Rejane C. Marques

Neurodevelopment of Amazonian Infants: Antenatal and Postnatal Exposure to Methyl- and Ethylmercury

Neurodevelopment as Gesell development scores (GDSs) in relation to mercury exposure in infants (<6 months of age) of one urban center and two rural villages, respectively, of fisherman and cassiterite miners. Mean total hair-Hg (HHg) concentrations of infants from Itapuã (3.95 ± 1.8 ppm) were statistically (P = 0.0001) different from those of infants from Porto Velho (3.84 ± 5.5 ppm) and Bom Futuro (1.85 ± 0.9 ppm). Differences in vaccine coverage among these populations resulted in significantly higher (P = 0.0001) mean ethylmercury (EtHg) exposure in urban infants (150 μg) than in infants from either village (41.67 μg, Itapuã; 42.39 μg, Bom Futuro). There was an inverse significant (Spearman r = −0.2300; P = 0.0376) correlation between HHg and GDS for infants from Porto Velho, but not for the rural infants from Bom Futuro (Spearman r = 0.1336; P = 0.0862) and Itapuã (Spearman r = 0.1666; P = 0.5182). Logistic regression applied to variables above or below the median GDS showed that EtHg exposure (estimated probability = −0.0157; P = 0.0070) and breastfeeding score (estimated probability = −0.0066; P = 0.0536) score were significantly associated with GDS. Conclusion. In nurslings whose mothers are exposed to different levels of fish-MeHg (HHg), a higher score of neurological development at six months was negatively associated with exposure to additional TCV-EtHg. Results should be interpreted with caution because of unaccounted variables.

Fish Consumption during Pregnancy, Mercury Transfer, and Birth Weight along the Madeira River Basin in Amazonia

Birth weight can be a predictor of maternal health issues related to nutrition and environmental contaminants. Total hair mercury (HHg) concentration was studied as an indicator of both fish consumption and methylmercury exposure in mothers (and newborns) living in selected low income areas of the Madeira River basin, Amazonia, Brazil. This cohort study (n = 1,433) consisted of traditional riverines (n = 396), riverines who had moved to urban (n = 676) and rural (n = 67) settings, and tin miner settlers (n = 294). Median maternal HHg was significantly different (p = 0.00001) between riverine (12.1 µg·g−1), rural (7.82 µg·g−1), urban (5.4 µg·g−1), and tin miner (4.5 µg·g−1) groups studied. The same trend (of medians) was observed for newborns’ HHg which also showed significant differences between riverine (3.0 µg·g−1), rural (2.0 µg·g−1), urban (1.5 µg·g−1), and tin miner (0.8 µg·g−1) groups. The correlation between maternal and newborn HHg was statistically significant in the riverine (r = 0.8952; p = 0.0001), urban (r = 0.6744; p = 0.0001), and rural (r = 0.8416; p = 0.0001) groups but not in the mother-infant pairs in the tin miner group (r = 0.0638; p = 0.2752). Birth weight was significantly different among groups but did not show a pattern consistent with that of fish consumption (and HHg). A multiple regression analysis showed that only family income and gestational age had a significant impact on birth weight. Conclusions: Maternal HHg is an important biomarker of maternal fish consumption and of methylmercury exposure during pregnancy. However, in these Amazonian groups, only maternal education and gestational age seemed to affect birth weight positively.

Infants' exposure to aluminum from vaccines and breast milk during the first 6 months

The success of vaccination programs in reducing and eliminating infectious diseases has contributed to an ever-increasing number of vaccines given at earlier ages (newborns and infants). Exposure to low levels of environmental toxic substances (including metals) at an early age raises plausible concerns over increasingly lower neuro-cognitive rates. Current immunization schedules with vaccines containing aluminum (as adjuvant) are given to infants, but thimerosal (as preservative) is found mostly in vaccines used in non-industrialized countries. Exclusively, breastfed infants (in Brazil) receiving a full recommended schedule of immunizations showed an exceedingly high exposure of Al (225 to 1750 μg per dose) when compared with estimated levels absorbed from breast milk (2.0 μg). This study does not dispute the safety of vaccines but reinforces the need to study long-term effects of early exposure to neuro-toxic substances on the developing brain. Pragmatic vaccine safety needs to embrace conventional toxicology, addressing especial characteristics of unborn fetuses, neonates and infants exposed to low levels of aluminum, and ethylmercury traditionally considered innocuous to the central nervous system.

Neonate exposure to thimerosal mercury from hepatitis B vaccines.

Infant exposure to ethylmercury (EtHg) has not only increased but is starting earlier as a result of the current immunization schedule that uses thimerosal-containing vaccines (TCVs). Although vaccination schedule varies considerably between countries, infants in less-developed countries continue to be exposed to EtHg derived from more affordable TCVs. We studied the exposure of newborns to EtHg from hepatitis B vaccines; hospital records (21,685) were summarized for the years 2001 to 2005 regarding date of birth, vaccination date, and birth weight. Most of the vaccinations occurred in the first 24 hours postdelivery; over the 5 years, there was an increase in vaccinations within hours of birth (same day), from 7.4% (2001) to 87.8% (2005). Nearly 94.6% of infants are now being vaccinated within the first 24 hours. Range of mercury exposure spread from 4.2 to 21.1 microg mercury/kg body weight for those receiving TCVs with the highest thimerosal concentration; these exposure levels are conservative for 2% of children receiving vaccines within 2 to 3 postnatal days, when they are still going through physiological postnatal weight loss. Because of the particular timing (transitioning from in utero to ex utero metabolism) and specific aspects of exposure (i.e., parenteral mode, bypassing gastroenteric barriers) and dose (related to vaccine manufacturer and with variation in birth weight), this study reveals critical issues that can modulate toxicokinetics and toxicodynamics of organomercurials in neonates.

Milestone Achievement and Neurodevelopment of Rural Amazonian Toddlers (12 to 24 Months) with Different Methylmercury and Ethylmercury Exposure

Neurological outcomes (Gesell development schedules [GDS]), age of walking, and age of talking were studied in 299 toddlers (12 to 24 mo) in relation to environmental (fish consumption and tin mining) exposure. Exposure to fish methylmercury (MeHg) consumption and iatrogenic ethylmercury (EtHg) in Thimerosal-containing vaccines (TCV) was quantified in toddlers from two rural villages (n = 91, Itapuã; n = 218, Bom Futuro) respectively populated by fishers and cassiterite miners. Median total hair Hg (HHg) concentrations of infants from Itapuã (3.5 μg/g) were significantly higher than those of infants from Bom Futuro (2.2 μg/g). Median EtHg exposure from TCV was also significantly higher in toddlers from Itapuã (137.5 μg) than in those from Bom Futuro (112.5 μg). There were no significant differences between groups for any of the Gesell schedules; however, there were proportionally more compromised toddlers (GDS < 70) in Itapuã than Bom Futuro. Median age of talking was not statistically different but median age of walking was significantly higher in Bom Futuro. In toddlers from both villages, of fishers and miners, HHg concentrations were significantly correlated with family fish consumption. A logistic regression model was applied to all infants after classification into two groups: above or below the median Gesell schedules. Overall, there was no distinctive pattern of neurodevelopment associated with either HHg or EtHg exposure; however, nutritional status was significantly associated with GDS. In conclusion, milestone achievement was delayed in toddlers from tin-ore mining communities. Despite significantly higher exposure to both forms of organic Hg (MeHg from maternal fish consumption, and EtHg from TCV) in toddlers from the fishing village, significant differences were seen only among the proportions of most severely affected toddlers (GDS < 70).

Poor psychometric scores of children living in isolated riverine and agrarian communities and fish-methylmercury exposure

Because of heavy dependence on fish, Amazonian riparian communities are chronically exposed to high levels of methylmercury (MeHg). We studied fish-MeHg exposure (total hair-Hg, HHg) as a determinant of neurocognitive scores of children living in two geographically distant, culturally distinct and isolated poor communities of non-urban environments: Amazonian riverines (Riparians, n=38) of the Puruzinho Lake community in the Rio Madeira Basin and rural agrarians from Iúna, Espírito Santo (Agrarians, n=32). Nutritional status was estimated by anthropometry (Z-scores) and individual cognitive abilities were assessed by the Wechsler Intelligence Scale for Children-III (WISC-III) and the Human Figure Drawings (HFD), both validated versions for Brazilian children. Anthropometric assessment showed slightly elevated Z-scores for the Agrarian children (not statistically significant) but median HHg concentrations were 14.4 and 0.25microgg(-1) respectively for Riparian and Agrarian children (p=0.000). Despite paradoxical MeHg exposures, both groups showed comparable HFD scores but very poor performance in WISC-III test battery; median of sum of WISC-III subtests scores (SigmaTOT) were 17.9 and 28.6 (p<0.000) for Riparian and Agrarian children, respectively (percentage scale). Spearman correlation between nutritional status (attained growth) and psychometric scores were statistically significant between height-for-age Z-score and Object Assembly subtest (r=0.269; p=0.043), SigmaTOT (r=0.319; p=0.016), Performance-IQ (r=0.311; p=0.019) and Perceptual Organization Index scores (r=0.302; p=0.023). In these isolated communities there are stronger determinants of neurocognitive poor performance than MeHg exposure. Global strategies for reducing human exposure to MeHg by curtailing fish consumption are unrealistic options for riverine subsistence populations and are not justifiable to prevent low cognitive scores.

Time of perinatal immunization, thimerosal exposure and neurodevelopment at 6 months in breastfed infants.

Aim: Brazilian newborns immunized with hepatitis‐B (thimerosal containing vaccine, TCV) receive the first dose within 24 h if delivered in public hospitals, but at a later time if born in private hospitals. We compared neurodevelopment (ND) in infants born in a state hospital (immunized within 24 h) and in privately run hospitals (immunized 2–4 days postnatally).

Neurodevelopment of Amazonian children exposed to ethylmercury (from Thimerosal in vaccines) and methylmercury (from fish)

Few studies have addressed co-occurring methylmercury (MeHg) from maternal origin and ethylmercury (EtHg) from Thimerosal-containing vaccines (TCVs) during infants neurodevelopment. We studied children (n=1139) from the Western Amazon based on combined (low, intermediate, and high) exposure to chronic MeHg from fish consumption and acute TCV- EtHg. Neurodevelopment outcomes were age of walking and age of talking, and the Bayley Scale of Infant Development (BSID). The Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) were measured at six and 24 months of age. Median hair-Hg (HHg) at birth was 6.4µgg(-1) in mothers, and 1.94µgg(-1) in newborns; total (pregnancy and infancy) EtHg exposure ranged from 0 to 187.5µg. The combined (MeHg+EtHg) exposure showed significant differences for MDI but not for PDI; however, there was a significant decrease in both MDI and PDI scores at 24 months. The increase in BSID delays (scores <80) between six and 24 months was not discernible with regards to EtHg or MeHg exposure. We found a statistically significant increase in neurodevelopmental (BSID) delays related to the combined exposure to Hg (MeHg>EtHg). Neurodevelopment delays due to low-doses of organic mercury (albeit undiscernible) are not predictable but can be avoided by choosing low-Hg fish and providing Thimerosal-free vaccines.

Vaccine Adverse Events Reported during the First Ten Years (1998–2008) after Introduction in the State of Rondonia, Brazil

Despite good safety records, vaccines given to young children can cause adverse events. We investigated the reported adverse events following immunization (AEFI) of vaccines given to children of less than seven years of age during the first ten years (1998 to 2008) in the state of Rondonia, Brazil. We worked with the events related to BCG (Bacillus Calmett-Guérin), HB (hepatitis B), DTwP/Hib (diphtheria-tetanus-pertussis+Hemophillus influenza b), DTP (diphtheria-tetanus-pertussis), MMR (mumps, measles, rubella), and YF (yellow fever) vaccines because they were part of the recommended scheme. The number of doses of vaccines given was 3,231,567 with an average of AEFI of 57.2/year during the studied period. DTwP/Hib was responsible for 298 (57.8%), DTP 114 (22.9%), HB 31 (6%), MMR 28 (5.4%), BCG 24 (4.7%), and YF 20 (3.9%) of the reported AEFI. The combination of the AEFI for DTwP/Hib vaccines showed the highest number of systemic (61.4%) and local events (33.8%). Young children (≤1-year old) were more susceptible to AEFI occurring in the 6 hours (54.2%) following vaccine uptake. This study suggests significant differences in reactogenicity of vaccines and that despite limitations of the AEFI Brazilian registry system we cannot ignore underreporting and should use the system to expand our understanding of adverse events and effects.

Mercury levels and human health in the Amazon Basin.

Abstract Context: Environmental mercury in the Amazon mostly originates from geochemical sources with some from artisanal gold mining (AGM). Geochemical-originated methylmercury (MeHg) reaches the aquatic food chain, ending up in fish. Inorganic Hg used in AGM is responsible for localised environmental contamination and occupational exposure of adults. In addition to this, iatrogenic ethylmercury (EtHg) derived from Thimerosal-containing vaccines (TCVs) exposes immunised infants. Objective: To understand Hg exposure in the Amazon in relation to environmental fish-MeHg exposure, occupational AGM activities and low-doses of TCV-EtHg. Methods: Medline and Thomson-Reuter Web of Science were searched to retrieve and select papers addressing Hg exposure and human health. Results and conclusion: Environmental-Hg studies addressed health effects associated with birth weight, infant linear growth and neurodevelopment, while, in adults, environmental and occupational studies addressed immune and neurological issues. No widespread clinical toxicity was reported due to fish-MeHg. However, mixed results associated with Hg exposure can be found. Reducing children’s exposure to EtHg is possible using Thimerosal-free vaccines, but it is difficult to interfere with fish consumption without consequences to riverine subsistence populations. Policies to diminish Hg exposure should focus on controlling and/or curbing widespread use of Hg (in gold amalgamation) and promotion of Thimerosal-free vaccines for pregnant women and young children.