Mechanistic Pathways of Probiotic Supplementation in Optimizing Iron and Hematological Status Among Pregnant Females at Risk of Iron Deficiency Anemia - Maternal iron deficiency anemia (IDA) is associated with maternal and infant mortality and profound perinatal and neonatal comorbidities, including adverse effects on offspring neurocognitive development and health. The use of oral prenatal supplements containing iron as a prophylatic approach to prevent IDA is suboptimal as evidenced by upwards of 18% of pregnant females still experiencing IDA despite being prescribed a prenatal supplement containing iron. Clearly, there is room for improvement and a need for novel and efficacious strategies to prevent the development of maternal IDA with a focus on those who are most vulnerable. Probiotics are “live micro-organisms which, when administered in adequate amounts, can confer a health benefit on the host”. There is increasing evidence that consuming the probiotic Lactiplantibacillus plantarum 299v (LP299V®) can enhance dietary iron absorption and improve iron status including in the context of pregnancy. The proposed study will be the first to test the efficacy of this accessible, low-cost, safe, innovative approach to optimizing iron status in individuals at risk for IDA in pregnancy [1st trimester hemoglobin (Hb) 11.0-11.9 g/dL and 2nd trimester Hb 10.5-11.5 g/dL]. We will conduct a prospective, double-blind, placebo-controlled randomized study of a commercially available oral LP299V® supplement taken twice daily with a standard prenatal supplement containing iron from 10-16 weeks gestational age (GA) until the time of labor in 200 individuals. Adherence will be monitored remotely by smart cap/bottle with associated researcher interface. We hypothesize that pregnant females consuming LP299V® will have stable or improved Hb and iron status parameters and lower rates of IDA at 24-28 weeks GA, 34-36 weeks GA and at the time of labor compared to participants taking a placebo and prenatal supplement with iron. We will extend findings to the neonate to determine if infants born to participants receiving LP299V®, compared to placebo, have superior markers of cord iron status and cord and heel stick Hb. We will explore intervention effects on infant neurodevelopment at birth using auditory brainstem response (ABR) testing. Lastly, we will examine gut microbial, placental and iron regulatory mechanisms through which LP299V® imposes its effect on iron metabolism. Our approach is rigorous given the double-blind placebo-controlled design and is comprehensive as we are: 1) targeting a sample of pregnant females at risk of IDA; 2) extending effects to the neonate; 3) determining mechanisms of effect and 4) exploring impact on child neurodevelopment. Our team is well positioned to successfully conduct the study given our history of collaboration and active perinatal research infrastructure. This trial has the potential to transform prenatal care and health outcomes for hundreds of thousands of pregnant females and their children in the U.S. annually and millions worldwide.
