Interacting and joint effects of assisted reproductive technology and gestational diabetes mellitus on preterm birth and the mediating role of gestational diabetes mellitus: a cohort study using a propensity score

ObjectiveTo investigate whether gestational diabetes mellitus (GDM) mediates the association between assisted reproductive technology (ART) and preterm birth (PTB), and to examine the interaction and joint effects of ART and GDM on PTB.MethodsThis retrospective cohort study utilized data from 20,721 mothers with singleton live births at Sichuan Jinxin Xinan Women and Children's Hospital from January 2020 to December 2023. The exposures were ART and GDM, and the outcome was PTB. Multivariate logistic regression assessed the separate associations of ART and GDM with PTB. Mediation, interaction, and joint effects were analyzed using R software.Results1,053 (5.08%) women experienced PTB. ART (OR 1.60; 95% CI 1.27-2.03) and GDM (OR 1.51; 95% CI 1.19-1.92) were both associated with increased PTB risk. GDM partially mediated the ART-PTB relationship (PM 2.72%; 95%CI 0.47%-8.86%). No additive interaction was found between GDM and ART for PTB in the general population. However, a significant additive interaction was observed in women aged >= 35 years (RERI 1.22; 95%CI 0.27-2.39). Compared to the spontaneous conception (SC)-non-GDM group, the SC-GDM (OR 1.56; 95%CI 1.07-2.29), ART-non-GDM (OR 1.63; 95%CI 1.22-2.18), and ART-GDM (OR 2.42; 95%CI 1.74-3.37) groups had higher PTB risk.ConclusionsART was associated with higher PTB risk, partially mediated by GDM. Women undergoing ART who develop GDM may face greater PTB risk than those exposed to only one factor, with a synergistic effect in older pregnancies.