Dr. Brown's research focuses on intrauterine growth restriction (IUGR). IUGR increases neonatal morbidity and mortality and also predisposes an individual for long term health problems including diabetes and heart disease. Dr. Brown is interested in how IUGR adversely affects fetal skeletal muscle development. Adults who began life with IUGR have reduced muscle mass, which contributes to their increased risk of developing cardiovascular disease and diabetes. Dr. Brown’s research goal is to define the mechanisms responsible for poor fetal muscle growth and the potential reversibility of these fetal adaptations such that chronic adulthood diseases like diabetes and heart disease might be prevented.
BIRCWH project title: Functional and structural adaptations of fetal skeletal muscle to nutrient and anabolic hormone deficiencies under conditions of placental insufficiency and IUGR
Current research focus: My research goals are to improve muscle growth and body composition of fetuses and neonates affected by intrauterine growth restriction (IUGR). Compelling associations link low birth weight from IUGR and decreased muscle mass to insulin resistance, development of the metabolic syndrome and type 2 diabetes, and risk for cardiovascular events later in life. Thus, my primary research interest is to understand the basic biology of fetal muscle growth, including the physiological, molecular, and cellular mechanisms that link fetal nutrient availability to muscle growth using both animal (sheep) models and human pregnancies. I blend in vivo physiology and molecular/cellular biology techniques to understand how interactions among nutrient and oxygen delivery to the fetus and circulating fetal hormones impact fetal whole-body growth, protein accretion, and skeletal muscle growth. This knowledge will lead the development of innovative strategies to improve fetal growth early in the lifespan.
How Dr. Brown became interested in this work: I became interested in studying fetal metabolism because it is an understudied area, yet growth problems in the developing fetus have grave consequences for lifelong metabolic health. I am a neonatologist, and one of the most important things we do every day in our practice is to ensure optimal growth of a neonate who is in the NICU for a variety of medical and/or surgical reasons. I am very interested in optimizing nutritional practices as well as methods to assess "balanced" growth of a neonate, such that the lean mass/muscle mass is growing at the same rate as adipose tissue.
Clinical significance of this research: Current nutritional practices in the NICU favor adipose growth over lean mass/muscle growth, in part because the number of skeletal muscle fibers is set at birth, thus limiting postnatal growth to hypertrophic growth of the myofiber. My work allows me to bring together the basic science research to understand the physiological processes for how the skeletal muscle of a fetus grows in the womb during adverse pregnancy conditions (placental insufficiency, overnutrition from the placenta, hypoxia) in order to optimize clinical nutritional practices to provide balanced growth of the neonate.
Relevance of this work to women's health or sex/gender differences: Up to 10% of pregnancies are affected by intrauterine growth restriction. Women's health issues such as diabetes, obesity, and hypertension can all contribute to the risk of an IUGR pregnancy, and often the reason for an IUGR pregnancy is idiopathic (not known). The consequences of an IUGR pregnancy affect both the pregnant mother as well as the child born after IUGR, in terms of longer term metabolic disease risk. If the child born after IUGR is female, the transgenerational cycle can continue.