Mercury as a hapten: A review of the role of toxicant-induced brain autoantibodies in autism and possible treatment considerations.

BACKGROUND: Mercury has many direct and well-recognized neurotoxic effects. However, its immune effects causing secondary neurotoxicity are less well-recognized. Mercury exposure can induce immunologic changes in the brain indicative of autoimmune dysfunction, including the production of highly specific brain autoantibodies. Mercury, and in particular, Thimerosal, can combine with a larger carrier, such as an endogenous protein, thereby acting as a hapten, and this new molecule can then elicit the production of antibodies. METHODS: A comprehensive search using PubMed and Google Scholar for original studies and reviews related to autism, mercury, autoantibodies, autoimmune dysfunction, and haptens was undertaken. All articles providing relevant information from 1985 to date were examined. Twenty-three studies were identified showing autoantibodies in the brains of individuals diagnosed with autism and all were included and discussed in this review. RESULTS: Research shows mercury exposure can result in an autoimmune reaction that may be causal or contributory to autism, especially in children with a family history of autoimmunity. The autoimmune pathogenesis in autism is demonstrated by the presence of brain autoantibodies (neuroantibodies), which include autoantibodies to: (1) human neuronal progenitor cells; (2) myelin basic protein (MBP); (3) neuron-axon filament protein (NAFP); (4) brain endothelial cells; (5) serotonin receptors; (6) glial fibrillary acidic protein (GFAP); (7) brain derived neurotrophic factor (BDNF); (8) myelin associated glycoprotein (MAG); and (9) various brain proteins in the cerebellum, hypothalamus, prefrontal cortex, cingulate gyrus, caudate putamen, cerebral cortex and caudate nucleus. CONCLUSION: Recent evidence suggests a relationship between mercury exposure and brain autoantibodies in individuals diagnosed with autism. Moreover, brain autoantibody levels in autism are found to correlate with both autism severity and blood mercury levels. Treatments to reduce mercury levels and/or brain autoantibody formation should be considered in autism.

A ten year longitudinal examination of the incidence rate and age of childhood encephalopathy diagnoses in an autism spectrum disorder diagnosed cohort.

Autism spectrum disorder (ASD) is defined by persistent deficits in social communication/interaction and stereotypic behaviors with many diagnosed persons experiencing a developmental regression at >1 year­old. It was hypothesized that progressive childhood encephalopathy is an important etiological factor in ASD pathogenesis. This hypothesis­testing study examined the relationship between diagnosed childhood encephalopathy and ASD. The Independent Healthcare Research Database is composed of de­identified linked eligibility and claim healthcare records prospectively generated from the Florida Medicaid system. A cohort of 101,736 persons eligible for Florida Medicaid from 1990­2009 and continuously eligible with ≥10 outpatient office visits during the 120 month period following birth were examined using SAS software. There were 1,397 persons (7,223 person­years) in the ASD diagnosed cohort and 100,339 persons (980,786 person­years) in the undiagnosed cohort. The incidence rate of encephalopathy was examined using Cox proportional hazards ratio models. In the ASD cohort relative to the undiagnosed cohort, a significantly increased incidence rate of diagnosed encephalopathy was observed in the unadjusted and adjusted models. The risk for an encephalopathy diagnosed at >1 year­old was greater than for an encephalopathy diagnosed at <1 year­old. This study provides important new evidence supporting the hypothesis that a significant number of children with an eventual ASD diagnosis experience a progressive childhood en cephalopathy diagnosed at >1 year­old.

Examining the evidence that ethylmercury crosses the blood-brain barrier.

Scientific research can provide us with factual, repeatable, measurable, and determinable results. As such, scientific research can provide information that can be used in the decision-making process in the care of patients and in public policy. Although it has been suggested that ethylmercury (C2H5Hg+)-containing compounds do not cross the blood-brain barrier (BBB), this review examines the literature that addresses the question as to whether ethylmercury-containing compounds cross the BBB. The review will begin with cellular studies that provide evidence for the passive and active transport of mercury species across the BBB. Then, animal and clinical studies will be presented that specifically examine whether mercury accumulates in the brain after exposure to ethylmercury-containing compounds or Thimerosal (an ethylmercury-containing compound used as a preservative in vaccines and other drugs that metabolizes or degrades to ethylmercury-containing compounds and thiosalicylate). The results indicate that ethylmercury-containing compounds are actively transported across membranes by the L (leucine-preferring)-amino acid transport (LAT) system, the same as methylmercury-containing compounds. Further, 22 studies from 1971 to 2019 show that exposure to ethylmercury-containing compounds (intravenously, intraperitoneally, topically, subcutaneously, intramuscularly, or intranasally administered) results in accumulation of mercury in the brain. In total, these studies indicate that ethylmercury-containing compounds and Thimerosal readily cross the BBB, convert, for the most part, to highly toxic inorganic mercury-containing compounds, which significantly and persistently bind to tissues in the brain, even in the absence of concurrent detectable blood mercury levels.

Down syndrome as a genetic model to evaluate the role of oxidative stress and transsulfuration abnormalities in autism spectrum disorder: A 10-year longitudinal cohort study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which evidence reveals oxidative stress and transsulfuration pathway abnormalities. Down syndrome (DS) is a genetic disorder characterized by similar oxidative stress and transsulfuration pathway abnormalities. This hypothesis-testing longitudinal cohort study determined whether transsulfuration abnormalities and oxidative stress are important susceptibility factors in ASD etiology by evaluating the rate of ASD diagnoses in DS as compared to the general population. The Independent Healthcare Research Database was analyzed for healthcare records prospectively generated in Florida Medicaid. A cohort of 101,736 persons (born: 1990-1999) with ≥10 outpatient office visits and continuously followed for 120 months after birth was examined. There were 942 children in the DS cohort (ICD-9 code: 758.0) and 100,749 children in the undiagnosed cohort (no DS diagnosis). ASD diagnoses were defined as autistic disorder (ICD-9 code: 299.00) or Asperger's disorder/pervasive developmental disorder-not otherwise specified (ICD-9 code: 299.80). ASDs were diagnosed in 5.31% of the DS cohort and 1.34% of the undiagnosed cohort. The risk ratio of being diagnosed with an ASD in the DS cohort as compared to the undiagnosed cohort was 3.97-fold significantly increased with a risk difference of 3.97%. Among children diagnosed with DS, less than 6% were also diagnosed with an ASD. Among children diagnosed with an ASD, less than 5% were also diagnosed with DS. Children diagnosed with DS are apparently more susceptible to ASD diagnosis relative to the general population suggesting oxidative stress and transsulfuration pathway abnormalities are important susceptibility factors in ASD.

A Cross-Sectional Study of Blood Ethylmercury Levels and Cognitive Decline Among Older Adults and the Elderly in the United States.

Cognitive health is an emerging public health concern for the aging American population. Mercury (Hg) is a toxic element that can cause nervous system damage. This hypothesis-testing study evaluated the relationship between blood ethyl-Hg levels and cognitive decline in an older adult and elderly American population. A total of 1,821,663 weighted-persons between 60-80 years old with detectable blood ethyl-Hg levels within the 2011-2012 National Health and Nutritional Examination Survey were examined. Those persons with blood ethyl-Hg levels greater than the median were deemed the higher ethyl-Hg exposure group and those with ethyl-Hg levels less than the median were deemed the lower ethyl-Hg exposure group. Three tests were utilized to measure cognitive function: 1) Consortium to Establish a Registry for Alzheimer's Disease - Word List Learning (CERAD W-L) delayed recall test, 2) animal fluency test, and 3) Digit Symbol Substitution Test. Each cognitive test score was categorized as higher for those with scores greater than the median and lower for those with scores less than the median. Survey logistic regression modeling with covariates was used to analyze the data for the relationship between blood ethyl-Hg levels and cognitive function scores. Significantly increased risks for lower animal fluency test (odds ratio (OR) = 13.652, p = 0.0029) and CERAD W-L delayed recall test (OR = 6.401, p = 0.0433) scores were observed among the higher ethyl-Hg exposure group as compared to the lower ethyl-Hg exposure group. This study supports the hypothesis that increased ethyl-Hg exposure is associated with significant cognitive decline in older adult and elderly Americans.

Childhood MMR vaccination and the incidence rate of measles infection: a ten year longitudinal cohort study of American children born in the 1990s.

BACKGROUND: Measles (rubeola) is a highly contagious disease with significant morbidity/mortality. Measles-Mumps-Rubella (MMR) is a live-attenuated vaccine used in the United States (US) since the early 1970s to prevent measles infection. This retrospective longitudinal cohort study examined childhood MMR vaccination effectiveness (VE) on preventing diagnosed measles cases. METHODS: The Independent Healthcare Research Database (IHRD) is composed of non-identifiable linked eligibility and claim healthcare records prospectively generated from the Florida Medicaid system. The SAS system was utilized to examine a cohort of 101,736 persons eligible for Florida Medicaid from 1990 to 2009 and continuously eligible with ≥10 outpatient office visits during the 120-month period following birth. There were 32,870 persons (224,492 person-years) in the cohort receiving a single dose of childhood MMR vaccine (vaccinated) and 43,538 persons (434,637 person-years) in an unvaccinated cohort (no exposures to measles-containing vaccine). The frequency of diagnosed measles (ICD-9 code: 055xxx) was examined. Cox proportional hazards models evaluated MMR vaccination and diagnosed measles over time. RESULTS: MMR vaccinated cohort members were at significantly reduced risk of measles in the unadjusted (VE = 83.6, 95% CI = 67.2-91.8%) and adjusted (VE = 80.7, 95% CI = 61.5-83.9%) models as compared to the unvaccinated cohort. VE = 80% among younger MMR recipients (12-15 months), whereas VE = 90% among older MMR recipients (16-20 months) as compared to the unvaccinated cohort. CONCLUSION: Routine childhood MMR vaccination significantly reduced the incidence rate of childhood measles infections, and the VE was greater in the older recipients (16-20 months) than in the younger recipients (12-15 months).

A cross-sectional study of the relationship between reported human papillomavirus vaccine exposure and the incidence of reported asthma in the United States.

OBJECTIVES: Asthma is a chronic disorder that affects persons of all ages impacting the quality of their lives. This cross-sectional hypothesis-testing study evaluated the relationship between human papillomavirus vaccine and the risk of an incident asthma diagnosis in a defined temporal period post-vaccination. METHODS: The 2015-2016 National Health and Nutrition Examination Survey data were examined for a group of 60,934,237 weighted persons between 9 and 26 years old in Statistical Analysis Software. RESULTS: Reported incident asthma significantly clustered in the year of reported human papillomavirus vaccination. When the data were separated by gender, the effects observed remained significant for males but not females. CONCLUSION: The results suggest that human papillomavirus vaccination resulted in an excess of 261,475 asthma cases with an estimated direct excess lifetime cost of such persons being US$42 billion. However, it is unclear what part of the vaccine and/or vaccine medium may have increased an individual's susceptibility to an asthma episode, whether the asthma diagnosis represented one asthma episode or if it is chronic, and how much therapeutic support was needed (if any) and for how long, which would impact cost. Despite the negative findings in this study, routine vaccination is an important public health tool, and the results observed need to be viewed in this context.

Demographic and neonatal risk factors for childhood asthma in the USA.

OBJECTIVE: Asthma is the most common chronic condition diagnosed among children worldwide according to the World Health Organization (WHO). This study evaluated on a longitudinal basis prospectively collected medical records for demographic and neonatal information among United States (US) children diagnosed with childhood asthma in comparison to controls. DESIGN: The Vaccine Safety Datalink (VSD) database was examined to identify cases (n = 5907) diagnosed with International Classification of Disease, ninth revision (ICD-9) healthcare provider diagnosed childhood asthma (493.xx) and controls (n = 11,662). PATIENTS: All cases and controls were health maintenance organization (HMO)-enrolled from birth until diagnosis or sufficient time to ensure that they were unlikely to receive a diagnosis, respectively. MAIN OUTCOME MEASURES: Child's gestational age in weeks at birth, birth weight in grams, maternal age in years at birth, Appearance-Pulse-Grimace-Activity-Respiration (APGAR) score at 1 minute and 5 minutes following birth, gender, and race. RESULTS: The study results revealed childhood asthma was diagnosed significantly more frequently among males than females, and significantly more frequently among minority populations (Black > Hispanic > Native American > Asian) than White populations. Cases diagnosed with childhood asthma had significantly decreased mean values for the following neonatal risk factors: gestational age, maternal age, birth weight, and APGAR scores at 1 and 5 minutes following birth in comparison to controls. CONCLUSIONS: This study offers healthcare providers important demographic and neonatal factors significantly associated with childhood asthma, and should help aid in the early diagnosis and treatment of childhood asthma.

Premature Puberty and Thimerosal-Containing Hepatitis B Vaccination: A Case-Control Study in the Vaccine Safety Datalink.

Studies suggest a relationship between exposure to endocrine disrupters, such as mercury (Hg), and premature puberty. Hg exposure from Thimerosal-containing hepatitis B vaccine, administered at specific intervals within the first six months of life, and the child's long-term risk of being diagnosed with premature puberty (ICD-9 code: 259.1), was retrospectively examined, using a hypothesis-testing, longitudinal case-control design on prospectively collected data, in the Vaccine Safety Datalink (VSD). Cases diagnosed with premature puberty were significantly more likely to have received increased exposure to Hg from hepatitis B vaccines preserved with Thimerosal given in the first month after birth (odds ratio (OR) = 1.803), first two months after birth (OR = 1.768), and first six months after birth (OR = 2.0955), compared to control subjects. When the data were separated by gender, the effects remained among females but not males. Female cases, as compared to female controls, were significantly more likely in a dose-dependent manner to have received a greater exposure to Hg from hepatitis B vaccines preserved with Thimerosal, given in the first six months after birth (OR = 1.0281 per µg Hg). The results of this study show a dose-dependent association between increasing organic Hg exposure from Thimerosal-containing hepatitis B vaccines administered within the first six months of life and the long-term risk of the child being diagnosed with premature puberty.

A longitudinal ecological study of seasonal influenza deaths in relation to climate conditions in the United States from 1999 through 2011.

Introduction: Influenza is an acute respiratory disease with significant annual global morbidity/mortality. Influenza transmission occurs in distinct seasonal patterns suggesting an importance of climate conditions on disease pathogenesis. This hypothesis-testing study evaluated microenvironment conditions within different demographic/geographical groups on seasonal influenza deaths in the United States. Materials and methods:The United States Centers for Disease Control and Prevention (CDC) Wonder online computer interface was utilized to integrate and analyze potential correlations in data generated from 1999 through 2011 for climate conditions of mean daily sunlight (KJ/m2), mean daily maximum air temperature (oC), mean daily minimum air temperature (oC), and mean daily precipitation (mm) from the North America Land Data Assimilation System (NLDAS) database and on influenza mortality (ICD-10 codes:J09, J10, or J11) from the Underlying Cause of Death database. Results and discussion:Significant inverse correlations between the climate conditions of temperature, sunlight, and precipitation and seasonal influenza death rate were observed. Similar effects were observed among males and females, but when the data were separated by race and urbanization status significant differences were observed. Conclusion: This study highlights key factors that can help shape public health policy to deal with seasonal influenza in the United States and beyond.

Cerebral hypoperfusion in autism spectrum disorder.

Cerebral hypoperfusion, or insufficient blood flow in the brain, occurs in many areas of the brain in patients diagnosed with autism spectrum disorder (ASD). Hypoperfusion was demonstrated in the brains of individuals with ASD when compared to normal healthy control brains either using positron emission tomography (PET) or single­photon emission computed tomography (SPECT). The affected areas include, but are not limited to the: prefrontal, frontal, temporal, occipital, and parietal cortices; thalami; basal ganglia; cingulate cortex; caudate nucleus; the limbic system including the hippocampal area; putamen; substantia nigra; cerebellum; and associative cortices. Moreover, correlations between symptom scores and hypoperfusion in the brains of individuals diagnosed with an ASD were found indicating that the greater the autism symptom pathology, the more significant the cerebral hypoperfusion or vascular pathology in the brain. Evidence suggests that brain inflammation and vascular inflammation may explain a part of the hypoperfusion. There is also evidence of a lack of normal compensatory increase in blood flow when the subjects are challenged with a task. Some studies propose treatments that can address the hypoperfusion found among individuals diagnosed with an ASD, bringing symptom relief to some extent. This review will explore the evidence that indicates cerebral hypoperfusion in ASD, as well as the possible etiological aspects, complications, and treatments.

Mercury-associated diagnoses among children diagnosed with pervasive development disorders.

Nelson and Bauman (Pediatrics 111:674-679, 2003) previously hypothesized that pervasive developmental disorder (PDD) was not associated with mercury (Hg) exposure because the medical conditions associated with Hg exposure were not associated with PDD. A hypothesis-testing longitudinal case-control study evaluated the frequency of medically diagnosed conditions previously associated with Hg poisoning, including: epilepsy, dysarthria, failure to thrive, cerebral palsy, or contact dermatitis and other eczema among children preceding their eventual PDD diagnosis (cases) compared to controls. A retrospective examination of medical records within the Vaccine Safety Datalink (VSD) was undertaken. Cases diagnosed with PDD (n = 534) were born from 1991 to 2000 and continuously enrolled until their PDD diagnosis. Controls (n = 26,367) were born from 1991 to 1993 and continuously enrolled from birth for 7.22 years. Within the first 5 years of life, cases compared to controls were significantly (p < 0.0001) more likely to be assigned a diagnosis of contact dermatitis and other eczema (odds ratio (OR) = 2.033), dysarthria (OR = 23.992), epilepsy (OR = 5.351), failure to thrive (OR = 25.3), and cerebral palsy (OR = 4.464). Similar results were observed when the data were separated by gender. Overall, the results of the present study and recently published studies provide direct evidence supporting a link in twelve of twelve categories (100%) of Hg poisoning associated symptoms as defined by Nelson and Bauman (Pediatrics 111:674-679, 2003) and symptoms observed in those with a PDD diagnosis. The results of this study support the biological plausibility of Hg poisoning to induce PDD diagnoses and rejection of the Nelson and Bauman (Pediatrics 111:674-679, 2003) hypothesis because those with a PDD diagnosis have an increased frequency of conditions previously associated with Hg poisoning.

The risk of neurodevelopmental disorders following Thimerosal-containing Hib vaccine in comparison to Thimerosal-free Hib vaccine administered from 1995 to 1999 in the United States.

Investigators postulated that early-life exposure to organic mercury (Hg) significantly increases the risk of childhood neurodevelopmental disorders (NDs). The Vaccine Adverse Event Reporting System database was utilized to conduct a hypothesis testing case-control study by evaluating 3486 total adverse event reports reported following Haemophilus influenza type b (Hib) vaccination. Exposed subjects received a Thimerosal-containing formulation (HIBTITER™, Wyeth-Lederle), while unexposed subjects received a Thimerosal-free formulation (PEDVAXHIB™, Merck). Subjects were included if they received either of these two Hib vaccine formulations between 1995 and 1999. Cases were defined as adverse event reports with a reported outcome of autism, developmental delay, psychomotor delay, or NDs in general. Cases with reported outcomes of febrile convulsions, pyrexia, or injection site pain, all of which have no biologically plausible relation to Hg exposure, were also examined. Controls were defined as adverse event reports without any mention of the specific case outcome examined. Cases of reported autism (odds ratio (OR) = 2.75, p < 0.02), developmental delay (OR = 5.39, p < 0.01), psychomotor disorder (OR = 2.38, p < 0.03), and neurodevelopmental disorder in general (OR = 2.70, p < 0.001) were each significantly more likely than their respective controls to receive Thimerosal-containing Hib vaccine than Thimerosal-free Hib vaccine. Significant effects for neurodevelopmental disorder in general were observed for males (OR = 2.52, p < 0.005), but not females when separated by gender. For the outcomes that had no biologically plausible relation to Hg exposure, the cases were no more likely than their respective controls to receive Thimerosal-containing Hib vaccine than Thimerosal-free Hib vaccine. This study provides suggestive evidence of an association between Thimerosal and neurodevelopmental outcomes and provides support for carrying out additional well-designed studies examining the association between Thimerosal-containing vaccines and a wide range of neurodevelopmental outcomes.

A cross-sectional study of the relationship between infant Thimerosal-containing hepatitis B vaccine exposure and attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by a marked pattern of inattention and/or hyperactivity-impulsivity that is inconsistent with developmental level and interferes with normal functioning in at least two settings. This study evaluated the hypothesis that infant Thimerosal-containing hepatitis B vaccine (T-HepB) exposure would increase the risk of an ADHD diagnosis. This cross-sectional study examined 4393 persons between 13 and 19 years of age from the combined 1999-2004 National Health and Nutritional Examination Survey (NHANES) by analyzing demographic, immunization, socioeconomic, and health-related variables using the SAS system. Three doses of T-HepB exposure in comparison to no exposure significantly increased the risk of an ADHD diagnosis using logistic regression (adjusted odds ratio=1.980), linear regression (adjusted beta-coefficient=0.04747), Spearman's rank (Rho=0.04807), and 2×2 contingency table (rate ratio=1.8353) statistical modeling even when considering other covariates such as gender, race, and socioeconomic status. Current health status outcomes selected on an a priori basis to not be biologically plausibly linked to T-HepB exposure showed no relationship with T-HepB. The observed study results are biologically plausible and supported by numerous previous epidemiological studies, but because the NHANES data is collected on a cross-sectional basis, it is not possible to ascribe a direct cause-effect relationship between exposure to T-HepB and an ADHD diagnosis. During the decade from 1991 to 2001 that infants were routinely exposed to T-HepB in the United States (US), an estimated 1.3-2.5 million children were diagnosed with ADHD with excess lifetime costs estimated at US $350-$660 billion as a consequence of T-HepB. Although Thimerosal use in the HepB in the US has been discontinued, Thimerosal remains in the HepB in developing countries. Routine vaccination is an important public health tool to prevent infectious diseases, but every effort should be made to eliminate Thimerosal exposure.

A Cross-Sectional Study of the Association between Infant Hepatitis B Vaccine Exposure in Boys and the Risk of Adverse Effects as Measured by Receipt of Special Education Services.

The National Center for Education Statistics reported that between 1990-2005 the number of children receiving special education services (SES) rose significantly, and then, from 2004-2012, the number declined significantly. This coincided with the introduction of Thimerosal-containing hepatitis B vaccine in 1991, and the subsequent introduction of Thimerosal-reduced hepatitis B vaccine in the early 2000s. This study examined the potential relationship between infant exposure to mercury from three doses of Thimerosal-containing hepatitis B vaccine and the risk of boys being adversely affected (as measured by receipt of SES). This cross-sectional study examined 1192 boys (weighted n = 24,537,123) 7-8 years of age (born: 1994-2007) from the combined 2001-2014 National Health and Nutritional Examination Survey (NHANES). Survey logistic regression modeling revealed that an exposed population receiving three doses of infant Thimerosal-containing hepatitis B vaccine (weighted n = 11,186,579), in comparison to an unexposed population (weighted n = 704,254), were at an increased risk of receipt of SES. This association was robust (crude odds ratio = 10.143, p = 0.0232), even when considering covariates, such as race and socioeconomic status (adjusted odds ratio = 9.234, p = 0.0259). Survey frequency modeling revealed that receipt of SES for the population that was exposed to three doses of Thimerosal-containing hepatitis B vaccine in infancy (12.91%) was significantly higher than the unexposed population (1.44%) (prevalence ratio = 8.96, p = 0.006, prevalence attributable rate = 0.1147). Despite the limitation of this cross-sectional study not being able to ascribe a direct cause-and-effect relationship between exposure and outcome, it is estimated that an additional 1.2 million boys received SES with excess education costs of about United States (US) $180 billion associated with exposure to Thimerosal-containing hepatitis B vaccine. By contrast, exposure to Thimerosal-reduced hepatitis B vaccine was not associated with an increased risk of receiving SES. Therefore, routine childhood vaccination is important to reduce the morbidity and mortality of infectious diseases, but every effort should be made to eliminate Thimerosal from all vaccines.

A cross-sectional study of the relationship between blood lead levels and reported attention deficit disorder: an assessment of the economic impact on the United States.

Attention deficit disorder (ADD) is characterized by a pattern of inattention and/or impulsivity that is inconsistent with developmental level and interferes with normal functioning in at least two settings. A recent meta-analysis suggested a significant relationship between lead (Pb) exposure and attention deficit symptoms. This study evaluated the potential relationship between increasing blood Pb levels and the risk of a reported ADD diagnosis. This cross-sectional study examined a sample of 2109 persons (32,762,158 weighted-persons) between 10 and 19 years-old from the 2003-2004 National Health and Nutritional Examination Survey (NHANES). This study analyzed demographic, socioeconomic, health related-questions, and laboratory tests using survey logistic and frequency modeling in SAS. On a microgram (µg)/deciliter (dL) basis, a significant dose-response relationship between increasing blood Pb levels and the risk of a reported ADD outcome was confirmed (odds ratio (OR) = 1.237, p = 0.0227). The relationship between increasing blood Pb levels and the risk of a reported ADD remained consistent when examining covariates such as gender, race, and socioeconomic status (OR = 1.292, p = 0.0301). Control outcomes selected on an a priori basis to not be biologically plausibly linked to blood Pb levels showed no relationship with increasing blood Pb levels. This NHANES analysis revealed an estimated 380,000 persons born in the United States (US) from 1984 to 1993 were reported to have an ADD outcome as a consequence of elevated blood Pb levels and the excess lifetime costs of these persons would be about US $100 billion. Every effort should be made to eliminate childhood Pb exposure.

Systematic Assessment of Research on Autism Spectrum Disorder (ASD) and Mercury Reveals Conflicts of Interest and the Need for Transparency in Autism Research.

Historically, entities with a vested interest in a product that critics have suggested is harmful have consistently used research to back their claims that the product is safe. Prominent examples are: tobacco, lead, bisphenol A, and atrazine. Research literature indicates that about 80-90% of studies with industry affiliation found no harm from the product, while only about 10-20% of studies without industry affiliation found no harm. In parallel to other historical debates, recent studies examining a possible relationship between mercury (Hg) exposure and autism spectrum disorder (ASD) show a similar dichotomy. Studies sponsored and supported by industry or entities with an apparent conflict of interest have most often shown no evidence of harm or no "consistent" evidence of harm, while studies without such affiliations report positive evidence of a Hg/autism association. The potentially causal relationship between Hg exposure and ASD differs from other toxic products since there is a broad coalition of entities for whom a conflict of interest arises. These include influential governmental public health entities, the pharmaceutical industry, and even the coal burning industry. This review includes a systematic literature search of original studies on the potential relationship between Hg and ASD from 1999 to August 2015, finding that of the studies with public health and/or industry affiliation, 86% reported no relationship between Hg and ASD. However, among studies without public health and/or industry affiliation, only 21% find no relationship between Hg and ASD. The discrepancy in these results suggests a bias indicative of a conflict of interest.

Blood Lead Levels and Learning Disabilities: A Cross-Sectional Study of the 2003-2004 National Health and Nutrition Examination Survey (NHANES).

Difficulties in the acquisition and use of listening, speaking, reading, writing, reasoning or mathematical abilities are present among persons diagnosed with learning disabilities (LDs). Previous studies suggest a significant relationship between lead (Pb) exposure and LDs. This study evaluated the potential dose-response relationship between blood Pb levels and the risk of LDs. This cross-sectional study examined 1411 children (32,788,743 weighted-persons) between 6 and 15 years old from the 2003-2004 National Health and Nutrition Examination Survey (NHANES) by analyzing demographics, health related-questions, and laboratory tests using survey logistic and frequency modeling in SAS. On a µg Pb/dL basis, a significant dose-dependent relationship between increasing blood Pb levels and increasing risk of LDs was observed (odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.03-1.43). The relationship remained significant when examining covariates such as gender and race (OR = 1.19, 95% CI = 1.00-1.40). By contrast, no dose-dependence was observed between increasing blood Pb levels and the risk of hay fever in the last year (OR = 0.77, 95% CI = 0.56-1.056), a non-plausibly biologically related outcome of blood Pb levels. Persons in the 50th-75th (12.80%) and 75th-100th (17.14%) percentiles of blood Pb were significantly more likely to have LDs than persons in the 0-50th percentile of blood Pb (8.78%). An estimated 1 million persons born in the US from 1989 to 1998 developed LDs from elevated blood Pb levels. Overall, this study revealed a significant dose-dependent association between increasing childhood blood Pb levels and the risk of a LD diagnosis, but it was not possible to ascribe a direct cause-effect relationship between blood Pb exposure and LD diagnosis. Childhood Pb exposure should be considered when evaluating children with LDs, and continuing efforts should be made to reduce Pb exposure.

Increased risk for an atypical autism diagnosis following Thimerosal-containing vaccine exposure in the United States: A prospective longitudinal case-control study in the Vaccine Safety Datalink.

BACKGROUND: Thimerosal is an organic-mercury (Hg)-containing compound (49.55% Hg by weight) historically added to many multi-dose vials of vaccine as a preservative and still added to some vaccines today. Concerns about the toxic effects from Thimerosal-containing childhood vaccines and the risk of an atypical autism diagnosis were evaluated in this study. METHODS: A hypothesis-testing, prospective longitudinal, case-control study assessed exposure to Hg from Thimerosal-containing hepatitis B vaccines (TM-HepB) among cases diagnosed with atypical autism (n=164) and controls (n=15,216). Automated medical records for subjects born from 1991 to 2000 and continuously enrolled in the Vaccine Safety Datalink (VSD) database were examined. RESULTS: Cases diagnosed with atypical autism were statistically significantly more likely to have received greater overall and dose-dependent exposures to Hg from TM-HepB vaccines administered within the first month of life, first two months of life, and first six months of life than the controls. Similar phenomena were observed when cases and controls were separated by gender. CONCLUSIONS: Routine childhood vaccination is an important public health tool to reduce infectious diseases. The present study provides important epidemiological evidence significantly associating increasing Hg exposure from Thimerosal-containing childhood vaccines and the subsequent risk of atypical autism diagnosis, and suggests that Thimerosal should be eliminated from vaccines.