Effects of Early Vitamin A Supplementation on the Risk for Retinopathy of Prematurity in Extremely Preterm Infants

Retinopathy of prematurity (ROP) is a common retinal neovascular disorder and major cause of vision impairment or blindness, despite current treatment of late stage ROP. Because the visual disorders after treatment are often poor, preventive therapy for ROP is still lacking. Although ROP is a multifactorial disease, the altered regulation of vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF-1) have been implicated in the pathogenesis of ROP. The vascular endothelial growth factor (VEGF) is a hypoxia-inducible cytokine and a vascular endothelial cell mitogen. If VEGF is suppressed, normal vessel growth is inhibited, but if in excess, retinal neovascularization is precipitated. This indicates that VEGF is a critical factor in retinal neovascularization. Inhibition of VEGF at the neovascular phase might prevent destructive neovascularization. However, the choice of any intervention for the inhibition of VEGF should be taken into account very carefully, because VEGF also promotes normal physiological development of blood vessels in many tissues. In addition, this intervention can be applied to all preterm infants when potential side effects are almost minimal.

Vitamin A is one of the most important micronutrients affecting the health of children. Supplementing newborn infants with vitamin A within the first 2 days of life reduced infant mortality by almost 25%, with the greatest benefit to those of low birth weight. Vitamin A has been used in this population prophylactically for chronic lung disease with the large doses and no reported significant adverse effect exists. It is suggested that vitamin A-retinoids and their active metabolite, retinoic acid (RA) have highly potent antiangiogenic activity by inhibiting VEGF expression. Vitamin A (retinol) is converted into retinoic acid in cells. However, the significance of Vitamin A administration has not been investigated to our knowledge in an experimental ROP infant. The aim of this study was to demonstrate the preventive effect of Vitamin A on ROP.

Methods

This prospective, multicenter, randomized study was performed from August 2015 to March 2017 in neonatal intensive care units in China. This study was approved by the Life Science Ethics Committee of Zhengzhou University and the local research ethics committees at the participating centers. Written informed consent was obtained from both parents when an infant was admitted to the NICU.

Patient Population