Introduction Reduced growth and delayed maturation have been previously described in children with sickle cell disease (SCD) due to multifactorial causes including chronic anemia and increased hemolysis. Interventions that decrease anemia and inflammation may have a beneficial effect on growth in children with SCD. Previous studies have demonstrated that children with SCD treated with hydroxyurea (HU) and chronic red cell transfusion therapy (CRCT) experience linear growth and increase in body mass index (BMI) compared to their counterparts not on therapy. Unfortunately, most of these studies were limited due to small sample size, cross-sectional study design or were conducted from single or a few center(s). DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) is a large, NHLBI (National Heart, Lung, and Blood Institute) funded consortium to improve stroke prevention implementation in SCD. DISPLACE includes the largest database of children with SCD from 28 different centers in the US. These data allow for an optimal assessment of growth in children with SCD on different disease modifying therapies. Using the DISPLACE database, we conducted a cross-sectional sub-study to evaluate how HU and CRCT affect growth in children over time. Methods The DISPLACE study collected data on 5,247 children aged 2-19 years with SCD from 28 centers in the US between 2012-2016. The majority of children have data collected from at least five years of continuous care. At baseline and annually thereafter, all children had routine standard of care anthropometric measurements including height and weight, vital signs, laboratory tests including complete blood count and chemistries and SCD-related therapies including chronic blood transfusion therapy and hydroxyurea therapy. Body mass index was converted to z-scores (zBMI) based on the Centers for Disease Control guide for age and sex. Children were categorized based on the zBMI score as underweight, normal, and overweight/obese. Our inclusion criteria included children with documented results of weight, height, vital signs, clinical and laboratory tests at baseline. Children who do not have sufficient data for evaluation (at least one missing anthropometric measurement or laboratory value) were excluded. Results Of the 3,305 children included in the study, 19.8%, 66.1%, 14.2% were underweight, normal, and overweight/obese at their initial (baseline) visit respectively. Children who were overweight/obese had a significantly higher hemoglobin level (p<0.0001) and significantly lower reticulocyte count (p = 0.0334) at baseline than normal and underweight children. Children who are overweight/obese had a significantly higher systolic and diastolic blood pressure compared to those who are normal or underweight (p = 0.0079 and p = 0.0003 respectively). A higher proportion of children who were overweight/obese were on CRCT at baseline compared to children with normal or underweight zBMI (p = 0.0002). The proportion of children on HU therapy at baseline was similar across zBMI categories (p = 0.2412). The multivariable adjusted model showed that the baseline hemoglobin levels were associated with the odds of being underweight (OR 0.93, 95% CI: 0.86 - 0.99), or overweight/obese (OR: 1.26, 95% CI: 1.17 - 1.36) compared with normal zBMI. At baseline, blood transfusion was associated with being overweight/obese versus normal (OR: 1.85, 95% CI: 1.31 - 2.60). After two years of therapy, there was a statistically significant increase in median zBMI from baseline among children initiating blood transfusion versus controls, (p = 0.0481), but the zBMI difference in hydroxyurea therapy versus controls remain same. (p=0.3925). Conclusion In our US-based study, the majority of children with SCD (70%) had normal zBMI. As baseline hemoglobin is associated with zBMI, that may predict who is at risk for being underweight or overweight. In addition, patients treated with CRCT are more likely to be overweight and have higher blood pressure. These findings suggest that individuals on CRCT should be monitored and may need lower calories than those not on disease modifying therapies. Disclosures Kanter: bluebird bio, inc: Consultancy, Honoraria; Novartis: Consultancy; Sanofi: Consultancy; Medscape: Honoraria; Guidepoint Global: Honoraria; GLG: Honoraria; Jeffries: Honoraria; Cowen: Honoraria; Wells Fargo: Honoraria; NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; AGIOS: Membership on an entity's Board of Directors or advisory committees; BEAM: Membership on an entity's Board of Directors or advisory committees.