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  Research Article The Age at Diagnosis of Autism Spectrum Disorder inChildren in Japan Shigeki Kurasawa  , 1 Kiyomi Tateyama, 2 Ryoichiro Iwanaga, 3 Taro Ohtoshi, 1 Ken Nakatani, 1 and Katsushi Yokoi 4 󰀱 Department of Rehabilitation Sciences, Kansai University of Welfare Sciences, 󰀳-󰀱󰀱-󰀱 Asahigaoka, Kashiwara 󰀵󰀸󰀲-󰀰󰀰󰀲󰀶, Japan 󰀲 Department of Occupational Terapy, School of Comprehensive Rehabilitation, College of Health and Human Sciences,Osaka Prefecture University, 󰀳-󰀷-󰀳󰀰 Habikino, Habikino, Osaka 󰀵󰀸󰀳-󰀸󰀵󰀵󰀵, Japan 󰀳 Department of Health Sciences, Nagasaki University Graduate School of Biomedical Sciences, 󰀱-󰀱󰀲-󰀴 Sakamoto,Nagasaki 󰀸󰀵󰀲-󰀸󰀵󰀲󰀳, Japan 󰀴 Department of Occupational Terapy, Faculty of Health Sciences, Morinomiya University of Medical Sciences,󰀱-󰀲󰀶-󰀱󰀶, Nankoukita, Suminoe-ku, Osaka 󰀵󰀵󰀹-󰀰󰀰󰀲󰀴, Japan Correspondence should be addressed to Shigeki Kurasawa; kurasawa.shige@gmail.com Received 19 November 2017; Revised 24 March 2018; Accepted 2 April 2018; Published 7 May 2018 Academic Editor: Namik Y. Ozbek Copyright © 󰀲󰀰󰀱󰀸 Shigeki Kurasawa et al. Tis is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the srcinal work is properly cited. Background  . No large-scale study o the timing o autism spectrum disorder (ASD) diagnosis has been perormed in Japan to date.Te aim o this study was to examine sex differences and annual trends in age at diagnosis o ASD using clinical data.  Methods .Clinical data or children aged less than 󰀱󰀸 years diagnosed with ASD between January 󰀱, 󰀲󰀰󰀰󰀹, and December 󰀳󰀱, 󰀲󰀰󰀱󰀳, and inwhom ollow-up was possible 󰀱 year afer diagnosis, were extracted.  Results . Te mean age at ASD diagnosis was 󰀷.󰀲  ±  󰀴.󰀲 years andthe mode age was 󰀳 years. No sex difference was observed or age at diagnosis (  = 0.157 ). An annual trend o earlier diagnosiswas observed when 󿬁scal years were compared (  < 0.001 ).  Conclusion.  Tis study highlighted the need to develop and provideappropriate early intervention methods and services or ASD children in Japan. 1. Introduction In the International Statistical Classi󿬁cation o Diseases andRelated Health Problems (ICD-󰀱󰀰), pervasive developmentaldisorder (PDD) is classi󿬁ed into childhood autism, atypicalautism, Rett syndrome (RS), overactive disorder associ-ated with mental retardation and stereotyped movements,Asperger’s syndrome, other childhood disintegrative disor-ders, and PDD-unspeci󿬁ed. Meanwhile, the Diagnostic andStatisticalManualoMentalDisordersFifhEdition(DSM-󰀵)considers PDDs, with the exception o RS, to be synonymouswithautismspectrumdisorder(ASD).TeprevalenceoASDis approximately 󰀱% and an upward trend has been reported[󰀱–󰀴]. Many reports are skeptical that the increase in ASD is the result o an increase in risk actors, and many are o theopinionthattheincreaseistheresultochangestodiagnosticcriteria and a younger age at diagnosis [󰀱, 󰀳]. Many studies o the increase in ASD are underway, and research intotherapeutic interventions is also ongoing. Nonpharmacolog-ical therapies or ASD include approaches based on appliedbehavior analysis (e.g., the Lovaas approach), structuredteaching (e.g., reatment and Education o Autistic andrelated Communication Handicapped Children), and tar-geted skill-based intervention (e.g., Picture Exchange Com-munication System). All o these therapies have con󿬁rmedevidence levels [󰀱, 󰀵], with some interventions reported to be more effective when implemented early [󰀱, 󰀶, 󰀷], leading to increased interest in the early diagnosis o ASD.Tere have been several reviews and large-scale study reports o age at ASD diagnosis [󰀸–󰀱󰀰]. However, studies o  age at ASD diagnosis have major problems. Te 󿬁rst is thepotential or the residential area o the child to have an effecton the timing o ASD diagnosis [󰀸, 󰀱󰀱]. It is easily conceivable thatthetimingoASDdiagnosisisaffectedbythemedicalor HindawiInternational Journal of PediatricsVolume 2018, Article ID 5374725, 5 pageshttps://doi.org/10.1155/2018/5374725  󰀲 International Journal o Pediatrics 󰁡󰁢󰁬󰁥 󰀱: Characteristics o JMDC clinical data.Number o medical institutions  †1 No. o JMDC-contracted medical institutions JMDC coverageHospital †2 Clinic †3 Hospital †2 Clinic †3 Hospital †2 Clinic †3 󰀲󰀰󰀰󰀹 󰀸,󰀷󰀳󰀹 󰀹󰀹,󰀶󰀳󰀵 󰀷,󰀳󰀹󰀸 󰀸󰀱,󰀷󰀷󰀹 󰀸󰀴.󰀷% 󰀸󰀲.󰀱%󰀲󰀰󰀱󰀰 󰀸,󰀶󰀷󰀰 󰀹󰀹,󰀸󰀲󰀴 󰀷,󰀵󰀵󰀶 󰀸󰀴,󰀵󰀵󰀸 󰀸󰀷.󰀲% 󰀸󰀴.󰀷%󰀲󰀰󰀱󰀱 󰀸,󰀶󰀰󰀵 󰀹󰀹,󰀵󰀴󰀷 󰀷,󰀶󰀴󰀱 󰀸󰀷,󰀱󰀲󰀷 󰀸󰀸.󰀸% 󰀸󰀷.󰀵%󰀲󰀰󰀱󰀲 󰀸,󰀵󰀶󰀵 󰀱󰀰󰀰,󰀱󰀵󰀲 󰀷,󰀶󰀵󰀸 󰀸󰀶,󰀵󰀸󰀲 󰀸󰀹.󰀴% 󰀸󰀶.󰀵%󰀲󰀰󰀱󰀳 󰀸,󰀵󰀴󰀰 󰀱󰀰󰀰,󰀵󰀲󰀸 󰀷,󰀵󰀲󰀹 󰀸󰀴,󰀳󰀸󰀴 󰀸󰀸.󰀲% 󰀸󰀳.󰀹% †1 Number o medical acilities according to a Ministry o Health, Labour and Welare survey.  †2 Medical acilities with 󰀲󰀰 or more beds.  †3 Medical acilitieswith 󰀰–󰀱󰀹 beds. JMDC Calamus DatabaseAcquired clinical data(1) ose diagnosed with PDD between Jan 1, 2009 and Dec 31, 2013(2) ose aged less than 18 years at diagnosis(3) ose in whom follow-up was possible 1 year aer diagnosis n  = 8270 n  = 8264Analysis n  = 6Exclusion of those diagnosed with RS F󰁩󰁧󰁵󰁲󰁥 󰀱: Flowchart o the process rom data sample extraction to analysis. healthcaresystemothearea.StudiesoageatASDdiagnosisthereore need to examine age by country and region. Tesecond problem is the uncertainty regarding the existence o asexdifferenceinthetimingoASDdiagnosis.Somereportshave suggested that the timing o ASD or AS diagnosis isdelayed in girls without mental and behavioral disorders [󰀲,󰀹]. However, no large-scale survey o the timing o diagnosishas been conducted in Japan. Te third problem is whetherannualtrendscanbeseenintheageatASDdiagnosis.WorldAutismAwarenessDaywasestablishedattheUnitedNationsGeneral Assembly in 󰀲󰀰󰀰󰀷 and has likely increased socialawareness o ASD. ools have also been developed to allow or the early diagnosis o ASD [󰀴, 󰀱󰀲]. Tese changes could cause annual trends in the age at ASD diagnosis.Te aim o this study was to examine sex differences andannual trends in age at diagnosis o ASD using clinical data. 2. Materials and Methods 󰀲.󰀱. Materials and Methods󰀲.󰀱.󰀱. Subject Data and Extraction of Samples.  Clinical datawere acquired rom Japan Medical Data Center Co., Ltd.(JMDC),whichisJapan’slargestprovideroclinicaldata.Tedata are a consolidation o all clinical data o insured per-sons held by multiple contracted health insurance societies,thereby acilitating the understanding o inormation such asconsultations and transers by multiple medical institutionswithout omissions. Te acquired clinical data included thebasicattributesopatients,thetypeomedicalinstitution,thedisease name (ICD-󰀱󰀰 classi󿬁cation codes), and the contento therapy. able 󰀱 shows the characteristics o the JMDCdata including the coverage. JMDC clinical data includeddata rom 󰀸󰀰% or more o hospitals and clinics in Japanrom 󰀲󰀰󰀰󰀹 through 󰀲󰀰󰀱󰀳. A 󿬂owchart o the process romsample extraction to analysis is presented in Figure 󰀱. In thepresentstudy,thedatathatmetallotheollowingconditionswere extracted rom among the clinical data held by theJMDC: (󰀱) those diagnosed with PDD between January 󰀱,󰀲󰀰󰀰󰀹,andDecember󰀳󰀱,󰀲󰀰󰀱󰀳;(󰀲)thoseagedlessthan󰀱󰀸yearsat diagnosis; and (󰀳) those in whom ollow-up was possible 󰀱year afer diagnosis. At the end, those with RS ( 󽠵 = 6 ) wereexcluded and 󰀸󰀲󰀶󰀴 samples were used in the 󿬁nal analysis. 󰀲.󰀲. Analysis Methods.  Descriptive statistics o the acquiredsamples were used to understand the basic attributes o thesubjects, the diagnosing medical institution, and the clinicaldepartment, afer which sex differences in age at diagnosiswere examined by type o ASD using the Mann-Whitney   U  test. Tereafer, annual trends in age at ASD diagnosis wereexamined by the Kruskal-Wallis test. Te level o signi󿬁cancewas set at 󰀵%, and IBM SPSS ver. 󰀲󰀴.󰀰 was used or statisticalanalyses. 󰀲.󰀳. Research Ethics.  Te clinical data used in the presentstudy wereprovidedby JMDCwiththeconsentotheJMDCethical review board. Tis study was also approved by theResearch Ethics Committee o Kansai University o WelareSciences (approval number: 󰀱󰀵-󰀰󰀱). 3. Results Te basic attributes o the subjects are presented in able 󰀲.Te mean age at ASD diagnosis was  7.2 ± 4.2  years and themode age was 󰀳 years. Te male-to-emale ratio was 󰀷󰀶.󰀱%males and 󰀲󰀳.󰀹% emales. Te diagnostic criteria or ASDusing ICD-󰀱󰀰 were as ollows: childhood autism (󰀳󰀳.󰀶%),atypical autism (󰀲.󰀹%), Asperger’s syndrome (󰀹.󰀴%), other  International Journal o Pediatrics 󰀳 󰁡󰁢󰁬󰁥 󰀲: Basic attributes o the subjects  (󽠵 = 8264) .Age at diagnosis in yearsModal age 󰀳.󰀰Median (󰀲󰀵th–󰀷󰀵th percentile) 󰀶.󰀰 (󰀴.󰀰–󰀱󰀰.󰀰)Mean  ±  SD 󰀷.󰀲  ±  󰀴.󰀲Sex  󽠵  (%)Male 󰀶󰀲󰀸󰀵 (󰀷󰀶.󰀱)Female 󰀱󰀹󰀷󰀹 (󰀲󰀳.󰀹)Autism spectrum disorder †1 󽠵  (%)Childhood autism 󰀲󰀷󰀷󰀸 (󰀳󰀳.󰀶)Atypical autism 󰀲󰀴󰀱 (󰀲.󰀹)Asperger’s syndrome 󰀷󰀷󰀳 (󰀹.󰀴)Other pervasive developmental disorder 󰀵󰀶 (󰀰.󰀷)Pervasive developmental disorder, unspeci󿬁ed 󰀳󰀹󰀳󰀱 (󰀴󰀷.󰀶)Dual and multiple diagnosis 󰀴󰀸󰀵 (󰀵.󰀹)Medical acilities  󽠵  (%)National hospital, public hospital 󰀱󰀹󰀸󰀹 (󰀲󰀴.󰀱)University hospital 󰀳󰀹󰀲 (󰀴.󰀷)Other hospital 󰀱󰀵󰀰󰀹 (󰀱󰀸.󰀳)Medical office 󰀴󰀳󰀷󰀴 (󰀵󰀲.󰀹)Diagnosis and treatment department  󽠵  (%)Paediatrics 󰀲󰀹󰀹󰀱 (󰀳󰀶.󰀲)Neuropsychiatry 󰀲󰀳󰀶󰀸 (󰀲󰀸.󰀷)Internal medicine 󰀲󰀰󰀲󰀵 (󰀲󰀴.󰀵)Orthopedics 󰀱󰀶󰀷 (󰀲.󰀰)Obstetrics and gynecology 󰀱󰀱󰀴 (󰀱.󰀴)Otolaryngology 󰀴󰀶 (󰀰.󰀶)Radiology 󰀴󰀴 (󰀰.󰀵)Ophthalmology 󰀳󰀸 (󰀰.󰀵)Neurosurgery 󰀲󰀲 (󰀰.󰀳)Urology 󰀱󰀷 (󰀰.󰀲)Others 󰀴󰀳󰀲 (󰀵.󰀲) †1 Subtype o PDD using the 󿬁rst date o diagnosis (exclusion o RS). pervasive developmental disorder (󰀰.󰀷%), and PDD-unspec-i󿬁ed (󰀴󰀷.󰀶%). O the 󰀵.󰀹% o subjects who were diagnosed ashaving overlapping conditions with PDD during their 󿬁rstconsultation, 󰀷󰀲% were diagnosed with childhood autismand PDD-unspeci󿬁ed (data not shown). Furthermore, otherorms o childhood disintegrative disorder and overactivedisorder associated with mental retardation and stereotypedmovements were not included in the dataset. Te diagnosingmedicalinstitutionwasamedicalofficeinmostcases(󰀵󰀲.󰀹%),ollowed by a national hospital or public hospital (󰀲󰀴.󰀱%),university hospital (󰀴.󰀷%), and other medical institutions(󰀱󰀸.󰀳%). Te clinical department was pediatrics or 󰀳󰀶.󰀲%o the subjects, neuropsychiatry or 󰀲󰀸.󰀷%, and internalmedicine or 󰀲󰀴.󰀵%. Tese three clinical departments madeapproximately 󰀹󰀰% o diagnoses.able󰀳showsthesexdifferencesinageatASDdiagnosis.Te mean age at diagnosis was 󰀷.󰀱󰀸 years in males and 󰀷.󰀴󰀲years in emales, and there was no signi󿬁cant difference (  =0.157 ). Te median age was 󰀶.󰀰 years or both males andemales, and the modal age was 󰀳 years. 12345678910111213141516170Age (years)Year20092010201120122013050100150200250300    N  u  m    b  e  r F󰁩󰁧󰁵󰁲󰁥 󰀲: Annual trends in age at diagnosis and patient numbers. 12345678910111213141516170Age (years).020.040.060.080.0100.0    C  u  m  u    l  a   t   i  v  e    (   %    ) Year20092010201120122013 F󰁩󰁧󰁵󰁲󰁥 󰀳: Annual trends in age at diagnosis and cumulativepercentage o patients. Figure 󰀲 shows the sample size at the age at diagnosis oreach 󿬁scal year. Te mode age was 󰀳 years in all 󿬁scal years,and a tapering in the requency o occurrence was observedas the age increased beyond 󰀳.able 󰀴 shows the results o a comparison between theage at diagnosis and 󿬁scal year. Te age at diagnosis oreach 󿬁scal year was as ollows: 󰀷.󰀸 years in 󰀲󰀰󰀰󰀹, 󰀸.󰀲 yearsin 󰀲󰀰󰀱󰀰, 󰀷.󰀵 years in 󰀲󰀰󰀱󰀱, 󰀷.󰀱 years in 󰀲󰀰󰀱󰀲, and 󰀶.󰀳 yearsin 󰀲󰀰󰀱󰀳. Te median age at diagnosis was 󰀷.󰀰 years in 󰀲󰀰󰀰󰀹,󰀸.󰀰 years in 󰀲󰀰󰀱󰀰, 󰀷.󰀰 years in 󰀲󰀰󰀱󰀱, 󰀵.󰀰 years in 󰀲󰀰󰀱󰀲, and󰀴.󰀰 years in 󰀲󰀰󰀱󰀳. A statistical difference was observed whenthe age at diagnosis was compared with 󿬁scal year using theKruskal-Wallistest(  < 0.001 ).Comparisono󿬁scalyearsinpairs revealed the ollowing: the age at diagnosis in 󰀲󰀰󰀰󰀹 wassigni󿬁cantly higher than 󰀲󰀰󰀱󰀲 and 󰀲󰀰󰀱󰀳; the age at diagnosisin 󰀲󰀰󰀱󰀰 was signi󿬁cantly higher than 󰀲󰀰󰀱󰀱, 󰀲󰀰󰀱󰀲, and 󰀲󰀰󰀱󰀳;and the age at diagnosis in 󰀲󰀰󰀱󰀲 was signi󿬁cantly higher than󰀲󰀰󰀱󰀳.Atrendtowardsyoungerageatdiagnosisinrecentyearswas also observed in Figure 󰀳, which shows the requency o occurrence as cumulative percentages. 4. Discussion Te basic attributes o the subjects showed a male-to-emaleratio o 󰀳:󰀱. Te male-to-emale ratio o ASD is generally considered to be 󰀴:󰀱 [󰀲]. However, this 󿬁nding needs to beexamined careully to establish i it is speci󿬁c to Japan. Te  󰀴 International Journal o Pediatrics 󰁡󰁢󰁬󰁥 󰀳: Sex differences in age (years) at ASD diagnosis. 󽠵  Modal age Median(󰀲󰀵th–󰀷󰀵th) Mean  ±  SD    valueMale 󰀶󰀲󰀸󰀵 󰀳.󰀰 󰀶.󰀰 (󰀴.󰀰–󰀱󰀰.󰀰) 󰀷.󰀲  ±  󰀴.󰀲 󰀰.󰀱󰀵󰀷Female 󰀱󰀹󰀷󰀹 󰀳.󰀰 󰀶.󰀰 (󰀳.󰀰–󰀱󰀱.󰀰) 󰀷.󰀴  ±  󰀴.󰀴 Note . Mann-Whitney   U   test. 󰁡󰁢󰁬󰁥 󰀴: Annual trends in age (years) at ASD diagnosis.Year Mean  ±  SD Median    or difference(󰀲󰀵–󰀷󰀵%ile) 󰀲󰀰󰀰󰀹 󰀲󰀰󰀱󰀰 󰀲󰀰󰀱󰀱 󰀲󰀰󰀱󰀲 󰀲󰀰󰀱󰀳󰀲󰀰󰀰󰀹 󰀷.󰀸  ±  󰀴.󰀳 󰀷.󰀰 (󰀴.󰀰–󰀱󰀱.󰀰) — NS NS  ∗ ∗∗ 󰀲󰀰󰀱󰀰 󰀸.󰀲  ±  󰀴.󰀳 󰀸.󰀰 (󰀴.󰀰–󰀱󰀲.󰀰) — —  ∗∗ ∗∗ ∗∗ 󰀲󰀰󰀱󰀱 󰀷.󰀵  ±  󰀴.󰀵 󰀷.󰀰 (󰀳.󰀰–󰀱󰀱.󰀰) — — — NS  ∗ 󰀲󰀰󰀱󰀲 󰀷.󰀱  ±  󰀴.󰀶 󰀵.󰀰 (󰀳.󰀰–󰀱󰀱.󰀰) — — — — NS󰀲󰀰󰀱󰀳 󰀶.󰀳  ±  󰀴.󰀳 󰀴.󰀰 (󰀳.󰀰–󰀹.󰀰) — — — — — Note.  Kruskal-Wallis test  ( < 0.001) ; Pairwise Kruskal-Wallis test; NS: not signi󿬁cant;  ∗  < 0.05 ;  ∗∗  < 0.01 . criteria or sample extraction in the present study differedrom normal methods o calculating prevalence. Sampleswere extracted longitudinally in the present study, whichmeans that potential bias resulting rom a period effectcannot be ruled out. However, a study in Yokohama City,Japan,thatusedICD-󰀱󰀰diagnosticcriteriacalculatedamale-to-emale ratio o 󰀲.󰀵:󰀱 [󰀱󰀳], which was close to that o thepresent study. Te present study was a large-scale study thataccumulated data over a 󰀵-year period; thereore, the male-to-emale ratio o ASD observed in the present study canbe generalized. No sex difference was observed in the age atASD diagnosis, and the mode age o both males and emaleswas 󰀳 years. Te mode age or each 󿬁scal year was also 󰀳years. Under Japanese maternal and child health practice,health diagnoses are perormed at 󰀱󰀸 months and 󰀳 yearso age, when the majority o inants undergo screening by aphysician.Ourdatashowedthatthepeakageatdiagnosiswasthe age o 󰀳, highlighting the contribution o ASD screeningsduringinanthealthcheckupsinJapan.However,thenumberodiagnosedpatientsaferthepeakageo󰀳showedagradualdeclining curve, which cannot be underestimated. Concernabout undiagnosed cases o Asperger’s syndrome and high-unctioning autism has been reported [󰀱󰀴]. Consequently,there is a need to examine the association between delays inASD diagnosis and the ASD subtypes. A decreasing trend inthe age at diagnosis was observed when the age at diagnosiswas compared or each 󿬁scal year. Tis may be due toincreasedsocialawarenessoASD,butitmightalsoberelatedto the development o effective diagnostic ASD screeningtests and costs [󰀴, 󰀱󰀲]. On the other hand, early diagnosis suggeststheneedtodevelopandprovidemoreeffectiveearly-stage ASD rehabilitation interventions. Inants with ASDhave comorbid sleep disorders associated with disruptions inthe autonomic nervous system and hypersensitivity [󰀱󰀵, 󰀱󰀶]. Sleep disorders in ASD may affect the school lie o thechildreninareassuchassocialinteraction,academicachieve-ment and behavioral problems [󰀱󰀵, 󰀱󰀷]. However, there is no sufficient evidence yet o effective interventions addressingsleeping disorders o inants with ASD. Furthermore, thereis not much clear evidence o the therapeutic effects o the various traditional nonpharmacological therapies on inants[󰀱]. Te 󿬁ndings o the present study highlighted the need todevelopandprovideappropriate,earlyinterventionmethods,and services or children with ASD. 5. Limitations Tis study has several limitations. Te 󿬁rst was the inability to conduct a simple comparison o data with other previousstudies since the present study, unlike cohort studies, ana-lyzed the data o patients who voluntarily sought consulta-tions. Tere might have also been a bias in󿬂uencing parents’decision-making during consultations o the children in thisstudy. Te second limitation was that the sample used in thisstudy included no regional data such as place o residence.It was thereore not possible to examine actors includingdifferences in regional medical services, and the possibility o bias in the 󿬁ndings related to age at diagnosis cannot beruled out. Te third limitation was that it was not possibleto gain an accurate understanding o the total populationwithin the ollow-up period. It was thereore not possible toconsider the prevalence o ASD in the process o examiningthe incidence by 󿬁scal year. However, the total speci󿬁c birthrate in Japan rom 󰀱󰀹󰀹󰀰 to 󰀲󰀰󰀱󰀳 was within the range o 󰀱.󰀲󰀶–󰀱.󰀵󰀷, indicating no major variation [󰀱󰀸]. Te 󿬁ndings o this study are thereore considered reasonable. 6. Conclusions Te age at ASD diagnosis was examined by the subtype o ASDusingJapaneseclinicaldata.Terewasnosexdifferencein age at ASD diagnosis. An annual trend o earlier diagnosiswas observed when 󿬁scal years were compared. Te 󿬁ndingso the present study highlighted the need to develop andprovideappropriate,earlyinterventionmethods,andservicesor children with ASD.
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