Abstract
Introduction: Vertical transmission of Escherichia coli (E. coli) is an important pathway for neonatal colonization and infection, yet the bacterial genetic determinants underlying transmission remain poorly understood. Methods: In this cohort study, 1611 pregnant women underwent rectovaginal screening at 35–37 gestation weeks and subsequently delivered at the same hospital between 2015 and 2017. Vertical transmission was defined as paired maternal-neonatal culture positivity for E. coli. Whole-genome sequencing was performed on maternal-neonatal paired isolates. Clinical risk factors and transmission-associated virulence genes were evaluated, and a virulence factor score (VFscore) was developed using LASSO regression. Results: A total of 224 maternal-neonatal paired E. coli isolates were analyzed, including 91 transmission and 133 non-transmission cases. Maternal age and duration of premature rupture of membranes (PROM) were independently associated with vertical transmission. A VFscore derived from 13 virulence-associated genes was significantly higher among transmission isolates and remained independently associated with transmission after adjustment for clinical covariates. Mediation analyses demonstrated an asymmetric relationship between PROM and VFscore, with 41.5% of the effect of PROM on transmission mediated through VFscore, whereas only 13.8% of the VFscore effect was mediated through PROM. A combined model incorporating clinical factors and VFscore showed excellent discrimination for transmission (AUC 0.903, 95% CI 0.866–0.940). Conclusion: Both host and bacterial determinants contribute to maternal-neonatal transmission of E. coli. A cumulative virulence burden quantified by VFscore was independently associated with transmission and provided complementary information beyond established clinical risk factors, highlighting the importance of host-pathogen interactions in vertical transmission.