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

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.

To elucidate potential effects of lithium exposure through drinking water during pregnancy on fetal size.

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.

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 (β -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).

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.