Publications by authors named "Janet K Kern"

83 Publications

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

J Trace Elem Med Biol 2020 Dec 19;62:126504. Epub 2020 May 19.

Institute of Chronic Illnesses, Inc., Silver Spring, MD, USA; CoMeD, Inc., Silver Spring, MD, USA.

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.
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http://dx.doi.org/10.1016/j.jtemb.2020.126504DOI Listing
December 2020

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

Acta Neurobiol Exp (Wars) 2020 ;80(1):66-75

Institute of Chronic Illnesses, Inc, Silver Spring, MD, USA.

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. This study provides important new evidence supporting the hypothesis that a significant number of children with an eventual ASD diagnosis experience a progressive childhood en cephalopathy diagnosed at >1 year‑old.
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December 2020

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

Environ Toxicol Pharmacol 2020 Feb 9;74:103312. Epub 2019 Dec 9.

Institute of Chronic Illnesses, Inc, Silver Spring, MD, USA; CoMeD, Inc, Silver Spring, MD, USA.

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 (CHHg)-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.
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http://dx.doi.org/10.1016/j.etap.2019.103312DOI Listing
February 2020

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

Dev Neurobiol 2019 09 4;79(9-10):857-867. Epub 2019 Dec 4.

Institute of Chronic Illnesses, Inc., Silver Spring, MD, USA.

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.
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http://dx.doi.org/10.1002/dneu.22726DOI Listing
September 2019

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

J Alzheimers Dis 2019 ;72(3):901-910

Institute of Chronic Illnesses, Inc., Silver Spring, MD, USA.

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.
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http://dx.doi.org/10.3233/JAD-190894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918911PMC
November 2020

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

BMC Pediatr 2019 09 10;19(1):325. Epub 2019 Sep 10.

Institute of Chronic Illnesses, Inc, 14 Redgate Ct, Silver Spring, MD, 20905, USA.

Background: Measles (rubeola) is a highly contagious disease with significant morbidity/mortality. Measles-Mumps-Rubella (MMR) is a live-attenuated vaccine used in the United States (US) since the early 1970s to prevent measles infection. This retrospective longitudinal cohort study examined childhood MMR vaccination effectiveness (VE) on preventing diagnosed measles cases.

Methods: The Independent Healthcare Research Database (IHRD) is composed of non-identifiable linked eligibility and claim healthcare records prospectively generated from the Florida Medicaid system. The SAS system was utilized to examine a cohort of 101,736 persons eligible for Florida Medicaid from 1990 to 2009 and continuously eligible with ≥10 outpatient office visits during the 120-month period following birth. There were 32,870 persons (224,492 person-years) in the cohort receiving a single dose of childhood MMR vaccine (vaccinated) and 43,538 persons (434,637 person-years) in an unvaccinated cohort (no exposures to measles-containing vaccine). The frequency of diagnosed measles (ICD-9 code: 055xxx) was examined. Cox proportional hazards models evaluated MMR vaccination and diagnosed measles over time.

Results: MMR vaccinated cohort members were at significantly reduced risk of measles in the unadjusted (VE = 83.6, 95% CI = 67.2-91.8%) and adjusted (VE = 80.7, 95% CI = 61.5-83.9%) models as compared to the unvaccinated cohort. VE = 80% among younger MMR recipients (12-15 months), whereas VE = 90% among older MMR recipients (16-20 months) as compared to the unvaccinated cohort.

Conclusion: Routine childhood MMR vaccination significantly reduced the incidence rate of childhood measles infections, and the VE was greater in the older recipients (16-20 months) than in the younger recipients (12-15 months).
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http://dx.doi.org/10.1186/s12887-019-1710-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734418PMC
September 2019

A critique that misses the mark.

Int J Hyg Environ Health 2019 03;222(2):309-310

The Institute of Chronic Illnesses, Inc, Silver Spring, MD, USA; CoMeD, Inc, Silver Spring, MD, USA.

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http://dx.doi.org/10.1016/j.ijheh.2018.11.006DOI Listing
March 2019

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

SAGE Open Med 2019 8;7:2050312118822650. Epub 2019 Jan 8.

Institute of Chronic Illnesses, Inc., Silver Spring, MD, USA.

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.
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http://dx.doi.org/10.1177/2050312118822650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329017PMC
January 2019

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

Toxics 2018 Nov 15;6(4). Epub 2018 Nov 15.

Institute of Chronic Illnesses, Inc., 14 Redgate Court, Silver Spring, MD 20905, USA.

Studies suggest a relationship between exposure to endocrine disrupters, such as mercury (Hg), and premature puberty. Hg exposure from Thimerosal-containing hepatitis B vaccine, administered at specific intervals within the first six months of life, and the child's long-term risk of being diagnosed with premature puberty (ICD-9 code: 259.1), was retrospectively examined, using a hypothesis-testing, longitudinal case-control design on prospectively collected data, in the Vaccine Safety Datalink (VSD). Cases diagnosed with premature puberty were significantly more likely to have received increased exposure to Hg from hepatitis B vaccines preserved with Thimerosal given in the first month after birth (odds ratio (OR) = 1.803), first two months after birth (OR = 1.768), and first six months after birth (OR = 2.0955), compared to control subjects. When the data were separated by gender, the effects remained among females but not males. Female cases, as compared to female controls, were significantly more likely in a dose-dependent manner to have received a greater exposure to Hg from hepatitis B vaccines preserved with Thimerosal, given in the first six months after birth (OR = 1.0281 per µg Hg). The results of this study show a dose-dependent association between increasing organic Hg exposure from Thimerosal-containing hepatitis B vaccines administered within the first six months of life and the long-term risk of the child being diagnosed with premature puberty.
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http://dx.doi.org/10.3390/toxics6040067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316152PMC
November 2018

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

Infect Ecol Epidemiol 2018 16;8(1):1474708. Epub 2018 May 16.

Research Department, The Institute of Chronic Illnesses, Inc, Silver Spring, MD, USA.

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. 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/m), mean daily maximum air temperature (C), mean daily minimum air temperature (C), 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. 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. This study highlights key factors that can help shape public health policy to deal with seasonal influenza in the United States and beyond.
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http://dx.doi.org/10.1080/20008686.2018.1474708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5965040PMC
May 2018

Cerebral hypoperfusion in autism spectrum disorder.

Acta Neurobiol Exp (Wars) 2018 ;78(1):21-29

Faculty of Public Health, Inland Norway University of Applied Sciences, Elverum, Norway; Department of Research, Innlandet Hospital Trust, Brumunddal, Norway.

Cerebral hypoperfusion, or insufficient blood flow in the brain, occurs in many areas of the brain in patients diagnosed with autism spectrum disorder (ASD). Hypoperfusion was demonstrated in the brains of individuals with ASD when compared to normal healthy control brains either using positron emission tomography (PET) or single‑photon emission computed tomography (SPECT). The affected areas include, but are not limited to the: prefrontal, frontal, temporal, occipital, and parietal cortices; thalami; basal ganglia; cingulate cortex; caudate nucleus; the limbic system including the hippocampal area; putamen; substantia nigra; cerebellum; and associative cortices. Moreover, correlations between symptom scores and hypoperfusion in the brains of individuals diagnosed with an ASD were found indicating that the greater the autism symptom pathology, the more significant the cerebral hypoperfusion or vascular pathology in the brain. Evidence suggests that brain inflammation and vascular inflammation may explain a part of the hypoperfusion. There is also evidence of a lack of normal compensatory increase in blood flow when the subjects are challenged with a task. Some studies propose treatments that can address the hypoperfusion found among individuals diagnosed with an ASD, bringing symptom relief to some extent. This review will explore the evidence that indicates cerebral hypoperfusion in ASD, as well as the possible etiological aspects, complications, and treatments.
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September 2018

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

Int J Hyg Environ Health 2018 05 14;221(4):677-683. Epub 2018 Mar 14.

The Institute of Chronic Illnesses, Inc, Silver Spring, MD, USA.

Investigators postulated that early-life exposure to organic mercury (Hg) significantly increases the risk of childhood neurodevelopmental disorders (NDs). The Vaccine Adverse Event Reporting System database was utilized to conduct a hypothesis testing case-control study by evaluating 3486 total adverse event reports reported following Haemophilus influenza type b (Hib) vaccination. Exposed subjects received a Thimerosal-containing formulation (HIBTITER™, Wyeth-Lederle), while unexposed subjects received a Thimerosal-free formulation (PEDVAXHIB™, Merck). Subjects were included if they received either of these two Hib vaccine formulations between 1995 and 1999. Cases were defined as adverse event reports with a reported outcome of autism, developmental delay, psychomotor delay, or NDs in general. Cases with reported outcomes of febrile convulsions, pyrexia, or injection site pain, all of which have no biologically plausible relation to Hg exposure, were also examined. Controls were defined as adverse event reports without any mention of the specific case outcome examined. Cases of reported autism (odds ratio (OR) = 2.75, p < 0.02), developmental delay (OR = 5.39, p < 0.01), psychomotor disorder (OR = 2.38, p < 0.03), and neurodevelopmental disorder in general (OR = 2.70, p < 0.001) were each significantly more likely than their respective controls to receive Thimerosal-containing Hib vaccine than Thimerosal-free Hib vaccine. Significant effects for neurodevelopmental disorder in general were observed for males (OR = 2.52, p < 0.005), but not females when separated by gender. For the outcomes that had no biologically plausible relation to Hg exposure, the cases were no more likely than their respective controls to receive Thimerosal-containing Hib vaccine than Thimerosal-free Hib vaccine. This study provides suggestive evidence of an association between Thimerosal and neurodevelopmental outcomes and provides support for carrying out additional well-designed studies examining the association between Thimerosal-containing vaccines and a wide range of neurodevelopmental outcomes.
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http://dx.doi.org/10.1016/j.ijheh.2018.03.004DOI Listing
May 2018

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

Metab Brain Dis 2018 06 6;33(3):949-960. Epub 2018 Mar 6.

The Institute of Chronic Illnesses, Inc, 14 Redgate Ct, Silver Spring, MD, USA.

Nelson and Bauman (Pediatrics 111:674-679, 2003) previously hypothesized that pervasive developmental disorder (PDD) was not associated with mercury (Hg) exposure because the medical conditions associated with Hg exposure were not associated with PDD. A hypothesis-testing longitudinal case-control study evaluated the frequency of medically diagnosed conditions previously associated with Hg poisoning, including: epilepsy, dysarthria, failure to thrive, cerebral palsy, or contact dermatitis and other eczema among children preceding their eventual PDD diagnosis (cases) compared to controls. A retrospective examination of medical records within the Vaccine Safety Datalink (VSD) was undertaken. Cases diagnosed with PDD (n = 534) were born from 1991 to 2000 and continuously enrolled until their PDD diagnosis. Controls (n = 26,367) were born from 1991 to 1993 and continuously enrolled from birth for 7.22 years. Within the first 5 years of life, cases compared to controls were significantly (p < 0.0001) more likely to be assigned a diagnosis of contact dermatitis and other eczema (odds ratio (OR) = 2.033), dysarthria (OR = 23.992), epilepsy (OR = 5.351), failure to thrive (OR = 25.3), and cerebral palsy (OR = 4.464). Similar results were observed when the data were separated by gender. Overall, the results of the present study and recently published studies provide direct evidence supporting a link in twelve of twelve categories (100%) of Hg poisoning associated symptoms as defined by Nelson and Bauman (Pediatrics 111:674-679, 2003) and symptoms observed in those with a PDD diagnosis. The results of this study support the biological plausibility of Hg poisoning to induce PDD diagnoses and rejection of the Nelson and Bauman (Pediatrics 111:674-679, 2003) hypothesis because those with a PDD diagnosis have an increased frequency of conditions previously associated with Hg poisoning.
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http://dx.doi.org/10.1007/s11011-018-0211-9DOI Listing
June 2018

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

J Trace Elem Med Biol 2018 Mar 8;46:1-9. Epub 2017 Nov 8.

Institute of Chronic Illnesses, Inc, Silver Spring, MD, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jtemb.2017.11.001DOI Listing
March 2018

Developmental neurotoxicants and the vulnerable male brain: a systematic review of suspected neurotoxicants that disproportionally affect males.

Acta Neurobiol Exp (Wars) 2017 ;77(4):269-296

Institute of Chronic Illnesses, Inc., Silver Spring, MD, USA; CoMeD, Inc., Silver Spring, MD, USA; CoMeD, Inc., Silver Spring, MD, USA.

The prevalence of neurodevelopmental disorders (NDs), including autism spectrum disorder, attention‑deficit/hyperactivity disorder, tic disorder, obsessive‑compulsive disorder, and emotional disturbances, has increased notably in the past few decades. To date, debate continues as to the origins of NDs. Increases in widespread exposure to and bioaccumulation of chemical neurotoxicants have paralleled the upsurge in NDs, and are suggested to be causal agents for NDs. One consistent aspect of NDs is the male preponderance. This review considers the issue of male preponderance by reviewing the gender‑specific neurotoxic effects of recognized neurotoxicant chemicals to assess their possible etiology in NDs. This investigation consisted of a systematic literature review of original studies published from 1970-2016 on suspected neurotoxicants, to examine whether they have a disproportionate adverse effect based on gender. Based on that review, the neurotoxicants exhibiting consistent gender‑specific effects, with exposed males being more affected (than similarly exposed females), were: lead, Thimerosal/ethylmercury, some organochlorine pesticides (e.g., dieldrin, endosulfan, and heptachlor), and air pollution. The next group identified were neurotoxicants exhibiting gender‑specific neurotoxic effects, with males being somewhat (but not consistently) more affected than females: mercury vapor, polychlorinated biphenyls (PCBs), and organophosphate pesticides. Finally, there was a group of studies in which the neurotoxicants exhibited apparent gender‑related neurotoxic effects but failed to show whether exposed males were consistently more affected than females: inorganic mercury salts, methylmercury species, and certain endocrine disruptors (e.g., phthalates and BPA). The overall conclusion from the studies reviewed was that the brain in males is more vulnerable to many toxic exposures than it is in females. Evidence suggests that the reasons for the male brain being more vulnerable include: (1) greater glutathione availability in females; (2) greater sulfate‑based detoxification capacity in females; (3) potentiating effects of co‑exposure to neurotoxicants and testosterone; (4) greater neuroinflammatory response in males; (5) reduced vulnerability to oxidative stress in females; and (6) neuroprotective effects of female hormones (estrogen and progesterone), especially in the reduction of inflammation and oxidative stress.
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August 2018

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

Int J Environ Res Public Health 2018 01 12;15(1). Epub 2018 Jan 12.

Institute of Chronic Illnesses, Inc., Silver Spring, MD 20905, USA.

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 = 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 = 11,186,579), in comparison to an unexposed population (weighted = 704,254), were at an increased risk of receipt of SES. This association was robust (crude odds ratio = 10.143, = 0.0232), even when considering covariates, such as race and socioeconomic status (adjusted odds ratio = 9.234, = 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, = 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.
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http://dx.doi.org/10.3390/ijerph15010123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800222PMC
January 2018

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.

Metab Brain Dis 2018 02 13;33(1):201-208. Epub 2017 Nov 13.

Institute of Chronic Illnesses, Inc, 14 Redgate Ct, Silver Spring, MD, 20905, USA.

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.
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http://dx.doi.org/10.1007/s11011-017-0146-6DOI Listing
February 2018

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

Sci Eng Ethics 2017 12;23(6):1691-1718

Institute of Chronic Illnesses, Inc, 14 Redgate Court, Silver Spring, MD, 20905, USA.

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.
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http://dx.doi.org/10.1007/s11948-017-9983-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705731PMC
December 2017

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

J Matern Fetal Neonatal Med 2019 Mar 29;32(5):833-837. Epub 2017 Oct 29.

a The Institute of Chronic Illnesses Inc , Silver Spring , MD , USA.

Objective: Asthma is the most common chronic condition diagnosed among children worldwide according to the World Health Organization (WHO). This study evaluated on a longitudinal basis prospectively collected medical records for demographic and neonatal information among United States (US) children diagnosed with childhood asthma in comparison to controls.

Design: The Vaccine Safety Datalink (VSD) database was examined to identify cases (n = 5907) diagnosed with International Classification of Disease, ninth revision (ICD-9) healthcare provider diagnosed childhood asthma (493.xx) and controls (n = 11,662).

Patients: All cases and controls were health maintenance organization (HMO)-enrolled from birth until diagnosis or sufficient time to ensure that they were unlikely to receive a diagnosis, respectively.

Main Outcome Measures: Child's gestational age in weeks at birth, birth weight in grams, maternal age in years at birth, Appearance-Pulse-Grimace-Activity-Respiration (APGAR) score at 1 minute and 5 minutes following birth, gender, and race.

Results: The study results revealed childhood asthma was diagnosed significantly more frequently among males than females, and significantly more frequently among minority populations (Black > Hispanic > Native American > Asian) than White populations. Cases diagnosed with childhood asthma had significantly decreased mean values for the following neonatal risk factors: gestational age, maternal age, birth weight, and APGAR scores at 1 and 5 minutes following birth in comparison to controls.

Conclusions: This study offers healthcare providers important demographic and neonatal factors significantly associated with childhood asthma, and should help aid in the early diagnosis and treatment of childhood asthma.
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http://dx.doi.org/10.1080/14767058.2017.1393068DOI Listing
March 2019

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

Int J Environ Res Public Health 2017 10 10;14(10). Epub 2017 Oct 10.

Institute of Chronic Illnesses, Inc., 14 Redgate Ct, Silver Spring, MD 20905, USA.

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.
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http://dx.doi.org/10.3390/ijerph14101202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664703PMC
October 2017

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

J Trace Elem Med Biol 2017 Jul 9;42:18-24. Epub 2017 Mar 9.

The Institute of Chronic Illnesses, Inc, Silver Spring, MD, 20905, United States; CoMeD, Inc, Silver Spring, MD, 20905, United States. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jtemb.2017.03.005DOI Listing
July 2017

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

Dose Response 2017 Jan-Mar;15(1):1559325817690849. Epub 2017 Mar 16.

Department of Research, The Institute of Chronic Illnesses, Inc, Silver Spring, MD, USA.

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 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 ( < .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.
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http://dx.doi.org/10.1177/1559325817690849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433557PMC
March 2017

A longitudinal ecological study of household firearm ownership and firearm-related deaths in the United States from 1999 through 2014: A specific focus on gender, race, and geographic variables.

Prev Med Rep 2017 Jun 12;6:329-335. Epub 2017 Apr 12.

The Institute of Chronic Illnesses, Inc., 14 Redgate Ct, Silver Spring, MD 20905, USA.

Firearms have a longstanding tradition in the United States (US) and are viewed by many with iconic stature with regards to safety and personal freedom. Unfortunately, from a public health point of view, firearm-related deaths (FRDs) in the US have reached a crisis point with an estimated > 31,000 deaths and 74,000 nonfatal injuries resulting from firearms each year. This longitudinal ecological study analyzed variations in FRDs following firearm assaults (FAs) and law enforcement incidents involving a firearm (LEIF) in comparison to variations in household firearm ownership (HFO) among different geographic and demographic groups in the US from 1999 to 2014. The Underlying Cause of Death database was examined on the CDC Wonder online interface. Records coded with ICD-10 codes: FA (X93 - assault by handgun discharge, X94 - assault by rifle, shotgun, and larger firearm discharge, or X95 - assault by other and unspecified firearm discharge) and LEIF (Y35.0) were examined, and the prevalence of HFO was determined using the well-established proxy of the percentage of suicides committed with a firearm. Gender, ethnicity, Census Division, and urbanization significantly impacted the death rates from FA and LEIF. Significant direct correlations between variations in HFO and death rates from FAs and LEIF were observed. Understanding the significant impacts of gender, race, Census Division, and urbanization status may help shape future public health policy to promote increased firearm safety.
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http://dx.doi.org/10.1016/j.pmedr.2017.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403795PMC
June 2017

Histone deacetylase inhibitors, Thimerosal, and autism spectrum disorder.

Environ Res 2017 07 11;156:843-844. Epub 2017 Apr 11.

The Institute of Chronic Illnesses, Inc, Silver Spring, MD, USA; CoMeD, Inc, Silver Spring, MD, USA.

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http://dx.doi.org/10.1016/j.envres.2017.04.007DOI Listing
July 2017

Thimerosal exposure and disturbance of emotions specific to childhood and adolescence: A case-control study in the Vaccine Safety Datalink (VSD) database.

Brain Inj 2017 19;31(2):272-278. Epub 2017 Jan 19.

a The Institute of Chronic Illnesses, Inc, Silver Spring , MD , USA.

Background: 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.

Methods: 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.

Results: 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).

Conclusions: The results show a significant relationship between Hg exposure from Thimerosal-containing childhood vaccines and the subsequent risk of an ED diagnosis.
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http://dx.doi.org/10.1080/02699052.2016.1250950DOI Listing
January 2018

Immune dysfunction and neuroinflammation in autism spectrum disorder.

Acta Neurobiol Exp (Wars) 2016 ;76(4):257-268

Departamento de Zoología, Facultad de Ciencias Naturales y Oceanográficas, Universidad de Concepción, Concepción, Chile.

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.
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http://dx.doi.org/10.21307/ane-2017-025DOI Listing
February 2017

A Two-Phase Case-Control Study of Autism Risk Among Children Born From the Late 1990s Through the Early 2000s in the United States.

Med Sci Monit 2016 Dec 29;22:5196-5202. Epub 2016 Dec 29.

Department of Research, Institute of Chronic Illnesses, Inc., Silver Spring, MD, USA.

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.
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http://dx.doi.org/10.12659/msm.900257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5218387PMC
December 2016

Concerns about environmental mercury toxicity: do we forget something else?

Environ Res 2017 01 8;152:514-516. Epub 2016 Sep 8.

Institute of Chronic Illnesses, Inc, and CoMeD, Silver Spring, MD, USA; CONEM US Autism Research Group, Allen, TX, USA.

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http://dx.doi.org/10.1016/j.envres.2016.08.038DOI Listing
January 2017

Thimerosal-containing Hepatitis B Vaccine Exposure is Highly Associated with Childhood Obesity: A Case-control Study Using the Vaccine Safety Datalink.

N Am J Med Sci 2016 Jul;8(7):297-306

Department of Research, Institute of Chronic Illnesses Inc., MD, USA; Department of Research, CoMeD, Inc., Silver Spring, MD, USA.

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.
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http://dx.doi.org/10.4103/1947-2714.187148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982359PMC
July 2016

Examining genotypic variation in autism spectrum disorder and its relationship to parental age and phenotype.

Appl Clin Genet 2016 28;9:121-9. Epub 2016 Jul 28.

Research Department, The Institute of Chronic Illnesses, Inc; Research Department, CoMeD, Inc, Silver Spring, MD.

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.
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http://dx.doi.org/10.2147/TACG.S112712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4968978PMC
August 2016