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Objectives: To estimate the association between childhood vaccination and subsequent morbidity and mortality by adjusting for environmental and host factors. Further, to examine the degree of residual confounding in such observational studies., Design: Register-based cohort study including 1 122 929 Danish children., Participants: All children born in Denmark in the period 1999-2016 who survived until 16 months of age without prior migration followed from 16 months until the first of the following: event of interest, migration, 5 years of age or 31 December 2016., Main Outcome Measures: Adjusted HRs (aHRs) and absolute risks were calculated for the three outcomes: mortality, hospitalisation for infection and asthma using register data on deaths, specific hospital contacts and dispensed prescribed medication. The exposure was the combination of the routine vaccines against diphteria-tetanus-pertussis-polio- Haemophilus influenzae type b and measles-mumps-rubella (DTP and MMR in short) administered in early childhood. Hospitalisation due to accidents was analysed as a negative control outcome to examine residual confounding., Results: Children with 3DTP+MMR had a lower hazard of mortality than the reference group with 3DTP, adjusted HR (aHR)=0.45 (95% CI: 0.35 to 0.57), whereas the children with 1 or 2 DTP had higher hazards of dying, aHR=1.55 (95% CI: 1.14 to 2.13) and aHR=1.96 (95% CI: 1.34 to 2.89). The vaccination group 3DTP+MMR was associated with a reduced hazard of asthma aHR=0.94 (95% CI: 0.92 to 0.96). Also, the vaccination group 3DTP+MMR was associated with a reduced hazard of hospitalisation due to accidents, aHR=0.83 (0.80 to 0.85) compared with the reference group with 3 DTP., Conclusions: The results suggested a beneficial impact of MMR on under-five mortality but did not support the hypothesis that DTP is detrimental, since the group of children with fewer DTP vaccinations experienced increased mortality. The results of the study may to some degree be prone to residual confounding since an unexpected association between MMR vaccination and hospitalisation for accidents was observed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The hypothesized link between the measles, mumps, rubella (MMR) vaccine and autism continues to cause concern and challenge vaccine uptake., Objective: To evaluate whether the MMR vaccine increases the risk for autism in children, subgroups of children, or time periods after vaccination., Design: Nationwide cohort study., Setting: Denmark., Participants: 657 461 children born in Denmark from 1999 through 31 December 2010, with follow-up from 1 year of age and through 31 August 2013., Measurements: Danish population registries were used to link information on MMR vaccination, autism diagnoses, other childhood vaccines, sibling history of autism, and autism risk factors to children in the cohort. Survival analysis of the time to autism diagnosis with Cox proportional hazards regression was used to estimate hazard ratios of autism according to MMR vaccination status, with adjustment for age, birth year, sex, other childhood vaccines, sibling history of autism, and autism risk factors (based on a disease risk score)., Results: During 5 025 754 person-years of follow-up, 6517 children were diagnosed with autism (incidence rate, 129.7 per 100 000 person-years). Comparing MMR-vaccinated with MMR-unvaccinated children yielded a fully adjusted autism hazard ratio of 0.93 (95% CI, 0.85 to 1.02). Similarly, no increased risk for autism after MMR vaccination was consistently observed in subgroups of children defined according to sibling history of autism, autism risk factors (based on a disease risk score) or other childhood vaccinations, or during specified time periods after vaccination., Limitation: No individual medical charts were reviewed., Conclusion: The study strongly supports that MMR vaccination does not increase the risk for autism, does not trigger autism in susceptible children, and is not associated with clustering of autism cases after vaccination. It adds to previous studies through significant additional statistical power and by addressing hypotheses of susceptible subgroups and clustering of cases., Primary Funding Source: Novo Nordisk Foundation and Danish Ministry of Health.

Introduction: Measles, mumps and rubella (MMR) vaccination is part of the Danish Childhood Vaccination Programme. It is known that children may react with anaphylaxis to MMR vaccines containing traces of egg protein. In Denmark, national clinical guidelines recommend that children with egg allergy be referred to vaccination at a paediatric ward despite changed recommendations in other countries. The purpose of this study was to determine whether children with egg allergy presented with anaphylactic/allergic reactions to MMR vaccination and to discuss whether Danish recommendations should be upheld., Material and Methods: Data collected through evaluation of the histories of children referred to the Paediatric Ward at Hillerød Hospital from 01.01.2008 to 28.02.2011 and coded according to action diagnosis and/or supplementary diagnosis in International Classification of Diseases 10 (ICD-10) for food allergy, oedema angioneurotica and tentative diagnosis as well as the procedure code for oral food challenge. A total of 32 patients were included, all were both sensitized to egg and had been MMR vaccinated., Results: The 32 patients had received a total of 41 doses of MMR vaccine. None of them had shown anaphylactic/allergic reactions to the MMR vaccines. 23% of the vaccines were given with considerable delay., Conclusion: Based on our study, we conclude that the Priorix MMR vaccine may be administered just as safely to children diagnosed with egg allergy as to other children. We found no evidence in support of the current Danish recommendations. We therefore recommend that the Statens Serum Institut, the Danish Paediatric Society and/or the Danish Health and Medicines Authority reconsider these recommendations., Funding: not relevant, Trial Registration: not relevant.

The assessment of rare adverse events following vaccination may not be possible within a single country due to an insufficiently large denominator population. In 2008 a European consortium (VAESCO) was funded to perform collaborative vaccine safety studies. To help assess the feasibility of multi-country collaboration England and Denmark, who have established vaccine safety research infrastructures, undertook to work to a common protocol and share results and data to estimate the risk of a known true adverse event, thrombocytopenic purpura (TP) following measles-mumps-rubella (MMR) vaccination. TP is a known rare reaction to MMR and therefore provided an opportunity to assess whether two countries would produce similar results when working collaboratively. Despite some initial problems with ensuring data were comparable, the two countries gave very similar estimates of the relative incidence in the 6 weeks after vaccination and a pooled relative incidence estimate of 2.13 (95% confidence interval 1.55-2.94) and attributable risk of 1 in 50,000 doses. Both countries used hospital admissions for TP and the analysis was performed using the self controlled case series method which is particularly suited to collaborative studies because of its implicit control for individual level confounding. The study therefore shows the potential for vaccine safety collaborations across Europe to detect true associations through use of common protocols and sharing of results or data., (Copyright © 2011 Brighton Collaboration. Published by Elsevier Ltd.. All rights reserved.)

Background: A rarely used opportunity in pharmacovigilance is data mining for adverse drug reactions (ADRs) in population-based healthcare databases., Objective: To evaluate the potential of data mining for ADRs in the nationwide Danish healthcare databases. We specifically considered hospital contacts following measles, mumps and rubella (MMR) immunization., Methods: We constructed a cohort consisting of all children born in Denmark from 1995 to 2007 (n = 918,831) with individual-level linked data on childhood vaccinations and hospital contacts from the nationwide Danish healthcare databases. We applied a cohort-based data mining methodology to compare the observed versus the expected incidence of adverse event in different time periods relative to immunization. With this approach we evaluated temporal associations between MMR immunization and 5915 different diagnoses occurring in the cohort. In order to evaluate the ability of our approach to detect signals, we singled out a set of four adverse events previously recognized as being associated with the MMR vaccine., Results: We were able to link a total of 3,162,251 hospital contacts and 5915 different diagnoses to the children in the cohort. Previously recognized temporal associations between adverse events (febrile convulsions, idiopathic thrombocytopenic purpura, lymphadenopathy and rash) and MMR immunization were identified in the Danish databases by our method., Conclusions: Data mining in the Danish population-based healthcare databases provides adequate ability to detect adverse events. Pharmacovigilance using electronic healthcare databases holds potential as an important supplement to traditional pharmacovigilance.

A suggested association between certain childhood vaccines and autism has been one of the most contentious vaccine safety controversies in recent years. Despite compelling scientific evidence against a causal association, many parents and parent advocacy groups continue to suspect that vaccines, particularly measles-mumps-rubella (MMR) vaccine and thimerosal-containing vaccines (TCVs), can cause autism.

The efficacy, the ability to confer protection against a target disease and the safety of a vaccine are assessed in great detail before licensure. However, inherent limitations in the prelicensure assessment necessitate continued epidemiological evaluations of efficacy and safety issues after the introduction of vaccines into use. In Denmark, the opportunities available for epidemiological research are unique. In 2001, an initiative was undertaken to take advantage of these opportunities to study the postlicensure epidemiology of childhood vaccination with respect to effectiveness and safety. First, we describe the unique opportunities for postlicensure research in Denmark with respect to the data sources available and the epidemiological and statistical methods used. We then describe a number of recent postlicensure studies of effectiveness and safety that took advantage of these opportunities. Specifically, studies on the effectiveness of Haemophilus influenzae type b vaccination, the effectiveness of pertussis vaccination, the impact of a preschool pertussis booster on infant pertussis, measles-mumps-rubella vaccine and autism, thimerosal-containing vaccine and autism, measles-mumps-rubella vaccine and febrile seizures, childhood vaccination and Type 1 diabetes, and childhood vaccination and nontargeted infectious disease are discussed.

Introduction: The aim of this study was to investigate why parents in one county of Denmark leave vaccination against measles, mumps and rubella (MMR) undone, with special reference to evaluating the possibilities of increasing the acceptance of the MMR vaccination program., Materials and Methods: Data were collected through semi-structured, tape-recorded telephone interviews. The interviewees were 17 strategically chosen parents of children 15 months and 12 years old who had not received the MMR vaccination in 2002. The method of analysis was Systematic Text Condensation., Results: The parents had consulted many sources in their search for information about MMR vaccination. Many referred to their own or others' good experiences with going through the natural illnesses and bad experiences with vaccination. It is a common view that naturally occurring illnesses strengthen the immunity more effectively than vaccination does, and this approach is preferred by some of the parents. The risk of vaccination is viewed as greater than that of going through the natural illnesses. This, however, is not in accordance with scientific knowledge. There was no evidence that leaving vaccination undone was due to the parents' lack of knowledge, forgetfulness or lack of interest in MMR vaccination, and it was rare that only one reason was mentioned., Conclusion: The results of the study indicate that doctors can profit by preparing a dialogue with parents who are in doubt about MMR vaccination. Especially it seems that a profound knowledge of the scientific evidence of virus-caused diseases, of their risks and of immunology is necessary to balance parents' most essential misconceptions and their reasons for not choosing vaccination.

Context: The rate of febrile seizures increases following measles, mumps, and rubella (MMR) vaccination but it is unknown whether the rate varies according to personal or family history of seizures, perinatal factors, or socioeconomic status. Furthermore, little is known about the long-term outcome of febrile seizures following vaccination., Objectives: To estimate incidence rate ratios (RRs) and risk differences of febrile seizures following MMR vaccination within subgroups of children and to evaluate the clinical outcome of febrile seizures following vaccination., Design, Setting, and Participants: A population-based cohort study of all children born in Denmark between January 1, 1991, and December 31, 1998, who were alive at 3 months; 537,171 children were followed up until December 31, 1999, by using data from the Danish Civil Registration System and 4 other national registries., Main Outcome Measures: Incidence of first febrile seizure, recurrent febrile seizures, and subsequent epilepsy., Results: A total of 439,251 children (82%) received MMR vaccination and 17,986 children developed febrile seizures at least once; 973 of these febrile seizures occurred within 2 weeks of MMR vaccination. The RR of febrile seizures increased during the 2 weeks following MMR vaccination (2.75; 95% confidence interval [CI], 2.55-2.97), and thereafter was close to the observed RR for nonvaccinated children. The RR did not vary significantly in the subgroups of children that had been defined by their family history of seizures, perinatal factors, or socioeconomic status. At 15 to 17 months, the risk difference of febrile seizures within 2 weeks following MMR vaccination was 1.56 per 1000 children overall (95% CI, 1.44-1.68), 3.97 per 1000 (95% CI, 2.90-5.40) for siblings of children with a history of febrile seizures, and 19.47 per 1000 (95% CI, 16.05-23.55) for children with a personal history of febrile seizures. Children with febrile seizures following MMR vaccinations had a slightly increased rate of recurrent febrile seizures (RR, 1.19; 95% CI, 1.01-1.41) but no increased rate of epilepsy (RR, 0.70; 95% CI, 0.33-1.50) compared with children who were nonvaccinated at the time of their first febrile seizure., Conclusions: MMR vaccination was associated with a transient increased rate of febrile seizures but the risk difference was small even in high-risk children. The long-term rate of epilepsy was not increased in children who had febrile seizures following vaccination compared with children who had febrile seizures of a different etiology.

It has been suggested that vaccination with the measles-mumps-rubella (MMR) vaccine causes autism. The wide-scale use of the MMR vaccine has been reported to coincide with the apparent increase in the incidence of autism. Case reports have described children who developed signs of both developmental regression and gastrointestinal symptoms shortly after MMR vaccination.A review of the literature revealed no convincing scientific evidence to support a causal relationship between the use of MMR vaccines and autism. No primate models exist to support the hypothesis. The biological plausibility remains questionable and there is a sound body of epidemiological evidence to refute the hypothesis. The hypothesis has been subjected to critical evaluation in many different ways, using techniques from molecular biology to population-based epidemiology, and with a vast number of independent researchers involved, none of which has been able to corroborate the hypothesis.

The prevalence of atopic dermatitis increased markedly in the period 1960s to the 1990s. Earlier findings indicate that infections acquired in early life enhance or suppress the expression of atopic disease as a result of a change in immune reactivity. Our objectives were to examine the association between measles, mumps and rubella vaccination, measles infection and the risk of atopic dermatitis. A random sample of 9,744 children were followed up from birth to 3-15 years. Their parents responded to a questionnaire including highly structured questions on atopic dermatitis, measles, mumps and rubella vaccination and measles infection. Information on parental educational level was obtained from Statistics Denmark. The cumulative incidence of atopic dermatitis at age 14 was 19.7%. The confounder adjusted incidence ratio of atopic dermatitis among measles, mumps and rubella vaccinated children versus children not subjected to measles, mumps and rubella vaccination and measles infection was 1.86 (95% CI 1.25-2.79); the incidence ratio for measles-infected children was similar. The incidence of atopic dermatitis increased after measles, mumps and rubella vaccination and measles infection, which is surprising in view of the hygiene hypothesis. We suggest further study of the possible short-term and long-term effects of virus and bacteria on the immune responses and expression of atopic disease.

Introduction: It has been suggested that the measles-mumps-rubella (MMR) vaccination causes autism., Material and Methods: We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was established based on data from the Danish Civil Registration System. A unique person identifiable number given to all subjects enabled linkage with other national registries. 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 from psychiatric hospitals, psychiatric wards, 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: In the cohort of 537,303 children (2,129,864 person-years), 440,655 children had been MMR vaccinated. We identified 316 children with a diagnosis of autistic disorder and 442 with a diagnosis of other spectrum disorders. After adjusting for potential confounders, the risk for autistic disorder and other spectrum disorders was not increased in vaccinated compared with unvaccinated children (relative risk 0.92; 95 percent confidence interval, 0.68 to 1.24 and relative risk 0.83; 95 percent confidence interval, 0.65 to 1.07). There was no association between age at vaccination, time since vaccination or calendar period at time of vaccination and development of autistic disorder., Discussion: This study provides strong evidence against the hypothesis that MMR vaccination causes autism.

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., (Copyright 2002 Massachusetts Medical Society)