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 PDD. 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 (VSD) database who were Health Maintenance Organization (HMO)-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 (APGAR) scores at 1 minute (PDD=7.82 vs CP=6.37 or MR=6.76) and 5 minutes (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

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

AbstractEpidemiological 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

Immune dysfunction and neuroinflammation in autism spectrum disorder

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 frequently present in those with ASD. It was found 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, a significant portion of individuals diagnosed with ASD have elevated peripheral cytokines and chemokines and associated neuroinflammation. In conclusion, immune dysregulation and inflammation are important components in the diagnosis and treatment of ASD

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

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

The risk of neurodevelopmental disorders following a thimerosal-preserved DTaP formulation in comparison to its thimerosal-reduced formulation in the vaccine adverse event reporting system

Abstract: Mercury (Hg) exposure in human infants and fetuses has long been known to be significantly associated with neurodevelopmental disorders (NDs). Thimerosal (49.55% Hg by weight) is an ethyl-Hg containing compound added to many childhood vaccines as a preservative. A hypothesis testing case-control study was undertaken in the Vaccine Adverse Event Reporting System (VAERS) database (updated through September 2013) by examining 5,591 adverse event reports entered following Thimerosal-preserved Diphtheria-Tetanus-acellular-Pertussis (DTaP) (Tripedia TM , Sanofi) administered from 1997-1999 (exposed) and following Thimerosal-reduced DTaP (Tripedia TM , Sanofi) administered from 2004-2006 (unexposed). Cases were defined as individuals with adverse event reports with the outcomes of autism, speech disorder, mental retardation, or ND (at least of one these aforementioned specific outcomes being mentioned in the adverse event report). Controls were defined as individuals with adverse event reports without any mention of the specific case outcomes examined. Cases reported with the outcomes of autism (odds ratio = 7.67, p &lt; 0.0001), speech disorders (odds ratio = 3.49, p &lt; 0.02), mental retardation (odds ratio = 8.73, p &lt; 0.0005), or ND (odds ratio = 4.82, p &lt; 0.0001) were significantly more likely than controls to have received Thimerosalpreserved DTaP vaccine (exposed) in comparison to Thimerosal-reduced DTaP vaccine (unexposed). Though routine childhood vaccination is considered an important public health tool to reduce the morbidity and mortality associated with certain infectious diseases, this study supports a significant relationship between increased organic-Hg exposure from Thimerosal-preserved childhood vaccines and the child&apos;s subsequent risk of a ND diagnosis