A trial of vitamin A therapy to facilitate ductal closure in premature infants. Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. Trial of vitamin A supplementation in very low birth weight infants at risk for bronchopulmonary dysplasia. Clinical trial of vitamin A supplementation in infants susceptible to bronchopulmonary dysplasia. Randomised controlled trial of oral vitamin A supplementation in preterm infants to prevent chronic lung disease. A comparison of three vitamin A dosing regimens in extremely-low-birth-weight infants.
To determine whether postnatal vitamin A therapy increased ductal closure rate in premature infants.
                This was a prospective, double-blind, placebo-controlled trial. Subjects (n=40) were recruited on day of life 1. Inclusion criteria were premature neonates weighing 500 to 1500 g with an indwelling umbilical line. Vitamin A was administered intramuscularly on days 1, 3, and 7. Blood vitamin A and retinol binding protein levels were obtained on days 1 and 3. Echocardiography was performed on days 1, 3, 7, and 14. Failure of ductal closure was defined as the presence of a moderate to large patent ductus arteriosus on day 14, indomethacin therapy, or surgical ligation.
                Comparison between the treatment and placebo groups revealed no differences in gestational age, weight, or oxygenation index. Vitamin A and retinol binding protein levels did not differ between the groups at entry but increased significantly after vitamin A treatment. Failure of ductal closure occurred in 22 of 40 babies without any difference between the groups (12/22 vs 10/18, P=NS). Four infants required surgical ligation, all in the treatment group (P=.04). Clinical outcome did not vary between groups.
                Postnatal vitamin A therapy did not improve ductal closure rates in premature infants. 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. 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. 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. 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 reduces bronchopulmonary dysplasia (BPD)/death in extremely low birth weight neonates. It was hypothesized that compared with the standard regimen of 5000 IU 3 times per week for 4 weeks, (1) a higher dose (10,000 IU 3 x per week) would increase serum retinol and retinol binding protein (RBP) and lower relative dose responses (RDR), and (2) once-per-week dosing (15,000 IU once per week) would lead to equivalent levels, RBP, and RDR.
                Extremely low birth weight neonates (n = 120) receiving O(2)/mechanical ventilation at 24 hours were randomly assigned to (1) standard, (2) higher dose, or (3) once-per-week regimens. Measures of vitamin A deficiency were serum retinol <20 microg/dL, RBP <2.5 mg/dL, and/or RDR >10% on day 28. BPD was defined as O(2)/mechanical ventilation at 36 weeks' postmenstrual age.
                Groups were similar at enrollment (median gestational age, 25 weeks; birth weight, 689 g). Possible toxicity was seen in <5%. The higher dose regimen did not increase retinol or RBP, decrease RDR, or improve outcomes. Infants in the once-per-week regimen had lower retinol levels and higher RDR without an effect on outcomes.
                Compared with the standard regimen, once-per-week dosing worsened, and higher doses did not reduce, vitamin A deficiency. Therefore, the standard regimen is recommended.
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.