Three-dimensional ultrasound diagnosis of cleft palate: reverse face, flipped face or oblique face which method is best?

Ultrasound Obstet Gynecol 2009; 33: 399 406 Published online 24 December 2008 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/uog.6257 Three-dimensional ultrasound diagnosis of cleft palate: reverse face, flipped face or oblique face which method is best? P. MARTÍNEZ TEN*, J. PÉREZ PEDREGOSA*, B. SANTACRUZ*, B. ADIEGO*, E. BARRÓN* and W. SEPÚLVEDA *DELTA-Ultrasound Diagnostic Center in Obstetrics and Gynecology, Madrid, Spain and Fetal Medicine Center, Department of Obstetrics and Gynecology, Clínica Las Condes, Santiago, Chile KEYWORDS: ultrasound cleft lip; cleft palate; congenital anomalies; fetal palate; prenatal diagnosis; three-dimensional ultrasound; ABSTRACT Objectives To compare the performance of three sonographic techniques, the reverse-face, flipped-face and oblique-face methods, for visualizing the hard and soft palate in diagnosing cleft lip and palate (CLP). Methods A total of 60 fetuses (10 with CLP) with a gestational age ranging from 20 to 33 weeks were examined. We compared visualization of the secondary palate with the previously described reverse-face and flipped-face methods (the latter modified by us) and the oblique-face method developed by us using Oblique View imaging technology. Results Among the 10 fetuses with CLP the defect involved the lip, alveolus and secondary palate in seven, and the primary palate only in the remaining three. The upper lip and alveolar ridge were well visualized in all cases with all three methods. Involvement of the hard palate was diagnosed correctly in 71% (5/7) of the cases using the reverse-face view, in 86% (6/7) with the flippedface view, and in 100% (7/7) with the oblique-face view; the hard palate was correctly found to be intact in 78%, 84% and 86%, respectively, of the 50 normal fetuses examined with each view. Involvement of the soft palate was diagnosed correctly in only one of the seven fetuses with defects of the secondary palate in flipped-face and oblique-face views, and was correctly considered intact in only 16% of normal fetuses in flipped-face view and in 26% in oblique-face images. Conclusions Accurate visualization of the soft palate requires an excellent initially acquired volume, fluid between the fetal tongue and palate, and curving of the plane to follow the structure of the palate. The obliqueface or flipped-face views make it possible to visualize the soft palate well in selected cases. Copyright 2008 ISUOG. Published by John Wiley & Sons, Ltd. INTRODUCTION Cleft lip and palate (CLP), a congenital structural abnormality resulting from failed closure of a subset of facial processes during embryonic development, is one of the most common malformations in live newborns. Its incidence varies among continents, races and populations from one in 700 to one in 1500 newborns 1,2.Thismalformation is involved in more than 100 syndromes, and trisomy 13 is the most frequently associated chromosomal anomaly 3. In one recent series of 1623 patients with CLP, 15% had associated malformations, which were most frequent in patients with unilateral involvement of the lip and palate (37%), followed in decreasing order by isolated cleft palate (23%), bilateral CLP (20%), cleft lip with or without cleft alveolar ridge (17%), and submucosal cleft (3%) 4. The most frequent location of associated malformations is the facial region (21%), followed by the ocular system, central nervous system, skeletal system, cardiovascular system, neck, auricular system, gastrointestinal system and urogenital system. Fissures in the primary palate and rare facial fissures involving facial processes occur during embryogenesis after the sixth week of uterine life, whereas fissures in the secondary palate occur after the eighth week of intrauterine life. The different embryonic origins of the primary and secondary palate account for the difference Correspondence to: Dr P. Martínez Ten, DELTA-Ecografía, Centro de Diagnóstico por la Imagen en Obstetricia, Ginecología y Mama, Paseo de la Habana 204, bajo-1, 28036 Madrid, Spain (e-mail: p.m.ten@terra.es) Accepted: 14 May 2008 Copyright 2008 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER

400 Martínez Ten et al. in the genetic background of these defects. Cleft lip with or without cleft secondary palate has been associated with different sites in the genome (OFC1-10) and specific genes such as MSX1, IRF6, PVRL1 and TP73L. However, only one gene (TBX22) has been identified as involved in isolated secondary palate defects without cleft lip, although many more are thought to be involved 5. The secondary palate consists of the hard palate, a horizontal plate located behind the incisor foramen, and the soft palate or velum, which curves downward and backward from the posterior process of the hard palate and ends at the uvula. The hard palate in the fetus is approximately twice as long as the soft palate, which is an elastic structure similar in thickness to the bones of the hard palate. Defects of the lip and alveolar ridge are diagnosed successfully and with relative ease by conventional twodimensional (2D) ultrasonography 6 9, but diagnosis of abnormalities of the hard and soft secondary palate remains a challenge for sonographers. With the advent of three-dimensional (3D) ultrasound imaging a number of techniques have been developed to explore the secondary palate. These techniques include the reverse-face view described by Campbell et al. 10, the flipped-face view described by Platt et al. 11, the one proposed by Faure et al. 12 and variants of these 13. These techniques can visualize the palate in coronal or transverse planes in 3D multiplanar or 3D rendered modes. The aim of this study was to compare the performance of the reverse-face and flipped-face methods with a new approach we termed oblique face for the diagnosis of CLP. METHODS Between January 2006 and March 2007 we used 3D ultrasound imaging to study 60 fetuses, including 10 with CLP, at a mean gestational age of 27 (range, 20 33) weeks. The 50 fetuses without CLP were chosen randomly, and the only inclusion criterion for the present analysis was good acquisition of the facial volume with no shadowing owing to dorsal anterior position or interposition of the umbilical cord or limbs. The 10 cases with CLP were initially detected as having a cleft lip by conventional 2D ultrasonography at the time of the second-trimester detailed ultrasound examination. Volumes were acquired with high-resolution 3D ultrasound equipment using a multifrequency transabdominal volume transducer (Voluson 730 Expert, GE Medical Systems, Zipf, Austria; Accuvix XQ, Medison, Seoul, South Korea). In all cases we obtained one to three static volumes of the fetal face with a 2D image in the midsagittal plane. Whenever possible we waited until the fetus was swallowing fluid so that the tongue and palate were clearly separated by a crescent-shaped sonolucent area. We also tried to obtain volumes in which the fetal head was slightly deflected so that the angle of insonation of the palate was slightly oblique, as recommended by Pilu and Segata 13. Care was taken to obtain volumes of the face when it was not obstructed by the limbs, umbilical cord or placenta. The initial plane for volume acquisition was a strict mid-sagittal plane from which volumes were captured at a sweep angle of 50 to 70 from one lateral side of the face to the other (Figure 1). Volumes were acquired in high-2 quality mode, and were stored and analyzed later by the same sonologist (P.M.T.). Brightness and contrast were adjusted for multiplanar and rendered images, as were threshold and transparency. Surface rendering was done with a 60/40 to 40/60 mixture. We used different imaging modes provided by 4D View (version 2.1) data management software (Luminary, GE Medical Systems), including multiplanar and surface rendering in gradient light mode. We also used 3D-XI software (3D extended Imaging, Accuvix XQ, Medison), which includes the new Oblique View option for examination through a non-standard plane, and DynamicMR (XI-MR image postprocessing system) to enhance images. All volumes were manipulated to obtain images of the palate in all three viewing modes described below. Reverse-face view In accordance with the technique described by Campbell et al. 10 we scrolled the viewbar from the anterior to the posterior part of the palate. This yielded coronal reconstructions of the palate rendered from the inside out (Figures 2b, 3b and c, and 4b and c). Flipped-face view In accordance with the technique described by Platt et al. 11, we rotated the fetal face through 90 from a supine mid-sagittal position to obtain axial planes of the secondary palate, scrolling from the chin to the nose to render the surface. To compensate for the concave shape Figure 1 Multiplanar ultrasound images showing the optimum mid-sagittal plane used for initial volume acquisition, with a sweep angle of 50 70. The volume sweep was performed from one side of the face to the other. A hypoechogenic crescent of fluid can be seen separating the tongue and the palate. The head is slightly deflexed, requiring an oblique angle of insonation for the palate.

Three-dimensional ultrasound diagnosis of cleft palate 401 Figure 2 (a) Flipped-face technique, with multiplanar images on the left. A-plane: initial plane of volume acquisition with the face profile rotated 90 and the volume box viewbar curved to follow the shape of the hard and soft palate. B-plane: coronal plane of the face showing the viewbar curved to follow the shape of the hard palate. C-plane: axial plane at the level of the nasal septum. Surface-rendered view on the right shows an axial plane of the maxilla with alveolar ridges, hard palate (asterisk) and soft palate (arrow). (b) Reverse-face technique, with multiplanar images on the left. A-plane: initial plane of volume acquisition with the face profile rotated 90 and the volume box viewbar situated to the right for an inside-out facial sweep. B-plane: coronal plane of the face. C-plane: axial plane at the level of the nasal septum. Surface-rendered view on the right shows a coronal plane of the orbits, nasal bones, hard palate (arrow) and tongue (asterisk). (c) Oblique-face technique showing a profile of the fetal face with the viewbar curved to follow the shape of the palate, visualizing the upper lip, maxilla and hard palate. The plane perpendicular to the viewbar delimits a curved axial plane that includes the lip, maxilla, alveolar foramina and hard palate. (d) Oblique-face technique. The viewbar was placed anterior-to-posterior to traverse the hard palate. The image on the right is a coronal plane similar to that obtained in the reverse-face view, showing the orbits, nasal bones, hard palate (arrow) and tongue. of the palate, we modified this technique by curving the viewbar around the palate to improve image quality. The curvature was adjusted by taking the coronal plane in the multiplanar study as a reference point for the upper and inferolateral limits of the palate, and the sagittal plane as the reference point for the upper and posterior limits of the palate (Figures 2a, 3d and e, and 4d and e). Oblique-face view For this technique we used the Oblique View (nonstandard plane) option enhanced with DynamicMR image processing. Starting with a volume obtained from the face imaged in the mid-sagittal plane, we specified a surface that encompassed the lip, alveolar ridge and palate, and obtained an axial plane of the fetal face perpendicular to this surface; this plane included the palate. We then outlined the profile from the inside of the face in a cranial-tocaudal direction, and obtained a coronal plane that could be scrolled and rotated through the whole length and width of the palate (Figures 2c and d, 3f and g, and 4f). RESULTS Postnatal evaluation of all infants included in the study was performed by an expert pediatrician who explored the integrity of both the primary and secondary palate. None of the newborns affected had other major structural anomalies or abnormal karyotype. Of the 60 fetuses studied, 10 had cleft lip. In seven of these fetuses the defect involved the lip, alveolus and secondary palate (five unilateral and two bilateral), and in three others it involved the primary palate only (with cleft alveolar ridge in two fetuses and intact alveolar ridge in one). The upper lip and maxilla were well visualized in 100% of the cases with all three methods. Involvement of the hard palate was diagnosed correctly in 71.4% (5/7) of the cases with defects of the secondary palate in reverse-face view, 85.7% (6/7) in flipped-face view, and 100% (7/7) in oblique-face view; the hard palate was correctly found to be intact in 78% (39/50), 84% (42/50) and 86% (43/50), respectively, of the normal fetuses examined with each view. Involvement of the soft palate was diagnosed correctly in only 1/7 fetuses with defects of the secondary palate in flipped-face and oblique-face views, and was correctly considered intact in 16% (8/50) of normal fetuses in flipped-face view, and in 26% (13/50) in oblique-face images (Tables 1 and 2). In the two fetuses in which the hard palate was not well visualized in reverse-face views and in the fetus for which flipped-face images were unusable, gestational age was relatively low (from 20 to 22 weeks).

402 Martínez Ten et al. Figure 3 (a) Surface-rendered image of the fetal face at 27 weeks gestation, showing a unilateral cleft lip and palate involving the lip and alveolus. The labial fissure from the base of the nose causes nasal asymmetry, a deviated nasal septum and flattening of the alar cartilage. (b) Multiplanar images produced by reverse-face technique. A-plane: initial plane of volume acquisition with the face profile rotated 90 and the volume box viewbar situated to the right for an inside-out facial sweep. B-plane: coronal plane of the face. C-plane: axial plane at the level of the nasal septum. (c) Rendered image of a coronal plane showing the orbits and palate, and the communication between the oral cavity and nasal cavity (arrow). (d) Multiplanar images produced by flipped-face technique. A-plane: initial plane of volume acquisition with the face profile rotated 90 and the volume box viewbar curved to follow the shape of the hard and soft palate. B-plane: coronal plane of the face with the viewbar curved to follow the hard palate. C-plane: axial plane at the level of the nasal septum. (e) Surface-rendered image of an axial plane showing a unilateral cleft in the maxilla and absence of the part of the maxilla that would normally give rise to the lateral incisor on the side of the cleft. The arrow indicates a unilateral fissure that reaches the incisive foramen and asterisks indicate the limits of the defect in the alveolar ridge. (f) Oblique-face technique. Profile of the fetal face in which the viewbar is curved to follow the shape of the palate to sweep the upper lip, maxilla and hard palate. The plane perpendicular to the viewbar delimits a curved axial plane that includes the lip and cleft maxilla (arrow). (g) Oblique-face technique. The viewbar was placed anterior-to-posterior to traverse the hard palate. The coronal plane is similar to that obtained in the reverse-face view, showing the orbits, nasal bones and defect on one side only of the maxilla.

Three-dimensional ultrasound diagnosis of cleft palate 403 Figure 4 (a) Surface-rendered image of the fetal face at 23 weeks gestation, with bilateral cleft lip and palate involving the lip, maxilla and hard and soft palate. The defect completely clefts both sides of the lip. The anterior-projecting premaxilla is fused to the vomer and is separated from the maxilla, giving the face a characteristic appearance. (b) Multiplanar images produced by reverse-face technique. A-plane: initial plane of volume acquisition with the face profile rotated 90 and the volume box viewbar situated to the right for an inside-out facial sweep. B-plane: coronal plane of the face. C-plane: axial plane at the level of the nasal bones. (c) Rendered image of a coronal plane showing the orbits and vomer, visible in the center of the image (asterisk). The arrows indicate the bilateral defect in the hard palate. (d) Multiplanar images produced by flipped-face technique. A-plane: initial plane of volume acquisition with the face profile rotated 90 and the volume box viewbar curved to follow the shape of the hard and soft palate. B-plane: coronal plane of the face with the viewbar curved to follow the shape of the hard palate. C-plane: axial plane at the level of the nasal septum. (e) Surface-rendered image of an axial plane showing the cleft maxilla and the anterior-projecting premaxilla with the two central incisive foramina (asterisk), maxillary defect at the level of the lateral incisors (O), and absence of the part of the maxilla that would normally give rise to the lateral incisors. The arrows indicate a bilateral defect in the hard palate. (f) Oblique-face technique. Profile of the fetal face in which the viewbar is curved to follow the shape of the palate to sweep the premaxillary prolabium, the nasal septum and posteriorly the vomer. The plane perpendicular to the viewbar delimits a curved axial plane showing the premaxillary prolabium and the vomer, the communication between the premaxilla and the upper maxilla, the bilateral defect in the hard palate (arrows) and the soft palate (asterisk).

404 Martínez Ten et al. Table 1 Percentage of fetuses with cleft lip and palate (n = 10) in which abnormal findings were well visualized using each technique Feature Reverse-face Flipped-face Oblique-face Lip 100 (10/10) 100 (10/10) 100 (10/10) Alveolar ridge 100 (9/9) 100 (9/9) 100 (9/9) Hard palate 71.4 (5/7) 85.7 (6/7) 100 (7/7) Soft palate 0 (0/7) 14 (1/7) 14 (1/7) Table 2 Percentage of fetuses without cleft lip or palate (n = 50) in which different structures were well visualized using each technique Feature Reverse-face Flipped-face Oblique-face Lip 100 (50/50) 100 (50/50) 100 (50/50) Alveolar ridge 100 (50/50) 100 (50/50) 100 (50/50) Hard palate 78 (39/50) 84 (42/50) 86 (43/50) Soft palate 0 (0/50) 16 (8/50) 26 (13/50) DISCUSSION Although the birth of a child with CLP can have a severe emotional impact on the parents, antenatal diagnosis with ultrasonography helps to ameliorate the impact and prepare the parents psychologically. In a report by Davalbhakta and Hall of 124 children who underwent primary lip or palate repair, 30% were diagnosed antenatally, and their parents received prenatal counseling 14. Most parents (85%) felt that the information had prepared them psychologically for the birth of their child, and 92% indicated that they had never considered the possibility of voluntary termination of pregnancy. Prenatal diagnosis of CLP has the further advantage of allowing plastic surgeons to perform early lip repair. The number of palatal defects diagnosed by 3D ultrasound examination is small at this point. Campbell et al. reported eight cases 10, Pilu and Segata one 13, Platt and colleagues did not report the number of cases diagnosed 11, and Faure et al. reported none 12. The largest series is from Rotten and Levaillant 15 ; in a retrospective series of 96 cases of orofacial clefting they observed that the alveolus and maxilla were best seen in an axial plane and the secondary palate in a coronal plane. Although there was 87% concordance between the sonographic report and postnatal evaluation, five secondary palatal defects were missed and there were four false-positive diagnoses of defects in the secondary palate in fetuses with clefts of the lips and alveolus. Faure et al. 12 proposed a method of volume acquisition for the study of the palate that seems rather different from the method used by us and by most other authors who have dealt with this subject 10,11,13,15. Instead of using the mid-sagittal plane of the fetal face to start, they use an axial plane. According to the explanation in their article: To obtain an anatomic 3D image of the fetal palate, the green viewbar was placed above the two-dimensional anterior axial view of the maxilla. Care was taken to keep the transducer in strict anterior axial view 12. To allow a volume to be obtained in which the starting green viewbar is placed over an anterior axial view of the maxilla, the fetus has to be in a position in which the back is posterior and the face anterior, meaning that the fetus has to look towards the ceiling of the examination room. We performed our examinations from the 20 th week onwards, during which fetuses mainly adopt a position with their backs either to the left or to the right of the mother. A left- or right-sided fetal position helps in the acquisition of a volume from a sagittal plane. Sonologists are very familiar with the sagittal view of the fetal profile; in this plane we examine the nasal bone and nuchal translucency, we measure the frontomaxillary angle and obtain rendered images of the surface of the fetal face. This familiarity with the sagittal plane allows us to start from a strict mid-sagittal plane with very clear anatomical references, which is valuable in multiplanar imaging as the coronal and axial planes will be perpendicular, minimizing alterations required in the starting plane. In our opinion, utilization of the axial plane is complex; it is difficult to fix anatomical references that provide assurance that the plane is perfectly centered and it is also difficult to ensure that the palate is not affected by shadowing from the maxilla. Campbell shares our opinion, writing: Surprisingly, the authors do not report difficulties with shadowing of the palate by the maxilla 16. The images of Faure s group are excellent, but these authors have not presented any cases of palatal defects visualized using this technique and it is apparent from the high level of detail provided of the posterior edge of the hard palate that the soft palate was not visualized. Conventional viewing of multiplanar images has several limitations, the most important problem being the suboptimal image resolution in reconstructed planes. To evaluate the palate accurately it is important to obtain high-quality volumes because the structure of interest is small, curved and often shadowed by the maxilla. We feel it is also important to wait until the fetus is awake and in the act of swallowing, because the fluid between the tongue and palate allows the sonologist to rule out spurious images of the tongue and avoids confusing the tongue with the palate. Care should be taken to avoid obtaining images in which fluid is retained between the tongue and the secondary palate in the absence of active swallowing movements, because this can lead to inaccurate volume capture. In the few images published to date involving defects of the hard palate seen in axial planes with multiplanar or rendered mode, the margins of the lesion are poorly defined. We believe that curving the viewbar to follow the shape of the palate with either conventional volumetric studies (flipped-face technique) or the Oblique View tool provides well defined images that show details of the margins of the hard palate defect, as seen in Figures 3d, e and f, and 4d, e and f. We find that the lateral margins of the palate are not always clear, especially in the posterior half of the palate, and that it is not always possible to obtain good images

Three-dimensional ultrasound diagnosis of cleft palate 405 of the entire palate such as those described by Faure et al. 12. However, because defects in the hard palate can be located on either side of the midline, we believe that good visualization of the two palatine processes and two horizontal palatine bones rules out the presence of lesions in the hard palate with a reasonable degree of certainty. We believe that our work s merit lies in the help it offers in diagnosing defects of the soft palate. Campbell 16 thinks that there are difficulties in viewing the soft palate with his reverse-face technique because it hangs down nearly vertically and cannot be insonated correctly in a coronal section. He has also expressed skepticism that the soft palate can be visualized using the technique of Platt et al. 11 : The authors believed that the technique provided views of the soft palate, but in the image presented there was no clear evidence that the structure identified as the velum was not in fact the posterior part of the hard palate, especially as there appeared to be an interpalatal suture, which is typical of the hard palate 16. Regarding the work of Faure s group 12, as mentioned, it seems evident from the great detail with which the posterior edge of the palate is shown that the soft palate was not visualized. The way to view the soft palate is to curve the green viewbar, both in Window A (sagittal plane) and Window B (coronal plane) in the multiplanar view, and to carry it backwards and, to a greater degree, downwards, adapting it to the shape and direction of the soft palate. The ability to curve the green viewbar can be limited; not all 3D ultrasound machines include this function, and those allowing a degree of depth to the curve are limited by the size of the render box. The oblique-face method, proposed by us, offers unlimited possibilities in adapting the plane s curve exactly to follow the secondary palate (hard and soft). Therefore, we believe that the soft palate can be visualized adequately only by curving the plane sufficiently with the Oblique View technology, or by curving the viewbar of the volume box using the technique described by Platt et al. 11 as modified by us (Figures 5 and 6). Moreover, both techniques require initially acquired volumes of high quality, and the presence of fluid between the tongue and secondary palate. In fact, we were able to obtain good images of only one case in which the defect was bilateral and involved the soft palate. These technical considerations mean that the possibility of prenatal screening for isolated defects of the soft palate seems remote at present. Given the additional time and effort needed to achieve good insonation and visualization, these methods should be confined to certain cases in which a cleft lip or hard palate is suspected. Fortunately, isolated defects in the soft palate are easier to correct surgically, and their emotional impact on the parents if they are not diagnosed antenatally is less than in newborns with cleft lip or cleft hard palate. Figure 5 Surface-rendered axial image from a normal 28-week fetus in flipped-face view, showing the lip (1), maxilla (2), hard palate (3), soft palate (4) and larynx (5). Figure 6 Sagittal (left) and axial (right) images of the soft palate at 30 weeks gestation in oblique-face view showing the lip (1), maxilla (2), hard palate (poorly defined in the image) (3), soft palate (4), larynx (5) and tongue (6).

406 Martínez Ten et al. In practice, none of the three methods (reverse face, flipped face or oblique face) is likely to be notably superior to the others. It should be possible to use all three for any fetus as the only requirements are adequate volume acquisition and time to examine the images offline. However, when an immediate diagnosis is needed, the fastest and most straightforward method seems to be the oblique-face approach. We believe that, when initial volume acquisition is inadequate and image quality is less than optimum, the method that provides the most information is the reverse-face view or the oblique-face view in coronal planes. In summary, our experience suggests that accurate ultrasound imaging of the secondary palate requires adequate volume acquisition, the presence of fluid between the fetal tongue and palate, and curving of the plane so that the acquired volume follows the concave structure of the palate with either the oblique-face or flipped-face view. In certain cases these views can reveal information about the soft palate of potential use in prenatal diagnosis of defects. ACKNOWLEDGMENT We would like to thank K. Shashok for translating the original manuscript into English. REFERENCES 1. Gregg T, Bod D, Richardson A. The incidence of cleft lip and palate in Northern Ireland from 1980 1990. BrJOrthod1994; 21: 387 392. 2. Coupland MA, Coupland AI. Seasonality, incidence and sex distribution of cleft lip and palate births in Trent region (1973 82). Cleft Palate J 1988; 25: 33 37. 3. Nyberg DA, Sickler GK, Hegge FN, Kramer DJ, Kropp RJ. Fetal cleft lip with or without cleft palate: ultrasound classification and correlation with outcome. Radiology 1995; 195: 677 684. 4. Sekhon PS, Bhasker Rao C, Markus AF. Congenital anomalies associated with cleft lip and palate. Br J Oral Maxillofac Surg 2008; (in press). 5. Carinci F, Scapoli L, Palmieri A, Zollino I, Pezzetti F. Human genetic factors in nonsyndromic cleft lip and palate: an update. Int J Pediatr Otorhinolaryngol 2007; 71: 1509 1519. 6. Sohan K, Freer M, Mercer N, Soothill P, Kyle P. Prenatal detection of facial clefts. Fetal Diagn Ther 2001; 16: 196 199. 7. Cash C, Set P, Coleman N. The accuracy of antenatal ultrasound in the detection of facial clefts in a low-risk screening population. Ultrasound Obstet Gynecol 2001; 18: 432 436. 8. Clementi M, Tenconi R, Bianchi F, Stoll C. Evaluation of prenatal diagnosis of cleft lip with or without cleft palate and cleft palate by ultrasound: experience from 20 European registries. EUROSCAN study group. Prenat Diagn 2000; 20: 870 875. 9. Ghi T, Perolo A, Banzi C, Contratti G, Valeri B, Savelli L, Morselli GP, Bovicelli L, Pilu G. Two-dimensional ultrasound is accurate in the diagnosis of fetal craniofacial malformation. Ultrasound Obstet Gynecol 2002; 19: 543 551. 10. Campbell S, Lees C, Moscoso G, Hall P. Ultrasound antenatal diagnosis of cleft palate by a new technique: the 3D reverse face view. Ultrasound Obstet Gynecol 2005; 25: 12 18. 11. Platt LD, Devore GR, Pretorius DH. Improving cleft palate/cleft lip antenatal diagnosis by 3-dimensional sonography: the flipped face view. J Ultrasound Med 2006; 25: 1423 1430. 12. Faure JM, Captier G, Baumler M, Boulot P. Sonographic assessment of normal fetal palate using three-dimensional imaging: a new technique. Ultrasound Obstet Gynecol 2007; 29: 159 165. 13. Pilu G, Segata M. A novel technique for visualization of the normal and cleft fetal secondary palate: angled insonation and three-dimensional ultrasound. Ultrasound Obstet Gynecol 2007; 29: 166 169. 14. Davalbhakta A, Hall PN. The impact of antenatal diagnosis on the effectiveness and timing of counselling for cleft lip and palate. Br J Plast Surg 2000; 53: 298 301. 15. Rotten D, Levaillant JM. Two- and three-dimensional sonographic assessment of the fetal face. 2. Analysis of cleft lip, alveolus and palate. Ultrasound Obstet Gynecol 2004; 24: 402 411. 16. Campbell S. Prenatal ultrasound examination of the secondary palate. Ultrasound Obstet Gynecol 2007; 29: 124 127.