DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS …often late) description of CP, to one of referral for intervention which occurs immediately once an infant is considered “at risk”

CEREBRAL PALSY—DON’T DELAY

Sarah McIntyre,1,2,3* Cathy Morgan,1,3 Karen Walker,2,4 and Iona Novak1,3

1Cerebral Palsy Alliance, Research Institute, New South Wales, Australia

2The University of Sydney, School of Paediatrics and Child Health, New South Wales, Sydney, Australia

3The University of Notre Dame, School of Medicine, New South Wales, Sydney, Australia

4Grace Center for Newborn Care, The Children’s Hospital at Westmead, New South Wales, Australia

Cerebral palsy (CP) is the most severe physical disability within thespectrum of developmental delay. CP is an umbrella term describing agroup of motor disorders, accompanied by many associated impairments.The disability is a result of injuries to the developing brain occurring anytime from the first trimester of pregnancy through to early childhood.However, for the great majority, their full etiological causal pathwayremains unclear. It is important to discriminate as early as possiblebetween: (a) mild or nonspecific motor delay, (b) developmental coordi-nation disorder, (c) syndromes, (d) metabolic and progressive conditions,and (e) CP with its various motor types and distributions. The most prom-ising predictive tool for CP is the general movements assessment, whichassesses the quality of spontaneous movements of infants in the first 4months of life. We propose a change in diagnostic practice. We recom-mend a shift away from referral for intervention following a formal (mostoften late) description of CP, to one of referral for interventionwhich occurs immediately once an infant is considered “at risk” of CP.VC 2013 Wiley Periodicals, Inc. Dev Disabil Res Rev 2011;17:114–129.

Key words: cerebral palsy; early diagnosis; general movements;

perinatal risk factors; neonatal risk factors; brain injury

INTRODUCTION

Global developmental delay is an umbrella term thatdescribes two or more delays in the area of speechand language, social and emotional, cognitive and

motor development. Children with cerebral palsy (CP) oftenfall under the umbrella of global developmental delay, but CPcannot be considered “delay,” as children do not “grow outof it.” Health professionals need to understand what clinicalfeatures distinguish CP from other motor disorders, so themost effective interventions can be commenced earlier. TheAmerican Academy of Pediatrics have developed a policy forthe surveillance and screening of developmental disorders(Council on Children with disabilities et al., 2006), howeverthis paper focusses specifically on CP. The objectives of thisreview are fivefold:

1. Describe the nature of CP and what makes it different to

other motor or learning disorders.

2. Outline the prevalence of CP.

3. Determine who is at high risk of CP, what are the predictors

and early signs?

4. Identify tools that help clinicians to accurately predict CP.

5. Present an evidence based algorithmic approach to recogniz-

ing CP and developing intervention plans.

In the early months of life, global developmental delayand CP present similarly, if delayed, acquisition of develop-mental milestones is the only comparator. It is the movementdisorders (e.g., spasticity and dystonia), the level of functionalimpairment, and the associated impairments that set CP apartfrom other milder motor disorders or learning disorders suchas developmental coordination disorder (DCD). DCD is lesssevere and 25 times more common than CP affecting �5–6%the population and current practice is not to diagnose beforethe age of 5. As a result, the diagnosis of CP is often delayedwhile the possibility of DCD is explored.

DCD is primarily a learning problem where childrencan achieve normal movement patterns and skills but haveproblems with learning and planning the movements. CPconversely is a physical disorder, where children are not ableto achieve the normal movement patterns and the primaryproblem is motoric not learning, although deficits in learningmay compound the motor problem.

DCD is used to refer to children who fulfill a certaincriteria; poor motor performance which significantly interfereswith activities of daily living which are not explained by anymedical, neurological, or psychosocial condition. Thus a childwith CP whose motor disability is neurological cannot have adiagnosis of DCD [Blank et al., 2011]. The physical disabilityof CP is life-long whilst DCD is more apparent in the win-dow where the child is learning key motor skills for example,catching a ball, dressing independently, and handwriting.

WHAT IS CEREBRAL PALSY?CP is an umbrella term which “describes a group of dis-

orders of the development of movement and posture, causingactivity limitations, which are attributed to nonprogressive dis-turbances that occurred in the developing fetal or infant brain.

*Correspondence to: Sarah McIntyre, Cerebral Palsy Alliance, The University of

Sydney, The University of Notre Dame, Australia. E-mail: [email protected] 3 September 2012; accepted 5 October 2012View this article online in Wiley Online Library (wileyonlinelibrary.com)DOI: 10.1002/ddrr.1106

DEVELOPMENTAL DISABILITIESRESEARCH REVIEWS 17:114–129 (2011)

' 2013Wiley Periodicals, Inc.

The motor disorders of CP are oftenaccompanied by disturbances of sensa-tion, cognition, communication,perception, and/or behavior, and/or bya seizure disorder” [Bax et al., 2005].This most recent definition acknowl-edges the complexity of the conditionand the impact of the associatedimpairments.

What are the Fundamental FactsWe Know About Cerebral Palsy?

Classification of cerebral palsy guides inter-vention decision making

CP is a heterogeneous condition,and to elucidate prognosis and guideselection of the most appropriate inter-ventions (e.g., constraint inducedmovement therapy for hemiplegia andselective dorsal rhizotomy for diplegia)three major classifications are applied;motor-type, topography, and function.Clinicians often remark that a child mayhave two or three different descriptionsof their CP within one medical file, evi-dencing the poor reliability of thesetraditional classification systems. Tables1 and 2 outline the traditional motortypes and topographies of CP and theproportions of a CP population witheach type. In this paper, we refer to theAustralian Cerebral Palsy Register(ACPR) when reporting rates and forinternational comparisons the SwedishRegister and a study by Reid et al.[2011a] where registers throughout theworld are compared.

To solve the problem of low inter-rater (and sometimes intra-rater) reliability

when identifying topographical subtype,the Surveillance of Cerebral Palsy Europe[SCPE, 2000] has recommended that tra-ditional topographies be combined intotwo easily definable topographies: Unilat-eral (one side of the body), Bilateral (bothsides of the body). The ACPR insteadapplies a limb by limb coding using theAustralian Spasticity Assessment Scale(ASAS) [Love, 2007]. The ASAS scoresthe muscles’ response to rapid passivemovement without the subjectivity andwording ambiguities of the modified Tar-dieu and Ashworth scales [Mutlu et al.,2008]. Nonspastic motor types are alsocoded, resulting in a “stick figure dia-gram” of motor impairment, whichprovides an objective picture of the CP.Figure 1 presents the CP descriptionform. The descriptive form is also clini-cally useful for treatment decision-making, such as pharmacological options

and contracture management. The ASASis currently undergoing further reliabilitystudies, but it is freely available foruse along with the description of CPform: http://www.kemh.health.wa.gov.au/services/register_developmental_anomalies/documents/CP%20Description%20Form%20-%20WARDA%20website.pdf.

The gold standard tool for reliablydescribing motor function in CP is thegross motor function classification sys-tem (GMFCS) [Palisano et al., 1997].GMFCS provides a common languagethat conjures up a “picture” of a childwith CP. GMFCS is a five level classifi-cation system of gross motor functionin people with CP. The classification isbased on the person’s ability to self ini-tiate movement with a focus on sitting,transferring, and mobilizing [Palisanoet al., 1997]. Different classificationdescriptions exist at different agegroups. Table 3 summarizes the systemfor 2–4-year olds, to coincide with themost common time of recognition andthe proportion in a CP population witheach level of GMFCS.

It should be noted that whilst theGMFCS classification can be applied toinfants, about 40% change classificationlevels by age 2. After 2 years, the classifi-cation system is stable and thus GMFCSreassessment is recommended after age 2[Gorter et al., 2008]. This is clinicallyand diagnostically very important,because parents are anxious to learn earlyabout the severity of their child’s condi-tion for future planning but in reality themost accurate description of function andseverity can only be given at 2 years.

The presence of associated impairments andfunctional limitations affects the child’soutcome

For many children with CP, it isnot just a physical disability. Whenseeking to prognosticate the severity of

Table 1. Classification by Motor Type

ACPRa 1Reid, 2011a

Spasticty: Overactive muscles that display a velocity-dependentresistance to stretch. Spasticity can cause secondaryimpairments such as loss of muscle length, jointdislocation and pain.

85 – 91%

Dyskinesia: Dyskinesia is either athetosis or dystonia. Athetoid CP ishypotonic with hyperkinesia characterized by involun-tary writhing-stormy movement and canco-occur with chorea. In contrast, dystonic CP ishypokinetic, involving involuntary, abnormal twistingpostures or repetitive movements with hypertonia.Tone is typically fluctuating.

4 – 7%

Ataxia: Ataxia results in tremors with a shaky quality. AtaxicCP involves a loss of muscular coordination wheremovements have abnormal force, rhythm, and accuracy.

4 – 6%

Hypotonia: Pure, generalized hypotonia (decreased muscle tone) is theleast common CP motor-type. Some argue that purehypotonia should not even be considered a cerebral palsysub-type.

2%

aAustralian Cerebral Palsy Register.

Table 2. Classification by Topography

ACPRa

Hemiplegia: Hemiplegia/monoplegia is the involvement of one side of thebody. The upper limb is usually more affected than thelower limb. Strong early hand preference or hand disregardis sometimes the first sign of a problem.

38%

Diplegia: Diplegia is where both the legs are affected and are moreaffected than the upper limbs.

36%

Quadriplegia(Tetraplegia)

Quadriplegia refers to the presence of spasticity in all fourlimbs; where the affect on the arms is equal or more thanthe legs. Trunk and oro-facial involvement is also to beexpected. In rare cases, one limb is spared and this isreferred to as triplegia.

26%

aAustralian Cerebral Palsy Register.

115DEV DISABIL RES REV � CEREBRAL PALSY—DON’T DELAY � MCINTYRE ET AL

CP and determine intervention plans,assessment of associated impairmentsmust also occur. The likelihood and se-verity of associated impairments increasewith the severity of motor impairment[Himmelmann et al., 2006; Oddinget al., 2006]. Some have reported thatassociated impairments impact more onfunction and quality of life than themotor impairment [Himmelmann andUvebrant, 2011]. A meta-analysis of CPregisters calculated the overall rates ofassociated impairments and functionallimitations in the CP population to be:three in four are in pain; one in twohave an intellectual disability; one inthree cannot walk; one in three have ahip displacement; one in four cannottalk; one in four have epilepsy; one infour have a behavior disorder; one infour have bladder control problems; onein five have a sleep disorder; one in fivedribble; 1 in 10 are blind; 1 in 15 aretube fed; and 1 in 25 are deaf [Novaket al., in press]. Many will have a num-ber of these impairments, and thepresence of these impairments compli-cates therapy, decreases health status andquality of life for the individual andtheir family, and increases costs for thefamily and to society. The associatedimpairments of CP will now be dis-cussed briefly.Epilepsy. Epilepsy can potentiallyseverely limit the quality of life for theperson with CP and their family, andadults with CP and epilepsy are less likelyto find employment [Michelsen et al.,2005]. Epilepsy occurs in 30% of individ-uals with CP [Arnaud et al., 2008;ACPR Group, 2009]. In 2% of individu-als with CP, their epilepsy will beresolved by the time they turn 5 years ofage [ACPR Group, 2009]. For thosewhose seizures are not resolved, epilepsyis a lifelong condition. Rates of epilepsyare higher in those with: spasticity born

at term (48%) compared with preterm(28%); bilateral CP (34–87%) comparedwith unilateral (23%); and those withintellectual impairment (61%) comparedwith no intellectual impairment (19%)[Carlsson et al., 2003; Wichers et al.,2005; Himmelmann et al., 2006].Intellectual impairment. Intellectualimpairment can be defined by low gen-eral intellectual functioning as measuredby IQ scores, in combination with diffi-culties with adaptive behavior, allmanifesting before the age of 18. Practi-cally, this means that people with anintellectual impairment have memorydeficits, difficulty reasoning, learningnew skills, attending and organizing in-formation. 50% of individuals with CPhave an intellectual impairment andbetween 20 and 30% [Jarvis et al., 2005;McManus et al., 2006] have a severe in-tellectual impairment. Formal assessmentof intellect is essential (but at times diffi-cult) for an individual with CP.Communication. Communication dis-ability can have a major impact on theindividual with CP and their family.Impairment in this domain can impacton both understanding of language andexpression. For individuals who havesevere communication impairment,social isolation and poor self-esteem canresult. Between 20 and 30% of peoplewith CP are nonverbal which meansthat systems to support other forms ofcommunication are required [Arnaudet al., 2008; ACPR Group, 2009;Andersen et al., 2010; Parkes et al.,2010]. They are more likely to be non-verbal if they are non-ambulatory(GMFCS IV-V, 57%) compared tothose who are able to walk (GMFCS I-III, 4%) [Shevell et al., 2009]. Augment-ative and alternative communication(AAC) systems, which can range fromlow/light technology systems such assigning or use of alphabet charts to high

technology systems such as speechgenerating devices, may be used tocommunicate. It is a fundamentalhuman right to have the opportunity tocommunicate; however, high technol-ogy AAC systems are expensive,requiring wait listing and for some indi-viduals will mean that they are unableto access systems that would supportthem to communicate.Vision. Vision impairments can rangefrom mild requiring glasses, to func-tionally blind. About 5–12% ofindividuals with CP have a severeimpairment, or are functionally blind[McManus et al., 2006; ACPR Group,2009]. Another 30% will have a mild tomoderate vision impairment.Hearing. Hearing impairments can alsorange from a mild impairment to bilat-eral deafness. Bilateral deafness occursin 2% of people with CP while otherhearing impairments occur in a further10% [Surman et al., 2006; ACPRGroup, 2009]. Assessment of vision andhearing in children with CP should bethorough and done early, as it canimpact greatly on their ability to learnand achieve milestones.Other. Other impairments stronglyassociated with CP are hip dislocation(8%), displacement (27–35%) [Hagglundet al., 2005; Soo et al., 2006] and spinedeformities, sleep disorders (23%)[Newman et al., 2006], pain (70%)[Jahnsen et al., 2004; Arnaud et al.,2008], eating (8% tube fed) [Shevellet al., 2009; Sigurdardottir and Vik,2011], excessive drooling (22%) [Parkeset al., 2010], bladder and bowel controlcomplaints (24%) [Roijen et al., 2001],and behavior difficulties (26%) [Parkeset al., 2008]. These less well-understoodimpairments are more likely to occurwith bilateral CP and intellectualimpairment.

CP is the most common physical disabilityin childhood with prevalence unchanged for60 years

The overall prevalence of CP is�0.2% of the population (i.e., 1 in 500)in developed countries. As can be seenby a projected age distribution of onestate in Australia (Fig. 2), even thoughthe injury responsible for CP occurs inthe developing brain, it is a lifelongcondition, with most patients having anormal life expectancy. In reality, CP isnot just a condition of childhood.

The true incidence of CP cannotbe estimated as there are a proportion ofinfants who die in the intrapartum, neo-natal and infant period, who had brainlesions that may or may not have met

Table 3. Classification by Gross Motor Function at 2-4 Years

ACPRa

Level I: Floor sits independently, hands-free. Walks withoutassistive devices.

32%

Level II: Floor sits independently, hands-free with balanceaffected. Walks using an assistive mobility device.

27%

Level III: Floor sits using w-sitting. Walks short distances indoorsusing a hand-held mobility device with assistance.

12%

Level IV: Floor sits when placed, uses hands for balance. Rolls,creeps or crawls for short distances.

14%

Level V: Unable to sit independently. No form of independentmobility.

15%

aProportion in Australia with each level of GMFCS.

116 DEV DISABIL RES REV � CEREBRAL PALSY—DON’T DELAY � MCINTYRE ET AL

the criteria for CP. It has been suggestedtherefore that the closest rate to inci-dence (for CP) is prevalence of neonatalsurvivors (NNS). Western Australia(WA) is one register that reports in thismanner, and is also one of the longestrunning CP Registers in the world. CPis mandatorily reported in WA, there-fore it is assumed that this register has asclose to a total population cohort as ispossible. WA’s CP rates reported in2006 are 2.78/1,000 NNS increasing to3.9/1,000 when post-neonatal CP istaken into account [Blair and Watson,2006; Watson et al., 2006]. NNS areimportant when rates are reported bygestational age stratum. The lower thegestational age stratum, the more ratesdiffer between NNS and live births. It isparticularly important for those at theyoungest gestational ages. When report-ing rates in the birth years 2005 and2006 for those born between 20 and 27weeks in WA, the rate per 1,000 NNSwas 72 (95% CI 32–110) compared to

live births 51 (95% CI 24–79) [Watson,2012, personal communication]. If neo-natal deaths are not taken into account,live births give a misleading lower rate.In term births (371 weeks), where therate of intrapartum/neonatal death isproportionally much less, the differencebetween NNS 1.7 (95% CI 1.4–2.1)and live births 1.7 (95% CI 1.4–2.0)becomes inconsequential. Despite thisdenominator being the most accurate,for comparison live births are the mostwidely used denominator.

Estimates of prevalence through-out the world vary depending on themethodology of “count,” percentageascertained and variations in selectioncriteria. CP Registers have identifiedrates ranging between 1.4 and 2.77/1,000 live births; surveillance programsrange between 2.1 and 3.6/1,000 livebirths; and cross-sectional surveys rangebetween 1.05 and 4.1/1,000 live births.The two largest data sets, the ACPRand the SCPE both have an overall

birth prevalence of 2/1,000 live births.In developing countries, it is thoughtthat incidence is higher as the publichealth measures that help prevent someCP cases are not freely available indeveloping countries [Blair and Watson,2006]. All data sets across the worldagree there is a higher proportion ofboys diagnosed with CP. Although CPis found across all socio-economicclasses, there is a clear associationbetween low birth weight and lowsocio-economic status, and in normalbirth weight ranges, rates of CP are2.42/1,000 live births for those in thelowest socio-economic groups, com-pared to 1.29/1,000 for the mostaffluent groups.

The overall rate of 2/1,000 hasbeen fairly stable over the last 60 yearsin contrast to the dramatic falls in peri-natal mortality rates. However, therehave been some trends in gestationalage stratum, shown in Figure 3. Ratesin the extremely and very low

Figure 1 Cerebral palsy description form. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.].


gestational groups rose during the1980s, but are now trending down.Moderately premature infants’ rateshave decreased slightly, while in terminfants the rates are unchanged [Blairet al., 2001; Watson et al., 2006].Because the majority (>73%) of infantsare born over 32 weeks gestational age,the increases and decreases in theextremely and very preterm groupshave made little difference to the over-all rate.

Identification of infants “at-risk of cerebralpalsy” is possible; assessment and screeningshould follow

Since there are no identifiablebiomarkers to accurately predict CP,and clinical risk factors only identifysubpopulations of infants at risk [McA-dams and Juul, 2011], understandingthe term “causal pathways” is impor-tant. CP atiologies are described interms of causal pathways, as there isvery rarely one specific cause of braindamage severe enough to cause CP.Much research has been published thatattempts to discern the risk factors thatlie on one or more causal pathways toCP. What researchers are beginning torealize is how little is known abouthow these risk factors interact on causalpathways. Risk factors can be describedaccording to when they occur or whenthey are identified. The followingexamples have been identified for CP:

� Prior to conception: Previous gynecolog-

ical history of stillbirths/multiple miscar-

riages/neonatal death/premature birth,

family history of CP and other genetic

predispositions, maternal diagnoses, for

example, intellectual impairment, epi-

lepsy and low socioeconomic status.

� Early pregnancy: Infection, birth defects,

multiple births, male gender, and other

genetic predispositions.

� During pregnancy: Maternal disease, for

example, thyroid disorders, pregnancy

complications, for example, preeclampsia

and bleeds in the second and third trimes-

ter, infection and inflammation,

intrauterine growth restriction (IUGR),

placental abnormalities and other precur-

sors to premature birth.

� Around the time of birth and the neonatal

period: An acute intrapartum hypoxic

event, stroke, seizures, hypoglycemia, jaun-

dice, and infection.

� Postnatal period: Infections, accidental

and nonaccidental injuries, stroke both

spontaneous and following surgery.

The rate of CP in neonatal survi-vors varies significantly with level ofrisk at birth. To describe the risk ofdeveloping CP, infants have been sepa-rated into three distinct groups shownin Figure 4: (1) premature infants (30–40% of all CP); (2) term born infantswho shortly after birth have neonatalencephalopathy (NE), a clinicallydefined syndrome of disordered neona-tal brain function (15–20% of all CP);and (3) term born “healthy” infants,who do not require special care in theneonatal period (40–50% of all CP) anddo not appear to have identifiable riskfactors at birth [Badawi et al., 2005;Wu et al., 2006; McIntyre et al., 2011].Premature infants. When consideringwhich babies are at risk of CP, preterminfants commonly come to mind. Therisk of CP increases as gestational age

Figure 2 Estimated number of people living with CP in New South Wales, Australia. [Color figure can be viewed in the online issue, which is avail-able at wileyonlinelibrary.com.]

Figure 3 Gestational age specific rates/1,000 live births in WA, 1980–2006. [Color figure canbe viewed in the online issue, which is available at wileyonlinelibrary.com.]


decreases, therefore babies born at 36weeks’ gestation are at much lower riskthan those born at 24 weeks. As aresult, rates in premature infants rangebetween 3 and 80/1,000 neonatal survi-vors, reflecting the wide variation inlevels of risk across premature gesta-tions. Premature infants constitute up to40% of infants who develop CP [Kirbyet al., 2011]. So why are prematureinfants at increased risk of CP, andwhich ones are at the highest risk?

The group of preterm infants canbe separated according to gestationalage, with the first subgroup beingextreme prematurity, generally consid-ered less than 28 weeks’ gestation.There is much data in the literaturewhich depicts the outcomes ofextremely premature infants and muchresearch has been conducted in this agegroup [Hoon and Faria, 2010; Reidet al., 2011b]. In the 1970s and 1980s,the frequency of CP in this gestationalage group increased. This was attributedto the increasing survival of extremelypreterm infants and their predilection togerminal matrix hemorrhage and peri-ventricular leukomalacia (PVL) [Stanleyand Watson, 1992; Hagberg et al.,1996]. Evidence from population-basedsamples in Europe, Australia and theUnited States, and analyses from CPRegisters in Australia and Europedescribing trends in prevalence, sub-types, and severity, suggest that this risein frequency of CP in extremely pre-term infants has reached its peak and isnow decreasing [SCPE, 2000; Reidet al., 2011b; Watson, 2012, personalcommunication]. Up to 10% ofextremely preterm infants (variations inreports exist from as low as 3–10%) andup to 5% of infants between 28 and 31weeks gestation will be described ashaving CP [Himpens et al., 2008; Wat-son, 2012, personal communication].Practice point. Mothers whose labor isimminent (and prior to 30 weeks gesta-tion) should now be offered magnesiumsulphate for neuroprotection of theirchild. Meta analyses have shown thatCP can be reduced by 30% for infantsunder 30 weeks gestation [Crowtheret al., 2002].

CP Registers in Europe reportthat this trend for decreasing rates con-tinues into the group of late preterminfants (32–36 weeks’ gestation or1,500–2,499 g) [Andersen et al., 2011].The overall prevalence of CP in thesechildren had dropped from 12.2 per1,000 live births in 1983 to 4.5 per1,000 in 1997. There is conflicting evi-dence in Australia, with the rate being

maintained at between 5 and 7/1,000live births since the early 1980s [Wat-son et al., 2006].

Cerebral lesions in particularPVL, intraventricular hemorrhage(IVH) and intracranial hemorrhage(ICH) grade III and IV, are the mostimportant predictors of CP in very pre-term infants [Tran et al., 2005; Beainoet al., 2010; Himpens et al., 2010]. Inparticular, PVL lesions in the coronaradiata above the posterior limb of theinternal capsule (PLIC) observed in cor-onal sections have been used toaccurately predict motor prognosis[Nanba et al., 2007]. The presence oflesions in this region was highly predic-tive of CP (GMFCS 1 or higher) withsensitivity 100% and specificity 97%. Astudy by Himpens et al. [2010] thatinvestigated the predictive value ofultrasound in brain injury found thatdeep grey matter lesions are a signifi-cant predictor for severe versus mildand moderate CP (OR 5 6), and thatcerebral infarction and hemorrhagegrade IV are strong predictors of unilat-eral spastic CP versus bilateral spasticCP (OR 5 49 and 24, respectively, P< 0.001).

Recently, there has been increas-ing interest in and evidence regardingthe possible effects of intrauterine infec-tion or inflammation early in thepostnatal course, leading to CP. Carloet al. [2011] recently argued that a lateprenatal and/or early neonatal exposureto inflammation may predispose infantsto neurodevelopmental impairment.Wu and Colford [2000] also found thatclinical chorioamnionitis was associatedwith an increase in CP in preterminfants (OR 5 1.9) and term infants(OR 5 4.7).

Transient hypothyroxinaemia,bronchopulmonary dysplasia (BPD),and necrotizing enterocolitis have alsobeen associated with premature birthand a later description of CP. A recentstudy of 1,047 preterm infants (<28weeks) demonstrated that while allinfants with BPD had a higher risk ofCP those who were mechanically ven-tilated until 36 weeks PMA had at leasta fourfold increased risk of CP [VanMarter et al., 2011]. In addition, pre-term infants who have had surgery torepair a patent ductus arteriosus, orwho required home oxygen have alsobeen identified as at increased risk ofCP [Tran et al., 2005].Practice point. Infants born prematureare at high risk of CP if they haveabnormal cerebral imaging and a morecomplex course. These infants should

receive a general movements (GM)assessment before term equivalent age,and be referred to active surveillanceand early intervention when they leavethe hospital. (see Pathway A Figure 5,to be discussed in the followingsection).

Term infants with and without neonatalencephalopathy

The overall rate of CP for terminfants has been consistently 1.4–1.7/1,000 live births over the past 30 years[Watson et al., 2006; Himmelmannet al., 2010]. Multiple births born atterm are at four times the risk of CPthan singletons born at term. The riskrises again for surviving twins after thedeath of a cotwin [Pharoah, 2006].Risk factors associated with the devel-opment of CP in the term populationalso include congenital malformations,maternal age over 35 years, chorioam-nionitis, preeclampsia, placentalabnormalities, meconium aspirationsyndrome, IUGR, transient metabolicabnormalities, respiratory distress syn-drome, neonatal infections and seizures.[Shankaran, 2008; McIntyre et al.,2012]. One of the most well knownrisk factors for term-born infants is NE.

The second piece of the pie (Fig.4), with a well-recognized predilectionto develop CP are term or near terminfants with NE. For term born infants

with NE, the rate of CP is between

100 and 125/1,000 neonatal survivors,

and those born with severe NE are at

the highest risk of CP of all infants.

Infants with moderate to severe (Sarnat

Stage 2 or 3) NE account for one in

four cases of term CP [Badawi et al.,2005]. Kurinczuk et al. [2010] report

an incidence of NE between 2.5 and

3.5 per 1,000 live births and that �30%

of cases in developed countries are asso-

ciated with evidence of an acute

intrapartum hypoxic event. These

include sentinel birth events that are

also rare but important risk factors for

CP in term infants, such as placental

abruption, cord prolapse, severe intra-

partum hemorrhage, severe shoulder

dystocia, and a tight nuchal cord. It is

estimated that up to 8% of CP is attrib-

utable to an acute intrapartum event

with moderate to severe NE [Blair and

Stanley, 1997].Practice point. Infants with moderate tosevere NE following an acute intrapar-tum event benefit from hypothermia.This intervention prevents CP in oneout of eight of those treated [Jacobs andTarnow-Mordi, 2010]. A number of


adjuvant therapies to help those that donot respond to cooling alone are cur-rently in animal model and phase 1neonatal studies, for example, erythro-poietin, melatonin, xenon, andtopiramate [Gonzalez and Ferriero,2009].

In term infants with moderate tosevere NE, imaging showing basal gan-glia/thalamus injury has a positivepredictive value for CP of 88% [deVries et al., 2011]. In a study of 173term infants with NE, the basal ganglia/thalamus pattern of injury was associ-ated with the most severe motor andcognitive outcomes at 30 months[Miller et al., 2005].Practice point. Term infants with mod-erate to severe NE and a basal ganglia/thalamus injury should be automaticallydescribed as “At high risk,” and gostraight to Pathway B (Figure 5). Theyshould receive a GMs Assessment, bereferred to active surveillance and earlyintervention when they leave thehospital.

The remaining infants with NEthat go on to be described as havingCP have antenatal risks such as IUGR,intrauterine infection, metabolic abnor-malities, syndromes, and birth defects[Badawi et al., 1998; Kurinczuk et al.,2010]. Perinatal arterial stroke occurs in�1.7/100,000 live births. In the new-born period, it can also result in NE,but the majority of these infants presentafter the immediate neonatal periodwith seizures or hemiparesis. Motherswith preeclampsia and infants who haveIUGR are at risk of perinatal arterialstroke [Shankaran, 2008]. Stroke withabnormalities involving the cerebralpeduncle are also highly predictive ofCP PPV 78% [de Vries et al., 2011].Practice point. Infants with a cerebralbirth defect, or stroke with involvement

of the cerebral peduncle should beidentified as “at risk” of CP and shouldjoin Pathway B (Figure 5) at“assessment for CP.”

The risk of developing CP in terminfants who have received routine care atbirth, the third group of infants who goon to develop CP, is �1/1,000 neonatalsurvivors and these infants are at the low-est risk. However, they represent 45% ofall infants with CP and numerically com-prise the largest group (Fig. 4). Why dothese apparently “neurologically normal”children at birth develop CP, and can weidentify them earlier so they can haveaccess to active surveillance and earlyintervention?

From a total population case con-trol study in Western Australia,McIntyre et al. [2011] compared theclinical descriptions of 295 term infantswith CP with 442 term control infantsnone of which required special care.They identified six independent predic-tors of CP in the neonatal period:abnormal fontanelle OR 4.4 (95% CI0.8–23); abnormal tone OR 7.3 (95%CI 2–26.8); birth defects identifiable inthe newborn period OR 5.2 (95% CI2.4–10); ventilatory assistance restrictedto the labor room only OR 2.9 (95%CI 2.2–12); abnormal consciousnessreferred to irritability and lethargy, butnone were comatosed OR 3.7 (95% CI2–7); and in the small group withabnormal temperature regulation tem-perature was down or fluctuating, nothigh OR 4.1 (95% CI 1.2–14). A num-ber of these predictors are reminiscentof criteria for mild NE, and the pres-ence of two or more of these factorsyielded a high specificity (99%), butlow sensitivity (14%) for CP. This isnot surprising considering the unknownetiology of this group of infants. Of thislow risk group who had CP, 58% did

not have any of these neonatal factors,yet 60% of these infants had moderateto severe CP.

This is not the first time a findinglike this has been reported. TheNational Collaborative Perinatal Projectreported that most children with CPdid not derive from groups at high risk(low Apgar scores, or the presence ofneonatal signs). About 43% were exam-ined and classified as “neurologicallynormal” in the neonatal period andconcluded that a large proportion ofCP cases remain unexplained [Nelsonand Ellenberg, 1986; Ellenberg andNelson, 1988]. Earlier still, in 1970,Eva Alberman attempted to modelwhat were at that time the three mostimportant risks around birth: (1) parity>4; (2) abnormal method of delivery—breech, face or shoulder delivery, inter-nal version, or delivery by an untrainedperson; and (3) neonatal illness in the1st week of life—convulsions, cyanoticattacks, cerebral signs, hypothermia,jaundice, Rh incompatibility, or seriousillness. Infants were at the highest riskof disability when all three of these riskswere apparent. They were only a smallgroup (0.1% of total births), but moreimportantly only 0.2% of those with adisability. When any combination ofthese three risks were used, 13.2% of alllive births were classified as at risk, andthis identified 26.3% of all those with adisability. A striking finding was that74% of all those with CP, severe mentalhandicap, hearing, and sight impair-ments could not be identified using thismodel.

Very little has changed for thoseborn at term without any noticeable signsduring the neonatal period since the firststudies of these cohorts in the 1950s. Forthese infants, failure to reach majormotor milestones, such as rolling, sittingor standing, have often been the catalystfor the commencement of developmen-tal assessments and interventions. Giventhat the window for milestone attain-ment in typically developing children isquite broad [WHO Multicenter GrowthReference Study Group, 2006], this usu-ally leads to a “wait and see” approachwhere infants receive no interventionduring their period of rapid neural devel-opment. In view of the fact that everysecond child with CP will be born atterm and requires no special care in theneonatal period, it is imperative thatfrontline health professionals such aspediatricians, general practitioners andallied health practitioners have a bestpractice pathway to follow when a parent

Figure 4 Rate of CP in NeoNatal Survivors. [Color figure can be viewed in the online issue,which is available at wileyonlinelibrary.com.]


presents with a child who falls into thiscategory.Practice point. When parents bringtheir term born child (3 months to 3years of age) that did not require specialcare when born to a health professionalwith concerns regarding motor devel-opment or abnormal posturing theyshould go straight to Pathway B at“screen for CP.” We propose that atiered approach as developed by Rose-nbaum et al. [2009] should be adopted.They recommend using the ages andstages questionnaire 1 three extra ques-

tions for parents. Consideration shouldalso be given to risk factors duringpregnancy and signs of mild NE in theneonatal period. When an abnormalresult is derived, Pathway B (Figure 5)should be followed to “assessment forCP” through standardized motorassessments.

The description of cerebral palsy is tradition-ally given late but can be given earlier

This review is timely as “it isnow universally accepted that the ear-liest possible diagnosis and treatment (of

CP) are essential to prevent, or at least

minimize, the handicapping effects of a

disability and to make the most of the

assets a child possesses” [Alberman and

Goldstein, 1970]. Yet, paradoxically, 40

years later families are not automatically

receiving early intervention while they

“wait and see” whether their child will

“catch up” from simply a slower motor

developmental trajectory or if their

child actually has CP or DCD or an in-

tellectual impairment with associated

motor difficulties.

Figure 5 Recommended assessment for identification of infants at risk of CP.


CP registers indicate the averageage for a description of CP to be givenis 19 months, but the range is wide.For those with severe motor impair-ment the description of CP can begiven as early as 1 week but may takeup to 3 years, and less surprisingly forthose with mild or moderate motorimpairment the description of CP isgiven anywhere between 1 week and 5years of age [Watson et al., 2006]. Theburgeoning body of recent neuroplas-ticity literature suggests that intensive,repetitive, task-specific intervention forCP ought to commence very early

while the brain is most plastic (i.e., inthe first 2 years of life), which is almostnever the case when the family is takingpart in “wait and see” monitoring priorto description.

Good evidence shows that earlierdetection of CP is both possible andaccurate and, more importantly, diag-nostic-specific early intervention istherefore possible. Rather than waitingfor a formal description of CP to begiven, infants should be identified as “athigh risk of CP” when they are highrisk, and therefore commence diagnos-tic-specific early intervention straight

away. For those who are not at highrisk but have early signs, they should beregularly comprehensively assessed toensure access to the most appropriateearly intervention.

Why is Cerebral Palsy Missed andWhy is the Description so Difficultfor Doctors to Make?

Health professionals hesitate to usethe terminology CP early for a numberof reasons, but importantly the conditionis not a diagnosis; it is a “clinicaldescription.” There are no biologicalmarkers or definitive tests for CP. The

Figure 5 (Continued)


term does not infer etiology, and it hasno prognostic value as severity and asso-ciated impairments are incrediblyvariable. However, 86% of parents knowsomething is wrong with their childbefore a description of CP is given [Bairdet al., 2000]. Leading up to this point intime, most parents experience being toldby their medical team that the plan is to“wait and see.” When health professio-nals use the term “wait and see,” theintention is to use this time to rule outother diagnoses, delay the delivery of

bad news or provide time for the childto grow out of it.

Rule out other diagnosesDoctors first rule out other diag-

noses that may explain the symptoms.This is an important step as there areother conditions that mimic the earlysigns of CP which can have importanttreatment implications, such as: neuro-degenerative conditions (e.g., AtaxiaTelangiectasia); metabolic syndromes(e.g., Glutaric acidemia); and genetic

conditions (e.g., Trisomy 18, AngelmanSyndrome, Cornelia de Lange syn-drome) [Badawi et al., 1998].

Delay the delivery of bad newsDoctors sometimes delay the

delivery of bad news while exploringthe possibility of a less severe, morecommon disorder such as DCD. Differ-ential diagnosis is critical as it informsthe selection of intervention strategiessuited to the specific condition. Forexample, effective intervention for

Figure 5 (Continued)


DCD involves cognitive approachesbest suited to school-aged children,whereas CP intervention uses a varietyof pharmacological, motor, social andcognitive intervention approaches thatcan commence early in life. It is there-fore important that children with CPare differentiated earlier in order to getthe right interventions early.

Provide opportunity to grow out of itDoctors sometimes delay the

delivery of bad news to provide enoughtime for the possibility that the childmay “grow out of it.” However forthose few whose motor signs resolve,commonly they transpire to have an in-tellectual impairment or behavioralproblems [Nelson and Ellenberg, 1981].

The brain injury responsible forCP may be suspected or even con-firmed in the neonatal period, but thediagnosis for many does not occur untilthe motor impairments and activity lim-itations inherent in the definition areobservable. This lag time is not usefulto families or to the child.

“. . .. . .I am very worried about myson, he is 5 months old, and over the lastmonth I have noticed he seems to go

into strange positions, I especially noticeit each time I pick him up. I went to theGP, who agreed and thought I shouldsee a pediatrician. I went to the pediatri-cian who agreed they were unusual andsaid let us see how he is when he is 10months old. That is too long to wait! So Iwent to another pediatrician who agreedagain, it was abnormal, so now I ambooked to go to a physiotherapist for fur-ther tests, and after that they will decidewhat to do” but I do not know what todo now. . .” (Personal communication,February 4, 2012, parent discussion withfirst author over the phone).

System barriers to description arealso potentially at work. For example,for any mother and her newborn,obstetricians hold vital informationabout maternal-fetal health. If the babyis premature or ill, care is immediatelytransferred to neonatal specialists, wherethe primary patient is now the infant,not the mother, and some of the rele-vant preconception and pregnancyhistory about risk factors for CP maynot be passed on. When the infant iswell and discharged from hospital, careis likely to be transferred to a commu-nity based general practitioner or

pediatrician who may lack access to therelevant maternal-fetal and/or neonatalmedical history. The pediatrician maythen be assessing a healthy baby thatmay just appear slightly “delayed,” andit is not until later in infancy that thegravity of the problem may be evident,precipitating a late diagnosis.

What are the Most ImportantThings that can be Done in ClinicalPractice to Describe Cerebral PalsyEarlier?

We propose a new clinical path-way that is designed to circumvent theexisting screening and diagnostic barriersby tying together the relevant evidenceneeded to make an earlier diagnosis andcommence earlier intervention (seePathways A and B). These pathwayshave been developed using GRADElevel evidence [Guyatt et al., 2008] and“traffic lights” to signify the effective-ness of the interventions [Novak andMcIntyre, 2010]. Green equals “go,”(high quality evidence to supportthe use of the intervention, thereforeuse this approach). Yellow equals“measure” (low quality or conflictingevidence supporting the effectiveness ofthe intervention). Red equals “stop”(high quality evidence indicating inef-fective interventions) [Novak andMcIntyre, 2010].

The serious nature of these stand-ard care limitations has led us toconclude that “waiting and seeing” ispotentially harmful to children with CPand their families. We therefore haveidentified solutions to three of themajor problems relating to the late di-agnosis of CP, which are timely andpossible for the health system to redress:

New clinical diagnostic and interventionpathways

When the system fails to recog-nize a child with CP very early due tousing the “wait and see” monitoringmode, this decision essentially ensuresthat infants receive limited or no diag-nostic-specific intervention within thecritical window of brain development.The window of brain development,where the brain is actively sproutingand pruning in response to activity, isoften misspent in children with CP. InPathways A and B, we review the evi-dence for early intervention possibilitiesin CP. The evidence tells us quiteclearly that general early interventionand parent interventions, designed toenhance in-home care characterized bypositive interactions, categoricallyimprove a child’s cognition with the

Figure 6


best effect seen in children of lowsocio-economic status. However, morerecent neuroplasticity evidence suggeststhat a skill-based, high-intensity practiceapproach to early intervention isrequired to impact on motor outcomes,as is the case in most adult brain inju-ries. These newer types of motorlearning approaches, which are effectivein older children with CP, requireurgent study within the CP infant pop-ulation. It is therefore the responsibilityof the health professional who observesmajor risk factors or a motor delay toinvestigate further, diagnose “at risk ofCP” early, and refer to early interven-tion at a minimum to optimize theircognitive function. We outline a wayto do this via systematic use of risk fac-tor history taking, neurobehavioralpredictive tools, in addition to MRI(Pathways A and B).

Promotion of a climate for new research thatwill improve outcomes

Late description of CP is creatinga major problem for recruitment ofinfants to promising early rehabilitativeand potentially curative studies. Lack ofdiagnosis is impeding the advancementof regenerative medicine, early inter-vention and other well-recognizedtreatments for CP yet to be tested inthe earlier years, for example, medicalinterventions for tone management,reflux, and epilepsy. When a healthprofessional identifies an infant at highrisk for CP, coupled with referral toearly intervention trials, it will help toaccelerate future discoveries for thesechildren and change the landscape ofthe diagnosis and prognosis.

Promotion of good family mental health andresilience for the long-term

If late description is not helpinginfants or research, are we helpingparents by sheltering them from badnews? A population study conducted inBritain found that parental dissatisfac-tion with delayed diagnosis of CP isassociated with higher rates of parentaldepression [Baird et al., 2000]. So itwould appear that sparing parents frombad news is unhelpful. Therefore earlyrecognition and provision of early pre-ventative mental health support forfamilies may help parents manage theinevitable stress, which could helpimprove family outcomes long-term.

The concept of “at risk” is not anew one. During the 1960s in theUnited Kingdom, there were “at risk”registers, with the usual accompanyingdebate over their value and cost effec-

tiveness. It was deemed not practicableto have universal screening of all chil-dren, but it was felt essential that allchildren at risk be monitored. In a letterto the Lancet in 1967 defending theconcept, Dr Ronald Mac Keith and col-leagues wrote, “by the criterion ofidentifying handicaps which are in somecases undoubtedly, and in other casesprobably, benefited by having treatmentstarted without delay, developmentaland neurological assessment from theage of 5 months is neither difficult norinefficient” [Mac Keith et al., 1967].The concept itself was deemed by mostto be a sound one. The problem at thistime was the “at risk” criteria used wasidentifying up to 60% of all live birthsin an area. The goal of these programswas to screen 10–20% of all births toidentify the majority of the invisiblehandicaps that is, those that would oth-erwise not be identified until the 4thand 5th years of life. We recommendthat the “wait and see” period isreframed to the “wait and be” period,where children are diagnosed “at risk ofCP” early and are immediately referredto diagnostic-specific early intervention.

What Tools can be Used toAccurately Predict and IdentifyEarly Signs of Cerebral Palsy?

Imaging

Practice point. All children with a pre-sumed or suspected brain injury shouldhave magnetic resonance imaging (MRI).

Neuroimaging is used as an inte-gral part of the diagnostic process[Krageloh-Mann and Horber, 2007].MRI is the gold-standard neuroimagingtechnique for elucidating the pathoge-nesis of CP: white matter damage ofimmaturity (WMDI) including PVL,lesions of the deep grey matter, malfor-mations, focal infarcts, and cortical andsubcortical lesions [Bax et al., 2006].Cranial ultrasound (CUS) is a safe andinexpensive alternative used in the neo-natal intensive care unit (NICU) todetect structural changes in the new-born brain. However, MRI has highersensitivity and specificity than CUS as apredictor of CP in very low birthweight (VLBW) infants [Mirmiranet al., 2004]. Despite strong correlationsbetween clinical findings and MRI, 12–14% of children with CP will have nor-mal MRIs [Bax, 2006; Krageloh-Mannand Horber, 2007] and therefore MRIshould not be used in isolation for mak-ing the description of CP.

Newer techniques and technolo-gies are being developed which arelikely to advance the role of imaging inthe diagnostic process and treatmentselection process. Advanced neuroimag-ing techniques such as diffusionweighted imaging (DWI) and diffusiontensor imaging (DTI) have been uti-lized to more specifically identifydiffuse or subtle white matter injuries[Hoon and Faria, 2010]. Magnetic reso-nance spectroscopy (MRS), providesmeasures of brain biochemistry and isproving an effective tool in understand-ing prognosis in NE and preterminfants [Ancora et al., 2010; Van Kooijet al., 2012]. Large deformation diffeo-morphic metric mapping (LDDMM),where a 3D atlas of the brain is pro-duced, shows great promise forilluminating the structural brain abnor-malities that occur in CP with thepotential for informing selection,design, and measurement of rehabilita-tion interventions [Faria et al., 2011].

General neuromotor and developmentalassessments

Many neuromotor and develop-mental assessments with soundpsychometric properties exist for infantsand young children. For diagnostic pur-poses, tools with predictive propertiesare the most worthwhile. However,there has been a historical preference bypediatricians and neonatal follow-upteams to use discriminative tools thatassess a combination of: abnormal mus-cle tone of the trunk and extremities;the presence of primitive reflexes; thequality and quantity of voluntary move-ment (e.g., milestone acquisition); andthe presence of involuntary movement.The problem with this persistent prac-tice is that these tools are only usefulfor discriminating between infants whoare developing typically from thosewho are not. Determining who is typi-cally developing and who is not is evenmore complicated in premature infantsbecause they have their own develop-mental trajectory [Heineman andHadders-Algra, 2008; Spittle et al.,2008a]. Routinely used neuro observa-tions and standardized developmentaltests were not designed to specificallydetect the presence of CP and thus fur-ther compound the complexity of theCP diagnostic process. They may behelpful to some diagnosticians but willlack adequate specificity for most.

Ideally the aim of monitoringought to be to differentiate why somechildren are not developing normally,to enable diagnostic-appropriate best-


available evidence-based intervention tobe provided. This paper will now focuson the evidence for the best availabletools for predicting and recognizingCP, distinct from tools better suited tosuspecting global developmental delay(GDD). Clinometric reviews indicatethat different tools need to be used atdifferent ages to describe and detect CPand that a combination of tools is bestpractice [Heineman and Hadders-Algra,2008; Spittle et al., 2008a].Practice point. A combination of riskfactor history taking, neurological ex-amination that includes assessment ofquality of movement, volitional move-ment and neuroimaging are required. Ahealth professional with clinical exper-tise and experience in motordevelopment should interpret and eval-uate the findings generated by theseassessments (Figure 6).

Tools predictive of cerebral palsy

Qualitative assessment of general movements[Einspieler et al., 2004)]. Of all thetools available to predict CP, GMs isconsistently the most predictive, withspecificity and sensitivity rates higherthan MRI [Burger and Louw, 2009].The GMs assessment measures the qual-ity of spontaneous movements with theinfant lying supine. Scoring is done bytrained assessors via observation ofvideo footage and can be used from thepreterm period until 20 weeks postterm age (PTA). Two distinct timeperiods for assessment exist; the writh-ing period (up to 9 weeks PTA) andthe fidgety period (from 9 to 20 weeksPTA). In both periods, the infant isscored with “normal” or “abnormal”GMs. Abnormal GMs are then furtherclassified. In the writhing period,abnormal GMs known as “crampedsynchronized” have been shown to behighly predictive of CP (sensitivity5100%; specificity 5 40%; PPV59.4%;NPV5 100% [Spittle et al., 2009]. Ifthe abnormal GM of “cramped syn-chronized” is followed by the abnormalGM “absent fidgety” (in the fidgety pe-riod) this has consistently shown thehighest predictive value for CP (Darsa-klis and Snider, 2011).

A recent systematic review of 17studies demonstrated the accuracy ofthe GMs assessment in predicting neu-rodevelopmental outcomes in infants upto 2 years with a sensitivity �92% andspecificity �82% [Burger, 2009]. TheGMs assessment has been found to besuperior to ultrasound findings in pre-dicting CP [Einspieler et al., 2004]

When correlated with MRI findings,namely white matter injury, the GMsassessment (specifically “absent fidgety”)has been shown to accurately predictCP 100% of the time in very preterminfants [Spittle et al., 2008a] Evidenceof the predictive value of GMs in fullterm infants with hypoxic ischemicencephalopathy (HIE) has also beendemonstrated [Prechtl et al., 1993].Importantly, the GMs assessment hasgood clinical utility because it is quick,inexpensive, and noninvasive. Ratertraining is provided by the GMs trust.Hammersmith infant neurological assessment[Haataja et al., 1999]. The Hammer-smith assessment is based on theDubowitz and Dubowitz [1981] assess-ment of the newborn and is a simplemethod of examining infants between 2and 24 months of age. There are threeparts to the examination: neurologicsigns, developmental milestones, andbehavior. In the first section, the neu-rologic exam, an optimality score isobtained from the assessment of cranialnerve function, posture, quality andquantity of movement, tone, andreflexes and reactions. The second andthird sections do not form part of theoverall score but give important addi-tional information regardingdevelopmental progress. Recent studieshave demonstrated the predictive valueof the Hammersmith infant neurologicalassessment (HINE) for CP. A largestudy [Pizzardi et al., 2008] of 658infants who were either preterm orterm with NE were prospectively stud-ied from birth until 12 monthscorrected age. ROC curve analysis wasused to test the predictive power of theHINE. Global HINE scores showedhigh prediction of CP at all ages (ROCcurve areas above 0.9), but most impor-tantly movement quality and quantitytest items had even higher predictivepower.

A retrospective study of 70 infantsdiagnosed at 2 years with CP observeda strong (r 5 282) negative correlationbetween HINE scores at 3–6 months ofage and levels of GMFCS [Romeoet al., 2008a]. Infants in GMFCS levels3–5 scored below 40, whereas those inlevels 1–2 scored between 40 and 60.Combined use of the HINE and GMsat 3 months PTA can be used todescribe an infant as at “high risk” ofCP [Romeo et al., 2008b].

Practice point. Routine follow-up forpreterm and sick infants should bescheduled at three-months and six-months corrected, not the conventional

four-months, to enable medical teamsto use the best predictive tools to helpmake the description of CP earlier.

Practice point. When examining infants,do not discount CP when spasticity ordyskinesia is not identified. A period oftime lapses between the original damageto the developing brain, whether inutero or during early infancy/child-hood, and the appearance ofimpairments. It is well known that thebrain, which begins development inutero, continues to develop duringchildhood. Thus a child’s neural devel-opment is “age-specific,” so braindysfunction will manifest according tothe brain’s development at that age[Hadders-Algra, 2004]. Compared witha mature brain which responds to injurywith specific and localized signs, ayoung infant may present with general-ized and nonspecific signs (e.g.,hypotonia) [Kuban and Leviton, 1994;Hadders-Algra, 2004]. It is proposedthat further brain development in aninfant, including myelination of axonsand maturation of basal ganglia neurons,must occur before spasticity and dyski-nesia can manifest [Kuban and Leviton,1994]. The infant with hypotonia maythus “develop” spasticity and dyskinesiaby the age of 1 or 2 years, as the com-plexity of neural functions increases[Kuban and Leviton, 1994; Hadders-Algra, 2004].Movement assessment of infants [Chandleret al., 1980]. The movement assess-ment of infants (MAI) is a criterion-referenced scale that evaluates neuro-motor dysfunction in high risk infantsat 4, 6, 8, and 12 months of age. Theassessment is carried out by a therapistand takes 30–60 min to complete,requiring a manual but no specializedequipment. The MAI assesses tone,primitive reflexes, equilibrium reactions,and volitional movement. The test hasbeen shown to be twice as sensitive asthe Bayley scales of infant developmentin detecting early signs of CP [Harris,1987]. Studies of predictive values at 4and 8 months of age report sensitivityrates ranging from 73.5 to 96.0 andspecificity of 62.7–78.2 [Spittle et al.,2008b]. A recent investigation of thepredictive validity of the MAI at 6months of age demonstrated a signifi-cant correlation between MAI scoresand Bayley scales of infant developmentat 12 months, although sensitivity andspecificity for CP were not reported[Metgud et al., 2011].Other useful assessments. Several otherneuromotor assessments, such as the test


of infant motor performance (TIMP)[Campbell, 2005], The neuro-sensorymotor development assessment(NSMDA) [Burns et al., 1989], and theAlberta infant motor scale (AIMS)[Piper and Darrah, 1994], are appropri-ately used to discriminate infants withabnormal motor function from thosetypically developing. All have soundpsychometrics. Of these tools, theTIMP has been shown to be sensitiveto change in response to intervention[Campbell et al., 1995].Assessment summary.

� High risk infants should be routinely

assessed using the GMs preferably three

times; during early admission, around

term corrected (if preterm) and at 9–14

weeks (corrected for gestational age).

� “High risk of CP” designation should

be given to infants at 9–14 weeks (cor-

rected) with a combination of absent

fidgety GMs and white matter injury

on MRI.

� After 20 weeks (corrected), use the

HINE or MAI.

� MRI is the best imaging tool to eluci-

date the pathogenesis of CP and should

be offered to all infants who have

abnormal findings.

� Use the CP description form to

describe motor type and severity to

inform intervention planning.

CONCLUSIONUntil recently, CP was considered

unpreventable, incurable, and almostuntreatable. However, preventive effortsincluding: rubella vaccination, iodinesupplementation in areas of severe irondeficiency, anti-D vaccination, prevent-ing methyl–mercury contamination,reducing the number of embryos trans-ferred in invitro fertilization (IVF) (inAustralia), and enforcing laws for seatbelts and fencing around swimmingpools have been successful preventionstrategies. Recently, magnesium sulfateand hypothermic intervention have alsostarted to prevent a small proportion ofCP. Both of these interventions occurvery early and require health professio-nals to be mindful of CP as a potentialoutcome that could be prevented orcured. With advances in medical, publichealth, and allied health research, thelikelihood of further breakthroughs areprobable.

Further research is required todetermine why infants born at term, notat “high risk” of CP in the newborn pe-riod go on to develop CP. Healthprofessionals need to be aware that 45%

of all CP falls into this category. There-fore we recommend prompt response toparental concerns with screening andassessments as outlined, followed by im-mediate referral for intervention forthose infants then considered “at risk.”

Premature and term infants withbrain injury identified on MRI are athigh risk of CP. We have identifiedpathways which make recognizing “athigh risk” of CP easier for health pro-fessionals. We propose a change indiagnostic practice, a shift away fromreferral for intervention following a for-mal (most often late) description to oneof referral when an infant is “at highrisk” of CP. This will provide the op-portunity for targeted research in earlyintervention, thus providing optimaloutcomes for children with CP.

ACKNOWLEDGMENTSMany thanks to the families that

participate in CP Registers and researchthroughout the world, the clinicianswho work in this important area, andDr. Monique Hines for her fine edito-rial skills. This research was conductedat Cerebral Palsy Alliance ResearchInstitute, The University of NotreDame, Australia.

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DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS …often late) description of CP, to one of referral for intervention which occurs immediately once an infant is considered “at risk”