Assessment of the gap between the fetal nasal bones at 11 to 13 + 6 weeks of gestation by three-dimensional ultrasound.

OBJECTIVE: To detect the presence of a gap between the fetal nasal bones at 11 to 13 + 6 weeks of gestation and to verify if this gap could lead to the erroneous diagnosis of absent nasal bone. METHODS: Three-dimensional (3D) ultrasound was used to assess the fetal nose in 450 singleton pregnancies, immediately after two-dimensional (2D) evaluation of the nasal bones and screening for chromosomal defects by a combination of maternal age and the measurement of fetal nuchal translucency at 11 to 13 + 6 (median, 12) weeks of gestation. A 3D volume of the fetal face was acquired and then analyzed using the multiplanar mode. A sequence of transverse views was used to confirm the presence or absence of the nasal bones and when they were present any visible gap between them was measured. A perfectly mid-sagittal plane was then examined to determine if the nasal bone was visible or not. RESULTS: In 421/450 (93.6%) cases the nasal bone was present during 2D ultrasound. Using the multiplanar mode of 3D ultrasound, in 83/421 (19.7%) fetuses a gap between the nasal bones could be demonstrated and in 36/83 (43.4%) cases the nasal bone was found to be absent in the perfect mid-sagittal view. In 29/450 (6.4%) cases the nasal bones were absent during the 2D scan. In the 3D assessment there was absence of both bones in 25/29 (86.2%) cases and absence of one of the two bones in 4/29 (13.8%) cases. Chorionic villus sampling demonstrated that the fetal karyotype was normal in 404 and abnormal in 46 cases, including 31 cases of trisomy 21. There was absence of one or both nasal bones in three (0.7%) of the chromosomally normal fetuses, in 19 (61.3%) with trisomy 21 and in seven (46.7%) with other chromosomal defects. CONCLUSIONS: At 11 to 13 + 6 weeks of gestation there is a gap between the nasal bones in about 20% of fetuses, and in about 40% of these cases in the perfect mid-sagittal plane the nasal bone may erroneously be considered to be absent.     

A histological and radiological investigation of the nasal bone in fetuses with Down syndrome.

OBJECTIVES: Previous studies of nasal bone development in Down syndrome have used radiographs or ultrasound for the detection of nasal bone length or nasal bone absence. The aim of this study was to investigate the presence and size of the nasal bones in postmortem Down syndrome fetuses by means of radiographs and histological examination. METHODS: Thirty-three aborted human fetuses (gestational age 14-25 weeks) with Down syndrome were included. A mid-sagittal tissue block was excised from the skull base to the foramen magnum and along the lateral aspect of the spine. Radiographs of the tissue block were taken in lateral, frontal and axial projections. The length of the nasal bone was measured. The tissue blocks were cut in serial sections and stained. The crown-rump length (CRL), foot length (FL) and number of ossified bones in the hand and foot (CNO) were recorded. RESULTS: A total of 8/33 fetuses had bilateral nasal bone absence and two had unilateral absence. In fetuses with radiographically diagnosed nasal bone absence, no nasal bone could be found histologically. The majority of the Down syndrome fetuses had CRL, FL and CNO values within the range of those for normal age-matched fetuses. Nasal bone length was normal or reduced. CONCLUSIONS: Absence of the nasal bone was registered by postmortem examination in one-third of fetuses with Down syndrome. In some fetuses this could be a result of delayed maturation associated with Down syndrome. The phenotypic differences in nasal bone appearance may reflect genotypic differences in the Down syndrome group.     

Comparison of fetal nasal bone assessment by ultrasound at 11-14 weeks and by postmortem X-ray in trisomy 21: a prospective observational study.

OBJECTIVE: To compare nasal bone assessment by ultrasound examination at 11-14 weeks' gestation and postmortem X-ray examination in fetuses with trisomy 21. METHODS: Twenty-one fetuses with trisomy 21 which had undergone sonographic examination at 11-14 weeks for measurement of nuchal translucency thickness and assessment of the nasal bones were examined by postmortem X-ray following termination of pregnancy. RESULTS: The nasal bones were absent in 11/21 (52.4%) fetuses on ultrasound examination at 11-14 weeks and in 10/21 (47.6%) fetuses on X-ray examination at 14 to 25 + 5 weeks. Ultrasound and X-ray findings were discordant in 9/21 (42.9%) cases. Eight of 11 (72.7%) fetuses with absent nasal bones on ultrasound examination had a nuchal translucency thickness > 95th centile. CONCLUSION: The high incidence of absent nasal bones in first-trimester fetuses with trisomy 21 is compatible with a developmental delay. Prior to inclusion of nasal bone assessment into risk calculation for trisomy 21, the independence of absence of nasal bones by ultrasound and increased nuchal translucency above the 95th centile at 11-14 weeks should be investigated more extensively.     

Phenotypic characteristics of absent and hypoplastic nasal bones in fetuses with Down syndrome: description by 3-dimensional ultrasonography and clinical significance.

OBJECTIVE: To determine the frequency and clinical significance of bilateral and unilateral hypoplastic nasal bones for the detection of Down syndrome by 3-dimensional ultrasonography. METHODS: Thirty-seven volumes of the fetal skull from fetuses with Down syndrome and 37 from fetuses without abnormalities were analyzed by 1 investigator blinded to fetal karyotype. The maximum intensity projection algorithm was used to reconstruct nasal bones. Ossification patterns were identified in anteroposterior and profile views. Sensitivity, false-positive rates (FPRs), and likelihood ratios (LRs) for detection of Down syndrome were calculated. RESULTS: After exclusions (coronal acquisition [n = 11], hand in front of the face [n = 4], poor imaging [n = 2], incomplete follow-up [n = 2], and anomalies detected after delivery [n = 2]), 53 volumes were analyzed (26 fetuses with Down syndrome and 27 without abnormalities; median gestational age, 21 6/7 weeks [interquartile range, 19 6/7-25 2/7 weeks]). Rendered profile views revealed absent nasal bones in 18.9% (10 of 53) of the fetuses, and, among these, 90% (9 of 10) had Down syndrome (sensitivity, 34.6% [9 of 26]; FPR, 3.7% [1 of 27]; LR, 9.3 [95% confidence interval (CI), 1.3-68.7]). Three ossification patterns were identified in anteroposterior views: (1) normally developed, (2) delayed ossification, and (3) absent nasal bones. Sensitivity, FPR, and LR of absent nasal bones for detecting Down syndrome were 34.6% (9 of 26), 3.7% (1 of 27), and 9.0 (95% CI, 1.3-68.7), respectively. Sensitivity, FPR, and LR of delayed ossification for detecting Down syndrome were 42.3% (11 of 26), 22% (6 of 27), and 1.83 (95% CI, 0.8-4.4). CONCLUSIONS: Absence of nasal bones is associated with the highest risk of Down syndrome. Delayed ossification is associated with a lower risk of Down syndrome than absent nasal bones. These ossification patterns may be indistinguishable on 2-dimensional ultrasonography.     

产前超声评估胎儿颜面轮廓及相关遗传学疾病

目的 探讨产前超声评估胎儿颜面轮廓的可行性及对胎儿遗传学疾病的提示价值.方法 应用产前二维及三维超声观察20胎胎儿的颜面正中矢状面,评估颜面轮廓异常,并与染色体分析结果进行对照.结果 发现9胎21-三体、4胎18-三体、1胎13-三体和1胎4p-,5胎染色体正常.20胎中,鼻骨缺失或发育不良共8胎(6胎21-三体,2胎染色体正常);鼻前组织增厚9胎(8胎21-三体,1胎4p-);小下颌8胎(4胎18-三体,1胎21-三体,1胎13-三体,1胎4p-及1胎染色体正常);颜面扁平5胎(2胎21-三体,2胎Larsen综合征,1胎染色体正常);上颌前突2胎(1胎13-三体,1胎18-三体).结论 颜面正中矢状面有助于提示胎儿染色体异常及遗传综合征,其中鼻骨及下颌评估对21-三体及18-三体的提示意义明确,可作为中孕期筛查的常规内容.     

中晚孕期胎儿鼻骨异常预测21-三体

目的 评价中晚孕期胎儿鼻骨异常对21-三体的诊断价值。方法 分析在我院接受胎儿产前超声检查的5460名孕妇的资料,以常规超声检查胎儿及其附属物,如发现胎儿鼻骨异常,行羊膜腔穿刺或抽取脐带血进行染色体核型分析。结果 共发现10胎鼻骨异常。4胎鼻骨缺失,其中1胎骨骼发育障碍,染色体正常;余3 胎均为21-三体合并心脏或其他系统异常。6胎鼻骨发育不良,表现为鼻骨短小、一侧鼻骨缺失或鼻骨骨化不良,其中1胎为21-三体合并其他系统异常;1胎为地中海贫血,染色体正常;余4胎未合并其他系统异常,为孤立性鼻骨发育不良,染色体正常。结论 鼻骨缺失是21-三体的超声常见表现,但孤立性鼻骨发育不良对21-三体的诊断价值需要进一步探讨。     

Three-dimensional evaluation of mid-facial hypoplasia in fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation.

OBJECTIVE: To investigate the mid-facial hypoplasia of fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation, by three-dimensional (3D) evaluation of the maxilla and the nasal bones. METHODS: A 3D volume of the fetal head was obtained before fetal karyotyping at 11 + 0 to 13 + 6 (median 12) weeks of gestation in 80 fetuses that were subsequently found to have trisomy 21 and in 862 fetuses subsequently found to be chromosomally normal. The multiplanar mode was used to obtain a sequence of transverse views of the fetal face and to demonstrate the maxilla, the adjacent rami of the mandible and the nasal bones. The maxillary depth, defined as the distance between the alveolus of the maxilla in the midline anteriorly and the midpoint of the line joining the rami posteriorly, was measured. Ossification of the nasal bones was considered to be normal if both bones were more echogenic than the overlying skin. RESULTS: In the chromosomally normal group the maxillary depth increased linearly with crown-rump length (CRL) from 3.1 mm at a CRL of 45 mm to 4.8 mm at a CRL of 84 mm, and in the trisomy 21 fetuses the depth was significantly smaller than normal (mean difference = - 0.3 mm, P < 0.001). There was no significant association between the delta maxillary depth and delta nuchal translucency thickness in either the trisomy 21 or the chromosomally normal fetuses. Impaired ossification of the nasal bones was observed in 3.1% of the chromosomally normal fetuses and in 60.0% of those with trisomy 21. The mean maxillary depth was significantly smaller in fetuses demonstrating impaired ossification than in those with normal ossification of the nasal bones (mean difference = -0.2 mm; 95% CI, -0.3 to -0.1, P = 0.001). CONCLUSIONS: In a high proportion of fetuses with trisomy 21 there is sonographic evidence of mid-facial hypoplasia at 11 + 0 to 13 + 6 weeks of gestation.     

Nasal bone hypoplasia in trisomy 21 at 15-22 weeks' gestation.

OBJECTIVE: To investigate the potential value of ultrasound examination of the fetal profile for present/hypoplastic fetal nasal bone at 15-22 weeks' gestation as a marker for trisomy 21. METHODS: This was an observational ultrasound study in 1046 singleton pregnancies undergoing amniocentesis for fetal karyotyping at 15-22 (median, 17) weeks' gestation. Immediately before amniocentesis the fetal profile was examined to determine if the nasal bone was present or hypoplastic (absent or shorter than 2.5 mm). The incidence of nasal hypoplasia in the trisomy 21 and the chromosomally normal fetuses was determined and the likelihood ratio for trisomy 21 for nasal hypoplasia was calculated. RESULTS: All fetuses were successfully examined for the presence of the nasal bone. The nasal bone was hypoplastic in 21/34 (61.8%) fetuses with trisomy 21, in 12/982 (1.2%) chromosomally normal fetuses and in 1/30 (3.3%) fetuses with other chromosomal defects. In 3/21 (14.3%) trisomy 21 fetuses with nasal hypoplasia there were no other abnormal ultrasound findings. In the chromosomally normal group hypoplastic nasal bone was found in 0.5% of Caucasians and in 8.8% of Afro-Caribbeans. The likelihood ratio for trisomy 21 for hypoplastic nasal bone was 50.5 (95% CI 27.1-92.7) and for present nasal bone it was 0.38 (95% CI 0.24-0.56). CONCLUSION: Nasal bone hypoplasia at the 15-22-week scan is associated with a high risk for trisomy 21 and it is a highly sensitive and specific marker for this chromosomal abnormality.     

First‐Trimester Assessment of the Nasal Bones Using the Retronasal Triangle View

Objective. The purpose of this study was to evaluate a new sonographic technique for identifying the nasal bones using the retronasal triangle view, ie, the coronal plane at which the palate and frontal processes of the maxilla are simultaneously visualized. Methods. Three‐dimensional (3D) volumes were acquired from women undergoing first‐trimester sonographic screening for aneuploidy by 2 accredited operators. Those data sets in which the fetal face was clearly identified were selected for offline analysis by 2 other observers who were unaware of the sonographic or clinical findings. The nasal bones were classified as both present, only 1 present (right or left), or absent according to the presence or absence of 2 small paired echogenic linear structures at the upper tip of the retronasal triangle as determined by 3D navigation in the coronal plane and compared to those findings obtained by 3D navigation in the sagittal plane. Additional 3D data sets involving a subset of 4 first‐trimester fetuses with trisomy 21 and absent nasal bones were also analyzed retrospectively and included randomly in the study group. Results. A total of 110 3D data sets were analyzed, of which 86% were obtained transabdominally and 14% transvaginally. The quality of nasal bone identification was classified subjectively by the observers as good in 67% of cases, fair in 29%, and poor in 4%. The nasal bones were classified as at least 1 present in 106 of the cases (96%) and absent in 4 (4%), with complete agreement between observers in both the sagittal and coronal planes (κ = 1). Discrimination between the right and left nasal bones was possible in 89% and 93% for observer A and in 96% and 96% for observer B by assessing the sagittal and coronal views, respectively (right nasal bone: κ = 0.90 [95% confidence interval (CI), 0.79–1]; left nasal bone: κ = 0.85 [95% CI, 0.60–0.99]). The nasal bones were not identified at the level of the retronasal triangle view in any of the fetuses with trisomy 21 and absent nasal bones. Conclusions. This study shows that the nasal bones can be confidently identified as paired echogenic structures located at the upper tip of the retronasal triangle. This coronal view of the fetal face offers the possibility of screening for the presence or absence of the nasal bones in the first trimester, especially when the standard midsagittal views of the fetal face are suboptimal because of fetal or maternal factors. Because both nasal bones can be evaluated simultaneously in the coronal plane, the retronasal triangle view may be advantageous over the conventional midsagittal view assessment, in which only 1 of the 2 nasal bones is evaluated.     

Fetal nose bone length: a marker for Down syndrome in the second trimester.

OBJECTIVE: To evaluate the significance of nasal bone length in relation to the detection of Down syndrome in the second trimester. METHODS: We evaluated consecutive fetuses referred to our facility between 15 and 20 weeks' gestation for sonography and amniocentesis because of an increased risk of aneuploidy. A detailed structural survey, biometric measurements, and measurement of the nasal bone were obtained at the time of amniocentesis and subsequently compared with karyotype. The characteristics of the fetuses with Down syndrome were compared with those of the euploid fetuses. RESULTS: A total of 239 fetuses were evaluated. Sixteen fetuses (7%) had Down syndrome, and 223 were euploid. In fetuses with Down syndrome, 6 (37%) of 16 did not have detectable nose bones, compared with 1 (0.5%) of 223 control fetuses, yielding a likelihood ratio of 83. Detectable nasal bones were seen in 10 fetuses with Down syndrome and 222 euploid fetuses. A receiver operating characteristic curve for the biparietal diameter-nasal bone length ratio showed that a value of 9 or greater detected 100% of fetuses with Down syndrome and 22% of euploid fetuses. If the ratio were 10 or greater, then 81 % fetuses with Down syndrome and 11 % of euploid fetuses would have been identified. If the ratio were 11 or greater, 69% of fetuses with Down syndrome would be identified, compared with 5% of euploid fetuses. CONCLUSIONS: The absence of a nasal bone is a powerful marker for Down syndrome. A short nasal bone is associated with an increased likelihood for fetal Down syndrome in a high-risk population.     

中晚孕期胎儿鼻骨缺失及染色体异常的超声诊断分析

目的：探讨孕16-34周超声筛查胎儿鼻骨缺失在染色体异常诊断中的应用价值。方法2008至2013年中晚孕期在北京协和医院超声筛查发现鼻骨缺失的20例胎儿均行染色体检查并随访至引产或出生后,总结胎儿鼻骨缺失超声声像图特征。结果20例胎儿产前超声显示：（1）双侧鼻骨缺失17例,面部正中矢状切面及横切面扫查均不能显示鼻梁皮肤下方的鼻骨强回声。其中5例胎儿合并多发畸形：4例胎儿心脏畸形（房室间隔缺损3例,房室间隔缺损合并大血管异常1例）,1例胎儿十二指肠梗阻。其他微小结构异常包括：股骨及肱骨短,肠管回声增强,迷走右锁骨下动脉,单侧侧脑室临界增宽,双肾盂轻度增宽,吐舌征,双手姿势形态异常。（2）单侧鼻骨缺失3例,面部横切面扫查仅能显示胎儿一侧鼻骨强回声。其中2例合并心脏畸形（房室间隔缺损1例,室间隔缺损1例）;合并其他微小结构异常包括：股骨及肱骨短,肠管回声增强,颈背部皮肤增厚。（3）染色体检查：17例双侧鼻骨缺失胎儿中9例为21-三体,1例为4p-（Wolf-Hirschhorn综合征）,7例为正常核型;3例单侧鼻骨缺失胎儿中2例为21-三体,1例为正常核型。（4）产后检查及随访：20例胎儿超声及染色体检查后引产12例（尸检1例）,出生8例,5例随访无明显异常,3例失访;12例胎儿产前超声与产后检查结果均符合。结论中晚孕期鼻骨缺失胎儿超声图像特征为双侧或单侧鼻骨强回声缺失,且多伴微小结构异常,超声检出胎儿鼻骨缺失应行染色体核型分析,减少21-三体等染色体异常胎儿的出生。     

Metopic suture in fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation.

OBJECTIVE: To investigate the development of the frontal bones and metopic suture in fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation. METHODS: Three-dimensional (3D) ultrasound was used to measure the height of and gap between the frontal bones in 75 fetuses with trisomy 21 and these were compared to the measurements in 200 normal fetuses at 11 + 0 to 13 + 6 (median, 12 + 6) weeks of gestation. RESULTS: In the fetuses with trisomy 21, compared to the normal fetuses, there was no significant difference in either the height of the frontal bones (mean difference 0.16 SD, range -1.78 to 2.17 SD; P = 0.369) or the gap between them (mean difference 0.012, 95% CI -0.073 to 0.097; P = 0.780). Additionally, within the group of trisomy 21 fetuses there were no significant differences in the development of the frontal bones and metopic suture between those with absent (n = 46) and those with present (n = 29) nasal bone. CONCLUSIONS: In trisomy 21 the development of the frontal bones and metopic suture is as normal and is independent from the development of the nasal bones.     

The nasal bone in fetuses with trisomy 21: sonographic versus pathomorphological findings.

OBJECTIVE: To compare the sonographic findings of the nasal bone in fetuses with trisomy 21 with pathomorphological findings to determine whether the bone is truly absent. METHODS: Seventeen first-trimester fetuses with trisomy 21 were identified; the median gestational age was 12 weeks (range, 11-14) and the median maternal age was 38 (range, 27-47) years. Transabdominal ultrasound examination, preceding transabdominal chorionic villus sampling (TA-CVS) for karyotyping, included assessment of the fetal nose. The nasal bone was determined to be 'hypoplastic' or 'absent' and its length was measured. All pregnancies underwent termination after diagnosis. Serial sagittal sectioning with hematoxylin and eosin-staining of formalin fixed tissue was performed. RESULTS: Of the 17 cases, the nasal bone was sonographically evident, but with severe hypoplasia in 10 cases, absent in six, and in the remaining case it was not able to be assessed due to fetal position. Histomorphologically, in 16 cases a nasal bone was present, detectable by the evidence of an ossification center, and in one case the ossification structure was not clearly visualized. Retrospective review of ultrasound images could identify nasal bones in five of the six cases in which they were initially reported as being absent on ultrasound examination. These were visible, but less distinct and had decreased echogenicity, hence misinterpretation led to the false finding of an absent nasal bone when it was in fact present but hypoplastic. CONCLUSION: Sonographic assessment of the fetal nasal bone should not distinguish between 'present' and 'absent', but instead between 'normal' and 'hypoplastic'. For reproducible results it is necessary to standardize the sonographic examination. The sonographic landmarks of the fetal nose are: the nasal bone, the skin above and the cartilaginous tip of the nose.     

Intra- and interoperator variability in fetal nasal bone assessment at 11-14 weeks of gestation.

OBJECTIVES: Examination of the fetal nasal bones by ultrasound between 11 and 14 weeks of gestation has been proposed as an additional tool in the detection of trisomy 21 in a high-risk population. However the variability in the identification of fetal nasal bones by ultrasound has not yet been investigated. The aim of this study was to assess the intraobserver and interobserver reproducibility of fetal nasal bone identification by ultrasound between 11 and 14 weeks of gestation. METHODS: A total of 1040 consecutive ultrasound examinations were performed at 11-14 weeks of gestation for nuchal translucency (NT) measurement and nasal bone identification by ultrasound. A total of 657 consecutive video-loops were assessed by three experienced operators. Each operator assigned cases to one of three categories, namely present, uncertain or absent nasal bones, and the results were compared between operators. To assess the intraoperator variability each operator reviewed 100 randomly selected videos out of the 657 loops and again used the same classification. Results were compared by pairwise unweighted and weighted Kappa index to evaluate the inter- and intraoperator variability. RESULTS: Among the 1040 fetuses, there were 51 (4.9%) with an NT measurement above the 95th centile. Nasal bones were identified by ultrasound in 948, not seen in eight and impossible to assess in 84 fetuses. Four fetuses had trisomy 21 including three with absent nasal bones and increased NT and one with present nasal bones and normal NT. The Kappa and weighted Kappa values for interoperator variability between the three operators were between 0.26 and 0.37 and 0.33 and 0.44, respectively. The Kappa and weighted Kappa values for intraoperator variability were between 0.35 and 0.48 and 0.43 and 0.55, respectively. CONCLUSION: The assessment of fetal nasal bones is only fairly reproducible. Although the performance of the test in fetuses at high risk for trisomy 21 has been reported to be good, its implementation as an additional screening technique in the general population must be accompanied by teaching and quality control programs.     

Three-dimensional sonographic description of abnormal metopic suture in second- and third-trimester fetuses.

OBJECTIVE: To describe patterns of abnormal development of the metopic suture in association with fetal malformations during the second and third trimesters of pregnancy. METHODS: This was a cross-sectional study of the frontal bones and metopic suture in 11 fetuses at 17-32 weeks of gestation. Cases were selected because there were obvious abnormalities in the metopic sutures. In each case, a malformation was detected by two-dimensional (2D) ultrasound and the abnormality of the metopic suture was detected and evaluated on three-dimensional (3D) ultrasound, using transparent maximum mode. RESULTS: There were essentially four patterns of abnormality in the metopic suture: firstly, delayed development with a V- or Y-shaped open suture, which is found in normal fetuses at 12-16 weeks; secondly, a U-shaped open suture, presumably due to upward growth of the frontal bones with delayed closure; thirdly, premature closure of the suture, which is normally observed after 32 weeks; fourthly, the presence of additional bone between the frontal bones. Premature closure of the suture or additional bone between the frontal bones was observed in fetuses with holoprosencephaly and abnormalities of the corpus callosum, whereas the V-, Y- and U-shaped metopic sutures were observed in fetuses with facial defects involving the orbits, nasal bones, lip, palate and mandible, in the absence of holoprosencephaly and abnormal corpus callosum. CONCLUSIONS: This preliminary study describes the pattern of possible abnormalities of the metopic suture and should stimulate further investigation to establish the prevalence and evolution of abnormal sutures as well as the incidence and pattern of other associated defects.     

Screening for trisomy 21 during the routine second-trimester ultrasound examination in an unselected Chilean population.

OBJECTIVE: To evaluate the performance of a detailed ultrasound examination during the second trimester as a screening test for Down syndrome in an unselected Chilean population. METHODS: This was part of an ongoing longitudinal study. Included were 3071 women with singleton pregnancies who underwent routine ultrasound examination between 21 + 0 and 25 + 6 gestational weeks as a screening test for chromosomal abnormalities and major congenital structural defects, and who were diagnosed as having trisomy 21 or being chromosomally normal. Maternal age, and eight soft markers and cardiac defects associated with Down syndrome were evaluated as a screening test using logistic regression analysis. RESULTS: The incidence of Down syndrome was 0.6%, and the mean maternal age was 29.4 +/- 6.2 years. At least one of four soft markers (absent nasal bone, nuchal edema, short femur, echogenic foci) and/or cardiac defects was present in 77.8% of Down syndrome fetuses and in 3.1% of normal fetuses. Furthermore, with a false-positive rate of 1%, the detection rate using the combined model of ultrasound markers and maternal age was 72.2%. CONCLUSIONS: Second-trimester ultrasound markers are able to detect over 70% of Down syndrome fetuses with only a 1% false-positive rate.     

Three-dimensional ultrasound in the prenatal diagnosis of cleidocranial dysplasia associated with B-cell immunodeficiency.

A patient with a singleton pregnancy was referred for three-dimensional ultrasonography (3DUS) at 18 + 3 weeks for suspected hypomineralization of the skull bones and absence of the nasal bones. Three-dimensional rendered images of the fetal skull revealed widening of the coronal sutures, absence of the squamous portion of the temporal bone, and absence of the occipital bone, except for two areas of ossification. In addition, a fractured right clavicle was identified. The remainder of the fetal anatomy was normal and biometry was appropriate for gestational age. Genetic amniocentesis revealed a 46,XX fetal karyotype. Family history was positive for a 5-year-old sibling with an open anterior fontanelle. Cleidocranial dysplasia was suspected. A female neonate was delivered by elective repeat Cesarean section at 40 + 3 weeks of gestation without complications and discharged home 3 days after delivery. Prenatal diagnosis was confirmed by physical and radiological evaluation.The infant died at 8 weeks of age due to respiratory syncytial virus pneumonia secondary to B-cell deficiency. RUNX2 mutations were not detected by molecular analysis. There are three relevant aspects to this case: (1) clear visualization of the widened fontanelles and hypomineralized occipital bones was possible with the use of 3DUS; (2) a clavicular fracture was identified in utero with combined high-resolution two-dimensional and 3DUS; and (3) although absence of the nasal bones is most commonly observed in fetuses with chromosomal disorders (e.g. trisomy 21 and trisomy 18), a careful examination of the skeleton should be considered in fetuses with absent nasal bones and a normal karyotype.     

唐氏综合征胎儿鼻骨的超声研究

目的探讨唐氏综合征(又称21三体综合征)与胎儿鼻骨发育不良的关系。方法产前超声测量901例正常中孕期及570例中孕期唐氏综合征高风险胎儿鼻骨,并对22例引产胎儿的鼻骨行X线检查及大体解剖观察。结果1471例胎儿鼻骨超声检测成功率96%(1413例)。22例唐氏综合征胎儿中,产前超声诊断鼻骨缺失1例,鼻骨发育不良(测值小于2.5mm,包括1例鼻骨缺失)11例。结论唐氏综合征胎儿与鼻骨发育不良有密切关系。     

Metopic suture in fetuses with Apert syndrome at 22-27 weeks of gestation.

OBJECTIVES: To examine the possible association of skull deformity and the development of the cranial sutures in fetuses with Apert syndrome. METHODS: Three-dimensional (3D) ultrasound was used to examine the metopic and coronal sutures in seven fetuses with Apert syndrome at 22-27 weeks of gestation. The gap between the frontal bones in the transverse plane of the head at the level of the cavum septi pellucidi was measured and compared to findings in 120 anatomically normal fetuses undergoing routine ultrasound examination at 16-32 weeks. RESULTS: In the normal group, the gap between the frontal bones in the metopic suture at the level of the cavum septi pellucidi, decreased significantly with gestation from a mean of 2.2 mm (5th and 95th centiles: 1.5 mm and 2.9 mm) at 16 weeks to 0.9 mm (5th and 95th centiles: 0.3 mm and 1.6 mm) at 32 weeks. In the seven cases with Apert syndrome, two-dimensional ultrasound examination demonstrated the characteristic features of frontal bossing, depressed nasal bridge and bilateral syndactyly. On 3D examination there was complete closure of the coronal suture and a wide gap in the metopic suture (15-23 mm). CONCLUSION: In normal fetuses, cranial bones are believed to grow in response to the centrifugal pressure from the expanding brain and proximity of the dura to the suture is critical in maintaining its patency. In Apert syndrome, the frontal bossing may be a mere consequence of a genetically predetermined premature closure of the coronal suture. Alternatively, there is a genetically predetermined deformation of the brain, which in turn, through differential stretch of the dura in the temporal and frontal regions, causes premature closure of the coronal suture and impaired closure of the metopic suture.     

Contribution of three-dimensional computed tomography in the assessment of fetal skeletal dysplasia.

OBJECTIVE: To compare the diagnostic accuracy of two-dimensional (2D) ultrasound and three-dimensional (3D) computed tomography (CT) for the diagnosis of fetal skeletal anomalies. METHODS: Eleven pregnant women underwent 2D ultrasound and 3D-CT. Ten fetuses presented skeletal anomalies on 2D ultrasound and one fetus had a normal ultrasound exam but a familial history of osteopetrosis. We compared retrospectively the diagnoses established on 2D ultrasound and 3D-CT with the neonatal and/or postmortem work-up, which were used as the gold standard. RESULTS: 2D ultrasound provided the correct diagnosis in only two of the 11 cases. CT yielded the correct diagnosis in eight; in six of these, 2D ultrasound had been inconclusive. 3D-CT was more accurate than was 2D ultrasound in visualizing vertebral anomalies (abnormal shape of the vertebral bodies, abnormal interpedicular distance), pelvic bone malformations (delayed ossification of the pubic bones, abnormal acetabular shape) and enlarged metaphysis or synostoses in long bones. In three cases, neither 2D ultrasound nor CT provided the correct diagnosis. CONCLUSION: In this series, which included a variety of skeletal dysplasias, 3D-CT had a better diagnostic yield than did 2D ultrasound. Both imaging techniques are useful in the management of fetal dysplasia; 2D ultrasound is a useful screening test and 3D-CT is a valuable complementary diagnostic tool.