A recent review published in Pediatric Investigation examines the intricate relationship between anemia and retinopathy of prematurity (ROP), particularly focusing on iron deficiency and its molecular mechanisms. ROP is a leading cause of vision impairment among preterm infants, especially those with extremely low birth weight. The study highlights how anemia, prevalent in these infants due to frequent blood draws and missed maternal iron transfer during pregnancy, might contribute to ROP development through hypoxia, oxidative stress, and inflammation. The article calls for more targeted clinical trials to better understand this connection and improve treatment strategies.

The prevalence of anemia in premature infants is significant, with nearly 90% requiring at least one blood transfusion. This condition often arises from the medical necessity of regular blood sampling during critical care. Moreover, preterm infants miss out on the crucial third trimester when most maternal iron transfers occur, increasing their risk of iron deficiency. The onset of anemia can lead to reduced oxygen delivery to the retina, which exacerbates tissue hypoxia. Iron deficiency further complicates this by inhibiting prolyl hydroxylase domain activity, essential for activating hypoxia-inducible factor 1-alpha (HIF-1α). When HIF-1α is translocated to the nucleus under conditions of hypoxia and iron deficiency, it triggers the transcription of angiogenic factors such as vascular endothelial growth factor (VEGF), promoting abnormal retinal vessel growth characteristic of ROP.

Beyond hypoxia, oxidative stress and inflammation also play crucial roles in ROP development. Preterm infants, with lower antioxidant levels, are more susceptible to reactive oxygen species (ROS) produced during oxidative metabolism. Accumulation of ROS damages endothelial cells and delays retinal vasculature development. Additionally, anemia induces a pro-inflammatory response, elevating cytokine levels like interferon-gamma and tumor necrosis factor-alpha, worsening retinal injury. A paradox exists regarding the severity of anemia; early anemia increases ROP risk significantly, whereas chronic non-transfused anemia may decrease it, suggesting protective effects of iron deficiency. However, variations in transfusion protocols and iron supplementation across neonatal units complicate understanding the precise role of anemia in ROP.

Dr. Ellen C. Ingolfsland from the University of Minnesota emphasizes the need for well-designed randomized controlled trials to clarify anemia's impact on ROP and explore involved molecular mechanisms. These studies should account for timing, severity, and management of anemia alongside other confounding factors. Understanding these mechanisms could lead to improved prevention and treatment strategies for ROP. Such advancements are crucial for enhancing clinical outcomes for vulnerable premature infants facing both anemia and ROP challenges.

This review underscores the importance of investigating the complex interplay between anemia and ROP. By addressing knowledge gaps concerning molecular mechanisms linking iron deficiency anemia to ROP, researchers aim to develop more effective strategies. These efforts could significantly enhance the quality of life for preterm infants, ensuring they have the best possible chance at healthy visual development.