title: Environmental exposure to lithium during pregnancy and fetal size: a longitudinal study in the Argentinean Andes.
abstract: 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.
  
  
  OBJECTIVE
  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 (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).
  
  
  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.
authors: Unit of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden.
authors: Florencia
authors: F
authors: Harari
authors: Unit of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden.
authors: Margareta
authors: M
authors: Langeén
authors: Supervisor Intermedio de Atención Primaria de la Salud, Área Operativa XXIX, Hospital Dr. Nicolás Cayetano Pagano, San Antonio de los Cobres, 4411 Salta, Argentina.
authors: Esperanza
authors: E
authors: Casimiro
authors: Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden.
authors: Matteo
authors: M
authors: Bottai
authors: Unit of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden.
authors: Brita
authors: B
authors: Palm
authors: Unit of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden.
authors: Helena
authors: H
authors: Nordqvist
authors: Unit of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden. Electronic address: Marie.Vahter@ki.se.
authors: Marie
authors: M
authors: Vahter
mesh_terms: D000293:Adolescent; D000328:Adult; D001118:Argentina; D001827:Body Height / Q000187:drug effects; D060766:Drinking Water / Q000737:chemistry*; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D006801:Humans; D007231:Infant, Newborn; D008094:Lithium / Q000097:blood / Q000633:toxicity* / Q000652:urine; D008297:Male; D015999:Multivariate Analysis; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D060766:Drinking Water; D008094:Lithium
keywords: Birth weight; Early-life exposure; Fetal size; Lithium; Water pollutants