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A comparison of three vitamin A dosing regimens in extremely-low-birth-weight infants
Namasivayam Ambalavanan1, Tzong-Jin Wu, Jon E Tyson
1Department of Pediatrics, University of Alabama at Birmingham, School of Medicine, Birmingham, Alabama, USA. ambal@uab.edu
Insights
Higher doses or once-weekly vitamin A supplementation did not improve outcomes in extremely low birth weight neonates. The standard regimen remains recommended to prevent vitamin A deficiency and related complications.
Area of Science:
- Neonatal Medicine
- Nutritional Science
- Pediatric Critical Care
Background:
- Vitamin A supplementation is crucial for reducing bronchopulmonary dysplasia (BPD) and mortality in extremely low birth weight (ELBW) neonates.
- Standard vitamin A regimens aim to prevent deficiency but optimal dosing and frequency require further investigation.
Purpose of the Study:
- To evaluate the efficacy of higher-dose and once-weekly vitamin A supplementation regimens compared to the standard regimen in ELBW neonates.
- To assess the impact of different vitamin A regimens on serum retinol, retinol-binding protein (RBP), and relative dose response (RDR).
Main Methods:
- A randomized controlled trial involving 120 ELBW neonates receiving oxygen or mechanical ventilation.
- Infants were assigned to standard (5000 IU 3x/week), higher-dose (10,000 IU 3x/week), or once-weekly (15,000 IU 1x/week) vitamin A regimens.
- Vitamin A deficiency was assessed by serum retinol, RBP levels, and RDR on day 28; BPD was defined by oxygen/ventilation at 36 weeks' postmenstrual age.
Main Results:
- The higher-dose regimen did not increase serum retinol or RBP, nor did it decrease RDR or improve BPD outcomes.
- The once-weekly regimen resulted in lower serum retinol levels and higher RDR, without improving clinical outcomes.
- No significant toxicity was observed in any of the groups.
Conclusions:
- Neither higher-dose nor once-weekly vitamin A supplementation improved vitamin A status or clinical outcomes in ELBW neonates compared to the standard regimen.
- Once-weekly dosing appeared to worsen vitamin A deficiency markers.
- The standard vitamin A supplementation regimen is recommended for ELBW neonates.
Objective:
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.
Study Design:
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.
Results:
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.
Conclusions:
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.