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Ultrasound images of a normal fetus (a) and a fetus with trisomy 21 (b) showing nasal bone length (caliper 1) and prenasal thickness (caliper 2) measurements.
Source publication
To study the ratio of prenasal thickness (PT) to nasal bone length (NBL) in normal and trisomy-21 fetuses in the second and third trimesters of pregnancy.
The PT and NBL were measured retrospectively in 106 normal fetuses (in three-dimensional (3D) volumes) and in 30 fetuses with trisomy 21 (10 on two-dimensional (2D) images and 20 in 3D volumes)....
Contexts in source publication
Context 1
... and volumes were stored and examined either offline on 4D View software version 7.0 (GE Medical Systems) or on stored images in the GE ultrasound system. The nasal bone was measured from the nasion -defined as the most anterior point of the junction between the frontal and nasal bones -to the distal end of the white ossification line (Figure 1). Care was taken not to include the frontal bone in the measurement as the frontal bone extends posteriorly of the nasal bone 9 .PT was measured as the shortest distance between the nasion (same landmark as used for measuring the NBL) and the frontal skin (Figure 1). ...
Context 2
... nasal bone was measured from the nasion -defined as the most anterior point of the junction between the frontal and nasal bones -to the distal end of the white ossification line (Figure 1). Care was taken not to include the frontal bone in the measurement as the frontal bone extends posteriorly of the nasal bone 9 .PT was measured as the shortest distance between the nasion (same landmark as used for measuring the NBL) and the frontal skin (Figure 1). Calipers were placed on the outermost borders of the skin or bone, and the mean of three measurements was used for analysis. ...
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Citations
... However, this marker has differences in the normal ranges among races and ethnicities [8,11,12], and when using reference ranges from other countries the detection rate has been found to be lower than expected in Asians [23]. Recently, the PT to NBL (PT/NBL) ratio has been widely reported as the most effective sonomarker for Down syndrome screening [7,10,11,[24][25][26]. These studies reported detection rates of PT/NBL for Down syndrome of 86-100%. ...
... These studies reported detection rates of PT/NBL for Down syndrome of 86-100%. However, there is only one study from Asia, which was done in Chinese women, which found a lower detection rate of 46% for PT/NBL for Down syndrome screening when using 3D ultrasound [15], although the mean PT/NBL ratio in euploid fetuses and cut-off for Down syndrome screening were different from previous studies [7,12,15,24,25]. ...
... Our study found as in other studies that a facial profile view of a fetus using a 2D ultrasound scan during the second trimester was not difficult to perform and could be done with a high level of reproducibility [11,16] and high inter-and intra-observer agreements. A previous study reported that measuring facial ultrasound markers with 2D ultrasound as a screening protocol in the clinic had a comparable efficacy with 3D ultrasound [25]. However the use of 3D ultrasound can be limited in a difficult circumstance such as a low level of amniotic fluid [27], and if acquisition of a midsagittal facial plane image is not accomplished, the NBL measurement may be overestimated [28]. ...
Background
To establish the reference ranges and evaluate the efficacy of the fetal facial sonomarkers prenasal thickness (PT), nasal bone length (NBL), PT/NBL ratio and NBL/PT ratio for Down syndrome screening in the second trimester of high-risk pregnancies using two-dimensional (2D) ultrasound.
Methods
A prospective study was done in Thai pregnant women at high risk for structural and chromosomal abnormalities between May 2018 and May 2019. The main exclusion criteria were any fetal anatomical anomaly detected on ultrasonography or postpartum examination, abnormal chromosome or syndrome other than Down syndrome. Ultrasounds were performed in 375 pregnant women at 14 to 22 weeks’ gestation and the fetal facial parameters were analyzed. Down syndrome results were confirmed by karyotyping. The reference ranges of these facial ultrasound markers were constructed based on the data of our population. The Down syndrome screening performance using these facial ultrasound markers was evaluated.
Results
In total, 340 euploid fetuses and 11 fetuses with Down syndrome met the inclusion criteria. The PT, NBL, and PT/NBL ratios in the euploid fetuses gradually increased with gestation progression while the NBL/PT ratio gradually decreased between 14–22 weeks’ gestation. The NBL, PT/NBL ratio, and NBL/PT ratio all had 100% sensitivity and PT had 91% sensitivity. These facial markers had 100% negative predictive value for Down syndrome screening in the second trimester. The Bland–Altman analysis showed the intra- and inter-observer variations of PT and NBL had high intraclass correlation coefficients (ICC) in both operators, with ICCs of 0.98 and 0.99 and inter-observer ICCs of 0.99 for both operators.
Conclusion
The facial ultrasound markers are very useful for second trimester Down syndrome screening in our population. These facial ultrasound markers were easily identifiable and highly consistent either intra- or inter-operator by using widely-available 2D ultrasound. However, the reference ranges for these markers need to be constructed based on individual populations.
Trial registration
Registration number: REC 61–029-12–3. Date of registration: 18 May 2018.
... In subsequent studies, the PT/NBL ratio was reported to be the most effective facial sonomarker for Down syndrome screening in the second trimester, with a detection rate of 86-100%. [3,4,13,14] On the other hand, the normal ranges of these ultrasonographic markers may differ between races and ethnicities. A study of Chinese women reported 46% of lower detection rate for the PT/NBL ratio in Down syndrome screening. ...
... In only 1 (0.4%) of 242 fetuses, the PT/NBL ratio was above 0.8, which was defined as the cutoff value for predicting Down syndrome in the previous studies. [4,14] This fetus had an increase in PT without nasal bone hypoplasia. On the other hand, nasal bone hypoplasia was detected in 2.1% (n=5) of fetuses. ...
... This finding was similar to the results of the previous studies conducted in the European population. [4,14] On the other hand, in an Asian study, the PT/NBL ratio increased gradually during the second trimester. [3] Moreover, the threshold values for NBL, PT, and PT/NBL ratio in both the European and Asian population were different from those in our study. ...
... This space was 7 mm at 21 weeks (corresponding to >95th percentile [Levaillant et al., 2005 Dec]) during the scan examination in the first pregnancy and 4.6 mm at 17 weeks (corresponding to >95th percentile (Levaillant et al., 2005) during the scan performed in the second pregnancy ( Figure 1a). The thickness of the prefrontal space has been described in the literature as an ultrasound marker of Down's syndrome (De Jong-Pleij et al., 2012;Persico et al., 2008). However, it represents a non-specific ultrasound sign, which is also common to different genetic diseases. ...
Background
Rhizomelic chondrodysplasia punctata (RCDP) is a clinical entity resulting from defects of peroxisomal metabolism whose clinical phenotype is characterized by rhizomelia, calcified foci in periarticular cartilage, coronal lesions of vertebral bodies, cataracts and severe cognitive delay. Usually, survival does not exceed the first decade of life. Transmission is autosomal recessive and is related to mutations in the PEX7, GNPAT or AGPS.
Methods
A detailed description of the prenatal ultrasound signs of RCDP found in two successive pregnancies in a consanguineous couple is reported. Molecular genetic investigations included the study of the coding regions and the exon–intron junctions of the GNPAT (high-throughput amplification and sequencing performed with Roche NimbleGen SeqCap Target kit on Illumina platform); the confirmation test was carried out by amplification and Sanger sequencing with automatic capillary sequencer.
Results
In addition to the typical prenatal ultrasound signs described in the literature in association with RCDP, the presence of prefrontal oedema, never previously described, has been detected in both pregnancies. Moreover, genetic investigations have found a new splicing variant c.924+1G>A of the homozygous GNPAT.
Conclusion
The role of mutation in the GNPAT suggests a likely association with the clinical phenotype.
... [14][15][16][17] The retrospective study by De Jong-Pleij et al. showed a sensitivity of 100% and a specificity of 95% for the detection of DS using PNT/NBL ratio in a population of 30 DS and 106 controls. 18 In the study by Tournemire et al., the optimal PNT/NBL cut-off ratio was 0.98, with a sensitivity of 88.5% (76.2-100%) and a specificity of 100%. 6 The predictive value of PNT alone is low. ...
... Another theory suggesting that delayed migration of the neural crest cells alters the membranous ossification of the nasal bones supports the independency of these two markers. 18 However, studies by Persico et al. 14 and De Jong-Pleij et al. 18 found no significant correlation between PNT-multiple-of-median (MoM) and NBL-MoM of DS fetuses, indicating the independency of these two markers. There is no study that has investigated the relationship between NBL and NF thickness. ...
... Another theory suggesting that delayed migration of the neural crest cells alters the membranous ossification of the nasal bones supports the independency of these two markers. 18 However, studies by Persico et al. 14 and De Jong-Pleij et al. 18 found no significant correlation between PNT-multiple-of-median (MoM) and NBL-MoM of DS fetuses, indicating the independency of these two markers. There is no study that has investigated the relationship between NBL and NF thickness. ...
Objective: To define normal values of second trimester fetal corpus callosum (CC) length and width in a low-risk population and to compare the presented nomograms to those in the literature. Methods: The prenatal records of singleton fetuses who underwent second trimester anomaly screening at 18.0–22.0 weeks of pregnancy were retrospectively analyzed for CC width and length. A total of 710 fetuses, whose anomaly scans were completely normal, were included in the study. The correlations between CC and biparietal diameter (BPD), head circumference (HC) and gestational age (GA) were evaluated. Results: At 18.0–22.0 weeks of pregnancy, the mean CC length was 19.7±2.8 mm, while the mean CC thickness was 1.98±0.4 mm. In assessment of the correlations between the CC length and thickness values and the HC, BPD and GA values by Pearson’s correlation coefficient, there was a stronger correlation between the CC length measurements and the BPD, HC and GA values (r=0.233 vs r=0.505, p<0.001). Conclusion: Assessment of the presence of corpus callosum as well as its length and thickness during routine fetal anomaly evaluation may be important owing to the relationship between corpus callosum measurements and certain neurological disorders. Studies indicate that populations should create their own nomograms due to different values reported in the literature.
... In another study by Persico et al. 4 it was shown that PNT alone could prove a very sensitive method of second-trimester screening for Down syndrome. It has been also highlighted that the PNT/NBL ratio is a good marker for sonographic screening for Down syndrome in low-risk populations 17 . Szabo et al. 18 also mentioned that the ratio has high sensitivity and specificity. ...
... Szabo et al. 18 also mentioned that the ratio has high sensitivity and specificity. In various studies, it was presented that the PNT/NBL ratio was stable during pregnancy and mean level for PNT/NBL ratio was 0.61 mm in healthy fetuses 16,17 . These results are in line with our study. ...
... It has been pointed out in previous reports that cleidocranial dysplasia can also be related to the phenotype of nasal bone loss [21], which is consistent with our case study.In our study, some other genetic variations or chromosomal aneuploidies related to the nasal bone loss phenotype are also found, such as the ARSE gene c.331C>T variation and trisomy 21.ARSE gene mutation is related to X-linked recessive chondrodysplasia punctata, which is manifested as nasal dysplasia and distal phalanx dysplasia [22], which is consistent with the phenotype observed during fetal ultrasound testing.Trisomy 21 is the most frequent form of mental retardation caused by a microscopically demonstrable chromosomal aberration, is characterized by well-de ned and distinctive phenotypic features and natural history [23]. It has been reported that nasal bone dysplasia is a common detected phenotype of fetal trisomy 21 [24], which is consistent with the phenotype of a trisomy 21 case found in our study. Therefore, in the diagnosis of fetal skeletal abnormalities, nasal bone dysplasia may be another typical indication of ultrasound abnormality in addition to short limbs. ...
Background:Fetal skeletal dysplasia is a disease that is difficult to distinguish these types of diseases during the fetal period. Due to the difficulty of fetal ultrasound diagnosis, the severity of fetal skeletal dysplasia is extremely difficult to assess.
Methods: 79 fetal samples of skeletal dysplasia from the third affiliated hospital of Zhengzhou University, China from August 2018 to April 2020, which had undergone prenatal whole exome sequencing(WES) were analyzed and the results of whole-exome sequencing and fetal ultrasound test results were compared.
Results:We find that the fetal short limb phenotype found in the range of FL<-4.0SD or HL<-4.0SD through ultrasound test is closely related to FGFR3 gene mutation , and the correlation is stronger when accompanied by macrocephaly. We also find that the fetal limb curved phenotype is closely related to COL1A1 gene mutation. At the same time, we find that nasal dysplasia during fetal period is also a common phenotype of abnormal results detected by whole exome sequencing.
Conclusions: Our research shows that WES has different detection rates for various skeletal abnormalities according to the different types of ultrasound detection results, which provides a meaningful guidance for clinical diagnosis of fetal skeletal dysplasia.
... Several second and third trimester studies have investigated PT alone or in combination with nasal bone length (NBL), using the PT/NBL ratio or Gaussian risk calculation [5][6][7][8][9][10][11]. The PT is increased in affected fetuses [5,6,8,12] and combinations of PT and NBL show even higher proportions with high levels [8][9][10][11][12]. ...
... Several second and third trimester studies have investigated PT alone or in combination with nasal bone length (NBL), using the PT/NBL ratio or Gaussian risk calculation [5][6][7][8][9][10][11]. The PT is increased in affected fetuses [5,6,8,12] and combinations of PT and NBL show even higher proportions with high levels [8][9][10][11][12]. ...
... Several second and third trimester studies have investigated PT alone or in combination with nasal bone length (NBL), using the PT/NBL ratio or Gaussian risk calculation [5][6][7][8][9][10][11]. The PT is increased in affected fetuses [5,6,8,12] and combinations of PT and NBL show even higher proportions with high levels [8][9][10][11][12]. ...
Purpose
To perform a multicenter prospective study of ultrasound prenasal thickness (PT), and nasal bone length (NBL) measurement at 11–14 weeks’ gestation.
Methods
Ultrasound PT and NBL determination was performed in 504 normal fetuses and 17 fetuses with Down's syndrome (DS). Measurements were made from mid-sagittal 2D images acquired using a standardized technique during nuchal translucency (NT) examination. PT and NBL values were expressed in multiples of the gestation-specific normal median (MoM) and as the PT/NBL ratio. Information on PT and NBL MoMs was also combined using logistic regression. Results were classified as positive according to whether they were greater than the normal 95th centile for PT, PT/NBL and the DS risk from logistic regression equation or below the 5th centile for NBL.
Results
The median value in DS cases and unaffected controls were: PT 1.26 and 0.996 MoM; and NBL 0.596 and 0.993 MoM. The proportion of DS fetuses with positive results was 41% for PT, 65% for NBL, and 82% for both the PT/NBL ratio and DS risk from the logistic regression equation. PT/NBL levels did not vary according to gestational age.
Conclusion
The PT/NBL ratio is a valuable first trimester DS screening marker that can be easily determined concomitant with the NT measurement.
... [6] Persico et al. [7] reported that PT increased significantly in fetuses with Down syndrome and that PT was >95th percentile in 73.1% of the cases. De Jong-Pleij et al. [8] reported in their study that PT presented significant positive correlation with the week of gestation and prenasal thickness/nasal bone length (PT/NBL) ratio remained constant during the week of gestation, and emphasized that the PT/NBL ratio was >95th percentile in all of 30 fetuses with Down syndrome included in their study and PT/NBL ratio was a strong marker. Özcan et al. [9] evaluated 242 cases with normal karyotype and 24 cases with Down syndrome, and reported PT at >95th percentile in 54.2% of the cases with Down syndrome; however, they stated that there was 80% chance to identify the syndrome with 5% false positivity ratio for PT/NBL >0.75 threshold value. ...
... p<0.01), and they reported mean PT values between 2.4 and 4.6 mm in 135 cases during 16-24 weeks of gestation. De Jong-Pleij et al. [8] reported median PT values 2.3-6.1 mm in 106 cases during 15-33 weeks of gestation and found that the correlation was better during these weeks of gestation (R=0.85; p<0.001). ...
... The reason was reported that the use of PT/NBL ratio seen as a single and constant ratio was easier and more applicable method since PT increases together with the week of gestation and therefore a separate threshold value is required for each week of gestation. [5][6][7][8][9][10] Yang et al. [12] also reported that PT/NBL ratio remained constant during 12-33 weeks of gestation (R=0.12; p>0.10) and 95th percentile value was 0.93. ...
... Szabo et al. also stressed that the ratio has high sensitivity and specificity [17]. In several studies, it was shown that the PNT/NBL ratio was stable and was 0.61 and 0.57 throughout gestation and the second trimester, respectively [3,18]. Moreover, in another study, at 11-14 weeks of gestation it was reported that the ratio was 0.6 and are not altered by Crown-Rump Length [19]. ...
Background:
The aim of the present study was to establish the normal ranges for foetal nasal bone length (NBL), prenasal skin thickness (PNT), interocular distance (IOD), and ratio of prenasal thickness to- nasal bone length (PNT/ NBL) at 18-24 weeks using two-dimensional (2D) ultrasound.
Methods:
This study was a retrospective study of prenatal ultrasonographic records from 407 foetuses between 18 and 24 weeks gestational age (GA). The NBL, PNT, IOD, PNT/ NBL ratio, biparietal diameter (BPD), and femur length (FL) were investigated. The relationships among NBL, PNT, IOD, PNT/ NBL, and GA were evaluated. Additionally, descriptive statistics for NBL, PNT, and IOD values for each gestational week were obtained.
Results:
There was a significant association between GA and NBL, PNT, and IOD between 18 and 24 weeks. NBL increased from a mean of 5.5 mm to 8.3 mm, PNT increased from a mean of 3.5 mm to 5.1 mm, and IOD increased from a mean of 11.1 mm to 14.5 mm. PNT/NBL ratio did not change with gestational age.
Conclusions:
This study showed normal ranges for NBL, PNT, IOD, and PNT/ NBL ratios for foetuses between 18 and 24 weeks in low-risk pregnancies. There was a positive linear relationship between GA and NBL, PNT, and IOD. The PNT/NBL ratio might be a more useful measurement than NBL or PNT alone.
... Others have measured the ratio between the prenasal thickness and the nasal bone length. This combination of markers was found to be abnormal in about 85% of the cases with trisomy 21 [6,8]. ...
... Maymon et al. combined the prenasal thickness with the nasal bone length and detected 70% of fetuses with trisomy 21 [18]. Similarly, Vos et al. used the prenasal thickness-to-nose bone ratio and detected 86% of the affected fetuses for a false positive rate of 5% [6,8]. Others have proposed to use the prefrontal space ratio, a marker that combines prenasal thickness and midfacial hypoplasia in fetuses with trisomy 21. ...
PurposeTo examine the maxillary length of euploid and aneuploid fetuses in the second and third trimester. Methods
Retrospective study utilizing stored 2D images of second and third trimester fetal profiles obtained at the University of Tuebingen, Germany. The length of the maxilla was measured as a straight line between the anterior ventral and posterior ventral edges of the maxilla. ResultsThe study population consisted of 347 euploid fetuses and 122, 36, 5, 8, and 4 fetuses with trisomy 21, 18, and 13, Turner syndrome, and triploidy. In the euploid and aneuploid group, mean gestational age was 22.3 and 22.7 weeks, respectively. The maxilla length in euploid fetuses was significantly dependent on gestational age and it was significantly shorter in fetuses with trisomy 21, 18, and 13, and triploidy but not in those with Turner syndrome. In 75.4 and 14.8%, and 11 fetuses with trisomy 21, the maxilla was below the mean, the 5th and 1st centile of the euploid population. Conclusions
In fetuses with trisomy 21, 18, and 13 and triploidy, the maxilla is significantly shorter, but the difference is only settled, so that it is unlikely that the maxilla length will play a role in second and third screening for aneuploidy.
