31518028ddb3a2d814b6bdc5288a7fae

Clinical Review & Education
JAMA Pediatrics | Review
Early Intervention for Children Aged 0 to 2 Years

With or at High Risk of Cerebral Palsy
International Clinical Practice Guideline Based on Systematic Reviews
Catherine Morgan, PhD; Linda Fetters, PhD; Lars Adde, PhD; Nadia Badawi, PhD; Ada Bancale, NPT;
Roslyn N. Boyd, PhD; Olena Chorna, CCRP; Giovanni Cioni, MD; Diane L. Damiano, PhD; Johanna Darrah, PhD;
Linda S. de Vries, PhD; Stacey Dusing, PhD; Christa Einspieler, PhD; Ann-Christin Eliasson, PhD;
Donna Ferriero, MD; Darcy Fehlings, MD; Hans Forssberg, MD; Andrew M. Gordon, PhD; Susan Greaves, PhD;
Andrea Guzzetta, PhD; Mijna Hadders-Algra, PhD; Regina Harbourne, PhD; Petra Karlsson, PhD;
Lena Krumlinde-Sundholm, PhD; Beatrice Latal, PhD; Alison Loughran-Fowlds, PhD; Catherine Mak, PhD;
Nathalie Maitre, MD; Sarah McIntyre, PhD; Cristina Mei, PhD; Angela Morgan, PhD;
Angelina Kakooza-Mwesige, PhD; Domenico M. Romeo, PhD; Katherine Sanchez, PhD; Alicia Spittle, PhD;
Roberta Shepherd, PhD; Marelle Thornton, DipEd; Jane Valentine, PhD; Roslyn Ward, PhD;
Koa Whittingham, PhD; Alieh Zamany, DPT; Iona Novak, PhD
Editorial
IMPORTANCE Cerebral palsy (CP) is the most common childhood physical disability. Early Supplemental content
intervention for children younger than 2 years with or at risk of CP is critical. Now that an
evidence-based guideline for early accurate diagnosis of CP exists, there is a need to
summarize effective, CP-specific early intervention and conduct new trials that harness
plasticity to improve function and increase participation. Our recommendations apply
primarily to children at high risk of CP or with a diagnosis of CP, aged 0 to 2 years.
OBJECTIVE To systematically review the best available evidence about CP-specific early
interventions across 9 domains promoting motor function, cognitive skills, communication,
eating and drinking, vision, sleep, managing muscle tone, musculoskeletal health, and
parental support.
EVIDENCE REVIEW The literature was systematically searched for the best available evidence
for intervention for children aged 0 to 2 years at high risk of or with CP. Databases included
CINAHL, Cochrane, Embase, MEDLINE, PsycInfo, and Scopus. Systematic reviews and
randomized clinical trials (RCTs) were appraised by A Measurement Tool to Assess Systematic
Reviews (AMSTAR) or Cochrane Risk of Bias tools. Recommendations were formed using the
Grading of Recommendations Assessment, Development, and Evaluation (GRADE)
framework and reported according to the Appraisal of Guidelines, Research, and Evaluation
(AGREE) II instrument.
FINDINGS Sixteen systematic reviews and 27 RCTs met inclusion criteria. Quality varied. Three
best-practice principles were supported for the 9 domains: (1) immediate referral for
intervention after a diagnosis of high risk of CP, (2) building parental capacity for attachment,
and (3) parental goal-setting at the commencement of intervention. Twenty-eight
recommendations (24 for and 4 against) specific to the 9 domains are supported with key
evidence: motor function (4 recommendations), cognitive skills (2), communication (7),
eating and drinking (2), vision (4), sleep (7), tone (1), musculoskeletal health (2), and parent
support (5).
CONCLUSIONS AND RELEVANCE When a child meets the criteria of high risk of CP, intervention
should start as soon as possible. Parents want an early diagnosis and treatment and support
implementation as soon as possible. Early intervention builds on a critical developmental time
for plasticity of developing systems. Referrals for intervention across the 9 domains should be
specific as per recommendations in this guideline.
Author Affiliations: Author
affiliations are listed at the end of this
article.
Corresponding Author: Iona Novak,
PhD, University of Sydney, Level 7,
Western Ave, D18–Susan Wakil Health
Building, Sydney 2006, NSW,
JAMA Pediatr. doi:10.1001/jamapediatrics.2021.0878 Australia
Published online May 17, 2021. ([email protected]).
(Reprinted) E1
© 2021 American Medical Association. All rights reserved.
Clinical Review & Education Review Early Intervention for Children Aged 0 to 2 Years With or at High Risk of Cerebral Palsy
C
erebral palsy (CP) is the most common childhood physical
disability. Variation in birth prevalence exists in high- Key Points
income countries (1.4 to 2.5 affected children per 1000 live Question What are the evidence-based recommendations to
births) and is higher again in low- to middle-income countries.1-5 Ce- guide early intervention in children aged 0 to 2 years who have or
rebral palsy occurs because of a lesion or maldevelopment in the de- are at high risk of cerebral palsy?
veloping brain. Often, the full causal pathway is unclear. Cerebral
Findings In this systematic review, there was good-quality
palsy is a clinical diagnosis of movement disorders, resulting in either evidence for involvement of parents in intervention programs and
spasticity (92%), dyskinesia (4%), ataxia (1%), hypotonia (not clas- task-specific and context-specific interventions to improve motor
sified in all countries; 2%), or mixed types.2 Dyskinesia, ataxia, and and cognitive outcomes in children with cerebral palsy. The
hypotonia typically affect all 4 limbs. Spasticity is categorized topo- evidence in other developmental domains is not as strong, and
graphically, as unilateral (hemiplegia; 59%) or bilateral (including conditional recommendations are based on other high-risk
populations.
diplegia, with the lower limbs more affected than upper limbs [10%]
and quadriplegia or tetraplegia, with 4 limbs and trunk affected Meaning It is critical that early intervention for cerebral palsy
[31%]).2 Infants and children have remarkable brain plasticity and starts at diagnosis and the associated impairments are monitored
aptitude for learning; taking advantage of this window of oppor- and treated according to recommendations.
tunity with evidence-based intervention for those with early brain
injury maximizes functional outcomes and minimizes complica-
tions. However, not all interventions are suitable for all children with ing the PICO questions; (2) when systematic reviews were not
CP, because age, type, topography, severity, parental variables, en- available, conducting a new systematic review to identify random-
vironmental variables, and principles of neuroplasticity drive the ized clinical trials (RCTs) or the best available lower levels of evi-
choice of best treatment.6 Co-occurring impairments and func- dence when systematic reviews and RCTs were not available12; or
tional limitations are common (including pain [75%], epilepsy [35%], (3) when no or limited data on CP in children aged 0 to 2 years
intellectual disability [49%], musculoskeletal deformities [eg, hip were published, conducting searches to identify RCTs in patients
displacement; 28%], behavioral disorders [26%], sleep disorders with other neurodevelopmental disabilities or older children with
[23%], and/or vision [11%] and hearing [4%] impairments7) and may CP (Table).
have a greater effect on function and quality of life than motor im- Topic literature was appraised by 9 domain-specific working
pairment. Children with involvement in 4 limbs experience higher groups using A Measurement Tool to Assess Systematic Reviews
rates of comorbidities and worse outcomes (especially when epi- (AMSTAR)97 for existing systematic reviews (eTable 2 in the Supple-
lepsy and intellectual disability are present),7 and conversely, chil- ment) or the Cochrane Risk of Bias tool98 for RCTs (eTable 3 in the
dren with involvement of fewer limbs and fewer comorbidities have Supplement). Groups summarized the certainty of supporting evi-
better responses to intervention. dence and formulated recommendations using the GRADE evi-
These guideline recommendations apply to children aged 0 to dence to decision framework (eTable 4 in the Supplement).99 GRADE
2 years who are at high risk or have a diagnosis of CP, as defined in uses a 4-part continuum for recommendations, using the terms
the 2017 diagnostic international guideline,8 but not infants born pre- strong for, conditional for, conditional against, and strong against.
term without identifiable brain injury, since many of these infants We assessed (1) the balance between desirable and undesirable
will not have CP.9 To assign the interim clinical diagnosis of high risk consequences of using different intervention strategies or not pro-
of CP, the infant must have motor dysfunction (an essential crite- viding the intervention; (2) evidence quality; (3) family prefer-
rion) and at least 1 of 2 additional criteria, namely abnormal neuro- ences, including benefits vs risks and inconvenience; and (4) costs.
imaging or a clinical history indicating a risk for CP.8 We refer read- The entire author panel reviewed the text, evidence tables, and
ers to the 2017 guideline8 for more detailed information regarding supporting literature. Consensus agreement on recommendations
early and accurate diagnosis of CP. arising from the appraised evidence was reached by discussion. Rati-
Our objective was to develop clinical guidelines for early inter- fication of the final recommendations, including resolution of dis-
vention (treatment and management) in children at high risk of CP agreements among coauthors, was completed by the lead authors
and their families. This has been developed through a systematic (C.M., L.F., and I.N.).
review of the best available evidence for improving 9 domains in
children aged 0 to 2 years with or at high risk of CP.
Results
Sixteen systematic reviews and 25 RCTs met inclusion criteria of
Methods the 9 topics. Evidence quality was variable, and only a few strong
This guideline was developed using the Grading of Recommenda- recommendations are made (Table; Figure). The Table and Figure
tions Assessment, Development, and Evaluation (GRADE) frame- indicate the population evidence source. The strongest of the 28
work and the Appraisal of Guidelines, Research, and Evaluation recommendations are derived from the literature on children
(AGREE) II tool.10 Comprehensive systematic searches, using the younger than 2 years with or at risk for CP. Recommendations
Cochrane method, were conducted for the 9 topics within the tar- derived from infants born preterm, older children with CP or other
get age range using Patient, Intervention, Comparison, and Out- neurological conditions, or infants and children developing typically
come (PICO)11 searches (eTable 1 in the Supplement). The inclusion were coded as conditional because they were downgraded for
criteria specified (1) gathering existing systematic reviews answer- imprecision.
E2 JAMA Pediatrics Published online May 17, 2021 (Reprinted) jamapediatrics.com

Early Intervention for Children Aged 0 to 2 Years With or at High Risk of Cerebral Palsy Review Clinical Review & Education
Table. Recommendations
No. Domain Strength Direction Intervention Key recommendations Target population

Skills development
1 Motor Strong (1) For Early intervention (1) We recommend beginning intervention at the time of Children with or at
and (2) suspected diagnosis8 to harness neuroplasticity through high risk of unilateral
against specific training8,13 and respecting parent requests for or bilateral CP
early intervention14,15 and (2) we recommend against
waiting and seeing because the critical window for
neuromuscular plasticity is misused.8,13
2 Motor Strong For Task-specific motor We recommend task-specific motor training that includes Children with or at
training self-discovery of the environment and solutions to high risk of unilateral
overcome movement challenges,16-24 selection of or bilateral CP
challenging but achievable motor tasks that require
persistence for success,16,18,20-22,25,26 daily repeated
practice (as possible) for skills acquisition and refinement,
parental coaching to structure practice beyond scheduled
therapy sessions (for adequate dosing), and creating
enriched environments promoting movement variety and
intense, enjoyable practice.13,27,28
3 Motor Strong Against Passive movement We recommend against passive, therapist-controlled Children with or at
handling techniques for movement activation or high risk of unilateral
activities.6,17,29,30 or bilateral CP
4 Motor Strong For CIMT or bimanual We recommend CIMT and/or bimanual training as soon Children with
therapy as a unilateral CP diagnosis is suspected, since benefits unilateral CP
outweigh the risk of harm from unused plasticity
windows8,13 and false-positive diagnoses.22,31 We
recommend short intervals of CIMT (30-60 min of
therapist-supervised home programs for 6 wk) in early
infancy, increasing in intensity with age.31,32
5 Cognitive Strong For Cognitive We recommend targeted cognitive interventions, because Children with or at
intervention motor impairment hampers social interactions and high risk of CP (all
exploration of the environment and toys restricting motor types)
discovery-based learning.16,17,29 We recommend cognitive
interventions that include active, self-initiated,
self-generated movements of real tasks with observable
consequences; social interaction with people and
objects19,33-35; multimodal learning (cognitive, language,
and motor); challenging tasks with incremented
complexity16,19,36; parent participation37; and
best-practice early-years enrichment (eg, adequate
nutrition, interactive, child-led learning).38
6 Cognitive Conditional Against Generic We recommend against generic developmental education Children with or at
developmental alone and/or a sole focus on motor development using high risk of CP (all
education alone passive motor interventions to improve cognition (eg, motor types)
and/or with a sole neurodevelopmental therapy [original format], handling,
focus on passive postural reactions and alignment).34,35,39
movement
7 Communication Conditional For Face-to-face We suggest parents engage their infant via face-to-face to Preverbal infants
nurturing with talk, singing, using baby talk, and showing emotion when with or at high risk of
vocalizations, joint communicating,40-42 since infants have a clear preference CP (all motor types)
attention, and for faces and share affect states with caregivers. We
reciprocal- suggest learning to read the infant’s microexpressions and
interaction eye pointing when motor impairment precludes nonverbal
interventions gestures41,43; face-to-face interactions with the parent or
caregiver’s face as the visual target for infants with a visual
impairment41,44; assessment of parental mental health for
its effect on communication40; and watchful interpretation
to understand whether the cause of impaired vocalization
and gestural skills is motoric, communicative, cognitive, or
all of these.
8 Communication Conditional For Transactional We suggest teaching parents and caregivers to build Children with or at
speech-language relational connections and reciprocal communication high risk of CP
and exchanges to foster active communication.45,46 We suggest suspected to be
communication parent-infant transaction programs and Hanen therapy for nonverbal or with
interventions improvements in communication skills and expressive emerging verbal
language acquisition47,48; the Mother-Infant Transaction ability
Program (from a neonatal intensive care unit stay to 90 d
postdischarge) to foster parental understanding of infant
state regulation, sleep-wake cycles, joint interaction, and
engagement47,49; PremieStart to recognize and minimize
stress responses in infants born preterm47; and Hanen It
Takes Two to Talk therapy (6-8 sessions) to foster parental
understanding of responsivity to their child’s attempts at
communication in a positive, prompt, and intentional
manner.50
9 Eating and Conditional For Softer food We suggest softened food consistencies to enhance feeding Children with or at
drinking consistencies safety and efficiency.51-55 high risk of CP and
dysphagia
(continued)
jamapediatrics.com (Reprinted) JAMA Pediatrics Published online May 17, 2021 E3

Table. Recommendations (continued)

10 Eating and Conditional (1) For Slightly reclined or (1) We suggest a slightly reclined or upright position to Children with or at
drinking and (2) upright positioning enhance feeding safety and efficiency51-53 and (2) we high risk of CP and
against suggest against very reclined positions that may dysphagia
exacerbate swallowing deficits.53
Complication prevention
11 Vision Conditional For Correction of We suggest surgical correction of strabismus coupled with Children with or at
strabismus esotropia and/or exotropia to achieve good alignment of high risk of mild CP
the eyes and sensorial binocular fusion.56 and strabismus,
by 2 y of age
12 Vision Conditional For Visual training We suggest early visual training programs to improve visual Children with or at
functions and attention to visual stimuli.57 high risk of CP and
cerebral visual
impairment
13 Vision Conditional For Color contrast cues We suggest early provision of high-contrast/color visual Children with or at
stimulation in an interactive and contingent manner to high risk of CP and
improve visual orientation and mobility58-61 and social and cerebral visual
physical environment adaptations to accommodate vision, impairment
such as high-contrast stimuli and light directed at the
visual target.
14 Sleep Conditional For Sleep hygiene We suggest implementing sleep hygiene, including Children with or at
structuring a bedtime routine in a dark and quiet high risk of CP (all
environment,62-66 positive routines, controlled crying and motor types)
comforting, and gradual extinction or sleep remodeling, as
well as written diaries to monitor sleep patterns.66
15 Sleep Strong Against Stimulating We recommend against stimulating activities, such as Children with CP (all
activities before watching television or other screens and vigorous play motor types)
bedtime during the lead-in to bedtime; this is to avoid inadequate or
62-65,67
poor sleep plus excessive daytime sleepiness.
16 Sleep Conditional For Melatonin We suggest considering melatonin after discussing risks, Children with or at
benefits, and family preferences.68-76 Note: melatonin has high risk of CP and
not been approved for adults, children, or infants by the US poor sleep onset
Food and Drug Administration. and/or cerebral
visual impairment
17 Sleep Conditional For Apnea We suggest conventional staged apnea management Children with or at
management approaches (eg, continuous positive airway pressure, high risk of CP and
steroids, surgical management) and referral to a sleep sleep apnea
specialist.77-79
18 Sleep Conditional For Spasticity We suggest trialing baclofen and/or botulinum toxin to Children with or at
management to reduce spasms and pain in an effort to improve sleep high risk of CP and
improve sleep behavior.80,81 sleep disturbance
from spasticity
19 Sleep Conditional Against Sleep positioning We recommend against using sleep positioning systems; Children with or at
systems they elevate the risk for gastroesophageal reflux, breathing high risk of CP and
difficulties, and death from unintentional sleep disturbance
asphyxiation.64,82,83
20 Sleep Conditional Against Complementary We recommend against osteopathy and acupuncture for Children with or at
and alternative improving sleep.84,85 Benefits do not appear to outweigh high risk of CP and
medicine harms (eg, anecdotal reports of serious adverse events and sleep disturbance
poor tolerance, including crying and elevating cortisol
levels), and effective alternatives exist.
21 Tone Conditional For Comprehensive We suggest commencement of comprehensive, Children with or at
hypertonia goal-directed hypertonia management for hypertonia high risk of CP and
management causing pain or interfering with motor development.86,87 hypertonia
Hypertonia management should be considered in
conjunction with the selection of motor interventions.88
22 Musculoskeletal Conditional For Regular use of We suggest regular use of standing equipment for Children with or at
standing positioning as part of an active intervention program, to high risk of CP and
equipment for potentially decrease hip migration percentage and risk of hip dysplasia,
positioning maintain hip abduction range of motion.89-91 at the age when
weight-bearing in
standing would begin
in children who are
non–weight bearing
23 Musculoskeletal Conditional For Ankle-foot orthosis We suggest ankle-foot orthoses should be worn to improve Children with CP at
or maintain dorsiflexion range of motion.92 Note: risk of ankle
ankle-foot orthoses may restrict active movement (eg, contracture
pulling to stand) but provide stability in standing. The
optimal timing for prescription is unknown.
Parent support
24 Mental health Conditional For Evidence-based We suggest targeted, evidence-based mental health Parents/caregivers
mental health interventions.93 experiencing stress,
therapies for anxiety, depression,
parents or trauma
(continued)

Table. Recommendations (continued)

25 Mental health Conditional For Cognitive We suggest psychological interventions grounded in Parents/caregivers
behavioral therapy cognitive behavioral therapy93,94 to decrease parental experiencing stress,
depression and anxiety. anxiety, depression,
or trauma
26 Parenting Conditional For Supporting parents We suggest kangaroo care to promote maternal All infants born
to carry out psychological adjustment and strengthening the relational preterm or at low
kangaroo care bond.95 birth weight with or
at high risk of CP and
their mothers
27 Parenting Conditional For Musical therapy, We suggest music therapy including musical interactions Infants born preterm
including musical between parents and their infants to promote infant with or at high risk of
interactions well-being and reduce maternal anxiety.96 CP and their parents
28 Parenting Conditional For Attachment support We suggest coaching parental sensitivity and mutually All children with or at
and coaching enjoyable parent-infant interactions (from birth onwards) to high risk of CP and
foster good parental mental health and well-being and their parents
strengthen relational bonds.94
Abbreviations: CIMT, constraint-induced movement therapy; CP, cerebral palsy.
General Best Practice Guiding Principles metry, both are recommended with clinical reasoning, including pa-
Best practice principles should guide professional interactions and rental preferences to determine the best approach for each child.104
intervention provided to children for all 9 domains (Figure).
1. Children diagnosed with or at high risk of CP should be immedi- Interventions to Improve Cognition (Recommendations 5-6),
ately referred for CP-specific and age-specific intervention.8 Applicable to All Types of Cerebral Palsy
2. Goals should be set that are task-specific and context-specific, There were no CP-specific cognitive systematic reviews found for
at the appropriate level of challenge, and updated regularly.25,100 children younger than 2 years. Eleven RCTs16,19,23,29,33-35,39,105-108
Clinicians should provide coaching and education to increase measured effects of early intervention strategies. A Cochrane
knowledge and impart support for parents and caregivers. meta-analysis109 on the effectiveness of early intervention for infants
3. Clinicians should support parents and caregivers to build paren- bornpretermsupportedsmallsustainedgainsforcognition.Moststud-
tal capacity and expertise, prioritizing a positive parent-child re- ies excluded infants with brain injuries, limiting the application of re-
lationship. Parents’ goals and aspirations must be central to the sults to CP.109 Early technology is assumed important to advance cog-
intervention, with parent participation essential. Of particular im- nitionininfantswithseverephysicaldisability.Onesystematicreview110
portance is the need for frequent practice of the activities that of the benefits of assistive technology in infants and young children
lead to skilled movement and functional independence. Inter- (3 months to 8 years and 9 months) with a range of disabilities
vention environments and professional input are not suffi- supported moderate to large effects on cognitive outcomes. Specific
ciently frequent to achieve the goals of early intervention information on CP could not be extracted from this review.110
programs.16,25,101 Environmental enrichment plus family engagement in task-
specific and context-specific active learning that incorporates infant-
Skills Development generated motor and cognitive actions has a positive outcome.19,111
Interventions to Improve Motor Skills (Recommendations 1-4), Tasks and toys may require adaptation or careful selection to accom-
Applicable to All Types of Cerebral Palsy modate the physical disability, without minimizing environmental and
Two systematic reviews17,102 and 9 RCTs16,18-22,25,26,103 were iden- cognitive task demands. Relying on generic developmental educa-
tified. Child-initiated movement, targeted motor training activi- tion or assuming benefits to cognition resulting from motor inter-
ties, and task-specific and context-specific exercises have the po- vention alone is insufficient.111 There are no risks for providing age-
tential to maximize functional outcomes.100 Repetition and intensity appropriate and skill level–appropriate environmental enrichment and
of practice optimize outcomes. Coaching families to engage their encouraging active learning. Parents want to be engaged in support-
child in playful but targeted training ensures an adequate dose of ing their children’s development but need support.112 However, mo-
practice. Therapy approaches that rely on specific therapist han- tor interventions with limited engagement of the child or that pro-
dling techniques, such passive simulation of normal movements, vide very general developmental education may not affect cognitive
were not supported by the evidence. It is important to support fami- development in children with CP younger than 2 years.105,113
lies to prioritize their relationship with their child, embed practice
into daily routines, and use environmental enrichment to stimulate Interventions to Promote Communication (Recommendations 7-8)
learning.17,102 There were no CP-specific child speech and language interventions
found. Two systematic reviews43,45 addressed communication for
Interventions to Improve Motor Skills (Recommendations 1-4), children at high risk, defined as those requiring neonatal intensive
Applicable to Unilateral Cerebral Palsy (Hemiplegia) care or with other diagnoses who are at high risk for developmen-
Constraint-induced movement therapy (CIMT) and bimanual tal delays. Recommendations do not apply to children with severe
therapy22,26 improve function of the upper limbs in children with uni- hearing loss.
lateral CP, and both are effective in older children with CP at an equal Newborns are nonverbal but communicative. The acquisition of
dose.6 Based on recent studies in children with upper limb asym- verbal speech and comprehension develops during early childhood.

Figure. General Best Practice Guiding Principles
Diagnosis of CP or high risk of CP

Strong recommendation for use
Strong recommendation against use
General best practice principles
• Refer to early intervention Conditional recommendation for use
• Foster parent expertise
• Elicit parents' goals for Conditional recommendation for use based on interpolated evidence
early intervention
1.0 CP-specific early 2.0 Task-specific 3.0 Passive

A. Skills development Motor Bilateral
intervention motor training movement
4.0 CIMT or
Unilateral
bimanual therapy
5.0 Cognitive 6.0 Generic developmental

Cognition All subtypes
interventions education alone
7.0 Face-to-face nurturing interactions with vocalizations,

Communication Preverbal
joint attentions, and reciprocal interaction
Suspected nonverbal 8.0 Hanen
10.0 Semireclined/upright
Eating and drinking Dysphagia 9.0 Soft food
positioning
B. Complication prevention Vision Strabismus 11.0 Surgical correction of strabismus
Cerebral visual
12.0 Vision training 13.0 Color contrast cues
impairment
15.0 Stimulation before

Sleep All infants 14.0 Sleep hygiene
bedtime
Poor sleep onset 16.0 Melatonin
17.0 Apnea
Apnea
management
Spasticity causing 18.0 Spasticity

pain management
20.0 Complementary and

Sleep disturbance 19.0 Sleep systems
alternative medicine
21.0 Comprehensive
Tone Hypertonia
management
Musculoskeletal Non–weight bearing 22.0 Standing equipment for positioning
Risk of ankle 23.0 Ankle-foot

contracture orthoses
C. Parent support Mental health Stress, anxiety, 24.0 Evidence-based mental health therapies
and depression
Trauma 25.0 Cognitive behavioral therapy
28.0 Attachment
Relational bond with 26.0 Kangaroo 27.0 Music therapy support and
Parenting or without respiration care in NICU in NICU coaching
CIMT indicates constraint-induced movement therapy; CP, cerebral palsy; NICU, neonatal intensive care unit.

Preverbal communication depends on the auditory processing of dren developing typically; surgeries completed by 2 years are opti-
speech sounds and interpretation of social cues.40,114-116 Children who mal. Some experts recommend early surgery for mild CP, to gain
are developing typically perceive language as a social behavior and de- better-quality fusion.
tect differences between languages and the emotional intent of
communicators.117 One in 2 children with CP have difficulties engag- Applicable to Infants and Children With Confirmed or Suspected
ing in reciprocal verbal speech,118-120 and between 19% and 32% are Cerebral Visual Impairment | Early commencement of visual training
nonverbal118,120,121 and may require augmentative and alternative is recommended to improve attention to visual stimuli and the use of
communication.122 The 3 studies on augmentative and alternative available visual functions.58 Within the context of parent-child inter-
communication110 identifiedwereofinsufficientqualitytomakestrong actions and goal-oriented play, the social and physical environment
recommendations. Clinicians need to comprehensively consider par- should be visually adapted to meet the child’s needs.133 High-
ents’ preferences when offering this intervention. contrast stimuli, light directed at the visual target, and multisensory
Longitudinal studies assessing speech outcomes in toddlers experiences are recommended.57,59
with CP indicate that an inability to speak at 2 years is associated with
poorer speech and language ability at 4 years.123 For children with Interventions to Promote Sleep (Recommendations 14-20)
emerging verbal communication and those suspected of being
nonverbal, the benefits of parent-child transactional programs Applicable to All Types of Cerebral Palsy | No systematic reviews or
(eg, Hanen) include improvements in communication skills and ex- RCTs were identified on sleep intervention for children younger than
pressive language acquisition.43,45 Coaching assists parents or care- 2 years. Most of the published research on interventions was about
givers to create an effective environment for child communication. other neurodevelopmental disorders.62-65,134,135
The intensity and group nature of some of the programs might limit Children with CP are 5 times more likely to have a sleep disor-
feasibility. der than children developing typically.62-65 Sleep disturbances nega-
tively affect quality of life for children and parents, with treatment
Interventions to Promote Eating and Drinking (Recommendations having the potential to improve the well-being of the whole family.134
9-10), Applicable to Infants and Children With Dysphagia Caregiver-provided interventions for children younger than 2 years
There were 9 systematic reviews found.51-53,124-129 One review52 fo- were ranked as the most preferable interventions in a large survey
cused exclusively on children younger than 2 years, with others in- of parents of children with CP. Untreated sleep disturbance can se-
cluding broader age groups (eg, 16 months-3 years). riously affect academic performance and behavior.136 Clinicians
Evidence supports the use of softer food consistencies and up- should identify the cause of the disturbance (eg, apnea, epilepsy,
right supported positioning. No risks were reported for modifying food anxiety, pain, spasticity, cerebral visual impairment, reflux) and ap-
consistencies; however, different food consistencies have been as- ply evidence-based interventions.63,65,135
sociated with different levels of risk.54,55 Although improvements124 Treatment for sleep disorders should establish good sleep hy-
in swallowing may be achieved through positioning modifications, giene with parent-based education and behavioral interventions with
reclined positions may exacerbate particular swallowing deficits.53 parental preferences for sleep interventions.62,66,67,137-139 A struc-
Although interventions (ie, oral sensorimotor therapy, parent train- tured, age-appropriate bedtime routine and a dark and quiet envi-
ing, feeding devices, and modifications to positioning and food con- ronment should be promoted. Maintaining regular bedtime and wak-
sistency) may provide benefits, further high-quality research is ing times may strengthen and train circadian mechanisms to promote
needed. rapid sleep onset. Potentially stimulating activities, such as watch-
There is insufficient evidence regarding the benefits and harms ing television or other screens and vigorous play, should be avoided
of neuromuscular electrical stimulation, oral sensorimotor therapy, prior to bedtime.62-65 Educating parents about sleep and the treat-
or surgical interventions (eg, gastrostomy) to inform recommenda- able influences that promote or disrupt sleep is recommended, as
tions. For children at considerable risk of aspiration, gastrostomy may is creating a quiet but enjoyable bedtime routine and moving gradu-
be the only viable intervention to provide adequate nutrition. ally toward the child’s sleep onset.137,138
Controlled crying or modified extinction (ie, structured fading
Complication Prevention of parental/caregiver presence and physical contact to teach toler-
Interventions to Improve Vision (Recommendations 11-13) ance) is recommended to reduce crying and teach solo sleeping in
One in 10 children with CP have severe vision impairment or infants developing typically. The approach is supported by mul-
blindness7; up to 70% have some cerebral visual impairment.130 Ce- tiple clinical trials and efficacious for fading resistance to bedtime
rebral visual impairment is not often diagnosed in children younger and nighttime awakenings in toddlers.139 Sleep experts have cau-
than 2 years. One systematic review131 found only a few studies on tioned against using extinction behavioral techniques in infants
vision interventions in infants and children with CP or at risk. younger than 6 months, because crying increases cortisol levels (po-
tentially affecting brain development) and affects attachment.140
Applicable to Infants and Children With Mild CP and Strabismus | Chil- These concerns are less prevalent for modified extinction proto-
dren with CP may have strabismus.56 Untreated strabismus causes cols incorporating parent responsivity.141 These recommendations
a loss of depth perception, double vision, visual disorientation, and may be applicable, despite the lack of empirical research in the CP
lower self-esteem.132 For children with amblyopia, occlusion therapy population, and have been conditionally recommended.
using an eye patch to cover the nonamblyopic eye is usual care.56
Early surgical correction of esotropia and exotropia may be benefi- Applicable to Infants and Children With Poor Sleep Onset | Specific
cial when performed to approximate surgery schedules for chil- drugs, such as melatonin, are used for disturbed sleep in children

with neurological dysfunction, including those with visual impair- should consider the child’s functional, personal, and environmen-
ment with poor day-night light differentiation.65,68-73 Melatonin can tal factors and be goal directed. There is limited evidence to sug-
increase seizure activity in rare cases74; however, recent studies have gest botulinum toxin is safe and effective for hypotonia manage-
not confirmed this proconvulsive effect of melatonin, even in chil- ment in children younger than 2 years when administered within a
dren with active epilepsy.75,142 comprehensive treatment program. The outcome of botulinum toxin
on developing muscle is unknown, and a conservative approach is
Applicable to Infants and Children With Sleep Apnea | Infants and chil- recommended. A systematic review150 identifying the rate of ad-
dren with CP can have sleep apnea, and the risks of harm from verse events in children younger than 2 years was consistent with
untreated apnea are serious.62,143 Conventional, staged apnea man- the existing literature for children older than 2 years, in whom ad-
agement approaches are recommended (eg, continuous positive air- verse events are typically mild and localized.151 Management must
way pressure, steroids, and surgical management).77,78 be regularly monitored using standardized measurements of tone
There is little research posthospital discharge on effective treat- to inform decision-making.
ment of apnea in infants and children with or at high risk of cerebral
palsy; nor is there consensus from systematic reviews on apnea man- Interventions to Prevent Musculoskeletal Impairments
agement in children developing typically.78,79 Less invasive inter- (Recommendations 22-23)
ventions are tried, first including continuous positive airway pres- There were no systematic reviews or RCTs found for interventions
sure and intranasal steroids, although infants and children often have to prevent musculoskeletal impairments for our population. There
poor tolerance to continuous positive airway pressure.78,79 Refer- are 2 RCTs92,152 for older children with CP. There is high-quality evi-
ral to a sleep specialist is recommended. dence with promising results for increasing bone mineral density with
a standing program.89 Several studies included children younger than
Applicable to Infants and Children With Sleep Disturbance Due to 5 years in addition to older children. Prevention of impairments
Spasticity | Infants with severe physical disability may experience se- should begin before age 2 years, and there is evidence of effective
vere sleep disturbance from involuntary movements, pain arising from treatments for children older than 2 years.
muscle spasms, and/or hypertonia. Given the long-term detrimental
effects of sleep disorders, baclofen and/or Botulinum toxin A should Applicable to Infants and Children Who Are Non–Weight Bearing | The
be considered to reduce spasms and pain to improve sleep.80,144 benefits of weight-bearing through standing is supported even in
children younger than 5 years with CP. Standing equipment, includ-
Applicable to Infants and Children With Sleep Disturbance | For in- ing prone and supine standers and thermoplastic standing shells, are
fants awoken by extraneous movements, nonpharmacological commonly used in infants and children requiring support. In older
management, including safe swaddling, may help dampen these children with CP, regular standing in equipment is associated with
movements.82 Care should be taken to ensure the hips are not po- improved bone density,153 but this appears not to have been con-
sitioned in extension and adduction because of the risk of hip firmed in those younger than 2 years. Standing support should be
dysplasia.83 Sleep positioning systems are not recommended64 for used when necessary to complement a treatment plan that primar-
infants, given the elevated risk for gastroesophageal reflux, breath- ily promotes action.
ing difficulties, and death.
Families may wish to trial complementary and alternative medi- Applicable to Infants and Children With Risk of Ankle Contracture |
cine treatments (such as osteopathy or massage), but the evi- Ankle-foot orthoses may be beneficial92 for maintaining range of
dence is sparse and controversial for improving sleep.84,145-147 There motion and standing but may restrict active movement. There was
are anecdotal reports of harm and low tolerance. Potential ben- insufficient evidence to recommend the timing of ankle-foot ortho-
efits vs harms need to be weighed (such as crying during treat- ses in infants and children with CP.
ment, procedural anxiety), and the treatments are not recom-
mended because effective alternatives exist. Parent Support
Mental Health and Parenting (Recommendations 24-28), Applicable
Interventions to Promote Reduction in Muscle Tone to Parents Who Experience Stress, Anxiety, Depression, or Trauma
(Recommendation 21), Applicable to Infants and Children No systematic reviews and 3 RCTs19,33,105 met inclusion criteria.
With Hypertonia Using broader age search terms and snowballing, a further 6
There was 1 systematic review found for the study population.88 reviews93,94,96,154,155 were identified.
Management of tone in young children is not well described, with Parents of children with CP are at higher risk of mental health
minimal high-quality evidence supporting pharmacological man- problems. Interventions targeting parent-infant interaction, psy-
agement for children younger than 2 years. chosocial support, and psychoeducation may be helpful for
Hypertonicity is a major contributor to secondary impairments strengthening parent-infant relationships and parental mental
that progressively leads to activity and participation restrictions.148 health.154 For the infant in intensive care, skin-to-skin contact
Secondary impairments include the development of contractures and (kangaroo care)95 and music therapy96 can be helpful. Cognitive
deformities,149 muscle stiffness, and abnormal motor control. Phar- behavioral therapy has benefits for ameliorating parental depres-
macological management of hypertonia in children with CP is the stan- sive and anxious symptoms.93,94 Parenting interventions that
dard of care in most high-income countries. incorporate acceptance and commitment therapy demonstrate
For hypertonia causing pain or interfering with motor develop- improvements in maternal mental health for families of older
ment, management should be considered. Treatment planning children.156

tive communication appears promising, but more rigorous studies

Discussion are needed. Interventions to improve visual function and cognition
are lacking, despite these co-impairments affecting quality of life.
We strongly recommend a comprehensive multidisciplinary The heterogeneity of motor severity compounded by varying
approach. When an infant is diagnosed with or at high risk for CP, comorbidities confound between-group differences in RCTs. Inter-
we recommend comprehensive screening for comorbidities. Feed- vention trials may discover true effects when samples include par-
ing and sleep disorders may interfere with motor and cognitive ticipants with similar types, topographies, or severities. Chal-
skills because the infant is trying to learn in a suboptimal back- lenges, such as small sample sizes, heterogeneity, and group designs
ground of pain, low caloric fuel, and irritability. Anticipating second- that calculate mean results, are problematic. Advanced statistical
ary impairments enables timely access to interventions, which techniques, such as bayesian modeling, pragmatic trials, and adap-
requires intentional communication among professionals.14,112 tive designs, might provide answers.
Evidence-based and empathic communication with parents is nec-
essary as new issues and concerns are raised, empowering parents Limitations
to seek help.157 Supporting parents and their relationship with their There are limited studies from the target population. Many trials are
child is fundamental to comprehensive early intervention; how- currently underway, and recommendations may change. We ex-
ever, it is not always prioritized. Evidence from studies of parents of cluded literature published in languages other than English.
infants born preterm indicates probable benefits from interven-
tions that focus on the supporting parenting role; however, we
found little evidence that specifically addressed parent interven-
Conclusions
tions after an early diagnosis.158 Evidence-based mental health
interventions are applicable to parents of infants and children Intervention should begin at diagnosis of CP or high risk of CP. Early
newly diagnosed with CP. targeted intervention builds on a critical developmental time for
There were no CP-specific RCTs found on improving sleep or plasticity of developing systems. Intervention referrals for each
communication. Low-level evidence for augmentative and alterna- domain should be specific to the recommendations.
ARTICLE INFORMATION Melbourne, Australia (Greaves, A. Morgan); Valentine, Ward, Whittingham, Zamany, Novak.
Accepted for Publication: March 12, 2021. Department of Pediatrics, University of Groningen, Drafting of the manuscript: C. Morgan, Fetters,
University Medical Center Groningen, Groningen, Boyd, Chorna, Dusing, Greaves, Harbourne,
Published Online: May 17, 2021. the Netherlands (Hadders-Algra); Duquesne Krumlinde-Sundholm, Maitre, A. Morgan, Romeo,
doi:10.1001/jamapediatrics.2021.0878 University, Pittsburgh, Pennsylvania (Harbourne); Sanchez, Spittle, Valentine, Ward, Whittingham,
Author Affiliations: Cerebral Palsy Alliance University Children’s Hospital Zurich, Zurich, Zamany, Novak.
Research Institute, Brain Mind Centre, Discipline of Switzerland (Latal); Nationwide Children’s Hospital, Critical revision of the manuscript for important
Child and Adolescent Health, The University of The Ohio State University, Columbus (Maitre); intellectual content: C. Morgan, Fetters, Adde,
Sydney, Sydney, New South Wales, Australia Orygen, Parkville, Victoria, Australia (Mei); Badawi, Bancale, Boyd, Cioni, Damiano, Darrah,
(C. Morgan, Badawi, Karlsson, McIntyre, Thornton); University of Melbourne, Parkville, Victoria, de Vries, Dusing, Einspieler, Eliasson, Ferriero,
University of Southern California, Los Angeles Australia (Mei, A. Morgan); Murdoch Children’s Fehlings, Forssberg, Gordon, Guzzetta,
(Fetters, Dusing); Department of Clinical and Research Institute, Melbourne, Victoria, Australia Hadders-Algra, Karlsson, Krumlinde-Sundholm,
Molecular Medicine, Norwegian University of (Mei, A. Morgan, Sanchez, Spittle); Makerere Latal, Loughran-Fowlds, Mak, Maitre, McIntyre,
Science and Technology, Trondheim, Norway University, Kampala, Uganda (Kakooza-Mwesige); Mei, A. Morgan, Kakooza-Mwesige, Romeo,
(Adde); Clinic and Clinical Services, St Olavs Pediatric Neurology Unit, Fondazione Policlinico Sanchez, Spittle, Shepherd, Thornton, Valentine,
Hospital, Trondheim University Hospital, Universitario A. Gemelli, Universitá Cattolica del Whittingham, Zamany, Novak.
Trondheim, Norway (Adde); Grace Centre for Sacro Cuore, Rome, Italy (Romeo); Department of Statistical analysis: Mak, Sanchez.
Newborn Care, Children’s Hospital at Westmead, Physiotherapy, University of Melbourne, Parkville, Obtained funding: Sanchez.
Westmead, New South Wales, Australia (Badawi, Victoria, Australia (Spittle); The University of Administrative, technical, or material support:
Loughran-Fowlds); IRCCS Fondazione Stella Maris, Sydney, Sydney, Australia (Shepherd, Novak); Perth C. Morgan, Bancale, Chorna, Damiano, Dusing,
Pisa, Italy (Bancale, Chorna, Cioni, Guzzetta); Children’s Hospital, Nedlands, Western Australia, Harbourne, Mei, A. Morgan, Sanchez, Spittle,
The University of Queensland, St Lucia, Australia (Valentine); Curtin University, Perth, Shepherd, Valentine, Ward, Zamany, Novak.
Queensland, Australia (Boyd, Mak, Whittingham); Australia (Ward); Eugene Child Development and Supervision: Fetters, Adde, Badawi, de Vries,
University of Pisa, Pisa, Italy (Cioni, Guzzetta); Rehabilitation Center, Oregon Health and Science Eliasson, Guzzetta, Hadders-Algra, Maitre,
National Institutes’ of Health, Bethesda, Maryland University, Eugene (Zamany). Kakooza-Mwesige, Romeo, Novak.
(Damiano); Faculty of Rehabilitation Medicine, Author Contributions: Drs C. Morgan and Fetters Other—consumer representation in research:
University of Alberta, Edmonton, Alberta, Canada had full access to all of the data in the study and Thornton.
(Darrah); University Medical Center Utrecht, take responsibility for the integrity of the data and Conflict of Interest Disclosures: Dr C. Morgan
Utrecht University, Utrecht, the Netherlands the accuracy of the data analysis. reported grants from National Health and Medical
(de Vries); Division of Phoniatrics, Medical Concept and design: C. Morgan, Fetters, Adde, Research Council during the conduct of the study
University of Graz, Austria (Einspieler); Karolinska Badawi, Boyd, Cioni, de Vries, Dusing, Ferriero, and being a trust-certified tutor with General
Institutet, Stockholm, Sweden (Eliasson, Gordon, Greaves, Guzzetta, Loughran-Fowlds, Movements outside the submitted work.
Krumlinde-Sundholm); University of California, Maitre, Romeo, Sanchez, Spittle, Shepherd, Dr Harbourne reported grants from the US
San Francisco, San Francisco (Ferriero); Holland Valentine, Novak. Department of Education outside the submitted
Bloorview Kids Rehabilitation Hospital, Department Acquisition, analysis, or interpretation of data: work. Dr Maitre reported receiving consultancy
of Paediatrics, University of Toronto, Toronto, C. Morgan, Fetters, Adde, Bancale, Boyd, Chorna, fees and equity from Thrive Neuromedical outside
Ontario, Canada (Fehlings); Department of Damiano, Darrah, Dusing, Einspieler, Eliasson, the submitted work; in addition, Dr Maitre had a
Women’s and Children’s Health, Karolinska Fehlings, Forssberg, Guzzetta, Hadders-Algra, patent for provisional application (GMAT; No.
Institutet, Stockholm, Sweden (Forssberg); Harbourne, Karlsson, Krumlinde-Sundholm, Latal, 2020-029) licensed to Enlighten Mobility outside
Teachers College, Columbia University, New York, Mak, Maitre, McIntyre, Mei, A. Morgan, the submitted work. Dr Kakooza-Mwesige reported
New York (Gordon); The Royal Children’s Hospital, Kakooza-Mwesige, Sanchez, Spittle, Thornton, grants from Swedish Research Council to fund a

cerebral palsy study in Uganda during the conduct 12. Burns PB, Rohrich RJ, Chung KC. The levels of 26. Chamudot R, Parush S, Rigbi A, Horovitz R,
of the study. No other disclosures were reported. evidence and their role in evidence-based Gross-Tsur V. Effectiveness of modified
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through a Fulbright Senior Scholar Award for doi:10.1097/PRS.0b013e318219c171 with bimanual therapy home programs for infants
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15-96 from the Mariani Foundation of Milan. 14. Byrne R, Noritz G, Maitre NL; NCH Early 27. Will B, Galani R, Kelche C, Rosenzweig MR.
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Clinical Review & Education

JAMA Pediatrics | Review

Early Intervention for Children Aged 0 to 2 Years

E2 JAMA Pediatrics Published online May 17, 2021 (Reprinted) jamapediatrics.com

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No. Domain Strength Direction Intervention Key recommendations Target population

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Table. Recommendations (continued)

No. Domain Strength Direction Intervention Key recommendations Target population

E4 JAMA Pediatrics Published online May 17, 2021 (Reprinted) jamapediatrics.com

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Table. Recommendations (continued)

No. Domain Strength Direction Intervention Key recommendations Target population

Abbreviations: CIMT, constraint-induced movement therapy; CP, cerebral palsy.

jamapediatrics.com (Reprinted) JAMA Pediatrics Published online May 17, 2021 E5

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Figure. General Best Practice Guiding Principles

Diagnosis of CP or high risk of CP

1.0 CP-specific early 2.0 Task-specific 3.0 Passive

5.0 Cognitive 6.0 Generic developmental

7.0 Face-to-face nurturing interactions with vocalizations,

Suspected nonverbal 8.0 Hanen

B. Complication prevention Vision Strabismus 11.0 Surgical correction of strabismus

15.0 Stimulation before

Poor sleep onset 16.0 Melatonin

Spasticity causing 18.0 Spasticity

20.0 Complementary and

Musculoskeletal Non–weight bearing 22.0 Standing equipment for positioning

Risk of ankle 23.0 Ankle-foot

Trauma 25.0 Cognitive behavioral therapy

E6 JAMA Pediatrics Published online May 17, 2021 (Reprinted) jamapediatrics.com

© 2021 American Medical Association. All rights reserved.

jamapediatrics.com (Reprinted) JAMA Pediatrics Published online May 17, 2021 E7

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E8 JAMA Pediatrics Published online May 17, 2021 (Reprinted) jamapediatrics.com

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tive communication appears promising, but more rigorous studies

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© 2021 American Medical Association. All rights reserved.

© 2021 American Medical Association. All rights reserved.

© 2021 American Medical Association. All rights reserved.

© 2021 American Medical Association. All rights reserved.

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