Exposure to lithium through drinking water and calcium homeostasis during pregnancy: A longitudinal study.

There is increasing evidence of adverse health effects due to elevated lithium exposure through drinking water but the impact on calcium homeostasis is unknown. This study aimed at elucidating if lithium exposure through drinking water during pregnancy may impair the maternal calcium homeostasis. In a population-based mother-child cohort in the Argentinean Andes (n=178), with elevated lithium concentrations in the drinking water (5-1660µg/L), blood lithium concentrations (correlating significantly with lithium in water, urine and plasma) were measured repeatedly during pregnancy by inductively coupled plasma mass spectrometry and used as exposure biomarker. Markers of calcium homeostasis included: plasma 25-hydroxyvitamin D3, serum parathyroid hormone (PTH), and calcium, phosphorus and magnesium concentrations in serum and urine. The median maternal blood lithium concentration was 25µg/L (range 1.9-145). In multivariable-adjusted mixed-effects linear regression models, blood lithium was inversely associated with 25-hydroxyvitamin D3 (-6.1nmol/L [95%CI -9.5; -2.6] for a 25µg/L increment in blood lithium). The estimate increased markedly with increasing percentiles of 25-hydroxyvitamin D3. In multivariable-adjusted mixed-effects logistic regression models, the odds ratio of having 25-hydroxyvitamin D3<30nmol/L (19% of the women) was 4.6 (95%CI 1.1; 19.3) for a 25µg/L increment in blood lithium. Blood lithium was also positively associated with serum magnesium, but not with serum calcium and PTH, and inversely associated with urinary calcium and magnesium. In conclusion, our study suggests that lithium exposure through drinking water during pregnancy may impair the calcium homeostasis, particularly vitamin D. The results reinforce the need for better control of lithium in drinking water, including bottled water.

Boron exposure through drinking water during pregnancy and birth size.

BACKGROUND: Boron is a metalloid found at highly varying concentrations in soil and water. Experimental data indicate that boron is a developmental toxicant, but the few human toxicity data available concern mostly male reproduction. OBJECTIVES: To evaluate potential effects of boron exposure through drinking water on pregnancy outcomes. METHODS: In a mother-child cohort in northern Argentina (n=194), 1-3 samples of serum, whole blood and urine were collected per woman during pregnancy and analyzed for boron and other elements to which exposure occurred, using inductively coupled plasma mass spectrometry. Infant weight, length and head circumference were measured at birth. RESULTS: Drinking water boron ranged 377-10,929µg/L. The serum boron concentrations during pregnancy ranged 0.73-605µg/L (median 133µg/L) and correlated strongly with whole-blood and urinary boron, and, to a lesser extent, with water boron. In multivariable-adjusted linear spline regression analysis (non-linear association), we found that serum boron concentrations above 80µg/L were inversely associated with birth length (B-0.69cm, 95% CI -1.4; -0.024, p=0.043, per 100µg/L increase in serum boron). The impact of boron appeared stronger when we restricted the exposure to the third trimester, when the serum boron concentrations were the highest (0.73-447µg/L). An increase in serum boron of 100µg/L in the third trimester corresponded to 0.9cm shorter and 120g lighter newborns (p=0.001 and 0.021, respectively). CONCLUSIONS: Considering that elevated boron concentrations in drinking water are common in many areas of the world, although more screening is warranted, our novel findings warrant additional research on early-life exposure in other populations.

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 25 µg/L (0.0036 mmol/L); range 1.9-145 µg/L (0.000027-0.021 mmol/L)] correlated significantly with those in urine and drinking water (rs = 0.84, p < 0.001, and rs = 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 = 0.20 mIU/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 111 µg/L, range 2.5-711 µg/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.

Environmental exposure to lithium during pregnancy and fetal size: a longitudinal study in the Argentinean Andes.

BACKGROUND: Lithium, used for treating bipolar disease, crosses freely the placenta and is classified as teratogenic. It is unclear to what extent environmental lithium exposure may affect fetal growth and development. OBJECTIVES: To elucidate potential effects of lithium exposure through drinking water during pregnancy on fetal size. METHODS: We developed a prospective population-based mother-child cohort (N=194) in an area with highly varying drinking water lithium concentrations (5-1600 µg/L) in northern Argentinean Andes. Blood and urinary lithium concentrations (sampled repeatedly during pregnancy) were measured using inductively coupled plasma mass spectrometry. We measured fetal size by ultrasound in second and third trimesters, and weight, length and head circumference at birth. Multivariable models were used to examine associations between lithium exposure (continuous and in tertiles) and fetal size measures. RESULTS: Lithium in maternal blood (median 25; range 1.9-145 µg/L) and urine (1645; 105-4600 µg/L) was inversely associated (apparently linearly) with all fetal measures (body, head and femur) in the second trimester, and with birth length (ß -0.53 cm per 25 µg/L increase in blood lithium, 95%CI -1.0; -0.052). An increase of 100 µg/L in blood was associated with 2 cm shorter newborns (about one standard deviation). CONCLUSIONS: Lithium exposure through drinking water was associated with impaired fetal size and this seemed to be initiated in early gestation. Further studies are warranted to confirm causality and to understand the mechanisms. If confirmed, these findings have public health relevance and emphasize the need for more data on lithium concentrations in drinking water, including bottled water.