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.

Risk of fetal loss after chorionic villus sampling in twin pregnancy derived from propensity score matching analysis.

OBJECTIVE: To estimate the risk of fetal loss associated with chorionic villus sampling (CVS) in twin pregnancy, using propensity score analysis. METHODS: This was a multicenter cohort study of women with twin pregnancy undergoing ultrasound examination at 11-13 weeks' gestation, performed in eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. The risk of death of at least one fetus was compared between pregnancies that had and those that did not have CVS, after propensity score matching (1:1 ratio). This procedure created two comparable groups by balancing the maternal and pregnancy characteristics that lead to CVS being performed, similar to how randomization operates in a randomized clinical trial. RESULTS: The study population of 8581 twin pregnancies included 445 that had CVS. Death of one or two fetuses at any stage during pregnancy occurred in 11.5% (51/445) of pregnancies in the CVS group and in 6.3% (515/8136) in the non-CVS group (P < 0.001). The propensity score algorithm matched 258 cases that had CVS with 258 non-CVS cases; there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non-CVS group (odds ratio (OR), 0.81; 95% CI, 0.48-1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss; when the background risk was higher, the risk of fetal loss after CVS decreased (OR, 0.46; 95% CI, 0.23-0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS increased (OR, 2.45; 95% CI, 0.95-7.13). The effects were statistically significantly different (P-value of the interaction = 0.005). For a pregnancy in which the background risk of fetal loss was about 6% (the same as in our non-CVS population), there was no change in the risk of fetal loss after CVS, but, when the background risk was more than 6%, the posterior risk was paradoxically reduced, and when the background risk was less than 6%, the posterior risk increased exponentially; for example, if the background risk of fetal loss was 2.0%, the relative risk was 2.8 and the posterior risk was 5.6%. CONCLUSION: In twin pregnancy, after accounting for the risk factors that lead to both CVS and spontaneous fetal loss and confining the analysis to pregnancies at lower prior risk, CVS seems to increase the risk of fetal loss by about 3.5% above the patient's background risk. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal loss after chorionic villus sampling in twin pregnancy.

OBJECTIVE: To estimate the chorionic villus sampling (CVS)-related risk of fetal loss in twin pregnancy after adjustment for chorionicity, nuchal translucency thickness (NT), intertwin discordance in crown-rump length (CRL), maternal demographic characteristics and serum pregnancy-associated plasma protein-A (PAPP-A) and free ß-human chorionic gonadotropin (ß-hCG). METHODS: This was a multicenter study from eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. Data were obtained prospectively from women with twin pregnancy undergoing routine ultrasound examination at 11-13 weeks' gestation. Multivariable logistic regression analysis with backward stepwise elimination was used to examine whether CVS provided a significant independent contribution to the prediction of risk of fetal loss after adjusting for maternal and pregnancy characteristics, including maternal age, racial origin and weight, method of conception, smoking status, parity, chorionicity, intertwin discordance in CRL, fetal NT ≥ 95th percentile and free ß-hCG and PAPP-A multiples of the median. Similarly, within the CVS group, multivariable logistic regression analysis was used to investigate the effect of the number of intrauterine needle insertions and size of the needle on the risk of fetal loss. RESULTS: The study population of 8581 twin pregnancies undergoing ultrasound examination at 11-13 weeks' gestation included 316 dichorionic and 129 monochorionic twins that had CVS. First, in twin pregnancies undergoing CVS, compared to those not undergoing CVS, there was a 2-fold increased risk of fetal loss at < 24 weeks' gestation and of loss at any stage in pregnancy. Second, the factors providing a significant independent contribution to the prediction of miscarriage or fetal loss in twin pregnancy were increased maternal weight, black racial origin, monochorionicity, and more so monoamnionicity, large intertwin discordance in CRL and increased fetal NT, and, in the case of fetal loss at any stage, there was also a contribution from assisted conception and low serum PAPP-A. Third, after adjustment for maternal and pregnancy characteristics, CVS did not provide a significant contribution to the risk of fetal loss. Fourth, in twin pregnancies that had CVS, there was no significant contribution to fetal loss from the number of intrauterine needle insertions or needle size. CONCLUSION: The 2-fold increased risk of fetal loss following CVS in twin pregnancy can, to a great extent, be explained by maternal and pregnancy characteristics rather than the invasive procedure itself. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Outcome of pregnancies with recent primary cytomegalovirus infection in first trimester treated with hyperimmunoglobulin: observational study.

OBJECTIVE: To examine the efficacy of hyperimmunoglobulin (HIG) treatment in women with a recent primary cytomegalovirus (CMV) infection up to 14 weeks' gestation. METHODS: This is an ongoing observational study conducted at the prenatal medicine departments of the University Hospitals of Tübingen, Bonn, Cologne and Erlangen, Germany, as well as at the Laboratory Prof. Gisela Enders and Colleagues in Stuttgart, Germany and the Institute for Medical Virology at the University of Tübingen, Tübingen, Germany. Enrolment criteria were the presence of confirmed recent primary CMV infection in the first trimester and a gestational age at first HIG administration of ≤ 14 weeks. The following inclusion criteria indicated a recent primary infection: low anti-immunoglobulin (Ig)-G levels, low anti-CMV-IgG avidity in the presence of a positive CMV-IgM test and no positive reactivity or just seroconversion anti-gB2-IgG-reactivity. HIG administration was started as soon as possible within a few days after the first visit. HIG was administered intravenously at a dose of 200 IU/kg maternal body weight and repeated every 2 weeks until about 18 weeks' gestation. The primary outcome was maternal-fetal transmission at the time of amniocentesis. Multivariate logistic regression analysis was used to determine significant covariates that could predict maternal-fetal transmission. RESULTS: We included 149 pregnancies (153 fetuses) that completed the treatment. Median maternal age and weight were 32.0 years and 65.0 kg, respectively. Median gestational age at the time of first referral to one of the four centers was 9.4 weeks. Median anti-CMV-IgG level, anti-CMV-IgM index and CMV-IgG avidity were 5.7 U/mL, 2.5 and 22.3%, respectively. HIG treatment was started at a median gestational age of 10.6 weeks and ended at a median of 17.9 weeks. Within this time frame, HIG was administered on average four times in each patient. Amniocentesis was carried out at a median gestational age of 20.4 weeks. In 143 (93.5%) of the 153 cases, the fetus was not infected. Maternal-fetal transmission occurred in 10 cases (6.5% (95% CI, 3.2-11.7%)). On uni- and multivariate logistic regression analysis, the level of anti-IgM index was the only factor associated significantly with maternal-fetal transmission at amniocentesis. However, only four (40.0%) of the 10 cases with maternal-fetal transmission had an anti-IgM index above 11.4, which corresponds to the 95th centile of pregnancies without transmission. CONCLUSIONS: HIG is a treatment option to prevent maternal-fetal transmission in pregnancy with a primary CMV infection. However, HIG treatment seems to be beneficial primarily in women with a recent primary infection in the first trimester or during the periconceptional period, and when it is administered at a biweekly dose of 200 IU/kg. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of 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.

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.

Prevention of maternal-fetal transmission of cytomegalovirus after primary maternal infection in the first trimester by biweekly hyperimmunoglobulin administration.

OBJECTIVE: To examine the efficacy of biweekly hyperimmunoglobulin (HIG) administration to prevent maternal-fetal transmission of cytomegalovirus (CMV) in women with primary first-trimester CMV infection. METHODS: This was a prospective observational study of women with confirmed primary CMV infection in the first trimester who had the first HIG administration at or before 14 weeks' gestation. All women had biweekly HIG treatment until 20 weeks' gestation at a dose of 200 IU/kg of maternal body weight. Each subject underwent amniocentesis at least 6 weeks after first presentation at about 20 weeks. Primary outcome was maternal-fetal transmission at the time of amniocentesis, and secondary outcome was the frequency of congenital CMV infection at birth. The results were compared with a historic cohort of women with first-trimester CMV infection who did not undergo HIG treatment and who had amniocentesis at about 20 weeks. RESULTS: Subjects were 40 pregnant women with a primary CMV infection, with a median gestational age at first presentation of 9.6 (range, 5.1-14.3) weeks. On average, HIG administration started at 11.1 weeks and continued until 16.6 weeks. Within this interval, HIG was administered between two and six times in each patient. While CMV immunoglobulin-G (IgG) monitoring showed periodic fluctuations during biweekly HIG administration cycles, high CMV-IgG avidity indices remained stable over the whole treatment period. Maternal-fetal transmission before amniocentesis occurred in only one of the 40 cases (2.5% (95% CI, 0-13.2%)). At delivery, two additional subjects were found to have had late-gestation transmission. Considering all three cases with maternal-fetal transmission, the transmission rate was 7.5% (95% CI, 1.6-20.4%) in our 40 cases. All infected neonates were asymptomatic at birth. The matched historical control group consisted of 108 pregnancies. Thirty-eight transmissions (35.2% (95% CI, 26.2-45.0%)) occurred in the control group, which was significantly higher (P < 0.0001) than the transmission rate in the HIG treatment group. CONCLUSION: After a primary maternal CMV infection in the first trimester, biweekly HIG administration at a dose of 200 IU/kg prevents maternal-fetal transmission up to 20 weeks' gestation. 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.

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.

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.

Quality Requirements for the early Fetal Ultrasound Assessment at 11-13+6 Weeks of Gestation (DEGUM Levels II and III).

The early fetal ultrasound assessment at 11 - 13(+6) weeks of gestation remains the cornerstone of care despite the progress in diagnosing fetal chromosomal defects using cell-free fetal DNA (cffDNA) from the maternal circulation. The measurement of nuchal translucency (NT) allows the risk calculation for the fetal trisomies 21, 18 and 13 but also gives information on those fetal chromosomal defects which are at present unable to be detected using cffDNA. Nuchal translucency is the only auditable parameter at 11 - 13(+6) weeks and gives thus information on the quality of the first trimester anomaly scan. In addition it gives indirect information on the risks for fetal defects and for cardiac anomalies. Also the chances for a healthy live baby can be estimated. As experience with first trimester anomaly scanning increases, and the resolution of the ultrasound equipment has increased substantially, more and more details of the fetal anatomy become accessible at the first trimester scan. Therefore fetal anatomical defects and complex anomalies have become amenable to examination in the first trimester. This guideline describes compulsory and optional parameters for investigation at the first trimester scan and outlines a structured method of examining a first trimester fetus at 11 - 13(+6) weeks of gestation.

First-trimester contingent screening for trisomies 21, 18 and 13 by fetal nuchal translucency and ductus venosus flow and maternal blood cell-free DNA testing.

OBJECTIVE: To examine performance of screening for major trisomies by a policy of first-line assessment of risk according to maternal age, fetal nuchal translucency thickness (NT) and ductus venosus pulsatility index for veins (DV-PIV) followed by cell-free DNA (cfDNA) testing in pregnancies with an intermediate risk. METHODS: We estimated the distribution of risks based on maternal age, fetal NT and DV-PIV in a dataset of 86 917 unaffected and 491 trisomic pregnancies undergoing prospective screening for trisomies. Performance of screening for trisomies by cfDNA testing was derived from a meta-analysis of clinical validation studies. We estimated performance and cost of screening for trisomies using different combinations of ultrasound screening and cfDNA testing. RESULTS: Screening for trisomies 21, 18 and 13 according to a combination of maternal age, fetal NT and DV-PIV in all pregnancies, followed by invasive testing in the high-risk group (≥ 1:10) and cfDNA testing in the intermediate-risk group (1:11-1:3000) can potentially detect about 96%, 95% and 91% of cases, respectively, with a false-positive rate (FPR) of 0.8%. On the assumption that the costs for ultrasound screening, cfDNA testing and invasive testing are €150, €500 and €1000, respectively, the overall cost of such a policy would be about €250 per patient. The alternative policy, of universal screening by cfDNA testing, can potentially detect about 99%, 97% and 92% of cases of trisomies 21, 18 and 13, but at an overall cost of more than €500 per patient. CONCLUSION: Incorporation of cfDNA testing into a contingent policy of early screening for the major trisomies, based on the risk derived from first-line screening by a combination of maternal age, fetal NT and DV-PIV, can detect a high proportion of affected cases with a low FPR.

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.

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.