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

Project Summary
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.

Grant Number: 1K08HD114850-01A1
NIH Institute/Center: NIH
Principal Investigator: Katherine CAMERON