Biologic Mechanisms of Labor Dysfunction: A Systems Biology Approach

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Maternal mortality in the United States continues to rise, exceeding rates in most other developed nations. Dysfunctional labor is a significant contributor to maternal morbidity and mortality, particularly among individuals with elevated body mass index (BMI > 30 kg/m²). These individuals face higher rates of unplanned cesarean delivery, often due to delayed initiation or progression of labor. Current research suggests that lipotoxicity—a metabolic condition resulting from excess free fatty acid deposition in non-adipose tissues—may impair uterine contractility and coordination. However, BMI is a limited predictor of lipotoxicity, and knowledge gaps remain regarding the mechanisms linking metabolic dysfunction to labor outcomes across a range of BMI scores. We will recruit 200 individuals in early pregnancy who intend to give birth in a community-based care setting characterized by minimal routine medical intervention and expanded prenatal education. After delivery, a structured chart review of term, healthy singleton births will identify cases and controls for comparative analysis. Lipidomic features will then be compared between groups to identify predictive biomarkers of labor dysfunction. The proposed study will apply a systems biology approach to investigate the development of metabolic and lipid perturbations throughout pregnancy and determine the extent to which lipotoxicity contributes to labor dysfunction (Aim 1), then examine associations between labor dysfunction-associated lipid profiles and clinical measures (adipose hormone levels or body fat percentage), pregnancy behaviors (nutrition and physical activity) (Aim 2), or prenatal care setting, using data from an existing cohort of similar individuals who received care in a nearby hospital system (Aim 3). This research leverages advanced omics technologies and a multidisciplinary team to address a critical gap in maternal health. Findings from this work are expected to advance early detection, targeted intervention, and potential prevention strategies for labor dysfunction, contributing to improved maternal outcomes.

Grant Number: 5R01NR019254-05
NIH Institute/Center: NIH
Principal Investigator: Nicole Carlson