Genomic Insights into Maternal-Fetal Interactions: Investigating Genetic Factors Influencing Pregnancy Outcomes and Preterm Birth

Abstract

Background: Preterm birth (PTB) remains a significant global health challenge, influencing maternal and neonatal outcomes. Understanding genetic factors influencing pregnancy is vital for improving clinical interventions. Objective: To investigate the genetic factors contributing to pregnancy outcomes, particularly preterm birth, by analyzing maternal and fetal genetic variations and their relationship with adverse pregnancy outcomes. Methods: This study was conducted at the Department of Obstetrics and Gynecology and Maternal–Fetal Medicine at the University of Texas Southwestern Medical Center. A total of 134 patients were included, with data collected between January 2023 and June 2024. Participants underwent genomic analysis using genome-wide association studies (GWAS) and next-generation sequencing (NGS) to identify genetic variants associated with PTB. Inflammatory markers, immune gene expression, and placental development genes were also analyzed. Statistical analysis was performed using SPSS, with significance set at p<0.05. Results: Among the 134 patients, 35% (47 patients) experienced preterm birth. Analysis of immune-related genes showed significant associations between variants in IL-6, TNF-α, and PTB (p<0.01). Genetic variations in placental function genes (VEGFA, PGF, and FLT1) were found to be significantly associated with PTB, with p-values of 0.02, 0.03, and 0.01, respectively. Further analysis revealed that fetal genetic factors contributed to a 23% increased risk of PTB. The average maternal age in the PTB group was 31.5 years (SD=3.2), with a higher risk observed in mothers aged 35 or older. Inflammatory markers, including CRP and IL-1β, had mean levels of 5.6 mg/L (SD=1.3) and 12.3 pg/mL (SD=4.5) in the PTB group, significantly higher than in the term birth group (p<0.05). The predictive model for PTB, based on maternal and fetal genetic factors, achieved an accuracy of 81%, sensitivity of 74%, and specificity of 88%. Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.85, indicating high diagnostic performance.  Conclusion: This study provides significant insights into the genetic factors contributing to preterm birth, emphasizing the role of maternal-fetal genomic interactions in influencing pregnancy outcomes.