Promotion of Exclusive Breastfeeding in Children with Sickle Cell Disease for Improved Health Outcomes - ABSTRACT Sickle cell disease (SCD) is an inherited red blood cell disorder that predominantly affects individuals of African descent. The physiologic hallmarks of SCD include chronic red blood cell hemolysis, oxidative stress, inflammation, vascular damage and end-organ damage. These physiologic sequelae lead to unpredictable vaso occlusive complications, such as pain and acute chest syndrome (ACS). Human breastmilk contains antioxidant, anti-inflammatory and immune-modulating properties proven to be protective against chronic inflammatory conditions, such as asthma, obesity and cardiovascular disease. The lasting impacts of human breastmilk have been demonstrated in adolescent and adult studies, wherein individuals that were breastfed as infants had lower levels of biological markers of inflammation in their bloodstream. Interestingly, breastmilk has even been demonstrated to be protective against the erosion of telomeres – which are the protective caps of DNA and established markers of oxidative stress and inflammation. The American Academy of Pediatrics and World Health Organization recommend exclusive breastfeeding (EBF) for the first 6 months of life, followed by 1 to 2 years of breastfeeding with nutritious supplementation. However, despite these recommendations and the well- established protective benefits of EBF, the gap between Healthy People 2020 breastfeeding goals and current rates of EBF is widest amongst African American women compared to all other racial and ethnic groups. Furthermore, the protective effects of EBF have never been explored in SCD. Several studies have noted a lack of breastfeeding role models and support networks as barriers to EBF among African American women. One community-based organization located in Birmingham (Alabama) — the Chocolate Milk Mommies —, specifically addresses these barriers through online and in-person education and support groups, certified lactation consultant services, free breast pump rentals for low-income mothers and a home visitation and peer- mentoring program. Chocolate Milk Mommies specifically targets African American mothers, given the lower rates of breastfeeding in this population. This group achieved a 6-month EBF rate of 83% in 2019, far exceeding state and national trends. Given the pervasive oxidative stress and inflammation in SCD, and the consequent risk for pain and poor lung health, it is essential to test the protective benefits of EBF and establish effective EBF- promoting interventions among this high risk population. The aims for this project are to: 1) test the association between EBF exposure and SCD complications, 2) test the association between EBF exposures and biological markers of oxidative stress and inflammation, and 3) pilot the feasibility to recruit and retain 20 mothers of children with SCD to a community-based EBF program (the Chocolate Milk Mommies) for ≥6 months, which will inform a future larger randomized controlled trial. The long-term goal for this research is to establish the protective benefits of breastfeeding in SCD and improve overall health outcomes through the promotion of EBF.