in LBW infants during their first year of life. Method. One hundred and thirty LBW infants (gestational age < 36 weeks and birth weight 950 - 1 700 g) were enrolled in the study. The infants were ra ndomly allocated to a vitamin A or placebo group. Infants in the vitamin A group received 25 000 IU of vitamin A (retinyl palmitate, Arovit drops, Roc he, Basle, Switzerland) on study days 1, 4 and 8. Study day 1 was between 3 6 and 60 hours after delivery. Infants in the placebo group received a plac ebo (formulated by Roche) with a similar appearance and packed in the same dropper bottles as the vitamin A drops. Results. Vitamin A supplementation markedly improved serum retinol levels. After the last vitamin A dose, the vitamin A group had higher mean serum re tinol concentrations than the placebo group (45.77 +/- 17.07 mu g/dl v. 12. 88 +/- 6.48 mu g/dl, P = 0.0001). There was no evidence? of improvement in neonatal or post-neonatal respiratory problems associated with vitamin A su pplementation. Vitamin A and placebo groups did not differ in the occurrenc e or duration of respiratory distress or the need for head-box oxygen. Ther e were also no significant differences in the cumulative probability of dev eloping lower or upper respiratory tract infection through the first year o f life. There was a slight suggestion of an increase in the risk of hospita lisation with pneumonia associated with vitamin A supplementation. The cumu lative probability of being hospitalised with pneumonia by 6 months of age was 24.6% (7 hospitalisations) in the vitamin A group compared with 7.4% (2 hospitalisations) in the placebo group (log rank test P = 0.04). After adj usting for risk factors this difference was no longer significant. Conclusion. Vitamin A supplementation in LBW neonates may not reduce incide nce or severity of respiratory infections. These results do not negate the importance of improving vitamin A status in children as an important public health measure to reduce morbidity and mortality from other childhood infe ctions.