Keywords::
Letter to the Editor
We read with interest the study by Moreira et al. on the impact of providing vitamin A to the routine pulmonary care of extremely low-birth weight infants (ELBW) [Citation1]. In their retrospective study, the authors demonstrated that the additional use of vitamin A was beneficial in preventing bronchopulmonary dysplasia in ELBW infants (decrease from 33% to 22%), although this result did not reach the level of statistical significance (p = 0.2). Moreover, no differences were found in the number of ventilator days or in the incidence of any other neonatal morbidity or mortality (intraventricular hemorrhage, necrotizing enterocolitis, or patent ductus arteriosus requiring surgical ligation). The authors conclude that a larger sample is necessary to demonstrate a significant impact of additional vitamin A administration in preventing BPD. We would like to add some additional data on this important issue.
Vitamin A can either be given orally, as an intramuscular injection, or intravenously. In the largest trial of parenteral vitamin A supplementation, vitamin A was given intramuscularly [Citation2]. In the study by Tyson et al., intramuscular administration of 5000 IU of vitamin A three times per week of 4 weeks reduced biochemical evidence of vitamin A deficiency and also decreased the risk of chronic lung disease in ELBW infants (number needed to treat 14–15) [Citation2].
Current treatment practice is administration of vitamin A intravenously (910 IU/kg/day) as part of a multivitamin supplement as long as the neonates are fed intravenously. Once enteral feeding has been established oral vitamin supplements are given, but doses are assumed to be too low [Citation3]. In Germany as well as in many other countries, neonates usually receive 2000 IU/day (not adjusted to birth weight). In ELBW infants, however, even very large enteral doses of vitamin A neither increase plasma concentrations of vitamin A significantly nor improve outcome [Citation3,Citation4].
During the first week of life—and most times even for a far longer period of time—ELBW infants have an intravenous access. Administering vitamin A intravenously thus does not require any additional painful procedure and might thereby increase the acceptance of vitamin A supplementation. Therefore, there is an urgent need to investigate intravenous administration in higher dosages as compared to current treatment practice.
In our multicenter, international RCT “NeoVitaA” we will investigate the effect of a continuous intravenous administration of vitamin A during the first week of life in ELBW infants (≤1000 g; ). The cumulative dose of vitamin A given intravenously over the first week of life corresponds to 70% of the cumulative dose which is recommended to be given over 4 weeks by intramuscular administration. Administration of 70% of the cumulative dose administered over the first week of life is assumed to be efficient and safe for the following reason: Preterm infants are known to be born with inadequate body stores of vitamin A [Citation5]. High doses of vitamin A are thus assumed to “fill” the body stores during the first week of life allowing to maintain adequate plasma concentrations not only during the first week of life but also during the following weeks. Furthermore, no increased toxicity could be shown when vitamin A was administered intramuscularly over 4 weeks in a cumulative dose three times as high as the dose we attempt to administer over 1 week [Citation6].
Figure 1. Outline of study trial (“NeoVitaA”).
By conducting this multicenter, international RCT (including >20 large European and Australian NICUs) we are hopeful to shed further light on this important issue, thus providing neonatologists with solid data as to whether early, high-dose intravenous vitamin A administration is beneficial in reducing the rate of BPD, as tentatively suggested by the study conducted by Moreira et al. [Citation1].
Declaration of Interest: The authors declared that the NeoVitaA Trial will be funded by the Deutsche Forschungsgemeinschaft (DFG: GZ: ME 3827 1/1).
References
- Moreira A, Caskey M, Fonseca R, Malloy M, Geary C. Impact of providing vitamin A to the routine pulmonary care of extremely low birth weight infants. J Matern Fetal Neonatal Med 2012;25:84–88.
- Tyson JE, Wright LL, Oh W, Kennedy KA, Mele L, Ehrenkranz RA, Stoll BJ, et al. Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med 1999;340:1962–1968.
- Kennedy KA. Epidemiology of acute and chronic lung injury. Semin Perinatol 1993;17:247–252.
- Wardle SP, Hughes A, Chen S, Shaw NJ. Randomised controlled trial of oral vitamin A supplementation in preterm infants to prevent chronic lung disease. Arch Dis Child Fetal Neonatal Ed 2001;84:F9–F13.
- Mactier H, Weaver LT. Vitamin A and preterm infants: what we know, what we don’t know, and what we need to know. Arch Dis Child Fetal Neonatal Ed 2005;90:F103–F108.
- Ambalavanan N, Wu TJ, Tyson JE, Kennedy KA, Roane C, Carlo WA. A comparison of three vitamin A dosing regimens in extremely-low-birth-weight infants. J Pediatr 2003;142:656–661.