Marika Mariuz

Mercury, arsenic and selenium exposure levels in relation to fish consumption in the Mediterranean area

In order to assess mercury (Hg), selenium (Se) and arsenic (As) exposure in the Mediterranean area, total mercury (THg), monomethylmercury (MeHg), Se and As levels were measured in umbilical cord blood and breast milk from Italian (n=900), Slovenian (n=584), Croatian (n=234) and Greek (n=484) women. THg, MeHg, As, and Se levels were also determined in blood samples of the same mothers from Italy and Croatia. In addition, THg and MeHg were determined in the same womens hair from all the countries involved in this study and As and Se levels were determined in the mothers urine samples from Italy, Croatia and Greece. Besides recording the consumption of other food items, the frequencies of fish consumption were assessed by detailed food frequency questionnaires, since fish represents an important source of Hg, Se and As in humans. The highest levels of THg and As were found in cord blood (Med((THg))=5.8 ng/g; Med((As))=3.3 ng/g) and breast milk (Med((THg))=0.6 ng/g; Med((As))=0.8 ng/g) from Greek women, while the highest Se levels were found in cord blood (Med=113 ng/g) from Italy. Significant linear correlations were found between Hg, Se and As in blood, cord blood and breast milk. In addition, significant relations were found between the frequencies of total fish consumption and biomarkers of As, MeHg and Se exposure, with the strongest Spearman rank coefficients between frequencies of total fish consumption and THg levels in cord blood (r(s)=0.442, p<0.001) or THg levels in hair (r(s)=0.421, p<0.001), and between frequencies of total fish consumption and As levels in cord blood (r(s)=0.350, p<0.001). The differences in Hg and As exposure between countries were probably due to different amounts of fish consumption and the consumption of different species of fish of different origin, while the highest Se levels in women from Italy were probably the consequence of the more frequent consumption of different non specific food items. Moreover, fish consumption, the possible common source of As, Hg and Se intake, could explain the correlations between the elements determined in cord blood, mothers blood or breast milk.

Associations of Prenatal Mercury Exposure From Maternal Fish Consumption and Polyunsaturated Fatty Acids With Child Neurodevelopment: A Prospective Cohort Study in Italy

Background Mercury is a neurotoxin, and limited prenatal exposure to it can affect long-term child neurodevelopment. However, results of epidemiologic studies of such exposure have been inconsistent. We examined the association of prenatal mercury exposure from maternal fish consumption with child neurodevelopment in northern Italy. Methods A population-based cohort of 606 children and their mothers was studied from pregnancy to age 18 months. Mercury levels were measured in maternal hair and blood during pregnancy and in umbilical cord blood and breast milk. Levels of polyunsaturated fatty acids (PUFAs) were measured in maternal serum. Maternal and child intakes of fish were assessed by using a food frequency questionnaire. The Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) was used to evaluate child neurodevelopment. Multivariate linear regression was used to examine the association of mercury exposure with BSID-III scores, after controlling for maternal fish intake, PUFAs during pregnancy, and several other confounders. Results Mean weekly fish intake during pregnancy was less than 2 servings. Mercury concentrations in biological samples were low (mean, 1061 ng/g in hair) and moderately correlated with fish intake, particularly of carnivorous species. Maternal ω-3 PUFA concentrations were poorly correlated with fish intake. Maternal intelligence quotient (IQ) and child intake of fish were significantly associated with neurodevelopment scores. In multivariate models, the level of Hg exposure was not associated with neurodevelopmental performance at 18 months. Conclusions In this Italian population, neurodevelopment at 18 months was associated with child intake of fresh fish and maternal IQ rather than with mercury exposure. The expected beneficial effect of maternal fish intake (from maternal ω-3 PUFAs) was not found.

The complex interaction between home environment, socioeconomic status, maternal IQ and early child neurocognitive development: a multivariate analysis of data collected in a newborn cohort study

Background The relative role of socioeconomic status (SES), home environment and maternal intelligence, as factors affecting child cognitive development in early childhood is still unclear. The aim of this study is to analyze the association of SES, home environment and maternal IQ with child neurodevelopment at 18 months. Methods The data were collected prospectively in the PHIME study, a newborn cohort study carried out in Italy between 2007 and 2010. Maternal nonverbal abilities (IQ) were evaluated using the Standard Progressive Matrices, a version of the Raven’s Progressive Matrices; a direct evaluation of the home environment was carried out with the AIRE instrument, designed using the HOME (Home Observation for Measurement of the Environment) model; the socioeconomic characteristics were evaluated using the SES index which takes into account parents occupation, type of employment, educational level, homeownership. The study outcome was child neurodevelopment evaluated at 18 months, with the Bayley Scales of Infant and Toddler Development Third Edition (BSID III). Linear regression analyses and mediation analyses were carried out to evaluate the association between the three exposures, and the scaled scores of the three main scales of BSID III (cognitive, language and motor scale), with adjustment for a wide range of potential explanatory variables. Results Data from 502 mother-child pairs were analyzed. Mediation analysis showed a relationship between SES and maternal IQ, with a complete mediation effect of home environment in affecting cognitive and language domains. A direct significant effect of maternal IQ on the BSID III motor development scale and the mediation effect of home environment were found. Conclusions Our results show that home environment was the variable with greater influence on neurodevelopment at 18 months. The observation of how parents and children interact in the home context is crucial to adequately evaluate early child development.

Neurodevelopmental effects of low-level prenatal mercury exposure from maternal fish consumption in a Mediterranean cohort: study rationale and design.

Background Mercury is a neurotoxic environmental pollutant. However, the literature on the neurodevelopmental effect of low-level prenatal mercury exposure from maternal fish intake is inconsistent. We assessed the association between prenatal mercury exposure and infant neurodevelopment in coastal areas of 4 Mediterranean countries. Methods This was a prospective cohort study that planned to enroll approximately 1700 mother–infant pairs. Pregnant women and their newborn children were recruited in selected hospitals of the study areas. Biological samples, including maternal hair and cord blood, were collected from mothers and children, and the concentrations of mercury and other elements were measured. Exposures to lifestyle, environmental, and social factors were assessed through questionnaires. The main outcome was child neurodevelopment at 18 months, as measured by the Bayley Scales of Infant and Toddler Development, Third Edition. Conclusions This cohort has a number of strengths. First, mercury concentration was measured in several biological samples, which allows for a better understanding of mercury kinetics and is useful for sensitivity analyses. Therefore, we expect to be able to adjust for the potential confounding effects of lifestyle and social factors and for the effects of other elements that were measured in the biological samples. Finally, this is a multinational study and thus permits assessment of the relation between mercury and child neurodevelopment in different populations.

CYP3A genes and the association between prenatal methylmercury exposure and neurodevelopment

BACKGROUND Results on the association between prenatal exposure to methylmercury (MeHg) and child neuropsychological development are heterogeneous. Underlying genetic differences across study populations could contribute to this varied response to MeHg. Studies in Drosophila have identified the cytochrome p450 3A (CYP3A) family as candidate MeHg susceptibility genes. OBJECTIVES We evaluated whether genetic variation in CYP3A genes influences the association between prenatal exposure to MeHg and child neuropsychological development. METHODS The study population included 2639 children from three birth cohort studies: two subcohorts in Seychelles (SCDS) (n=1160, 20 and 30months of age, studied during the years 2001-2012), two subcohorts from Spain (INMA) (n=625, 14months of age, 2003-2009), and two subcohorts from Italy and Greece (PHIME) (n=854, 18months of age, 2006-2011). Total mercury, as a surrogate of MeHg, was analyzed in maternal hair and/or cord blood samples. Neuropsychological development was evaluated using Bayley Scales of Infant Development (BSID). Three functional polymorphisms in the CYP3A family were analyzed: rs2257401 (CYP3A7), rs776746 (CYP3A5), and rs2740574 (CYP3A4). RESULTS There was no association between CYP3A polymorphisms and cord mercury concentrations. The scores for the BSID mental scale improved with increasing cord blood mercury concentrations for carriers of the most active alleles (β[95% CI]:=2.9[1.53,4.27] for CYP3A7 rs2257401 GG+GC, 2.51[1.04,3.98] for CYP3A5 rs776746 AA+AG and 2.31[0.12,4.50] for CYP3A4 rs2740574 GG+AG). This association was near the null for CYP3A7 CC, CYP3A5 GG and CYP3A4 AA genotypes. The interaction between the CYP3A genes and total mercury was significant (p<0.05) in European cohorts only. CONCLUSIONS Our results suggest that the polymorphisms in CYP3A genes may modify the response to dietary MeHg exposure during early life development.

A case-control study of sleep-related factors and occupational injuries at an Italian teaching hospital

Background: Sleep disorders have been associated with increased risk of occupational injuries in various settings. Purpose: We investigated the associations between sleep, daytime sleepiness, and chronotype (preference for morning or evening activities) and the risk of occupational injuries in an Italian teaching hospital. Methods: A case-control study of employees of the University Hospital of Udine, Italy, was conducted on 200 employees reporting occupational injuries and 183 controls. Information was collected on usual sleep quantity and quality. Sleepiness was assessed with the Epworth Sleepiness Scale. Chronotype was assessed with the Horne–Ostberg morningness–eveningness questionnaire. The association of sleep-related exposures with the risk of injury was assessed with multivariate unconditional logistic regression, adjusting for potentially confounding individual characteristics. Results: Among sleep-related variables, the number of reported sleep disturbances was positively related with occupational injuries, whereas daytime sleepiness was inversely associated with injuries. Cases had shorter usual sleep hours than controls, although the difference was not statistically significant. No association was found between usual sleep hours and injuries. Chronotype was not significantly associated with injury, although we observed a decreasing trend in risk of injury from morning to evening chronotypes. Conclusions: Self-reported sleep disturbance was positively associated with increased risk of occupational injury in an Italian hospital. However, contrary to expectation, daytime sleepiness was inversely related to injuries.

Relation of Fish Consumption to Biomarkers of Mercury, Selenium and Arsenic Exposure from Mediterranean Women

In order to assess mercury (Hg), selenium (Se) and arsenic (As) exposure in the Mediterranean area, total mercury (THg), monomethylmercury (MeHg), Se and As levels were measured in umbilical cord blood and breast milk from Italian (n=900), Slovenian (n=584), Croatian (n=234) and Greek (n=484) women. THg, MeHg, As, and Se levels were also determined in blood samples of the same mothers from Italy and Croatia. In addition, THg and MeHg were determined in the same womens hair from all the countries and As levels were determined in the mothers urine samples from Italy, Croatia and Greece. In addition to recording the consumption of other food items, the frequencies of fish consumption were assessed by detailed food frequency questionnaires, since fish can represents an important source of mercury, selenium and arsenic in humans. The highest levels of THg and As were found in cord blood (Med(THg) =5.8 ng/g ; Med(As) =3.3 ng/g) and breast milk (Med(THg) =0.6 ng/g ; Med(As) =0.8 ng/g) from Greek women, while the highest Se levels were found in cord blood (Med=113 ng/g) and mother’s blood (Med=117 ng/g) from Italy. Significant linear correlations were found between different biomarkers of Hg, As and Se exposure. In addition, significant relations were found between the frequencies of total fish consumption and Hg, As and Se biomarkers of exposure, possibly explaining the correlations between the elements determined in cord blood, mothers blood or breast milk. Moreover, the differences in As and Hg exposure between countries were probably due to different amounts of fish consumption and the consumption of different species of fish of different origin.

Longitudinal cohort study of prenatal exposure to mercury in the Mediterranean region

Neurotoxicity from prenatal exposure to mercury has been studied but no firm conclusions have been reached on the dose-response relationship, especially at levels of exposure less than 10_g/g. The ongoing Northern Adriatic and Eastern Aegean cohort studies will assess the impact of mercury exposure through fish consumption during pregnancy on the developing nervous system. This Mediterranean study will enrol a total of 1700 pregnant women and their children in Slovenia, Croatia, Italy and Greece as part of the European Commission funded project on the Public health impact of long-term, low-level mixed element exposure in susceptible population strata (PHIME). The overall purpose of this study is to permit researchers, policy makers and health professionals to orient futuremothers with precise, scientifically based recommendations regarding the implications of dietary intake of fish during pregnancy. Maternal hair, blood, urine and cord blood samples are collected at different times during pregnancy and after delivery. Information on fish consumption patterns is collected through brief and detailed food frequency questionnaires administered during pregnancy and 1– 3 months after delivery, respectively. The study is in progress and current mercury levels in hair are low, but there is a correlation between the consumption of fresh fish and hair total mercury levels. Recruitment for the Mediterranena cohorts will conclude in spring 2009. Testing of neurodevelopmental outcomes in children at 18 months of age started May 2008 and should conclude October 2010.