Epidemiology of Cerebral Palsy

Kate Himmelmann, Sarah McIntyre, Shona Goldsmith,Hayley Smithers-Sheedy, and Linda Watson

ContentsIntroduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Definition and Classification of CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Frequency and Patterns of Occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4Birth Prevalence: Overall Trends . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4Trends by Birth Weight and Gestational Age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7Trends in Motor Severity and CP Subtypes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7Accompanying Impairments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Survival in CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Major Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10Multiple Birth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10Congenital Anomalies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11Congenital Cytomegalovirus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Prevention of CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

AbstractThe epidemiology of cerebral palsy includesstudies across whole populations within adefined geographic area that center on deter-mining the frequency of the condition; identi-fying patterns, risk factors, and causalpathways; and evaluating the effectiveness ofinterventions for prevention and reducingseverity. This chapter uses population datafrom long-standing registers to give an updateon these studies. The rates of cerebral palsy indeveloped countries have fluctuated between1.5 and 3/1000 live births throughout the last50 years. There have been periods of reducingrates, which have been followed by increases

K. Himmelmann (*)Department of Pediatrics at Institute of Clinical Sciences,University of Gothenburg, Gothenburg, Swedene-mail: kate.himmelmann@vgregion.se

S. McIntyre · S. Goldsmith · H. Smithers-SheedyCerebral Palsy Alliance, University of Sydney, Sydney,NSW, Australiae-mail: smcintyre@cerebralpalsy.org.au;sgoldsmith@cerebralpalsy.org.au;hsmitherssheedy@cerebralpalsy.org.au

L. WatsonWestern Australian Register of Developmental Anomalies(WARDA), Western Australian Department of Health,Perth, Australiae-mail: linda.watson@health.wa.gov.au

# Springer Nature Switzerland AG 2018F. Miller et al. (eds.), Cerebral Palsy,https://doi.org/10.1007/978-3-319-50592-3_9-1

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in rates. We are currently in another decline,and the question is as follows: Can this declinecontinue under 1.5/1000 live births for the firsttime? It is now becoming increasingly impor-tant to measure frequencies in low- andmiddle-income countries, where frequenciesare expected to be higher, but with possibilitiesfor primary prevention. Patterns have emergedamong gestational age and birth weight cate-gories as well as motor type and topographicdistributions. We understand more aboutcausal pathways that include preterm birth,multiple births, infection, and congenitalanomalies which open more doors to primaryprevention and reduced severity than whenresearch was simply focused on birth asphyxia.

KeywordsCerebral palsy · Epidemiology · Prevalence ·Risk factors · Prevention

Introduction

The epidemiology of cerebral palsy (CP) is thestudy of the distribution and determinants of CP inspecified geographic populations and the applica-tion of this study to monitoring the condition andto communicating unexpected increases and, con-versely, expected or unexpected decreases. Assuch CP epidemiology is important as an indicatorof hazards and quality care, relevant to maternal,perinatal, and neonatal care (Hagberg et al. 1982).

Epidemiology of any condition has key pur-poses including the following: to (1) study thenatural history; (2) determine the frequency;(3) identify the patterns of occurrence; (4) identifyrisk factors, potential causes and causal pathways,and opportunities for prevention; and (5) evaluatethe effectiveness of preventive and amelioratinginterventions. The ultimate goal of epidemiologyis to apply this knowledge and to play a role in theimprovement of public health. This chapter willspecifically address the frequency, patterns ofoccurrence, some risk factors, potential causes,and effectiveness of preventive measures in CP.

Definition and Classification of CP

CP comprises a group of conditions, heteroge-neous in causation and manifestations. Themost recent definition of CP includes the namingof some accompanying impairments as putforward by the participants at an internationalworkshop on the definition and classificationof CP, in Washington in July 2004 (Rosenbaumet al. 2007):

Cerebral palsy (CP) describes a group of disordersof the development of movement and posture, caus-ing activity limitation, that are attributed tonon-progressive disturbances that occurred in thedeveloping fetal or infant brain. The motor disor-ders of cerebral palsy are often accompaniedby disturbance of sensation, cognition, communi-cation, perception, and/or behavior, and/or by aseizure disorder.

This new definition reflects a more comprehen-sive way of looking at CP. However, the classifi-cation rests firmly upon the type and distributionof motor impairment. Consensus in classification,regarding both CP definition and the differenttypes (Surveillance of Cerebral Palsy in Europe2002), is important to avoid misconceptions aboutthe etiology and severity of the disability (see▶Classification Terminology in Cerebral Palsy).Figure 1 presents a decision tree developed by theSurveillance of Cerebral Palsy in Europe (SCPE)(Surveillance of Cerebral Palsy in Europe 2000,2002) for inclusion or exclusion of a child with amotor disorder as appropriate for the umbrellaterm of “cerebral palsy.” Although there is agree-ment through Europe for this decision tree, thereare two areas of discrepancy with other surveil-lance groups across the world (Smithers-Sheedyet al. 2014). In Europe, (1) a child needs to surviveuntil the age of two to be included under theumbrella of CP; and (2) if a child meets the criteriafor CP, has generalized hypotonia and no ataxia,he or she is excluded from the umbrella term ofCP. These discrepancies have not hamperedresearch, comparisons, or collaboration, as datasets can be harmonized easily by removing thosewho die before the age of two and those with“hypotonic CP” for specific projects.

2 K. Himmelmann et al.

A common classification has also beendeveloped by the SCPE (Surveillance of CerebralPalsy in Europe 2000, 2002). This classifica-tion, illustrated by a classification tree (Fig. 2)

(Surveillance of Cerebral Palsy in Europe 2000),is in accordance with the recently proposed defi-nition and classification of CP (Cans et al. 2007;Rosenbaum et al. 2007). Besides the dyskinetic

Does the child have adisorder of movement orposture of central origin?

EXCLUDE

EXCLUDE

EXCLUDE

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EXCLUDE

Was the child at least 4years old when assessed?

Is the child still living?

Did the child die beforethe age of 2 years?

Does the child havegeneralised hypotonia?

Are there signs ofataxia?

Go back and reassessafter age 4

Look at Classification Tree Ataxic CP

Does the child have asyndrome/brain anomaly orchromosome abnormality?

*Recheck - Does the childmeet the criteria for thedefinition of CP?

Does the child have adisorder of motor function?

Is the condition progressive(loss of previously acquiredskills)?

Fig. 1 Decision tree for cerebral palsy. (Reproduced from SCPE Collaborative Group (2000))

Is there persistingincreased muscle tone in

one or more limbs?

Are both sides of thebody involved? Is the tone varying ?

Spastic Bilateral Spastic Unilateral Dyskinetic CP*

Increased activity- tone tends to be

decreased

Dystonic CP* Choreo-Athetotic CP*

Reduced activity- tone tends to be

increased

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Ataxic CP Non-classifiable

Is there generalised hypotoniawith signs of ataxia?

Fig. 2 Classification tree for subtypes of cerebral palsy. (Reproduced from SCPE Collaborative Group (2000))

Epidemiology of Cerebral Palsy 3

and ataxic subtypes, it includes the concept ofunilateral and bilateral spastic CP, and it empha-sizes and describes the dominant symptoms(Krägeloh-Mann et al. 2003). Spastic CP is themost common form and constitutes more than80% in most series (Reid et al. 2011; Sellieret al. 2016). The term bilateral spastic CP servesas an alternative to terms such as diplegia, tetra-plegia, double hemiplegia, and quadriplegia,which have varying definitions and cutoff linesbetween countries. Again, other surveillance sys-tems and registers around the world have chosento keep the terms hemiplegia, diplegia, and quad-riplegia, but when working with or comparing toSCPE, these terms are collapsed into bilateralspastic CP. The recommended age for classifica-tion into CP subtype is not younger than 4–5 yearsof age (Krägeloh-Mann et al. 2003).

The permanent brain maldevelopment orlesion that causes CP can usually be visualizedwith neuroimaging. The recommended method ismagnetic resonance imaging, MRI, performedafter 2 years of age, when most of the myelinationof the brain has taken place (Krägeloh-Mann2004) (see ▶Classification Terminology in Cere-bral Palsy). The SCPE has proposed a classifica-tion of MRI results based on the timing of injury(Himmelmann et al. 2017) (Table 1).

Early compromise affects the developmentand organization of the brain, leading tomaldevelopment. Late second and early thirdtrimester lesions are found in the periventricularwhite matter, while gray matter lesions andcortical or basal ganglia lesions are associatedwith lesions arising around term (Fig. 3). Peri-ventricular white matter lesions are associatedwith spastic CP, while basal ganglia lesions arefrequently found in dyskinetic CP.

Classification measures of function haveemerged over the past 15 years and facilitate anoverview of the distribution of functional levels,change over time, and constitute a basis for theplanning of interventions. The Gross Motor Func-tion Classification System (GMFCS) has becomean important and widespread tool to describegross motor function in a child with CP and, inconjunction with the Gross Motor Function Mea-sure, prognosis for future gross motor function

(Rosenbaum et al. 2002). Corresponding classifi-cations for fine motor function are the BimanualFine Motor Function (Beckung and Hagberg2002; Elvrum et al. 2016) and Manual AbilityClassification System (Eliasson et al. 2006); andfor communication and speech, the Communica-tion Function Classification System (Hideckeret al. 2011), Functional Communication Classifi-cation System (Barty et al. 2016), and the VikingSpeech Scale (Pennington et al. 2013) have allbeen developed and validated.

Frequency and Patterns of Occurrence

Population-based series are necessary for interna-tional comparisons and epidemiological studiesof trends. The basic measures of frequency inepidemiology are incidence and prevalence. CPepidemiology has unique challenges, due to the“umbrella” nature of many etiologies, which spananywhere from the first few weeks of pregnancyto 2 years’ post-neonatal, and as there is not a testor any point in time that CP becomes CP, it isimpossible to report on incidence. Instead we usethe term birth prevalence to approximateincidence. By using this measure, epidemiologistscan determine the frequency of CP withinpopulations and compare differences in CPamong populations.

Birth Prevalence: Overall Trends

CP is the most common cause of motor disabilityin childhood, affecting about 2/1000 live bornchildren in high-income countries (ACPR Group2016; Himmelmann and Uvebrant 2014). Preva-lence of CP is monitored by a growing number ofregisters across the world (Goldsmith et al. 2016).The overall prevalence of CP appears to have beenfairly stable over the years although it has fluctu-ated between 1.5/1000 live births to 3/1000 livebirths in long-standing registers where reportinghas occurred for 50 years plus (Fig. 4).

Western Sweden and Western Australia aretwo such long-standing registers, and here wecompare their total birth prevalence since the

4 K. Himmelmann et al.

1950s. In Western Australia, there was a periodwhen ascertainment was still increasing, and thefounders of that register believe that ascertain-ment was complete from birth years 1963 onward.It can be seen on the figure that two very differentgeographical areas of the world show similar dipsand increase over time, with two differences:(1) an overall higher rate continually for WesternAustralia (between 2.1 and 3.2/1000 live birthscompared to 1.5 and 2.5/1000 live births), some ofwhich can be explained by a higher rate of post-neonatal CP in Western Australia, while some isunexplained, and (2) a slight lag in the dips and

following increases, with Western Australia fol-lowing the trends of Western Sweden. The finalbirth cohort of 2007–2010 sees the two areas’ totalbirth prevalence is the most similar since the early1980s. The next two birth cohorts will be impor-tant to see if overall birth prevalence continues tofall or if another increase commences.

In Europe the current overall prevalence of CPranges from 1.04 to 2.52/1000 live births (EURO-PERISTAT Project with SCPE EUROCAT andEURONEOSTAT 2008) and with a reportedmean rate of 2.08/1000 live births in the birth-year period 1980–1990 (Surveillance of Cerebral

Table 1 The harmonized classification of MRI, based on pathogenic patterns (MRICS, Magnetic Resonance ImagingClassification System) proposed by SCPE Network. For categories A2 and D, the findings are to be given as free text.Severity categories of B.1. and C.1. are defined according to previous publications (Krägeloh-Mann et al. 1995, 2002)

A. Maldevelopments

A.1. Disorders of cortical formation (proliferation and/or migration and/or organization)A.2. Other maldevelopments (e.g., holoprosencephaly, Dandy-Walker malformation, corpus callosum agenesis,cerebellar hypoplasia)

B. Predominant white matter injury

B.1. Periventricular leucomalacia, PVL (mild/severe)B.2. Sequelae of intraventricular hemorrhage (IVH) or periventricular hemorrhagic infarction (PVHI)B.3. Combination of PVL and IVH sequelae

C. Predominant gray matter injury

C.1. Basal ganglia/thalamus lesions (mild/moderate/severe)C.2. Cortical-subcortical lesions only (watershed lesions in parasagittal distribution/multicystic encephalomalacia) notcovered by C3C.3. Arterial infarctions (middle cerebral artery/others)

D. Miscellaneous (e.g., cerebellar atrophy, cerebral atrophy, delayed myelination,

ventriculomegaly not covered by B, hemorrhage not covered by B, brainstem lesions, calcifications)

E. Normal

Fig. 3 Systematic overview on brain development, pathogenic patterns, and timing. (Reproduced from Himmelmannet al. (2017))

Epidemiology of Cerebral Palsy 5

Palsy in Europe 2002). In Australia, the overallprevalence of CP between states ranges between2 and 2.7/1000 live births with a combined rate of2.1/1000 live births in the birth years 1993–2009(ACPR Group 2016). From one of fewpopulation-based studies in the United States,the Center of Disease Control and Prevention inAtlanta reported a rate of 2.2/1000 in childrenborn in 1985–2002 at 8 years of age (Van NaardenBraun et al. 2016).

In low- and middle-income countries (LMIC),the rates and etiological spectrum of CP maydiffer considerably from what is reported above;however research describing this population isboth scarce and varying. The few available reportsof CP prevalence in LMIC settings report a rangeof rates. Some are similar to that in high-incomecountries at around 2.0/1000 live births, such asthat reported from a study from Egypt (El-Tallawyet al. 2011) and from a large Indian survey(Banerjee et al. 2009). Other studies suggest CP

may be more prevalent in LMIC settings withestimates from 3.6/1000 live births from anotherregion of Egypt (El-Tallawy et al. 2014), 4.4/1000live births in Turkey (Serdaroglu et al. 2006), andup to as high as 10/1000 live births in South Africa(Couper 2002). These ranges may be real or ratherreflect variation in the inclusion criteria for CPand/or the types of research methodologies used,e.g., questionnaires and cross-sectional studies(Gladstone 2010).

In addition to potential differences in preva-lence, it seems likely that the etiological profile ofCP may differ in LMIC. In Australia, 5.6% of CPwas due to post-neonatally acquired causes(ACPR Group 2016); however in NorthernIndia, rates of CP are reported to be higher dueto higher frequencies of post-neonatally acquiredkernicterus, meningitis, and head trauma (Singhiand Saini 2013) (see ▶ Post-natal Causes ofCerebral Palsy). Differences or availability ofneonatal care facilities, in high versus low

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Fig. 4 Total birth prevalence of cerebral palsy in Western Sweden and Western Australia

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resource settings, also likely impact both rates ofsurvival and severity of CP (Benfer et al. 2014).However, without population-based surveillance,the epidemiology of CP in LMIC settings remainslargely unknown. Systematic population-basedhealth surveillance is required to provide real esti-mates of CP prevalence in LMIC settings. It ishoped that the recent establishment of new CPRegisters in Bangladesh (Khandaker et al. 2015)and Sri Lanka will in the future provide importantinsights into both the prevalence and etiology ofCP and pave the way for the identification ofappropriate prevention strategies for each region.

Trends by Birth Weightand Gestational Age

Maternal, perinatal, and neonatal care have under-gone major changes, improving perinatal and neo-natal mortality in high-income countries.Improved survival rates in low birth weight andpreterm infants also increase the birth prevalenceof CP and other neurodevelopmental conditions(Wilson-Costello et al. 2005) (see ▶ Prematurityand the Relationship to Cerebral Palsy). But,although the new preterm survivors constitute ahigh-risk population for various kinds of disabil-ity, including CP, the advances in neonatal inten-sive care have allowed far more infants to survivewithout CP than with CP (Hagberg et al. 1982;Serenius et al. 2013). A recent Western Australianstudy looking at infants born at borderline viabil-ity showed that 5% of infants survived at22 weeks, rapidly increasing to 46% at23 weeks, and 77% at 24 weeks (Sharp et al.2017). 78% of the surviving babies were free ofmajor neurodisability when followed into child-hood. It is expected that the proportion expectedto survive at these gestational ages will continueto increase, and some of these new survivors willalso have a neurodisability.

Lower birth weight is correlated with higherCP rate, 48.4/1000 in children with a birth weightbelow 1500 g compared to 1.1/1000 in childrenwith a birth weight of more than 2500 g in aEuropean report (EURO-PERISTAT Project withSCPE EUROCAT and EURONEOSTAT 2008).

In a survey including 16 centers of the SCPE, adecreasing trend in prevalence over time wasshown among very low birth weight children,mainly due to a decrease in the bilateral spasticCP subtype (Platt et al. 2007). This trend has beenconfirmed in later birth-year cohorts (Sellier et al.2016) and in Australia (ACPR Group 2016).

There is a large difference in birth prevalenceof CP between different gestational age groups(Fig. 5). In birth years 2007–2010, the gestationalage-specific prevalence of CP was 5.1/1000 livebirths in children born 32–36 weeks and 1.2 inchildren born at term in Western Australia (ACPRGroup 2016) and an even larger difference inWestern Sweden, with 6/1000 live births and 1.2in children born at term. In children born 28 to31 weeks’ gestational age, the birth prevalence ofCP was 47.7/1000 live births, and similar (for thefirst time) in the lowest gestational age, under28 weeks at 49.2/1000 live births. Western Swe-den again had a larger difference in birth preva-lence between these gestational age stratum 45.7/1000 live births in children born at 32–36 weeksand 59/1000 live births in under 28 weeks (Fig. 5).Looking 20 years back, the prevalence has varied,but both in Western Sweden and WesternAustralia, a decline in CP prevalence in childrenborn extremely preterm can be seen. There is alsoa declining trend in term CP. As more children areborn at term, the latter trend will result in a greaterdecrease in absolute number of CP cases.

Trends in Motor Severity and CPSubtypes

The changes in severity of motor impairment overtime are small. About 60% of children with CPlearn to walk unaided (Fig. 6a, b) (Himmelmannet al. 2006; Himmelmann and Uvebrant 2011).Once again, the comparison between WesternAustralia andWestern Sweden overall showsmin-imal change in severity. But since the late 1980s,there is a consistently higher rate of moderate tosevere gross motor function (defined as requiringaids to walk or a wheelchair to ambulate) seen inWestern Australia (Fig. 6a, b).

Epidemiology of Cerebral Palsy 7

The mean proportion of children unable towalk was 28% in children born 1976–1996 inEurope, with very little variance within the timeperiod (see ▶ Functional Mobility and Gait inChildren and Youth with Cerebral Palsy). Walk-ing ability was strongly correlated with CP sub-type: 3% of children with unilateral spastic CP,10% of the children with ataxia, 43% of those withbilateral spastic CP, and 59% of the childrenwith dyskinetic CP did not walk (Beckung et al.2008). In Western Australia the proportion ofsevere motor impairment in CP was 25% (Watsonet al. 2006).

Changes have occurred in the various subtypesover time (Cans et al. 2008; Surveillance of Cere-bral Palsy in Europe 2002). CP is classified intosubtypes based on predominant neurological find-ings (Fig. 2). Spastic CP constitutes about 80% ofall CP. It is characterized by a velocity-dependentincrease in muscle tone. A decreasing trend inpreterm bilateral spastic CP has been reported(Platt et al. 2007), whereas reports on other CPsubtypes are contradictory. In recent Europeanand Australian studies, decreasing prevalence inbilateral spastic CP and a concomitant increase in

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Fig. 5 Gestational age-specific trends in CP prevalence in Western Sweden and Western Australia

8 K. Himmelmann et al.

unilateral spastic CP were reported for childrenwith normal and moderately low birth weights(Sellier et al. 2016) and at term gestational age(Reid et al. 2016; Himmelmann and Uvebrant2014). The proportion of dyskinetic CP, charac-terized by involuntary postures and move-ments, varies between registers and is reportedin up to 15% (Monbaliu et al. 2017). Afteran increase from the 1970s, the prevalence ofdyskinetic CP has remained stable (Himmelmannet al. 2009; Sellier et al. 2016).

Research is starting to emerge from low- andmiddle-income countries about severity and sub-type differences compared with high-income coun-tries. In a comparison between Bangladesh and

Australia, dystonia was more prevalent inthe former (Benfer et al. 2014). In India, a decreasein quadriplegia and an increase in diplegia arereported (Singhi and Saini 2013). In Botswanaand Uganda, more severe motor impairment andhigher proportions of accompanying impairmentsthan in Europe and Australia are reported (Beardenet al. 2016; Kakooza-Mwesige et al. 2015).

Accompanying Impairments

In addition to neurological symptoms such asspasticity, dyskinesia, and ataxia, function andactivity may be hampered by muscle weakness,

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Epidemiology of Cerebral Palsy 9

co-contraction, and lack of selective motor controland balance. In more than half of the children withCP, there are accompanying impairments, whichmay impact function and participation more thanthe motor impairment in some. Screening forthese conditions should be part of the evaluationof a child with CP. The occurrence of accompa-nying impairments like epilepsy, impaired vision,and intellectual impairment is correlated with theseverity of the motor impairment (see ▶Epilepsyin the Child with Cerebral Palsy and ▶TestingVisual Function and Visual Evaluation Outcomesin the Child with Cerebral Palsy). Epilepsy hasbeen found in 33–44%, severe visual impairmentin 17–20%, and intellectual impairment in 44%with little variation during the last 20 years inWestern Sweden (Himmelmann et al. 2006;Himmelmann and Uvebrant 2011; Pueyo et al.2009; Venkateswaran and Shevell 2008). Motorimpairment, epilepsy, and intellectual impairmentshare the same risk factors and appear to havedifferent expressions of severity of brain lesionsaccording to a case-control study (Ahlin et al.2017). Communication and feeding may also behampered, creating a need for alternative and aug-mentative communication (AAC) aids andgastrostomy for feeding (see ▶ Feeding in Chil-dren and Youth with Cerebral Palsy and ▶Aug-mented Communication Aids and Supports forCerebral Palsy). More subtle sensory and cogni-tive problems may become apparent at school age.There is emerging evidence of neuropsychiatricand behavioral disorders (Carlsson et al. 2008;Delobel-Ayoub et al. 2017; Kilincaslan andMukaddes 2009), but it is too early to report trendsfor these conditions (see ▶ Psychiatric Disordersin Children with Cerebral Palsy and ▶AutismSpectrum Disorder in the Child with CP). Thegrowing awareness of such conditions may affectfuture management of CP and promote earlydetection.

Survival in CP

Survival in individuals with CP is related to theseverity of motor impairment and accompanyingimpairments (see ▶Prognosis Assessment in the

Child with Cerebral Palsy). In a WesternAustralian study with birth years 1958–1994,Blair found intellectual disability to be the stron-gest predictor of mortality, while severe motorimpairment primarily increased early mortality(Blair et al. 2001). A Swedish study covering50 years showed similar results, in addition to adifference in survival between dyskinetic andspastic CP of the most severe motor impairment.There was also an increased risk of death in all CPsubtypes and age groups compared with the gen-eral population (Himmelmann and Sundh 2015).Respiratory causes are the most common causesof death (Himmelmann and Sundh 2015; Reidet al. 2012). In one study the presence ofgastrostomy was associated with early death(Westbom et al. 2011). There is conflicting evi-dence whether survival is improving (Brookset al. 2014; Himmelmann and Sundh 2015; Reidet al. 2012). However, CP may well be associatedwith full life expectancy.

Major Risk Factors

Multiple Birth

Infants born as part of a multiple birth are at fourtimes the risk of CP compared to singletons (Scheret al. 2002; Topp et al. 2004) (see ▶Risk Factorsfor Developing Cerebral Palsy). Higher ordermultiples likely have a further increased risk com-pared with twins (Petterson et al. 1993; Pharoahand Cooke 1996). The increased risk may be dueto the following: growth deviation, both small andlarge for gestational age (Jarvis et al. 2003),co-twin deaths, the higher risk of preterm birthin multiples, increasing maternal age at birth, andthe advent of assisted reproductive technology(ART). Overall, ART approximately doubles therisk for CP (Hvidtjorn et al. 2009; Kallen 2014),while ovulation induction drugs increase CP riskto a lesser extent (Hvidtjorn et al. 2010). Theincreased risk after assisted conception is primar-ily attributed to the higher proportion of multipleand premature births (Hvidtjorn et al. 2010;Kallen et al. 2010). The use of assisted reproduc-tive technologies continues to rise; however as

10 K. Himmelmann et al.

usage varies significantly around the globe (Dyeret al. 2016), the influence on birth prevalence ofCP will also be regionally specific. While therecent shift toward single embryo transfer andresulting lower proportion of multiple births areexpected to decrease the association with CP(Kallen et al. 2010), in many regions the transferof multiple embryos remains a common practice(Dyer et al. 2016).

Congenital Anomalies

The presence of a congenital anomaly is associ-ated with an eightfold increase in risk of CP (see▶Genetic and Congenital Malformations as anEtiology of Cerebral Palsy) (McIntyre et al.2016). A congenital anomaly is defined as a struc-tural or functional abnormality that is present atconception or occurs before the end of pregnancy,a broader definition than that of maldevelopment.The proportion of children with pre�/perinatallyacquired CP and a major congenital anomalyranges between 15% and 32% in total populationdata linkage studies from regions of Europe andAustralia (Blair et al. 2007; Rankin et al. 2010).20% of children with a post-neonatal cause of CPare also reported to have a major congenital anom-aly (Blair et al. 2007). While congenital anomaliesare generally associated with preterm birth, theassociation between anomalies and CP is highestin children born at term (McIntyre et al. 2016).Children with a cerebral anomaly have a relativerisk for CP of 303 (Blair et al. 2007). Indeed,9–16% of children with pre�/perinatally acquiredCP have a major cerebral anomaly, and cerebralanomalies in CP are associated with more severeoutcomes (Blair et al. 2007; Rankin et al. 2010).Non-cerebral anomalies are found in 5–16% ofchildren with pre�/perinatally acquired CP (Blairet al. 2007; Rankin et al. 2010).

Much of the variation in reported prevalencemay be attributed to the lack of a universalcongenital anomaly definition as well as differ-ences in data collection methodology. This is cur-rently of high interest to CP Registers andcongenital anomaly registers in Europe andAustralia. A large study is currently underway,

The Comprehensive CA-CP Study (Goldsmithet al. 2018 under review), to answer the manyquestions around the prevalence of CP with acongenital anomaly and to identify opportunitiesfor primary prevention for these children.

Congenital Cytomegalovirus

Congenital cytomegalovirus (cCMV) has beendescribed as the most important congenital infec-tion leading to neurological sequelae in the devel-oped world (Cannon and Davis 2005; Manicklalet al. 2013) (see ▶ Infectious Etiologies ofCerebral Palsy). CMV is a common herpesvirusthat can cross the placenta, infect the fetus, andcause damage to the developing central nervoussystem, resulting in long-term sequelae includingsensorineural deafness, CP, and learning disability(Manicklal et al. 2013). A recent study inAustralia completed molecular testing of thestored newborn screening cards of 323 childrenwith CP, and 31 (9.6%, 95% CI 6.2–13.0) testedpositive for CMV DNA (Smithers-Sheedy et al.2017). This proportion was markedly higher thanthat found among newborns in the general com-munity (�0.6%) (Kenneson and Cannon 2007).

Prevention of CP

Recently two overviews of Cochrane Reviewshave been completed to outline the current pre-ventive strategies available for CP (see ▶Thera-pies in Newborn and Pediatric Intensive CareUnits for Neurological at Risk Infants) (Shepherdet al. 2016, 2017). Figure 7 outlines the key find-ings. There are only two interventions in currentpractice that have high-quality evidence to saythey are effective: Magnesium sulfate for theneuroprotection of the preterm fetus and therapeu-tic hypothermia for term newborns with hypoxicischemic encephalopathy. There were a largenumber of interventions that hadmoderate-qualityevidence that were either possibly effective, orno clear differences in outcome were found.There were also many interventions whereno conclusions were possible due to low-quality

Epidemiology of Cerebral Palsy 11

evidence, or no clear difference in outcomeswas found.

There were two main limitations identified inthese overviews. One was that although CP waslisted as a primary outcome for over 700 CochraneReviews, only 15% reported long-term outcomesthat included CP. The length of time it takes todescribe CP in a child (up to 5 years) is a problemfor large randomized controlled trial follow-up.Alternative follow-up processes need to be inves-tigated, such as linkage to CP Registers and theuse of interim measures, such as the GeneralMovements Assessment at 3–4 months of age.

Secondly, many of these interventions may havea small effect on CP, but the studies were notpowered for CP due to it being such a rare out-come, or because the intervention wasimplemented for a more proximal outcome, e.g.,antenatal corticosteroids for lung maturation(Table 2).

Congenital CMV is an important risk factor forCP not only because it may be more prevalent inthis population than previously thought butbecause it is potentially preventable (see▶Genetic and Congenital Malformations as anEtiology of Cerebral Palsy). While there is no

Hygiene precautions and behavioral interventions Hygiene precautions and behavioral interventions

• Do not share food, drinks, or utensils used • Do not share food, drinks, or utensils used by young childrenby young children

• Do not put a child’s dummy/soother/pacifier in your mouth• Do not put a child’s dummy/soother/pacifier in your mouth

• Avoid contact with saliva when kissing a child• Avoid contact with saliva when kissing a child

• Thoroughly wash hands with soap and water for 15• Thoroughly wash hands with soap and water for 15––20 seconds, especially after changing 20 seconds, especially after changing nappies/diapers, feeding a young child, nappies/diapers, feeding a young child, or wiping a young child’s nose or salivaor wiping a young child’s nose or saliva

Rawlinson et al 2017, Adler et al 1996, Revello et al 2015, ValoupRawlinson et al 2017, Adler et al 1996, Revello et al 2015, Valoup--Fellous et al 2009, Adler et al 2004Fellous et al 2009, Adler et al 2004

Fig. 7 Hygiene precautions and behavioral interventions to reduce risk of CMV in pregnancy

Table 2 Preventive strategies for CP: Cochrane Reviews of antenatal, intrapartum, and neonatal interventions

Intervention RCTs Participants RR (95% CIs)

Effective interventions: high-quality evidence

Magnesium sulfate for the neuroprotection of the preterm fetus 5 6145 0.68(0.54–0.87)

Therapeutic hypothermia for term newborns with hypoxic ischemicencephalopathy

7 881 0.66(0.54–0.82)

Possibly effective interventionsa: moderate-quality evidence

Prophylactic methylxanthines (caffeine) for endotracheal extubation inpreterm infants

1 644 0.54(0.32–0.92)

No conclusions possibleb: low- to very low-quality evidence

Antenatal corticosteroids for accelerating fetal lung maturation in thepreterm fetus

5 904 0.6 (0.34–1.03)

Possibly ineffective interventionsa: moderate-quality evidence

Prophylactic antibiotics for mothers in preterm labor with intactmembranes

1 3173 1.82(0.99–3.34)

Preterm babies with suspected fetal compromise being born immediatelycompared with those for whom birth was deferred

1 507 5.88(1.33–26.02)

Early (< 8 days of age) postnatal corticosteroids for preventing chroniclung disease in preterm infants

12 1452 1.45(1.06–1.98)

aThere were no clear differences for cerebral palsy for five neonatal interventions and one antenatal interventionbThere were no clear differences for cerebral palsy for 27 neonatal interventions and 9 antenatal interventionsRCTs randomized controlled trials, RR relative risk

12 K. Himmelmann et al.

available vaccine, there are effective public healthstrategies to reduce maternal risk of CMV in preg-nancy. These preventive strategies consist of sim-ple hygiene precautions that have been shown tobe both acceptable to pregnant women and effec-tive in reducing CMV seroconversion (Revelloet al. 2015; Vauloup-Fellous et al. 2009). Therecently published consensus guideline (Rawlin-son et al. 2017) recommends that “all pregnantwomen and health-care providers should be edu-cated about congenital cytomegalovirus infectionand preventive measures” (Fig. 7). The time hasarrived for a public health campaign to buildgreater awareness of congenital CMV as a causeof neurodevelopmental disability and to promotethese simple prevention strategies.

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