Elsa Cernichiari

Prenatal methylmercury exposure from ocean fish consumption in the Seychelles child development study

INTRODUCTION Exposure to methylmercury (MeHg) before birth can adversely affect childrens neurodevelopment. The most common form of prenatal exposure is maternal fish consumption, but whether such exposure harms the fetus is unknown. We aimed to identify adverse neurodevelopmental effects in a fish-consuming population. METHODS We investigated 779 mother-infant pairs residing in the Republic of Seychelles. Mothers reported consuming fish on average 12 meals per week. Fish in Seychelles contain much the same concentrations of MeHg as commercial ocean fish elsewhere. Prenatal MeHg exposure was determined from maternal hair growing during pregnancy. We assessed neurocognitive, language, memory, motor, perceptual-motor, and behavioural functions in children at age 9 years. The association between prenatal MeHg exposure and the primary endpoints was investigated with multiple linear regression with adjustment for covariates that affect child development. FINDINGS Mean prenatal MeHg exposure was 6.9 parts per million (SD 4.5 ppm). Only two endpoints were associated with prenatal MeHg exposure. Increased exposure was associated with decreased performance in the grooved pegboard using the non-dominant hand in males and improved scores in the hyperactivity index of the Conners teacher rating scale. Covariates affecting child development were appropriately associated with endpoints. INTERPRETATION These data do not support the hypothesis that there is a neurodevelopmental risk from prenatal MeHg exposure resulting solely from ocean fish consumption.

Impact of Maternal Seafood Diet on Fetal Exposure to Mercury, Selenium, and Lead

Umbilical cord blood from 1,023 consecutive births in the Faroe Islands showed a median blood-mercury concentration of 121 nmol/l (24.2 micrograms/l); 250 of those samples (25.1%) had blood-mercury concentrations that exceeded 200 nmol/l (40 micrograms/l). Maternal hair mercury concentrations showed a median of 22.5 nmol/g (4.5 micrograms/g), and 130 samples (12.7%) contained concentrations that exceeded 50 nmol/g (10 micrograms/g). Frequent ingestion of whale meat dinners during pregnancy and, to a much lesser degree, frequent consumption of fish, and increased parity or age were associated with high mercury concentrations in cord blood and hair. Blood-mercury levels were slightly lower if the mother had occasionally ingested alcoholic beverages. Mercury in blood correlated moderately with blood selenium (median, 1.40 mumol/l). Increased selenium concentrations were associated with intake of whale meat, alcohol abstention, delivery after term, and high parity. Lead in cord blood was low (median, 82 nmol/l), particularly if the mothers had frequently had fish for dinner and had abstained from smoking.

Comparison of Blood and Brain Mercury Levels in Infant Monkeys Exposed to Methylmercury or Vaccines Containing Thimerosal

Thimerosal is a preservative that has been used in manufacturing vaccines since the 1930s. Reports have indicated that infants can receive ethylmercury (in the form of thimerosal) at or above the U.S. Environmental Protection Agency guidelines for methylmercury exposure, depending on the exact vaccinations, schedule, and size of the infant. In this study we compared the systemic disposition and brain distribution of total and inorganic mercury in infant monkeys after thimerosal exposure with those exposed to MeHg. Monkeys were exposed to MeHg (via oral gavage) or vaccines containing thimerosal (via intramuscular injection) at birth and 1, 2, and 3 weeks of age. Total blood Hg levels were determined 2, 4, and 7 days after each exposure. Total and inorganic brain Hg levels were assessed 2, 4, 7, or 28 days after the last exposure. The initial and terminal half-life of Hg in blood after thimerosal exposure was 2.1 and 8.6 days, respectively, which are significantly shorter than the elimination half-life of Hg after MeHg exposure at 21.5 days. Brain concentrations of total Hg were significantly lower by approximately 3-fold for the thimerosal-exposed monkeys when compared with the MeHg infants, whereas the average brain-to-blood concentration ratio was slightly higher for the thimerosal-exposed monkeys (3.5 ± 0.5 vs. 2.5 ± 0.3). A higher percentage of the total Hg in the brain was in the form of inorganic Hg for the thimerosal-exposed monkeys (34% vs. 7%). The results indicate that MeHg is not a suitable reference for risk assessment from exposure to thimerosal-derived Hg. Knowledge of the toxicokinetics and developmental toxicity of thimerosal is needed to afford a meaningful assessment of the developmental effects of thimerosal-containing vaccines.

Simple solvent extraction technique for elimination of matrix interferences in the determination of methylmercury in environmental and biological samples by ethylation-gas chromatography-cold vapor atomic fluorescence spectrometry

A solvent extraction technique involving no critical clean-up steps was developed for the determination of methylmercury (MeHg) in environmental and biological samples by aqueous phase ethylation, room temperature precollection, gas chromatographic separation and cold vapor atomic fluorescence spectrometric detection. Samples were first digested with KOH-methanol. then acidified prior to extraction with methylene chloride. MeHg was back-extracted from the solvent phase into water prior to aqueous phase ethylation. Recoveries close to 100% were obtained with RSDs less than 5% for all samples analyzed, making direct standardization possible. The detection limits were about 0.08 ng g(-1) when analyzing 0.1 g of dry sea plant homogenate and 0.02 ng g when analyzing 0.5 g of wet sediment samples. Various certified reference materials and intercomparison samples, including sediments, sea plants and tissues, were analyzed, and the results were in good agreement with the certified values. The technique was applied to the determination of MeHg in both sea plants from the Atlantic and the red blood protein of dolphins from the Mediteranean Sea. in sediments from the Mediterranean Sea and Minnesota rivers and in soils from different origins. Concentrations of MeHg in dolphin red blood protein samples were as high as 300 ng g(-1).

Associations of maternal long-chain polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child Development Nutrition Study.

Fish consumption during gestation can provide the fetus with long-chain polyunsaturated fatty acids (LCPUFA) and other nutrients essential for growth and development of the brain. However, fish consumption also exposes the fetus to the neurotoxicant, methyl mercury (MeHg). We studied the association between these fetal exposures and early child development in the Seychelles Child Development Nutrition Study (SCDNS). Specifically, we examined a priori models of Omega-3 and Omega-6 LCPUFA measures in maternal serum to test the hypothesis that these LCPUFA families before or after adjusting for prenatal MeHg exposure would reveal associations with child development assessed by the BSID-II at ages 9 and 30 months. There were 229 children with complete outcome and covariate data available for analysis. At 9 months, the PDI was positively associated with total Omega-3 LCPUFA and negatively associated with the ratio of Omega-6/Omega-3 LCPUFA. These associations were stronger in models adjusted for prenatal MeHg exposure. Secondary models suggested that the MeHg effect at 9 months varied by the ratio of Omega-6/Omega-3 LCPUFA. There were no significant associations between LCPUFA measures and the PDI at 30 months. There were significant adverse associations, however, between prenatal MeHg and the 30-month PDI when the LCPUFA measures were included in the regression analysis. The BSID-II mental developmental index (MDI) was not associated with any exposure variable. These data support the potential importance to child development of prenatal availability of Omega-3 LCPUFA present in fish and of LCPUFA in the overall diet. Furthermore, they indicate that the beneficial effects of LCPUFA can obscure the determination of adverse effects of prenatal MeHg exposure in longitudinal observational studies.

Neurodevelopmental Effects of Maternal Nutritional Status and Exposure to Methylmercury from Eating Fish during Pregnancy

Fish contain nutrients that promote optimal brain growth and development but also contain methylmercury (MeHg) that can have toxic effects. The present study tested the hypothesis that the intake of selected nutrients in fish or measures of maternal nutritional status may represent important confounders when estimating the effects of prenatal methylmercury exposure on child development. The study took place in the Republic of Seychelles, an Indian Ocean archipelago where fish consumption is high. A longitudinal cohort study design was used. A total of 300 mothers were enrolled early in pregnancy. Nutrients considered to be important for brain development were measured during pregnancy along with prenatal MeHg exposure. The children were evaluated periodically to age 30 months. There were 229 children with complete outcome and covariate data for analysis. The primary endpoint was the Bayley Scales of Infant Development-II (BSID-II), administered at 9 and 30 months of age. Combinations of four secondary measures of infant cognition and memory were also given at 5, 9 and 25 months. Cohort mothers consumed an average of 537 g of fish (nine meals containing fish) per week. The average prenatal MeHg exposure was 5.9 ppm in maternal hair. The primary analysis examined the associations between MeHg, maternal nutritional measures and childrens scores on the BSID-II and showed an adverse association between MeHg and the mean Psychomotor Developmental Index (PDI) score at 30 months. Secondary analyses of the association between the PDI and only MeHg alone or nutritional factors alone showed only a borderline significant association between MeHg and the PDI at 30 months and no associations with nutritional factors. One experimental measure at 5 months of age was positively associated with iodine status, but not prenatal MeHg exposure. These findings suggest a possible confounding role of maternal nutrition in studies examining associations between prenatal MeHg exposures and developmental outcomes in children.

Mercury levels in newborns and infants after receipt of thimerosal-containing vaccines.

OBJECTIVES. Thimerosal is a mercurial preservative that was widely used in multidose vaccine vials in the United States and Europe until 2001 and continues to be used in many countries throughout the world. We conducted a pharmacokinetic study to assess blood levels and elimination of ethyl mercury after vaccination of infants with thimerosal-containing vaccines. METHODS. Blood, stool, and urine samples were obtained before vaccination and 12 hours to 30 days after vaccination from 216 healthy children: 72 newborns (group 1), 72 infants aged 2 months (group 2), and 72 infants aged 6 months (group 3). Total mercury levels were measured by atomic absorption. Blood mercury pharmacokinetics were calculated by pooling the data on the group and were based on a 1-compartment first-order pharmacokinetics model. RESULTS. For groups 1, 2, and 3, respectively, (1) mean ± SD weights were 3.4 ± 0.4, 5.1 ± 0.6, and 7.7 ± 1.1 kg; (2) maximal mean ± SD blood mercury levels were 5.0 ± 1.3, 3.6 ± 1.5, and 2.8 ± 0.9 ng/mL occurring at 0.5 to 1 day after vaccination; (3) maximal mean ± SD stool mercury levels were 19.1 ± 11.8, 37.0 ± 27.4, and 44.3 ± 23.9 ng/g occurring on day 5 after vaccination for all groups; and (4) urine mercury levels were mostly nondetectable. The blood mercury half-life was calculated to be 3.7 days and returned to prevaccination levels by day 30. CONCLUSIONS. The blood half-life of intramuscular ethyl mercury from thimerosal in vaccines in infants is substantially shorter than that of oral methyl mercury in adults. Increased mercury levels were detected in stools after vaccination, suggesting that the gastrointestinal tract is involved in ethyl mercury elimination. Because of the differing pharmacokinetics of ethyl and methyl mercury, exposure guidelines based on oral methyl mercury in adults may not be accurate for risk assessments in children who receive thimerosal-containing vaccines.

Postnatal Exposure to Methyl Mercury from Fish Consumption: a Review and New Data from the Seychelles Child Development Study

BACKGROUND Fish is an important source of nutrition worldwide. Fish contain both the neurotoxin methyl mercury (MeHg) and nutrients important for brain development. The developing brain appears to be most sensitive to MeHg toxicity and mothers who consume fish during pregnancy expose their fetus prenatally. Although brain development is most dramatic during fetal life, it continues for years postnatally and additional exposure can occur when a mother breast feeds or the child consumes fish. This raises the possibility that MeHg might influence brain development after birth and thus adversely affect childrens developmental outcomes. We reviewed postnatal MeHg exposure and the associations that have been published to determine the issues associated with it and then carried out a series of analyses involving alternative metrics of postnatal MeHg exposure in the Seychelles Child Development Study (SCDS) Main Cohort. METHODS The SCDS is a prospective longitudinal evaluation of prenatal MeHg exposure from fish consumption. The Main Cohort includes 779 subjects on whom recent postnatal exposure data were collected at the 6-, 19-, 29-, 66-, and 107-month evaluations. We examined the association of recent postnatal MeHg exposure with multiple 66- and 107-month outcomes and then used three types of alternative postnatal exposure metrics to examine their association with the childrens intelligence quotient (IQ) at 107 months of age. RESULTS Recent postnatal exposure at 107 months of age was adversely associated with four endpoints, three in females only. One alternative postnatal metric was beneficially associated with 9-year IQ in males only. CONCLUSIONS We found several associations between postnatal MeHg biomarkers and childrens developmental endpoints. However, as has been the case with prenatal MeHg exposure in the SCDS Main Cohort study, no consistent pattern of associations emerged to support a causal relationship.

Methylmercury contamination of laboratory animal diets

In the midst of research focusing on the neurodevelopmental effects of mercury vapor in rats, we detected significant levels of mercury (30–60 ng/g) in the blood of nonexposed control subjects. We determined that the dominant form of the mercury was organic and that the standard laboratory chow we used in our vivarium was the source of the contamination. The dietary levels were deemed of potential biologic significance, even though they might have fallen below the limits of measurement specified by the supplier. All investigators employing animals in research must assess such potential contamination because dietary agents may alter a) conclusions based on intentionally administered doses, b) outcomes by interacting with other agents that are the primary focus of the research, and c) outcomes of research unrelated to the toxic effects of experimentally administered agents.

Segmental hair mercury evaluation of a single family along the Upper Madeira Basin, Brazilian Amazon

Mercury pollution (MeHg) up the aquatic food chains in the Amazonian ecosystems has been a major concern in environmental health. Riverside people (ribeirinhos) along the Upper Madeira river are heavy fish eaters. Hair is the best biomarker for MeHg exposure. By assuming a constant hair growth rate, it is possible to evaluate a temporal profile of Hg exposure over the recent defined past. In this paper we present the segmental total hair Hg concentrations from a single family from which some of the 10 persons investigated had high hair Hg concentrations (peak of 339 ppm). We also presented the hair MeHg content from 4 out of the 10 family members investigated. There was a wide variation in total hair Hg concentrations (8 to 339 ppm) among these individuals, who were mostly sharing their meals; there was also a wide variation in total Hg concentrations in the same individual over time (136 to 274 ppm). Hg speciation showed a mean and standard deviation in the MeHg content of 62% and 6%, respectively. The wide variation in total hair Hg concentration strongly indicated that it is possible to mitigate critical Hg exposure levels by conducting a fish advisory.