Weak evidence supports intensive, task-oriented, early intervention with parent support for infants with, or at high risk of, cerebral palsy

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Critically Appraised Paper
Weak evidence supports intensive, task-oriented, early
intervention with parent support for infants with, or at high
risk of, cerebral palsy
Synopsis
Hadders-Algra,M.,Boxum,A.G.,Hielkema,T.&Hamer,
E. G. (2017). Effect of early intervention in infants at very
high risk of cerebral palsy: A systematic review. Develop-
mental Medicine and Child Neurology, 59(3), 246–258.
doi:10.1111/dmcn.13331
Objective: Review the evidence for early intervention with
infants with, or at risk of, cerebral palsy.
Design: Systematic review
Methods: PubMed, CINAHL, Embase, reference lists,
review articles and Developmental Medicine and Child Neurol-
ogy were searched to January 2016. Inclusion criteria: peer-
reviewed research of moderate to high methodological
quality; written in English; a prospective group design
with comparison group or period; mean age of the infants
at study entry less than 12 months corrected age and indi-
vidual infants younger than 18 months; and intervention
intended to influence neurodevelopmental outcome. Exclu-
sion was severe comorbidity unrelated to cerebral palsy.
Outcomes of interest were motor, cognitive and family and
parental wellbeing, and their relationship to brain lesion
and type and dose of intervention. Three reviewers inde-
pendently extracted data, completed quality appraisal and
reached consensus through discussion.
Main findings: Seven randomised trials (high (n=1) and
moderate (n=6) methodological quality) of 299 infants
(groups sizes 6–54) with brain lesion, “neurological
deviancy”, “high suspicion” of cerebral palsy or abnormal
general movements were included. Heterogeneity of inter-
vention type and intensity precluded pooling of results
and drawing firm conclusions. Weak evidence suggests
that developmental stimulation may improve cognitive
outcomes (two of three studies showed a positive effect)
and parent support improves family wellbeing (three out
of three studies). No convincing evidence that neurodevel-
opmental therapy (one of two studies suggested positive
effect) or developmental stimulation (one of four studies)
improves motor outcomes. Insufficient evidence to draw
conclusions about the impact of sensory input (one study).
Insufficient information was available to identify a relation-
ship between type of brain lesion and intervention effec-
tiveness. Several flaws in the evidence base were noted
including small sample size, ill-defined brain lesions, short
follow-up, inadequate comparison group description, and
adherence to intervention fidelity not addressed.
Authors’ conclusions: Weak evidence in the included stud-
ies leads to the suggestion that intensive early intervention
and multifaceted intervention may be required to optimise
outcomes for infants with, or at risk of, cerebral palsy. Sub-
stantial high-quality research is required to advance the
field.
Contact details of original author:MHadders-Algra,
m.haddersalgra@umcg.nl
Margaret Wallen
CAPs Advisory Board Member
Email: margaret.wallen@acu.edu.au
Synopsis
Morgan,C.,Darrah,J.,Gordon,A.M,Harbourne,R.,
Spittle, A., Johnson, R. & Fetters, L. (2016). Effectiveness
of motor interventions in infants with cerebral palsy: A
systematic review. Developmental Medicine and Child
Neurology, 58(9), 900–909. doi:10.1111/dmcn.13105
Objective: To review the evidence for effectiveness of inter-
ventions to improve motor outcomes for children with
cerebral palsy aged 0–2years.
Design: Systematic review
Methods: Systematic searches of six databases (PubMed,
Embase, CINAHL, Cochrane, Web of Knowledge, PEDro)
were undertaken in 2014 and updated in 2015. Inclusion
criteria: all research designs with participants aged birth-
2 years diagnosed with, or at high risk of, cerebral palsy;
motor intervention implemented and motor outcomes
assessed. Motor intervention defined as “therapeutic inter-
vention with motor development or skills as one primary
outcome” (p. 901). Studies were excluded if not written in
English or if the intervention was medical, pharmaceutical
or surgical. Reviewers independently selected studies for
inclusion. Interventions were classified by reviewer con-
sensus using the International Classification of Functioning
Disability and Health framework. Risk of bias was assessed
©2017 Occupational Therapy Australia
Australian Occupational Therapy Journal (2017) 64, 423–425 doi: 10.1111/1440-1630.12426

using American Academy of Cerebral Palsy and Develop-
mental Medicine guidelines. Effect sizes assessed according
to Cohen’s dand quality and strength of evidence ranked
using the Grading of Recommendations Assessment,
Development and Evaluation system. Meta-analysis was
not possible due to heterogeneity.
Main findings: Thirty-six included papers reported 34 stud-
ies published 1984–2015; 10 randomised controlled trials
(RCT), 4 cohort, 10 single-subject design and 10 case stud-
ies or case series designs. Methodological quality collec-
tively assessed as low. The median sample size of the
RCTs and the cohort study with a control group was 26.
Confirmed diagnosis at study exit ranged from 22% to
77%. Activity level outcomes were most commonly mea-
sured. Only 4 (of 10) RCTs reported statistically significant
findings with “effect sizes ranging from 0.14 (small) to 0.75
(moderate-high)” (p. 906). The single-subject and case ser-
ies designs all showed positive findings. Duration and
intensity of intervention varied from 6-days/week for
6 weeks to monthly for 12 months. Interventions included
neurodevelopmental therapy, Vojta (passive application of
reciprocal limb movements), environmental enrichment
and constraint-induced movement therapy. Interventions
were complex; the most common component was parent
education. The commonly included intervention elements
in the two RCTs with largest effect sizes were child-
initiated movement, task specific training and environmen-
tal modifications.
Authors’ conclusions: Low quality evidence was ‘weakly
positive.’ Recommendationsweretoimplementearly,
intensive motor intervention with infants with, or at high
risk of, cerebral palsy consistent with contemporary prac-
tice around neuroplasticity and motor learning principles,
and positive outcomes identified in studies of older chil-
dren –that is, interventions which elicit active movement
in task-oriented activities in a high intensity program.
Contact details of original author: Catherine Morgan,
cmorgan@cerebralpalsy.org.au
Christine Imms
CAPs Advisory Board Member
Email: christine.imms@acu.edu.au
Commentary
Premature birth, brain lesions and abnormalities place
infants at high risk of cerebral palsy (CP). Recently, the
increased use of magnetic resonance imaging (MRI), com-
bined with prognostic tools such as the General Move-
ments Assessment (GMs) and the Hammersmith Infant
Neurological Examination (HINE), has made detection of
infants with, or at risk of, CP possible during the first half-
year of life (McIntyre, Morgan, Walker & Novak, 2011;
Romeo, Ricci, Brogna & Mercuri, 2016). Early detection is
crucial, as animal studies show that the timing of interven-
tion is the most critical factor for maximising treatment
outcomes (Friel, Chakrabarty, Kuo & Martin, 2012). Further
to this, is evidence that most gross motor and bimanual
performance potential in children with CP is experienced
in the first 2 years of development (Nordstrand, Eliasson &
Holmefur, 2016; Rosenbaum et al., 2002). Early detection
should trigger immediate referral to infant specific inter-
vention programs. But what is the evidence for these pro-
grams? Two recent papers aimed to systematically review
the evidence for early intervention for infants with, or at
high risk of CP (Hadders-Algra, Boxum, Hielkema &
Hamer, 2017; Morgan et al., 2016).
These two reviews fill an important knowledge gap by
focussing specifically on children younger than 2 years of
age when intervention can drive neural circuit develop-
ment during the most dynamic phase of plasticity. Had-
ders-Algra et al. (2017) made special effort to highlight
differences in methodology compared to the earlier review
by Morgan et al. (2016). These include a focus on children
<1 years old, methods used for rating the quality of
included studies, inclusion of family outcomes, the effect of
disease state on intervention response and the dose and
type of intervention provided. These differences led to
inclusion of significantly fewer studies in Hadders-Algra
et al. (n=7) compared with Morgan et al. (2016) (n=34).
Despite this, outcomes for each review are similar. Evi-
dence for intervention remains weak. Studies are mostly
small with low methodological quality. There is consider-
able heterogeneity across studies including participants,
interventions and outcome measures. As a result, meta-
analysis of data for pooled effect, the ability to make defini-
tive conclusions on the effect of disease state on treatment
response, or on the dose and type of intervention provided,
are not possible. Both reviews concluded that trends in the
data support intervention models based on motor learning
theory (e.g., child-initiated movement), environmental
enrichment and parent education underpinned by ecologi-
cal and family-centred frameworks.
One point of difference between the reviews relates to
neurodevelopmental therapy (NDT). Hadders-Algra et al.
(2017) suggested that minimal hands on postural support
techniques may be useful for infants with CP. Morgan et al.
(2016) suggested that trends in data do not support neuro-
maturational approaches such as NDT. Despite these dif-
ferences, we agree with comments by Morgan et al. that
whatever the intervention type, a comprehensive descrip-
tion of the key ingredients is essential, especially where
there is a diversity of interpretation (Mayston, 2016).
While evidence remains weak, the consistent outcomes
and emerging evidence described by both reviews, have
important implications for occupational therapists. Work-
ing with infants with CP means focussing on occupation,
rather than using neuro-maturational approaches that seek
to normalise movement. The core philosophies of our occu-
pation-based profession are entirely consistent with the
key ingredients of evidence-based models of early inter-
vention proposed in these reviews including child-initiated
movement, task specificity, environmental modification
and parent support and education.
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424 CRITICALLY APPRAISED PAPER

Paediatric occupational therapists should abandon gen-
eralised, low intensity models of intervention. Alongside a
specific, targeted, therapist-guided program, interventions
should include a goal-directed home program as a prag-
matic solution to achieving optimal intensity and to ensure
generalisation of skills (Novak, Cusick & Lannin, 2009).
Evidence-based occupational therapy with infants at high
risk of CP includes collaborating with medical profession-
als in the early detection of CP by using diagnostic tools
such as the GMs and HINE; confident application of evi-
dence-based early intervention models including COPing
with and CAring for Infants with Special Needs (COPCA)
(Dirks, Blauw-Hospers, Hulshof & Hadders-Algra, 2011),
Goals, Activity and Motor Enrichment (GAME) (Morgan,
Novak, Dale, Guzzetta & Badawi, 2014), baby constraint-
induced movement therapy (Eliasson, Sjostrand, Ek, Krum-
linde-Sundholm & Tedroff, 2014) and bimanual therapy
(Hoare & Greaves, 2017). New measures such as the Hand
Assessment for Infants (HAI) (Krumlinde-Sundholm et al.,
2015) and the Mini-Assisting Hand Assessment (Greaves,
Imms, Dodd & Krumlinde-Sundholm, 2013) are available
and enable targeting of upper limb interventions to the just
right challenge, and objective evaluation of outcomes of
early intervention.
In Australia, the introduction of the National Disability
Insurance Scheme provides great opportunity for families
of children with CP to access occupational therapy. For
children older than 2 years of age with CP, there are effec-
tive interventions supported by strong evidence (Novak
et al., 2013). Evidence-based interventions implemented
with strong treatment fidelity in clinical practice, including
for younger infants, are required. Current evidence-based
interventions are not transdisciplinary approaches, but are
highly specific and targeted interventions provided by
skilled therapists who have gained experience in, and
knowledge about, working with very young infants.
Organisations need to ensure specialist training opportuni-
ties for staff, adapt services based on the evolving evi-
dence, and foster and recognise clinical expertise.
Brian Hoare
Department of Paediatrics Monash University and School of
Occupational Therapy,
La Trobe University,
Melbourne, Victoria, Australia
Email: brianhoare@cpteaching.com
Susan Greaves
Occupational Therapy Department, The Royal Children’s
Hospital,
Melbourne, Victoria, Australia
Email: sue.greaves@rch.org.au
References
Dirks, T., Blauw-Hospers, C. H., Hulshof, L. J. & Hadders-Algra, M.
(2011). Differences between the family-centered “COPCA” program
and traditional infant physical therapy based on neurodevelopmen-
tal treatment principles. Physical Therapy,91,1303–1322.
Eliasson, A. C., Sjostrand, L., Ek, L., Krumlinde-Sundholm, L. & Tedr-
off, K. (2014). Efficacy of baby-CIMT: Study protocol for a ran-
domised controlled trial on infants below age 12 months, with
clinical signs of unilateral CP. BMC Pediatrics,14, 141. https://doi.
org/10.1186/1471-2431-14-141.
Friel, K., Chakrabarty, S., Kuo, H.-C. & Martin, J. (2012). Using motor
behavior during an early critical period to restore skilled limb move-
ment after damage to the corticospinal system during development.
Journal of Neuroscience,32, 9265–9276.
Greaves, S., Imms, C., Dodd, K. & Krumlinde-Sundholm, L. (2013).
Development of the Mini-Assisting Hand Assessment: Evidence for
content and internal scale validity. Developmental Medicine and Child
Neurology,55, 1030–1037.
Hadders-Algra, M., Boxum, A. G., Hielkema, T. & Hamer, E. G. (2017).
Effect of early intervention in infants at very high risk of cerebral
palsy: A systematic review. Developmental Medicine and Child Neurol-
ogy,59,246–258. https://doi.org/10.1111/dmcn.13331.
Hoare, B. & Greaves, S. (2017). Unimanual versus bimanual therapy in
children with unilateral cerebral palsy: Same, same, but different.
Journal of Pediatric Rehabilitation Medicine,10,47–59. https://doi.org/
10.3233/PRM-170410.
Krumlinde-Sundholm, L., Sicola, E., Ek, L., Guzzetta, A., Sj€
ostrand, L.,
Cioni, G. et al. (2015). The Hand Assessment for Infants, a new test
for measuring use of hands and possible asymmetry in infants
3–10 months of age. Developmental Medicine and Child Neurology,57
(Suppl 5), 54–55. https://doi.org/10.1111/dmcn.87_12887.
Mayston, M. (2016). Bobath and NeuroDevelopmental Therapy: What
is the future? Developmental Medicine and Child Neurology,58, 994.
https://doi.org/10.1111/dmcn.13221.
McIntyre, S., Morgan, C., Walker, K. & Novak, I. (2011). Cerebral palsy
–Don’t delay. Developmental Disabilities Research Reviews,17,114–129.
Morgan, C., Novak, I., Dale, R. C., Guzzetta, A. & Badawi, N. (2014).
GAME (Goals –Activity –Motor Enrichment): Protocol of a single
blind randomised controlled trial of motor training, parent education
and environmental enrichment for infants at high risk of cerebral
palsy. BMC Neurology,14, 203. https://doi.org/10.1186/s12883-014-
0203-2.
Morgan, C., Darrah, J., Gordon, A. M., Harbourne, R., Spittle, A., John-
son, R. et al. (2016). Effectiveness of motor interventions in infants
with cerebral palsy: A systematic review. Developmental Medicine and
Child Neurology,58,900–909. https://doi.org/papers3://publi
cation/doi/10.1111/ dmcn.13105.
Nordstrand, L., Eliasson, A.-C. & Holmefur, M. (2016). Longitudinal
development of hand function in children with unilateral spastic
cerebral palsy aged 18monthsto 12years. Developmental Medicine
and Child Neurology,58,1042–1048. https://doi.org/papers3://publi
cation/doi/10.1111/ dmcn.13106.
Novak, I., Cusick, A. & Lannin, N. (2009). Occupational therapy home
programs for cerebral palsy: Double-blind, randomized, controlled
trial. Pediatrics,124, e606–e614.
Novak,I.,McIntyre,S.,Morgan,C.,Campbell,L.,Dark,L.,Morton,N.
et al. (2013). A systematic review of interventions for children with
cerebral palsy: State of the evidence. Developmental Medicine and Child
Neurology,55, 885–910. https://doi.org/10.1111/dmcn.12246.
Romeo, D. M., Ricci, D., Brogna, C. & Mercuri, E. (2016). Use of the
Hammersmith Infant Neurological Examination in infants with cere-
bral palsy: A critical review of the literature. Developmental Medicine
and Child Neurology,58,240–245. https://doi.org/10.1111/dmcn.
12876.
Rosenbaum, P. L., Walter, S. D., Hanna, S. E., Palisano, R. J., Russell, D.
J.,Raina,P.et al. (2002). Prognosis for gross motor function in cere-
bral palsy: Creation of motor development curves. The Journal of the
American Medical Association,288, 1357–1363.
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