Donald School Journal of Ultrasound in Obstetrics and Gynecology
Volume 17 | Issue 2 | Year 2023

Three-dimensional/Four-dimensional Ultrasound: The Key for the Precise Assessment of Fetal Malformations

Eberhard Merz1, Sonila Pashaj2

1,2Center for Ultrasound and Prenatal Medicine, Frankfurt am Main, Germany

Corresponding Author: Eberhard Merz, Center for Ultrasound and Prenatal Medicine, Frankfurt am Main, Germany, Phone: +49 6976806559, e-mail:

Received on: 02 April 2023; Accepted on: 25 April 2023; Published on: 30 June 2023


Three-dimensional/four-dimensional (3D/4D) ultrasound has a high diagnostic potential in the detection and visualization of fetal malformations. Compared to two-dimensional (2D) ultrasound, which only allows the demonstration of individual planes, 3D/4D ultrasound allows the storage of volumes that can be examined using different visualization modes. As a result, fetal structures can be represented in controlled reformatted planes, in multiple parallel (tomographic) planes, or in rendered surface or transparent images. Fetal malformations can thus be demonstrated with the optimal visualization mode and from the best viewing angle. In the case of a presumed fetal malformation during a 2D ultrasound examination, or in the case of an increased recurrence risk of a certain fetal malformation, the different viewing modes, in particular the surface mode, can be used to convincingly show the parents the absence of such a malformation.

How to cite this article: Merz E, Pashaj S. Three-dimensional/Four-dimensional Ultrasound: The Key for the Precise Assessment of Fetal Malformations. Donald School J Ultrasound Obstet Gynecol 2023;17(2):158–164.

Source of support: Nil

Conflict of interest: None

Keywords: Prenatal diagnosis, Fetal malformations, Three-dimensional ultrasound, Four-dimensional ultrasound, Visualization modes

This paper has been previously published as Eberhard Merz, Sonila Pashaj. 3D/4D ultrasound: The key for the precise assessment of fetal malformations. In: Chervenak FA, Kupesic Plavsic S, Kurjak A. Donald School The Fetus as a Patient: Current Perspectives. Jaypee Brothers, New Delhi, India, 2019, pp 217–225.


There is no doubt that most fetal malformations can be detected with conventional 2D ultrasound. However, all of the described abnormalities can only be displayed in single planes. In contrast to 2D ultrasound, 3D/4D ultrasonography provides the examiner with several different visualization modes1-3 and displays images not previously viewed in 2D ultrasound. This gives the operator the opportunity to identify both, the normal and the abnormal anatomy in the most appropriate mode.1 Furthermore, 3D/4D ultrasound technology offers the possibility of digital volume storage without any quality loss. By reloading the volumes in the absence of the patient, virtual examinations can be performed by navigating through the volumes without causing any stress to the patient.2 In counseling patients, rendered images help the parents to understand the severity of an existing malformation or to give them the certainty of the absence of any fetal abnormality. This is particularly useful in cases with an increased recurrence risk for a specific fetal malformation.3

Technical Aspects

Despite the fact that most ultrasound companies have incorporated 3D/4D technology in their ultrasound units today and are offering both transvaginal and transabdominal 3D/4D probes, there are still distinct differences concerning routine handling of the equipment, in addition to differences in the image quality. However, an indispensable prerequisite for high-quality 3D/4D images is the availability of good-quality 2D images, considering that 3D/4D ultrasound technology is invariably based on 2D ultrasound.1

In any volume acquisition procedure, it has to be ensured that the region of interest (ROI) is completely inside the volume box. Structures that are not completely inside the volume box are cut and may thus simulate a malformation (e.g., missing hands or feet).

Once the volume is acquired and stored in the memory of the ultrasound unit, a choice between the different display modes1,3 listed in Table 1 can be made.

Table 1: Overview of 3D/4D visualization modes appropriate for prenatal diagnosis modification after Merz and Pashaj3
3D display mode 4D display mode
Multiplanar mode Multiplanar mode
Omniview Omniview
Volume contrast imaging (VCI) VCI
3D surface mode 3D surface mode
HDlive mode HDlive mode
HDlive studio mode HDlive studio mode
HDlive silhouette mode HDlive silhouette mode
Transparent mode Transparent mode
Minimum mode Minimum mode
Inversion mode Inversion mode
Glass body mode Glass body mode
3D-animation (cine) mode STIC

The tri- or multiplanar mode is, in all cases, the basic display mode which shows all three perpendicular planes at the same time on the monitor.2,3 By navigating through the volume, the observed plane is always controlled by the two other orthogonal planes, thus allowing a precise demonstration of the preferred anatomical structure.

By choosing the tomographic mode (parallel-plane display), it becomes possible to demonstrate parallel planes on the monitor, similar to computed tomography or magnetic resonance imaging.2,3

Omniview is a technique that allows the definition of a specific sectional plane by drawing a reference line, a polyline, or a curve in the A-plane. The corresponding perpendicular plane will be shown immediately next to the A-plane on the monitor.3

Volume contrast imaging represents a thick slice technique that enables imaging of thin volumes with high contrast resolution.2

The surface mode provides the examiner with 3D images of the fetal surface.1-3 For the application of this mode, it is important to ensure both the presence of sufficient amniotic fluid in front of the ROI and the absence of overlying structures.2

HDlive mode is a more recently introduced mode for the display of the fetal surface, providing the most realistic pictures of the embryo and the fetus.4-6 A virtual light source enables illuminating the fetus from different angles.

HDlive studio mode is similar to the HDlive mode. However, it allows the operator to illuminate the fetus using three different virtual light sources from different angles.3

HDlive silhouette mode enables two different demonstrations of the embryo and the fetus. The adjustment to “Low Silhouette” is useful in the demonstration of external structures, while the “High Silhouette” mode reveals internal structures.3

With the transparent mode, the bony structures of the fetus can be demonstrated while the soft tissue is greatly attenuated.1-3

In the minimum mode, only the minimum grey levels are displayed. This mode can be applied for the demonstration of vessels and hollow or cystic structures.2,3

With the inversion mode, anechoic structures can be converted into hyperechoic structures.2

The glass body mode is a combination of greyscale 3D images and color Doppler, allowing the precise spatial demonstration of the blood flow in the fetus as if viewed in a glass model.2

The 3D animation mode or cine mode provides images of the ROI at different angles. In this manner, the physician and the patient can both see the object of interest rotating on the screen and obtain a better spatial impression thereof.2 The 3D cine mode can be used together with the different surface modes, the transparent mode, and the glass body mode.

Four-dimensional (4D) ultrasound (real-time 3D) enables the fast acquisition of volumes with the demonstration of the movements of the embryo and the fetus without artifacts.2

Spatiotemporal image correlation (STIC) allows an automatic volume acquisition of several heart cycles. According to spatial and temporal image correlation, they are merged together to form one single fetal heart cycle.1,7-9 Using this technology, the moving fetal heart can be analyzed offline. The combination of STIC and color Doppler provides the examiner with a detailed view of the cardiac blood flow.2

Assessment of Fetal Malformations

The use of the different display modes permits the operator to demonstrate a large number of visible abnormalities in the most appropriate mode, revealing the extent of the lesion interactively in all dimensions.3 Once a suspicious ROI is stored in a volume, even subtle anatomical defects can be demonstrated by a detailed examination of the volumes. Because any plane can be reformatted from the volume, 3D ultrasonography can depict image planes that are not accessible with conventional 2D ultrasound. Furthermore, rotation of the volume in all three directions enables the operator to align the fetus or the ROI into an exact upright position.

The usefulness of 3D ultrasound in the assessment of fetal malformations has been shown in a number of different studies.10-14 A comparison between 2D and 3D techniques in a study of 102 malformations showed 3D sonography to be advantageous in 60.8% of the defects.13

In the first trimester, the triplanar verification of the median plane allows precise control of the nuchal translucency (Fig. 1) and the demonstration of palatine clefts15 or retrognathia. The presence or absence of the nasal bone can be identified in a slightly paramedian plane3 (Fig. 1). Using the surface mode, early surface defects, such as cleft lip (Fig. 2), limb defects, or hexadactyly can be detected.

Fig. 1: Multiplanar (triplanar) display (slightly paramedian plane) of a fetus with enlarged nuchal translucency (7.4 mm) and absent nasal bones at 13 + 3 weeks of gestation. After volume acquisition, the fetus was rotated into an upright position

Fig. 2: Surface-rendered view of a unilateral cleft lip left (←) at 13 + 4 weeks of gestation

In the second trimester, the multiplanar view of the fetal head does not only reveal a flat profile, frontal bossing, a depressed nasal bridge, cleft lip and palate or micrognathia,16-23 but also confirms brain abnormalities such as agenesis or partial agenesis of the corpus callosum24-26 (Fig. 3). Further identifiable are another brain anomalies27,28 as, for example dilated ventricles, plexus cysts, arachnoidal cysts, the absence of gyri, holoprosencephaly, schizencephaly, hypoplasia, the absence of the vermis cerebelli, or encephalocele. The coronal and axial planes allow an exact comparison of symmetric structures, for example of the left and right brain ventricle, the left and right orbital diameter, as well as the precise demonstration of orbital and eye malformations.3 The transparent mode enables the identification of the presence of ossification of the skull, revealing abnormal width of the metopic suture, premature closure of the sutures29,30 (Fig. 4), or the absence or hypoplasia of the nasal bones.31

Figs 3A to D: (A) Surface display of the median cut plane of a fetus with agenesis of corpus callosum (→) (35 weeks of gestation); (B) Axial surface plane of a fetus with agenesis of the corpus callosum, showing typical tear-shaped brain ventricles (22 weeks of gestation); (C) Surface display of the median cut plane of a fetus with partial agenesis of corpus callosum (posterior part of the corpus callosum is missing (←) at 31 weeks of gestation; (D) Same fetus as in c. The glass body mode reveals the pericallosal artery only in the anterior part of the corpus callosum, while the posterior part shows no perfusion (←)

Fig. 4: Transparent view of a fetal skull with craniosynostosis in the metopic suture (→) (37 weeks of gestation)

The surface modes enable the operator to verify surface defects of the head or face (exencephaly, cyclopia with proboscis, cleft lip/palate2,16,32-34 (Figs 5 and 6), or retrognathia), ear anomalies13 and protruding structures16 like an anterior or posterior encephalocele, epignathus, or a preauricular tag (Fig. 7). The surface mode can further be used to demonstrate surface views of cut planes of the brain. With the use of this mode, brain anomalies, such as holoprosencephaly, dilated brain ventricles, or plexus cysts3,13 can be seen from a bird’s eyes view.

Fig. 5: Surface-rendered view of unilateral cleft lip left (HDlive) at 29 weeks of gestation

Figs 6A and B: Combination of Omniview and VCI mode, presenting isolated cleft palate (34 weeks of gestation). (A) Omniview mode allows freehand tracing along the palate, VCI mode produces a thick slice of 4 mm; (B) 3D view perpendicular to the traci

Fig. 7: Surface-rendered view (HDlive) of a low set left ear with preauricular tag at 30 weeks of gestation

In examinations of the spine, the transparent mode enables to verification of the demonstration of axis abnormalities (Fig. 8) or hemivertebrae, while spina bifida is best seen with one of the surface modes13 (Fig. 8).

Figs 8A to C: (A) Transparent view of severe scoliosis (29 weeks of gestation); (B) Surface-rendered view (HDlive) of partial rachischisis in the lumbar and sacral part of the spine (19 weeks of gestation); (C) Surface-rendered side view (HDlive) (median cut plane) of a meningocele (21 weeks of gestation)

For the assessment of thorax abnormalities, the transparent mode can be used to identify abnormalities in the ossification of the bony thorax.13 Lung abnormalities35 or diaphragmatic hernia are best seen with the multiplanar view, the tomographic view (Fig. 9), or with the surface view of specific cut planes.

Fig. 9: Tomographic view of cystic adenomatoid lung malformation type I on the right side at 26 weeks of gestation

To demonstrate heart malformations, the glass body mode, STIC technology, and the STIC color mode are the applications of choice.7-9 Complex anomalies can be demonstrated and the blood flow can be controlled three-dimensionally (Fig. 10).

Figs 10A and B: (A) Color STIC mode at 27 weeks of gestation, showing singular ventricle; (B) Color STIC mode at 32 weeks of gestation, demonstrating overriding aorta in a fetus with tetralogy of Fallot

Abdominal anomalies2,3,10 can be shown using the multiplanar mode, tomographic ultrasound imaging (TUI) mode, or one of the surface modes (Fig. 11). The High HDlive silhouette mode can be used to reveal the internal structures of an omphalocele (Fig. 11).

Figs 11A and B: (A) Surface-rendered view (HDlive) of gastroschisis at 21 weeks of gestation; (B) HDlive High silhouette view showing liver (*) and bowel (→) inside the sac of the omphalocele (22 weeks of gestation)

The multiplanar mode, TUI mode, minimum mode, inversion mode, and surface mode are used to visualize urogenital malformations. Cystic structures of the kidneys or dilated ureters can be converted to solid structures with the inversion mode3 (Fig. 12), while genital abnormalities3 can best be shown with one of the surface modes (Fig. 13).

Figs 12A and B: (A) Surface-rendered view (HDlive) of an axial cut plane of a multicystic kidney at 25 weeks of gestation; (B) The inversion mode is converting the cysts of the multicystic kidney into solid hyperechogenic structures

Figs 13A and B: (A) Surface-rendered view (HDlive studio) of the male gender with micropenis at 32 weeks of gestation; (B) Surface-rendered view (HDlive) of the female gender with clitoromegaly at 30 weeks of gestation

Defects of the limbs13 (Fig. 14) or deviation of the limb axis3 (Fig. 15) are best demonstrated with the surface mode, while bone abnormalities like a missing bone (Fig.16), bowing of the bone, or fractures (Fig.16) can be visualized with the transparent mode.3 In addition, 4D ultrasound demonstrates any pathologic movement of the limbs, which may be observed in severe spina bifida.

Figs 14A to C: (A) Surface-rendered view (HDlive studio) of overlapping fingers in a fetus with trisomy 18 (23 weeks of gestation); (B) Surface-rendered view (HDlive studio) of a hand with syndactyly of digits 3 and 4 (35 weeks of gestation); (C) Surface-rendered view (HDlive) of a left hand with postaxial hexadactyly (19 weeks of gestation)

Fig. 15: Surface-rendered view (HDlive studio) of a clubfoot right with a pronounced deviation of the foot axis in a case with spina bifida (21 weeks of gestation)

Figs 16A and B: (A) Transparent view of a left arm with the demonstration of radius aplasia and severe deviation of the hand axis. The hand shows only four fingers (23 weeks of gestation); (B) Transparent view of a femur with a central fracture in a fetus with osteogenesis imperfecta type II (27 weeks of gestation)

Malformations affecting twins such as conjoined twins36,37 can readily be shown in the first trimester with the multiplanar mode, the TUI mode, the surface mode, and the glass body mode.


Over the past three decades, 3D ultrasound has undergone tremendous development.38 In expert hands, 3D/4D ultrasound today represents an excellent complementary tool to conventional 2D ultrasound in prenatal diagnosis. The different display modes provide the operator with images that cannot be achieved with 2D ultrasound. This is of particular value in the demonstration of subtle defects in the embryo and the fetus. Moreover, the digital storage of volumes without any quality loss enables virtual ultrasound examinations while the patient is absent. Furthermore, the demonstration of fetal malformations to the parents or the pediatric surgeon is significantly easier with 3D than with 2D ultrasound, due to the fact that the future parents and the doctors are able to see such defects as a cleft lip or spina bifida immediately with their own eyes. This represents an invaluable aid in providing correct counseling to the parents.

The continuing development of high-end matrix probes will enable the operator to acquire volumes significantly more rapidly than with the use of mechanical devices and thus help to avoid artifacts caused by the moving fetus. With the ongoing development of computer technology, it might further become possible to provide the operator with extended 3D views of the fetus and thus serve as a helpful tool in the second half of pregnancy.


1. Merz E. Current 3D/4D ultrasound technology in prenatal diagnosis. Eur Clin Obstet Gynecol 2005;1:184–193. DOI: 10.1007/S11296-005-6

2. Merz E, Abramowicz JS. 3D/4D ultrasound in prenatal diagnosis: is it time for routine use? Clin Obstet Gynecol 2012;55(1):336–351. DOI: 10.1097/GRF.0b013e3182446ef7

3. Merz E, Pashaj S. Advantages of 3D ultrasound in the assessment of fetal abnormalities. J Perinat Med 2017;45(6):643–650. DOI: 10.1515/jpm-2016-0379

4. Pooh RK, Kurjak A. Novel application of three-dimensional HDlive imaging in prenatal diagnosis from the first trimester. J Perinat Med 2015;43(2):147–158. DOI: 10.1515/jpm-2014-0157

5. Merz E. Surface reconstruction of a fetus (28+2 GW) using HDlive technology. Ultraschall Med 2012;33(3):211–212.

6. Bonilla-Musoles F, Raga F, Osborne NG, et al. Multimodality 3-dimensional volumetric ultrasound in obstetrics and gynecology with an emphasis in HDlive technique. Ultrasound Q 2013;29(3):189–201. DOI: 10.1097/RUQ.0b013e31829a582b

7. DeVore GR, Falkensammer P, Sklansky MS, et al. Spatio-temporal image correlation (STIC): new technology for evaluation of the fetal heart. Ultrasound Obstet Gynecol 2003;22(4):380–387. DOI: 10.1002/uog.217

8. Chaoui R, Hoffmann J, Heling KS. Three-dimensional (3D) and 4D color Doppler fetal echocardiography using spatio-temporal image correlation (STIC). Ultrasound Obstet Gynecol 2004;23(6):535–545. DOI: 10.1002/uog.1075

9. Paladini D, Vassallo M, Sglavo G, et al. The role of spatio-temporal image correlation (STIC) with tomographic ultrasound imaging (TUI) in the sequential analysis of fetal congenital heart disease. Ultrasound Obstet Gynecol 2006;27(5):555–561. DOI: 10.1002/uog.2749

10. Merz E, Bahlmann F, Weber G. Volume scanning in the evaluation of fetal malformations: a new dimension in prenatal diagnosis. Ultrasound Obstet Gynecol 1995;5(4):222–227. DOI: 10.1046/j.1469-0705.1995.05040222.x

11. Bonilla-Musoles F, Raga F, Osborne NG, et al. Use of three-dimensional ultrasonography for the study of normal and pathologic morphology of the human embryo and fetus: preliminary report. J Ultrasound Med 1995;14(10):757–765. DOI: 10.7863/jum.1995.14.10.757

12. Dyson RL, Pretorius DH, Budorick NE, et al. Three-dimensional ultrasound in the evaluation of fetal anomalies. Ultrasound Obstet Gynecol 2000;16(4):321–328. DOI: 10.1046/j.1469-0705.2000.00183.x

13. Merz E, Welter C. 2D and 3D ultrasound in the evaluation of normal and abnormal fetal anomaly in the second and third trimesters in a level III center. Ultraschall Med 2005;26(1):9–16. DOI: 10.1055/s-2004-813947

14. Kurjak A, Miskovic B, Andonotopo W, et al. How useful is 3D and 4D ultrasound in perinatal medicine? J Perinat Med 2007;35(1):10–27. DOI: 10.1515/JPM.2007.002

15. Lakshmy SR, Deepa S, Rose N, et al. First-trimester sonographic evaluation of palatine clefts: a novel diagnostic approach. J Ultrasound Med 2017;36(7):1397–1414. DOI: 10.7863/ultra.16.05084

16. Merz E, Weber G, Bahlmann F, et al. Application of transvaginal and abdominal three-dimensional ultrasound for the detection or exclusion of malformations of the fetal face. Ultrasound Obstet Gynecol 1997;9(4):237–243. DOI: 10.1046/j.1469-0705.1997.09040237.x

17. Pretorius DH, House M, Nelson TR, et al. Evaluation of normal and abnormal lips in fetuses: comparison between three- and two-dimensional sonography. AJR Am J Roentgenol 1995;165(5):1233–1237. DOI: 10.2214/ajr.165.5.7572510

18. Lee W, Kirk JS, Shaheen KW, et al. Fetal cleft lip and palate detection by three-dimensional ultrasonography. Ultrasound Obstet Gynecol 2000;16(4):314–320. DOI: 10.1046/j.1469-0705.2000.00181.x

19. 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(4):402–411. DOI: 10.1002/uog.1718

20. Lee W, McNie B, Chaiworapongsa T, et al. Three-dimensional ultrasonographic presentation of micrognathia. J Ultrasound Med 2002;21(7):775–781. DOI: 10.7863/jum.2002.21.7.775

21. Merz E, Abramowicz J, Baba K, et al. 3D imaging of the fetal face – recommendations from the international 3D focus group. Ultraschall Med 2012;33(2):175–182. DOI: 10.1055/s-0031-1299378

22. Andresen C, Matias A, Merz E. Fetal face: the whole picture. Ultraschall Med 2012;33(5):431–440. DOI: 10.1055/s-0031-1299482

23. 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(2):166–169. DOI: 10.1002/uog.3877

24. Pashaj S, Merz E. Detection of fetal corpus callosum abnormalities by means of 3D ultrasound. Ultraschall Med 2016;37(2):185–194. DOI: 10.1055/s-0041-108565

25. Tonni G, Grisolia G, Sepulveda W. Second trimester fetal neurosonography: reconstructing cerebral midline anatomy and anomalies using a novel three-dimensional ultrasound technique. Prenat Diagn 2014;34(1):75–83. DOI: 10.1002/pd.4258

26. Contro E, Nanni M, Bellussi F, et al. The hippocampal commissure: a new finding at prenatal 3D ultrasound in fetuses with isolated complete agenesis of the corpus callosum. Prenat Diagn 2015;35(9):919–922. DOI: 10.1002/pd.4645

27. Timor-Tritsch IE, Monteagudo A, Santos R. Three-dimensional inversion rendering in the first- and early second-trimester fetal brain: its use in holoprosencephaly. Ultrasound Obstet Gynecol 2008;32(6):744–750. DOI: 10.1002/uog.6245

28. Gedikbasi A, Yildirim G, Saygi S, et al. Prenatal diagnosis of schizencephaly with 2D-3D sonography and MRI. J Clin Ultrasound 2009;37(8):467–470. DOI: 10.1002/jcu.20589

29. Helfer TM, Peixoto AB, Tonni G, et al. Craniosynostosis: prenatal diagnosis by 2D/3D ultrasound, magnetic resonance imaging and computed tomography. Med Ultrason 2016;18(3):378–385. DOI: 10.11152/mu.2013.2066.183.3du

30. Tutschek B, Blaas HK, Abramowicz J, et al. Three-dimensional ultrasound imaging of the fetal skull and face. Ultrasound Obstet Gynecol 2017;50(1):7–16. DOI: 10.1002/uog.17436

31. Benoit B, Chaoui R. Three-dimensional ultrasound with maximal mode rendering: a novel technique for the diagnosis of bilateral or unilateral absence or hypoplasia of nasal bones in second-trimester screening for down syndrome. Ultrasound Obstet Gynecol 2005;25(1):19–24. DOI: 10.1002/uog.1805

32. Levaillant JM, Nicot R, Benouaiche L, et al. Prenatal diagnosis of cleft lip/palate: the surface rendered oro-palatal (SROP) view of the fetal lips and palate, a tool to improve information-sharing within the orofacial team and with the parents. J Craniomaxillofac Surg 2016;44(7):835–842. DOI: 10.1016/j.jcms.2016.04.006

33. Merz E, Pashaj S. Prenatal detection of orofacial clefts. Ultraschall Med 2016:37(2):133–135. DOI: 10.1055/s-0042-104405

34. Cavaco-Gomes J, Duarte C, Pereira E, et al. Prenatal ultrasound diagnosis of tessier number 7 cleft: case report and review of the literature. J Obstet Gynaecol 2017;37(4):421–427. DOI: 10.1080/01443615.2017.1285274

35. Miric Tesanic D, Merz E, Wellek S. Fetal lung volume measurements using 3D ultrasonography. Ultraschall Med 2011;32(4):373–380. DOI: 10.1055/s-0029-1245832

36. Merz E. 3D image of Siamese twins at12+3 gestational weeks. Ultraschall in Med 2013;34:109.

37. Pajkrt E, Jauniaux E. First-trimester diagnosis of conjoined twins. Prenat Diagn 2005;25(9):820–826. DOI: 10.1002/pd.1267

38. Merz E. 25 years of 3D ultrasound in prenatal diagnosis (1989-2014). Ultraschall Med 2015;36(1):3–8. DOI: 10.1055/s-0034-1398866

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