Randomised controlled trial of oral vitamin A supplementation in preterm infants to prevent chronic lung disease. Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. Vitamin A status in children who are prone to respiratory tract infections. Clinical trial of vitamin A supplementation in infants susceptible to bronchopulmonary dysplasia. Effects of moderate doses of vitamin A as an adjunct to the treatment of pneumonia in underweight and normal-weight children: a randomized, double-blind, placebo-controlled trial. Trial of vitamin A supplementation in very low birth weight infants at risk for bronchopulmonary dysplasia.
Intramuscular supplementation with vitamin A in large doses may reduce the incidence of chronic lung disease.
                To investigate whether oral supplementation with vitamin A would reduce the incidence of chronic lung disease in a group of extremely low birthweight infants.
                Infants with birth weight < 1000 g were randomised at birth to receive oral vitamin A supplementation (5000 IU/day) or placebo for 28 days. The primary outcome was oxygen dependency at 28 days of age or death.
                A total of 154 infants were randomised; 77 received vitamin A (median birth weight (interquartile range) 806 (710-890) g), and 77 received placebo (median birth weight (interquartile range) 782 (662-880) g). Plasma vitamin A concentrations in the supplemented group were significantly higher at 24 hours of age but did not differ significantly at birth, 12 hours of age, 7 days, or 28 days of life. There were no significant differences in the proportion of infants who survived, required oxygen at 28 days, required oxygen at 36 weeks postmenstrual age, survived without chronic lung disease at 36 weeks, survived without significant retinopathy, or who survived without significant intraventricular haemorrhage.
                Oral supplementation with 5000 IU vitamin A in extremely low birthweight infants does not significantly alter the incidence of chronic lung disease. However, this dose may have been inadequate to achieve optimal serum retinol concentrations. Vitamin A supplementation may reduce the risk of chronic lung disease and sepsis in extremely-low-birth-weight infants. The results of our pilot study suggested that a dose of 5000 IU administered intramuscularly three times per week for four weeks was more effective than the lower doses given in past trials.
                We performed a multicenter, blinded, randomized trial to assess the effectiveness and safety of this regimen as compared with sham treatment in 807 infants in need of respiratory support 24 hours after birth. The mean birth weight was 770 g in the vitamin A group and 769 g in the control group, and the respective gestational ages were 26.8 and 26.7 weeks.
                By 36 weeks' postmenstrual age, 59 of the 405 infants (15 percent) in the vitamin A group and 55 of the 402 infants (14 percent) in the control group had died. The primary outcome - death or chronic lung disease at 36 weeks' postmenstrual age - occurred in significantly fewer infants in the vitamin A group than in the control group (55 percent vs. 62 percent; relative risk, 0.89; 95 percent confidence interval, 0.80 to 0.99). Overall, 1 additional infant survived without chronic lung disease for every 14 to 15 infants who received vitamin A supplements. The proportions of infants in the vitamin A group and the control group who had signs of potential vitamin A toxicity were similar. The proportion of infants with serum retinol values below 20 microg per deciliter (0.70 micromol per liter) was lower in the vitamin A group than in the control group (25 percent vs. 54 percent, P<0.001).
                Intramuscular administration of 5000 IU of vitamin A three times per week for four weeks reduced biochemical evidence of vitamin A deficiency and slightly decreased the risk of chronic lung disease in extremely-low-birth-weight infants. The effect of Vitamin A supplementation on susceptibility to acute respiratory infections was investigated in a randomized controlled trial. One hundred and forty-seven preschool-age children with a history of frequent respiratory illness were randomized into Vitamin A supplemented (450 micrograms/day) and placebo groups. Respiratory symptoms were recorded on a daily basis over a period of 11 months. The children who received the supplement experienced 19% fewer episodes of respiratory symptomatology (P less than 0.05) than their placebo counterparts, despite the fact that their plasma retinol levels did not change. Children with a prior history of lower respiratory illness or of allergy benefited most from supplementation. The plausibility of a role for Vitamin A in the aetiology of respiratory proneness is reviewed. We conducted a randomized, double-blind, controlled trial to determine whether vitamin A supplementation from early postnatal life could reduce the morbidity associated with bronchopulmonary dysplasia in very low birth weight (VLBW) neonates. Forty VLBW neonates (700 to 1300 g birth weight, 26 to 30 weeks gestational age), who were oxygen dependent and required mechanical ventilation for at least 72 hours after birth, were given by the intramuscular route either supplemental vitamin A (retinyl palmitate 2000 IU) or 0.9% saline solution on postnatal day 4 and every other day thereafter for a total of 14 injections over 28 days. The study groups were comparable in gestational maturity, clinical characteristics, initial lung disease, and vitamin A status at entry into the trial. Vitamin A administration resulted in significantly higher mean plasma concentrations of vitamin A and retinol-binding protein in treated infants compared with controls. Bronchopulmonary dysplasia was diagnosed in nine of 20 infants given vitamin A supplement and in 17 of 20 control infants (P less than 0.008). Four of 19 infants in the vitamin A group and 11 of 20 in the control group required mechanical ventilation on study day 28 (P less than 0.029). The need for supplemental oxygen, mechanical ventilation, and intensive care was reduced in infants given vitamin A supplement compared with controls. Airway infection and retinopathy of prematurity were less frequent in the vitamin A group. We conclude that vitamin A supplementation at the dosage used in this trial in VLBW neonates not only improves their vitamin A status but also appears to promote regenerative healing from lung injury, as evidenced by a decrease in the morbidity associated with bronchopulmonary dysplasia. Randomized controlled trials have shown inconsistent responses of childhood pneumonia to the use of vitamin A as an adjunct to the standard treatment of pneumonia.
                We evaluated the effect of a moderate dose of vitamin A as an adjunct to standard antimicrobial treatment on the duration of respiratory signs in children with pneumonia.
                Children, aged 2-59 mo, with pneumonia and weight-for-age <50th percentile who had been admitted to the Baca Ortíz Children's Hospital in Quito, Ecuador, were randomly assigned to receive 50,000 IU (aged 2-12 mo) or 100,000 IU (aged >12-59 mo) vitamin A or a placebo.
                Of the 287 children enrolled, 145 received vitamin A and 142 received placebo. No overall differences were observed between the 2 groups in the duration of signs of pneumonia. Multiple linear regression showed a significant interaction between basal serum retinol concentration and vitamin A group for the time (in h) to remission of respiratory signs (beta = -3.57, SE = 1.09, P = 0.001). Duration of clinical signs was less in children with basal serum retinol concentrations >200 microg/L who received vitamin A supplements than in children with similar concentrations who received placebo (69.9 +/- 49.9 h compared with 131.3 +/- 143.9 h; P = 0.049).
                Overall, we found no effect of a moderate dose of vitamin A supplementation on the duration of uncomplicated pneumonia in underweight or normal-weight children aged <5 y. However, a beneficial effect was seen in children with high basal serum retinol concentrations. We performed a randomized, double-blind, controlled trial to determine whether vitamin A supplementation in a group of very low birth weight infants would reduce the incidence of bronchopulmonary dysplasia. Forty-nine infants (birth weight 700 to 1100 gm) requiring mechanical ventilation and supplemental oxygen at 96 hours age were randomly assigned to receive either 2000 IU retinyl palmitate (n = 27) or saline placebo (n = 22) intramuscularly every other day for up to 14 doses. There were no differences between treatment groups in the incidences of bronchopulmonary dysplasia at 31 days of postnatal age (vitamin A group 48%, placebo group 55%; p = 0.776), supplemental oxygen requirement at 34 weeks of postconceptional age, or other complications of prematurity. The vitamin A group had higher mean plasma vitamin A concentrations than the placebo group, but mean plasma vitamin A concentrations were greater than 20 micrograms/dl (suggesting sufficiency) in both groups after the first study week. By study day 28, only one fourth of the infants in either group had plasma vitamin A concentrations less than 20 micrograms/dl. In contrast to an earlier report, we found no change in the incidence of BPD with vitamin A supplementation. Our findings may reflect a low baseline incidence of vitamin A deficiency in the study population and recent changes in the respiratory care of very low birth weight infants. The latter may have lessened the potential impact of vitamin A deficiency on lung disease.
Whether clinicians decide to utilise repeat intramuscular doses of vitamin A to prevent chronic lung disease may depend upon the local incidence of this outcome and the value attached to achieving a modest reduction in this outcome, balanced against the lack of other proven benefits and the acceptability of treatment. Information on long-term neurodevelopmental status suggests no evidence of either benefit or harm from the intervention.