Complication rate after termination of pregnancy for fetal defects.

OBJECTIVES: To assess the risk of complications in women undergoing termination of pregnancy (TOP) for fetal defects and to examine the impact of gestational age on the complication rate. METHODS: This was a retrospective study of women with a singleton pregnancy undergoing TOP at the University Hospital of Tübingen, Germany, between 2018 and 2021. TOP was performed by experienced operators according to the national protocol; dilatation and curettage (D&C) or evacuation (D&E) was used in the first and early second trimesters and induction was used later in pregnancy. The following were considered to be significant procedure-related complications: blood loss of more than 500 mL, uterine perforation, need for blood transfusion, allergic reaction, creation of a false passage (via falsa), systemic infection, readmission to hospital, any unplanned surgical procedure, such as repeat D&C/D&E or hysterectomy, and maternal death. RESULTS: The search of the hospital database identified 416 pregnancies that met the study criteria. Median maternal and gestational age at termination were 34.1 years and 17.4 weeks, respectively. In the first, second and third trimesters, respectively, 84 (20.2%), 278 (66.8%) and 54 (13.0%) pregnancies were terminated, for which D&C or D&E was used in 80 (95.2%), 21 (7.6%) and 0 (0.0%) cases. Seventy-seven (18.5%) women had at least one previous Cesarean section and 169 (40.6%) had at least one previous spontaneous delivery. Overall, 95 (22.8%) women had complications during or after TOP. A significantly higher complication rate was noted for terminations performed later in pregnancy. The median gestational age at termination was 16.6 weeks in women who did not experience complications and 20.7 weeks in those with complications (P < 0.001). The respective complication rates in the first, second and third trimesters were 6.0%, 27.0% and 27.8%. CONCLUSION: In women undergoing TOP for fetal defects, the risk of complications increases with advancing gestational age. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Performance of IOTA Simple Rules, Simple Rules risk assessment, ADNEX model and O-RADS in differentiating between benign and malignant adnexal lesions in North American women.

OBJECTIVES: To apply the International Ovarian Tumor Analysis (IOTA) Simple Rules (SR), the IOTA Simple Rules risk assessment (SRR), the IOTA Assessment of Different NEoplasias in the adneXa (ADNEX) model and the Ovarian-Adnexal Reporting and Data System (O-RADS) in the same cohort of North American patients and to compare their performance in preoperative discrimination between benign and malignant adnexal lesions. METHODS: This was a single-center diagnostic accuracy study, performed between March 2018 and February 2021, which included 150 women with an adnexal lesion. Using the ADNEX model, lesions were classified prospectively, whereas the SR, SRR assessment and O-RADS were applied retrospectively. Surgery with histological analysis was performed within 6 months of the ultrasound exam. Sensitivity and specificity were determined for each testing modality and the performance of the different modalities was compared. RESULTS: Of the 150 women, 110 (73.3%) had a benign ovarian tumor and 40 (26.7%) had a malignant tumor. The mean risk of malignancy generated by the ADNEX model without CA 125 was significantly higher in malignant vs benign lesions (63.3% vs 11.8%) and the area under the receiver-operating-characteristics curve (AUC) of the ADNEX model for differentiating between benign and malignant adnexal masses at the time of ultrasound examination was 0.937. The mean risk of malignancy generated by SRR assessment was also significantly higher in malignant vs benign lesions (74.1% vs 15.9%) and the AUC was 0.941. To compare the ADNEX model, SRR assessment and O-RADS, the malignancy risk threshold was set at ≥ 10%. This cut-off differentiates O-RADS low-risk categories (Category ≤ 3) from intermediate-to-high-risk categories (Categories 4 and 5). At this cut-off, the sensitivity of the ADNEX model was 97.5% (95% CI, 85.3%-99.9%) and the specificity was 63.6% (95% CI, 53.9%-72.4%), and, for the SRR model, the sensitivity was 100% (95% CI, 89.1%-100%) and the specificity was 51.8% (95% CI, 42.1%-61.4%). In the 113 cases to which the SR could be applied, the sensitivity was 100% (95% CI, 81.5%-100%) and the specificity was 95.6% (95% CI, 88.5%-98.6%). If the remaining 37 cases, which were inconclusive under SR, were designated 'malignant', the sensitivity remained at 100% but the specificity was reduced to 79.1% (95% CI, 70.1%-86.0%). The 150 cases fell into the following O-RADS categories: 17 (11.3%) lesions in Category 2, 34 (22.7%) in Category 3, 66 (44.0%) in Category 4 and 33 (22.0%) in Category 5. There were no histologically proven malignant lesions in Category 2 or 3. There were 14 malignant lesions in Category 4 and 26 in Category 5. The sensitivity of O-RADS using a malignancy risk threshold of ≥ 10% was 100% (95% CI, 89.1%-100.0%) and the specificity was 46.4% (95% CI, 36.9%-56.1%). CONCLUSIONS: When IOTA terms and techniques are used, the performance of IOTA models in a North American patient population is in line with published IOTA results in other populations. The IOTA SR, SRR assessment and ADNEX model and O-RADS have similar sensitivity in the preoperative discrimination of malignant from benign pelvic tumors; however, the IOTA models have higher specificity and the algorithm does not require the use of magnetic resonance imaging. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Single and repeat cervical-length measurement in twin gestation with threatened preterm labor.

OBJECTIVE: To examine the effectiveness of single and repeat sonographic cervical-length (CL) measurement in predicting preterm delivery in symptomatic women with a twin pregnancy. METHODS: This was a retrospective study of women with a twin gestation who presented with painful and regular uterine contractions at 24 + 0 to 33 + 6 weeks' gestation at the perinatal unit of the University Hospital of Tübingen, Tübingen, Germany between 2012 and 2018. CL was measured on transvaginal ultrasound at the time of admission and a few days later after cessation of contractions. Treatment included administration of tocolytics (usually oral nifedipine), for no more than 48 h, and administration of steroids if CL was ≤ 25 mm. Patients were clustered into five groups according to the CL measurement obtained at first assessment: < 10.0 mm; between 10.0 and 14.9 mm; between 15.0 and 19.9 mm; between 20.0 and 24.9 mm; and ≥ 25.0 mm. For each group, we calculated the test performance of CL measurement for prediction of preterm delivery within the subsequent 7 days and before 34 weeks' gestation. Regression analysis was used to evaluate the test performance of the second CL measurement for predicting preterm delivery within 7 days after the second assessment. RESULTS: The study population consisted of 257 twin pregnancies, of which 80.2% were dichorionic diamniotic. Median maternal and gestational ages at the time of admission were 32.0 years and 29.9 weeks' gestation, respectively. Preterm birth within 7 days of admission occurred in 23 (8.9%) pregnancies, and 82 (31.9%) patients delivered prior to 34 weeks' gestation. Median CL for the entire study population was 17.0 mm. Delivery within 7 days after the first assessment occurred in 29.0%, 10.6%, 4.2%, 6.3% and 0% of women with CL < 10.0 mm, 10.0-14.9 mm, 15.0-19.9 mm, 20.0-24.9 mm and ≥ 25.0 mm, respectively. There was a weak, but significant, association between the CL measurement at the time of admission and the time interval between admission and delivery (interval = 27.9 + 0.58 × CL; P = 0.003, r = 0.184). CL was measured again after a median time interval of 3 (interquartile range (IQR), 2-5) days in 248 cases. Median second CL measurement was 17.0 (IQR, 11.5-22.0) mm. Delivery occurred within the subsequent 7 days after the second measurement in 25/248 (10.1%) cases. Binary regression analysis indicated that the first (odds ratio (OR), 0.895; P = 0.003) and second (OR, 0.908; P = 0.002) CL measurements, but not the difference between the two measurements (OR, 0.961; P = 0.361), were associated significantly with delivery within 7 days after the second measurement. Receiver-operating-characteristics (ROC)-curve analysis for the prediction of delivery within 7 days after the second assessment did not show a significant difference between the predictive performance of the first (area under ROC curve (AUC), 0.676 (95% CI, 0.559-0.793)) and the second (AUC, 0.661 (95% CI, 0.531-0.790)) measurement. CONCLUSION: Sonographic measurement of CL can be helpful in predicting preterm delivery within 7 days of presentation in symptomatic women with a twin gestation; however, the test performance is relatively weak. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Artificial intelligence and amniotic fluid multiomics: prediction of perinatal outcome in asymptomatic women with short cervix.

OBJECTIVE: To evaluate the application of artificial intelligence (AI), i.e. deep learning and other machine-learning techniques, to amniotic fluid (AF) metabolomics and proteomics, alone and in combination with sonographic, clinical and demographic factors, in the prediction of perinatal outcome in asymptomatic pregnant women with short cervical length (CL). METHODS: AF samples, which had been obtained in the second trimester from asymptomatic women with short CL (< 15 mm) identified on transvaginal ultrasound, were analyzed. CL, funneling and the presence of AF 'sludge' were assessed in all cases close to the time of amniocentesis. A combination of liquid chromatography coupled with mass spectrometry and proton nuclear magnetic resonance spectroscopy-based metabolomics, as well as targeted proteomics analysis, including chemokines, cytokines and growth factors, was performed on the AF samples. To determine the robustness of the markers, we used six different machine-learning techniques, including deep learning, to predict preterm delivery < 34 weeks, latency period prior to delivery < 28 days after amniocentesis and requirement for admission to a neonatal intensive care unit (NICU). Omics biomarkers were evaluated alone and in combination with standard sonographic, clinical and demographic factors to predict outcome. Predictive accuracy was assessed using the area under the receiver-operating characteristics curve (AUC) with 95% CI, sensitivity and specificity. RESULTS: Of the 32 patients included in the study, complete omics, demographic and clinical data and outcome information were available for 26. Of these, 11 (42.3%) patients delivered ≥ 34 weeks, while 15 (57.7%) delivered < 34 weeks. There was no statistically significant difference in CL between these two groups (mean ± SD, 11.2 ± 4.4 mm vs 8.9 ± 5.3 mm, P = 0.31). Using combined omics, demographic and clinical data, deep learning displayed good to excellent performance, with an AUC (95% CI) of 0.890 (0.810-0.970) for delivery < 34 weeks' gestation, 0.890 (0.790-0.990) for delivery < 28 days post-amniocentesis and 0.792 (0.689-0.894) for NICU admission. These values were higher overall than for the other five machine-learning methods, although each individual machine-learning technique yielded statistically significant prediction of the different perinatal outcomes. CONCLUSIONS: This is the first study to report use of AI with AF proteomics and metabolomics and ultrasound assessment in pregnancy. Machine learning, particularly deep learning, achieved good to excellent prediction of perinatal outcome in asymptomatic pregnant women with short CL in the second trimester. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

First-trimester ductus venosus velocity ratio as a marker of major cardiac defects.

OBJECTIVES: To examine ductus venosus (DV) flow in fetuses with and those without a cardiac defect and to evaluate different phases of DV flow in addition to the standard assessment of DV pulsatility index for veins (PIV) and the a-wave. METHODS: This was a retrospective study of singleton pregnancies that underwent first-trimester ultrasound screening, which included DV flow assessment, at the University of Tübingen (between 2010 and 2017) or the University of Cologne (between 2013 and 2016). The study population comprised normal fetuses and fetuses with major cardiac defects at a ratio of 10:1. For each fetus, the following parameters of the DV waveform were evaluated: qualitative assessment of the a-wave, PIV measurement and ratios of flow velocities during the S-wave (S) or D-wave (D) and the a-wave (a) or v-wave (v). Reproducibility of DV-PIV and DV flow ratios was evaluated in 30 fetuses in which the DV flow was assessed twice. RESULTS: Our study population included 480 anatomically normal fetuses and 48 with a cardiac defect. Median fetal nuchal translucency (NT) in the normal and in the affected group was 1.9 mm and 2.6 mm, respectively. In five (1.0%) of the normal and 18 (37.5%) of the affected cases, fetal NT thickness was above the 99th centile. In the normal group, the DV a-wave was reversed in 15 (3.1%) cases and the DV-PIV was above the 95th centile in 25 (5.2%). In the cases with cardiac defects, the a-wave was reversed and the DV-PIV measurement was above the 95th centile in 26 (54.2%). The reproducibility of measurement of the ratios of DV flow velocities was similar to that of the DV-PIV. Most cardiac defects were associated with an abnormal a/S or a/D ratio. If the cut-off for these two ratios was set at the 5th centile of the normal distribution, the detection rate of fetal cardiac anomalies would be 62.5%. This compares favorably with the DV-PIV, which detects 26 (54.2%) of the affected fetuses for the same threshold. CONCLUSION: In the first trimester, the a/S ratio has the potential to detect approximately 60% of congenital cardiac defects for a false-positive rate of 5%. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

First-trimester risk assessment based on ultrasound and cell-free DNA vs combined screening: a randomized controlled trial.

OBJECTIVE: This was a randomized controlled trial to compare risk assessment by first-trimester combined screening (FTCS) with an approach that combines a detailed ultrasound examination at 11-13 weeks' gestation and cell-free DNA (cfDNA) analysis. METHODS: Pregnant women with a normal first-trimester ultrasound examination at 11-13 weeks' gestation (fetal nuchal translucency (NT) ≤ 3.5 mm and no fetal defects) were randomized into one of two groups. In the first group, risk of aneuploidy was assessed using FTCS based on the most recent UK Fetal Medicine Foundation algorithm. In the second group, risk assessment was based on ultrasound findings and cfDNA analysis. An additional tube of blood was collected for FTCS in case the cfDNA analysis was uninformative. Primary outcome was false-positive rate in screening for trisomy 21. A case was considered false positive if the karyotype was not trisomy 21 and if the risk for trisomy 21 was >1:100, irrespective of the method of risk calculation. Results were compared using 95% CIs using the Clopper-Pearson method. RESULTS: Between October 2015 and December 2016, 1518 women with singleton pregnancy underwent first-trimester screening. Thirty-one (2.0%) pregnancies were not eligible for randomization due to increased NT (> 3.5 mm) and/or fetal defect. After exclusion of women who declined randomization (n = 87) and cases of fetal death and loss to follow-up (n = 24), 688 pregnancies were randomized into the FTCS arm and 688 into the ultrasound + cfDNA analysis arm. There were no differences in maternal and gestational age, maternal weight and BMI, ethnicity, use of assisted reproduction and cigarette smoking between the two arms. In the ultrasound + cfDNA analysis arm, median risk for trisomy 21 was 1 in 10 000. None of the cases had a risk above 1: 100 (95% CI, 0.0-0.5%). In the FTCS arm, the median risk for trisomy 21 was 1 in 3787 and in 17 cases, the risk was higher than 1:100, which corresponds to 2.5% (95% CI, 1.5-3.9%) of the FTCS study-arm population. CONCLUSION: Our study has shown that first-trimester risk assessment for trisomy 21 that includes a detailed ultrasound examination as well as NT measurement and is followed by cfDNA testing is associated with a significant reduction in the false-positive rate compared with FTCS. This approach obviates the need for maternal serum free ß-human chorionic gonadotropin and pregnancy-associated plasma protein-A in screening for fetal aneuploidy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Sphenofrontal distance in euploid and aneuploid fetuses.

OBJECTIVE: To examine the sphenofrontal distance (SFD) in a large series of aneuploid fetuses in the second and third trimesters and compare findings with those of a euploid population. METHODS: The database at our unit was searched to identify pregnancies with a diagnosis of trisomy 21, 18 or 13, triploidy or Turner syndrome after 15 weeks' gestation. Stored ultrasound images obtained between 19 and 22 weeks were reviewed. For the normal population, two euploid fetuses matched for gestational age were selected randomly for each aneuploid case. The SFD was measured from the anterior edge of the sphenoid bone to the lowest posterior edge of the frontal bone using on-screen calipers. The SFD measurement was parallel to the long axis of the maxilla. If the sphenoid bone did not extend superiorly enough for direct measurement of the SFD, a tangential line was drawn at the anterior wall of the sphenoid bone and extended cranially. In these cases, the distance between the extended line and the frontal bone was measured. One operator measured the SFD twice and was blinded to the results and karyotype. RESULTS: The study population consisted of 591 pregnancies: 394 euploid fetuses, 122 fetuses with trisomy 21, 45 with trisomy 18, 16 with trisomy 13, eight with Turner syndrome and six with triploidy. For both euploid and aneuploid groups, mean gestational age at examination was 22.8 (range: euploid, 15.0-40.7; aneuploid, 15.0-40.3) weeks. For euploid fetuses, mean SFD was 1.27 cm and measurements ranged from 0.53 cm to 2.56 cm. SFD was significantly dependent on gestational age (SFD = 0.138 + 0.005 × gestational age, P < 0.001, r = 0.802). Mean SFD was significantly smaller in each aneuploid group compared with the euploid population (trisomies 21, 18 and 13: all P < 0.001; triploidy: P = 0.026; Turner syndrome: P = 0.047). For 32 (26.2%), nine (20.0%) and six (37.5%) fetuses with trisomy 21, 18 and 13, respectively, SFD was < 5th percentile. Only one (12.5%) fetus with Turner syndrome and none with triploidy had SFD < 5th percentile. CONCLUSION: In aneuploid fetuses, the SFD is smaller than in their euploid counterparts. However, for a false-positive rate of 5%, the detection rate of trisomy 21 is only 26%. Therefore, using the method we have proposed, it is unlikely that this marker will play a major role in second- and third-trimester screening for aneuploidy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Repeat Measurement of Cervical Length in Women with Threatened Preterm Labor.

OBJECTIVE: To examine the value of a repeat measurement some days after the first cervical length measurement done at the time of preterm contractions. STUDY DESIGN: Retrospective study involving women with singleton pregnancies who presented with preterm contractions at 24 to 33 + 6 weeks of gestation. The cervical length was measured at the time of presentation and some days afterwards. RESULTS: The study population consisted of 17 cases with a preterm delivery within 14 days and 288 uneventful pregnancies. Univariate logistic regression analysis indicated a significant correlation between delivery within 14 days and both, the first and second cervical length measurements as well as the difference between the two measurements. Up to a false positive rate of 20 %, ROC curve analysis showed an improved detection rate for preterm delivery by inluding both measurements. At a false positive rate of 10 % - which corresponds to a first and second cervical length of 10 and 9 mm - the detection rate was 17.6 % with the first cervical length measurement, 47.0 % with the second and 52.9 % if the difference between both measurements was added. CONCLUSION: Our results indicate that in women with symptoms of preterm labor it is worth to repeat the measurement some days later and to take into account the difference between both measurements.

Frontal space distance in facial clefts and retrognathia at 11-13 weeks' gestation.

OBJECTIVE: To examine the frontal space (FS) distance in first-trimester fetuses with bilateral, unilateral or median cleft lip and palate and in those with retrognathia. METHODS: This was a retrospective study using stored two-dimensional ultrasound images of fetal profiles that were recorded at the time of the nuchal translucency (NT) scan at three prenatal medical centers. Images of 300 normal fetuses and 53 fetuses with facial defects were obtained. To measure the FS distance, a line was drawn between the anterior edge of the mental protuberance of the mandible and anterior edge of the maxilla (MM line) and extended upwards in front of the forehead. The perpendicular distance (FS distance) between the MM line and the skin at the point of largest excursion of the fetal forehead was measured. In cases in which the MM line was located anteriorly to the forehead, the distance was measured in the same fashion but was multiplied by -1. Two operators measured the FS distance twice, independently of each other. FS distances were transformed into Z-scores based on the linear relationship with crown-rump length (CRL) in normal fetuses. The distribution of FS distances in fetuses with bilateral, unilateral or median cleft lip and palate and those with retrognathia were compared with that in the normal group using Student's t-test. RESULTS: A search of the centers' databases identified 53 abnormal cases including 20, nine and eight with a bilateral, unilateral and median cleft lip and palate, respectively, and 16 cases of retrognathia. In fetuses with bilateral, unilateral and median clefts and those with retrognathia, median delta NT was 1.00 mm, 0.37 mm, 4.00 mm and 0.26 mm, respectively. Among these affected groups, 12 (60.0%), six (66.7%), two (25.0%) and eight (50.0%) fetuses had an abnormal karyotype. In the normal population, FS distance was dependent on CRL measurement (FS = 6.62 - (0.08 × CRL); r = -0.539; P < 0.0001). In fetuses with a bilateral and median cleft and in those with retrognathia, FS distance was significantly different from that in the normal population (all P < 0.0001), however, the difference was not significant in fetuses with unilateral clefts (P = 0.103). The respective Z-scores of FS distance for fetuses with bilateral, unilateral and median clefts and retrognathia were -9.7 ± 2.0, -3.1 ± 5.1, 8.2 ± 3.4 and -7.3 ± 2.3. Measurements were ≥ 99(th) and ≤ 1(st) centiles in all but one (98.1%) case. CONCLUSION: The FS distance appears to be a helpful tool in the detection of facial clefts at 11-13 weeks' gestation. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

First-trimester screening for trisomies 18 and 13, triploidy and Turner syndrome by detailed early anomaly scan.

OBJECTIVE: To examine the performance of first-trimester ultrasound screening for trisomies 18 and 13, triploidy and Turner syndrome based on fetal nuchal translucency thickness (NT), additional fetal ultrasound markers including anatomy of the nasal bone (NB), blood flow across the tricuspid valve (TV) and through the ductus venosus (DV) and a detailed fetal anomaly scan at 11-13 weeks' gestation. METHODS: This was a retrospective case-matched study involving pregnant women at 11-13 weeks' gestation. The study population consisted of fetuses with trisomy 18, trisomy 13, triploidy or Turner syndrome. For each fetus with an abnormal karyotype, 50 randomly selected euploid fetuses were added to the study population. In all cases, the crown-rump length and NT were measured. In addition NB, TV flow and DV flow were examined. The summed risk for trisomies 21, 18 and 13 was computed based on: first, maternal age (MA); second, MA and fetal NT; third, MA, NT and one of the markers NB, TV flow or DV flow; fourth, MA, NT and all these markers combined; fifth, MA, NT and fetal anomalies; and, finally, MA, NT, all markers and fetal anomalies. RESULTS: The study population consisted of 4550 euploid and 91 aneuploid fetuses. Median NT was 1.8 mm in euploid fetuses and 4.8, 6.8, 1.8 and 10.0 mm in fetuses with trisomy 18, trisomy 13, triploidy and Turner syndrome, respectively. The NB, TV flow and DV flow were abnormal in 48 (1.1%), 34 (0.7%) and 99 (2.2%) euploid fetuses, respectively, and in 42 (46.2%), 31 (34.1%) and 62 (68.1%) aneuploid fetuses, respectively. At least one defect was found in 60 (1.3%) euploid and in 76 (83.5%) aneuploid fetuses. For a false-positive rate of 3%, the detection rate for screening based on MA and fetal NT was 75.8%. It increased to 84.6-86.8% when including one of the additional ultrasound markers and it was 90.1% when all three markers were included. When screening was based on MA, fetal NT and a detailed anomaly scan, the detection rate was 94.5% and increased to 95.6% with the addition of NB, TV flow and DV flow. CONCLUSION: A detailed anomaly scan at 11-13 weeks' gestation can identify about 95% of fetuses with trisomy 18, trisomy 13, triploidy and Turner syndrome. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Cell-free fetal DNA screening in the USA: a cost analysis of screening strategies.

OBJECTIVES: To determine whether implementation of primary cell-free fetal DNA (cffDNA) screening would be cost-effective in the USA and to evaluate potential lower-cost alternatives. METHODS: Three strategies to screen for trisomy 21 were evaluated using decision tree analysis: 1) a primary strategy in which cffDNA screening was offered to all patients, 2) a contingent strategy in which cffDNA screening was offered only to patients who were high risk on traditional first-trimester screening and 3) a hybrid strategy in which cffDNA screening was offered to all patients ≥ 35 years of age and only to patients < 35 years who were high risk after first-trimester screening. Four traditional screening protocols were evaluated, each assessing nuchal translucency (NT) and pregnancy-associated plasma protein-A (PAPP-A) along with either free or total beta-human chorionic gonadotropin (ß-hCG), with or without nasal bone (NB) assessment. RESULTS: Utilizing a primary cffDNA screening strategy, the cost per patient was 1017 US$. With a traditional screening protocol using free ß-hCG, PAPP-A and NT assessment as part of a hybrid screening strategy, a contingent strategy with a 1/300 cut-off and a contingent strategy with a 1/1000 cut-off, the cost per patient was 474, 430 and 409 US$, respectively. Findings were similar using the other traditional screening protocols. Marginal cost per viable case detected for the primary screening strategy as compared to the other strategies was 3-16 times greater than the cost of care for a missed case. CONCLUSIONS: Primary cffDNA screening is not currently a cost-effective strategy. The contingent strategy was the lowest-cost alternative, especially with a risk cut-off of 1/1000. The hybrid strategy, although less costly than primary cffDNA screening, was more costly than the contingent strategy.

Facial markers in second- and third-trimester fetuses with trisomy 18 or 13, triploidy or Turner syndrome.

OBJECTIVE: To examine the effectiveness of nasal bone (NB) evaluation (including NB length (NBL)), prenasal thickness (PT) measurement, the PT:NBL ratio and the prefrontal space ratio (PFSR) in the identification of fetuses with trisomy 18 or 13, triploidy or Turner syndrome. METHODS: This was a retrospective study using stored midsagittal two-dimensional images of the facial profile of fetuses with trisomy 18 or 13, triploidy or Turner syndrome in the second and third trimesters. For images of acceptable quality, measurements were obtained of NBL (where NB was present), PT, the PT:NBL ratio and PFSR, and these measurements were compared with previously published normal ranges. RESULTS: The search of databases identified 189 fetuses that met the study criteria: 132 (69.8%) with trisomy 18, 40 (21.2%) with trisomy 13, 10 (5.3%) with triploidy and seven (3.7%) with Turner syndrome. The NB was either absent or its measurement was below the 5(th) centile in 67 (50.8%), 20 (50.0%), five (50.0%) and two (28.6%) of the fetuses with trisomy 18, trisomy 13, triploidy and Turner syndrome, respectively. The PT measurement was above the 95(th) centile in 24 (18.2%), six (15.0%), one (10.0%) and one (14.3%) of the affected fetuses, respectively. The PFSR was abnormal in 72 (54.5%), 29 (72.5%), seven (70%) and four (57.1%) of the cases and the PT:NBL ratio was above the 95(th) centile or the nasal bone was absent in 72 (54.5%), 20 (50.0%), six (60.0%) and four (57.1%) cases, respectively. CONCLUSION: Although each of the facial markers considered provides some useful information in screening for trisomy 18, trisomy 13, triploidy and Turner syndrome, the performance of none of the markers appears to be as good as that in screening for trisomy 21.

Optimal caliper placement: manual vs automated methods.

OBJECTIVE: To examine the inter- and intra-operator repeatability of manual placement of callipers in the assessment of basic biometric measurements and to compare the results to an automated calliper placement system. METHODS: Stored ultrasound images of 95 normal fetuses between 19 and 25 weeks' gestation were used. Five operators (two experts, one resident and two students) were asked to measure the BPD, OFD and FL two times manually and automatically. For each operator, intra-operator repeatability of the manual and automated measurements was assessed by within operator standard deviation. For the assessment of the interoperator repeatability, the mean of the four manual measurements by the two experts was used as the gold standard.The relative bias of the manual measurement of the three non-expert operators and the operator-independent automated measurement were compared with the gold standard measurement by means and 95% confidence interval. RESULTS: In 88.4% of the 95 cases, the automated measurement algorithm was able to obtain appropriate measurements of the BPD, OFD, AC and FL. Within operator standard deviations of the manual measurements ranged between 0.15 and 1.56, irrespective of the experience of the operator.Using the automated biometric measurement system, there was no difference between the measurements of each operator. As far as the inter-operator repeatability is concerned, the difference between the manual measurements of the two students, the resident, and the gold standard was between -0.10 and 2.53 mm. The automated measurements tended to be closer to the gold standard but did not reach statistical significance. CONCLUSION: In about 90% of the cases, it was possible to obtain basic biometric measurements with an automated system. The use of automated measurements resulted in a significant improvement of the intra-operator but not of the inter-operator repeatability, but measurements were not significantly closer to the gold standard of expert examiners.

The cavum septi pellucidi in euploid and aneuploid fetuses.

OBJECTIVE: To examine whether the cavum septi pellucidi (CSP) is larger in second- and third-trimester fetuses with chromosomal abnormalities than in euploid fetuses. METHODS: This was a retrospective study utilizing stored two-dimensional images of second- and third-trimester fetuses between 18 and 40 weeks' gestation from three centers in Germany. The width of the CSP was measured by placing the calipers on the inner portion of its lateral borders. Two operators, both of whom were blinded to the fetal karyotype and to the measurements obtained by the other, measured the CSP width. The normal range in euploid fetuses was computed based on the biparietal diameter (BPD) by applying univariate regression analysis. The CSP width in euploid and aneuploid fetuses was transformed into Z-scores and compared using Student's t-test. Univariate regression analysis was used to determine the dependency of Z-score on head biometry. RESULTS: The study population consisted of 406 singleton pregnancies, 267 with euploid fetuses, 81 with trisomy 21, 50 with trisomy 18 and eight with trisomy 13. In the euploid group, the mean CSP width was 4.5 (range, 1.8-7.4) mm. Regression analysis showed a significant dependency of CSP width on BPD (CSP width = 0.658 + (0.064 × BPD), r = 0.781, P < 0.0001; both parameters in mm). The mean CSP width increased from 3.2 to 7.1 mm for BPD values of 40 to 100 mm, respectively. In the groups of fetuses with trisomy 21, 18 and 13, mean CSP width was 5.7 (range, 2.8-10.5), 7.9 (range, 3.5-12.8) and 5.8 (range, 4.0-9.0) mm, respectively. In 42.0% of the fetuses with trisomy 21, CSP width was above the 95(th) centile. In trisomy 18 and 13, CSP width was above the 95(th) centile in 92.0% and 37.5% of cases, respectively. CONCLUSION: A large CSP width should prompt a detailed ultrasound examination to further assess the risk for chromosomal abnormalities.

Comparison of three methods of cervical measurement in the first trimester: single-line, two-line, and tracing.

OBJECTIVES: To compare three methods of cervical length measurements using ultrasound in the first trimester: single-line, two-line, and tracing. METHODS: Images appropriate for cervical length measurements were obtained using transvaginal ultrasound between 11 + 0 and 13 + 6 weeks' gestation. The cervix was measured on stored images using three methods: a single straight line, two segments (two-line method), and by tracing the distance along the cervical canal. Results were compared for intraoperator repeatability and interoperator variability. The degree of the cervical curvature was measured. RESULTS: The mean cervical measurement using the single-line measurement was 32.8 (SD 4.4) mm. The mean cervical length was essentially the same using the two-line and tracing measurement: 34.4 (SD 4.7) mm and 34.5 (SD 4.7) mm, respectively. Both intra- and interoperator agreement was high. The degree of curvature of the cervical canal was variable, with a resultant variability in the difference between the single straight line measurement and the other two types of measurement. CONCLUSIONS: Using stored images, each of the measurement techniques is highly reproducible. Both the two-line and the tracing methods yield larger measurements than the single-line technique. Therefore, it appears that in select cases the straight line measurement significantly underestimates the actual cervical length.