nursing outcome in patients with cleft lip and palate who underwent operation
TRANSCRIPT
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An update on the prevalence of cerebral palsy: asystematic review and meta-analysis
Aims
The aim of this study was to provide a comprehensive updateon (1) the overall prevalence of cerebral palsy (CP); (2) theprevalence of CP in relation to birthweight; and (3) theprevalence of CP in relation to gestational age
Method ! systematic review and meta"analysis was conducted andreported# based on the P$%&'! (Preferred $eporting %tems for&ystematic $eviews and 'eta"analyses) statement Population"based studies on the prevalence of CP in children born in 1*or after were selected &tatistical analysis was carried out usingcomputer pac+age $# version 21,
Results
! total of , studies were selected for this review The pooledoverall prevalence of CP was 211 per 1--- live births (*.confidence interval /C%0 122*) The prevalence of CPstratified by gestational age group showed the highest pooledprevalence to be in children weighing 1--- to 1,g at birth(*1 per 1--- live births; *. C% *3--1)# althoughthere was no significant difference on pairwise meta"regressionwith children weighing less than 1---g The prevalence of CPepressed by gestational age was highest in children bornbefore 2 wee+s4 gestation (111- per 1--- live births; *. C%*3155; p6--325)
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Interpretation
The overall prevalence of CP has remained constant in recentyears despite increased survival of at"ris+ preterm infants
1 'aryam 7s+oui1#8#2 9ran:ina Coutinho2#3 onathan 3and* Tamara Pringsheim,
!rticle first published online? 2, != 2-13
Abstract Aims
The aim of this study was to provide a comprehensive update
on (1) the overall prevalence of cerebral palsy (CP); (2) theprevalence of CP in relation to birthweight; and (3) theprevalence of CP in relation to gestational age
Method
! systematic review and meta"analysis was conducted andreported# based on the P$%&'! (Preferred $eporting %tems for
&ystematic $eviews and 'eta"analyses) statement Population"based studies on the prevalence of CP in children born in 1*or after were selected &tatistical analysis was carried out usingcomputer pac+age $# version 21,
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Results
! total of , studies were selected for this review The pooledoverall prevalence of CP was 211 per 1--- live births (*.
confidence interval /C%0 122*) The prevalence of CPstratified by gestational age group showed the highest pooledprevalence to be in children weighing 1--- to 1,g at birth(*1 per 1--- live births; *. C% *3--1)# althoughthere was no significant difference on pairwise meta"regressionwith children weighing less than 1---g The prevalence of CPepressed by gestational age was highest in children bornbefore 2 wee+s4 gestation (111- per 1--- live births; *. C%
*3155; p6--325)
Interpretation
The overall prevalence of CP has remained constant in recentyears despite increased survival of at"ris+ preterm infants
What this paper adds
• This is the first worldwide CP prevalence estimate providedby meta"analysis
• The overall prevalence of CP worldwide is 211 per 1--- live
births
• The prevalence of CP has remained constant in recent
years# despite improved survival of at"ris+ preterm infants
Cerebral palsy (CP) encompasses a heterogeneous group of
early"onset# non"progressive# neuromotor disorders that affectthe developing fetal or infant brain/10 CP is one of the mostcommon causes of childhood physical disability# with anestimated lifetime cost# for persons born in the @nited &tates in2---# of 11* billion dollars/20 !ccurate prevalence estimates
http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0001http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0002http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0002http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0001
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are needed to guide operational health policies and to aid withappropriate resource allocation
%n the past decade# two limited reviews on the prevalence of CP
have been published/3# ,0 The first# published in 2--5# loo+edat both the overall prevalence of CP and the prevalencereported by birthweight in preterm infants The overall medianprevalence estimate reported was 2, per 1--- live births/30 9or preterm infants# a median prevalence of 112 per 1---live births was reported among children weighing between1*--g and 2,g at birth# and 3* per 1--- live births amongchildren weighing less than 1*--g This review did not follow
the P$%&'! (Preferred $eporting %tems for &ystematic $eviewsand 'eta"analyses) statement and had several methodologicallimitations 7nly Anglish"language articles were included#published between 1 anuary 1- and 31 anuary 2--*#searching a single bibliographic database (Pub'ed) ! meta"analysis was not performed; rather# the overall prevalenceestimates of selected studies were combined eBually to providea median estimate &tudies reporting prevalence estimates with
different denominators (live births# neonatal survivors# childrenat a certain age) were combined# and studies includingparticipants born before 1* were included
! second systematic review# published in 2--# eamined theprevalence of CP only in relation to gestational age anddemonstrated a significant decrease in the prevalence of CPwith increasing gestational age/,0 The prevalence ranged from
1, (*. confidence interval /C%0 12*15-) per 1--- childrenborn at 22 to 25 wee+s of gestation# steadily declining thereafter to an estimated 2 (*. C% ,5) per 1--- children born at 2to 31 wee+s# 5 (*. C% ) per 1--- at 32 to 3 wee+s4gestation# and 113 (*. C% -3-1,) per 1--- in term"borninfants This systematic review used rigorous methodology#
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searching four bibliographic databases ('A
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$eferences from 'A
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population surveyed and denominator used (live births#neonatal survivors# children at a specified age)
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including terms for the start and end years of data collection foreach study These were chosen as surrogates for year"by"yearprevalence estimates# which were often not provided by thestudies To address the decision to combine studies that
included postneonatal cases with those that did not# a stratifiedanalysis was completed to see whether these groups of studieswere different from each other ! cumulative meta"analysis wasconducted on the overall prevalence of CP per 1--- live birthsto assess the impact of studies published since the last reviewon the overall estimate Publication bias was assessed usingthe Agger regression test# Eegg and 'a:umdar correlation test#and a visual inspection of funnel plots ! sensitivity analysis was
also carried out to assess the effect of the methodologicalBuality on the results
9or all tests# p6--* was deemed to be significant &tatisticalanalyses were carried out in $ version 21,/50 The metapac+age (version 21-# 2-12 was used to produce the pooledestimates and forest plots %n accordance with the randomeffects model# the studies were weighted according to the
inverse of their variance along with the between"studyheterogeneity (tau"sBuared) arrived at with a
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additional 1 abstracts
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Reference LocationBirthcohort
Data/sourcemethodology
(a)
1998 database
iurdardottiret al.[1]
*celand1990–#003
Administrativedatabase and ot!ersources
+onan et al.[15]
*reland1990–1999
Administrativedatabase and ot!ersources
&ol' et al. [1,]-ort!ern*reland /
198$–199$
+ultile sources2aencies arents+&
4ic!ers et al.[1$]
-et!erlands
198,–1988
Administrativedatabase and ot!ersources
Andersen et al.[18]
-or6a199,–1998
Administrativedatabase
"ie et al.[19] -or6a198,–
1995
Administrative
database
%aber et al.[#0]
6eden1991–199
Administrativedatabase
%aber et al. 6eden 198$– Administrative
http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0014http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0015http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0016http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0017http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0018http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0019http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0020http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0014http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0015http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0016http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0017http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0018http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0019http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0020
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Reference LocationBirthcohort
Data/sourcemethodology
(a)
[#1] 1990 database
%immelmannet al.[##]
6eden1995–1998
%osital clinicalc!art revie6 andot!er
%immelmannet al.[#3]
6eden1999–#00#
%osital clinicalc!art revie6 andre!abilitationreorts
%7ern and !ornren :ernec'[#]
6eden198$–1993
Administrativedatabase
-ordmar' et al.[#5]
6eden1990–1993
%osital;c!artrevie6
4estbom et al.[#,]
6eden1990–199$
Administrativedatabase and ot!ersources
rmed b t6o+&s
http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0021http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0022http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0023http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0024http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0025http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0026http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0027http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0021http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0022http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0023http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0024http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0025http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0026http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0027
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Reference LocationBirthcohort
Data/sourcemethodology
(a)
Colver et al.[#8]
/ 1989–1993
Administrativedatabase and ot!er
in!a et al.[#9] / 1985–198$
Administrativedatabase
urman et al.[30]
/ 198$–1995
Administrativedatabase and ot!ersources
?!aroa! et al.[31]
cotland/
1985–1999
%osital clinicalc!art revie6 andot!er
Arneson et al.[3#]
/A 1999Administrativedatabase and ot!ersources
@!asin et al.[33]
/A199,#000
%osital clinicalc!art revie6 andot!er
?etrini et al.[3]
/A #000–#00
Administrativedatabase
4inter et al.[35]
/A 198,–1991
Administrativedatabase and ot!er
http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0028http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0029http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0030http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0031http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0032http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0033http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0034http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0035http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0028http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0029http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0030http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0031http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0032http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0033http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0034http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0035
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Reference LocationBirthcohort
Data/sourcemethodology
(a)
sources
earinAllsoet al.[3,]
/A 199 +ultile sources
Table 1. Selected studies. (a) Selected studies on oe
studies on cerebral !alsy !realence in infants born !
Reference LocationBirthcohort
Agea
$umber%ith "#
$usur
1. a
Age: age at ascertainment (years). The study by Serdaroglu et al.[37] was e
#uestionnaire or children born in $%%&. 'ut o $ &$ children sur*eyed+ $aged /0$&y. 12+ "hysicians 4A+ not a*ailable.
/. 5A+ gestational age 689+ extremely low birthweight 89+ birthwe
(b)
&ole et al.
[38]
Australia #005 # 1,
&ole et al.[39]
Australia1985–198$
# 1#
Roberts et al. Australia 199$ 8 1,
http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0036http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-note-0001http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0037http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0038http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0039http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0036http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-note-0001http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0037http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0038http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0039
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Reference LocationBirthcohort
Agea
$umber%ith "#
$usur
[0]
Bra et al.[1]
Australia1989–199,
# 30
utton et al.[#]
Australia199#–1993
1 #
4eber et al.
[3] Austria
1999–
#001 1 $0
Robertsonet al.[]
Canada198,–#003
# ,5
incer et al.[5]
Canada1993–#003
# ,,
"eDebvreet al.[,]
Canada 198$–199#
1.5 3$
:acobs et al.[$]
Canada1990–199
1.5–#
#
alo'oriet al.[8]
Einland1991–199
#$
ommis'aet al.[9]
Einland199,–199$
1.5 #3
@eaino et al.[50]
Erance 199$ 5 159
http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0040http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0041http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0042http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0043http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0044http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0045http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0046http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0047http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0048http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0049http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0050http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0040http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0041http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0042http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0043http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0044http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0045http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0046http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0047http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0048http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0049http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0050
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Reference LocationBirthcohort
Agea
$umber%ith "#
$usur
+arret et al.[51] Erance 199$ 5 $,
@uruetet al.[5#]
Erance1990–199#
# ##
alleur et al.[53]
Erance199#–199$
, 1$
4ere and@6ibo[5]
ena -otrovided
# 1
"eversenet al.[55]
-or6a1999–#000
# #,
+arlo6 et al.[5,]
/ and*reland
1995 , 3#
o!r et al.[5$]
/A1993–1998
1.5 ,0,
Figure 1. 9low chart of study selection
http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0051http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0052http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0053http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0054http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0055http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0056http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0057http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0051http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0052http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0053http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0054http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0055http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0056http://onlinelibrary.wiley.com/doi/10.1111/dmcn.12080/full#dmcn12080-bib-0057
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Overall prevalence of cerebral palsy
The study by &inha et al/20 was ecluded from analysisbecause it focused on a small ethnic community with a high rate
of consanguinity that did not represent a true population"basedestimate in the study region Pooling 1 studies that reportedestimates using live births as the denominator# the overallprevalence of CP was 211 per 1--- live births (*. C% 122*; 9ig 2a) The cumulative meta"analysis demonstrates thatthe overall prevalence of CP has remained stable with theaddition of new studies over the past 1- years (9ig 2b) Therewas no significant difference in overall prevalence per 1--- live
births between studies using population"based data (13; *.C% 1221) and studies using administrative data (21; *.C% 2-2235) ! meta"regression sorting the studies by startyear of each cohort and end year of cohort was also conducted#and showed no significant difference by either start ( pI-3,) orend year ( p I -*,) Ghen assessing the importance ofincluding postneonatal cases# the overall estimates of the twogroups of studies were almost identical &tudies including these
cases had a prevalence of 21- (1323-) and thoseecluding the cases had a prevalence of 211 (2-321) Theoverall prevalence appeared higher using studies reportingchildren at a specific age (range 1moy) as the denominator(9ig &1# supporting information published online)# with a pooledprevalence of 21 per 1--- children (*. C% 2133)
Figure . 7verall prevalence of cerebral palsy per 1--- livebirths
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Prevalence of cerebral palsy by birthweight
The pooled prevalence of CP in children per 1--- live birthswas calculated by birthweight category (9ig 3) The prevalence
was highest in children weighing 1--- to 1,g (*1 per 1---live births; *. C% ,3353*)# and lowest in childrenweighing over 2*--g (133 per 1--- live births; *. C% 111,) The prevalence among children weighing under 1---gwas not significantly different from the prevalence among thoseweighing 1--- to 1,g ( pI-1*)# but in both cases wassignificantly higher than among children weighing 1*-- to2,g ( p6---1) The prevalence among children weighing over
2*--g was significantly lower than in all other birthweightgroups ( p6---1)
Figure !. Prevalence of cerebral palsy (CP) in relation tobirthweight (a) Eirthweight less than 1---g; (b) birthweightbetween 1---g and 1,g; (c) birthweight between 1*--g and2*--g; (d) birthweight over 2*--g
Three studies reported the prevalence of CP in relation tobirthweight per 1--- neonatal survivors? --, (*. C% ,*21123) in children under 1*--g# 33 (*. C% *3313-3) in
children weighing between 1*--g and 2,g# and 11 (*. C%1-,12) in children weighing over 2*--g The prevalence ofCP is significantly lower among children weighing between1*--g and 2,g than in those weighing under 1*--g( p6---1) !mong children with a birthweight over 2*--g the
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prevalence of CP was significantly lower than in all other groups( p6---1)
Prevalence of cerebral palsy in relation togestational age
The pooled prevalence per 1--- live births was calculated foreach gestational age group (9ig ,) The prevalence washighest# at 111- (*. C% *3155)# among children bornbefore 2 wee+s of gestation and lowest# at 13* (*. C% 11*1*)# for children born after 3 wee+s Pairwise meta"regression showed that the prevalence of CP was significantly
lower among children born between 2 and 31 wee+s4 gestationthan in children born before 2 wee+s4 gestation ( pI--325)Prevalence was significantly lower among children bornbetween 32 and 3 wee+s4 gestation than among those bornmore preterm ( p6---1)# and was significantly lower amongchildren born after 3 wee+s4 gestation than in all other groups( p6---1) There were fewer studies reporting the prevalence of CP in neonatal survivors in relation to gestational age group
The prevalence was 111- (*. C% *3155) per 1---neonatal survivors born before 2 wee+s and 1,,52 (*. C%3513251) per 1--- neonatal survivors born between2 wee+s and 31 wee+s; the number of studies was too small tocalculate a pooled prevalence in older gestational age groups
Figure ". Prevalence of cerebral palsy (CP) in relation togestational age per 1--- live births (a) Jestational age less than2 wee+s; (b) gestational age between 2 wee+s and 31 wee+s;
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(c) gestational age between 32 wee+s and 3 wee+s; (d)gestational age over 3 wee+s
Prevalence of cerebral palsy per gestational
wee in extremely preterm infants
The pooled prevalence per 1--- neonatal survivors at apredetermined age was calculated per gestational wee+ from 23to 25 wee+s (see 9ig &2# supporting material published online)The pooled prevalence was highest in children born at23 wee+s4 gestation (21,2; *. C% 1,-*2,3,) andlowest in children born at 25 wee+s4 gestation (1-25-; *. C%
,,1*55) Pairwise meta"regression showed that theprevalence among children born at 25 wee+s4 gestation wassignificantly lower than that among children born at 23 wee+s4gestation ( pI---3)
!valuation of potential bias
9or the overall prevalence estimate of CP per 1--- live births#
no significant publication bias was detected on visual inspectionof funnel plots of the standard error by the logit of theprevalence rate and supported by statistical testing 9or theEegg and 'a:umdar ran+ correlation test# Kendall4s tau"b is-1**, ( p"value -1**-2) Agger4s regression test showed anintercept of 2,1 (*. C% -21*, to *211*)#with t I1*2,11# dfI2- ( p"value --51*5) 9or the prevalenceestimate of CP in preterm survivors# no significant publication
bias was detected on visual inspection of funnel plots of thestandard error by the logit of the prevalence rate and supportedby statistical testing 9or the Eegg and 'a:umdar ran+correlation test# Kendall4s tau"b is -13 ( p"value -11512)Agger4s test showed an intercept of 1-251 (*. C% ,-1*3 to 1*1*)# with t I-52,2,# dfI15 ( p"value -233)
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%n our selection process# 12 studies were ecluded based onlanguage? three were written in &panish# five in Chinese# one inPolish# two in apanese# and one in Jerman 7f these# twopresented data on live births# five presented data on children at
a particular age# of which three reported on the samepopulation# and four presented data on preterm survivors
#iscussionMain findings
This study# through a systematic review and meta"analysis ofthe available literature# provides an updated estimate of theoverall prevalence of CP# as well as its relationship withgestational age and birthweight The most commonly reporteddenominators were live births# neonatal survivors# and survivorsat a predetermined age 7verall prevalence estimates weresimilar using live births or neonatal survivors; however# in thepreterm subgroup the estimates are epected to differ asperinatal mortality is higher among preterm infants have in term"born newborn infants There were fewer studies reporting theprevalence of CP per neonatal survivors in relation togestational age group The pooled estimate for children born atgestational age 2 to 31 wee+s is unepectedly higher thanchildren born at a gestational age of less than 2 wee+s;however# there were fewer studies reporting the former groupand the pooled estimate shows a larger confidence interval# andthis difference was not significant in a pairwise meta"regressionanalysis 'ost studies reporting estimates on preterm survivorswere based on population"based registries following groups ofinfants born preterm 9or overall prevalence# sources of caseascertainment varied considerably between studies 'ost
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Auropean studies used population"based patient registries withmultiple sources of case ascertainment and uniformly applieddiagnostic inclusion criteria %n =orth !merica# several statesreported data from population"based registries; however# both
Canadian studies used administrative databases with %C
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above 1*--g This prevalence estimate was similar irrespectiveof the denominator used in the calculation# that is per 1--- livebirths or per 1--- neonatal survivors 7ne of the reasons forthis similarity in prevalence estimates could be the small
number of high"Buality studies included that report prevalenceof CP using neonatal survivors as the denominator andinclusion of term"born low"birthweight infants# among whommortality may be lower !s reported in an earlier meta"analysis#the prevalence of CP shows an inverse relationship togestational age/,0 The prevalence estimate for preterm birthsvaried significantly based on the denominator# though a declinein CP prevalence was observed with increased gestational age
/3# ,0 Ghen reported as a proportion of neonatal survivors# theprevalence estimates were# as epected# larger than thecorresponding estimates reported as a proportion of live births#although these proportions revealed a similar declining trendwith increasing gestational age
Strengths and limitations
This review is based on rigorous methods and Bualityassessment of the selected studies Afforts were made to reportthe meta"analysis based on the P$%&'! statement/*0 !dditionally# analysis using the random effects modelaimed to account for heterogeneity between studies %ncomparison with previous reviews# our meta"analysis analyseda greater number of studies# used only data from study cohortsborn in or after 1* to account for changes in clinical practice#
and computed pooled prevalence estimates based oncomparable common denominators !ll efforts were made toadLust for potential bias
Though many studies used administrative data# the diagnosis of CP based on %C
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validated in these databases !dministrative databases aresusceptible to limitations such as inaccuracy in diagnostic codeentry# resulting in possible misclassification bias# multipleentries from varying sources# a lac+ of universal case
definitions# and financial incentives in coding in some countries/*0 =orth !merican studies are also restricted to a fewprovinces or states# with Buestionable generali:ability of theavailable data to the rest of the country# where demographicand social variables may differ
There was significant heterogeneity across studies# and anattempt was made to adLust for this by using a random effects
model and by pooling only studies with similar denominatorsThere were several factors contributing to potential selectionbias in our review 9irst# there is a potential ascertainment biasby individual studies using different definitions and age atdiagnosis of CP without reference to functional severity'ortality in the first years of life would lead to eclusion of moresevere cases# while a late age of diagnosis or ascertainmentonly through rehabilitation facilities may eclude milder cases
This may have had an impact on the numerator# though theetent of impact cannot be established 9urthermore# estimatingthe impact on health care costs and planning of services wouldneed to ta+e into consideration the severity of dysfunction inaffected children# which is not provided in most studies !second potential source of selection bias is referral filter bias# assome studies reported cases from academic institutions# whichmay impose a bias in access to care %n this meta"analysis# data
from of the , studies were hospital based These hospital"based studies were included as the institutes were consideredto be centres of ecellence and representative of the populationthey served
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! third potential source of selection bias is publication bias !lthough efforts were made to ma+e the search strategy ascomprehensive as possible# the search did not includeunpublished material or data from the Mgrey literatureN Dowever#
based on inspection of funnel plots and supported by statisticaltesting# we did not find significant evidence of publication biasfor either the overall prevalence estimate or the estimate inpremature survivors
The fourth potential source of selection bias in this review islanguage bias# as only studies published in Anglish and 9renchwere selected The impact of ecluding studies published in
languages other than Anglish has been shown to havegenerally little effect on summary treatment effect estimates/-0 %n our selection process# 12 studies were ecluded basedon language ! language bias cannot be ecluded
$onclusions
This meta"analysis provides updated prevalence estimates ofCP across different populations# showing a constant overallestimate per live births in recent years despite the addition ofnew data and increased survival of at"ris+ preterm infants
!lthough the prevalence of disease is unchanged# futurestudies are needed to evaluate a change over time in thephenotypic spectrum of CP &tudies on the prevalence of CP in
adolescence and adulthood would also be important futuregoals as the maLority of children with CP are epected tosurvive into adulthood 9urther studies are also needed in =orth
!merica and Canada# as the available data are restricted to afew regions# principally regions in Canada
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databases is needed to establish the validity of the diagnosis ofCP in the latter# as administrative databases are increasinglyused for surveillance because of their larger sampling frame#lower operational cost# and availability of longitudinal data
!ccurate and updated prevalence estimates are imperative inestimating the burden of illness and planning appropriate healthresource allocation for this vulnerable patient population
Ac%nowledgements
This study was funded by an operational grant from the PublicDealth !gency of Canada (PD!C) in conLunction with the=eurological Dealth charities of Canada (=DCC)The PD!Cand the =DCC did not participate in the design and conduct ofthe study; in the collection# analysis# and interpretation of thedata; or in the preparation# review# or approval of themanuscript
#isclosures
= ett> is an !lberta %nnovates Dealth &olutions PopulationDealth %nvestigator and holds a Canada $esearch Chair Tier 2in =eurological Dealth &ervices $esearch T Pringsheimreceives salaryOresearch support from !lberta Dealth and
Gellness# the Canadian %nstitute of Dealth $esearch# and thePublic Dealth !gency of Canada