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.

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.

Comparison of three first trimester screening algorithms for trisomy 21 with and without adjustment for maternal characteristics.

PURPOSE: Comparison of three algorithms (DoE 2007 and DoE 2011 algorithm of the FMF Germany and MoM algorithm of the FMF UK) in first trimester biochemical screening for trisomy 21 based on maternal and gestational age, free ß-hCG, and PAPP-A and assessment of relevant maternal characteristics. MATERIALS AND METHODS: Data from 22 449 euploid singleton pregnancies undergoing combined screening for trisomy 21 at 11 to 13 weeks of gestation were examined. The measured maternal free ß-hCG and PAPP-A concentrations were converted into DoE 2007 and DoE 2011 values according to the algorithm of the FMF Germany and into MoM values according to the algorithm of the FMF UK. In each pregnancy, patient-specific risks and false-positive rates (FPR) were computed according to the three algorithms and were stratified according to gestational age, maternal ethnicity, maternal weight, and smoking status. RESULTS: Free ß-hCG and PAPP-A MoM and DoE 2011 were acceptably independent from maternal characteristics and gestational age, while there was a strong relationship between maternal weight and the DoE 2007 values. For a risk cut-off that corresponds to an overall 5 % FPR rate for each algorithm, the FPR in each group were around 5 % at gestational week 11 - 13. The FPR of the DoE 2007 algorithm increased linearly with maternal weight from 3.6 % in women of 50 kg or less to 11.8 % in women of more than 110 kg. CONCLUSION: Especially maternal weight has a significant impact on the risk calculation. In contrast to the DoE 2007 algorithm, the DoE 2011 and MoM algorithms both adjust for maternal weight.

First-trimester combined screening for trisomy 21 with different combinations of placental growth factor, free ß-human chorionic gonadotropin and pregnancy-associated plasma protein-A.

OBJECTIVE: To examine placental growth factor (PlGF) in euploid and trisomy 21 pregnancies at 11-13 weeks' gestation and to model the impact on first-trimester combined screening. METHODS: PlGF was measured in 509 (409 euploid and 100 trisomic) fetal serum samples derived from prospective first-trimester combined screening for trisomy 21 at 11-13 weeks' gestation. The serum samples were stored at -80°C, following the measurement of free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels, for median time spans of 0.9 and 4.1 years in the euploid and trisomy 21 pregnancies, respectively. The effect of additional PlGF measurement at the time of combined screening was investigated by simulating fetal nuchal translucency (NT) measurements and multiples of the median (MoM) values for PAPP-A, free ß-hCG and PlGF for 20,000 euploid and 20,000 trisomy 21 pregnancies. Patient-specific combined risks were calculated based on maternal age and fetal NT in addition to free ß-hCG, PAPP-A and PlGF, PAPP-A and PlGF or free ß-hCG and PlGF, and detection and false-positive rates were calculated. RESULTS: Median PlGF-MoM was 1.0 (95% confidence interval (CI), 0.96-1.04) in euploid fetuses and significantly lower, at 0.73 (95% CI, 0.70-0.76), in trisomy-21 fetuses (P < 0.0001). There was no significant dependency between PlGF-MoM and either gestational age at the time of blood sampling (r = 0.087, P = 0.392) or sample storage time (r = 0.028, P = 0.785). Modeled detection and false-positive rates for first-trimester combined screening (based on maternal and gestational age, fetal NT and maternal serum biochemistry) without PlGF were 85% and 2.7% for a fixed risk cut-off of 1:100. The addition of PlGF increased the detection rate to 87% and reduced the false-positive rate to 2.6%. Screening by maternal age and fetal NT in combination with PlGF and PAPP-A or in combination with PlGF and free ß-hCG provided detection rates of 82% and 79%, with false-positive rates of 2.7% and 3.0%, respectively. CONCLUSION: In pregnancies with trisomy 21 PlGF is reduced. The impact on the overall screening performance for trisomy 21 is low and does not justify the measurement of PlGF solely for trisomy 21 screening. However, as PlGF is measured with the aim of assessing the risk for pre-eclampsia, further improvement in screening for trisomy 21 can be considered as an added benefit.

Impact of bias in crown-rump length measurement at first-trimester screening for trisomy 21.

OBJECTIVE: To assess the repeatability of crown-rump length (CRL) measurement and examine the effect of its over- and underestimation on first-trimester combined screening. METHODS: Intra- and interoperator repeatability of CRL measurement at 11-13 weeks of gestation was assessed in 124 cases by two operators. Raw data were transformed into gestational age and intra- and interoperator repeatability was evaluated by within-operator standard deviation (SD) and the SD of differences in measurements between both operators. Modeling techniques were used to assess the impact of CRL measurement error on general population screening and on the operator-specific screening performance. The impact of errors in CRL measurement were investigated by simulating fetal nuchal translucency (NT) measurements and multiple of the median (MoM) values for pregnancy-associated plasma protein A (PAPP-A) and free ß-human chorionic gonadotropin (ß-hCG) for 500 000 euploid and 500 000 trisomy 21 pregnancies at 12 weeks and 9 weeks of gestation, and adding to or subtracting from each CRL value up to 10 mm and recalculating patient-specific risks. RESULTS: Within-operator SD of the CRL measurement was 1.27 days of gestation. The SD of the differences in CRL measurement between operators was 1.37 days of gestation. Both intra- and interoperator 95% limits of agreement were around ± 5 mm. In general population-based screening, a CRL measurement error SD of 5 mm accounts for an estimated 5% of the SD of log MoM PAPP-A and less than 1% of the SD of log MoM free ß-hCG. Modeling the effect of removing this measurement error on overall screening performance showed a minimal impact. For a risk cut-off of 1 in 100, the benefit in terms of overall screening performance would be an increase in detection rate of about 1% and a reduction in false-positive rate of less than 0.1%. With regard to the operator-specific screening performance, a consistent 5-mm underestimation of CRL reduces the detection rate from 84% to 79% and the false-positive rate from 2.4% to 1.2%. With a consistent 5-mm overestimation the rates would be 88% and 5.6%, respectively. CONCLUSION: The impact of the interoperator variability in CRL measurement on patient-specific risk needs to be taken into account when interpreting first-trimester screening results. A systematic under- or overestimation of CRL should be avoided.

[Sonographic criteria for the differentiation of benign and malignant breast lesions using real-time spatial compound imaging in combination with XRES adaptive image processing]. / Dignitätskriterien der Mammasonografie unter Anwendung des Real-Time Compound Image in Kombination mit dem XRES Adaptiv Image Processing.

PURPOSE: The purpose of the study was to analyze sonographic criteria for the differentiation of benign and malignant breast lesions using real-time spatial compound imaging (CT) in combination with adaptive image processing (XRES). MATERIALS AND METHODS: In a retrospective analysis of 460 patients, the sonographic criteria: shape, orientation, margin, echo pattern and posterior acoustic features were determined using CT and XRES. All investigations were performed using a 12 MHz linear transducer. The findings were classified according to the DEGUM criteria analogous to BIRADS and were histologically confirmed by core needle or vacuum biopsy. Statistical analysis was performed using a Chi-square test, logistic uni- and multivariate regression analysis and an ROC-curve analysis to detect the false-positive rate. RESULTS: All investigated diagnostic criteria were significant in the descriptive analysis (Chi-squared). The multivariate analysis showed that the criteria of irregular shape versus round, and not circumscribed margin versus circumscribed margin as well as the posterior acoustic features of enhanced versus reduced have a significant influence on the prediction of a malignant finding. The univariate analysis also showed a statistical significance using the indifferent and not parallel orientation versus parallel. To attain a detection rate of > 95 %, a false-positive rate of 60 % must be expected. CONCLUSION: This study shows that when using CT in combination with XRES, the analyzed sonographic criteria for the differentiation of benign and malignant breast lesions are still of diagnostic value. In particular, the shape, margin and posterior sonographic features are important.

Prospective detection of open spina bifida at 11-13 weeks by assessing intracranial translucency and posterior brain.

We describe a case series of six fetuses with open spina bifida (OSB) from four different prenatal units, where the anomaly was detected at the routine 11-13-week ultrasound examination. Crown-rump length ranged from 49 to 78 mm. All cases were first suspected during nuchal translucency thickness measurement in the mid-sagittal plane of the face. OSB was lumbosacral in five fetuses and cervical in one. The intracranial translucency (IT) was obliterated in two cases, but some fluid was found in the other four cases. However, in all cases the typical landmarks of a normal posterior brain and normal IT were absent. In all six cases the ratio of brainstem diameter to brainstem-occipital bone distance was increased (≥ 1). This detection of an abnormal posterior brain led to a targeted examination and detection of the spinal lesion during the same examination in five cases, whereas in one suspicious case the patient was recalled at 17 weeks, when the abnormality was detected. Two fetuses had both multiple anomalies and trisomy 18. These prospective cases demonstrate the feasibility of using the standard mid-sagittal plane commonly used for NT measurement to assess the IT and the posterior brain and to determine the presence of OSB during NT screening.

[Pierre Robin Sequence: interdisciplinary treatment after prenatal diagnosis]. / Pierre Robin Sequenz: Pränatale Diagnostik und interdisziplinäre Therapie.

BACKGROUND: Pierre Robin Sequence (PRS) is characterised by mandibular micrognathia and/or retrognathia, glossoptosis and upper airway obstruction (UAO). In severe cases, UAO and cyanosis occur immediately after birth and endoscopic intubation may become necessary. Therefore, prenatal diagnosis with referral to a specialized department is important. METHOD: A non-invasive interdisciplinary treatment protocol is presented. The postnatal adjustment of the preepiglottic baton plate (PEBP) as early as possible is essential in this concept. EVIDENCE: In a randomised cross-over trial with 11 patients with isolated PRS, the PEBP was found to reduce the apnoea index significantly and to be superior to a conventional palatal plate. An uncontrolled longitudinal study indicated that the UAO had normalised 3 months after discharge; all infants showed adequate weight gain with bottle feeding. In a comparative study with 34 healthy children and 34 children with isolated PRS, no significant differences in cognitive outcome was found. CONCLUSIONS: Interdisciplinary co-operation between prenatal care, neonatology and orthodontics is a pre-requisite for optimal postnatal therapy. Complications of UAO can be avoided by early and adequate treatment, resulting in good results for feeding, speech and facial profile. Invasive surgical treatment options like tongue-lip-adhesion, mandibular extension or distraction should be obsolete.

[Cross-validation of the first trimester screening algorithm of the FMF London on 38,700 pregnancies in Germany]. / Cross-Validierung des Screening-Algorithmus der FMF London an 38,700 Ersttrimester-Untersuchungen in Deutschland.

PURPOSE: Validation of the performance of the new algorithm of the FMF London for screening for trisomy 21 using a combination of maternal age, fetal nuchal translucency (NT) and maternal serum free ß-hCG and PAPP-A. MATERIALS AND METHODS: Between 2002 and 2007, NT was measured prospectively in 39,004 pregnancies in the context of routinely performed first trimester screening in Germany. Individual trisomy 21 risks were calculated by a combination of NT, maternal age, free ß-hCG, and PAPP-A using the FMF algorithm in force at the time of investigation. In this study we recalculated the trisomy 21 risks applying the new algorithm of the FMF UK that includes the new mixture model for the NT measurement. RESULTS: 38,751 singleton pregnancies could be included in the study of which 109 (0.3 %) had a trisomy 21. Only 35 % of the NT measurements of euploids were above the median and 25 % of the NT measurements were below the 5th percentile of the FMF UK. For sonographers that were qualified according to level II or III of the German DEGUM system, the median NT of fetuses with trisomy 21 was 0.9 mm above the median of the FMF UK and only 0.5 mm above the median for all other sonographers. Despite the limited performance of the NT measurement, the overall detection rate for a trisomy 21 was 90.8 % when combining the NT with maternal age, PAPP-A and free ß-hCG. The overall false-positive rate for a trisomy 21 was 6.5 % at a cut-off value of 1:300. CONCLUSION: In this study we were able to show that the use of the new risk algorithm of the FMF UK leads to a trisomy 21 detection rate of about 90 % at a 5 % false-positive rate in a German collective despite a significant underestimation of the NT.

Impact of the maternal age-related risk in first-trimester combined screening for trisomy 21.

OBJECTIVE: To examine the impact of the maternal age-related risk in first-trimester combined screening for trisomy 21. METHODS: Prospective assessment of risk for trisomy 21 by a combination of maternal age, fetal NT thickness and maternal serum PAPP-A and free ß-hCG at 11+0 to 13+6 weeks of gestation between April 2002 and February 2007. Screening for trisomy 21 by patient-specific risks based on the maternal and gestational age-related risk multiplied by a likelihood ratio for NT and for maternal serum biochemistry were compared with a screening policy that is only based on the combined likelihood ratio for fetal NT and maternal serum biochemistry. RESULTS: The study population consisted of 38,603 euploid pregnancies and 109 fetuses with trisomy 21. In screening for trisomy 21 by fetal NT and maternal serum biochemistry in combination with and without maternal age with a fixed false-positive rate of 3%, the detection rate was 82.6 and 79.8%, respectively. In the group of women with a maternal age of less than 30 years and between 30 and 35 years, there was no difference in the detection rate. For women with a maternal age of 35 years or older, the detection rate increased from 77.1% without maternal age to 94.3% with maternal age, respectively. CONCLUSION: The overall difference between first-trimester screening based on fetal NT and maternal serum biochemistry with and without maternal age is about 3%. In screening with a fixed cut-off, the maternal age-related risk keeps the false-positive rate low in younger women and increases the detection rate in older women.

Impact of bias in serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A multiples of the median levels on first-trimester screening for trisomy 21.

OBJECTIVE: To examine the effect of bias in median multiples of the median (MoM) levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (ß-hCG) on first-trimester combined screening for trisomy 21. METHODS: The effects of deviations in the MoM levels of free ß-hCG and PAPP-A were investigated by simulating nuchal translucency (NT) at 12 weeks and MoM values for PAPP-A and free ß-hCG for 500 000 euploid and 500 000 trisomy 21 pregnancies at 9 and at 12 weeks of gestation. Likelihoods were calculated using the mixture model for NT and the standard Gaussian model for log MoM PAPP-A and free ß-hCG values. Deviations in MoM marker levels were simulated by applying percentage changes of 5% to 20% to MoM values. Detection and false-positive rates were calculated with and without adjustments of the maternal serum marker levels by taking the proportion of euploid and aneuploid cases above given thresholds for each maternal age and then taking a weighted average with respect to the maternal age distribution. RESULTS: With median MoM levels on target, the modeled detection and false-positive rates in combined screening for trisomy 21 at 12 weeks of gestation with a fixed risk cut-off of 1 in 100 were 85% and 2.5%, respectively. For median MoM levels of free ß-hCG and PAPP-A between 0.8 and 1.2 MoM, detection rates ranged from 77% to 91%, with corresponding false-positive rates ranging from 1.0% to 6.1%. CONCLUSION: In first-trimester screening for trisomy 21, biases in the serum marker MoM levels of 10% can increase false-positive rates by over 50%, whilst biases of 20% can more than double false-positive rates.

Prenatal diagnosis of a fetus with terminal deletion of chromosome 1 (q43) in first-trimester screening: is there a characteristic antenatal 1q deletion phenotype? A case report and review of the literature.

The terminal deletion of chromosome 1q is a disease of rare incidence. It might be hereditary or caused by spontaneous changes within the chromosome. Phenotypic characteristics including typical facial appearance, microcephaly, psychomotor retardation and variable other anomalies are suggested to be based on the loss of macrochromosomal materials within the long arm of chromosome 1. The number of symptoms is related to the loss of genetic material. To date, only very few cases of terminal 1q deletion syndrome have been diagnosed in utero, mainly after 20 weeks of gestation. Here, we present a case of del(1q)syndrome in a first-trimester fetus. Besides other structural anomalies of the fetus, prenatal ultrasound at 13 weeks' gestation demonstrated severe microgenia and suspicion of cardiac defect. Chorionic villous sampling was performed, and cytogenetic analysis showed a de novo terminal chromosome 1 long arm deletion. We discuss the structural features of antenatally diagnosed fetuses with terminal deletion of chromosome 1 and try to give an answer to the question whether there is a characteristic antenatal 1q deletion phenotype.

Assessment of the ductus venosus, tricuspid blood flow and the nasal bone in second-trimester screening for trisomy 21.

OBJECTIVE: To examine the prevalence of reversed a-wave in the ductus venosus, tricuspid regurgitation and absent nasal bone, in a second-trimester population undergoing amniocentesis, after exclusion of major fetal defects and to estimate the performance in screening for trisomy 21 based on maternal age and these markers in a general population. METHODS: This was a retrospective study involving pregnancies undergoing amniocentesis due to increased risk for trisomy 21, mainly because of advanced maternal age. Before the invasive procedure, an ultrasound examination was carried out to exclude major fetal defects and to examine the ductus venosus, tricuspid blood flow and the presence of the fetal nasal bone. Modeling techniques were used based on 20 000 euploid pregnancies and 20 000 pregnancies with trisomy 21 to assess the screening performance in a general population. RESULTS: The study population consisted of 3613 euploid pregnancies and 35 cases with trisomy 21. In the euploid group, reversed flow in the ductus venosus, tricuspid regurgitation and an absent nasal bone was observed in 1.7%, 1.5% and 0.1% of cases, respectively. In the trisomic group, these markers were found in 14.3%, 11.4% and 14.3% of cases, respectively. For a 5% false-positive rate, the detection rate in screening for trisomy 21, based on maternal age and either ductus venosus, tricuspid blood flow or nasal bone would be 33.8%, 32.4% or 31.4%, respectively. Screening by maternal age alone would detect 29.0% of the fetuses with trisomy 21. Receiver-operating characteristics curve analysis showed a slight but significant improvement in screening performance for trisomy 21 based on the inclusion of these markers. CONCLUSION: Second-trimester ultrasound screening for trisomy 21 based on maternal age with additional assessment of the ductus venosus, tricuspid blood flow and the fetal nasal bone in otherwise normal-appearing fetuses is only marginally better than is screening by maternal age alone.

Two-stage first-trimester screening for trisomy 21 by ultrasound assessment and biochemical testing.

OBJECTIVES: This study was carried out to examine the performance of a contingent policy in first-trimester screening for trisomy 21, in which the estimated risk was first derived by a combination of maternal age, fetal nuchal translucency (NT) thickness, presence/absence of the nasal bone, blood flow in the ductus venosus or flow across the tricuspid valve, and biochemical testing was carried out only in those who were found to have an intermediate risk. We also examined the performance of a policy in which the estimated risk was first derived by a combination of maternal age and biochemical testing, and ultrasound examination was carried out only in those with an intermediate risk. METHODS: The data for this study were derived from prospective screening for trisomy 21 in singleton pregnancies, using, as markers, a combination of maternal age, fetal NT thickness and maternal-serum free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein-A (PAPP-A), in a one-stop clinic for first-trimester assessment of risk at 11 + 0 to 13 + 6 weeks of gestation. Assessment of the fetal nasal bone, ductus venosus flow and tricuspid flow were also routinely performed by appropriately trained sonographers. The performance of different screening policies was examined. RESULTS: The study population consisted of 19 614 pregnancies with a normal karyotype or delivery of a phenotypically normal baby (euploid group) and 122 cases of trisomy 21. The best performance was achieved by a contingent policy in which first-stage screening was based on maternal age, fetal NT thickness and either tricuspid valve or ductus venosus blood flow, followed by biochemical testing only those with an intermediate risk, of 1 in 51 to 1 in 1000 (which constituted about 20% of the total). The performance of contingent screening in which first-stage testing relies on biochemistry was poorer than when first-stage screening was performed by ultrasound examination because, in order to achieve the same detection rate, the false-positive rate was twice as high. CONCLUSION: Effective first-trimester screening for trisomy 21 can be achieved by a contingent policy in which first-stage testing is based on ultrasound examination and second-stage biochemical testing is carried out in only 20% of the patients.

Prenatal diagnosis and management of a fetal intra-abdominal teratoma: a case report and review of the literature.

We report on a case of a large intra-abdominal teratoma diagnosed antenatally and managed successfully after birth. Intra-abdominal teratomas are rare in prenatal life. Ultrasound examination shows a heterogenic tumor with cystic and solid components. After postpartum surgical removal, the prognosis is generally good.

Prospective validation of first-trimester combined screening for trisomy 21.

OBJECTIVE: To examine the performance of the new algorithm in screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A). METHODS: This was a prospective screening study for trisomy 21 in singleton pregnancies at 11 + 0 to 13 + 6 weeks of gestation using an algorithm combining maternal age, fetal NT thickness based on the mixture model for the assessment of NT, and maternal serum free beta-hCG and PAPP-A based on a multiple regression model for the assessment of serum biochemistry. The NT measurements were performed by 60 operators who had obtained The Fetal Medicine Foundation certificate of competence in the 11-13-week scan. RESULTS: The study population consisted of 19 614 pregnancies with a normal karyotype or delivery of a phenotypically normal baby (euploid group) and 122 cases of trisomy 21. In the euploid fetuses the NT was above the previously defined 50(th), 95(th) and 99(th) centiles in 10 033 (51.2%), 618 (3.2%) and 123 (0.6%) cases and the respective values for trisomy 21 were 117 (95.9%), 94 (77.0%) and 57 (46.7%). The median fetal NT was within 0.1 mm of the expected in 47 (78.3%) of the 60 sonographers and within 0.2 mm in all. In the euploid fetuses the median free beta-hCG was 1.0 (range, 0.1-29.4) multiples of the median (MoM) and the median PAPP-A was 1.0 (range, 0.2-3.3) MoM. The median MoM values were 1.0 or close to 1.0 MoM for each subgroup of pregnancy characteristics, including gestations of 11, 12 and 13 weeks, maternal weight of < 60 kg, 60-80 kg and > 80 kg, different ethnic origins, cigarette smokers and non-smokers, natural conception and in vitro fertilization. For a false-positive rate of 3%, the detection rate of trisomy 21 in screening by maternal age and fetal NT was 81% (95% CI, 73-89%), by maternal age and maternal serum biochemistry it was 63% (95% CI, 56-72%) and by combined screening based on maternal age, fetal NT and maternal serum biochemistry it was 90% (95% CI, 84-96%). CONCLUSION: This study has validated the new risk algorithm and demonstrated that in combined screening for trisomy 21 based on maternal age, fetal NT and free beta-hCG and PAPP-A the detection rate is about 90% for a 3% false-positive rate.

Effect of deviation of nuchal translucency measurements on the performance of screening for trisomy 21.

OBJECTIVES: To examine the effect of deviations in median nuchal translucency thickness (NT) and the spread in measurements on the performance of screening for trisomy 21 by maternal age and fetal NT, and by maternal age, fetal NT and maternal serum biochemistry. METHODS: We simulated the NT and multiples of the median values for pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) for 500 000 euploid and 500 000 trisomy 21 pregnancies at 12 weeks of gestation. Detection rates for trisomy 21 and false-positive rates were calculated without adjustments in NT and by adding or subtracting values ranging from 0.1 to 1.0 mm to each observed measurement. In addition, the effects of variation in the scatter of NT measurements were examined by applying a multiplicative factor ranging from 0.5 to 2 to the SD. RESULTS: The detection rate of trisomy 21 for a fixed false-positive rate of 3% in screening by maternal age and fetal NT was 72%, and in screening by maternal age, fetal NT and serum free beta-hCG and PAPP-A it was 86%. A consistent underestimate or overestimate in the measured NT reduced the detection rate of trisomy 21 for a fixed-false positive rate. At a fixed screen-positive cut-off an underestimate in fetal NT reduced the detection rate whereas an overestimate in NT increased the false-positive rate. A widening in the scatter of measurements had only a small impact on the detection rate but it caused a major increase in the false-positive rate. CONCLUSIONS: High performance of screening necessitates appropriate measurement of fetal NT. This paper demonstrates the effect of deviations in the median and SD of NT from the expected on the performance of screening and can form the basis of audit of results of individual sonographers.