Trends in Serial Measurements of Ultrasound Markers in Second and Third Trimester Down Syndrome Fetuses.

OBJECTIVES: To evaluate trends of nasal bone length (NBL), prenasal thickness (PT), nuchal fold (NF), prenasal thickness to nasal bone length (PT-NBL) ratio, and prefrontal space ratio (PFSR), measured serially in second- and third-trimester Down syndrome (DS) fetuses. METHODS: Prenatal databases were searched for cases of continuing DS pregnancies with serial measurements, taken at least two weeks apart. Trends were plotted on previously reported normal ranges. RESULTS: Serial measurements were available in 25 Down syndrome fetuses. Median gestational age (GA) was 25 weeks; average number of visits per case was 2.44, with a median interval of 39 days between investigations. In DS fetuses, NBL and PT showed fairly stable trends with gestation. PFSR, but especially NF, had a more unpredictable trend. The PT-NBL ratio was the most stable marker, remaining unchanged in 95% of cases. NBL, PT, and NF showed more deviance from the normal range with advancing gestation, but MoM values remained stable. All but two fetuses had ultrasound markers or structural anomalies, especially heart defects. CONCLUSIONS: The PT-NBL ratio is the most constant DS marker throughout gestation, following a predictable trend.

Facial profile markers in second- and third-trimester fetuses with trisomy 18.

OBJECTIVES: To evaluate nasal bone length (NBL), maxilla-nasion-mandible (MNM) angle, fetal profile (FP) line, prenasal thickness (PT), prenasal thickness to nasal bone length (PT:NBL) ratio and prefrontal space ratio (PFSR) as markers of trisomy 18 in the second and third trimesters of pregnancy. METHODS: The NBL, MNM angle, FP line, PT, PT:NBL ratio and PFSR were measured retrospectively from stored two-dimensional images or three-dimensional volumes of trisomy-18 fetuses, and were compared with our previously reported normal ranges for euploid fetuses. Additional ultrasound findings were noted at initial routine second-trimester scan and at subsequent advanced ultrasound examination performed after referral for karyotyping. RESULTS: A total of 43 trisomy-18 fetuses were included in the analysis. At initial examination, median gestational age was 21 + 2 weeks. NBL and PT were correlated with gestational age (P < 0.001), but the other markers were not. Mean NBL, MNM angle, PT, PT:NBL ratio and PFSR were 3.76 mm, 16.67°, 4.25 mm, 1.39 and 0.87, respectively. The FP line was zero (normal) in 53.7% of cases and negative (abnormal) in 46.3%. All markers were significantly associated with trisomy 18, with the PT:NBL ratio yielding the highest detection rate (88.4%) followed by NBL (83.7%), MNM angle (56.4%), FP line (46.3%), PT (27.9%) and the PFSR (20.5%) (for a 5% false-positive rate for the continuous variables). Various combinations of the four best markers (NBL, FP line, MNM angle and PT:NBL ratio) yielded detection rates of between 72% and 95%. Structural anomalies were not detected in 22% of fetuses at the initial scan and in 2% at the advanced scan. CONCLUSIONS: The PT:NBL ratio and NBL are robust second- and third-trimester markers for trisomy 18. A negative FP line has a 0% false-positive rate and the potential to differentiate between trisomy 18 and Down syndrome, as in the latter the FP line is often positive. No major anomaly was observed at the initial scan in about a quarter of trisomy-18 fetuses, underlining the role of second-trimester facial marker evaluation.

Fetal facial profile markers of Down syndrome in the second and third trimesters of pregnancy.

OBJECTIVES: To investigate the use of the maxilla-nasion-mandible (MNM) angle and fetal profile (FP) line to assess the degree of midfacial hypoplasia in Down-syndrome fetuses in the second and third trimesters of pregnancy. METHODS: The MNM angle and FP line were measured retrospectively in stored two-dimensional images or three-dimensional volumes of fetuses with Down syndrome. Data collected from January 2006 to July 2013 were retrieved from the digital databases of participating units. The MNM angle was expressed as a continuous variable (degrees) and the FP line as positive, negative or zero. Measurements were obtained from stored images in the midsagittal plane by two experienced examiners and compared with our previously reported normal ranges for euploid fetuses. A MNM angle below the 5(th) centile of the reference range and a positive or negative FP line were considered as abnormal. RESULTS: A total of 133 fetuses with Down syndrome were available for analysis, eight of which were subsequently excluded because of inadequate images. The MNM angle was not influenced by gestational age (P = 0.48) and was significantly smaller in Down-syndrome fetuses than in euploid fetuses (mean, 12.90° vs 13.53°, respectively; P = 0.015). The MNM angle was below the 5th centile for euploid fetuses in 16.8% of fetuses with Down syndrome (P < 0.01). In the cohort of Down-syndrome fetuses, a positive FP line was present in 41.6% of cases (with a false-positive rate (FPR) of 6.3%) and was positively correlated with Down syndrome and gestational age (P < 0.01). There was no case with a negative FP line. In cases of Down syndrome, a positive FP line was correlated with a small MNM angle (P < 0.01). CONCLUSIONS: A small MNM angle and a positive FP line can be regarded as novel markers for Down syndrome. The FP line is an easy marker to measure, has a low FPR, does not require knowledge of normal reference values and has the potential to differentiate between Down syndrome and trisomy 18, as, in the latter, the FP line is often negative.

Is 3D technique superior to 2D in Down syndrome screening? Evaluation of six second and third trimester fetal profile markers.

OBJECTIVE: The objective of this article is to investigate whether in the clinical setting of second trimester ultrasound (US) investigations, 3D multiplanar correction prior to the measurement of Down syndrome (DS) facial markers (nasal bone length, prenasal thickness, fetal profile line, maxilla-nasion-mandible angle, prenasal thickness to nasal bone length ratio, and prefrontal space ratio) is superior to subjective judgment of a correct midsagittal plane by 2D technique. METHODS: Measurements were performed on 2D images and 3D volumes (corrected to the midsagittal plane), acquired during the same scanning session. RESULTS: All six markers were measured in 105 datasets (75 of euploid fetuses and 30 of DS fetuses). The maxilla-nasion-mandible angle measured on 2D images was significantly larger than on 3D volumes (p < 0.01). In all other markers, there was no significant difference between measurements performed on 2D images or 3D volumes. No statistical difference was found for any marker between measurements performed on images acquired by either 2D or 3D US in their ability to discriminate between normal and DS fetuses. CONCLUSIONS: Nasal bone length, prenasal thickness, fetal profile line, prenasal thickness to nasal bone length ratio, and prefrontal space ratio can be confidently used as DS markers in second trimester US examinations performed by 2D US. © 2014 John Wiley & Sons, Ltd.

Nasal bone length, prenasal thickness, prenasal thickness-to-nasal bone length ratio and prefrontal space ratio in second- and third-trimester fetuses with Down syndrome.

OBJECTIVES: To evaluate nasal bone length (NBL), prenasal thickness (PT), prenasal thickness-to-nasal bone length (PT-NBL) ratio and prefrontal space ratio (PFSR) as markers for Down syndrome in the second and third trimesters. METHODS: NBL, PT, PT-NBL ratio and PFSR were measured retrospectively in stored two-dimensional images or three-dimensional volumes (corrected to the mid-sagittal plane) of fetuses with Down syndrome, which were retrieved from the digital databases of participating units. Measurements were performed on the stored images and volumes by two experienced operators, and the values obtained were compared to our previously reported normal ranges for euploid fetuses in order to assess the detection rates for Down syndrome. RESULTS: A total of 159 fetuses with Down syndrome were included in the analysis, six of which were excluded because of inadequate available images. Median maternal age was 36.0 years and median gestational age was 23 + 1 weeks. NBL and PT were correlated with gestational age (P < 0.001), but the PT-NBL ratio and PFSR were not. Mean NBL, PT, PT-NBL ratio and PFSR were 4.42 mm, 5.56 mm, 1.26 and 0.34, respectively. The nasal bone was absent in 23 (15.4%) cases. As a marker for Down syndrome, the PT-NBL ratio yielded the highest detection rate (86.2%), followed by PFSR (79.7%), PT (63.4%) and NBL (61.9%). All markers were abnormal in 33.6% of cases, whilst all were normal in 4.7%. At least one of the four markers was abnormal in 95.3%, and either the PT-NBL ratio or PFSR was abnormal in 93.8%. Detection rates were not related to gestational age. CONCLUSIONS: The PT-NBL ratio and PFSR are robust second- and third-trimester markers for Down syndrome. Both provide high detection rates and are easy to use, as the cut-off for normality is constant throughout gestation. Ltd.

Premaxillary protrusion assessment by the maxilla-nasion-mandible angle in fetuses with facial clefts.

OBJECTIVE: The aim of the study was to measure the degree of premaxillary protrusion in fetuses with orofacial clefts of various severities. METHODS: The maxilla-nasion-mandible (MNM) angle was measured retrospectively on by multiplanar corrected volumes. Sixty-two fetuses with orofacial clefts and known outcome volumes of the fetal head were available. RESULTS: In 48 of the 62 cases, the MNM angle could be measured [mean gestational age 23 (range, 18-30) weeks]. The mean MNM angle was normal in all nine cases with cleft lip and intact alveolar ridge (15.2°; range, 12.5°- 16.9°). In 24 cases with unilateral cleft lip with or without cleft palate (UCL/P), the mean MNM angle was 20.0° (range, 13.3-26.2°), being above the 95th percentile in 79% (n = 19) and normal in 21% (n = 5). In 14 bilateral cleft lip and palate (BCL/P) cases, the mean MNM angle was 26.5° (range, 19.2°-33.7°) and above the 95th percentile in all cases. There was no difference in MNM angle between isolated clefts and clefts associated with other anomalies. In one case with a Tessier 4 cleft, the MNM angle was above the 95th percentile (25.2°). CONCLUSION: The premaxilla tends to protrude in both BCL/P as UCL/P cases. The degree of protrusion varies greatly, especially in the BCL/P group.

Three-dimensional ultrasound and maternal bonding, a third trimester study and a review.

OBJECTIVE: To compare the effect of third trimester three-dimensional and four-dimensional (3D/4D) versus two-dimensional (2D) ultrasound (US) of the fetal face on maternal bonding. Studies quantifying the psychological effect of 3D/4D US on mothers, pregnant of a fetus with no detectable abnormalities, were reviewed. METHODS: One hundred sixty Caucasian women attended a third trimester 3D/4D or 2D US examination. Women filled out the Maternal Antenatal Attachment Scale (MAAS) 1 to 2 weeks before (MAAS1) and 1 to 2 weeks after (MAAS2) the US examination. Visibility, recognition and attractiveness were assessed. RESULTS: Within both US groups, the MAAS2 scores were significantly higher than the MAAS1 scores (p < 0.0001). No differences in MAAS scores between the US groups emerged. Visibility and recognition were significantly positively related with the increase in MAAS scores (p = 0.003 and p = 0.042) in the 3D/4D group. Of 13 psychological studies, eight studies evaluated bonding and found no difference between 3D/4D and 2D US. The effect of 3D/4D US on satisfaction or perception showed conflicting results, and on anxiety/stress, reduction was the same as after 2D US. CONCLUSIONS: Bonding increases after either a 3D/4D or 2D US. The effect of 3D/4D US on bonding is stronger at better degrees of visibility and recognition.

Prenasal thickness-to-nasal bone length ratio: a strong and simple second- and third-trimester marker for trisomy 21.

OBJECTIVES: 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. METHODS: 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). RESULTS: In normal fetuses the mean PT and NBL increased between 15 and 33 weeks' gestation from 2.3 to 6.1 mm (r = 0.85, P < 0.001) and from 3.3 to 9.6 mm (r = 0.87, P < 0.001), respectively. The PT : NBL ratio was stable throughout gestation, with a mean of 0.61 (95% CI, 0.59-0.63; r = - 0.04, P = 0.7). The 5(th) and 95(th) percentiles were 0.48 and 0.80, respectively. In trisomy-21 fetuses the mean PT and NBL increased between 14 and 34 weeks from 3.0 to 9.2 mm (r = 0.86, P < 0.001) and from 1.9 to 7.8 mm (r = 0.85, P < 0.001), respectively. The PT : NBL ratio was significantly higher than in normal fetuses (P < 0.001) but also stable throughout gestation, with a mean of 1.50 (95% CI, 1.20-1.80; r = - 0.35, P = 0.07). Twenty-three (77%) of the 30 fetuses with trisomy 21 had a PT above the 95(th) percentile and 20 (67%) had an NBL below the 5(th) percentile. All the trisomy-21 fetuses had a PT : NBL ratio above the 95(th) percentile. When the 95(th) percentile of the PT : NBL ratio was used as a cut-off value the detection and false positive rates for trisomy 21 were 100 (95% CI, 89-100)% and 5 (95% CI, 2-11)%, respectively. The positive likelihood ratio was 21.2. CONCLUSIONS: The PT : NBL ratio is stable in the second and third trimesters of pregnancy in both normal and trisomy-21 fetuses, but all trisomy-21 fetuses in this series had a PT : NBL ratio above the 95(th) percentile. The ratio is therefore a strong marker for trisomy 21.

Three-dimensional ultrasound imaging and measurement of nasal bone length, prenasal thickness and frontomaxillary facial angle in normal second- and third-trimester fetuses.

OBJECTIVES: To assess the feasibility of nasal bone length (NBL), prenasal thickness (PT) and frontomaxillary facial (FMF) angle measurements performed on the same three-dimensional (3D) multiplanar-corrected profile view in healthy second- and third-trimester fetuses, to create reference ranges and to review published measurement techniques. METHODS: 3D volumes of 219 healthy second- and third-trimester fetuses were retrospectively analyzed. The quality of images and measurability of the markers were assessed with 5-point and 3-point scoring systems, respectively. Measurements of NBL (with care to exclude the frontal bone), PT and FMF were obtained in the exact mid-sagittal plane. Reference ranges were constructed based on measurements from images with high-quality (4 or 5 points) and high measurability (2 or 3 points) scores and compared with those in the most relevant published literature. RESULTS: A high-quality score was assigned to 111 images. Among these, a high measurability score was significantly more often achieved for NBL (98.2%) and PT (97.3%) than for the FMF angle (26.1%) (P < 0.001). Both NBL (NBL = - 6.927 + (0.83 × GA) - (0.01 × GA(2))) and PT (PT = (0.212 × GA) - 0.873) (where GA = gestational age) showed growth with gestation, with less pronounced growth for NBL after 28 weeks. Our reference range for the NBL showed a systematically smaller length than those in other two-dimensional (2D) ultrasound-based publications. The FMF angle measurements that we obtained did not show a significant change with GA. CONCLUSIONS: NBL and PT are easily measured using 3D ultrasound whereas FMF angle measurement is more challenging. When it is measured in the exact mid-sagittal plane and care is taken to exclude the frontal bone, measurements of the NBL are systematically smaller than those in previous 2D ultrasound-based publications.

Maxilla-nasion-mandible angle: a new method to assess profile anomalies in pregnancy.

OBJECTIVES: To collect normative data and test the feasibility and reproducibility of measurement of the maxilla-nasion-mandible (MNM) angle between 16 and 36 weeks' gestation and its diagnostic ability in a group of pathological cases. METHODS: The MNM angle is defined as the angle between the intersection of the maxilla-nasion and mandible-nasion lines in the exact mid-sagittal plane. After assessing reproducibility, the MNM angle was measured in 3D volumes in 241 fetuses cross-sectionally and in 11 fetuses longitudinally. The MNM angle was then tested in 18 pathological cases with facial malformations or syndromes with specific facial features. RESULTS: The MNM angle could be measured in 92.3% of normal fetuses. Intra- and interobserver intraclass correlation coefficient (ICC) variability was 0.92 and 0.81, respectively. The difference between paired measurements performed by one or two observers was less than 2.5° and 3.6°, respectively in 95% of the cases. The mean MNM angle was 13.5° and did not change significantly during pregnancy (r = - 0.08, P = 0.25). The MNM angle was above the 95(th) centile in all cases of retrognathia and maxillary alveolar ridge interruption. The MNM angle was below the 5(th) centile in Apert syndrome, thanatophoric dysplasia and in two of the three Down syndrome cases. CONCLUSIONS: The feasibility and reproducibility of measurement of the MNM angle is good. The MNM angle can be used to evaluate the convexity of the fetal profile by enabling an objective assessment of the anteroposterior relationship of the jaws and it may therefore be of help in the diagnosis of retrognathia, maxillary alveolar ridge interruption and flat profile.

Three-dimensional multiplanar ultrasound is a valuable tool in the study of the fetal profile in the second trimester of pregnancy.

OBJECTIVES: To evaluate the additional value of three-dimensional (3D) multiplanar ultrasound in the examination of the fetal profile. METHODS: Two 3D volumes of the fetal head were obtained from 84 fetuses at 22 to 29 weeks' gestation. The volumes were taken starting at the midsagittal plane with the fetus facing the transducer. The success rate and acquisition time to obtain each volume and display the exact midsagittal plane by 3D multiplanar ultrasound were analyzed. The correction angles from the original two-dimensional (2D) profile view to the exact midsagittal plane were noted. Of six measurements, related to the fetal nose and jaws, the success rate and the intraobserver reproducibility between the 2D and the 3D multiplanar ultrasound were compared. RESULTS: In 81 (96.4%) cases we succeeded in obtaining a profile volume, 70% of the volumes being obtained within 10 min. It was possible to define by multiplanar mode the exact midsagittal plane in less than 1 min. The mean rotation necessary to obtain the exact midsagittal plane with 3D multiplanar mode was significantly larger around the y-axis (11.9 degrees ) than around the z-axis (4.3 degrees ) of the fetus. For between 5 and 12% of the six measurements under investigation it was not possible to obtain values with 2D ultrasound. However, 3D ultrasound made these measurements possible in at least one volume. The intraobserver reproducibility was higher with 3D multiplanar ultrasound than with 2D ultrasound, this difference being statistically significant for five of the six measurements. CONCLUSIONS: 3D multiplanar ultrasound improves the topographic depiction of the midsagittal profile view, enables correct measurement of anatomical details and improves intraobserver reproducibility. 3D multiplanar ultrasound is a powerful instrument for investigating the fetal profile.