Project Summary Through the proposed research and training plan, the PI seeks to develop into an independent investigator with the career goal of identifying targeted patient blood management interventions to improve outcomes in pediatric surgical patients. Patients undergoing spinal fusion surgery for Adolescent Idiopathic Scoliosis (AIS) are poised to benefit from many of these interventions. Spinal fusion carries a risk of large surgical blood losses and perioperative red blood cell transfusion, which are associated with adverse outcomes in this population. These patients are mostly adolescent females, a group more susceptible to iron deficiency and resulting anemia at baseline due to iron losses with menses, and who suffer an additional insult to iron stores during surgery. Nevertheless, iron status is not routinely monitored in this setting and there is no standard of care for preoperative iron supplementation. Iron is a nutritionally essential trace element important not only for red blood cell production, but also for muscle function and neurotransmitter synthesis and signaling. Therefore, the treatment of preoperative iron deficiency is an important target for optimizing hemoglobin prior to surgery, reducing transfusion rates, and improving patient outcomes. On its own and as the primary cause of anemia, iron deficiency was identified by our group as the only risk factor for transfusion which is modifiable preoperatively. In addition, iron supplementation is shown to alleviate impairments of physical and cognitive capacity associated with even mild forms of iron deficiency in adolescent females. A pilot study conducted at our institution identified iron deficiency in 36% of AIS patients prior to surgery, with preoperative iron status highly correlated with iron status during surgical recovery. Consequently, we plan to examine iron deficiency as a modifiable risk factor for transfusion and impaired postoperative cognitive and physical capacity in this vulnerable population. Previous trials of brief iron interventions in high-risk adult surgical patients, mostly with unknown iron status, do not inform the care of iron deficient adolescents and were not designed to address postoperative functional outcomes. We will therefore perform a single-center randomized controlled trial in which iron-deficient AIS patients identified using physiologically-based serum markers will be randomized to a 3-month preoperative regimen of daily oral iron or placebo, to test the hypotheses that preoperative iron supplementation 1) reduces the rate of red blood cell transfusion, 2) improves postoperative neurocognition compared to a preoperative baseline, and 3) improves patient-reported physical functioning during recovery. Our results will ultimately improve outcomes in this vulnerable pediatric population and provide evidence for patient blood management approaches to reduce transfusions amid recent severe blood shortages.

PROJECT NARRATIVE Pediatric patients undergoing spinal fusion surgery for the correction of Adolescent Idiopathic Scoliosis are at high risk of both preexisting and surgery-related iron deficiency, yet the means and evidence for optimizing iron status have not been described in this setting. The proposed study is a randomized controlled trial of preoperative oral iron supplementation, to identify whether iron deficiency is a modifiable risk factor for adverse surgical outcomes such as red blood cell transfusion and diminished postoperative cognitive and physical capacity in this vulnerable population of adolescents. Building evidence for patient blood management interventions such as iron supplementation is vital to ensuring high quality care of surgical patients and may reduce unnecessary transfusions amid recent blood shortages.