Interventions for congenital talipes equinovarus
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To evaluate the effectiveness of interventions for congenital talipes equinovarus.
Background
Description of the condition
Talipes equinovarus, also known as clubfoot, is a common congenital paediatric condition, occurring in 1 to 2 per 1000 newborns (Dobbs 2006). It is characterised by an excessively turned in foot (equinovarus) and high medial longitudinal arch (cavus) which, if left untreated leads to long‐term functional disability, deformity and pain (Ponseti 2005). Congenital talipes equinovarus is thought to begin as the limb buds form and can be diagnosed on ultrasound from 12 weeks gestation (Keret 2002). There are two types of congenital talipes equinovarus: idiopathic, and those associated with other syndromes or conditions. In both, the aetiology of the clubfoot is unknown. Pathogenesis is thought to be associated with transient gene activity as seen in developmental dysplasia of the hips (Ponseti 2005), neuromuscular disease (Handelsman 1982; Lovell 2007) or lack of foetal movement (Hester 2009). Congenital talipes equinovarus associated with other conditions such as arthrogryposis and spina bifida is often severe and more resistant to treatment (Janicki 2009).
Description of the intervention
Recently, clinicians have begun implementing a variety of more conservative interventions to reduce or resolve the congenital talipes equinovarus deformity with minimal or no surgical intervention. These include: stretching, for example the French Functional method (Richards 2008); varied serial casting (plaster casts) and bracing including Ponseti and Kite techniques (Sud 2007); minor surgical intervention, for example Achilles tenotomy, tibialis anterior tendon transfer and Achilles lengthening procedure; the use of external fixator devices (surgical application of a metal brace)(Ponseti 2005) and botulinum toxin injections (for example, Botox) (Alvarez 2005).
Unfortunately, relapses are common and occur in up to 37% of children within two years (Richards 2008) and in up to 47% before four years of age (Laaveg 1980). Causes for relapse include non compliance with bracing regimes such as the Ponseti method (Morcuende 2004), resilient clubfoot due to overactivity of the tibialis anterior tendon (Ponseti 2005) and progressive neuromuscular disease (Lovell 2007). When left untreated, the relapsed clubfoot gradually returns to its original position. In mild cases the child may overload the lateral border of their foot during walking and in extreme cases they may ambulate on the outside border of the foot (cuboid and fifth metatarsal) with resulting callosities and pain.
In children with relapsed congenital talipes equinovarus, intervention is required to prevent further progressive deformity. Historically, relapses were treated with major surgical intervention including muscle, ligament and joint releases (for example posteromedial soft tissue release) or bony operations (e.g. wedge osteotomies) (Dobbs 2000). Clinicians are beginning to employ the same conservative techniques used in initial congenital talipes equinovarus to treat relapses and avoid major surgical procedures.
How the intervention might work
Frequent stretching and active assisted movement is thought to increase joint function and range of motion of the foot and ankle, particularly in newborns. The French functional method is an example of this and has been shown to be effective in achieving joint alignment in patients less than two years of age with congenital idiopathic talipes equinovarus (Richards 2007).
Serial casting, involving sustained stretching for an extended period, is thought to improve the extensibility of surrounding tissue and joint capsules. Magnetic resonance imaging studies of babies with congenital talipes equinovarus showed that musculature, ligament and bony changes were possible when exposed to weekly serial casting (Pirani 2001). Studies have demonstrated increases in both length and numbers of sarcomeres when a muscle is immobilised in a lengthened position for an extended period of time (Cusick 1990).
Surgical procedures that are joint sparing or minor (i.e. do not involve the ankle or foot joints) are thought to result in good outcomes with pain free, functional feet (Dietz 2006). Achilles tenotomies have been shown in very young children to result in direct elongation of the tendon (De Gheldere 2008; Radler 2007). Tibialis anterior tendon transfer aims to restore the balance of musculature around the foot by making the tibialis anterior muscle a primary dorsiflexor and reducing supination during walking (Kuo 2001; Laaveg 1980). In severe cases, the relapsed congenital talipes equinovarus may require a combination of these procedures or major bone/joint surgery to correct the position of the foot and ankle.
Botulinum toxin, a potent neuromuscular agent, causes partial temporary muscular paralysis allowing for lengthening through sustained stretching (e.g. serial casting). When used in the triceps surae (calf muscle), it may prevent the need for Achilles tenotomy or other posterior release (Alvarez 2005).
Why it is important to do this review
The treatment of congenital talipes equinovarus remained varied and inconsistent until the Ponseti technique became widely practised. This technique has shown favourable long term outcomes (Cooper 1995), but relapses are common. A systematic review of all interventions for initial and relapsed congenital talipes equinovarus will assist the clinician in providing the most effective treatment in this population and allow for ongoing evaluation of these interventions in the future.
Objectives
To evaluate the effectiveness of interventions for congenital talipes equinovarus.
Methods
Criteria for considering studies for this review
Types of studies
All randomised or quasi‐randomised controlled trials of interventions for the treatment of congenital talipes equinovarus. Quasi‐randomised studies are those where systematic methods of allocation are used, e.g. date of birth, hospital number or date.
Types of participants
People of all ages with congenital talipes equinovarus of either one or both feet will be included.
Types of interventions
We will include any intervention aimed at reducing or eliminating the deformity associated with congenital talipes equinovarus (e.g. cavus, adductus, varus and equinus) including but not limited to the following.
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Stretching: for example passive and active stretching using taping, plaster casts (serial casting), etc.
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Surgery: for example muscle lengthening, tendon transfers, osteotomies (operations on bone) and external fixators (surgically applied brackets which can stretch joints).
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Other: for example botulinum toxin.
Types of outcome measures
Primary outcomes
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Function. Self‐reported or parent/proxy‐reported day‐to‐day function at a minimum of one year post‐treatment, as measured by any validated assessment tool eg. Clubfoot Disease Specific Index; physical component of the Child Health Questionnaire and physical subscale of the SF‐36.
Studies with different follow‐up periods will be combined with appropriate adjustments if the assumption of steady rates of change can be justified.
Secondary outcomes
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Foot alignment (measured by any validated assessment tool, for example, radiographic, foot posture index; Dimeglio Scale).
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Gait assessment (for example, pedobarography, 3D kinematics).
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Parent/patient reported health related quality of life (measured by any validated assessment tool, for example, Child Health Questionnaire).
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Adverse events (will be classified as 'any adverse event'; 'adverse event leading to withdrawal of treatment'; and 'life threatening (severe) adverse events (those requiring admission to hospital or adverse outcome leading to permanent disability or death).
We will be including a 'Summary of findings' table. Measures will be assessed at a minimum of one year. Studies with different follow‐up periods will be combined with appropriate adjustments if the assumption of steady rates of change can be justified. The following outcomes will be summarised:
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function (self‐ or parent/proxy‐report);
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foot alignment;
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gait assessment;
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health related quality of life;
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adverse events.
Search methods for identification of studies
Electronic searches
We will search the following databases up to the current date:
(1) MEDLINE from 1966;
(2) EMBASE from 1980;
(3) Cochrane Central Register of Controlled Trials (CENTRAL);
(4) CINAHL from 1982;
(5) PEDro from 1929;
(6) AMED (Allied and Complimentary Medicine) from 1985.
There will be no language or publication restrictions.
Searching other resources
We will review the bibliographies of the trials identified and, if appropriate, contact the authors as well as known experts in the field to identify additional studies. We will hand search the reference sections of retrieved articles, relevant thesis publications, and the reports and/or conference proceedings of relevant symposia eg the International Clubfoot Symposium, Pediatric Orthopaedic Society of North America Annual Meeting and the European Paediatric Orthopaedic Society Annual Meeting. We will contact registered expert clinicians in the field to identify additional published or unpublished data. There will be no limitations on language or year published.
Data collection and analysis
Selection of studies
Two review authors (KG and VP) will independently assess the titles and abstracts of trials identified by the search process. The same two authors will review full text copies of potentially relevant trials to assess methodological quality based on inclusion criteria.
Authorship and results will not be masked as the effect of the assessor masking has not been established by empirical evidence (Higgins 2008c). We will resolve disagreements by discussion between review authors or, if necessary, arbitration by a third review author (JB). If arbitration by the third reviewer does not resolve the dispute, we will contact the study authors for additional information. If this is unsuccessful, we will report the disagreement in the review.
Data extraction and management
Two review authors (KG and VP) will independently extract data using separate, standardised, prepared forms. We will contact trial authors in order to provide any missing information where possible. One author (KG) will enter data into the Cochrane software Review Manager (RevMan 2008) and second review author (VP) will check it. We will resolve disagreements by discussion between review authors or, if necessary, arbitration by a third review author (JB).
Assessment of risk of bias in included studies
Two review authors (KG and VP) will independently rate the methodological quality of the reviewed studies using a standardised grading system described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008). The grading system will consider the following criteria.
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Sequence generation
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Allocation concealment
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Blinding of participants, personnel and outcome assessors
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Other potential threats to validity (such as financial conflicts of interest, single author or single centre trials)
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Incomplete outcome data
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Selective outcome reporting
We will create a 'Risk of bias' table to present a description of what was reported within the published report for each criterion and to assign a judgement relating to the risk of bias for that entry. 'Yes' will indicate a low risk of bias, 'No' a high risk of bias and 'Unclear' an unknown risk of bias or that an entry is not relevant to the study at hand. We will generate a 'Risk of bias summary' figure using RevMan to present all of the judgements in a cross‐tabulation of study by entry.
Measures of treatment effect
If there is more than one trial with a specific intervention we will perform a meta‐analysis using the Cochrane statistical package RevMan. Where the same outcome measures are used, we will calculate mean differences (MD) and 95% confidence intervals (CIs) for continuous variables. Where outcome measures differ but measure the same construct, we will calculate standardised mean differences (SMD) and 95% CIs. For dichotomous outcomes, we will determine risk ratios (RRs) and 95% CIs using a fixed‐effect model, where heterogeneity permits (see 'Assessment of heterogeneity')
Unit of analysis issues
We will include cross‐over trials, if found, in the review. We will use the Generic Inverse Variance (GIV) facility in RevMan to combine the estimated difference in effects from each study with its standard error.
Dealing with missing data
When intention‐to‐treat analysis has not been performed by the original authors of a study and sufficient data are available to do so, we will perform intention‐to‐treat analysis before the entry of data into RevMan with the aim of limiting bias. If insufficient data are available, we will attempt a comparison of worst and best case scenarios.
Assessment of heterogeneity
We will assess clinical heterogeneity across trials and if trials are sufficiently clinically homogenous in terms of participants, intervention, and outcomes we will include them for meta‐analysis.
We will quantify inter‐trial statistical inconsistency using I2 (Higgins 2008a).
We will calculate the I2 value by:
I2 = 100% [Q‐df)/Q]
where Q is Cochrane's heterogeneity, Chi2 statistic and df is the degrees of freedom. We will determine the Cochrane's Q by summing the squared deviations of each trial's estimate from the overall meta‐analytic estimate and obtain a P value by comparing the statistic with an Chi2 distribution with k‐1 degrees of freedom (where k is the number of trials). We will use the following guide to interpret the I2 values:
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0 to 40% might not be important;
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30 to 60% may represent moderate heterogeneity;
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50 to 90% may represent substantial heterogeneity;
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75 to 100% considerable heterogeneity.
When there is unexplained heterogeneity, we will use a random‐effects modelto incorporate heterogeneous trials in the meta‐analysis.
Assessment of reporting biases
We will take the following measures to reduce reporting biases.
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We will perform comprehensive searches to identify randomised, quasi randomised and cross‐over trials.
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We will seek and include unpublished relevant studies, these will include those registered at inception.
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We will, where possible, detect reporting biases using funnel plots to assess for small study effects (Higgins 2008b).
Data synthesis
We will use RevManfor data analysis. One author (KG) will enter statistical data and a second review author (VP) will check the data entry. We will resolve any disagreement by discussion with a third review author (JB).
Subgroup analysis and investigation of heterogeneity
The following subgroup analyses will be performed, providing sufficient data are available.
i) Age: 0 to 2 years, 2 to 4 years, 4 to 10 years,10 to 20 yrs, over 20 years of age (relapses are most common in the 0 to 2 year range and decrease with age. The literature often provides subgroup analysis (Laaveg 1980; Richards 2008).
ii) Unilateral cases versus bilateral cases.
iii) Idiopathic versus congenital talipes equinovarus associated with other conditions.
iv) Initial versus relapsed congenital talipes equinovarus. Meta‐analysis of subgroups will follow the same methodological principles as the primary analysis.
Sensitivity analysis
If clinical heterogeneity is present, we will carry out sensitivity analysis by omitting from the meta‐analysis those trials which have problems with methodological quality, are unpublished, or funded by industry. Omissions will be made in order, e.g. studies with unclear or inadequate allocation concealment will be removed, the analysis re‐run, then all studies with unclear blinding will be removed, the analysis re‐run etc.
We will add cost‐benefit analysis of interventions for the treatment of relapsed congenital talipes equinovarus in the 'Discussion' of this review, making use of the non‐randomised data where necessary.
