Characterizing the Impact of Uterine Fibroids on the In-Utero Environment Offspring Consequences

Uterine fibroids are highly prevalent tumors, even in young reproductive-aged women. They are present in up to 10% of pregnancies, about half a million US births per year. These tumors display substantial inflammatory, hypoxic, angiogenic, and oxidative stress aberrations with conceivable implications during pregnancy on the developing placenta and offspring. However, to date the long-term impacts of uterine fibroids on offspring have not been examined. The overall goal of this proposal is to assess the impact of uterine fibroids on the In- Utero environment and offspring long-term cardiometabolic health by leveraging the existing resources of the Boston Birth Cohort (BBC), an ongoing large longitudinal, predominantly urban African-American birth cohort. Aim 1 will test the hypotheses that 1) the risk of maternal vascular malperfusion of the placenta is increased in the presence of any fibroid, regardless of location, 2) the risk of small-for-gestational age births is increased for women with uterine fibroids, and 3) women with uterine fibroids demonstrate unique metabolomic profiles compared to women without uterine fibroids. Aim 2 will test the hypothesis that that presence of uterine fibroids in utero will be associated with unique offspring metabolomic profiles, increased risk for offspring obesity/overweight status, elevated blood pressure, and increased leptin levels up to offspring up to age 21 years. This study will leverage extensive high-quality epidemiological and clinical data to allow for rich analysis of covariates (including shared risk factors between uterine fibroids and cardiometabolic dysfunction), along with biospecimens already obtained by the BBC. Dr. Cameron has built a nested cohort within the BBC of approximately 7000 mother-infant pairs (including close to 500 pairs with uterine fibroids present at time of delivery). This would be the first large-scale prospective birth cohort study to integrate cutting-edge metabolomics to address critical questions about the impact of uterine fibroids on early-life fetal programming and explore underlying mechanistic pathways. Dr. Cameron is a reproductive endocrinology and infertility specialist trained in clinical epidemiology. The additional training she proposes in molecular epidemiology, advanced statistical modeling including network analysis skills, and the creation and maintenance of multi-generational birth cohorts will help achieve her long- term goal of leading studies to investigate the impact of reproductive conditions on developmental origins of disease in diverse clinical contexts utilizing multiomics techniques with a lifecourse approach. This proposed study will lay a critical foundation for planned future R01 applications. Project Number: 1K08HD114850-01A1 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Katherine CAMERON | Institution: JOHNS HOPKINS UNIVERSITY, BALTIMORE, MD | Award Amount: $100,170 | Activity Code: K08 | Study Section: Obstetrics and Maternal-Fetal Biology Study Section[CHHD-B] View on NIH RePORTER: https://reporter.nih.gov/project-details/1K08HD11485001A1