Early-life selenium status and cognitive development

Selenium is an essential element that is found in food sources such as meat, fish, and cereals. The essentiality of selenium was demonstrated in the 1950s, and the interest in its health effects has been growing ever since. Deficiency is common world-wide, particularly in Europe and south-eastern Asia. It has been estimated that 0.5-1 billion people could be selenium deficient. Previous studies regarding health effects of selenium have focused on the impact of deficiency for the risk of cancer, cardiovascular disease, and decreased fertility and immune function. Lately, the importance for brain function has also become the focus of many studies assessing potential protection against cognitive decline and certain neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease. However, little is known about the importance for early-life development. In particular, the role of selenium in cognitive development has not been studied, even though the brain is one of the organs with highest selenium priority at deficient intake levels. Therefore, the overall aim of this thesis was to assess whether selenium status in early life is important for cognitive development.

The studies included in this thesis were based on data from a large mother-child cohort in rural Bangladesh. The cohort was nested in a randomized food and micronutrient supplementation trial that was established in 2001-2003, called the Maternal and Infant Nutrition Intervention, Matlab (MINIMat). Women were recruited to this nested cohort early in pregnancy (at pregnancy testing), and donated urine and blood samples continuously throughout pregnancy. The subsequently born children were divided into two groups for different outcome assessments. For cognitive assessment, children were followed-up at 1.5, 5, and 10 years, while assessment of immune function and various effect biomarkers was performed in the other group of children at 4.5 and 9 years of age. To evaluate the role of selenium in cognitive development, concentrations of the element were measured in urine and blood from the pregnant women, and also in blood, urine, and hair from the Bangladeshi children at different ages (n=223-1408). Results from the group of children who donated blood, urine, and hair, demonstrated that also hair selenium could be used for assessment of selenium status in the present population. Using multivariable-adjusted regression analyses, we found that adequate selenium status during pregnancy seemed important for the children’s cognitive development. Children born to mothers with higher selenium status performed better on the cognitive tests at 1.5, 5 and 10 years of age. Also the selenium status during early childhood seemed to be important for the cognitive abilities at the 5- and 10-year follow-ups. There was an indication of an upper limit for the positive association, in line with the narrow therapeutic interval for selenium. Assessment of influential factors for the selenium biomarkers indicated that exposure to arsenic and cadmium (both strong pro-oxidants) changed the distribution of selenium between different biological compartments (or vice versa). Importantly, malnourished children seemed to retain more selenium, supporting that the regulation of selenium occurs through changes in urinary excretion also in children.

To conclude, this research, based on different biomarkers of selenium status and comprehensive testing of cognitive abilities in large samples of children at 1.5 (n=729), 5 (n=1260) and 10 (n=1408) years of age provides substantial, new evidence of the importance of adequate early-life selenium status for brain development. Similar studies in other populations, as well as research on efficient ways to improve inadequate selenium status without risking selenium toxicity, are warranted.

List of scientific papers

I. Skröder H, Hamadani J, Tofail F, Persson LÅ, Vahter M, Kippler M. Selenium status in pregnancy influences children's cognitive function at 1.5 years of age. Clinical Nutrition. 2015 Oct;34(5):923-30.
https://doi.org/10.1016/j.clnu.2014.09.020

II. Skröder H, Kippler M, Nermell B, Tofail F, Levi M, Rahman SM, Raqib R, Vahter M. Major limitations in using element concentrations in hair as biomarkers of exposure to toxic and essential trace elements in children. Environmental Health Perspectives. 2017 Jun;29:125(6):067021.
https://doi.org/10.1289/EHP1239

III. Skröder H, Kippler M, Tofail F, Vahter M. Early-life selenium status and cognitive function in Bangladeshi children. Environmental Health Perspectives. 2017 Nov;125(11):117003.
https://doi.org/10.1289/EHP1691

IV. Skröder H, Kippler M, De Loma J, Raqib R, Vahter M. Predictors of selenium biomarker kinetics in 4-9-year-old Bangladeshi children. Environment International. 2018 Dec:121(1):842-51.
https://doi.org/10.1016/j.envint.2018.10.018