ncbi.nlm.nih.gov/pmc/articles/PMC4128611/ Measles-mumps-rubella vaccination timing and autism among young african american boys: a reanalysis of CDC data Brian S Hooker Translational Neurodegeneration BioMed Central Measles-mumps-rubella vaccination timing and autism among young african american boys: a reanalysis of CDC data Brian S Hooker Additional article information Abstract Background A significant number of children diagnosed with autism spectrum disorder suffer a loss of previously-acquired skills, suggesting neurodegeneration or a type of progressive encephalopathy with an etiological basis occurring after birth. The purpose of this study is to investigate the effectof the age at which children got their first Measles-Mumps-Rubella (MMR) vaccine on autism incidence. This is a reanalysis of the data set, obtained from the U.S. Centers for Disease Control and Protection (CDC), used for the Destefano et al. 2004 publication on the timing of the first MMR vaccine and autism diagnoses. Methods The author embarked on the present study to evaluate whether a relationship exists between child age when the first MMR vaccine was administered among cases diagnosed with autism and controls born between 1986 through 1993 among school children in metropolitan Atlanta. The Pearson’s chi-squared method was used to assess relative risks of receiving an autism diagnosis within the total cohort as well as among different race and gender categories. Results When comparing cases and controls receiving their first MMR vaccine before and after 36 months of age, there was a statistically significant increase in autism cases specifically among African American males who received the first MMR prior to 36 months of age. Relative risks for males in general and African American males were 1.69 (p=0.0138) and 3.36 (p=0.0019), respectively. Additionally, African American males showed an odds ratio of 1.73 (p=0.0200) for autism cases in children receiving their first MMR vaccine prior to 24 months of age versus 24 months of age and thereafter. Conclusions The present study provides new epidemiologic evidence showing that African American males receiving the MMR vaccine prior to 24 months of age or 36 months of age are more likely to receive an autism diagnosis. Keywords: Autism, Measles-mumps-rubella (MMR) vaccine Background Autism is defined by persistent deficits in social communication and social interaction across multiple contexts and restricted, repetitive patterns of behavior, interests, or activities [1]. Autism incidence has risen dramatically over the past two decades [2] and it has recently been reported that one in sixty-eight children have this disorder [3]. In addition to these core deficits, autism has also been characterized by many other comorbid conditions including gastrointestinal issues, sleep issues, eating disorders and sensory processing issues [4]. It has been estimated that as many as 62% of children with autism experience a period of regression during early childhood, characterized by loss of previously acquired skills [5]. This period has been reported as ranging between 6 and 36 months of age with the typical age of regression between 18 and 24 months [6]. This period of regression occurs within the same time period that children in the United States typically receive their required vaccinations and thus there have been many studies regarding the incidence of autism and the receipt of specific vaccines. One of the primary concerns has been the timing of the administration of the first measles-mumps-rubella (MMR) vaccine. The relationship between the MMR vaccine and autism was first hypothesized by Wakefield et al. [7] in 1999 after the observation of a regressive phenotype of autism that appeared in general after the administration of the first MMR vaccine. Although several studies have affirmed such a relationship between the MMR vaccine and neurodevelopmental disorders including autism [8,9], many other studies purport no statistical relationship between the MMR vaccine and autism incidence. The latter studies have been performed using cohorts from Denmark [10], Japan [11] and Poland [12], as well as the MMR vaccine and pervasive developmental disorder in Canada [13]. In addition, in 2004, Destefano et al. [14] published a paper describing a case–control study completed on children, in metropolitan Atlanta, who had been born between 1986 and 1993. Within this study, the age at the first MMR vaccine was assessed as a factor in the incidence of autism. Using conditional logistic regression, with first MMR age as the independent variable and autism incidence as the dependent variable, the study authors assessed relative risk for obtaining an autism diagnosis for those children receiving the first MMR vaccine before and after 18 months, 24 months and 36 months of age. Destefano et al. [14] found a statistically significant relative risk of 1.49 (95% confidence interval [CI]: 1.04 – 2.14) at the 36 month cut-off (i.e., in a comparison of children receiving the MMR before versus after 36 months). Rather than concluding that the first MMR vaccine could be playing a causal role in autism in these children, the study authors instead attributed the increased risk to greater numbers of autistic children receiving timely vaccinations in order to participate in State of Georgia special education services. In this paper, we present the results of a cohort study using the same data from the Destefano et al. [14] analysis. The focus of the current study is differences in results in specific gender and race groups. Methods Cohort data Cohort data were obtained directly as a “restricted access data set” from the Centers for Disease Control and Prevention (CDC) via a Data Use Agreement. Data were deidentified by the CDC in accordance with Family Education Rights and Privacy Act (FERPA) and the Health Insurance Portability and Accountability Act (HIPAA) prior to receipt by the study authors. Use of the CDC specifically for the study described herein was approved by the Simpson University Institutional Review Board, in accordance with U.S. Federal regulations. Study population As reported by Destefano et al. [14] (CDC) in the original publication, “Children with autism were identified by the CDC from the Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP), a multiple-source, population-based surveillance program that monitors the occurrence of selected developmental disabilities among children in the 5-county metropolitan Atlanta area”. And further, “Autism cases were identified via screening and abstraction of source files at schools, hospitals, clinics, and specialty providers”. Of the cases identified, vaccination records were located for 660 children. Control children were chosen from “regular” education programs and were within the same age group and schools of attendance or neighboring school as cases. Children missing a vaccination form or with incomplete vaccination forms (where the forms did not list at least 1 diphtheria-tetanus-pertusussis vaccine by 2 years of age or at least 1 MMR vaccine at any age) were excluded from the study. Children with religious or medical exemptions were not excluded from the study. The listed exclusions yielded a cohort size of 624 cases and 1824 controls. Vaccination histories Vaccination records were abstracted as described previously [14] from standardized state immunization forms that are required for all children who attend school and early intervention programs in Georgia. Demographic data Demographic data including birthdate, gender and race were obtained for both case and control children via birth certificates or registration forms kept as a part of each child’s permanent school record. Georgia state birth certificate information was used to further obtain each child’s birthweight. Although actual birthweight data were not released by the CDC, case and control children were lumped into birthweight categories: under 1500 grams, between 1500 and 2500 grams and over 2500 grams. All individuals less than 3 years of age at the time of testing (1996) were excluded from the analysis. Statistical analyses The Pearson’s chi -squared test contained in the SAS® software was utilized for current statistical analyses, and a two-sided p-value < 0.05 was considered statistically significant. This is in contrast to the original Destefano et al. [14] (CDC) study, where a case–control study design was used, where 3 control children were matched to each case child, and analyzed using conditional logistic regression dichotomized for the three age cut-offs at 18, 24 and 36 months. Pearson’s chi-squared is, in general, a more conservative analysis and therefore chosen for the present study. However, our results were also confirmed using a conditional logistic regression design similar to the Destefano et al. [14] (CDC) study. In the present study, frequencies of cases were determined for first MMR ages of less than versus greater than 18 months, 24 months and 36 months in each separate analysis. When accounting for cases in the cohort that excluded low birth weight (
Posted on: Thu, 28 Aug 2014 00:54:51 +0000
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