Time Trends in Autism and in MMR Immunization Coverage in California

BRIEF REPORT

Loring Dales, MD Context Considerable concern has been generated in the lay and medical commu- Sandra Jo Hammer, RN, PHN nities by a theory that increased measles-mumps-rubella (MMR) immunization among young children may be the cause of an apparent marked increase in autism occur- Natalie J. Smith, MD, MPH rence. N THE MID TO LATE 1990S, A MEDI- Objective To determine if a correlation exists in secular trends of MMR immuniza- cal investigative group in Great Brit- tion coverage among young children and autism occurrence. ain postulated that measles immu- Design, Setting, and Participants Retrospective analyses of MMR immuniza- nization and/or immunization with tion coverage rates among children born in 1980-1994 who were enrolled in Califor- Imeasles, mumps, and rubella vaccines nia kindergartens (survey samples of 600-1900 children each year) and whose school given combined at the same time or in immunization records were reviewed to retrospectively determine the age at which succession over a relatively short time they first received MMR immunization; and of autism caseloads among children born in these years who were diagnosed with autism and were enrolled in the California period might be a cause of the devel- Department of Developmental Services regional service center system. opmental disorder autism.1 Strong interest in and debate over this hypoth- Main Outcome Measures Measles-mumps-rubella immunization coverage rates esis has occurred. In this connection, as of ages 17 months and 24 months and numbers of Department of Developmental Services system enrollees diagnosed with autism, grouped by year of birth. some cite a 1999 report from the Cali- fornia Department of Developmental Results Essentially no correlation was observed between the secular trend of early Services2 showing an increase within the childhood MMR immunization rates in California and the secular trend in numbers of children with autism enrolled in California’s regional service center system. For the 1980- past 2 decades in its regional system 1994 birth cohorts, a marked, sustained increase in autism case numbers was noted, caseload of children with autism, won- from 44 cases per 100000 live births in the 1980 cohort to 208 cases per 100000 live dering if increasingly widespread com- births in the 1994 cohort (a 373% relative increase), but changes in early childhood bined measles-mumps-rubella (MMR) MMR immunization coverage over the same time period were much smaller and of immunization of young children might shorter duration. Immunization coverage by the age of 24 months increased from 72% have been responsible for this in- to 82%, a relative increase of only 14%, over the same time period. crease.3 Also, multiple news media sto- Conclusions These data do not suggest an association between MMR immuniza- ries and Internet Web site presenta- tion among young children and an increase in autism occurrence. tions on MMR vaccine and autism have JAMA. 2001;285:1183-1185 www.jama.com cited these California autism data.4,5 Autism, an incompletely understood data cannot be used as a true measure amined California data on early child- developmental disorder or group of re- of changes over time in autism inci- hood MMR immunization levels over lated disorders, varies in clinical presen- dence because other factors can affect time along with the data on autism case- tation, so diagnosis is not always straight- trends in system case numbers.2 Fur- loads during the same period. The com- forward. Further, temporal associations ther, “ecological correlations,” that is, bined MMR vaccine was licensed for use between receipt of MMR vaccine and au- observations of parallel trends over time in the United States in 1971, and over tism onset can occur by chance alone, or across geographic locations for 2 the remainder of the 1970s, almost since MMR vaccine is typically given at events, generally do not constitute completely replaced use of the indi- 12 to 15 months of age, and the median strong evidence for a causal associa- vidual measles, mumps, and rubella age at which parents of children with au- tion between the 2 events.7 Other events vaccines for routine immunization of tism first notice troubling signs in their besides a possible increase in early young children. Since 1979, the MMR children’s development is approxi- childhood immunization with MMR 6 Author Affiliations: Immunization Branch, Califor- mately 18 to 19 months of age. vaccine have occurred over the time pe- nia Department of Health Services, Berkeley. The aforementioned California De- riod of the increase in autism cases. Corresponding Author and Reprints: Loring Dales, MD, Immunization Branch, California Department of partment of Developmental Services re- Nonetheless, given concerns ex- Health Services, 2151 Berkeley Way, Room 712, Berke- port stresses that its patient caseload pressed about this matter, we have ex- ley, CA 94704 (e-mail: [email protected]).

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by the 21 regional centers.2 Because the of 24 months is presented to detect a Figure. Percentage of Children Receiving Measles-Mumps-Rubella (MMR) increase in this system’s autism case- potential secular trend on increasing Immunization in Second Year of Life and load occurred within the past 2 de- vaccine coverage that might have been Caseload of Children With Autism, by Year cades, we examined the data for chil- missed when the 17-month age check- of Birth, California, 1980-1994 dren born between 1980 and 1994, the point was used.

100 latter being the latest patient birth year By Age 24 mo RESULTS 80 for which a relatively complete system autism caseload count is currently avail- The upper 2 curves in the FIGURE show 60 able. The California Department of De- the percentages of children who re- 40 By Age 17 mo velopmental Services supplied casel- ceived MMR immunization by the age 20 oad numbers for the diagnostic category of 17 months and by the age of 24 Children Receiving Children MMR Immunization, % 0 “autistic disorder” (International Clas- months (including children immu- 1200 sification of Diseases, 9th Edition, code nized by 17 months of age), by birth 299.00), which excludes other perva- year, for each annual California kin- 1000 sive developmental disorders. dergarten retrospective immunization 800 The early childhood MMR immuni- survey sample cohort, for birth years 600 zation level estimates for California chil- 1980 through 1994. As can be seen from dren by year of birth come from the the 2 upper curves, for the 1980 400 California Department of Health Ser- through 1987 birth year cohorts, there 200 vices annual surveys of statewide ran- was almost no change in MMR cover- 0 dom samples of public and private age. A modest increase occurred with Cases of Children WithCases of Children Autism, No. 1980 1982 1984 1986 1988 1990 1992 1994 Birth Cohort school kindergarten pupils’ immuni- the 1988 birth cohort, followed again zation records. The number of chil- by a near plateau with little change in The upper 2 curves indicate the percentages of children included in the surveys’ random coverage over the next 6 years, through dren receiving MMR immunization by 17 and 24 months of age, respectively. The lower curve indi- samples selected each year increased the 1994 birth cohort. The relative in- cates the number of cases of children with autism2 (and from approximately 600 to 800 chil- crease in MMR coverage by age 24 California Department of Development Services, un- dren born each year in 1980 through months from birth year 1980 to 1994 published data, 2000). The vertical dotted line at birth year 1988 is provided as a temporal reference point 1984 to between 1000 and 1900 annu- was 14%, from 72% to 82%. in comparing the shapes of these curves. ally for children born in 1985 through The lower curve in the Figure shows 1994, but otherwise the sampling a major trend of increase in autistic dis- preparation used in the United States method remained virtually the same order cases beginning with the 1985 has not changed in composition. Thus, throughout the whole time period. birth year cohort (and possibly even for children born in California from School immunization records of the earlier), well before the MMR cover- 1980 onward, the secular trend in the kindergarten children sampled, who age increase that occurred with the 1988 proportion of children who received were 5 to 6 years of age at the time of birth cohort. Further, this trend of au- MMR immunization at an early age is the surveys, were assessed retrospec- tistic disorder caseload increase con- the logical parameter to compare with tively to determine at what earlier ages tinues at least through the 1994 birth the apparent trend of increasing au- they received their immunizations. Per cohort. Thus, the trend of increasing autism occurrence. standard national recommendations ex- tism caseload numbers persisted long tant over this time period, children after the MMR immunization cover- METHODS should have received their initial MMR age curve leveled off again with the Since the early 1970s, the California De- immunization at 12 to 15 months of 1988 birth cohort. partment of Developmental Services has age. Two immunization coverage mea- The trend of increasing numbers of funded a system of regional centers for sures are presented here: the propor- autistic disorder cases, from 176 cases persons with developmental disabili- tions of children in each year’s survey for birth year 1980 to 1182 cases for ties, including autism. These regional sample who had received MMR immu- birth year 1994 (a relative increase of centers, now 21 in number and cover- nization by the age of 17 months, and 572%), is many times greater in rela- ing all of the state’s 58 counties, func- the proportions that had received such tive magnitude than the modest in- tion as service hubs, coordinating, link- immunization by the age of 24 months. crease observed for MMR coverage. If ing, and funding services for eligible Immunization coverage by the age of the autistic disorder case data are com- persons. The 1999 report on trends in 17 months is presented because this age puted as rates, using annual numbers the system’s autism caseload com- just precedes the median age when par- of births in California as denomina- piled demographic and patient devel- ents of children with autism first note tors, the increase noted for the lower opmental evaluation record data elec- signs of developmental problems. Im- curve in the Figure is only slightly less tronically submitted to the department munization coverage through the age pronounced, increasing from 44 per

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100000 births for the 1980 birth co- posed to artifact, as well as evaluating ceived the combined MMR vaccine hort to 208 per 100000 births for the factors that may have contributed to any product vs separate injections of the 1994 birth cohort, representing a 373% true increases including immuniza- measles, mumps, and/or rubella com- relative increase. tions.2,8 Such investigations are in ponents. However, the historical infor- progress (Robert Byrd, MD, Univer- mation on MMR vaccine usage in the COMMENT sity of California Davis Medical Cen- United States, as well as information in The lack of correspondence between the ter, Department of Pediatrics, written the immunization coverage data set it- trends in MMR coverage and numbers communication, November 1, 2000). self, strongly suggest that separate in- of autistic disorder cases does not sup- However, the issue here is, assum- jections of measles, mumps and/or ru- port the hypothesis that increasingly ing that the secular trend noted in the bella vaccines to young children were widespread MMR immunization of report represents a true increase in au- rare during the time period under con- young children is associated with the tistic disorder incidence, what is the evi- sideration, particularly for the 1984- marked secular trend of increasing dence that MMR immunization may be 1994 birth cohorts, in which the trend numbers of autism cases enrolled in the associated with this trend? That is, does of increase in the system’s autistic dis- California Department of Developmen- an ecological correlation exist be- order caseload is most pronounced. tal Services regional service center sys- tween MMR immunization coverage Thus, examination of available data tem. Difficulties in interpreting the in- rates of young children and the sys- from California has been unable to dem- creasing numbers of autism cases are tem’s autism caseload? If MMR immu- onstrate a correlation between secular highlighted in the California Depart- nization of young children was associ- trends in early childhood MMR immu- ment of Developmental Services 1999 ated with a secular trend in autism nization coverage and autism case- report, which repeatedly stressed that incidence, one would expect a curve for load levels. A similar lack of correla- its data cannot be interpreted as mea- the numbers of autism cases among the tion between the trends in early suring trends in the actual incidence of 1980-1994 birth year cohorts that is childhood MMR immunization rates autism.2 It is unknown how many chil- very similar to the shapes of the curves and autism occurrence has been noted dren with autism have not enrolled in for temporal trends in MMR coverage. in Great Britain6 and Sweden.9 In con- the system and, as the system ex- That is, the numbers of cases should be clusion, to date, published observa- panded and matured over time, the pro- rather stable for the 1980-1987 co- tions based on empirical evidence do portions of California children enroll- horts, followed by a small increase and not suggest that increased MMR im- ing and the distribution of ages at then more or less a plateau at a new, munization among young children is enrollment likely changed over time as modestly higher level for the 1988- associated with secular increases in a result. Also, the proportions of chil- 1994 birth cohorts. As can be seen from cases of autism. dren enrolling in the system who were the lower curve in the Figure, how- born outside California may have ever, this is not the case. Author Contributions: Study concept and design: changed over this time period. In ad- The data presented herein have some Dales. dition, diagnostic methods and catego- limitations. It would have been useful Acquisition of data: Dales. rizations of persons with autism have to examine individual immunization Analysis and interpretation of data: Dales, Hammer, Smith. changed over time. Recommenda- and autism records on the same chil- Drafting of the manuscript: Dales. tions have been made for a detailed in- dren; however, these could not be Critical revision of the manuscript for important in- tellectual content: Dales Hammer, Smith. vestigation into the apparent secular in- linked. Further, the childhood immu- Statistical expertise: Dales, Smith. crease in autism cases, carefully nization coverage data used in this study Obtained funding: Dales, Hammer, Smith. Administrative, technical, or material support: Dales, evaluating the extent to which appar- do not provide precise quantification Hammer, Smith. ent increases in autism are real as op- of the percentages of children who re- Study supervision: Dales, Smith.

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