Descriptive Epidemiology of Clubfoot in Peru: A Clinic-Based Study

Abstract

congenital clubfoot is the most common birth defect of the musculoskeletal system and affects 1 in every 1000 live births each year.¹ Although there have been numerous studies of investigation, the etiology and pathogenesis of clubfoot remains unknown. To date, no epidemiological studies have been conducted in Peru to assess possible genetic and environmental risk factors associated with this deformity. The purpose of this study was to evaluate specific environmental and socioeconomic factors that may increase the risk of clubfoot.

A descriptive clinic-based study was conducted using structured questionnaires given to biological mothers of clinically confirmed clubfoot patients (n=72) and biological mothers of children between ages 0-18 with no first or second degree family history of clubfoot as controls (n=103). Phenotypic data from clubfoot subjects were also collected. We found that males were twice as likely to have clubfoot as females, and half of all clubfoot patients had bilateral clubfoot. There was no significant difference in the rate of left vs. right clubfoot.

Infant birth in the winter months correlated with an increased risk of clubfoot (p=0.01476). Maternal characteristics found to be significantly associated with increased risk of clubfoot were young maternal age at conception (p=0.04369) and low maternal education (p=0.003245). Young paternal age also had a correlation with increased risk of clubfoot in the child (p=0.0371). Both paternal smoking (p=0.00001) and the presence of any household smoking (p=0.00003) were strongly associated with an increased risk of clubfoot.

Introduction

Congenital talipes equinovarus, more commonly known as clubfoot, is a leading cause of disability world- wide¹. This birth defect is characterized by equinus of the ankle, varus of the hindfoot, as well as cavus and adductus of the forefoot with an associated atrophy of the calf muscles¹. The most common presentation of clubfoot is idiopathic; however, it may also be associated with other medical syndromes such as myelomeningocele or arthrogryposis². The incidence of clubfoot is approximately 1 in 1000 live births per year, with the global burden of this birth defect affecting more than 150,000 infants each year^3-9. Over 80% of cases occur in developing nations, where clubfoot is a major disease burden in low-resource areas^10,11. Despite many previous research studies and investigations, the etiology and pathogenesis of clubfoot has not been fully elucidated.

Previous studies have proposed several risk factors that are associated with clubfoot, including male gender, maternal smoking, maternal age, maternal marital status, parity, maternal education, and maternal diabetes^12-18. Currently, no epidemiological studies have been produced examining the risk factors associated with clubfoot in Peru. This study was designed to describe specific risk factors that may be associated with an increased risk of idiopathic clubfoot in Peru. Determining these risk factors will assist further understanding of the etiology of this deformity as well as providing information for further educational programming for parents.

Materials and Methods

The University of Iowa Institutional Review Board approved this study before implementation. A Spanish-speaking medical student recruited subjects and administered questionnaires over a period of ten weeks. The purpose of the study was explained in detail, and parents of case and control patients were provided a consent letter to read and sign prior to the interview. This study utilized a structured questionnaire to describe specific risk factors that could be associated with clubfoot.

The cohort for this case-control study included patients from two major children’s hospitals located in the capital city of Lima. Questionnaires were given to the biological mothers of children between the ages of 0-18 from live, singleton births. The population of cases included patients with a physician-confirmed diagnosis of idiopathic clubfoot who received treatment in pediatric orthopedic outpatient clinics. The population of controls included patients receiving treatment in the pediatric orthopedic outpatient clinics who did not have a diagnosis of idiopathic clubfoot. Additionally, the controls did not have a first- or second-degree family history of clubfoot or any other congenital abnormalities.

The anonymous questionnaire described data about the child, biological mother, and biological father. Information collected about the patient included gender, gestational age, birth weight, birth month, exposure to smoking, and location of birth. Information collected about the maternal pregnancy included age at conception, mode of delivery, presence of breech presentation, smoking history, education, marital status, and diabetes. Information collected about the biological father included age at the time of conception and smoking history. The data were recorded in Spanish, translated into English, and analyzed with EpiInfo version 7 using a student’s t-test. A p-value of < 0.05 indicated a statistically significant association.

Results

At the completion of the study, 72 cases of clubfoot and 103 control patients were enrolled in the study to respond to risk factor questionnaires.

Phenotypic characteristics of the clubfoot cases are located in Table 1. Of all clubfoot cases, 61% were male and 39% were female. Forty-two percent of the cases presented with bilateral clubfoot, while 53% of the cases presented with unilateral clubfoot. Of the 38 cases with unilateral clubfoot, 53% had an affected left foot and 47% had an affected right foot. Of the 72 families, 11% of the cases reported a known family history of clubfoot.

Table 1.

Descriptive Statistics of Cases

Phenotypic Characteristics	Cases (n=72)
Gender
Male	44 (61%)
Female	28 (39%)
Laterality
Bilateral	34 (47%)
Unilateral	38 (53%)
Left	20 (53%)
Right	18 (47%)
Known Family History
Yes	8 (11%)
No	64 (89%)

Descriptive statistics of possible risk factors associated with clubfoot are shown in Table 2. There was no significant association between gestational age or birth weight of the infant and clubfoot. Twenty-two percent of clubfoot cases were born before full term (<37 weeks gestation) compared to 20% of controls. Fourteen percent of clubfoot cases were born with birth weights less than 2500 grams compared to 11% of controls. We did find a significant association between season of birth and clubfoot; 63% of clubfoot patients were born in the winter months of March to August while 45% of control patients were born in winter months, corresponding to a p value of 0.01476. We did not find a significant association between clubfoot and method of birth, including breech presentation or Cesarean delivery. Four percent of clubfoot cases were born in breech presentation compared to 2% of controls. Thirty-five percent of clubfoot cases were delivered by Cesarean compared to 34% of controls.

Table 2.

Descriptive Statistics of Clubfoot Cases and Controls

Demographic Characteristics	Cases (n=72)	Controls (n=103)
Gestational Age
<37 weeks	16 (22%)	21 (20%)
37+ weeks	56 (78%)	82 (80%)
Birth Weight (grams)
=2500	10 (14%)	11 (11%)
≤ 2500	58 (81%)	91 (88%)
Missing	4 (6%)	1 (1%)
Birth Month p-0.01476
Mar-Aug	45 (63%)	46 (45%)
Sept-Feb	27 (38%)	57 (55%)
Breech Presentation
Yes	3 (4%)	2 (2%)
No	40 (61%)	65 (65%)
Missing	24 (34%)	33 (34%)
Cesarean
Yes	25 (35%)	36 (34%)
No	47 (65%)	67 (65%)
Maternal Age at Conception p-0.04369
<23	23 (32%)	20 (19%)
24-34	40 (56%)	63 (64%)
35+	9 (13%)	20 (17%)
Maternal smoking during
pregnancy	2 (3%)	3 (3%)
Yes	62 (97%)	100 (97%)
No
Maternal diabetes	0	0
Yes	64 (100%)	103 (100%)
No
Maternal Education p-0.003245	23 (32%)	14 (14%)
= High School	49 (68%)	89 (86%)
≤ High School
Maternal Marital Status	21 (29%)	35 (34%)
Married	51 (71%)	68 (66%)
Single
Paternal age at conception p-0.0371	14 (29%)	9 (9%)
<23	41 (57%)	47 (46%)
24-34	15 (21%)	47 (46%)
35+	1 (1%)	0
Missing
Paternal smoking p-0.003359	22 (31%)	13 (13%)
Yes	50 (69%)	90 (87%)
No
Any Household smoking p-0.00001192	34 (47%)	17 (17%)
Yes	38 (53%)	86 (83%)
No

Of the social and demographic maternal characteristics measured by the study, maternal age at conception and level of maternal education were statistically associated with clubfoot. While 32% of mothers of clubfoot patients were under the age of 23 at conception, 19% of control mothers were of young maternal age, corresponding to a p value of 0.04369. Thirty-two percent of mothers of clubfoot cases did not complete high school compared to 14% of control mothers, corresponding with a p value of 0.003245. Three percent of mothers of clubfoot cases smoked during the pregnancy compared to 3% of the control mothers. None of the mothers in either the clubfoot cases or the controls reported presence of maternal diabetes. Twenty-nine percent of mothers of clubfoot cases were married compared to 34% of control mothers.

Of the social and demographic paternal characteristics measured by the study, both paternal age at conception and paternal smoking were statistically associated with clubfoot. While 29% percent of fathers of clubfoot patients were under the age of 23 at conception, 9% of fathers of control patients were of young paternal age, corresponding to a p value of 0.0371. Thirty-one percent of fathers of clubfoot patients reported smoking during pregnancy compared to 13% of fathers of controls, corresponding with a p value of 0.003359.

Other characteristics of the child’s family found to be statistically significantly associated with clubfoot were presence of any smoking in the household and location of residence. Forty-seven percent of parents of clubfoot patients reported presence of any smoking in the household during the child’s pregnancy compared to 17% of control parents corresponding with a p value of 0.00001192. Forty-two percent of clubfoot patients resided in Lima and the surrounding area compared to 73% of control patients, corresponding with a p value of 0.000033.

Discussion

The results of this study support previously reported data in the literature indicating that males are twice as likely as females to be affected by clubfoot (61% of males and 39% of females, n=72), indicating that there is a genetic influence for male sex as a strong risk factor for clubfoot^12,13. Also, in concordance with the literature, approximately 50% of children were affected with bilateral clubfoot. In our study, there was no significant difference between cases of left or right unilateral clubfoot (53% left and 47% right, n=38), although previous studies have found an increased prevalence of right-sided clubfoot^19-21.

We did not find significant associations between clubfoot and low birth weight (<2500 g) or pre-term birth (< 37 weeks), both of which have been shown to have associations with clubfoot in previous studies^22-24. Our study did not find an association between breech presentation and clubfoot, which has been shown in previous studies¹⁴. Both the cases and controls had a high non-response rate to the question regarding breech presentation, possibly related to the high prevalence of birth by Cesarian section in both the case and control groups.

Our findings did show an association between seasonal variation and clubfoot^23-25. Previous studies have reported an increased prevalence of infants with clubfoot born in the winter season. In the southern hemisphere, the winter season lasts from March until August, and our data shows an increased prevalence of clubfoot during this time. Other studies have not found this seasonal variation²⁶.

The literature also reports several sociodemographic characteristics associated with increased risk of clubfoot that vary among populations, specifically maternal smok- ing^12-18. In Peru, female smoking habits have declined from 17.8% in 1999 to a 9% prevalence in 2009²⁷. Only 3% of case and 3% control mothers indicated smoking habits; however, there was a significant association between clubfoot and paternal smoking (31% cases, n=72 and 13% controls, n=103) as well as any household smoking present (47% cases, n=72 and 17% controls, n=103). Thus, these data support previous indications that second-hand smoke is a risk factor for clubfoot²⁸.

In our study, young maternal age (< 23 years old) was found to have a significant association with increased risk of clubfoot (32% case mothers, n=72 and 19% control mothers, n=103) in concordance with many other epidemiologic surveys^14,26. Similarly, we also found that young paternal age (< 23 years old) was significantly associated with increased risk of clubfoot (29% of case fathers, n=71 and 9% of control fathers, n=103). Mothers with an education level less than high school was also found to be a risk factor with a significant association with increased clubfoot prevalence, supporting previous data^12,14,15. Maternal diabetes and maternal marital status were not found to have significant association with clubfoot in our study population.

The project described was supported by Grant Number T37MD001453 from the National Institute On Minority Health And Health Disparities. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute On Minority Health And Health Disparities or the National Institutes of Health.

Conclusions

This study supports previously reported data stating that males are twice as likely to be affected by clubfoot and approximately 50% of clubfoot patients are affected bilaterally. In our study, there was no significant difference between left and right clubfoot in patients that are unilaterally affected. Many of these findings are universally reported by numerous studies, suggesting a strong genetic association with clubfoot. Our findings also confirm previous studies reporting associations with young maternal age, maternal education, young paternal age, paternal smoking habits, and household smoking habits. The absence of the association between maternal smoking and clubfoot in our study contradicts numerous studies that have shown a strong association. Differences in culture may have led to this disagreement. These preliminary findings provide the foundation for future epidemiologic studies in the Peruvian population as well as studies in the general South-American population in the future.