Citaat:
Measles, mumps and rubella (MMR) vaccination has no effect on cognitive development in children - The results of the Polish prospective cohort study
Author(s): Mrozek-Budzyn, D (Mrozek-Budzyn, Dorota)[ 1 ] ; Kieltyka, A (Kieltyka, Agnieszka)[ 1 ] ; Majewska, R (Majewska, Renata)[ 1 ] ; Augustyniak, M (Augustyniak, Malgorzata)[ 1 ]
Source: VACCINE Volume: 31 Issue: 22 Pages: 2551-2557 DOI: 10.1016/j.vaccine.2013.03.057 Published: MAY 24 2013
Abstract: Objectives: The aim of the study was to examine the hypothesis that MMR exposure has a negative influence on cognitive development in children. Furthermore, MMR was compared to single measles vaccine to determine the potential difference of these vaccines safety regarding children's cognitive development.
Methods: The prospective birth cohort study with sample consisted of 369 infants born in Krakow. Vaccination history against measles (date and the type of the vaccine) was extracted from physicians' records. Child development was assessed using the Bayley Scales of Infant Development (BSID-II) up to 3rd year of life, Raven test in 5th and 8th year and Wechsler (WISC-R) in 6th and 7th year. Data on possible confounders came from mothers' interview, medical records and analyses of lead and mercury level at birth and at the end of 5th year of life. Linear and logistic regression models adjusted for potential confounders were used to assess the association.
Results: No significant differences in cognitive and intelligence tests results were observed between children vaccinated with MMR and those not vaccinated up to the end of the 2nd year of life. Children vaccinated with MMR had significantly higher Mental BSID-II Index (MDI) in the 36th month than those vaccinated with single measles vaccine (103.8 +/- 10.3 vs. 97.2 +/- 11.2, p = 0.004). Neither results of Raven test nor WISC-R were significantly different between groups of children vaccinated with MMR and with single measles vaccine. After standardization to child's gender, maternal education, family economical status, maternal IQ, birth order and passive smoking all developmental tests were statistically insignificant.
Conclusion: The results suggest that there is no relationship between MMR exposure and children's cognitive development. Furthermore, the safety of triple MMR is the same as the single measles vaccine with respect to cognitive development. (C) 2013 Elsevier Ltd. All rights reserved.
Response to Measles-Mumps-Rubella Vaccine in Children with Autism Spectrum Disorders
Author(s): Gentile, I (Gentile, Ivan)[ 1 ] ; Bravaccio, C (Bravaccio, Carmela)[ 3 ] ; Bonavolta, R (Bonavolta, Raffaele)[ 3 ] ; Zappulo, E (Zappulo, Emanuela)[ 1 ] ; Scarica, S (Scarica, Sabrina)[ 1 ] ; Riccio, MP (Riccio, Maria Pia)[ 4 ] ; Settimi, A (Settimi, Alessandro)[ 3 ] ; Portella, G (Portella, Giuseppe)[ 3 ] ; Pascotto, A (Pascotto, Antonio)[ 4 ] ; Borgia, G (Borgia, Guglielmo)[ 1 ]
Source: IN VIVO Volume: 27 Issue: 3 Pages: 377-382 Published: MAY-JUN 2013
Abstract: Background/Aim: The etiology of autism spectrum disorders (ASD) is unknown. The measles-mumps-rubella (MMR) vaccination has been in the past implicated in ASD pathogenesis. The aim of our study was to evaluate the rate of seropositivity and the levels of antibodies against MMR antigens in a cohort of children with ASD compared to control children. Patients and Methods: In a cohort of children with ASD and same-age healthy controls, we measured levels and seropositivity of antibodies against MMR. Results: A total of 60 children, 31 with ASD and 29 controls were enrolled. The seropositivity rate and levels of all the three antibodies were similar in cases and controls. Conclusion: Children with ASD have a similar level and seropositivity rate of antibodies against the MMR vaccine to same-age controls. As persistent infections are typically associated with high antibody levels, our results support the arguments against a role of MMR vaccination as a causal factor or co-factor in development of ASD.
Study finds no association between autism and vaccination
Author(s): Roehr, B (Roehr, Bob)
Source: BRITISH MEDICAL JOURNAL Volume: 346 Article Number: f2095 DOI: 10.1136/bmj.f2095 Published: APR 3 2013
Geen abstract helaas.
The combined measles, mumps, and rubella vaccines and the total number of vaccines are not associated with development of autism spectrum disorder: The first case-control study in Asia
Abstract: Objective: The aim of this study was to investigate the relationship between autism spectrum disorder (ASD) and general vaccinations, including measles-mumps-rubella (MMR) vaccine, in Japanese subjects, a population with high genetic homogeneity.
Patients and methods: A case-control study was performed. Cases (n = 189) were diagnosed with ASD, while controls (n=224) were volunteers from general schools, matched by sex and birth year to cases. Vaccination history and prenatal, perinatal, and neonatal factors from the Maternal and Child Health handbook, which was part of each subject's file, were examined. To determine the relationship between potential risk factors and ASD, crude odds ratios (ORS) and 95% confidence intervals (95% CIs) were calculated, and the differences in mean values of the quantitative variables between cases and controls were analyzed using an unpaired t-test. Moreover, MMR vaccination and the effect of the number of vaccine injections were investigated using a conditional multiple regression model.
Results: For MMR vaccination, the OR was 1.04 (95% CI, 0.65-1.68), and no significant differences were found for the other vaccines. For all of the prenatal, perinatal and neonatal factors, there were no significant differences between cases and controls. Furthermore, regarding the presence of ASD, MMR vaccination and the number of vaccine injections had ORs of 1.10 (95% CI, 0.64-1.90) and 1.10 (95% CI, 0.95-1.26), respectively, in the conditional multiple regression model; no significant differences were found.
Conclusions: In this study, there were not any convincing evidences that MMR vaccination and increasing the number of vaccine injections were associated with an increased risk of ASD in a genetically homogeneous population. Therefore, these findings indicate that there is no basis for avoiding vaccination out of concern for ASD. (C) 2012 Elsevier Ltd. All rights reserved.
Vaccines for measles, mumps and rubella in children
Main results
We included five randomised controlled trials (RCTs), one controlled clinical trial (CCT), 27 cohort studies, 17 case-control studies, five time-series trials, one case cross-over trial, two ecological studies, six self controlled case series studies involving in all about 14,700,000 children and assessing effectiveness and safety of MMR vaccine. Based on the available evidence, one MMR vaccine dose is at least 95% effective in preventing clinical measles and 92% effective in preventing secondary cases among household contacts.
Effectiveness of at least one dose of MMR in preventing clinical mumps in children is estimated to be between 69% and 81% for the vaccine prepared with Jeryl Lynn mumps strain and between 70% and 75% for the vaccine containing the Urabe strain. Vaccination with MMR containing the Urabe strain has demonstrated to be 73% effective in preventing secondary mumps cases. Effectiveness of Jeryl Lynn containing MMR in preventing laboratory-confirmed mumps cases in children and adolescents was estimated to be between 64% to 66% for one dose and 83% to 88% for two vaccine doses. We did not identify any studies assessing the effectiveness of MMR in preventing rubella.
The highest risk of association with aseptic meningitis was observed within the third week after immunisation with Urabe-containing MMR (risk ratio (RR) 14.28; 95% confidence interval (CI) from 7.93 to 25.71) and within the third (RR 22.5; 95% CI 11.8 to 42.9) or fifth (RR 15.6; 95% CI 10.3 to 24.2) weeks after immunisation with the vaccine prepared with the Leningrad-Zagreb strain. A significant risk of association with febrile seizures and MMR exposure during the two previous weeks (RR 1.10; 95% CI 1.05 to 1.15) was assessed in one large person-time cohort study involving 537,171 children aged between three months and five year of age. Increased risk of febrile seizure has also been observed in children aged between 12 to 23 months (relative incidence (RI) 4.09; 95% CI 3.1 to 5.33) and children aged 12 to 35 months (RI 5.68; 95% CI 2.31 to 13.97) within six to 11 days after exposure to MMR vaccine. An increased risk of thrombocytopenic purpura within six weeks after MMR immunisation in children aged 12 to 23 months was assessed in one case-control study (RR 6.3; 95% CI 1.3 to 30.1) and in one small self controlled case series (incidence rate ratio (IRR) 5.38; 95% CI 2.72 to 10.62). Increased risk of thrombocytopenic purpura within six weeks after MMR exposure was also assessed in one other case-control study involving 2311 children and adolescents between one month and 18 years (odds ratio (OR) 2.4; 95% CI 1.2 to 4.7). Exposure to the MMR vaccine was unlikely to be associated with autism, asthma, leukaemia, hay fever, type 1 diabetes, gait disturbance, Crohn's disease, demyelinating diseases, bacterial or viral infections.
Suspected adverse reactions after vaccination. Results from the German Health Interview and Examination Survey for Children and Adolescents. Part I: descriptive analyses
Abstract: The decreasing incidence of vaccine-preventable infectious diseases and their complications redirects public attention to the safety risks of vaccinations. Collation of resilient vaccine adverse reaction data from passive and active surveillance systems as well as epidemiological studies is indispensable. From 2003-2006, the representative National Health Interview and Examination Survey for Children and Adolescents ("Kinder-und Jugendgesundheitssurvey," KiGGS) retrospectively collected information about vaccines, vaccination dates, and suspected vaccine-related adverse events. A total of 15,958 participants (< 17 years of age) were included in the analyses. Parents of 332 (2.1%; 95% CI 1.8-2.5) children and adolescents reported that one or more vaccinations were poorly tolerated. The reported adverse reactions were largely in accordance with information given in the summaries of product characteristics of the respective vaccines. Calculated rates of adverse reactions were below the known rates. KiGGS allowed the retrospective collection of suspected adverse reactions from a large number of vaccinations, thereby providing data even on rare adverse events. No unusual pattern was observed. The information obtained on suspected adverse reactions does not change the positive benefit-risk ratio of vaccinations.
Lack of association between thimerosal-containing vaccines and autism
Abstract: In Poland, administered childhood vaccines still contain thimerosal as a preservative. Despite the access to mercury free formulas, the most of children are still vaccinated by thimerosal-containing vaccines (TCV) owing to economical reasons. That circumstances caused the rising discussion on potential harmful influence of TCVs on children health. The objective of this analysis was to determine an association of TCVs exposure with the risk of autism. Study population included 96 cases diagnosed with childhood or atypical autism and 192 controls matched individually by year of birth, gender, and physician's practice. Data on autism diagnose and vaccination history were from GPs. Data on the other possible autism risk factors were collected from mothers. Conditional logistic regression was used to assess the risk of autism due to TCVs exposure. No significant association was found between TCVs exposure and autism. After adjusting to potential confounders, odds ratios of the risk of autism developing for infants vaccinated with TCVs were 1.52 (95% CI: 0.29-11.11) for doses 12.5-87.5 microg, 2.78 (95% CI: 0.29-11.11) for 100-137.5 microg and 1.97 (95% CI: 0.37-18.95) for these exposed > or = 150 microg. Our study revealed no evidence of an association between TCVs and autism.
Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study
Abstract: Background: The presence of measles virus (MV) RNA in bowel tissue from children with autism spectrum disorders (ASD) and gastrointestinal (GI) disturbances was reported in 1998. Subsequent investigations found no associations between MV exposure and ASD but did not test for the presence of MV RNA in bowel or focus on children with ASD and GI disturbances. Failure to replicate the original study design may contribute to continued public concern with respect to the safety of the measles, mumps, and rubella (MMR) vaccine.
Methodology/Principal Findings: The objective of this case-control study was to determine whether children with GI disturbances and autism are more likely than children with GI disturbances alone to have MV RNA and/or inflammation in bowel tissues and if autism and/or GI episode onset relate temporally to receipt of MMR. The sample was an age-matched group of US children undergoing clinically-indicated ileocolonoscopy. Ileal and cecal tissues from 25 children with autism and GI disturbances and 13 children with GI disturbances alone (controls) were evaluated by real-time reverse transcription (RT)-PCR for presence of MV RNA in three laboratories blinded to diagnosis, including one wherein the original findings suggesting a link between MV and ASD were reported. The temporal order of onset of GI episodes and autism relative to timing of MMR administration was examined. We found no differences between case and control groups in the presence of MV RNA in ileum and cecum. Results were consistent across the three laboratory sites. GI symptom and autism onset were unrelated to MMR timing. Eighty-eight percent of ASD cases had behavioral regression.
Conclusions/Significance: This study provides strong evidence against association of autism with persistent MV RNA in the GI tract or MMR exposure. Autism with GI disturbances is associated with elevated rates of regression in language or other skills and may represent an endophenotype distinct from other ASD.
A population-based study of measles, mumps, and rubella vaccination and autism
Abstract: Background: It has been suggested that vaccination against measles, mumps, and rubella (MMR) is a cause of autism.
Methods: We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was selected on the basis of data from the Danish Civil Registration System, which assigns a unique identification number to every live-born infant and new resident in Denmark. MMR-vaccination status was obtained from the Danish National Board of Health. Information on the children's autism status was obtained from the Danish Psychiatric Central Register, which contains information on all diagnoses received by patients in psychiatric hospitals and outpatient clinics in Denmark. We obtained information on potential confounders from the Danish Medical Birth Registry, the National Hospital Registry, and Statistics Denmark.
Results: Of the 537,303 children in the cohort (representing 2,129,864 person-years), 440,655 (82.0 percent) had received the MMR vaccine. We identified 316 children with a diagnosis of autistic disorder and 422 with a diagnosis of other autistic-spectrum disorders. After adjustment for potential confounders, the relative risk of autistic disorder in the group of vaccinated children, as compared with the unvaccinated group, was 0.92 (95 percent confidence interval, 0.68 to 1.24), and the relative risk of another autistic-spectrum disorder was 0.83 (95 percent confidence interval, 0.65 to 1.07). There was no association between the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autistic disorder.
Conclusions: This study provides strong evidence against the hypothesis that MMR vaccination causes autism.
No evidence for measles, mumps, and rubella vaccine-associated inflammatory bowel disease or autism in a 14-year prospective study
Source: LANCET Volume: 351 Issue: 9112 Pages: 1327-1328 DOI: 10.1016/S0140-6736(98)24018-9 Published: MAY 2 1998
MMR vaccination and pervasive developmental disorders: a case-control study
Abstract: Background Concern that measles-mumps-rubella (MMR) vaccination might cause autism has led to a fall in vaccine coverage. We investigated whether MMR vaccination is associated with an increased risk of autism or other pervasive developmental disorders.
Methods We did a matched case-control study using the UK General Practice Research Database. Cases were people born in 1973 or later who had first recorded diagnosis of pervasive developmental disorder while registered with a contributing general practice between 1987 and 2001. Controls were matched on age, sex, and general practice.
Findings 1294 cases and 4469 controls were included. 1010 cases (78.1%) had MMR vaccination recorded before diagnosis, compared with 3671 controls (82.1%) before the age at which their matched case was diagnosed. After adjustment for age at joining the database, the odds ratio for association between MMR and pervasive developmental disorder was 0 . 86 (95% CI 0 . 68-1.09). Findings were similar when restricted to children with a diagnosis of autism, to those vaccinated with MMR before the third birthday, or to the period before media coverage of the hypothesis linking MMR with autism.
Interpretation Our findings suggest that MMR vaccination is not associated with an increased risk of pervasive developmental disorders.
Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association
Abstract: Background. We undertook an epidemiological study to investigate whether measles, mumps, and rubella (MMR) vaccine may be causally associated with autism.
Methods. Children with autism born since 1979 were identified from special needs/disability registers and special schools in eight North Thames health districts, UK. Information from clinical records was linked to immunisation data held on the child health computing system. We looked for evidence of a change in trend in incidence or age at diagnosis associated with the introduction of MR IR vaccination to the UK in 1988. Clustering of onsets within defined postvaccination periods was investigated by the case-series method.
Findings. We identified 498 cases of autism (261 of core autism, 166 of atypical autism, and 71 of Asperger's syndrome). In 293 cases the diagnosis could be confirmed by the criteria of the International Classification of Diseases, tenth revision (ICD10: 214 [82%] core autism, 52 [31%] atypical autism. 27 [38%] Asperger's syndrome). There was a steady increase in cases by year of birth with no sudden "step-up" or change in the trend line after the introduction of MMR vaccination. There was no difference in age at diagnosis between the cases vaccinated before or after 18 months of age and those never vaccinated. There was no temporal association between onset of autism within 1 or 2 years after vaccination with MMR (relative incidence compared with control period 0.94 [95% Cl 0.60-1.47] and 1.09 [0.79-1.52]). Developmental regression was not clustered in the months after vaccination (relative incidence within 2 months and 4 months after MMR vaccination 0.92 [0.38-2.21] and 1.00 [0.52-1.95]). No significant temporal clustering for age at onset of parental concern was seen far cases of core autism or atypical autism with the exception of a single interval within 6 months of MMR vaccination. This appeared to be an artifact related to the difficulty of defining precisely the onset of symptoms in this disorder.
Interpretation. Our analyses do not support a causal association between MMR vaccine and autism. If such an association occurs, it is so rare that it could not be identified in this large regional sample.
Prenatal and Infant Exposure to Thimerosal From Vaccines and Immunoglobulins and Risk of Autism
Abstract: OBJECTIVE: Exposure to thimerosal, a mercury-containing preservative that is used in vaccines and immunoglobulin preparations, has been hypothesized to be associated with increased risk of autism spectrum disorder (ASD). This study was designed to examine relationships between prenatal and infant ethylmercury exposure from thimerosal-containing vaccines and/or immunoglobulin preparations and ASD and 2 ASD subcategories: autistic disorder (AD) and ASD with regression.
METHODS: A case-control study was conducted in 3 managed care organizations (MCOs) of 256 children with ASD and 752 controls matched by birth year, gender, and MCO. ASD diagnoses were validated through standardized in-person evaluations. Exposure to thimerosal in vaccines and immunoglobulin preparations was determined from electronic immunization registries, medical charts, and parent interviews. Information on potential confounding factors was obtained from the interviews and medical charts. We used conditional logistic regression to assess associations between ASD, AD, and ASD with regression and exposure to ethylmercury during prenatal, birth-to-1 month, birthto-7-month, and birth-to-20-month periods.
RESULTS: There were no findings of increased risk for any of the 3 ASD outcomes. The adjusted odds ratios (95% confidence intervals) for ASD associated with a 2-SD increase in ethylmercury exposure were 1.12 (0.83-1.51) for prenatal exposure, 0.88 (0.62-1.26) for exposure from birth to 1 month, 0.60 (0.36-0.99) for exposure from birth to 7 months, and 0.60 (0.32-0.97) for exposure from birth to 20 months.
CONCLUSIONS: In our study of MCO members, prenatal and early-life exposure to ethylmercury from thimerosal-containing vaccines and immunoglobulin preparations was not related to increased risk of ASDs. Pediatrics 2010;126:656-664
Lack of Association Between Measles-Mumps-Rubella Vaccination and Autism in Children A Case-Control Study
Abstract: Objective: The first objective of the study was to determine whether there is a relationship between the measles-mumps-rubella (MMR) vaccination and autism in children. The second objective was to examine whether the risk of autism differs between use of MMR and the single measles vaccine.
Design: Case-control study.
Study Population: The 96 cases with childhood or atypical autism, aged 2 to 15, were included into the study group. Controls consisted of 192 children individually matched to cases by year of birth, sex, and general practitioners.
Methods: Data on autism diagnosis and vaccination history were from physicians. Data on the other probable autism risk factors were collected from mothers. Logistic conditional regression was used to assess the risk of autism resulting from vaccination. Assessment was made for children vaccinated (1) Before diagnosis of autism, and (2) Before first symptoms of autism onset. Odds ratios were adjusted to mother's age, medication during pregnancy, gestation time, perinatal injury and Apgar score.
Results: For children vaccinated before diagnosis, autism risk was lower in children vaccinated with MMR than in the nonvaccinated (OR: 0.17, 95% CI: 0.06-0.52) as well as to vaccinated with single measles vaccine (OR: 0.44, 95% CI: 0.22-0.91). The risk for vaccinated versus nonvaccinated (independent of vaccine type) was 0.28 (95% CI: 0.10-0.76). The risk connected with being vaccinated before onset of first symptoms was significantly lower only for MMR versus single vaccine (OR: 0.47, 95% CI: 0.22-0.99).
Conclusions: The study provides evidence against the association of autism with either MMR or a single measles vaccine.
No evidence for a new variant of measles-mumps-rubella-induced autism
Results. The prevalence of childhood disintegrative disorder was 0.6/10000 (95% confidence interval: 0.02-3.6/10000); this very low rate is consistent with previous estimates and is not suggestive of an increased frequency of this form of pervasive developmental disorder in samples of children who are immunized with MMR. There was no difference in the mean age at first parental concern between the 2 samples exposed to MMR (19.3 and 19.2 months) and the pre-MMR sample (19.5 months). Thus, MMR immunization was not associated with a shift toward an earlier age for first parental concerns. Similarly, the rate of developmental regression reported in the post-MMR sample (15.6%) was not different from that in the pre-MMR sample (18.4%); therefore, there was no suggestion that regression in the developmental course of autism had increased in frequency since MMR was introduced. In the epidemiologic sample, the subset of autistic children with regression had no other developmental or clinical characteristics, which would have argued for a specific, etiologically distinct phenotype. Parents of autistic children with developmental regression detected the first symptoms at a very similar age (19.8 months) to those of autistic children without regression (19.3 months). Moreover, the mean intervals from MMR immunization to parental recognition of autistic symptoms were comparable in autistic children with or without regression (248 vs 272 days; not significant). In the epidemiologic sample, gastrointestinal symptoms were reported in 18.8% of children. Constipation was the most common symptom (9.4%), and no inflammatory bowel disorder was reported. Furthermore, there was no association between developmental regression and gastrointestinal symptoms (odds ratio: 0.63; 95% confidence interval: 0.06-3.2; not significant), and only 2.1% of the sample experienced both problems, a rate that did not exceed chance expectations. Conclusions. No evidence was found to support a distinct syndrome of MMR-induced autism or of "autistic enterocolitis." These results add to the recent accumulation of large-scale epidemiologic studies that all failed to support an association between MMR and autism at population level. When combined, the current findings do not argue for changes in current immunization programs and recommendations.
Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis
Design Time trend analysis of data from the UK general practice research database (GPRD).
Setting General practices in the United Kingdom.
Subjects Children aged 12 years or younger diagnosed with autism 1988-99, with further analysis of boys aged 2 to 5 years born 1988-93.
Main outcome measures Annual and age specific incidence for first recorded diagnoses of autism (that is, when the diagnosis of autism was first recorded) in the children aged 12 years or younger; annual, birth cohort specific risk of autism diagnosed in the 2 to 5 year old boys; coverage (prevalence) of MMR vaccination in the same birth cohorts.
Results The incidence of newly diagnosed autism increased sevenfold, from 0.3 per 10 000 person years in 1988 to 2.1 per 10 000 person years in 1999, The peak incidence was among 3 and 4 year olds, and 83% (254/305) of cases were boys. In an annual birth cohort analysis of 114 boys born in 1988-93, the risk of autism in 2 to 5 year old boys increased nearly fourfold over time, from 8 (95% confidence interval 4 to 14) per 10 000 for boys born in 1988 to 29 (20 to 43) per 10 000 for boys born in 1993. For the same annual birth cohorts the prevalence of MMR vaccination was over 95%.
Conclusions Because the incidence of autism among 2 to 5 year olds increased markedly among boys born in each year separately from 1988 to 1993 while MMR vaccine coverage was over 95% for successive annual birth cohorts, the data provide evidence that no correlation exists between the prevalence of MMR vaccination and the rapid increase in the risk of autism over time. The explanation for the marked increase in risk of the diagnosis of autism in the past decade remains
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