Association of urinary perchlorate, nitrate and thiocyanate with pregnancy loss risk among reproductive-aged women

Environmental pollution is recognized as a critical contributor to pregnancy loss. However, there is currently a paucity of evidence concerning the potential impact of perchlorate, thiocyanate and nitrate, which are known as sodium iodine symporter inhibitors. This study was therefore designed to investigate the potential association between urinary perchlorate, thiocyanate and nitrate concentration and the risk of pregnancy loss. Based on the National Health and Nutrition Examination Survey 2001-2002 and 2005-2020 cycles, a total of 3249 reproductive-aged women were enrolled, of whom 1729 (53.22 %) had a history of pregnancy loss encompassing miscarriages, stillbirths, ectopic pregnancies, or abortions. Logistic regression analyses revealed that urinary perchlorate levels were significantly associated with increased pregnancy loss prevalence. In the weighted quantile sum and Bayesian kernel machine regression models, co-exposure to three anions were also significantly associated with higher pregnancy loss odds, with perchlorate identified as the primary contributor. Additionally, the mediation analysis suggested that insulin resistance, represented by the triglyceride-glucose index, accounted for 6.08 % of the perchlorate-associated risk. In summary, our study revealed a potential role of perchlorate exposure in pregnancy loss. Further prospective studies are needed to confirm our findings and elucidate the underlying causative mechanistic links.