#VisualAbstract: Enteral water-soluble vitamin A in extremely preterm infants does not reduce severity of bronchopulmonary dysplasia

1. Daily enteral water-soluble vitamin A in extremely preterm infants did not significantly reduce the severity of BPD compared to patients that received placebo.

2. Infants who received daily enteral water-soluble vitamin A demonstrated significantly higher plasma levels of retinol when compared to patients who received placebo.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Intramuscular vitamin A has been shown to prevent bronchopulmonary dysplasia (BPD) when administered three times per week to extremely premature infants. However, it is rarely used because of hesitation to administer intramuscular injections regularly to these patients. In prior studies, enteral vitamin A showed no significant benefit in preventing BPD, which may be explained by its poor absorption. The present study aimed to assess if a smaller particle size of vitamin A in a water-soluble form may allow for improved absorption and therefore, reduce BPD severity in extremely preterm infants. To do this, a double-blind placebo-controlled randomized controlled trial (RCT) with infants born before 28 weeks gestational age was conducted. The vitamin A group received enteral 5000 IU of retinyl palmitate every day until 34 weeks’ postmenstrual age. BPD severity was measured by the right shift of the oxygen saturation vs partial pressure of inspired oxygen curve at 36 weeks’ postmenstrual age. Plasma retinol levels were higher in the vitamin A group as compared to the placebo group but the right shift was not significantly different between the two groups. The study demonstrates that although enteral water-soluble vitamin A increases plasma retinol levels, there may not be a significant effect on the prevention of BPD.

Click to read the study in Pediatrics

Relevant Reading: Randomised controlled trial of oral vitamin A supplementation in preterm infants to prevent chronic lung disease

In-Depth [randomized controlled trial]: To assess for the effectiveness of enteral water-soluble vitamin A to prevent BPD, this study carried out a double-blind placebo-controlled RCT of extremely preterm infants born before 28 weeks’ gestational age. The primary outcome measured was severity of BPD, calculated by the right shift of the oxygen saturation vs partial pressure of inspired oxygen curve at 36 weeks’ postmenstrual age. Plasma retinol levels and other secondary outcome measures were also gathered. A total of 188 patients were randomly assigned to each group with 94 in the vitamin A group and 94 in the control group. 79 shift tests were performed in the vitamin A group and 82 were performed in the control group. Daily 5000 IU of retinyl palmitate was given to those in the vitamin A group until 34 weeks’ gestation age. Baseline characteristics of the mothers and infants were similar between the two groups. The median difference in right shift at 36 weeks’ postmenstrual age did not differ significantly between the two groups (median difference 0.10, 95% CI -0.60 to 0.90; P = 0.730). Other secondary outcome measures also did not show significant difference between the two groups. However, plasma retinol levels were significantly higher in the vitamin A group than in the placebo group on day 28 (median in vitamin A group 26.4 and median in placebo group 14.9; P = 0.023) and at 34 weeks’ postmenstrual age (median in vitamin A group 21.5 and median in placebo group 18.1; P = 0.014). Furthermore, the plasma retinol levels and RDR at 28 days did not correlate with right shift (correlation 0.259 with P = 0.139 and correlation 0.010 with P = 0.955, respectively).