Causes of Clubfoot

NewsBot · Jun 20, 2018

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Clubfoot Etiology: A Meta-Analysis and Systematic Review of Observational and Randomized Trials
Chen, Cynthia, BA; Kaushal, Neil, MD; Scher, David M., MD; Doyle, Shevaun M., MD; Blanco, John S., MD; Dodwell, Emily R., MD, MPH, FRCSC
Journal of Pediatric Orthopaedics: June 18, 2018 - Volume Publish Ahead of Print - Issue - p

Background: Clubfoot is a common congenital anomaly with multiple potential risk factors. Identification of modifiable risk factors may minimize future incidence of clubfoot. The aim of this meta-analysis was to systematically review and analyze the best clinical evidence regarding risk factors associated with clubfoot.

Methods: Medline, Embase, and Cochrane databases were systematically searched from 1967 to May 11, 2016 for studies reporting risk factors for clubfoot. Randomized trials and observational studies were eligible for inclusion, and assessed in duplicate. Study quality was assessed with the Newcastle-Ottawa Scale or Cochrane risk of bias tool; low quality studies were excluded, all randomized trials were included. Two reviewers extracted data independently. This meta-analysis was conducted in accordance with PRISMA guidelines. Pooled effect estimates for the odds of clubfoot were calculated using random or fixed-effects models based on heterogeneity.

Results: Forty-two studies (28 case-control, 10 cohort, 4 randomized trials) comprising 31,844 clubfoot cases and 6,604,013 controls were included. Risk factors associated with increased odds of clubfoot included maternal smoking [odds ratio (OR)=1.65; 95% confidence interval (CI), 1.54-1.78], paternal smoking (OR=1.72; 95% CI, 1.05-2.84), maternal body mass index >30 (OR=1.46; 95% CI, 1.29-1.65), family history (OR=7.80; 95% CI, 4.04-15.04), amniocentesis (OR=2.08; 95% CI, 1.34-3.21), selective serotonin reuptake inhibitor exposure (OR=1.78; 95% CI, 1.34-2.37) maternal single status (OR=1.17; 95% CI, 1.11-1.23), gestational diabetes (OR=1.40; 95% CI, 1.13-1.72), nulliparity (OR=1.32; 95% CI, 1.19-1.45), male sex (OR=1.68; 95% CI, 1.48-1.94), and aboriginal Australian race (OR=2.35; 95% CI, 1.63-3.38).

Conclusions: Smoking, maternal obesity, family history, amniocentesis, and some selective serotonin reuptake inhibitor exposures are the most clinically relevant exposures associated with increased odds of clubfoot, with family history representing the greatest risk. Recognition of modifiable risk factors may help in counseling patients, and minimizing clubfoot incidence.
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Admin2 · Jun 20, 2018

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NewsBot · Jul 18, 2018

TRENDS OF SMOKING AMONG THE PARENTS OF CONGENITAL TALIPES EQUINOVARUS PATIENTS
Muhammad Junaid Akram et al
International Journal of Rehabilitation Sciences (IJRS), [S.l.], v. 7, n. 01, p. 16-19, june 2018. ISSN 2308-5363.

Background: Congenital Talipes Equino-Varus is one of the deformities of the lower limb that is most prevalent among males. Many epidemiological studies are in progress/going on to know the exact cause, even though it is suggested that genetic and environmental factors (smoking) play central role in causing the disorder.

Objectives: To evaluate the trends of smoking, economic status, educational and ethnic background in parents of patients with Congenital Talipes Equino-Varus

Methodology: The study was a descriptive cross section survey carried out at PIPOS Rehabilitation Services Program (PRSP), Peshawar from April 2014 to May 2014. A self-structured questionnaire was used to collect data from participants. Only the patients with clubfoot were included in the study. The data was analyzed by using SPSS V20.

Results: Number of the participants included in the study were n=107 and Mean age was 8.22± 6.10 years. 70 (65 %) participants were having bilateral clubfeet and 37 (35%) were unilateral clubfeet. There was not even a single participant whose mother did smoke but there were 47 (44%) participants whose father used to smoke during pregnancy. 4 (4%) of participants were having household smoking and 56 (52%) participants’ parents were not smoker. Data revealed that 69 (64%) of mothers were illiterate, 48 (48%) families of the participants were having average economic income, 81 (76%) of respondents were from rural area and 83 (78%) of respondent parents married within the family while 24 (22%) of respondent parents married outside the family.

Conclusion: This study clearly showed the trends of smoking among the family members of the clubfeet participants. Passive mother smoking, average income families, illiterate mothers and family marriages were common among clubfoot patients.
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NewsBot · Jul 24, 2018

Complex iatrogenic clubfoot: is it a real entity?
Dragoni, Massimiliano; Gabrielli, Armando; Farsetti, Pasquale; Bellini, Diego; Maglione, Pierluigi; Ippolito, Ernesto
Journal of Pediatric Orthopaedics B: September 2018 - Volume 27 - Issue 5 - p 428–434

In our study, we aimed to demonstrate whether a complex iatrogenic clubfoot really exists; identify the causative mechanisms; and determine the outcome if properly treated. We observed 54 clubfeet previously treated unsuccessfully by manipulation and casting elsewhere. All the feet had been classified at diagnosis as typical clubfeet. In 26 cases, the cast had slipped down, entrapping the foot in a plantar-flexed position. Nine clubfeet out of those 26 cases presented the clinical features of a complex iatrogenic deformity. These were treated with the modified Ponseti protocol and evaluated at follow-up according to the International Clubfoot Study Group Score. The length of follow-up averaged 7.2 years. Two feet showed an excellent result, five feet showed a good result, and two feet showed a fair result. The relapse rate was 55% in complex clubfeet. Relapsed clubfeet were treated by Achilles tenotomy or lengthening and anterior tibial tendon transfer. We believe that faulty manipulation and a poor casting technique may convert a typical clubfoot into a complex iatrogenic deformity. Risk factors include severe clubfoot, short and stubby foot, and unmolded casts slipping down.
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NewsBot · Aug 25, 2018

The etiology of idiopathic congenital talipes equinovarus: a systematic review
Vito PavoneEmanuele ChisariAndrea VescioLudovico LucentiGiuseppe SessaGianluca Testa
Journal of Orthopaedic Surgery and Research December 2018, 13:206

Also known as clubfoot, idiopathic congenital talipes equinovarus (ICTEV) is the most common pediatric deformity and occurs in 1 in every 1000 live births. Even though it has been widely researched, the etiology of ICTEV remains poorly understood and is often described as being based on a multifactorial genesis. Genetic and environmental factors seem to have a major role in the development of this disease. Thus, the aim of this review is to analyze the available literature to document the current evidence on ICTEV etiology.

Methods
The literature on ICTEV etiology was systematically reviewed using the following inclusion criteria: studies of any level of evidence, reporting clinical or preclinical results, published in the last 20 years (1998–2018), and dealing with the etiology of ICTEV.

Results
A total of 48 articles were included. ICTEV etiology is still controversial. Several hypotheses have been researched, but none of them are decisive. Emerging evidence suggests a role of several pathways and gene families associated with limb development (HOX family; PITX1-TBX4), the apoptotic pathway (caspases), and muscle contractile protein (troponin and tropomyosin), but a major candidate gene has still not been identified. Strong recent evidence emerging from twin studies confirmed major roles of genetics and the environment in the disease pathogenesis.

Conclusions
The available literature on the etiology of ICTEV presents major limitations in terms of great heterogeneity and a lack of high-profile studies. Although many studies focus on the genetic background of the disease, there is lack of consensus on one or multiple targets. Genetics and smoking seem to be strongly associated with ICTEV etiology, but more studies are needed to understand the complex and multifactorial genesis of this common congenital lower-limb disease.
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NewsBot · Jan 9, 2019

A novel contribution to clubfoot pathogenesis: the possible role of extracellular matrix proteins
Adam Eckhardt Tomas Novotny Ivan Miksik Lucia Hronkova Ludek Vajner Statis Pataridis Daniel Hadraba Lucie Kulhava Martin Plencner Jarmila Knitlova Jana Liskova
Jnl Orth Res: 07 January 2019 https://doi.org/10.1002/jor.24211

Idiopathic pes equinovarus (clubfoot) is a congenital deformity of the feet and lower legs. Clubfoot belongs to a group of fibro proliferative disorders but its origin remains unknown. Our study aimed to achieve the first complex proteomic comparison of clubfoot contracted tissue of the foot (medial side; n = 16), with non contracted tissue (lateral side; n = 13). We used label free mass spectrometry quantification and immunohistochemistry. Seven proteins were observed to be significantly upregulated in the medial side (asporin, collagen type III, V, and VI, versican, tenascin C, and transforming growth factor beta induced protein) and four in the lateral side (collagen types XII and XIV, fibromodulin, and cartilage intermediate layer protein 2) of the clubfoot. Comparison of control samples from cadavers brought only two different protein concentrations (collagen types I and VI). We also revealed pathological calcification and intracellular positivity of transforming growth factor beta only in the contracted tissue of clubfoot. Most of the 11 differently expressed proteins are strongly related to the extracellular matrix architecture and we assume that they may play specific roles in the pathogenesis of this deformity. These proteins seem to be promising targets for future investigations and treatment of this disease.
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NewsBot · Apr 22, 2020

The influence of laterality, sex and family history on clubfoot severity
Giada Salvatori, Camilla Bettuzzi, Caterina Novella Abati, Giuseppe Cucca, Alessandro Zanardi, Manuele Lampasi
Journal of Children's Orthopaedics:16 Apr 2020

Purpose
Epidemiological studies on idiopathic clubfeet have shown a typical distribution consistent across ethnic groups: bilaterality in about 50% of cases and a male to female ratio of 2:1. Whether this corresponds also to differences in severity according to laterality and sex has been poorly evaluated. As well, the correlation between family history and severity has not been previously investigated. The aim of this study was to investigate how laterality, sex and family history influence severity and treatment.

Methods
In all, 97 infants with idiopathic clubfoot (81 male, 16 female; 55 unilateral, 42 bilateral; 19 with a first or second-degree relative affected) consecutively treated with Ponseti method were prospectively enrolled. Initial severity (according to Dimeglio and Pirani scores) and treatment (number of casts and need for tenotomy) were analyzed in the different subgroups.

Results
Initial severity according to Pirani (p = 0.020) and Dimeglio score (p = 0.006), number of casts (p = 0.000) and tenotomy (p = 0.045) were significantly higher in bilateral than in unilateral cases. In bilateral cases, a significant correlation was found between the right and left foot of each patient in terms of initial severity, number of casts and tenotomy performed. No statistically significant difference was found according to sex and family history.

Conclusions
This study has confirmed the different behaviour of bilateral cases reported by previous studies; bilateral cases are more severe and show similar features in their right and left foot. This could be the result of different pathogenic mechanisms, likely on a genetic basis. Sex and family history did not seem to influence severity.
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NewsBot · Apr 25, 2022

Novel report on congenital talipes equinovarus (CTEV) following olanzapine exposure during pregnancy: case report and short review
Rajan Gyawali, Ashok Baral, Dikshya Upreti, Chandra Bhushan Yadav, Anoop Krishna Gupta, Miyuru Chandradasa & Sheikh Shoib
Archives of Women's Mental Health (2022)

Olanzapine is widely used during pregnancy to manage mood and psychotic disorders with overall beneficial effects. There have been past reports of olanzapine exposure during early pregnancy and clubfoot in two newborns from India and Israel. We report a woman in Nepal diagnosed with schizophrenia and treated with olanzapine throughout the pregnancy delivering a baby boy with congenital talipes equinovarus deformity. Like in many other low-income settings, pregnancy was unplanned, and pre-conception counselling was not done. Research in mice has revealed the negative effects of olanzapine on bone development. Further reports would strengthen this potential association between exposure to olanzapine in the first trimester and the occurrence of clubfoot in the baby.
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NewsBot · Apr 7, 2023

A prospective study on the role of foot evertor muscle activity in recurrence of clubfoot
Rama Priya Yasam et al
Foot (Edinb). 2023 Mar 25

Background: Even after corrective casting and bracing, clubfoot recurrence is challenging throughout childhood, with around 14-40 % recurrence rates. Most of the literature on recurrence was attributed to various factors, and minimal research was conducted to know the role of foot evertor muscle activity and its stimulation benefits. This study aimed to assess the role of foot evertor muscle activity in idiopathic congenital clubfoot recurrence by using clinical, sonographic, and electromyographic parameters.

Methods: A prospective cohort study was conducted at our tertiary care hospital from 2020 to 2022. The patient's demographic data, Pirani, Dimeglio, Clinical Evertor Muscle Activity scores, sonographic cross-sectional areas of leg muscle, and evertor motor activity using surface electromyography were recorded in adherence to the pre-defined intervals.

Results: In total, 51 patients (51 feet) were included in the study, and the overall recurrence rate was 27.5 % (14/51). In this study, around 47 % (24/51) of children had mild or poor clinical evertor activity; among them, 58 % (14/24) children had a recurrence, and the insufficient clinical evertor activity and recurrence were strongly correlated (p = 0.01). Evertor muscle cross-sectional area ratio, motor unit potentials, and recruitment were comparatively less in the recurred group; however, only the cross-sectional area ratio was statistically significant (p = 0.02).

Conclusion: Early detection of evertor muscle weakness can help to individualize the treatment plans by predicting recurrence. Therefore, it should be included in routine clinical evaluations. Further research is required to determine the advantages of evertor muscle-strengthening activities in preventing idiopathic clubfoot deformity.
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NewsBot · Oct 24, 2023

Investigating the association between vitamin D dietary intake during pregnancy and incidence of clubfoot in neonates
Haitham T Idriss, Martha M Werler
Birth Defects Res . 2023 Oct 18

Aims: Talipes equinovarus (clubfoot) is a congenital lower foot deformity that results from a neuromuscular deficiency, but the precise etiology remains elusive. Vitamin D is important for fetal neuromuscular development. In this study, we investigated the association between dietary vitamin D intake during pregnancy and incidence of clubfoot in neonates, since such a question has thus far been overlooked.

Methods: We conducted a secondary analysis of data collected in the United States, between 2007 and 2011 for a case-control study of children born with clubfoot. Participating mothers were interviewed by telephone about dietary and other health and life-style indicators. Exposure to vitamin D was recorded as the average daily intake of dietary vitamin D over a period of 6 months before pregnancy began. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression.

Results: The dataset included 2667 study participants, of which 663 were cases. Logistic regression showed no significant association between dietary vitamin D or log10 (Vitamin D) intake during pregnancy and incidence of clubfoot in neonates (OR = 1.00, CI = 1.00-1.00, OR = 1.51, CI = 0.83-2.82, respectively). No interaction in the regression model was found between vitamin D and other predictor variables. Results were not confounded by supplement intake of vitamin D during pregnancy.

Conclusions: Results show no evidence of an association between dietary vitamin D intake and incidence of clubfoot in neonates. The lack of association is not confounded by consumption of vitamin D supplements during pregnancy.
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