Reported asthma and dental amalgam exposure among adults in the United States: An assessment of the National Health and Nutrition Examination Survey.

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.

A Longitudinal Cohort Study of Precocious Puberty and Autism Spectrum Disorder.

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.

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.

Abnormal Brain Connectivity Spectrum Disorders Following Thimerosal Administration: A Prospective Longitudinal Case-Control Assessment of Medical Records in the Vaccine Safety Datalink.

BACKGROUND: Autism spectrum disorder (ASD), tic disorder (TD), and hyperkinetic syndrome of childhood (attention deficit disorder [ADD]/attention deficit hyperactivity disorder [ADHD]) are disorders recently defined as abnormal connectivity spectrum disorders (ACSDs) because they show a similar pattern of abnormal brain connectivity. This study examines whether these disorders are associated with exposure to thimerosal, a mercury (Hg)-based preservative. METHODS: A hypothesis testing case-control study evaluated the Vaccine Safety Datalink for the potential dose-dependent odds ratios (ORs) for diagnoses of ASD, TD, and ADD/ADHD compared to controls, following exposure to Hg from thimerosal-containing Haemophilus influenzae type b vaccines administrated within the first 15 months of life. Febrile seizures, cerebral degeneration, and unspecified disorders of metabolism, which are not biologically plausibly linked to thimerosal, were examined as control outcomes. RESULTS: On a per 25 µg Hg basis, cases diagnosed with ASD (OR = 1.493), TD (OR = 1.428), or ADD/ADHD (OR = 1.503) were significantly (P < .001) more likely than controls to have received increased Hg exposure. Similar relationships were observed when separated by gender. Cases diagnosed with control outcomes were no more likely than controls to have received increased Hg exposure. CONCLUSION: The results suggest that Hg exposure from thimerosal is significantly associated with the ACSDs of ASD, TD, and ADD/ADHD.

Quadrivalent human papillomavirus vaccine and autoimmune adverse events: a case-control assessment of the vaccine adverse event reporting system (VAERS) database.

Gardasil is a quadrivalent human papillomavirus (HPV4) vaccine that was approved for use by the US Food and Drug Administration in June 2006. HPV4 vaccine is routinely recommended for administration to women in the USA who are 11-12 years old by the Advisory Committee on Immunization Practices. Previous studies suggest HPV4 vaccine administration was associated with autoimmune diseases. As a consequence, an epidemiological assessment of the vaccine adverse event reporting system database was undertaken for adverse event reports associated with vaccines administered from 2006 to 2014 to 6-39 year-old recipients with a listed US residence and a specified female gender. Cases with the serious autoimmune adverse event (SAAE) outcomes of gastroenteritis (odds ratio (OR) 4.627, 95 % confidence interval (CI) 1.892-12.389), rheumatoid arthritis (OR 5.629, 95 % CI 2.809-12.039), thrombocytopenia (OR 2.178, 95 % CI 1.222-3.885), systemic lupus erythematosus (OR 7.626, 95 % CI 3.385-19.366), vasculitis (OR 3.420, 95 % CI 1.211-10.408), alopecia (OR 8.894, 95 % CI 6.255-12.914), CNS demyelinating conditions (OR 1.585, 95 % CI 1.129-2.213), ovarian damage (OR 14.961, 95 % CI 6.728-39.199), or irritable bowel syndrome (OR 10.021, 95 % CI 3.725-33.749) were significantly more likely than controls to have received HPV4 vaccine (median onset of initial symptoms ranged from 3 to 37 days post-HPV4 vaccination). Cases with the outcome of Guillain-Barre syndrome (OR 0.839, 95 % CI 0.601-1.145) were no more likely than controls to have received HPV4 vaccine. In addition, cases with the known HPV4-related outcome of syncope were significantly more likely than controls to have received HPV4 vaccine (OR 5.342, 95 % CI 4.942-5.777). Cases with the general health outcomes of infection (OR 0.765, 95 % CI 0.428-1.312), conjunctivitis (OR 1.010, 95 % CI 0.480-2.016), diarrhea (OR 0.927, 95 % CI 0.809-1.059), or pneumonia (OR 0.785, 95 % CI 0.481-1.246) were no more likely than controls to have received HPV4 vaccine. Confirmatory epidemiological studies in other databases should be undertaken and long-term clinical consequences of HPV-linked SAAEs should be examined.

A longitudinal cohort study of the relationship between Thimerosal-containing hepatitis B vaccination and specific delays in development in the United States: Assessment of attributable risk and lifetime care costs.

Epidemiological evidence suggests a link between mercury (Hg) exposure from Thimerosal-containing vaccines and specific delays in development. A hypothesis-testing longitudinal cohort study (n=49,835) using medical records in the Vaccine Safety Datalink (VSD) was undertaken to evaluate the relationship between exposure to Hg from Thimerosal-containing hepatitis B vaccines (T-HBVs) administered at specific intervals in the first 6months of life and specific delays in development [International Classification of Disease, 9th revision (ICD-9): 315.xx] among children born between 1991 and 1994 and continuously enrolled from birth for at least 5.81years. Infants receiving increased Hg doses from T-HBVs administered within the first month, the first 2months, and the first 6months of life were significantly more likely to be diagnosed with specific delays in development than infants receiving no Hg doses from T-HBVs. During the decade in which T-HBVs were routinely recommended and administered to US infants (1991-2001), an estimated 0.5-1million additional US children were diagnosed with specific delays in development as a consequence of 25µg or 37.5µg organic Hg from T-HBVs administered within the first 6months of life. The resulting lifetime costs to the United States may exceed $1 trillion.

A Prospective Longitudinal Assessment of Medical Records for Diagnostic Substitution among Subjects Diagnosed with a Pervasive Developmental Disorder in the United States.

BACKGROUND: Previously, investigators suggested that diagnostic substitution from other diagnoses, e.g., mental retardation (MR) and/or cerebral palsy (CP) to pervasive developmental disorder (PDD) is a driving factor behind increases in autism. This study evaluated potential diagnostic substitution among subjects diagnosed with PDD vs. MR or CP by examining birth characteristic overlap. METHODS: SAS(®) and StatsDirect software examined medical records for subjects within the Vaccine Safety Datalink database who were Health Maintenance Organization-enrolled from birth until diagnosed with an International Classification of Disease, 9th revision (ICD-9) outcome of PDD (299.xx, n = 84), CP (343.xx, n = 300), or MR (317.xx, 318.xx, or 319.xx, n = 51). RESULTS: Subjects with PDD had significantly (p < 0.01) increased: male/female ratio (PDD = 5.5 vs. CP = 1.5 or MR = 1.3), mean age of initial diagnosis in years (PDD = 3.13 vs. CP = 1.09 or MR = 1.62), mean gestational age in weeks at birth (PDD = 38.73 vs. CP = 36.20 or MR = 34.84), mean birth weight in grams (PDD = 3,368 vs. CP = 2,767 or MR = 2,406), and mean Appearance-Pulse-Grimace-Activity-Respiration scores at 1 min (PDD = 7.82 vs. CP = 6.37 or MR = 6.76) and 5 min (PDD = 8.77 vs. CP = 7.92 or MR = 8.04), as compared to subjects diagnosed with CP or MR. CONCLUSION: This study suggests diagnostic substitution cannot fully explain increased PDD prevalence during the 1990s within the United States.

Thimerosal as discrimination: vaccine disparity in the UN Minamata Convention on mercury.

When addressing toxins, one unmistakable parallel exists between biology and politics: developing children and developing nations are those most vulnerable to toxic exposures. This disturbing parallel is the subject of this critical review, which examines the use and distribution of the mercury (Hg)-based compound, thimerosal, in vaccines. Developed in 1927, thimerosal is 49.55% Hg by weight and breaks down in the body into ethyl-Hg chloride, ethyl-Hg hydroxide and sodium thiosalicylate. Since the early 1930s, there has been evidence indicating that thimerosal poses a hazard to the health of human beings and is ineffective as an antimicrobial agent. While children in the developed and predominantly western nations receive doses of mostly no-thimerosal and reduced-thimerosal vaccines, children in the developing nations receive many doses of several unreduced thimerosal-containing vaccines (TCVs). Thus, thimerosal has continued to be a part of the global vaccine supply and its acceptability as a component of vaccine formulations remained unchallenged until 2010, when the United Nations (UN), through the UN Environment Programme, began negotiations to write the global, legally binding Minamata Convention on Hg. During the negotiations, TCVs were dropped from the list of Hg-containing products to be regulated. Consequently, a double standard in vaccine safety, which previously existed due to ignorance and economic reasons, has now been institutionalised as global policy. Ultimately, the Minamata Convention on Hg has sanctioned the inequitable distribution of thimerosal by specifically exempting TCVs from regulation, condoning a two-tier standard of vaccine safety: a predominantly no-thimerosal and reduced-thimerosal standard for developed nations and a predominantly thimerosal-containing one for developing nations. This disparity must now be evaluated urgently as a potential form of institutionalised discrimination.

A prospective Cross-sectional Cohort Assessment of Health, Physical, and Behavioral Problems in Autism Spectrum Disorders.

OBJECTIVES: Autism spectrum disorder (ASD) is diagnostically defined by impaired socialization/communication and stereotypical behaviors. Health, physical, and behavioral problems have also been described in subjects diagnosed with an ASD, but have usually been examined in isolation. The purpose of the present study was to for the first time, systematically and quantitatively, examines health, physical and behavioral problems in a cohort of subjects diagnosed with an ASD. MATERIALS AND METHODS: A prospective cross-sectional ASD cohort (n=54) was evaluated for health, physical, and behavioral symptoms derived from parentally completed Autism Treatment Evaluation Checklist (ATEC) forms. The study protocol received Institutional Review Board (IRB) approval from Liberty IRB, Inc (Deland, FL). OUTCOMES: The results showed the following occurrence of symptoms among study participants: gastrointestinal disturbances=48%, incontinence=57%, sleep problems=57%, eating disorders=94%, hyperactivity=67%, lethargy=26%, sensory processing problems=85%, anxiety/fear=74%, behavioral problems=89%, and obsessive-compulsive behaviors=92%. Of all of the areas examined, eating problems, behavioral problems, and obsessive-compulsive behaviors, were reported by the parents to be the most serious and problematic. CONCLUSIONS: The present findings, taken together with previous research, suggest that subjects diagnosed with an ASD have significant health, physical, and behavioral problems beyond the symptoms evaluated in the diagnostic criteria used to diagnosis an ASD. The present findings also suggest the ATEC provides an economical means for healthcare providers to identify health, physical, and behavioral problems in subjects diagnosed with an ASD.

A significant relationship between mercury exposure from dental amalgams and urinary porphyrins: a further assessment of the Casa Pia children's dental amalgam trial.

Previous studies noted specific changes in urinary porphyrin excretion patterns associated with exposure to mercury (Hg) in animals and humans. In our study, urinary porphyrin concentrations were examined in normal children 8-18 years-old from a reanalysis of data provided from a randomized, prospective clinical trial that was designed to evaluate the potential health consequences of prolonged exposure to Hg from dental amalgam fillings (the parent study). Our analysis examined dose-dependent correlations between increasing Hg exposure from dental amalgams and urinary porphyrins utilizing statistical models with adjustments for the baseline level (i.e. study year 1) of the following variables: urinary Hg, each urinary porphyrin measure, gender, race, and the level of lead (Pb) in each subject's blood. Significant dose-dependent correlations between cumulative exposure to Hg from dental amalgams and urinary porphyrins associated with Hg body-burden (pentacarboxyporphyrin, precoproporphyrin, and coproporphyrin) were observed. Overall, 5-10% increases in Hg-associated porphyrins for subjects receiving an average number of dental amalgam fillings in comparison to subjects receiving only composite fillings were observed over the 8-year course of the study. In contrast, no significant correlations were observed between cumulative exposure to Hg from dental amalgams and urinary porphyrins not associated with Hg body-burden (uroporphyrin, heptacarboxyporphyrin, and hexacarboxyporphyrin). In conclusion, our study, in contrast to the no-effect results published from the parent study, further establishes the sensitivity and specificity of specific urinary porphyrins as a biomarker for low-level Hg body-burden, and also reveals that dental amalgams are a significant chronic contributor to Hg body-burden.

Thimerosal exposure in infants and neurodevelopmental disorders: an assessment of computerized medical records in the Vaccine Safety Datalink.

The study evaluated possible associations between neurodevelopmental disorders (NDs) and exposure to mercury (Hg) from Thimerosal-containing vaccines (TCVs) by examining the automated Vaccine Safety Datalink (VSD). A total of 278,624 subjects were identified in birth cohorts from 1990-1996 that had received their first oral polio vaccination by 3 months of age in the VSD. The birth cohort prevalence rate of medically diagnosed International Classification of Disease, 9th revision (ICD-9) specific NDs and control outcomes were calculated. Exposures to Hg from TCVs were calculated by birth cohort for specific exposure windows from birth-7 months and birth-13 months of age. Poisson regression analysis was used to model the association between the prevalence of outcomes and Hg doses from TCVs. Consistent significantly increased rate ratios were observed for autism, autism spectrum disorders, tics, attention deficit disorder, and emotional disturbances with Hg exposure from TCVs. By contrast, none of the control outcomes had significantly increased rate ratios with Hg exposure from TCVs. Routine childhood vaccination should be continued to help reduce the morbidity and mortality associated with infectious diseases, but efforts should be undertaken to remove Hg from vaccines. Additional studies should be conducted to further evaluate the relationship between Hg exposure and NDs.

Neurodevelopmental disorders, maternal Rh-negativity, and Rho(D) immune globulins: a multi-center assessment.

BACKGROUND: Many formulations of Thimerosal (49.55% mercury by weight)-containing Rho(D) immune globulins (TCRs) were routinely administered to Rh-negative mothers in the US prior to 2002. OBJECTIVES: It was hypothesized: (1) if prenatal Rho(D)-immune globulin preparation exposure was a risk factor for neurodevelopmental disorders (NDs) then more children with NDs would have Rh-negative mothers compared to controls; and (2) if Thimerosal in the Rho(D)-immune globulin preparations was the ingredient associated with NDs, following the removal of Thimerosal from all manufactured Rho(D)-immune globulin preparations from 2002 in the US the frequency of maternal Rh-negativity among children with NDs should be similar to control populations. METHODS: Maternal Rh-negativity was assessed at two sites (Clinic A-Lynchburg, VA; Clinic B-Rockville and Baltimore, MD) among 298 Caucasian children with NDs and known Rh-status. As controls, maternal Rh-negativity frequency was determined from 124 Caucasian children (born 1987-2001) without NDs at Clinic A, and the Rh-negativity frequency was determined from 1,021 Caucasian pregnant mothers that presented for prenatal genetic care at Clinic B (1980-1989). Additionally, 22 Caucasian patients with NDs born from 2002 onwards (Clinics A and B) were assessed for maternal Rh-negativity. RESULTS: There were significant and comparable increases in maternal Rh-negativity among children with NDs (Clinic: A=24.2%), autism spectrum disorders (Clinic: A=28.3%, B=25.3%), and attention-deficit-disorder/attention-deficit-hyperactivity-disorder (Clinic: A=26.3%) observed at both clinics in comparison to both control groups (Clinic: A=12.1%, B=13.9%) employed. Children with NDs born post-2001 had a maternal Rh-negativity frequency (13.6%) similar to controls. CONCLUSION: This study associates TCR exposure with some NDs in children.

A prospective assessment of androgen levels in patients with autistic spectrum disorders: biochemical underpinnings and suggested therapies.

Impairments in social relatedness and communication, repetitive behaviors, abnormal movement patterns, and sensory dysfunction characterize autism spectrum disorders (ASDs). Seventy consecutive patients with an ASD diagnosis (DSM-IV criteria, >/= 6 years-old) who presented to the Genetic Centers of America for outpatient genetic/developmental evaluations from 2005-2007 were examined. Patients were evaluated using CLIA-approved Laboratory Cooperation of America (LabCorp) testing for: serum testosterone, serum free testosterone, % free testosterone, serum/plasma dehydroepiandrosterone (DHEA), androstendione, and follicle-stimulating hormone (FSH). Morning blood samples collected following an overnight fast, compared to the pertinent reference means, showed significantly increased relative mean levels for: serum testosterone (158%), serum free testosterone (214%), percent free testosterone (121%), DHEA (192%), and androstenedione (173%). By contrast, compared to the pertinent reference mean, the relative mean level of FSH (51%) was significantly decreased. Additionally, at least one of the androgen attributes examined exceeded its recognized laboratory age- and sex-specific reference range in 81.4% (57 of 70) of the patients examined. With respect to their age- and sex-specific reference ranges, females had significantly higher overall mean relative testosterone and relative free testosterone levels than males. Increased androgens in patients diagnosed with ASDs may involve cyclical interactions between the androgen and the transsulfuration pathways, particularly following mercury exposure. A review of therapies that have significantly improved clinical outcomes in ASD patients indicates they share commonality in helping lower androgens. Thus, androgens should be routinely clinically measured in patients with an ASD diagnosis and appropriate androgen-lowering therapies considered for those who have significantly elevated levels.

A prospective assessment of porphyrins in autistic disorders: a potential marker for heavy metal exposure.

Autism was recently associated with a urinary porphyrin pattern indicative of mercury toxicity in a large cohort of French children. The IRB of the Institute for Chronic Illnesses approved the present study. A total of 37 consecutive American patients (> or = 7 years-old) with autism spectrum disorders (ASDs) (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-DSM IV), born from 1983-1998, that presented to the Genetic Centers of America for outpatient genetic evaluations were prospectively examined for urinary prophryin levels (LabCorp, Inc.) from June 2005-June 2006. Imaging and laboratory testing were conducted on each patient to rule-out other causal factors for their ASDs. As controls, age-, sex-, and race-matched neurotypical ASD siblings were examined. An apparent dose-response effect was observed between autism severity and increased urinary coproporphyrins. Patients with non-chelated autism (2.25-fold, 83% had levels > 2 SD above the control mean) and non-chelated ASDs (2-fold, 58% had levels > 2 SD above the control mean), but not patients with non-chelated pervasive developmental delay-not otherwise specified (PDD-NOS) or Asperger's disorder (1.4-fold, 46% had levels > 2 SD above the control mean), had significantly increased median coproporphyrin levels versus controls. A significant increase (1.7-fold) in median coproporphyrin levels was observed among non-chelated ASD patients versus chelated ASD patients. Porphyrins should be routinely clinically measured in ASDs, and potential ASD treatments should consider monitoring porphyrin levels. Additional research should be conducted to evaluate the potential role for mercury exposure in some ASDs.

A meta-analysis epidemiological assessment of neurodevelopmental disorders following vaccines administered from 1994 through 2000 in the United States.

BACKGROUND: Thimerosal is an ethylmercury-containing compound (49.6% mercury by weight) used as at the preservative level in vaccines (0.005% to 0.01%). METHODS: Statistical modeling in a meta-analysis epidemiological assessment of the Vaccine Adverse Event Reporting System (VAERS) for neurodevelopment disorders (NDs) reported following Diphtheria-Tetanus-whole-cell-Pertussis (DTP) vaccines in comparison to Diphtheria-Tetanus-whole-cell-Pertussis-Haemophilus Influenzae Type b (DTPH) vaccines (administered: 1994-1997) and following Thimerosal-containing Diphtheria-Tetanus-acellular-Pertussis (DTaP), vaccines in comparison to Thimerosal-free DTaP vaccines (administered: 1997-2000), was undertaken. RESULTS: Significantly increased adjusted (sex, age, vaccine type, vaccine manufacturer) risks of autism, speech disorders, mental retardation, personality disorders, thinking abnormalities, ataxia, and NDs in general, with minimal systematic error or confounding, were associated with TCV exposure. CONCLUSION: It is clear from the results of the present epidemiological study and other recently published data associating mercury exposure with childhood NDs, additional ND research should be undertaken in the context of evaluating mercury-associated exposures, especially from Thimerosal-containing vaccines.

An assessment of downward trends in neurodevelopmental disorders in the United States following removal of Thimerosal from childhood vaccines.

BACKGROUND: The US is in the midst of an epidemic of neurodevelopmental disorders (NDs). Thimerosal is an ethylmercury-containing compound added to some childhood vaccines. Several previous epidemiological studies conducted in the US have associated Thimerosal-containing vaccine (TCV) administration with NDs. MATERIAL/METHODS: An ecological study was undertaken to evaluate NDs reported to the Vaccine Adverse Event Reporting System (VAERS) from 1991 through 2004 by date of receipt and by date of vaccine administration. The NDs examined included autism, mental retardation, and speech disorders. Statistical trend analysis was employed to evaluate the effects of removal of Thimerosal on the proportion of NDs reported to VAERS. RESULTS: There was a peak in the proportion of ND reports received by VAERS in 2001-2002 and in the proportion of ND reports by date of vaccine administration in 1998. There were significant reductions in the proportion of NDs reported to VAERS as Thimerosal was begun to be removed from childhood vaccines in the US from mid-1999 onwards. CONCLUSIONS: The present study provides the first epidemiological evidence showing that as Thimerosal was removed from childhood vaccines, the number of NDs has decreased in the US. The analysis techniques utilized attempted to minimize chance or bias/confounding. Additional research should be conducted to further evaluate the relationship between TCVs and NDs. This is especially true because the handling of vaccine safety data from the National Immunization Program of the CDC has been called into question by the Institute of Medicine of the National Academy of Sciences in 2005.

An assessment of the impact of thimerosal on childhood neurodevelopmental disorders.

The prevalence of autism in the US has risen from 1 in approximately 2500 in the mid-1980s to 1 in approximately 300 children in the mid-1990s. The purpose of this study was to evaluate whether mercury from thimerosal in childhood vaccines contributed to neurodevelopmental disorders. Neurodevelopmental disorder dose-response curves for increasing mercury doses of thimerosal in childhood vaccines were determined based upon examination of the Vaccine Adverse Events Reporting System (VAERS) database and the 2001 US' Department of Education Report. The instantaneous dosage of mercury children received in comparison to the Food and Drug Administration (FDA)'s maximum permissible dose for the oral ingestion of methylmercury was also determined. The dose-response curves showed increases in odds ratios of neurodevelopmental disorders from both the VAERS and US Department of Education data closely linearly correlated with increasing doses of mercury from thimerosal-containing childhood vaccines and that for overall odds ratios statistical significance was achieved. Similar slopes and linear regression coefficients for autism odds ratios in VAERS and the US Department of Education data help to mutually validate each other. Controls employed in the VAERS and US Department of Education data showed minimal biases. The evidence presented here shows that the occurrence of neurodevelopmental disorders following thimerosal-containing childhood vaccines does not appear to be coincidental.