Preconception exposure to veterinary antibiotics, oxidative stress, and spontaneous abortion: Evidence from a couple-based prospective cohort

Few studies have evaluated the impact of preconception exposure to foodborne veterinary antibiotics (VAs) on spontaneous abortion (SA) in childbearing couples. Using data from the Reproductive Health of Childbearing Couple-Anhui Cohort (RHCC-AC), we explored the relationship between preconception exposure to foodborne VAs in couples and SA and investigated whether oxidative stress mediates this association. Generalized linear mixed models were used to estimate associations between VAs and SA, while multivariable logistic regression was applied to assess relationships between oxidative stress biomarkers and SA with adjusted odds ratios (aOR) and 95% confidence intervals (CI). Causal mediation analysis was conducted to quantify mediation effects. Meet-in-the-middle analysis identified oxidative stress biomarkers linked to both mixed VA exposure and SA. Sulfamonomethoxine (aOR=2.67, 95%CI: 2.05,3.47), thiamphenicol (aOR=8.70, 95%CI: 5.44, 13.91), and doxycycline (aOR=1.22, 95%CI: 1.01, 1.48) were associated with an increased risk of SA. 8-OHdG (aOR=26.37, 95%CI: 12.65, 54.95), HNEMA (aOR=1.92, 95%CI: 1.53, 2.41), and Alla (aOR=7.21, 95%CI: 4.78, 10.87) were linked to higher SA risk. 8-OHdG and Alla partially mediated the positive correlation between thiamphenicol and SA, with a mediation proportion of 14.51% and 27.51%, respectively. D, L-o-Tyr, and HNE-MA partially mediated the association between positive and negative VA exposure and SA, with a mediation proportion of 6.90% and 8.18%, respectively. Overall, preconception exposure to foodborne VAs was associated with increased SA risk in couples, and oxidative stress appeared to be an important mechanistic pathway.