- Email: [email protected]
Isolated clubfoot diagnosed prenatally: is karyotyping indicated?
Isolated Clubfoot Diagnosed Prenatally: Is Karyotyping Indicated? FERGAL D. MALONE, MD, TERESA MARINO, MD, DIANA W. BIANCHI, MD, KIM JOHNSTON, RN, AND MARY E. D’ALTON, MD Objective: To evaluate the appropriateness of fetal karyotyping after prenatal sonographic diagnosis of isolated unilateral or bilateral clubfoot. Methods: We retrospectively reviewed a database of fetal abnormalities diagnosed by ultrasound at a single tertiary referral center from July 1994 to March 1999 for cases of unilateral or bilateral clubfoot. Fetuses who had additional anomalies diagnosed prenatally, after targeted sonographic fetal anatomy surveys, were excluded. Outcome results included fetal karyotype diagnosed by amniocentesis, or newborn physical examination by a pediatrician. Results: During the 5-year period, 5731 fetal abnormalities were diagnosed from more than 27,000 targeted prenatal ultrasound examinations. There were 51 cases of isolated clubfoot. The mean maternal age at diagnosis was 30.5 years. The mean gestational age at diagnosis was 21.6 weeks. Twenty-three of the women (45%) were at increased risk of fetal aneuploidy, on the basis of advanced maternal age or abnormal maternal serum screening. Six women (12%) had positive family histories of clubfoot; however, no cases of aneuploidy were found by fetal karyotype evaluation or newborn physical examination. All cases of clubfoot diagnosed prenatally were confirmed at newborn physical examination, and no additional malformations were detected. Conclusion: After prenatal diagnosis of isolated unilateral or bilateral clubfoot, there appeared to be no indication to offer karyotyping, provided that a detailed sonographic fetal anatomy survey was normal and there were no additional indications for invasive prenatal diagnoses. (Obstet Gynecol 2000;95:437– 40. © 2000 by The American College of Obstetricians and Gynecologists.)
of the talo-calcaneo-navicular joint, with underdevelopment of the soft tissues on the medial side of the foot, and frequently of the calf and peroneal muscles.1 Clubfoot is one of the most common congenital defects, with an incidence of one per 1000 live births and a 2:1 male to female predisposition.2 Clubfoot might be associated with other structural anomalies in up to 10% of cases2 and is a feature of many genetic syndromes.3 Clubfoot can be diagnosed prenatally by ultrasonography.4,5 Whenever clubfoot has been diagnosed prenatally, a targeted fetal anatomic survey should be done for associated structural malformations.2 Isolated clubfoot is mostly idiopathic, but it can occur secondary to extrinsic mechanisms such as oligohydramnios or amniotic band syndrome. Inheritance of clubfoot is multifactorial. There is controversy about whether to offer fetal karyotyping when isolated clubfoot is diagnosed by prenatal sonography. There is little information to guide physicians on counseling women whose fetuses have been diagnosed prenatally with clubfoot without any additional sonographically identifiable abnormalities. It has been suggested that amniocentesis be offered in all cases of isolated clubfoot.5 The objective of this study was to evaluate the frequency of fetal karyotypic abnormalities after diagnosis of isolated unilateral or bilateral clubfoot.
Materials and Methods Clubfoot, or talipes equinovarus, is a positional deformity of the fetal foot resulting in the foot being fixed in adduction, supination, and varus. There is subluxation From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, Columbia-Presbyterian Medical Center, New York, New York; and the Division of Maternal-Fetal Medicine, Tufts University School of Medicine, New England Medical Center, Boston, Massachusetts.
VOL. 95, NO. 3, MARCH 2000
The Center for Prenatal Diagnosis at the New England Medical Center, Boston, MA, is a tertiary referral facility that offers screening and targeted fetal ultrasonography and invasive fetal diagnosis and therapy. Since July 1994, all abnormalities diagnosed prenatally at this center have been recorded and tracked using a Microsoft Access (Microsoft Corporation; Seattle, WA) anomalies database. A research nurse links the results of fetal karyotype evaluations to each fetal abnormality.
0029-7844/00/$20.00 PII S0029-7844(99)00582-7
437
Pregnancy and pediatric outcome information from each woman’s obstetric and pediatric care providers and a formal review of each infant’s medical record are collected and recorded by the research nurse. A detailed physical examination by a pediatrician or neonatologist after delivery is recorded and tracked in the anomalies database for each infant. The database of all fetal abnormalities diagnosed by ultrasound was reviewed from July 1994 to March 1999 for diagnoses of isolated unilateral or bilateral clubfoot. Exclusion criteria included multiple gestations and fetuses with additional structural anomalies diagnosed prenatally, or markers for aneuploidy noted at targeted ultrasound evaluations. Our policy during the study was not to offer amniocentesis solely on the indication of isolated clubfoot. However, amniocentesis was offered for standard indications, such as advanced maternal age (35 years or older at expected date of delivery) and abnormal maternal serum screen results. All results were tracked by the genetic counselors and research nurse and matched with the anomalies in the database. Outcome data included fetal karyotype evaluations, when done, and any physical examination findings by pediatricians after birth that suggested aneuploidy. All information was entered into a Microsoft Excel 2000 spreadsheet (Microsoft Corp., Seattle, WA), which was used to provide descriptive statistics. Our Institutional review board approved this study.
Results A total of 5731 fetuses with abnormalities were diagnosed at this center among more than 27,000 targeted prenatal fetal ultrasound examinations done between July 1994 and March 1999. From that database of anomalies, 51 fetuses were diagnosed prenatally with isolated clubfoot. Twenty-three of 51 pregnant women (45%) were at increased risk of fetal aneuploidy because of advanced maternal age or abnormal serum screening results. Six of those 23 (12%) had positive family histories of clubfoot. Indications for ultrasound examination included routine fetal anatomy survey in 23 cases (45%), advanced maternal age in 17 (33%), abnormal serum screening results in six (12%), and family history of clubfoot in five (10%). The mean maternal age at diagnosis was 30.5 years, and the mean gestational age at diagnosis of clubfoot was 21.6 weeks (standard deviation [SD] 6.2), range 15–39 weeks. In all cases, clubfoot was diagnosed by initial sonographic examination at our center.
438 Malone et al
Isolated Clubfoot
Figure 1. Prenatal ultrasound of fetal clubfoot demonstrating plantar surface of foot and lower leg in same plane.
There was an increased incidence of clubfoot in male fetuses, with a male-to-female ratio of 1.7:1. There were 19 cases (37%) of bilateral clubfoot and 32 cases (63%) of unilateral clubfoot. Of the cases of unilateral clubfoot, 19 (59%) affected the left limb and 13 (41%) affected the right limb. Karyotype results by amniocentesis were available in 23 cases (45%). In all 51 cases, results of detailed physical examinations of infants were collected from pediatricians or neonatologists. There were no cases of fetal aneuploidy on fetal karyotype evaluation or newborn physical examination, which searched specifically for newborn dysmorphic features. All cases of clubfoot diagnosed prenatally were confirmed at newborn physical examination, and no additional structural malformations were detected.
Discussion Clubfoot can be diagnosed prenatally with fetal ultrasonography.4,5 Ultrasound visualization of the plantar surface of the fetal foot, in the same plane as the bones of the lower leg, seen on multiple images, confirms the diagnosis (Figure 1). The diagnosis of clubfoot is often an isolated finding, but it can be associated with other structural abnormalities such as cleft lip and palate, congenital heart disease, or congenital hip dislocation. Clubfoot can be a component of many genetic syndromes and rarer chromosomal abnormalities such as trisomies 13 and 18.3 Other causes of positional fetal deformities, including oligohydramnios, multiple gestation, uterine tumors, and amniotic bands, also have been associated with clubfoot. Such positional deformities (extrinsic cause of clubfoot) are due to intrauterine confinement rather than true structural malformation (intrinsic cause of clubfoot). The fact that most cases of
Obstetrics & Gynecology
clubfoot in our series were unilateral might imply that positional deformity, rather than true structural malformation, is a more common cause of prenatally diagnosed clubfoot. When syndromic diagnoses are excluded, the most common mode of inheritance of clubfoot is believed to be multifactorial. Wynne-Davis6 reported a recurrence risk for siblings with normal parents that varied according to sex of the affected sibling, such that the sibling of an affected male had a 2% risk of recurrence and a female had a 5% risk of recurrence. There is controversy about whether to offer invasive prenatal diagnosis of fetal karyotype after detecting an isolated clubfoot. Clubfoot has been linked to fetal aneuploidy, but in almost all cases, the finding is not isolated. For example, in one study of 35 cases of prenatally diagnosed clubfoot, there were five cases of chromosomal abnormality, four of which were trisomy 18.7 All five of those fetuses had severe structural malformations that were detected easily on ultrasonography, and none of the seven with isolated clubfoot had chromosomal abnormalities.7 In a report by Shipp and Benacerraf in 1998,5 68 fetuses were diagnosed prenatally with isolated clubfoot. Thirty-four women had invasive fetal karyotyping, and four cases of aneuploidy were found, leading the authors to recommend invasive karyotype evaluation in all cases of isolated clubfoot. However, two of those four cases of aneuploidy were sex chromosome abnormalities (47,XXY and 47,XXX), which should be considered a coincidental finding, because clubfoot has not been reported as part of the phenotype of those syndromes. There was one case of trisomy 21, but clubfoot is not part of the typical phenotype of Down syndrome. The fourth aneuploidy was trisomy 18, but the fetus also had a two-vessel cord and clenched fists. Both those findings are easily detectable with prenatal ultrasonography, and if noted, would be a reasonable indication for invasive assessment of fetal karyotype. In our study of 51 cases of isolated clubfoot, there were no cases of aneuploidy on fetal karyotype or newborn physical examination. In a smaller study, Woodrow et al8 made a similar conclusion after finding no cases of abnormal fetal karyotypes in a series of 17 fetuses with isolated clubfoot. We believe that our interpretation of the earlier report by Shipp and Benacerraf,5 with the results of other studies,7,8 and our current study, suggest that invasive testing for fetal karyotype might not be warranted with isolated fetal clubfoot. However, these results also emphasize that after seeing fetal clubfoot, careful targeted sonographic survey of the remainder of the fetal anatomy is essential to rule out any additional abnormalities. If any abnormalities are detected, or if women have standard indi-
VOL. 95, NO. 3, MARCH 2000
cations for fetal karyotype analysis such as advanced maternal age, invasive testing should be offered. Also, we recommend that all infants with isolated clubfoot be examined carefully in the newborn period and be followed up to ensure that the diagnosis is correct because of its association with other genetic syndromes.3 Careful antenatal counseling has been recommended after prenatal diagnosis of clubfoot to ensure that women are informed adequately of the possibility of such associations.9 A limitation of this and all previous studies5,7,8 is that we cannot be certain that all infants who did not have karyotype evaluations were truly chromosomally normal. However, all infants were examined in the newborn period by an attending neonatologist or pediatrician, looking specifically for dysmorphic features, so we believe it highly unlikely that any cases of autosomal trisomy were missed. Another limitation of the studies is the small sample; therefore, the possible margins for error are relatively large. It is doubtful that any single center will ever accumulate a large enough series of fetuses with prenatally diagnosed isolated clubfoot to confirm a high degree of likelihood that an association with aneuploidy exists. We believe it is safe to conclude that the literature has never confirmed an association between isolated clubfoot and aneuploidy that would justify the risks associated with invasive prenatal testing.
References 1. Drvaric DM, Kuivila TE, Roberts JM. Congenital clubfoot. Etiology, pathoanatomy, pathogenesis, and the changing spectrum of early management. Orthop Clin North Am 1989;20:641–7. 2. Yamamoto H. A clinical, genetic and epidemiologic study of congenital clubfoot. Jpn J Hum Genet 1979;24:37– 44. 3. Jones KL, Smith DW, Fletcher J. Smith’s recognizable patterns of human malformations. 5th ed. Philadelphia: WB Saunders: 1996. 4. Benacerraf BR, Frigoletto FD. Prenatal ultrasound diagnosis of clubfoot. Radiology 1985;155:211–3. 5. Shipp TD, Benacerraf BR. The significance of prenatally identified isolated clubfoot: Is amniocentesis indicated? Am J Obstet Gynecol 1998;178:600 –2. 6. Wynne-Davis R. Genetic and environmental factors in the etiology of talipes equinovarus. Clin Orthop 1972;84:9 –13. 7. Rijhsinghani A, Yankowitz J, Kanis AB, Mueller GM, Yankowitz DK, Williamson RA. Antenatal sonographic diagnosis of clubfoot with particular attention to the implications and outcomes of isolated clubfoot. Ultrasound Obstet Gynecol 1998;12:103– 6. 8. Woodrow N, Tran T, Umstad M, Graham HK, Robinson H, de Crespigny L. Mid–trimester ultrasound diagnosis of isolated talipes equinovarus: Accuracy and outcome for infants. Aust N Z J Obstet Gynaecol 1998;38:301–5. 9. Burgan HE, Furness ME, Foster BK. Prenatal ultrasound diagnosis of clubfoot. J Pediatr Orthop 1999;1:11–3.
Malone et al
Isolated Clubfoot 439
Address reprint requests to:
Fergal D. Malone, MD Division of Maternal-Fetal Medicine Department of Obstetrics and Gynecology Columbia-Presbyterian Medical Center 630 West 168th Street, PH 16 New York, NY 10032 E-mail: [email protected]
440 Malone et al
Isolated Clubfoot
Received July 1, 1999. Received in revised form September 3, 1999. Accepted September 15, 1999.
Copyright © 2000 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
Obstetrics & Gynecology
of the talo-calcaneo-navicular joint, with underdevelopment of the soft tissues on the medial side of the foot, and frequently of the calf and peroneal muscles.1 Clubfoot is one of the most common congenital defects, with an incidence of one per 1000 live births and a 2:1 male to female predisposition.2 Clubfoot might be associated with other structural anomalies in up to 10% of cases2 and is a feature of many genetic syndromes.3 Clubfoot can be diagnosed prenatally by ultrasonography.4,5 Whenever clubfoot has been diagnosed prenatally, a targeted fetal anatomic survey should be done for associated structural malformations.2 Isolated clubfoot is mostly idiopathic, but it can occur secondary to extrinsic mechanisms such as oligohydramnios or amniotic band syndrome. Inheritance of clubfoot is multifactorial. There is controversy about whether to offer fetal karyotyping when isolated clubfoot is diagnosed by prenatal sonography. There is little information to guide physicians on counseling women whose fetuses have been diagnosed prenatally with clubfoot without any additional sonographically identifiable abnormalities. It has been suggested that amniocentesis be offered in all cases of isolated clubfoot.5 The objective of this study was to evaluate the frequency of fetal karyotypic abnormalities after diagnosis of isolated unilateral or bilateral clubfoot.
Materials and Methods Clubfoot, or talipes equinovarus, is a positional deformity of the fetal foot resulting in the foot being fixed in adduction, supination, and varus. There is subluxation From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, Columbia-Presbyterian Medical Center, New York, New York; and the Division of Maternal-Fetal Medicine, Tufts University School of Medicine, New England Medical Center, Boston, Massachusetts.
VOL. 95, NO. 3, MARCH 2000
The Center for Prenatal Diagnosis at the New England Medical Center, Boston, MA, is a tertiary referral facility that offers screening and targeted fetal ultrasonography and invasive fetal diagnosis and therapy. Since July 1994, all abnormalities diagnosed prenatally at this center have been recorded and tracked using a Microsoft Access (Microsoft Corporation; Seattle, WA) anomalies database. A research nurse links the results of fetal karyotype evaluations to each fetal abnormality.
0029-7844/00/$20.00 PII S0029-7844(99)00582-7
437
Pregnancy and pediatric outcome information from each woman’s obstetric and pediatric care providers and a formal review of each infant’s medical record are collected and recorded by the research nurse. A detailed physical examination by a pediatrician or neonatologist after delivery is recorded and tracked in the anomalies database for each infant. The database of all fetal abnormalities diagnosed by ultrasound was reviewed from July 1994 to March 1999 for diagnoses of isolated unilateral or bilateral clubfoot. Exclusion criteria included multiple gestations and fetuses with additional structural anomalies diagnosed prenatally, or markers for aneuploidy noted at targeted ultrasound evaluations. Our policy during the study was not to offer amniocentesis solely on the indication of isolated clubfoot. However, amniocentesis was offered for standard indications, such as advanced maternal age (35 years or older at expected date of delivery) and abnormal maternal serum screen results. All results were tracked by the genetic counselors and research nurse and matched with the anomalies in the database. Outcome data included fetal karyotype evaluations, when done, and any physical examination findings by pediatricians after birth that suggested aneuploidy. All information was entered into a Microsoft Excel 2000 spreadsheet (Microsoft Corp., Seattle, WA), which was used to provide descriptive statistics. Our Institutional review board approved this study.
Results A total of 5731 fetuses with abnormalities were diagnosed at this center among more than 27,000 targeted prenatal fetal ultrasound examinations done between July 1994 and March 1999. From that database of anomalies, 51 fetuses were diagnosed prenatally with isolated clubfoot. Twenty-three of 51 pregnant women (45%) were at increased risk of fetal aneuploidy because of advanced maternal age or abnormal serum screening results. Six of those 23 (12%) had positive family histories of clubfoot. Indications for ultrasound examination included routine fetal anatomy survey in 23 cases (45%), advanced maternal age in 17 (33%), abnormal serum screening results in six (12%), and family history of clubfoot in five (10%). The mean maternal age at diagnosis was 30.5 years, and the mean gestational age at diagnosis of clubfoot was 21.6 weeks (standard deviation [SD] 6.2), range 15–39 weeks. In all cases, clubfoot was diagnosed by initial sonographic examination at our center.
438 Malone et al
Isolated Clubfoot
Figure 1. Prenatal ultrasound of fetal clubfoot demonstrating plantar surface of foot and lower leg in same plane.
There was an increased incidence of clubfoot in male fetuses, with a male-to-female ratio of 1.7:1. There were 19 cases (37%) of bilateral clubfoot and 32 cases (63%) of unilateral clubfoot. Of the cases of unilateral clubfoot, 19 (59%) affected the left limb and 13 (41%) affected the right limb. Karyotype results by amniocentesis were available in 23 cases (45%). In all 51 cases, results of detailed physical examinations of infants were collected from pediatricians or neonatologists. There were no cases of fetal aneuploidy on fetal karyotype evaluation or newborn physical examination, which searched specifically for newborn dysmorphic features. All cases of clubfoot diagnosed prenatally were confirmed at newborn physical examination, and no additional structural malformations were detected.
Discussion Clubfoot can be diagnosed prenatally with fetal ultrasonography.4,5 Ultrasound visualization of the plantar surface of the fetal foot, in the same plane as the bones of the lower leg, seen on multiple images, confirms the diagnosis (Figure 1). The diagnosis of clubfoot is often an isolated finding, but it can be associated with other structural abnormalities such as cleft lip and palate, congenital heart disease, or congenital hip dislocation. Clubfoot can be a component of many genetic syndromes and rarer chromosomal abnormalities such as trisomies 13 and 18.3 Other causes of positional fetal deformities, including oligohydramnios, multiple gestation, uterine tumors, and amniotic bands, also have been associated with clubfoot. Such positional deformities (extrinsic cause of clubfoot) are due to intrauterine confinement rather than true structural malformation (intrinsic cause of clubfoot). The fact that most cases of
Obstetrics & Gynecology
clubfoot in our series were unilateral might imply that positional deformity, rather than true structural malformation, is a more common cause of prenatally diagnosed clubfoot. When syndromic diagnoses are excluded, the most common mode of inheritance of clubfoot is believed to be multifactorial. Wynne-Davis6 reported a recurrence risk for siblings with normal parents that varied according to sex of the affected sibling, such that the sibling of an affected male had a 2% risk of recurrence and a female had a 5% risk of recurrence. There is controversy about whether to offer invasive prenatal diagnosis of fetal karyotype after detecting an isolated clubfoot. Clubfoot has been linked to fetal aneuploidy, but in almost all cases, the finding is not isolated. For example, in one study of 35 cases of prenatally diagnosed clubfoot, there were five cases of chromosomal abnormality, four of which were trisomy 18.7 All five of those fetuses had severe structural malformations that were detected easily on ultrasonography, and none of the seven with isolated clubfoot had chromosomal abnormalities.7 In a report by Shipp and Benacerraf in 1998,5 68 fetuses were diagnosed prenatally with isolated clubfoot. Thirty-four women had invasive fetal karyotyping, and four cases of aneuploidy were found, leading the authors to recommend invasive karyotype evaluation in all cases of isolated clubfoot. However, two of those four cases of aneuploidy were sex chromosome abnormalities (47,XXY and 47,XXX), which should be considered a coincidental finding, because clubfoot has not been reported as part of the phenotype of those syndromes. There was one case of trisomy 21, but clubfoot is not part of the typical phenotype of Down syndrome. The fourth aneuploidy was trisomy 18, but the fetus also had a two-vessel cord and clenched fists. Both those findings are easily detectable with prenatal ultrasonography, and if noted, would be a reasonable indication for invasive assessment of fetal karyotype. In our study of 51 cases of isolated clubfoot, there were no cases of aneuploidy on fetal karyotype or newborn physical examination. In a smaller study, Woodrow et al8 made a similar conclusion after finding no cases of abnormal fetal karyotypes in a series of 17 fetuses with isolated clubfoot. We believe that our interpretation of the earlier report by Shipp and Benacerraf,5 with the results of other studies,7,8 and our current study, suggest that invasive testing for fetal karyotype might not be warranted with isolated fetal clubfoot. However, these results also emphasize that after seeing fetal clubfoot, careful targeted sonographic survey of the remainder of the fetal anatomy is essential to rule out any additional abnormalities. If any abnormalities are detected, or if women have standard indi-
VOL. 95, NO. 3, MARCH 2000
cations for fetal karyotype analysis such as advanced maternal age, invasive testing should be offered. Also, we recommend that all infants with isolated clubfoot be examined carefully in the newborn period and be followed up to ensure that the diagnosis is correct because of its association with other genetic syndromes.3 Careful antenatal counseling has been recommended after prenatal diagnosis of clubfoot to ensure that women are informed adequately of the possibility of such associations.9 A limitation of this and all previous studies5,7,8 is that we cannot be certain that all infants who did not have karyotype evaluations were truly chromosomally normal. However, all infants were examined in the newborn period by an attending neonatologist or pediatrician, looking specifically for dysmorphic features, so we believe it highly unlikely that any cases of autosomal trisomy were missed. Another limitation of the studies is the small sample; therefore, the possible margins for error are relatively large. It is doubtful that any single center will ever accumulate a large enough series of fetuses with prenatally diagnosed isolated clubfoot to confirm a high degree of likelihood that an association with aneuploidy exists. We believe it is safe to conclude that the literature has never confirmed an association between isolated clubfoot and aneuploidy that would justify the risks associated with invasive prenatal testing.
References 1. Drvaric DM, Kuivila TE, Roberts JM. Congenital clubfoot. Etiology, pathoanatomy, pathogenesis, and the changing spectrum of early management. Orthop Clin North Am 1989;20:641–7. 2. Yamamoto H. A clinical, genetic and epidemiologic study of congenital clubfoot. Jpn J Hum Genet 1979;24:37– 44. 3. Jones KL, Smith DW, Fletcher J. Smith’s recognizable patterns of human malformations. 5th ed. Philadelphia: WB Saunders: 1996. 4. Benacerraf BR, Frigoletto FD. Prenatal ultrasound diagnosis of clubfoot. Radiology 1985;155:211–3. 5. Shipp TD, Benacerraf BR. The significance of prenatally identified isolated clubfoot: Is amniocentesis indicated? Am J Obstet Gynecol 1998;178:600 –2. 6. Wynne-Davis R. Genetic and environmental factors in the etiology of talipes equinovarus. Clin Orthop 1972;84:9 –13. 7. Rijhsinghani A, Yankowitz J, Kanis AB, Mueller GM, Yankowitz DK, Williamson RA. Antenatal sonographic diagnosis of clubfoot with particular attention to the implications and outcomes of isolated clubfoot. Ultrasound Obstet Gynecol 1998;12:103– 6. 8. Woodrow N, Tran T, Umstad M, Graham HK, Robinson H, de Crespigny L. Mid–trimester ultrasound diagnosis of isolated talipes equinovarus: Accuracy and outcome for infants. Aust N Z J Obstet Gynaecol 1998;38:301–5. 9. Burgan HE, Furness ME, Foster BK. Prenatal ultrasound diagnosis of clubfoot. J Pediatr Orthop 1999;1:11–3.
Malone et al
Isolated Clubfoot 439
Address reprint requests to:
Fergal D. Malone, MD Division of Maternal-Fetal Medicine Department of Obstetrics and Gynecology Columbia-Presbyterian Medical Center 630 West 168th Street, PH 16 New York, NY 10032 E-mail: [email protected]
440 Malone et al
Isolated Clubfoot
Received July 1, 1999. Received in revised form September 3, 1999. Accepted September 15, 1999.
Copyright © 2000 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
Obstetrics & Gynecology