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(Radiology. 1999;211:447-451.)
© RSNA, 1999


Obstetric Imaging

Iliac Angle as a Marker for Down Syndrome in Second-Trimester Fetuses: CT Measurement1

Paula D. Zook, BA, Thomas C. Winter, III, MD and David A. Nyberg, MD

1 From the University of Washington School of Medicine, Seattle (P.D.Z.); the Department of Radiology, Division of Ultrasound, University of Washington Medical Center, Box 357115, 1959 NE Pacific Ave, Seattle, WA 98195-7115 (T.C.W.); and the Department of Ultrasound, Swedish Hospital Medical Center, Seattle, Wash (D.A.N.). From the 1997 RSNA scientific assembly. Received April 20, 1998; revision requested June 30; revision received August 20; accepted November 5. Address reprint requests to T.C.W.


    Abstract
 TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
PURPOSE: To determine if the iliac angle is greater in second-trimester fetuses with trisomy 21 than in euploid fetuses and to establish the best level and plane for measuring this angle by using three-dimensional computed tomography (CT).

MATERIALS AND METHODS: CT was performed in 18 formalin-preserved fetuses (eight trisomy 21, 10 euploid control fetuses), and the pelvic bone anatomy was reconstructed three-dimensionally. Iliac angles were measured in axial views at three levels in two planes. Data were analyzed nonparametrically with the Mann-Whitney test.

RESULTS: The mean gestational ages for trisomy 21 and control fetuses were 17.0 and 16.7 weeks, respectively. The external plane was the easiest to measure and the most reproducible. The mean iliac angles were significantly greater (P < .05) in the trisomy 21 fetuses than in the control fetuses and were as follows: superior level, 95.6° vs 76.4°; middle level, 84.5° vs 62.5°; and lower level, 78.1° vs 57.5°. With a 90° threshold, the superior iliac angle measurement had a sensitivity of 75%, a specificity of 89%, and an odds ratio of 24 for Down syndrome.

CONCLUSION: Second-trimester fetuses with trisomy 21 have a significantly greater iliac angle than euploid fetuses have. The iliac angle varies with the axial level, with the widest angle at the most superior level. Measurement of the iliac angle at the most superior level is supported as a potential marker for Down syndrome at prenatal ultrasonography.

Index terms: Computed tomography (CT), three-dimensional, 856.12117 • Down syndrome, 44.1841 • Fetus, abnormalities, 856.873 • Pelvis, measurement, 44.1211


    Introduction
 TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
A variety of ultrasonographic (US) findings have been associated with Down syndrome (trisomy 21) (113). These include both major anomalies, such as cardiac defects, and minor differences, such as increased nuchal thickening, echogenic bowel, renal pyelectasis, and echogenic intracardiac focus. Other minor findings are based on the differences between the bones of fetuses with trisomy 21 and the bones of normal fetuses, including shortened proximal long bones (femur and humerus), clinodactyly, and increased space between the first and second toes (sandal gap).

A widened iliac wing angle, as seen with conventional radiography, is a well-established feature of infants with Down syndrome (1416). Recently, an increased iliac angle has also been reported in second-trimester fetuses with trisomy 21 in studies in which prenatal US was used (1720). While these preliminary study findings suggest the potential value of a widened iliac angle as an additional marker for Down syndrome, the pelvic bones are complex in shape, and, to our knowledge the optimal plane and axial level for measuring the iliac angle have not been determined.

The purpose of this study was to determine if the iliac angle is greater in second-trimester fetuses with trisomy 21 than in euploid fetuses and to establish the optimal plane and level for measuring the iliac angle. Because of the complex shape of the pelvis, we used three-dimensional computed tomography (CT) as a tool for providing these answers.


    MATERIALS AND METHODS
 TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
We obtained 18 formalin-preserved fetuses (eight with trisomy 21, 10 euploid control fetuses) from our institution's (University of Washington, Seattle) birth defects laboratory. All of the fetuses had been previously characterized by karyotype and catalogued by gestational age, crown-rump length, sex, and any anomalies present. Fetuses were matched for gestational age; the mean gestational ages were 17.0 weeks (range, 15.9–18.0 weeks) for the trisomy 21 fetuses and 16.7 weeks (range, 14.4–18.0 weeks) for the euploid fetuses.

All fetuses were scanned with a HiSpeed Advantage CT scanner (GE Medical Systems, Milwaukee, Wis). Images were acquired with 1-mm collimation and 1-mm table increments in a craniocaudal direction throughout the entire fetus by using 120-kVp and 100-mA techniques. Three-dimensional images of the pelvic bones were obtained by using an Advantage Windows workstataion (GE Medical Systems) (Fig 1). Both maximum intensity projection and shaded-surface techniques were used.



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Figure 1a. Three-dimensional CT images of the pelvis demonstrate broad, laterally flared iliac wings (arrows) in (a) a fetus with trisomy 21 but not in (b) a euploid fetus.

 


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Figure 1b. Three-dimensional CT images of the pelvis demonstrate broad, laterally flared iliac wings (arrows) in (a) a fetus with trisomy 21 but not in (b) a euploid fetus.

 
The three-dimensional images were graphically rotated to obtain an axial view, and the angle between the right and left iliac wings was measured in both the internal and external (posterolateral) planes at three levels: superior, middle, and inferior. Angles were measured by using the graphic caliper on the computer. A true axial view was ensured by making all measurements when both iliac bones were of equal length and shape. All measurements and manipulations of the images were performed by the same examiner (P.D.Z.) with the same equipment. The examiner was blinded to the karyotype until completion of the measurements. Partially incomplete pelvic bone anatomy made it impossible to measure the angle at the inferior level in one fetus with trisomy 21 and the angle at both the inferior and superior levels in one euploid fetus.

Sensitivity, specificity, odds ratio, relative risk, and positive predictive value were calculated for the six measurements by using multiple cutoff points, and a receiver operating characteristic curve was generated for each of the six measurements to identify the optimal measurement. Data were analyzed nonparametrically by using the Mann-Whitney test, with a P value of less than .05 considered to indicate a significant difference.


    RESULTS
 TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Iliac angle measurements differed substantially depending on the level and plane of measurement, with the largest angles at the most cranial levels in the external plane and the smallest angles at the most caudal levels in the internal plane. The external plane was the easiest to measure and had the most reproducible measurements because the convex shape of the iliac wings allows for variation in the placement of a tangential line in the internal plane but makes the tangent more explicit in the external plane (Fig 2). By using the external plane, the mean iliac angle measurements for the trisomy 21 fetuses were as follows: superior level, 95.6°; middle level, 84.5°; and inferior level, 78.1° (Table 1). These measurements were significantly greater (P < .05) than the mean iliac angle measurements for the control fetuses: superior level, 76.4°; middle level, 62.5°; and inferior level, 57.5° (Fig 3).



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Figure 2a. Axial CT images of a euploid fetal pelvis at the middle level demonstrate iliac angles of (a) 69.5° in the external plane and (b) 47.2° in the internal plane. All measurements were obtained by placing a line (arrows) tangential to each iliac wing and measuring the angle between the lines at their intersection by using the graphic caliper on the computer.

 


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Figure 2b. Axial CT images of a euploid fetal pelvis at the middle level demonstrate iliac angles of (a) 69.5° in the external plane and (b) 47.2° in the internal plane. All measurements were obtained by placing a line (arrows) tangential to each iliac wing and measuring the angle between the lines at their intersection by using the graphic caliper on the computer.

 

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TABLE 1. Mean Iliac Angle Measurements
 


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Figure 3a. Axial CT images of the pelvis at the middle level in the external plane show iliac angles of (a) 89.6° in a fetus with trisomy 21 and (b) 69.5° in a euploid fetus, as measured at the intersection of the lines (arrows) tangential to each iliac wing.

 


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Figure 3b. Axial CT images of the pelvis at the middle level in the external plane show iliac angles of (a) 89.6° in a fetus with trisomy 21 and (b) 69.5° in a euploid fetus, as measured at the intersection of the lines (arrows) tangential to each iliac wing.

 
Table 2 summarizes the sensitivity and specificity for various angle thresholds at the middle and superior levels in the posterolateral plane. For the middle level, a 75° threshold showed the best balance of sensitivity (88%) and specificity (90%), whereas for the superior level, a threshold of 90° showed only a slightly lower sensitivity (75%) and specificity (89%).


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TABLE 2. Estimates of Sensitivity, Specificity, and Odds Ratio
 

    DISCUSSION
 TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Before karyotyping was available, pediatricians used physical characteristics to diagnose Down syndrome in children. Some of the most distinctive features in children with Down syndrome are radiographic differences in the pelvic bones, first described by Caffey and Ross in 1956 (14,15). Classic features observed in the frontal view include bilateral flattening of the iliac wings, elongated and tapered ischia, small acetabular angles, and bilateral widening and flaring of the iliac wings. Flaring of the iliac wings is due to rotation of the iliac wings toward the coronal plane at the sacroiliac joint (16). By measuring the acetabular and iliac angles on pelvic radiographs and by deriving from them the iliac index, Caffey and Ross (14,15) showed that this index was decreased in 70%–80% of children with Down syndrome.

The widened pelvis seen in newborns with trisomy 21 can also be detected in second-trimester fetuses (1720). The authors of several prenatal US studies (1720) have now evaluated the potential utility of widened iliac wings as a marker for Down syndrome by measuring the iliac angle on transverse views. While some variation is noted among studies, the findings of each study have shown that the iliac angle in fetuses with Down syndrome is significantly greater (P < .001) than the iliac angle in fetuses with a normal karyotype when measured during the second trimester (15–20 weeks). In a retrospective study of 19 fetuses with Down syndrome and 87 normal fetuses with a gestational age of 15–20 weeks, Kliewer et al (17) found that the mean iliac angle was 75° in fetuses with Down syndrome and 60° in normal fetuses. Similarly, in a retrospective study of 38 fetuses with Down syndrome and 46 control fetuses, Shipp et al (18) found a mean iliac angle of 78.8° ± 18.5 (SD) for Down syndrome fetuses and 66.9° ± 13.9 for normal fetuses. In two different prospective studies, Bork et al (19) found the mean iliac angle was 98.5° ± 11.3 for fetuses with Down syndrome and 68.2° ± 15.4 for normal fetuses, and Shipp et al (20) found an iliac angle of 80.1° ± 19.7 for fetuses with Down syndrome and 63.1° ± 20.3 for those with a normal karyotype.

It is interesting to compare results from the studies in which prenatal US was used with results from the current study in which CT and three-dimensional reconstruction of the pelvic bones were used. At the superiormost level, we found the mean iliac angle was 95.6° for trisomy 21 fetuses and 76.4° for normal fetuses. These measurements correlate closely with the results by Bork et al (19), who standardized their measurement of the iliac angle to the measurement at the superior aspect of the pelvis. They measured the iliac angle in the axial view at a level where both iliac bones were at their longest dimension and approximately equal in length. The retrospective studies by Kliewer et al (17) and Shipp et al (18) undoubtedly included a variety of levels, rather than only the superior level. The prospective study by Shipp et al (20), did not indicate whether the angle measurements were standardized to only the superior level.

The axial level of measurement clearly influences the iliac angle in the external plane. While in this study the iliac angle for fetuses with trisomy 21 was 95.6° at the superior level, this angle progressively narrowed to 84.5° at the middle level and 78.1° at the inferior level (Table 1). Similarly, for fetuses with a normal karyotype, the mean iliac angle varied between 76.4° and 57.5°, depending on the level of section. In a limited study of two fetuses, Shipp et al (18) also showed that the iliac angle varies greatly in any individual fetus, depending on the axial level of the image, with the widest angles being the most superior. While we found slightly greater sensitivity and specificity at the midpelvis, we support measurement of the pelvic angle at the superiormost level, as suggested by Bork et al (19), because measurement here should be easier to standardize at prenatal US.

To our knowledge, most studies have chosen a cutoff of 90° for determining whether the pelvis shows a widened iliac angle. Using a cutoff of 90°, Bork et al (19) reported a US detection rate of 91% for trisomy 21 and a false-positive rate of 5.5%. In contrast, using the same threshold, Shipp et al (20) reported a sensitivity of 36.8% and a false-positive rate of 12.8%. In the current study, we had a sensitivity of 75% and a false-positive rate of 11% at the superior level, but only 25% sensitivity and no false-positive findings at the middle level when we used the 90° threshold. Different results undoubtedly reflect variations in the method of measuring the iliac angle, including slight differences in the axial levels at which the measurements were made. In addition to the other variables, it is unknown whether the iliac angle measured at US is influenced by fetal position, such as anterior, posterior, or lateral orientation of the spine and pelvis.

While findings of each study have confirmed that fetuses with Down syndrome tend to show a wider iliac angle than fetuses with a normal karyotype, it remains uncertain whether this should be incorporated into a fetal survey when specifically searching for US markers of Down syndrome. In addition to the variability in sensitivity reported between centers, it is uncertain how often a widened iliac angle may be present as an isolated finding. Bork et al (19) reported that a widened iliac angle was the only US marker in two of 11 fetuses with trisomy 21 and that a third fetus showed only an echogenic intracardiac focus in addition to the widened iliac angle. Also, Shipp et al (20) reported that one of 19 fetuses with Down syndrome showed only a widened iliac angle (>90°) and that only two fetuses showed no US marker.

In summary, second-trimester fetuses with trisomy 21 have a significantly greater iliac wing angle than euploid fetuses have. However, the iliac angle progressively narrows from superior to inferior levels, making standardization of the axial level important. When it is used as a potential marker at prenatal US, we support measurement of the iliac angle at the superiormost level. As methods between centers will undoubtedly vary, each center may have to establish its own sensitivity and specificity for this measurement.


    Acknowledgments
 
We thank Paul Parsons, RT, and Charles Clute, RT, for their assistance with acquiring the CT images and Julie Mason, BS, for her help in acquiring the fetal specimens.


    Footnotes
 
Author contributions: Guarantors of integrity of entire study, P.D.Z., T.C.W.; study concepts, D.A.N., T.C.W.; study design, D.A.N., T.C.W., P.D.Z.; definition of intellectual content, P.D.Z.; literature research, P.D.Z.; clinical studies, P.D.Z., T.C.W.; data acquisition, P.D.Z.; data analysis, T.C.W.; statistical analysis, T.C.W.; manuscript preparation and review, P.D.Z.; manuscript editing, P.D.Z., T.C.W., D.A.N.


    References
 TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

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