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Eur J Epidemiol. 2016 Nov;31(11):1123-1134. doi: 10.1007/s10654-016-0151-9. Epub 2016 May 4.

Impact of prenatal exposure to cadmium on cognitive development at preschool age and the importance of selenium and iodine.

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Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77, Stockholm, Sweden.
Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77, Stockholm, Sweden.
Department of Social Medicine, Faculty of Medicine, University of Crete, 71003, Heraklion, Crete, Greece.
Centre for Research in Environmental Epidemiology (CREAL), 08003, Barcelona, Spain.
Municipal Institute of Medical Research (IMIM-Hospital del Mar), 08003, Barcelona, Spain.
National School of Public Health, 11521, Athens, Greece.
Department of Genetics and Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Universiteitssingel 40, PO Box 616, 6229 ER, Maastricht, The Netherlands.


The evidence regarding a potential link of low-to-moderate iodine deficiency, selenium status, and cadmium exposure during pregnancy with neurodevelopment is either contradicting or limited. We aimed to assess the prenatal impact of cadmium, selenium, and iodine on children's neurodevelopment at 4 years of age. The study included 575 mother-child pairs from the prospective "Rhea" cohort on Crete, Greece. Exposure to cadmium, selenium and iodine was assessed by concentrations in the mother's urine during pregnancy (median 13 weeks), measured by ICPMS. The McCarthy Scales of Children's Abilities was used to assess children's general cognitive score and seven different sub-scales. In multivariable-adjusted regression analysis, elevated urinary cadmium concentrations (≥0.8 µg/L) were inversely associated with children's general cognitive score [mean change: -6.1 points (95 % CI -12; -0.33) per doubling of urinary cadmium; corresponding to ~0.4 SD]. Stratifying by smoking status (p for interaction 0.014), the association was restricted to smokers. Urinary selenium was positively associated with children's general cognitive score [mean change: 2.2 points (95 % CI -0.38; 4.8) per doubling of urinary selenium; ~0.1 SD], although the association was not statistically significant. Urinary iodine (median 172 µg/L) was not associated with children's general cognitive score. In conclusion, elevated cadmium exposure in pregnancy of smoking women was inversely associated with the children's cognitive function at pre-school age. The results indicate that cadmium may adversely affect neurodevelopment at doses commonly found in smokers, or that there is an interaction with other toxicants in tobacco smoke. Additionally, possible residual confounding cannot be ruled out.


Cadmium; Cognitive development; Iodine; Prenatal exposure; Selenium; Urine

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Conflict of interest statement

The authors declare that they have no conflict of interest. Ethical approval In the present study all procedures involving human participants were in accordance with the ethical standards of the institutional and/or national research committee’s and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the present study.

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