Prevalence of Cerebral Palsy in Quebec: Alternative Approaches
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1 Originl Pper Received: My 25, 2012 Accepted: September 20, 2012 Published online: Jnury 24, 2013 Prevlence of Cerebrl Plsy in Quebec: Alterntive Approches M. Oskoui L. Joseph b L. Dgenis c M. Shevell Deprtment of Peditrics, Neurology nd Neurosurgery, nd b Deprtment of Biosttistics, McGill University, nd c Reserch Institute, Montrel Children s Hospitl, Montrel, Que., Cnd Key Words Prevlence Registry Cerebrl plsy Cnd Abstrct Aim: To provide n estimte of the period prevlence of cerebrl plsy (CP) in the province of Quebec. Methods: Children with CP were identified from three consecutive birth cohorts ( ) from the Quebec CP Registry, covering 6 of the 17 dministrtive helth regions of the province. Two inferentil pproches were pplied for period prevlence estimtion, frequentist nd byesin. Results: 228 children were identified with CP. Using frequentist pproch, the overll prevlence of CP ws 1.84 children ged 9 11 yers living in those res in 2010 (95% CI ). Using byesin pproch tking into ccount the uncertinty bout the registry s sensitivity in cpturing ll cses, the overll prevlence is higher t 2.30 children with 95% CI ( ). Conclusion: Using byesin pproch to djust for the registry s known high specificity nd lower sensitivity, the prevlence estimte is in concordnce with worldwide estimtes nd estimtes using dministrtive dtbses in western Cndin provinces. Future studies re needed to vlidte the dignosis of CP within dministrtive dtbses nd to evlute possible regionl trends cross Cnd in both prevlence nd helth service utiliztion, which my highlight disprities in helthcre delivery. Copyright 2013 S. Krger AG, Bsel Cerebrl plsy (CP) is the most common cuse of physicl impirment encountered in children with n estimted prevlence of live births in Western popultions [1]. Studies drwn from vriety of geogrphiclly dispersed popultion-bsed service registries, including recent study in Cliforni, suggest cler temporl trend towrds incresing survivl well into dulthood [2]. Longevity is inversely correlted with disbility, with most individuls without severe disbilities living to ge 35 yers nd beyond [3]. As chronic disorder cross the lifespn, with multiplicity of functionl limittions nd co-morbidities, it is not surprising tht CP hs substntil dditionl societl costs relted to dditionl medicl, rehbilittion nd eductionl needs ttched to ech individul cse [4]. Anticipting helth service needs should idelly be bsed on current locl prevlence estimtes. The overll prevlence of CP in Cnd hs only been studied in the provinces of British Columbi (BC) nd Albert using dministrtive dtsets. In BC, record serch of dministrtive dtbses for the birth cohorts ws conducted using the ICD-9 CP dignostic code 343 for cse scertinment recorded fter 3 yers of ge [5]. The reported period prevlence ws 2.68 live births. In Albert, dministrtive dtbses were serched using similr inclusion nd exclusion criteri s were used in BC [6]. The ICD-9 code 343 ws lso used for cse scertinment either recorded t 3 yers of ge or prior to 3 E-Mil krger@krger.com S. Krger AG, Bsel /13/ $38.00/0 Mrym Oskoui, MD, MSc, FRCPC Montrel Children s Hospitl 2300 Tupper Street, A-512 Montrel, QC H3H 1P3 (Cnd) E-Mil mcgill.c
2 yers if recorded t lest three times. The period prevlence ws 2.57 children live t 8 yers. Four Cndin studies hve lso exmined the prevlence of CP mong cohorts of preterm infnts Albert, Nov Scoti, BC nd Quebec [7 10]. There re no overll prevlence figures for CP in Quebec. The gol of this study is to provide n estimte of the period prevlence of CP in Quebec. M e t h o d s Cse Ascertinment The Multiregionl Cndin popultion-bsed CP Registry ws first estblished in Quebec s the Registre de l Prlyse Cérébrle de Québec (REPACQ). It is now being expnded through vriety of funding support to other provinces in Cnd including Albert, Ontrio, BC, Nov Scoti nd Newfoundlnd. Utilizing the frmework of the regionliztion of peditric rehbilittion service delivery, children with CP born between 1999 nd 2001 were enrolled within 6 of the province s 17 dministrtive helth regions cpturing 52.4% of ll children ged 9 11 yers living in Quebec s of The six dministrtive regions include: Cpitle-Ntionle, Estrie, Montrel, Outouis, Lnudière nd Lurentides. In the province of Quebec, peditric neurologists, developmentl peditricins nd physitrists working in the hospitl settings systemticlly refer children with CP to regionl rehbilittion centers s soon s the dignosis hs been estblished. Thus, scertinment for the CP Registry ws minly crried out in the rehbilittion centers. Children with CP were identified by physicins nd clinicl coordintors working t the CP clinics of the regionl rehbilittion centers. The list of children compiled from these clinics ws compred to the list of children seen t ech center by ll rehbilittion professionls for completeness, including physicl therpists, occuptionl therpists, speech therpists, psychologists nd udiologists. The scertinment strtegies nd timeline of registrtion nd follow-up for the registry re outlined in online supplementry figure 1 (see www. krger.com/doi/ / ). Overll, the men number of scertinment sources per child ws 3, the first being the CP clinics nd the second most common source being the lists from different professionls working with the children. Ethicl permission for the Registry s estblishment nd implementtion hs been obtined t the locl host institution (McGill University Helth Center Reserch Institute) nd ech prticipting peditric rehbilittion center. Once children were identified, prents or gurdins were pproched for consent to prticipte in the Registry. Non-prticipnts re lso indexed by gender nd region of residence for prevlence estimtions. Prticipnts in REPACQ re scertined only when child is beyond the ge of 2 yers nd confirmed fter 5 yers of ge. This voids the potentil flse cpture of young infnts with trnsitory neuromotor findings under 2 yers of ge [11]. The dignosis is confirmed fter 5 yers of ge bsed on medil record review t ech prticipting rehbilittion center, with direct communiction by the on-site reserch coordintor with the treting tem for ny clrifiction needed. The reserch coordintors re often members of the treting tem. CP is defined in ccordnce with recent consensus sttements s non-progressive motor impirment of erly onset, tht is presumbly cerebrl in origin, which my or my not be ssocited with developmentl delys, cognitive disbility, lnguge impirment, epilepsy, sensory (uditory or visul) loss, orthopedic bnormlities, or behviorl difficulties [12]. Mesures of Functionl Severity The Gross Motor Function Clssifiction System (GMFCS) is 5-level clssifiction system tht describes the gross motor function of children nd youth with CP, with well-estblished vlidity nd relibility [13]. Distinctions between levels re bsed on functionl bilities nd the need for ssistive technology with levels I III being mbulnt nd levels IV V being non-mbulnt. The GMFCS level for ech child ws recorded t 2 yers of ge nd ressessed when possible t 5 yers of ge. The most recent score ws used in our nlysis. The Mnul Ability Clssifiction System (MACS) is newer 5-level clssifiction system tht describes the typicl fine motor function for children with CP, with estblished vlidity nd relibility [14]. Distinctions between the levels re bsed on the child s bility to hndle objects nd their need for ssistnce or dpttions to perform mnul tsks in everydy life, rnging from level I with no restriction on ctivities of dily living to level V where totl ssistnt is needed for ctivities of dily living. The MACS becme vilble during the follow-up period of the registry nd scores re reported only when vilble t 5 yers of ge. Sttisticl Anlyses For this study, cses of CP (both prticipnts nd non-prticipnts) were identified from the REPACQ registry born between Jnury 1, 1999 nd December 31, A dtset ws compiled consisting of the number of individuls with CP within ech of the 6 dministrtive helth regions. PASW sttistics softwre version 18.0 (PASW, Chicgo, Ill., USA, 2009) ws used for dt entry nd frequentist sttisticl nlysis, nd the sttisticl softwre WINBUGS version ws used for byesin nlysis [15]. Two inferentil pproches were pplied for period prevlence estimtion, frequentist nd byesin. The frequentist pproch estimtes the prevlence of CP using the number of cses s the numertor nd the number of children of the sme ge living in the re s the denomintor, bsed on 2010 Cndin census dt for ech region. Prevlence within ech dministrtive helth region, s well s overll, ws estimted with 95% confidence intervl (CI). This pproch, however, ssumes tht ll identified cses re true positives nd represent ll the true positives within the popultion. The byesin pproch more relisticlly does not ssume tht the registry provides perfect dignostic informtion, leding to the possibility of both flse positive nd flse negtive scertinment of CP sttus. This pproch strts with prior probbility distributions for ll unknown prmeters (such s prevlence, the sensitivity nd specificity of the CP dignosis entry in the registry) nd uses the dt to updte these prmeters through the likelihood function into posterior probbility. The posterior probbility represents wht resercher should believe fter seeing the current dtset, nd ccounting for ny informtion input through the prior distributions [16 18]. A uniform prior distribution [ (1,1)], which sys ll possible vlues re eqully likely priori, ws used for the prevlence of CP, so tht the finl inferences re bsed on the dt nd not on ny prior knowledge bout the prevlence. Prior knowledge bout the sensitivity nd specificity of the dignosis of CP within the registry ws tken into considertion Prevlence of Cerebrl Plsy in Quebec D OI : /
3 nd prior distributions were determined by n expert pnel consensus (two neurologists nd one physicl therpist leding the registry) well wre of the strengths nd limittions of the registry. A prior distribution ws set for very high specificity of %, represented by uniform prior density rnging from to %, nd sensitivity rnge of 75 85%, represented by ( ) prior density. To evlute robustness of our estimtes, two dditionl sensitivity priors were used: pessimistic rnge from 65 to 75% represented by ( ) prior density, nd n optimistic rnge from 85 to 95% represented by ( ) prior density. R e s u l t s A totl of 228 children with CP were identified cross ll three birth cohorts, of which 186 fully prticipted in the registry. Follow-up informtion nd ressessment fter 5 yers of ge ws vilble on ll 186 of the prticipting children. Boys mde up 53.9% of ll children with CP. Informtion on GMFCS level ws vilble on ll 186 prticipting children. The mjority hd GMFCS level of I (48%), with 130 (70%) hving n mbulnt GMFCS level (I III). The MACS were vilble only on 137 children in the registry, with third hving level I nd the remining groups being eqully divided. The chrcteristics of these children re shown in tble 1. Per the frequentist nlysis, the overll prevlence of CP cross ll 6 regions for ll three birth cohorts combined ws 1.84 children living in those res in 2010 (95% CI ). The period prevlence estimtes per dministrtive helth region show importnt regionl differences ( tble 2 ), with the lowest prevlence estimte in the Lurentins, Lnudiere nd Outouis regions nd higher estimtes in Estrie, Cpitle-ntionle, nd Montrel regions. These differences could not be ccounted for by differences in popultion sizes for children 9 11 yers of ge. Using byesin pproch tking into ccount the uncertinty bout the registry s sensitivity in cpturing ll cses, the overll prevlence is higher t 2.30 children 9 11 yers with 95% credible intervl (CrI) ( ). This higher estimte reflects the imperfect sensitivity ccounting for the presence of flse negtive cses. To evlute the robustness of this estimte, the prevlence estimte using the pessimistic rnge of sensitivity llowing for greter number of flse negtives resulted in higher prevlence of 2.63 children ged 9 11 yers with 95% CrI ( ). The prevlence estimte using the optimistic sensitivity rnge llowing for smller number of flse negtives resulted in lower prevlence of 2.04 children ged 9 11 yers with 95% CrI ( ). Tble 1. C hrcteristics of children in REPACQ Discussion Totl (% vilble) CP t 5 yers, n Refusls, n b Boys, n (%) c 41 (53) 44 (59) 38 (50) 123 (54) GMFCS, n I (48) II (10) III (12) IV (14) V (16) MACS, n I (32) II (17) III (15) IV (17) V (19) Number of children identified with CP t 5 yers of ge (prticipnts ressessed t 5 yers nd non-prticipnts). b Number of non-prticipnts. c Number of boys (percentge of totl number of children identified with CP). This study provides the first estimtes of the overll prevlence of CP in Quebec, nd the first popultionbsed estimtes in Cnd. The two previous overll CP prevlence estimtes in Cnd were reported using different denomintors, mking comprison between the two more chllenging [5, 6]. Using live birth denomintor when the numertor is being cptured during lter time period (fter 2 yers of ge in CP) cn be misleding if migrtion of the popultion nd infnt mortlity re not ccounted for. This effect is more pronounced mong premture newborns tht hve higher mortlity rte. Furthermore, the two previous Cndin studies were bsed on dministrtive dtbses which re incresingly being used in epidemiologicl studies. Administrtive dt sources hve the benefit of being redily vilble t miniml cost nd llow ccess to longitudinl dt. However, they re primrily estblished for helth service reimbursement nd re not designed s ccurte sources of clinicl informtion. Furthermore, the dignosis of CP within dministrtive dtbses hs never been vlidted. Prevlence estimtes for CP using dministrtive dtbses hve been reported using only frequentist pproch, with misleding nrrow CIs for the point estimte when 266 Oskoui /Joseph /Dgenis /Shevell
4 Tble 2. R EPACQ regionl prevlence of CP (children live in 2010) Helth region CP, n Children live 9 11 yers in 2010, n b Frequentist pproch prevlence 95% CI B yesin pproch prevl ence 95% CrI Cpitle-Ntionle 29 17, Estrie 24 9, Montrél , Outouis 15 11, Lnudière 18 15, Lurentides 18 17, Totl , Vlues re bsed on the Cndin 2010 census dt. N umber of children with CP identified in REPACQ. b Number of children ged 9 11 yers living in the sme regions s per the 2010 Cnd census. very lrge popultion denomintors re used. Using byesin pproch llows reserchers to intuitively tke into ccount some of the uncertinty bout their dt. This pproch hs been used in prevlence studies on number of different conditions but hs not been pplied to CP [16]. The byesin prevlence estimtes from the registry fll within the children reported uniformly worldwide nd within the estimtes from dministrtive dtbses in western Cndin provinces. Although ll cses in the registry re expected to be true positives (high specificity), it is suspected tht ll cses of CP within these regions hve not been cptured (vrible sensitivity). Using byesin pproch to djust for this, the estimted prevlence is higher reflecting the uncertinty in complete cse scertinment. Regionl differences cn reflect vritions in sensitivity (incomplete cpture in some regions), or reflect tendency for fmilies to relocte to lrger urbn res with more service ccess for their child s profile of impirments. Over third of children in the registry hd GMFCS level within the mbulnt rnge, with n expected long-term survivl well into dulthood. There were 42 non-prticipting children with CP in our study, nd they were included in our numertor for overll prevlence estimtion. The limittions brought by this include n overestimting of the prevlence if indeed some of these children were found to hve different dignosis, or if these children moved out of these regions. Better chrcteriztion of the potentil misclssifiction within the REPACQ registry (possible missed cses sensitivity) would help trget improvements for cse scertinment. Future studies re lso needed to vlidte the dignosis of CP within existing dministrtive dtbses such s physicin billing clims nd to ssess the fesibility of using such dtbses for cse scertinment by compring these with ptient registry. The specificity nd sensitivity of the dignosis of CP within dministrtive dtbses hs not been evluted. It will lso be importnt to evlute possible regionl trends cross Cnd in both prevlence nd helth service utiliztion, which my highlight disprities in helthcre delivery. The Cndin Multiregionl CP Registry will offer this opportunity once enrollment is complete in ll res, with comprison possible with dministrtive dtbses vilble provincilly through the Cndin system of universl helth coverge. Adjusting for misclssifiction is essentil for obtining ccurte prevlence estimtes, which is needed to pln future helth service delivery to individuls nd their fmilies with CP. Only with ccurte nd relible dt cn plnning be rtionl nd comprehensive for both current nd future expecttions nd needs. Acknowledgements The Registre de l Prlyse Cérébrle de Québec (REPACQ) hs been funded by the Réseu de recherche sur le développement, l snté et le bien-être de l enfnt (RSDE) des Fonds de Recherche en Snté du Québec (FRSQ) nd NeuroDevNet Ntionl Centre of Excellence. Disclosure Sttement The uthors hve no conflicts of interest to disclose. Prevlence of Cerebrl Plsy in Quebec D OI : /
5 References 1 Hirtz D, Thurmn DJ, Gwinn-Hrdy K, Mohmed M, Chudhuri AR, Zlutsky R: How common re the common neurologic disorders? Neurology 2007; 68: Struss D, Shvelle R, Reynolds R, Rosenbloom L, Dy S: Survivl in cerebrl plsy in the lst 20 yers: signs of improvement? Dev Med Child Neurol 2007; 49: Hutton JL, Colver AF, Mckie PC: Effect of severity of disbility on survivl in north est Englnd cerebrl plsy cohort. Arch Dis Child 2000; 83: Oskoui M, Shevell MI: Cerebrl plsy nd the trnsition from peditric to dult cre. Continuum Neurol 2009; 15: Smith L, Kelly KD, Prkchin G, Voklnder DC: The prevlence of cerebrl plsy in British Columbi, Cn J Neurol Sci 2008; 35: Robertson CMT, Svenson LW, Joffres MR: Prevlence of cerebrl plsy in Albert. Cn J Neurol Sci 1998; 25(suppl 2): Robertson CMT, Wtt MJ, Ysui Y: Chnges in the prevlence of cerebrl plsy for children born very premturely within popultion-bsed progrm over 30 yers. JAMA 2007; 297: Vincer MJ, Allen AC, Joseph KS, Stinson DA, Scott H, Wood E: Incresing prevlence of cerebrl plsy mong very preterm infnts: popultion-bsed study. Peditrics 2006; 118:e1621 e Synnes AR, Ling EW, Whitfield MF, et l: Perintl outcomes of lrge cohort of extremely low gesttionl ge infnts (23 28 completed weeks of gesttion). J Peditr 1994; 125: Lefebvre F, Glorieux J, St-Lurent-Ggnon T: Neontl survivl nd disbility rte t ge 18 months for infnts born between 23 nd 28 weeks of gesttion. Am J Obstet Gynecol 1996; 174: Nelson KB, Ellenberg JH: Children who outgrew cerebrl plsy. Peditrics 1982; 69: Rosenbum P, Pneth N, Leviton A, et l: A report: the definition nd clssifiction of cerebrl plsy April Dev Med Child Neurol Suppl 2007; 109: Plisno R, Rosenbum P, Wlter S, Russell D, Wood E, Gluppi B: Development nd relibility of system to clssify gross motor function in children with cerebrl plsy. Dev Med Child Neurol 1997; 39: Elisson AC, Krumlinde-Sundholm L, Rösbld B, Beckung E, Arner M, Ohrvll AM, Rosenbum P: The Mnul Ability Clssifiction System (MACS) for children with cerebrl plsy: scle development nd evidence of vlidity nd relibility. Dev Med Child Neurol 2006; 48: Lunn DJ, Thoms A, Best N, Spiegelhlter D: WinBUGS byesin modelling frmework: concepts, structure, nd extensibility. Sttist Comput 2000; 10: Wyse JM, Joseph L, Brkun AN, Sewitch MJ: Accurcy of dministrtive clims dt for polypectomy. CMAJ 2011; 183:E743 E McV Messm LL, Brnscum AJ, Collins MT, Grdner IA: Frequentist nd byesin pproches to prevlence estimtion using exmples from Johne s disese. Anim Helth Res Rev 2008; 9: Joseph L, Gyorkos TW, Coupl L: Byesin estimtion of disese prevlence nd the prmeters of dignostic tests in the bsence of gold stndrd. Am J Epidemiol 1995; 141: Oskoui /Joseph /Dgenis /Shevell
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