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This hypothesis-testing study evaluated the relationship between fetal alcohol syndrome (FAS) and neurodevelopmental disorder (ND) diagnoses within the Independent Healthcare Research Database (IHRD).De-identified eligibility and claim healthcare records prospectively generated from the 1990-2012 Florida Medicaid system were analyzed using SAS software. There were 89,766 children continuously eligible with ≥10 outpatient office visits during the 120 month period following birth in the cohort examined. A total of 321 children were diagnosed with FAS. Autism spectrum disorder (ASD) (n = 922), tics (n = 551), attention deficit disorder/attention deficit-hyperactivity disorder (ADD/ADHD) (n = 20,260), mental retardation (MR) (n = 915), and specific delays in development (SDD) (n = 24,630) incidence rates were examined using frequency risk ratio (RR) and logistic regression models.The incidence rate of tics (RR = 5.68), ADD/ADHD (RR = 2.30), MR (RR = 7.83), SDD (RR = 2.88), and ASD (RR = 6.74) were significantly increased among FAS diagnosed children as compared to undiagnosed children. Adjusted (for gender, race, residency, and date of birth) odds ratios (ORs) were significantly increased for tics (OR = 4.87), ADD/ADHD (OR = 3.40), MR (OR = 7.91), SDD (OR = 9.56), and ASD (OR = 6.87) when comparing the FAS diagnosed children to undiagnosed children.Tens of thousands of American children with lifetime costs in the billions of US dollars were estimated to be impacted by FAS-associated NDs. These impacts are particularly tragic because FAS is dependent upon lifestyle.

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 year‑old. It was hypothesized that progressive childhood encephalopathy is an important etiological factor in ASD pathogenesis. This hypothesis‑testing study examined the relationship between diagnosed childhood encephalopathy and ASD. The Independent Healthcare Research Database is composed of de‑identified linked eligibility and claim healthcare records prospectively generated from the Florida Medicaid system. A cohort of 101,736 persons eligible for Florida Medicaid from 1990‑2009 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 person‑years) in the ASD diagnosed cohort and 100,339 persons (980,786 person‑years) 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 year‑old was greater than for an encephalopathy diagnosed at 1 year‑old.

BackgroundMeasles (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.MethodsThe 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.ResultsMMR 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.ConclusionRoutine 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).

This hypothesis-testing study evaluated the relationship between mercury (Hg)-based dental amalgams and arthritis diagnoses among adults in the United States (US). A total of 86 305 425 weighted-persons with ⩾1 dental amalgam filling surface (DAFS) (exposed group) and 32 201 088 weighted-persons with ⩾1 other dental filling surface (ODFS) (no DAFS, unexposed group) were examined in the 2015 to 2016 National Health and Nutritional Examination Survey (NHANES). All persons were 20 to 80 years-old with known demographic characteristics and arthritis status. Survey logistic regression and survey frequency modeling in SAS were employed with and without adjustment of covariates. The arthritis rate was significantly increased in the exposed group compared to the unexposed group in the unadjusted (7.68-fold) and adjusted (4.89-fold) models. Arthritis (per 10 000 weighted-person-years) was 6.0-fold significantly increased in the exposed group (6.2) compared to the unexposed group (1.06). A significant bimodal dose-dependent relationship between DAFS and arthritis rate was observed. The arthritis rate increased with increasing DAFS (peak among persons with 4-7 DAFS) and, subsequently, decreased among those with >6 DAFS. A significant decrease in arthritis rate among persons with >13 DAFS as compared to those persons with 4 to 7 DAFS was observed. A significant association between DAFS and arthritis risk and a dose-dependent DAFS associated immune-stimulation/immune-suppression with arthritis risk were observed. An estimated additional $96 835 814 US dollars (USD) are spent on annual medical costs and $184 797 680 USD are lost in annual wages from reported new onset arthritis attributably associated with DAFS (annual total cost = $281 633 494 USD).

Introduction: Autism spectrum disorder (ASD) is defined by persistent deficits in communication, socialization, and stereotypic behaviors. It was previously hypothesized that hormone dysfunction is a frequent occurrence among children diagnosed with an ASD. Objectives: A hypothesis-testing epidemiological study examined the relationship between precocious puberty (PP) (a known disorder of childhood sex hormone dysfunction) and ASD diagnoses. Methods: The Independent Healthcare Research Database is composed of de-identified linked eligibility and claims health-care records prospectively generated from the Florida Medicaid system. A cohort of 101,736 children eligible for Florida Medicaid from 1990 to 2009 and continuously eligible with ≥10 outpatient office visits during the 120-month period following birth were examined using SAS and StatsDirect software. There were 1,593 children (15,738 person-years) in the ASD diagnosed cohort utilizing the Diagnostic and Statistical Manual of Mental Disorders, 4th revision criteria (the International Code for Disease, 9th revision [ICD-9] codes: 299.00 or 299.80) and 100,143 children (996,835 person-years) in the undiagnosed cohort. Results: The incidence rate of PP (ICD-9 code: 259.1) was examined using Cox proportional hazards ratio (HR) and frequency models. PP per 10,000 person-years in the ASD cohort (43.2) relative to the undiagnosed cohort (13.7) was significantly increased in frequency modeling (risk ratio = 3.15, p < 0.0001) and Cox proportional HR modeling (adjusted HR = 4.64, p < 0.0001). Further analyses revealed the incidence rate of PP diagnosed after 3 years of age was significantly increased (adjusted HR = 5.16, p < 0.0001) in the ASD cohort relative to the undiagnosed cohort but not for the incidence rate of PP diagnosed before 3 years (adjusted HR = 1.57, p = 0.44). Conclusion: This hypothesis-testing study provides strong evidence of an increased incidence rate of PP among children diagnosed with an ASD.

Objective: Mercury (Hg)-based amalgam is a dental restorative material in common use. This hypothesis-testing study evaluated the relationship between dental amalgam exposure and the risk of reported asthma diagnoses in American adults. Methods: A total of 97,861,577 weighted-persons with one or more dental amalgam surfaces (exposed group) and 31,716,558 weighted-persons with one or more other dental surfaces (no dental amalgams, unexposed group) were examined in the 2015–2016 National Health and Nutrition Examination Survey. All persons were 20–80 years old and with known reported asthma status (only newly diagnosed asthma cases were examined). Survey logistic regression and survey frequency modeling in SAS were employed to evaluate the relative incidence rate of reported asthma diagnoses among those in the exposed group compared to the unexposed group. Covariates of gender, race, socioeconomic status, educational status, country of birth, and tobacco exposure were considered. Results: Survey logistic modeling revealed a significantly increased incidence rate of reported asthma in the exposed group as compared to the unexposed group in unadjusted (4.46-fold) and adjusted (4.84-fold) models. A dose–response relationship was observed for the risk of reported asthma per dental amalgam filling surface in unadjusted (1.073) and adjusted (1.076) models. Survey frequency modeling revealed that the frequency of reported asthma (per 10,000 weighted-person years) was 3.66-fold significantly increased in the exposed group (2.06) as compared to the unexposed group (0.56). Conclusion: Increased dental amalgam exposure was associated with an increased risk of reported asthma diagnoses in American adults, but future studies should further evaluate this relationship.

Measles (rubeola) is a highly contagious infectious disease with significant morbidity/mortality. Measles-Mumps-Rubella (MMR) is a live-attenuated vaccine used in the United States (US) to prevent measles. This retrospective longitudinal cohort study evaluated childhood MMR vaccination and the risk of a seizure episode and seizure disorder.The Independent Healthcare Research Database (IHRD) composed of records prospectively generated from Florida Medicaid was analyzed using SAS to identify persons continuously enrolled from birth for 120 months. Two cohorts were examined: 23,486 persons received at least one dose of MMR vaccine between 12 and 17 months (vaccinated) and 41,725 persons not receiving a measles-containing vaccine (unvaccinated). The daily incidence rate of an initial seizure episode (ICD-9 code: 780.3x) and seizure disorder (ICD-9 code: 345.xx) following an initial seizure episode diagnoses were examined using Cox proportional hazards ratio (HR) and time-trend models post-MMR vaccination compared to unvaccinated persons and in a self-controlled case-series (SCCS).The daily incidence rate of an initial seizure episode diagnosed from 6 to 11 days post-MMR vaccination in comparison to 12 to17 months among unvaccinated persons was significantly increased (unadjusted HR = 5.73, p 0.0001 and adjusted HR = 5.94, p 0.0001) in HR models. The daily incidence rate of an eventual seizure disorder diagnosis among those diagnosed with an initial seizure episode from 6 to 11 days post-MMR vaccination was significantly increased (unadjusted HR = 17.7, p 0.01 and adjusted HR = 17.4, p 0.01) in comparison to the daily incidence rate of an eventual seizure disorder diagnosis among those diagnosed with an initial seizure episode from 12 to 17 months among unvaccinated persons. Time-trend analyses revealed a significantly increased rate ratio (RR) for an initial seizure episode (RR = 4.64, p 0.0001) and seizure disorder (RR = 5.51, p 0.0001) diagnoses. Time-trend SCCS analyses revealed a significantly increased daily incidence rate of an initial seizure episode (RR = 3.80, p 0.0001) when comparing periods from 6 to 11 days post-MMR vaccination to 49-60 days post-MMR vaccination. The incidence rate of an eventual seizure disorder diagnosis among those with an initial seizure episode diagnosis from 6 to 11 days post-MMR vaccination compared to 49-60 days post-MMR vaccination was significantly increased (RR = 4.15, p 0.01).Seizure episode and seizure disorder are rare consequences of routine childhood MMR vaccination.

Autism spectrum disorder (ASD) is defined by persistent deficits in social communication/interaction and stereotypic behaviors with many diagnosed persons experiencing a developmental regression at1 year‑old. It was hypothesized that progressive childhood encephalopathy is an important etiological factor in ASD pathogenesis. This hypothesis‑testing study examined the relationship between diagnosed childhood encephalopathy and ASD. The Independent Healthcare Research Database is composed of de‑identified linked eligibility and claim healthcare records prospectively generated from the Florida Medicaid system. A cohort of 101,736 persons eligible for Florida Medicaid from 1990‑2009 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 person‑years) in the ASD diagnosed cohort and 100,339 persons (980,786 person‑years) 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 at1 year‑old was greater than for an encephalopathy diagnosed at1 year‑old. 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 at1 year‑old.

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

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.

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.

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.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).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.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.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.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.

Contradictory studies suggest that some neonatal factors may be associated with a pervasive developmental disorder (PDD) diagnosis, but limited data is available from longitudinal, prospective medical record assessments.The present hypothesis-testing longitudinal, case-control study evaluated birth characteristics among cases diagnosed with a PDD in comparison to controls by examining prospectively collected automated medical records within the Vaccine Safety Datalink (VSD) database.Cases were Health Maintenance Organization (HMO)-enrolled from birth until diagnosed with International Classification of Disease, 9th revision (ICD-9) PDD (299.xx) and controls were HMO-enrolled from birth for at least 4.75 years without a PDD diagnosis. The birth characteristics examined included: gender, gestational age in weeks at birth, mean birth weight in grams, Appearance-Pulse-Grimace-Activity-Respiration (APGAR) scores at 1 minute and 5 minutes, and maternal age in years at birth. Cases had a significantly increased male/female ratio relative to controls. By contrast, mean gestational age at birth, mean birth weight, mean maternal age at birth, and mean APGAR scores at 1 minute and 5 minutes were not statistically different among cases compared to controls.This study indicates that cases diagnosed with a PDD as compared to controls do not have significant differences in neonatal factors.

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.

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.

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.

This study evaluated Thimerosal-containing childhood vaccines and the risk of a diagnosis called disturbance of emotions specific to childhood and adolescence (ED). Thimerosal is an organic-mercury (Hg)-containing compound used in some vaccines.A hypothesis-testing prospective, longitudinal case-control study evaluated Hg exposure from Thimerosal in hepatitis B vaccines administered at specific times within the first 6 months of life and its association with medically diagnosed ED (313.xx) (n = 517) in children born between 1991-2000 in comparison to controls (n = 27 491) in the Vaccine Safety Datalink (VSD) database.Cases diagnosed with ED were significantly more likely than controls to have received increased Hg exposure within the first month of life (odds ratio (OR) = 1.3384), the first 2 months of life (OR = 1.3367) and the first 6 months of life (OR = 2.37). When the data were separated by gender, similar significant adverse effects were observed for males, but not females. On a per microgram Hg basis, cases diagnosed with ED were significantly more likely than controls to have received increased exposure within the first 6 months of life (OR = 1.025 per microgram Hg).The results show a significant relationship between Hg exposure from Thimerosal-containing childhood vaccines and the subsequent risk of an ED diagnosis.

BACKGROUND This study evaluated the hypothesis that the 1999 recommendation by the American Academy of Pediatrics (AAP) and US Public Health Service (PHS) to reduce exposure to mercury (Hg) from Thimerosal in US vaccines would be associated with a reduction in the long-term risk of being diagnosed with autism. MATERIAL AND METHODS A two-phase assessment utilizing a case (n=73) -control (n=11,783) study in the Vaccine Adverse Event Reporting System (VAERS) database (for hypothesis generating) and a more rigorous, independent matched case (n=40) -control (n=40) study (hypothesis testing) was undertaken. RESULTS Analysis of the VAERS database using logistic regression revealed that the odds ratio (OR) for being an autism case in the VAERS database significantly decreased with a more recent year of vaccination in comparison to controls (OR=0.65) from 1998 to 2003. Sex-separated analyses revealed similar significant effects for males (OR=0.62) and females (OR=0.71). Analyses of the matched case-control data revealed, using the t-test statistic, that the mean date of birth among cases diagnosed with an autism spectrum disorder (ASD) (2000.5±1.2) was significantly more in the past than in controls (2001.1±1.3). Logistic regression also revealed that the OR for being diagnosed with ASD significantly decreased with a more recent date of birth in comparison to controls (OR=0.67) from 1998-2003. CONCLUSIONS This study reveals that the risk of autism during from the late1990s to early 2000s in the US significantly decreased with reductions in Hg exposure from Thimerosal-containing childhood vaccines, but future studies should examine this phenomenon in other US populations. Vaccine programs have significantly reduced the morbidity and mortality associated with infectious disease, but Thimerosal should be removed from all vaccines.

The brain pathology in autism spectrum disorders (ASD) indicates marked and ongoing inflammatory reactivity with concomitant neuronal damage. These findings are suggestive of neuronal insult as a result of external factors, rather than some type of developmental mishap. Various xenobiotics have been suggested as possible causes of this pathology. In a recent review, the top ten environmental compounds suspected of causing autism and learning disabilities were listed and they included: lead, methyl-mercury, polychorinated biphenyls, organophosphate pesticides, organochlorine pesticides, endocrine disruptors, automotive exhaust, polycyclic aromatic hydrocarbons, polybrominated diphenyl ethers, and perfluorinated compounds. This current review, however, will focus specifically on mercury exposure and ASD by conducting a comprehensive literature search of original studies in humans that examine the potential relationship between mercury and ASD, categorizing, summarizing, and discussing the published research that addresses this topic. This review found 91 studies that examine the potential relationship between mercury and ASD from 1999 to February 2016. Of these studies, the vast majority (74%) suggest that mercury is a risk factor for ASD, revealing both direct and indirect effects. The preponderance of the evidence indicates that mercury exposure is causal and/or contributory in ASD.

David A Geier,1,2 Janet K Kern,1,3 Lisa K Sykes,2 Mark R Geier1,2 1Research Department, The Institute of Chronic Illnesses, Inc, 2Research Department, CoMeD, Inc, Silver Spring, MD, 3Research Department, CONEM US Autism Research Group, Allen, TX, USA Background: Previous studies on genetic testing of chromosomal abnormalities in individuals diagnosed with autism spectrum disorder (ASD) found that ~80% have negative genetic test results (NGTRs) and ~20% have positive genetic test results (PGTRs), of which ~7% were probable de novo mutations (PDNMs). Research suggests that parental age is a risk factor for an ASD diagnosis. This study examined genotypic variation in ASD and its relationship to parental age and phenotype.Methods: Phenotype was derived from detailed clinical information, and genotype was derived from high-resolution blood chromosome and blood whole-genome copy number variant genetic testing on a consecutive cohort (born: 1983–2009) of subjects diagnosed with ASD (N=218).Results: Among the subjects examined, 80.3% had NGTRs and 19.7% had PGTRs, of which 6.9% had PDNMs. NGTR subjects were born more recently (the risk of PDNMs decreasing by 12% per more recent birth year) and tended to have an increased male–female ratio compared to PDNM subjects. PDNM subjects had significantly increased mean parental age and paternal age at subject’s birth (the risk of a PDNM increasing by 7%–8% per year of parental or paternal age) compared to NGTR subjects. PGTR and NGTR subjects showed significant improvements in speech/language/communication with increasing age. PGTR subjects showed significant improvements in sociability, a core feature of an ASD diagnosis, with increasing age, whereas NGTR subjects showed significant worsening in sociability with increasing age.Conclusion: This study helps to elucidate different phenotypic ASD subtypes and may even indicate the need for differential diagnostic classifications. Keywords: genotype, phenotype, autism spectrum disorder, microarray, advanced age, gene, pervasive developmental disorder, parental age

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.

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.

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&rsquo, 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 &micro, g 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.

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.

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.

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.

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

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.

GARDASIL (Merck & Co., Inc., Whitehouse Station, NJ, USA) is a quadrivalent human papillomavirus (HPV4) vaccine. An epidemiological study was undertaken to evaluate concerns about the potential for HPV4 vaccination to induce serious autoimmune adverse events (SAAEs). The vaccine adverse event reporting system (VAERS) database was examined for adverse event reports associated with vaccines administered from January 2006 through December 2012 to recipients between 18 and 39 years old with a listed residence in the USA and a specified female gender. It was observed that cases with the SAAE outcomes of gastroenteritis (odds ratio (OR) = 4.6, 95 % confidence interval (CI) = 1.3–18.5), arthritis (OR = 2.5, 95 % CI = 1.4–4.3), systemic lupus erythematosus (OR = 5.3, 95 % CI = 1.5–20.5), vasculitis (OR = 4, 95 % CI = 1.01–16.4), alopecia (OR = 8.3, 95 % CI = 4.5–15.9), or CNS conditions (OR = 1.8, 95 % CI = 1.04–2.9) were significantly more likely than controls to have received HPV4 vaccine (median onset of SAAE symptoms from 6 to 55 days post-HPV4 vaccination). Cases with the outcomes of Guillain-Barre syndrome (OR = 0.75, 95 % CI = 0.42–1.3) or thrombocytopenia (OR = 1.3, 95 % CI = 0.48–3.5) were no more likely than controls to have received HPV4 vaccine. Cases with the general health outcomes of infection (OR = 0.72, 95 % CI = 0.27–1.7), conjunctivitis (OR = 0.88, 95 % CI = 0.29–2.7), or diarrhea (OR = 1.01, 95 % CI = 0.83–1.22) were no more likely than controls to have received HPV4 vaccine. Previous case series of SAAEs and biological plausibility support the observed results. Additional studies should be conducted to further evaluate the potential biological mechanisms involved in HPV4 vaccine-associated SAAEs in animal model systems, and to examine the potential epidemiological relationship between HPV4 vaccine-associated SAAEs in other databases and populations.

L-Carnitine is a naturally occurring substance required in mammalian energy metabolism that functions by facilitating long-chain fatty acid entry into cellular mitochondria, thereby delivering substrate for oxidation and subsequent energy production. It has been purposed that L-carnitine may improve and preserve cognitive performance, and may lead to better cognitive aging through the life span, and several controlled human clinical trials with L-carnitine support the hypothesis that this substance has the ability to improve cognitive function. We further hypothesized that, since L-carnitine is an important co-factor of mammalian mitochondrial energy metabolism, acute administration of L-carnitine to human tissue culture cells should result in detectable increases in mitochondrial function. Cultures of SH-SY-5Y human neuroblastoma and 1321N1 human astrocytoma cells grown in 96-well cell culture plates were acutely administered L-carnitine hydrochloride, and then, mitochondrial function was assayed using the colorimetric 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt cell assay kit in a VERSAmax tunable microplate reader. Significant increases in mitochondrial function were observed when human neuroblastoma or human astrocytoma cells were exposed to 100 nM (20 μg L-carnitine hydrochloride/L) to 100 μM (20 mg L-carnitine hydrochloride/L) concentrations of L-carnitine hydrochloride in comparison to unexposed cells, whereas no significant positive effects were observed at lower or higher concentrations of L-carnitine hydrochloride. The results of the present study provide insights for how L-carnitine therapy may significantly improve human neuronal function, but we recommend that future studies further explore different derivatives of L-carnitine compounds in different in vitro cell-based systems using different markers of mitochondrial function.

Autism spectrum disorder (ASD) is a neurological disorder in which a significant number of the children experience a developmental regression characterized by a loss of previously acquired skills and abilities. Typically reported are losses of verbal, nonverbal, and social abilities. Several recent studies suggest that children diagnosed with an ASD have abnormal sulfation chemistry, limited thiol availability, and decreased glutathione (GSH) reserve capacity, resulting in a compromised oxidation/reduction (redox) and detoxification capacity. Research indicates that the availability of thiols, particularly GSH, can influence the effects of thimerosal (TM) and other mercury (Hg) compounds. TM is an organomercurial compound (49.55% Hg by weight) that has been, and continues to be, used as a preservative in many childhood vaccines, particularly in developing countries. Thiol-modulating mechanisms affecting the cytotoxicity of TM have been identified. Importantly, the emergence of ASD symptoms post-6 months of age temporally follows the administration of many childhood vaccines. The purpose of the present critical review is provide mechanistic insight regarding how limited thiol availability, abnormal sulfation chemistry, and decreased GSH reserve capacity in children with an ASD could make them more susceptible to the toxic effects of TM routinely administered as part of mandated childhood immunization schedules.

The purpose of this study was to evaluate scores generated from the Autism Treatment Evaluation Checklist (ATEC), a parent-rated measure, and those derived from professionally completed Childhood Autism Rating Scale (CARS) evaluations. A cohort of 56 participants diagnosed with an autism spectrum disorder was used for the study, and each child was evaluated independently by the parent using the ATEC and a health care professional using the CARS. The Spearman's rank correlation statistic ρ was used to evaluate the correlation between ATEC and CARS scores. It was observed that there was a significant correlation between total ATEC and CARS scores (ρ = .71). Specific domains in the ATEC evaluation significantly correlated with CARS scores. Sensitivity, specificity, and receiver operating characteristic confirmed the association between CARS and ATEC domains. The results help to validate the utility of the parentally completed ATEC in comparison with an established, professional-related measure of autism.

Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder with a complex pathogenesis. Many studies over the last four decades have recognized altered immune responses among individuals diagnosed with ASD. The purpose of this critical and comprehensive review is to examine the hypothesis that immune dysfunction is present more frequently, and it is related to ASD in humans. It was found that that often individuals diagnosed with ASD have alterations in immune cells such as T cells, B cells, monocytes, natural killer cells, and dendritic cells. Also, many individuals diagnosed with ASD have alterations in immunoglobulins and increased autoantibodies. Finally, an important portion of individuals diagnosed with ASD has elevated peripheral cytokines and chemokines and associated neuroinflammation. In conclusion, immune dysregulation and inflammation are important components of ASD diagnosis and are key components of the diagnosis and treatment of ASD.

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.

Background: Obesity among children and adolescents in the United States has tripled since 1980, and has become a major public health concern. Aims: The purpose of this study was to evaluate the potential relationship between exposure to organic mercury from Thimerosal-containing hepatitis B vaccines and the children's subsequent risk of an obesity diagnosis. Materials and Methods: A hypothesis-testing, case-control study was undertaken to evaluate exposure to organic mercury from Thimerosal-containing hepatitis B vaccines, which were administered at specific intervals in the first 6 months of life, among cases diagnosed with childhood obesity and controls by examining automated medical records for children born from 1991 to 2000 who were continuously enrolled in the Vaccine Safety Datalink database. Results: This study found highly significant associations as follows. Cases diagnosed with obesity were significantly (P < 0.00001) more likely to have received greater exposure to organic mercury from Thimerosal-containing hepatitis B vaccines administered within the first month of life (odds ratio (OR) =1.511), first 2 months of life (OR = 1.486), and first 6 months of life (OR = 3.795) than the controls. Similar outcomes were observed when the overall data were separated by gender. In a dose-response manner, cases diagnosed with obesity were significantly more likely than controls to have received greater exposure to organic mercury from Thimerosal-containing hepatitis B vaccines, which were administered within the first 6 months of life (OR = 1.0375 per μg of mercury, P < 0.00001). Conclusions: In a dose-response manner, the present study associates an increased organic mercury exposure from Thimerosal-containing hepatitis B vaccines with an increased risk of obesity diagnosis, and suggests that Thimerosal is an obesogen. The results are biologically plausible and future studies are needed to examine this phenomenon.

(1) Background: Hyperkinetic syndrome of childhood (HKSoC) is an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) category in which the majority of the children are also diagnosed under the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR), where the umbrella term is “Attention-Deficit and Disruptive Behavior Disorders”. The diagnostic criteria for HKSoC are developmentally inappropriate inattention, hyperactivity, and impulsivity. Some studies have implicated mercury (Hg) exposure as a risk factor. (2) Methods: This hypothesis testing study; using the Vaccine Safety Datalink; assessed the toxicological effects of bolus exposure to organic-Hg from Thimerosal-containing vaccines (TCVs) by examining the relationship between Thimerosal-preserved hepatitis B vaccines (TM-HepB) given at varying levels and at specific intervals in the first six months after birth and the risk of a child being diagnosed with HKSoC. (3) Results: Children diagnosed with HKSoC were significantly more likely to be exposed to increased organic-Hg from TM-HepB doses given within the first month (odds ratio = 1.45; 95% confidence interval (CI) = 1.30–1.62); within the first two months (odds ratio = 1.43; 95% CI = 1.28–1.59); and within the first six months (odds ratio = 4.51; 95% CI = 3.04–6.71) than controls. (4) Conclusion: The results indicate that increasing organic-Hg exposure from TCVs heightens the risk of a HKSoC diagnosis.

Previous studies have found a higher body-burden of toxic metals, particularly mercury (Hg), among subjects diagnosed with an autism spectrum disorder (ASD) in comparison to neurotypical controls. Moreover, Hg body-burden was associated with ASD severity. This cross-sectional study examined the potential correlation between hair toxic metal concentrations and ASD severity in a prospective cohort of participants diagnosed with moderate to severe ASD. The Institutional Review Board at the University of Texas Southwestern Medical Center at Dallas (Dallas, TX) approved the present study. Qualifying study participants (n = 18) were evaluated for ASD severity using the Childhood Autism Rating Scale (CARS) and quantitatively for arsenic, Hg, cadmium, lead, chromium, cobalt, nickel, aluminum, tin, uranium, and manganese using hair toxic element testing by Doctor’s Data (a CLIA-approved laboratory). CARS scoring and hair toxic element testing were blinded to one another. Increasing hair Hg concentrations significantly correlated with increased ASD severity. In contrast, no significant correlations were observed between any other of the hair toxic metals examined and ASD severity. This study helps to provide additional mechanistic support for Hg in the etiology of ASD severity, and is supported by an increasing number of recent critical reviews that provide biological plausibility for the role of Hg exposure in the pathogenesis of ASDs.