Time-VaryingRelationship between Maternal Trace ElementExposure and Gestational Hypothyroidism

Trace elements, including endocrine-disrupting metals (EDMs) and nutritional trace metals (NTMs), are ubiquitous in the environment and originate from natural and anthropogenic sources. Evidence suggests their involvement in hormone homeostasis, yet their exposure patterns and links to gestational hypothyroidism remain unknown. Measuring trace elements in maternal hair using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) is a promising technique to assess both cumulative and time-resolved exposures. In this prospective nested case-control study, we characterized temporal variations in trace elements preceding gestational hypothyroidism diagnosis and examined their associations with the disease risk. Compared to controls, cases exhibited consistently elevated levels of arsenic (As), strontium (Sr), and barium (Ba), along with reduced zinc (Zn) levels, up to two months prior to diagnosis. An interquartile range increase in Zn levels was associated with a 39% lower risk of gestational hypothyroidism, while higher levels of As, Sr, and Ba were linked to increased risk (odds ratios: 1.32–1.42). The combination of Zn, As, Sr, and Ba achieved the highest predictive accuracy with an area under the receiver operating characteristic curve (AUC) of 0.80. These findings advance the understanding of the health impacts of trace element exposure and highlight their potential role in the pathogenesis of gestational hypothyroidism.