Exposure to Lithium and Cesium Through Drinking Water and Thyroid Function During Pregnancy: A Prospective Cohort Study

Background: Impaired thyroid function is a common side effect of lithium medication. Recent data indicate that lithium exposure through drinking water, although providing much lower doses than the medication, may also affect thyroid hormone levels. However, the effects in susceptible groups like pregnant women are not known. Methods: In a population-based mother-child cohort in the Argentinean Andes (n=194), an area with varying concentrations of lithium in the drinking water, we assessed lithium exposure repeatedly during pregnancy by measuring the concentrations in blood using inductively coupled plasma mass spectrometry. The markers of thyroid function included thyrotropin (TSH), free/total thyroxine (fT4/T4), free/total triiodothyronine (fT3/T3), thyroglobulin, and transthyretin in serum, sampled at the same time. Multiple potential confounders, including exposure to arsenic, cesium, and boron (elevated in water) as well as selenium and iodine (essential for thyroid function) were considered. Results: The lithium concentrations in blood [median 25g/L (0.0036mmol/L); range 1.9-145g/L (0.000027-0.021mmol/L)] correlated significantly with those in urine and drinking water (r(s)=0.84, p<0.001, and r(s)=0.40, p<0.001, respectively). Using linear quantile regression models, we found a positive association between blood lithium (log2 transformed) and TSH concentrations, particularly in the lowest percentiles of TSH (B=0.20mIU/L, [95% confidence interval 0.048-0.35] at the fifth percentile). We also found inverse associations of blood lithium with transthyretin, particularly at the highest percentiles, as well as with fT3 and T3, with less obvious variation across percentiles. Unexpectedly, blood cesium concentrations (median 111g/L, range 2.5-711g/L) were also inversely associated with fT3 and T3, particularly at the highest T3 percentiles, but not with TSH or transthyretin. Arsenic and boron exposure (also through drinking water) did not show any associations with the thyroid parameters. Conclusions: The study supports previous findings that lithium exposure through drinking water may impair thyroid function. The results regarding cesium exposure through drinking water are new. During pregnancy, impaired thyroid function may be detrimental for fetal development. The findings reinforce the need for better control of drinking water, including bottled water, as well as a health-based guideline value.