• Loading...
    Contact Us

    Birth Defects Epidemiology & Surveillance
    Mail Code 1964
    P.O. Box 149347
    Austin, TX 78714-9347

    Phone: 512-776-7232
    Fax: 512-776-7330


    Email comments or questions

BIRTH DEFECT RISK FACTOR SERIES: Talipes Equinovarus (Clubfoot)

Loading...

Click here for an Adobe PDF version of this document. (180KB PDF, Viewing Information)

NEW: Please take a moment to evaluate our birth defects risk factor series. Click here to take survey.

Definition        

Talipes equinovarus (TEV) more commonly referred to as clubfoot is a development disorder of the foot and ankle that affects one (unilateral) or both (bilateral) feet   The foot is in an incorrect anatomical position, and is inclined inward, axially rotated outward, and points downward (Miedzybrodzka 2003).  True TEV does not resolve itself, and the affected infant will likely need to undergo treatments including casting, manipulation, and, possibly, surgery in order place the foot in the correct anatomical position (Dietz 2002).  These corrective actions usually allow the infant to walk and run normally.

TEV can occur independently or as an isolated finding (ITEV) or as part of a genetic syndrome and as one problem among other abnormalities.  The effects of ITEV on the infant are limited to the lower limbs; this problem does not involve the other body systems or the mental ability of the affected infant (Miedzybrodzka 2003).  When TEV that occurs as part of a syndrome or with other abnormalities (such as neural tube defects, i.e. spina bifida) treatment may be more challenging and the infant may have other systemic problems that are unrelated to TEV (Cummings 2002). 


ETIOLOGY

While some cases of TEV are part of a recognized syndrome or sequence, many occur without a clear cause; this is known as isolated talipes equinovarus (ITEV). There are several theories about the etiology of ITEV, however the actual mechanism for this disorder is not known (Miedzybrodzka 2003).  TEV may be caused by mechanical forces within the uterus due to low amniotic fluid volume or insufficient expansion of the uterus.  The latter etiology is suggested because of the increased incidence in first-born children, in pregnancies in which there is low amniotic volume and twin pregnancies (Carey 2003, Byron-Scott 2005, Moorthi 2005, Engell 2006).  A second theory is that TEV is caused by an abnormality of the connective tissue of the fetus.  Other possible causes are bone malformations within the foot and ankle, in utero vascular disruption, or an underlying neurological disorder.  This theory is supported when TEV occurs with other neurological defects as part of a syndrome or sequence.  Finally, it has been theorized that TEV represents an arrest of the developmental process; that is, the lower limb does not rotate to its final anatomical position (Miedzybrodzka 2003). 

It is also possible that underlying all of these theories is a genetic cause.  Family history has been significantly associated with increased risk of ITEV (Lochmiller 1998), with the risk of increasing greatly if a first-degree family member (parent, sibling) also has it (Dietz 2002).  ITEV is also more common in specific ethnic/racial groups, including the Maori/Pacific Islanders and Australian Aborigines (Chapmen 2000, Carey 2003).  Within these groups, family lineages have indicated multiple instances of the defect.  Several studies have also suggested that a single as-yet unknown dominant gene or many interacting genes of small effect as the etiology of ITEV (Wynne-Davies 1982, de Andrade 1998, Chapman 2000, Dietz 2002, Miedzybrodzka 2003).

DEMOGRAPHIC AND REPRODUCTIVE FACTORS

The secular trend for ITEV has remained consistent throughout various recording periods (Carey 2005, Moorthi 2005).  The birth prevalence for this defect ranges from 0.39 to 6.8 per 1000 births (dependent on race/ethnicity and/or genetic background); the prevalence for the U.S. population was approximately 0.74 per 1000 births, excluding incidences of TEV that were part of a syndrome or associated with other defects. 

Race/ethnicity was not determined to be a risk factor for ITEV among Hispanics, African Americans, Chinese Americans, or Caucasians in some studies (Moorthi 2005, Lochmiller 1998).  However, it was found to be a risk factor among Australian Aborigines, Hawaiians, Pacific Islanders, and Maoris (Chapman 2000, Lochmiller 1998).

Infant sex is a risk factor for ITEV, with a consistent 2:1 (male:female) ratio found across demographic groups (Byron-Scott 2005, Carey 2005, Moorthi 2005, Lochmiller 1998).  The relationship between parity and TEV is unclear (Moorthi 2005), as is the relationship between ITEV and breech presentation at birth (Lochmiller 1998).  First-born children were also more likely to have TEV than children from subsequent pregnancies (Moorthi 2005). 

There is some evidence that advanced maternal age is a risk factor for ITEV (Hollier 2000).  However, this risk has been described as slightly higher, but not significant (Moorthi 2005, Barker 2002).  Paternal age has not been associated with this defect.

Mothers with a college education were less likely to have a child with ITEV than mothers who only had a high school education (Moorthi 2005).  This is likely due to the fact that college-educated women are more likely to have a higher socio-economic status, more access to healthcare, and better diets

Prevalence of ITEV has been tentatively associated with seasonality.  One study reported that a higher incidence of TEV was reported in July, while the fewest incidences were reported in March (Barker 2002, Lochmiller 1998).  Another study reported that infants born in autumn/winter had a slightly higher risk for TEV (OR 1.35) (Carey 2005), while another found no variation (Loder 2006).   

FACTORS IN LIFESTYLE OR ENVIRONMENT

Maternal smoking has been associated with ITEV (Skelly 2002, Honein 2000).  For those with a family history of TEV and exposure to maternal smoking, the risk is greatly increased (OR 20.30) (Honein 2000).  Additionally, exposure to maternal smoking appears to be dose related (Skelly 2002).  The risk of ITEV increased significantly, with the OR for maternal smoking of 20 or more cigarettes a day (without family history of ITEV) increasing to 4.6 (Skelly 2002). 

Low amniotic fluid volume (oligohydramnios) has been linked inconclusively to ITEV (Carey 2005, Miedzybrodzka 2003).  The hypothesis is that low amniotic fluid volume will lead to decreased uterine space, limiting the movements of and crowding the fetus.  Because of the effect on amniotic fluid volume, amniocentesis has also been tentatively linked to increasing risk for ITEV (Philip 2004); however, one study did not find later amniocentesis (15 to 16 weeks) to be linked to TEV (Miedzybrodzka 2003). 

A single study reported a link between maternal anemia and TEV; this same study indicated a connection between hypermesis gravidarium (very severe vomiting due to pregnancy) (Bryon-Scott 2005), and another found no association with in utero enterovirus infection (Loder 2006).

Maternal obesity and maternal diabetes have not been found to be a risk factor for ITEV (Cedergreen 2004, Becerra 1990).  Folic acid reduces the risk of most birth defects; however, its effect on ITEV is unclear (Green 2002); one study found no decrease in rates after folic acid fortification of the U.S. grain supply (Moorthi 2005). However, both folic acid and multivitamins have been proven effective at reducing the risk of numerous other birth defects.

Living in proximity to landfills or solid waste incinerators, exposure to nitrate or chlorination byproducts in drinking water, exposure to indoor pesticides or biomedical solvents does not increase the risk of ITEV (Harrison 2003, Cordier 2004). (Cedergren 2002 (Berkowitz 2003, Wennborg 2005).

Maternal alcohol consumption is not linked to TEV (Honein 2000).   Maternal consumption of marijuana and methamphetamines do not appear to be risk factors for TEV (Fried 2002, Jeng 2005).  However, it is not recommended that pregnant women consume alcohol or illicit drugs.

The use of chemotherapy does not increase the risk for TEV (Cardonick 2004), nor does the use of fluoxetine (Prozac™) (Chambers 1996).  Anticonvulsant drugs have multiple effects on the developing fetus, however TEV is not one of them (Holmes 2001).  Antihistamine drugs have not been found to increase the risk of TEV (Kallen 2002).  Corticosteroids and calcium channel blockers have not been found to increase the risk for TEV (Park-Wyllie 2000, Sorensen 2001).  Finally, the drug thalidomide has been found to cause serious limb defects.  However, thalidomide has not been found to cause TEV (Stromland 2002).

Prevalence

ITEV affects 7.4 pregnancies per 10,000 live births in Texas (Moorthi 2005).  Other studies have found the birth prevalence to be between 10.0 and  12.5 in other locations (Wynne-Davies 1972, Carey 2005). 

REFERENCES


Barker SL, Macnicol MF.  Seasonal distribution of idiopathic congeninal talipes equinovarus in Scotland.  J Pediatri Orthop Part B 2002;11:2;129-133.

Becerra JE, Khoury MJ, Cordero JF, Erickson JD.  Diabetes mellitus during pregnancy and the risks for specific birth defects: a population case-control study.  Pediatrics 1990; 85:1:1-9.

Berkowitz GS, Obel J, Deych E, Lapinski R, Godbold J, Liu Z, Landrigan PJ, Wolff MS.  Exposure to indoor pesticides during pregnancy in a multiethnic, urban cohort.  Environmental Health Perspectives 2003;111:1:79-84.

Byron-Scott R, Sharpe P, Hasler C, Cundy P, Hirte C, Chan A, Scott H, Baghurst P, Haan E.  A South Australian population-based study of congenital talipes equinovarus.  Paediatric and Perinatal Epidemiology 2005;19:227-237.

Cardonick E, Iacobucci A.  Use of chemotherapy during human pregnancy.  Lancet Oncology 2004;5:283-291.

Carey M, Bower C, Mylvaganam A, Rouse I.  Talipes equinovarus in Western Australia.  Paediatric and Perinatal Epidemiology 2003;17:187-194.

Carey M, Mylvaganam A, Rouse I, Bower C.  Risk factors for isolated talipes equinovarus in Western Australia, 1980-1994.  Paediatric and Perinatal Epidemiology 2005;19:238-245.

Cedergren MI.  Maternal morbid obesity and the risk of adverse pregnancy outcome.  Obstetrics and Gynecology 2004;103:2;219-224.

Cedergren MI, Selbing AJ, Lofman O, Kallen BAJ.  Chlorination byproducts and nitrate in drinking water and risk for congenital cardiac defects.  Environmental Research Section A 2002;89:124-130.

Chambers CD, Johnson KA, Dick LM, Felix RJ, Jones KL.  Birth outcomes in pregnant women taking fluoxetine.  New England Journal of Medicine 1996;335:14:1010-1015.

Chapman C, Stott NS, Port RV, Nicol RO.  Genetics of club foot in Maori and Pacific people.  J. Med.Genet. 2000:37:680-683.

Cordier S, Chevrier C, Robert-Gnansia E, Lorente C, Brula P, Hours M.  Risk of congenital anomalies in the vicinity of municipal solid waste incinerators.  Occup Environ Med 2004;61:8-15.

Cummings RJ, Davidson RS, Armstrong PF, Lehman WB.  Congenital clubfoot.  AAOS Instructional Course Lectures 2002;51:385-400.

de Andrade M, Barnholtz JS, Amos CI, Lochmiller C, Scott A, Risman M, Hecht JT. Segregation analysis of idiopathic talipes equinovarus in a Texan population. Am J Med Genet. 1998 Sep 1;79(2):97-102.

Dietz F.  The genetics of idiopathic clubfoot.  Clinical Orthopaedics and Related Research 2002:401:39-48.

Engell V, Damborg F, Andersen M, Kyvik KO, Thomsen K.J Club foot: a twin study. Bone Joint Surg Br. 2006 Mar;88(3):374-6.

Fried PA.  The consequences of marijuana use during pregnancy: a review of the human literature, in Women and Cannabis: Medicine, Science, and Sociology, Haworth Integrative Healing Press, 2002.

Green N.  Folic acid supplementation and prevention of birth defects.  J. Nutr. 2002;132:2356s-2360s.

Harrison RM.  Hazardous waste landfill sites and congenital anomalies.  Occup Environ Med 2003;2003:60:79-80.

Hollier LM, Leveno KJ, Kelly MA, McIntire DD, Cunningham FG.  Maternal age and malformations in singleton births.  Obster gynecol 2000;96:701-706.

Holmes LB, Harvey EA, Coull BA, Huntington KB, Khoshbin S, Hayes AM, Ryan LM.  The teratogenicity of anticonvulsant drugs.  The New England Journal of Medicine 2001:344:1132-1138.

Honein MA, Paulozzi LJ, Moore CA.  Family history, maternal smoking, and clubfoot: an indication of a gene-environment interaction.  American Journal of Epidemiology 2000;152:658-665.

Jeng W, Wong AM, Ting-A-Kee R, Wells PG.  Methamphetamine-enhanced embryonic oxidative DNA damage and neurodevelopmental deficits.  Free Radical Biology and Medicine 2005;29:317-326.

Kallen B.  Use of antihistamine drugs in early pregnancy and delivery outcome.  Journal of Maternal-Fetal and Neonatal Medicine 2002:11:146-152.

Karakurt L, Yilmaz E, Serin E, Bektas B, Cikim G, Gursu.  Plasma total homocysteine level in mothers of children with clubfoot.  Journal of Pediatric Orthopaedics 2003;23:658-660.

Lochmiller CL, Johnson D, Scott A, Risman M, Hecht JT.  Genetic epidemiology study of idiopathic talipes equinovarus.  American Journal of Medical Genetics 1998;79:90-96.

Loder RT, Drvaric DM, Carney B, Hamby Z, Barker S, Chesney D, Maffulli N. Lack of seasonal variation in idiopathic talipes equinovarus. J Bone Joint Surg Am. 2006 Mar;88(3):496-502.

Miedzybrodzka Z.  Congenital talipes equinovarus (clubfoot): a disorder of the foot but not the hand.  J. Anat. 2003;202:37-42.

Moorthi RN, Hashmi SS, Langois P, Canfield M, Waller DK, Hecht JT.  Idiopathic talepes equinovarus (ITEV) (clubfeet) in Texas.  American Journal of Medical Genetics 2005:132A:376-380.

Park-Wyllie L, Mazzotta P, Pastuszak A, Moretti ME, Beique L, Hunnisett L, Friesen MH, Jacobson S, Kasapinovic S, Chang D, Diav-Citrin O, Chitayat D, Nulman I, Einarson TR.  Birthdefects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies.  Teratology 2000;62:385-392.

Philip J, Silver RK, Wilson RD, Thom EA, Zachary JM, Mohide P, Mahoney MJ, Simpson JL, Platt LD, Pergament E, Hershey D, Filkins K, Johnson A, Shulman LP, Bang J, MacGregor S, Smith JR, Shaw D, Wapner RJ, Jackson LG; NICHD EATA TrialGroup. Late first-trimester invasive prenatal diagnosis: results of an internationalrandomized trial. Obstet Gynecol. 2004 Jun;103(6):1164-73.

Skelly AC, Holt VL, Mosca VS, Alderman BW.  Talipes eqinovarus and maternal smoking: a population-based case-control study in Washington state.  Teratology 2002;66:91-100.

Sorensen HT, Czeizel AE, Rockenbauer M, Steffensen FH, Olsen J.  The risk of limb deficiencies and other congenital abnormalities in children exposed in utero to calcium channel blockers.  Acta Abstet Gynecol Scand 2001;80:397-401.      

Stromland K, Philipson E, Gronlund MA.  Offspring of male and female parents with thalidomide embryopathy: birth defects and functional anomalies.  Teratology 2002;66:115-121.      

Vrijheid M, Dolk M, Stone D, Abramsky L, Alberman E, Scott JES.  Socioeconomic inequalities in risk of congenital anomaly.  Arch. Dis. Child. 2000:82:349-352.

Wennborg H, Magnusson LL, Bonde JP, Olsen J.  Congenital malformations related to maternal exposure to specific agents in biomedical research laboratories.  J Occup Environ Med. 2005;47:11-19.     

Wynne-Davies R. Genetic and environmental factors in the etiology of talipes equinovarus. Clin Orthop Relat Res. 1972 May;84:9-13.

Wynne-Davies R, Littlejohn A, Gormley J. Aetiology and interrelationship of some common skeletal deformities. (Talipes equinovarus and calcaneovalgus, metatarsus varus, congenital dislocation of the hip, and infantile idiopathic scoliosis). J Med Genet. 1982 Oct;19(5):321-8.

Please Note: The primary purpose of this report is to provide background necessary for conducting cluster investigations.  It summarizes literature about risk factors associated with this defect.  The strengths and limitations of each reference were not critically examined prior to inclusion in this report.  Consumers and professionals using this information are advised to consult the references given for more in-depth information. This report is for information purposes only and is not intended to diagnose, cure, mitigate, treat, or prevent disease or other conditions and is not intended to provide a determination or assessment of the state of health.  Individuals affected by this condition should consult their physician and when appropriate, seek genetic counseling.

 

DSHS Pub. No. Document E58-10957

Please Note: The primary purpose of this report is to provide background necessary for conducting cluster investigations. It summarizes literature about risk factors associated with this defect. The strengths and limitations of each reference were not critically examined prior to inclusion in this report. Consumers and professionals using this information are advised to consult the references given for more in-depth information. 

This report is for information purposes only and is not intended to diagnose, cure, mitigate, treat, or prevent disease or other conditions and is not intended to provide a determination or assessment of the state of health. Individuals affected by this condition should consult their physician and when appropriate, seek genetic counseling.

For more information:

Birth Defects Epidemiology and Surveillance
Texas Department of State Health Services
1100 W. 49th Street, Austin, Texas 78756
512-776-7232 Fax 512-776-7330

Return to Birth Defects Risk Factor Page

Last updated February 10, 2012