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.

Alkali dilution of blood samples for high throughput ICP-MS analysis-comparison with acid digestion.

OBJECTIVES: The direct dilution of blood with alkali has been introduced as an alternative to acid digestion for improvement of the analytical productivity when measuring trace elements using inductively coupled plasma mass spectrometry (ICP-MS). This study compared these two sample preparation methods for the ICP-MS determination of multiple elements in human blood and serum. METHODS: Aliquots (0.2 or 0.5 mL) of human whole blood and serum samples, including reference samples (whole blood and serum), were subjected to alkali dilution (ammonia solution) or acid digestion (nitric acid). The samples were then analysed for their concentrations of Li, B, Mg, P, S, K, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Mo, Cd, Sb, Cs, Ba, Pb and U with a quadrupole ICP-MS instrument equipped with a collision/reaction cell. RESULTS: Analysis of the reference materials showed that the alkali dilution and acid digestion methods provided equally good agreement with the reference values for Mg, Mn, Co, Ni, Cu, Zn, As, Se, Rb, Mo, Cd, Sb and Pb. The alkali dilution method generally gave better agreement with the reference values for Li, B, P, S, K, Cr and U, whereas acid digestion gave better agreement for Ca, Fe, Sr and Cs. Strong associations (R(2)>0.90) between the two methods were obtained for the concentrations of Li, B, Mn, Co, Cu, As, Se, Rb, Sr, Mo, Cd, Cs and Pb in the collected human whole blood and for Li, B, Mg, P, S, K, Fe, Co, Cu, Zn, As, Se, Rb, Sr, Sb and Cs in the collected serum. CONCLUSIONS: The results suggest that the alkali dilution method is suitable for the determination of Li, B, Mn, Co, Cu, Zn, As, Se, Rb and Sr in whole blood and serum; Mo, Cd and Pb in whole blood; and Sb in serum by ICP-MS. Acid digestion is preferred for Fe and for low concentrations of Cs.