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Abstract

The present work deals with Hg exposure and evaluates its association with
neurodevelopment of children exposed prenatally. The work combines the outcomes of
human biomonitoring (HBM) and complementary epidemiological studies carried out as
national or international research projects. The framework for assessment arose from the
methodological part of the thesis, which defined the analytical quality requirements for
HBM and the national reference population to derive background levels of internal exposure
to Hg and other potentially toxic (Pb, Cd, As) and essential (Se, Cu, Zn, Mn) elements.
The latter was selected from men and women of childbearing age, living in 12
geographically distinct areas, divided into rural, urban and potentially contaminated
(n=1084). This is the first reference population established in Slovenia. Analytical
performance of the methods to determine elemental concentrations in most commonly used
biological matrix, venous blood, was evaluated using measurement uncertainty, interlaboratory
variability and their contribution to the required sample size as compared to
the variability within a given population.
The second part of the thesis evaluated an association between low-level Hg exposure
in the most vulnerable period for developmental toxicity, the prenatal period, and
neurodevelopment of children in a birth cohort study from the western Mediterranean area
(n=1282). Neuropsychological development was monitored at 18 months of age using
Bayley Scales of Infant and Toddler Development (Bayley III). The association assessment
took into account non-genetic (demographic, socio-economic, dietary factors, and coexposure
to Pb and status of beneficial micronutrient Se), and in a subset of the study
population, the Slovenian and Croatian population groups, also genetic (apolipoprotein E
– APOE – polymorphism) factors (n=361). Prenatal Hg exposure in the overall population
was predominated by fish consumption and showed no negative associations with cognitive
and language development, with the majority of children being within the normal scales of
development. However, stratification by the APOE genotype revealed negative association
with cognitive score in children carrying ɛ4 allele. A weak but significant inverse relation
between total Hg levels and developmental motor scores at 18 months was observed, which
was independent of the genotype. The study groups residing in the former Hg mine area
(pregnant women and school-age children) had higher internal exposure than the residents
of the rural control areas, particularly to inorganic or elemental Hg, but most of them did
not exceed the values that could be associated with biological and/or potential adverse
health effects, and pregnant women showed normal oxidative response.
The overall work demonstrates the efficiency of HBM as a tool to monitor low-level
internal exposure, its use in classical epidemiological and exposome-based studies and the
key role of strict quality control. It further indicates an importance of accounting for
simultaneous exposure to different neurotoxic chemicals, non-genetic (e.g. diet) and genetic
factors that could influence exposure and/or health outcomes, particularly at low-levels of
chronic exposures. Complementary to the standardized neuropsychiatric assessments, ongoing
and future research are designed to use non-targeted approach to reveal also early
alterations in biological pathways that could lead to clinical manifestations later in life.