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Objectives: To assess the diagnostic accuracy of two‐dimensional ultrasound at 11–14 weeks' gestation as a screening test for individual fetal anomalies and to identify factors impacting on screening performance. Methods: This was a systematic review and meta‐analysis that was developed and registered with PROSPERO (CRD42018111781). MEDLINE, EMBASE, Web of Science Core Collection and the Cochrane Library were searched for studies evaluating the diagnostic accuracy of screening for 16 predefined, non‐cardiac, congenital anomalies considered to be of interest to the early anomaly scan. We included prospective and retrospective studies from any healthcare setting conducted in low‐risk, mixed‐risk and unselected populations. The reference standard was the detection of an anomaly on postnatal or postmortem examination. Data were extracted to populate 2 × 2 tables and a random‐effects model was used to determine the diagnostic accuracy of screening for the predefined anomalies (individually and as a composite). Secondary analyses were performed to determine the impact on detection rates of imaging protocol, type of ultrasound modality, publication year and index of sonographer suspicion at the time of scanning. Post‐hoc secondary analysis was conducted to assess performance among studies published during or after 2010. Risk of bias assessment and quality assessment were undertaken for included studies using the Quality Assessment of Diagnostic Accuracy Studies‐2 tool. Results: From 5684 citations, 202 papers underwent full‐text review, resulting in the inclusion of 52 studies comprising 527 837 fetuses, of which 2399 were affected by one or more of the 16 predefined anomalies. Individual anomalies were not equally amenable to detection on first‐trimester ultrasound: a high (> 80%) detection rate was reported for severe conditions, including acrania (98%), gastroschisis (96%), exomphalos (95%) and holoprosencephaly (88%); the detection rate was lower for open spina bifida (69%), lower urinary tract obstruction (66%), lethal skeletal dysplasias (57%) and limb‐reduction defects (50%); and the detection rate was below 50% for facial clefts (43%), polydactyly (40%) and congenital diaphragmatic hernia (38%). Conditions with a low (< 30%) detection rate included bilateral renal agenesis (25%), closed spina bifida (21%), isolated cleft lip (14%) and talipes (11%). Specificity was > 99% for all anomalies. Secondary analysis showed that detection improved with advancing publication year, and that the use of imaging protocols had a statistically significant impact on screening performance (P < 0.0001). Conclusions: The accurate detection of congenital anomalies using first‐trimester ultrasound is feasible, although detection rates and false‐positive rates depend on the type of anomaly. The use of a standardized protocol allows for diagnostic performance to be maximized, particularly for the detection of spina bifida, facial clefts and limb‐reduction defects. Highlighting the types of anomalies amenable to diagnosis and determining factors enhancing screening performance can support the development of first‐trimester anomaly screening programs. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Deep learning (DL) is a new technology that can assist prenatal ultrasound (US) in the detection of congenital heart disease (CHD) at the prenatal stage. Hence, an economic-epidemiologic evaluation (aka Cost-Utility Analysis) is required to assist policymakers in deciding whether to adopt the new technology. Methods: The incremental cost-utility ratios (CUR), of adding DL assisted ultrasound (DL-US) to the current provision of US plus pulse oximetry (POX), was calculated by building a spreadsheet model that integrated demographic, economic epidemiological, health service utilization, screening performance, survival and lifetime quality of life data based on the standard formula: CUR = Increase in Intervention Costs - Decrease in Treatment costs Averted QALY losses of adding DL to US & POX US screening data were based on real-world operational routine reports (as opposed to research studies). The DL screening cost of 145 USD was based on Israeli US costs plus 20.54 USD for reading and recording screens. Results: The addition of DL assisted US, which is associated with increased sensitivity (95% vs 58.1%), resulted in far fewer undiagnosed infants (16 vs 102 [or 2.9% vs 15.4%] of the 560 and 659 births, respectively). Adoption of DL-US will add 1,204 QALYs. with increased screening costs 22.5 million USD largely offset by decreased treatment costs (20.4 million USD). Therefore, the new DL-US technology is considered "very cost-effective", costing only 1,720 USD per QALY. For most performance combinations (sensitivity > 80%, specificity > 90%), the adoption of DL-US is either cost effective or very cost effective. For specificities greater than 98% (with sensitivities above 94%), DL-US (& POX) is said to "dominate" US (& POX) by providing more QALYs at a lower cost. Conclusion: Our exploratory CUA calculations indicate the feasibility of DL-US as being at least cost-effective. [ABSTRACT FROM AUTHOR]

Background: Prenatal detection of critical congenital heart disease (CCHD) optimises perinatal decision-making and neonatal outcomes. The objective of this study was to determine the prenatal screening performance, care pathways and perinatal outcomes for prenatally and postnatally diagnosed cases of CCHD over a four-year period. Study design: This retrospective cohort study in a tertiary centre and its two affiliated secondary sites examined all cases of CCHD, including cases of pregnancy termination and in-utero fetal death, neonatal death and liveborn babies that underwent cardiac catheterization or surgery in the first six weeks of life. Prenatal and postnatal data were ascertained from the first trimester assessment for all patients diagnosed prenatally. Cases requiring intervention that were first identified in the postnatal period were included to determine prenatal detection rates. Follow-up for all cases of CCHD continued to one year of age. Results: In a consecutive cohort of 49,950 pregnancies in a 4-year period 01/2019 to 12/2022, a prenatal diagnosis of CCHD was made in 96 cases, yielding a prevalence of 1.9 per 1000 births. The prenatal detection for right duct-dependant heart pathology and congenital heart block was 100%, 85% for left duct-dependant pathology and 93% for transposition of the great arteries (TGA). In the prenatally diagnosed group, 37% of cases were complicated by extracardiac structural abnormalities, a genetic diagnosis or both. All cases of prenatal detection were identified in the context of routine anatomy screening rather than specialist Fetal Cardiac screening services. Almost half of all pregnancies complicated by CCHD did not undergo neonatal cardiac intervention, by virtue of parental choice determined either prenatally or after birth. An additional eight babies were diagnosed with CCHD in the neonatal period, such that the prenatal detection rate for CCHD was 92% (96/104, 95% CI = 84%-96%). Survival at 1-year for infants deemed suitable for CCHD surgery was 85%. Conclusion: In a large unselected population, optimal rates of prenatal detection of critical congenital heart disease can be achieved by a protocolised approach to mid-trimester fetal anatomy ultrasound, underpinned by a programme of sonographer education and training. The cardiac abnormalities most likely to evade prenatal detection are left-sided obstructive lesions. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical value of positive copy number variations (CNVs) results by non‐invasive prenatal testing (NIPT) without fetal ultrasonography‐identified structural anomalies, especially with several known CNVs results. Methods: A total of 135,981 results of NIPT performed between April 1, 2017, and March 31, 2020, enrolled in the free NIPT service program implemented by the local government were retrospectively analyzed. Of these, 87 cases with positive NIPT screens for CNVs and no fetal ultrasonography‐identified anomalies were recalled and provided genetic counseling. After obtaining full informed consent, these cases were provided invasive prenatal diagnosis by karyotyping and chromosomal microarray analysis (CMA)/copy number variation sequencing (CNV‐seq) with follow‐up. One case was lost, while 86 cases were successfully followed up. Results: A total of 44 (50.6%) cases underwent invasive prenatal diagnosis, of which six cases were detected with abnormal karyotype. CMA/CNV‐Seq revealed 11 fetuses with positive results for CNVs, among whom eight were consistent with NIPT results, two were partially consistent, one was inconsistent, and positive predictive value (PPV) was 22.7% (10/44). For known CNVs, PPVs were 20% (15q11.2‐q13 microdeletion) and 33.3% (5p end deletions). Among 11 pregnant women with positive prenatal diagnosis, seven were confirmed to have pathogenic CNVs in their fetuses; four had CNVs of unknown clinical significance. Conclusions: Even in pregnancies without ultrasonography‐identified anomalies, a positive NIPT screen for CNVs must be interpreted with caution and validated by additional diagnostic study. [ABSTRACT FROM AUTHOR]

Objective: The diagnosis of posterior fossa abnormalities (PFA) in the intrauterine period and association with pregnancy outcomes are still controversial. PFA is generally referred to maternal-fetal medicine specialists. The primary purpose of PFA diagnosis is to screen for other accompanying abnormalities, provide prognostic information to families, and discuss the termination option. Material and Methods: This retrospective study was conducted in patients diagnosed with PFA between January 2013 and September 2020 in a tertiary perinatology clinic. All patients underwent routine second-trimester ultrasound screening and definitive diagnosis was made by fetal magnetic resonance imaging (MRI) in the presence of a suspected anomaly. Results: There were 164 fetal MRIs for fetal abnormalities during the study period and 22 (13.4%) were diagnosed with a PFA on fetal MRI. Indications for fetal MRI included four (18%) with Mega Cisterna Magna, two (9.1%) with rhomboencephalosynapsis, and thirteen (59.1%) with Vermian Hypoplasia-Dandy-Walker variant. Two patients, with neural tube defects and lumbosacral neural-tube defect are still alive. However, iniencephaly was detected in last patient who died in the postnatal period. Conclusion: Diagnosis of PFA abnormalities is complex, and the prognosis in PFA is often unclear. The prognosis is not affected by maternal and fetal factors and allows the recognition of additional accompanying abnormalities. Fetal MRI is an imaging method that can provide retrospective examination and research, especially in pregnancies with poor prognoses. [ABSTRACT FROM AUTHOR]

Background: Trisomy 13 (T13) and sex chromosome aneuploidies (SCA) are the vital causes of congenital malformations. This study was performed to identify the T13 and SCA with screening tests in the first trimester of pregnancy. Materials and Methods: In this cross-sectional study, first-trimester combined screening was conducted on 2100 pregnant women referred to Narges Genetics Laboratory, Ahvaz, Iran. Evaluating the first trimester screening tests, including nuchal translucency (NT), crown--rump length (CRL) and pregnancy-associated plasma protein-A (PAPP- A), and free beta of human chorionic gonadotropin (fβhCG) was performed. For a definitive diagnosis of T13 and SCA syndrome, fetal karyotype was evaluated. Results: The average NT and CRL in high-risk group for T13 were 5.96 mm and 61.7 mm respectively and in high- risk groups for SCA were 3.7 mm and 75.9 mm, respectively. Significant correlation was observed among NT, CRL and T13, SCA (P<0.05). The average serum fβhCG and PAAP-A levels in high-risk group for T13 were 0.42 and 0.31, respectively. Significant correlation was observed between decrease fβhCG, PAPP-A and T13 levels and increase fβhCG levels and SCA levels (P<0.05). No Significant correlation was observed between PAPP-A levels and SCA levels (P>0.05). Conclusion: Using special software and karyotype testing, the prenatal screening tests based on the maternal age and gestational age in the first trimester of pregnancy may determine the major risk of fetal chromosomal abnormalities. [ABSTRACT FROM AUTHOR]

Objective: We present a case with prenatal diagnosis of submucous cleft palate (SMCP) which was described using 2- and 3-dimensional (3D) ultrasonography in utero. Case Report: A 25-year-old pregnant woman was referred to our department for fetal ultrasound screening. After the detection of cardiac and spinal malformations of fetal, further detailed examination detected SMCP, which showed a gap within the hard palate on axial transversal view with the soft palate visible on sagittal view. The imaging of a defective hard palate in prenatal 3D ultrasonography is similar to that in postmortem 3D computed tomography reconstruction. Conclusion: A gap within the hard palate and verification of the visibility of the soft palate should be key points in the prenatal diagnosis of SMCP. Three-dimensional ultrasonic imaging is helpful for displaying the shape and extent of the bony defect in SMCP. [ABSTRACT FROM AUTHOR]

Objective: Socioeconomic status (SES) and distance of residence from tertiary care may impact fetal detection of congenital heart disease (CHD), partly through reduced access to and quality of obstetric ultrasound screening. It is unknown whether SES and remoteness of residence (RoR) affect prenatal detection of CHD in jurisdictions with universal health coverage. We examined the impact of SES and RoR on the rate and timing of prenatal diagnosis of major CHD within the province of Alberta in Canada.Methods: In this retrospective study, we identified all fetuses and infants diagnosed with major CHD in Alberta, from 2008 to 2018, that underwent cardiac surgical intervention within the first year after birth, died preoperatively, were stillborn or underwent termination. Using maternal residence postal code and geocoding, Chan SES index quintile, geographic distance from a tertiary-care fetal cardiology center and the Canadian Index of Remoteness (IoR) were calculated. Outcome measures included rates of prenatal diagnosis and diagnosis after 22 weeks' gestation. Risk ratios (RR) were calculated using log-binomial regression and stratified by rural (≥ 100 km from tertiary care) or metropolitan (< 100 km from tertiary care) residence, adjusting for year of birth and the obstetric ultrasound screening view in which CHD would most likely be detected (four-chamber view; outflow-tract view; three-vessel or three-vessels-and-trachea or non-standard view; septal view).Results: Of 1405 fetuses/infants with major CHD, prenatal diagnosis occurred in 814 (57.9%). Residence ≥ 100 km from tertiary care (adjusted RR, 1.19; 95% CI, 1.05-1.34) and higher IoR (adjusted RR, 1.9; 95% CI, 1.1-3.3) were associated with missed prenatal diagnosis of major CHD. Similarly, residence ≥ 100 km from tertiary care (adjusted RR, 1.41; 95% CI, 1.22-1.62) and higher IoR (adjusted RR, 3.6; 95% CI, 2.2-8.2) were associated with prenatal diagnosis after 22 weeks. Although adjusted and unadjusted analyses showed no association between Chan SES index quintile and prenatal-diagnosis rate overall nor for residence in rural areas, in metropolitan regions, lower SES quintiles were associated with missed prenatal diagnosis (quintile 1: RR, 1.24; 95% CI, 1.02-1.50) and higher risk of diagnosis after 22 weeks' gestation (quintile 1: RR, 1.46; 95% CI, 1.10-1.93; quintile 2: RR, 1.66; 95% CI, 1.24-2.23).Conclusions: Despite universal healthcare, rural residence in Alberta is associated with lower rate of prenatal diagnosis of major CHD and higher risk of late prenatal diagnosis (≥ 22 weeks). Within metropolitan regions, lower SES impacts negatively prenatal-diagnosis rate and timing. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the improved precision of nuchal translucency (NT) measurement used in antenatal screening for Down's syndrome observed over time as evidenced by a decrease in the multiple of the median (MoM) standard deviation requires a modification to the NT MoM truncation limits to maintain accurate risk estimation. Methods: Probability plots were derived from the measurements of NT MoM values used in a 2018 audit of 22,362 unaffected pregnancies. The plots were used to determine whether the NT MoM upper truncation limit should be lowered. Validation plots were used to assess the screening accuracy of Down's syndrome risk estimates calculated from observed NT MoM values in the 22,362 unaffected pregnancies and 69 Down's syndrome pregnancies for original and revised NT MoM truncation limits. Results: Probability plots indicated that with improved precision of NT measurements, there was deviation from a Gaussian distribution at less high MoM values than with less precise measurements. Validation plots showed that using the current NT MoM upper truncation limit of 2.5 MoM with improved precision NT measurements overestimates the Down's syndrome risk (median risk in highest risk category expressed as an odds was 53.3:1 and observed prevalence was 1:1.1). The large discrepancy was corrected by changing the NTupper truncation limit to 2.0 MoM (median risk in highest risk category expressed as an odds was 1:1.78 and observed prevalence 1:2.7). Conclusion: The NT MoM upper truncation limit should be reduced from 2.5 to 2.0 MoM. [ABSTRACT FROM AUTHOR]

Objective: To report on the routine clinical implementation of cell-free DNA (cfDNA) analysis of maternal blood for trisomies 21, 18 and 13, contingent on the results of the first-trimester combined test in twin pregnancy.Methods: Screening for trisomies 21, 18 and 13 was carried out in 959 twin pregnancies by assessment of a combination of maternal age, fetal nuchal translucency thickness, and serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein-A at 11-13 weeks' gestation in two UK NHS hospitals. Women in the high-risk group (risk ≥ 1 in 100) were offered the option of invasive testing, cfDNA testing or no further testing, and those in the intermediate-risk group (risk 1 in 101 to 1 in 2500 in the first phase of the study and 1 in 101 to 1 in 500 in the second phase) were offered cfDNA or no further testing. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or examination of the neonates.Results: In 42 (4.4%) of the 959 pregnancies, there was termination, miscarriage or stillbirth with no known karyotype or there was loss to follow-up. The 917 pregnancies with known trisomic status of both twins included six that were discordant for trisomy 21, four that were discordant for trisomy 18 and 907 with no trisomy 21, 18 or 13. Following combined screening, 47 (5.1%), 203 (22.1%) and 667 (72.7%) of the pregnancies were classified as high risk, intermediate risk and low risk, respectively. The high-risk group included five (83.3%) cases of trisomy 21 and three (75.0%) of trisomy 18. The cfDNA test was carried out in 224 pregnancies and results were provided in 214 (95.5%); this group included six pregnancies with trisomy 21, three with trisomy 18 and 206 with no trisomy 21, 18 or 13. The cfDNA test classified correctly as screen positive all six cases of trisomy 21 and two of the three with trisomy 18, and as screen negative for each of the trisomies all 206 unaffected pregnancies. Contingent screening led to prenatal detection of all cases of trisomy 21 and three of four with trisomy 18.Conclusion: This study has demonstrated the feasibility of introducing cfDNA testing, contingent on the results of the first-trimester combined test for major trisomies, in a routine population of twin pregnancies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To perform a decision and cost-effectiveness analysis comparing four screening strategies for the antenatal diagnosis of vasa previa in singleton pregnancies.Methods: A decision-analytic model was constructed comparing vasa previa screening strategies. Published probabilities and costs were applied to four transvaginal screening scenarios that were carried out at the time of mid-trimester ultrasound: no screening, ultrasound-indicated screening, screening only pregnancies conceived by in-vitro fertilization (IVF) and universal screening. Ultrasound-indicated screening was defined as performing transvaginal ultrasound at the time of the routine anatomy ultrasound scan in response to one of the following sonographic findings associated with an increased risk of vasa previa: low-lying placenta, marginal or velamentous cord insertion or bilobed or succenturiate lobed placenta. The primary outcome was cost per quality-adjusted life year (QALY) in US$. The analysis was performed from a healthcare system perspective with a willingness-to-pay threshold of $100 000 per QALY selected. One-way and multivariate sensitivity analysis (Monte-Carlo simulation) was performed.Results: This decision-analytic model demonstrated that screening pregnancies conceived by IVF was the most cost-effective strategy, with an incremental cost effectiveness ratio (ICER) of $29186.50/QALY. Ultrasound-indicated screening was the second most cost-effective, with an ICER of $56096.77/QALY. These data were robust to all one-way and multivariate sensitivity analyses performed.Conclusions: Within the baseline assumptions, transvaginal ultrasound screening for vasa previa appears to be most cost-effective when performed among IVF pregnancies. However, both IVF and ultrasound-indicated screening strategies fall within contemporary willingness-to-pay thresholds, suggesting that both strategies may be appropriate to apply in clinical practice. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

The rapid changes that have taken place in recent years in relation to techniques used to image the fetal heart have emphasized the need to have a detailed knowledge ofnormal cardiac anatomy. Without such knowledge, it is difficult, if not impossible, to recognize the multiple facets of congenital cardiac disease. From the inception of fetal echocardiographic screening, the importance of basic knowledge of cardiac anatomy has been well recognized. The current machines used for imaging, however, now make it possible potentially to recognize features not appreciated at the start of the specialty. So as to match the advances made in imaging, we have now revisited our understanding of normal cardiac anatomy in the mid-gestational fetus. This was made possible by our dissection of 10 fetal hearts, followed by production of addition histological sections that mimic the standard ultrasound views. The fetuses ranged in gestational age from between 20 and 28 weeks. We then correlated the obtained anatomic images with the corresponding ultrasonic images used in the standard fetal screening scan. We also interrogated the anatomic sections so as to clarify ongoing controversies regarding detailed features of the normal cardiac anatomy. We have been able to show that the views now obtained using current technology reveal many details of anatomy not always appreciated at earlier times. Knowledge of these features should now permit diagnosis of most congenital cardiac malformations. The anatomic-echocardiographic correlations additionally provide a valuable resource for both the understanding and teaching of fetal echocardiography. [ABSTRACT FROM AUTHOR]

This article reviews important features for improving the diagnosis of fetal arrhythmias by ultrasound in prenatal cardiac screening and echocardiography. Transient fetal arrhythmias are more common than persistent fetal arrhythmias. However, persistent severe bradycardia and sustained tachycardia may cause fetal hydrops, preterm delivery, and higher perinatal morbidity and mortality. Hence, the diagnosis of these arrhythmias during the routine obstetric ultrasound, before the progression to hydrops, is crucial and represents a challenge that involves a team of specialists and subspecialists on fetal ultrasonography. The images in this review highlight normal cardiac rhythms as well as pathologic cases consistent with premature atrial and ventricular contractions, heart block, supraventricular tachycardia (VT), atrial flutter, and VT. In this review, the details of a variety of arrhythmias in fetuses were provided by M-mode and Doppler ultrasound/echocardiography with high-quality imaging, enhancing diagnostic accuracy. Moreover, an update on the intrauterine management and treatment of many arrhythmias is provided, focusing on improving outcomes to enable planned delivery and perinatal management. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of high-resolution chromosomal microarray (CMA) as the standard diagnostic approach for genomic imbalances in pregnancies with increased risk based on combined first-trimester screening (cFTS).Methods: This was a retrospective study of genomic findings in a cohort of 575 consecutive pregnancies undergoing invasive testing because of a cFTS risk ≥ 1:300 on a publicly funded population-based screening program in the Central and Northern Regions of Denmark, between September 2015 and September 2016. Women with fetal nuchal translucency thickness ≥ 3.5 mm or opting for non-invasive prenatal testing (NIPT) were excluded. Comparative genomic hybridization was performed using a 180-K oligonucleotide array on DNA extracted directly from chorionic villus/amniocentesis samples. Genomic outcomes were reported in relation to cFTS findings.Results: Of the 575 pregnancies that underwent invasive testing, CMA detected 22 (3.8% (95% CI, 2.5-5.7%)) cases of trisomies 21, 18 and 13, 14 (2.4% (95% CI, 1.4-4.0%)) cases of other types of aneuploidy and 15 (2.6% (95% CI, 1.5-4.3%)) cases with a pathogenic or probably pathogenic copy number variant (CNV). Of the 15 CNVs, three were > 10 Mb and would probably have been detected by chromosomal analysis, but the other 12 would most probably not have been detected using conventional cytogenetic techniques; therefore, the overall detection rate of CMA (8.9% (95% CI, 6.8-11.5%)) was significantly higher than that estimated for conventional cytogenetic analysis (6.8% (95% CI, 5.0-9.1%)) (P = 0.0049). Reducing the cFTS risk threshold for invasive diagnostic testing to 1 in 100 or 1 in 50 would have led, respectively, to 60% or 100% of the pathogenic CNVs being missed.Conclusions: CMA is a valuable diagnostic technique that can identify an increased number of genomic aberrations in pregnancies at increased risk on cFTS. Limiting diagnostic testing to pregnancies with a risk above 1 in 100 or 1 in 50, as proposed in contingent NIPT/invasive testing models, would lead to a significant proportion of pathogenic CNVs being missed at first-trimester screening. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the use of third-trimester ultrasound screening for late fetal growth restriction (FGR) on a contingent basis, according to risk accrued in the second trimester, in an unselected population.Methods: Maternal characteristics, fetal biometry and second-trimester uterine artery (UtA) Doppler were included in logistic regression analysis to estimate risk for late FGR (birth weight < 3(rd) percentile, or 3(rd) -10(th) percentile plus abnormal cerebroplacental ratio or UtA Doppler, with delivery ≥ 34 weeks). Based on the second-trimester risk, strategies for performing contingent third-trimester ultrasound examinations in 10%, 25% or 50% of the cohort were tested against a strategy of routine ultrasound scanning in the entire population at 32 + 0 to 33 + 6 weeks.Results: Models were constructed based on 1393 patients and validated in 1303 patients, including 73 (5.2%) and 82 late FGR (6.3%) cases, respectively. At the second-trimester scan, the a-posteriori second-trimester risk (a-posteriori first-trimester risk (baseline a-priori risk and mean arterial blood pressure) combined with second-trimester abdominal circumference and UtA Doppler) yielded an area under the receiver-operating characteristics curve (AUC) of 0.81 (95% CI, 0.74-0.87) (detection rate (DR), 43.1% for a 10% false-positive rate (FPR)). The combination of a-posteriori second-trimester risk plus third-trimester estimated fetal weight (full model) yielded an AUC of 0.92 (95% CI, 0.88-0.96) (DR, 74% for a 10% FPR). Subjecting 10%, 25% or 50% of the study population to third-trimester ultrasound, based on a-posteriori second-trimester risk, gave AUCs of 0.81 (95% CI, 0.75-0.88), 0.84 (95% CI, 0.78-0.91) and 0.89 (95% CI, 0.84-0.94), respectively. Only the 50% contingent model proved statistically equivalent to performing routine third-trimester ultrasound scans (AUC, 0.92 (95% CI, 0.88-0.96), P = 0.11).Conclusion: A strategy of selecting 50% of the study population to undergo third-trimester ultrasound examination, based on accrued risk in the second trimester, proved equivalent to routine third-trimester ultrasound scanning in predicting late FGR. [ABSTRACT FROM AUTHOR]

Objectives: Cell-free DNA (cfDNA) analysis of maternal blood for detection of trisomies 21, 18 and 13 is superior to other methods of screening but is expensive. One strategy to maximize performance at reduced cost is to offer cfDNA testing contingent on the results of the first-trimester combined test that is used currently. The objectives of this study were to report the feasibility of implementing such screening, to examine the factors affecting patient decisions concerning their options for screening and decisions on the management of affected pregnancies and to report the prenatal diagnosis of fetal trisomies and outcome of affected pregnancies following the introduction of contingent screening.Methods: We examined routine clinical implementation of contingent screening in 11,692 singleton pregnancies in two National Health Service (NHS) hospitals in the UK. Women with a risk ≥ 1 in 100 (high-risk group) were offered options of invasive testing, cfDNA testing or no further testing, and those with a risk between 1 in 101 and 1 in 2500 (intermediate-risk group) were offered cfDNA testing or no further testing. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or by examination of the neonates.Results: In the study population of 11,692 pregnancies, there were 47 cases of trisomy 21 and 28 of trisomies 18 or 13. Screening with the combined test followed by invasive testing for all patients in the high-risk group potentially could have detected 87% of trisomy 21 and 93% of trisomies 18 or 13, at a false-positive rate of 3.4%; the respective values for cfDNA testing in the high- and intermediate-risk groups were 98%, 82% and 0.25%. However, in the high-risk group, 38% of women chose invasive testing and 60% chose cfDNA testing; in the intermediate-risk group 92% opted for cfDNA testing. A prenatal diagnosis was made in 43 (91.5%) pregnancies with trisomy 21 and all pregnancies with trisomies 18 or 13. In many affected pregnancies the parents chose to avoid testing or termination and 32% of pregnancies with trisomy 21 resulted in live births.Conclusions: Screening for fetal trisomies by cfDNA analysis of maternal blood, contingent on the results of the combined test, can be implemented easily in routine clinical practice. In the high-risk group from the combined test, most but not all women chose cfDNA testing rather than invasive testing. Performance of screening for trisomy 21 was superior by the cfDNA test than by the combined test. However, prenatal detection of trisomies and pregnancy outcome depend not only on performance of screening tests but also on parental choice. [ABSTRACT FROM AUTHOR]

Study Question: How does a national prenatal screening program for Down syndrome (DS) perform in detecting sex chromosome abnormalities (SCAs)-Turner syndrome (TS), Klinefelter syndrome, 47,XXX and 47,XYY syndromes.Summary Answer: The SCA detection rate resulting from DS screening was below 50% for all four groups of SCAs.What Is Known Already: The detection rates of SCAs are higher in countries with DS screening. TS is associated with greater nuchal translucency (NT) and lower pregnancy-associated plasma protein-A (PAPP-A). However, specific detection rates of SCAs using prenatal DS screening have not been determined. No clear trend in PAPP-A, free beta human chorionic gonadotropin (β-hCG) and NT has been found in the remaining SCAs. Several lines of inquiry suggest that it would be advantageous for individuals with SCA to be detected early in life, leading to prevention or treatment of accompanying conditions. There is limited information about pre- and perinatal status that distinguishes SCA embryogenesis from normal fetal development.Study Design, Size, Duration: A register-based case-control study from the Danish Central Cytogenetic Register (DCCR), cross-linked with the Danish Fetal Medicine Database (DFMD), was performed from 2008 to 2012. Groups of SCAs were compared with DS and then matched with non-SCA controls to assess differences between these groups in prenatal markers and birth outcomes.Participants/materials, Setting, Methods: We included cases with prenatal and post-natal SCA karyotypes (n = 213), DS (n = 802) and 168 056 controls. We screened 275 037 individuals examined prenatally. We retrieved information regarding maternal age, NT, β-hCG and PAPP-A, as well as details regarding maternal and newborn characteristics.Main Results and the Role Of Chance: The DS screening procedure detected 87 per 100 000 TS (42% of expected), 19 per 100 000 Klinefelter syndrome (13% of expected), 16 per 100 000 47,XXX (16% of cases) and 5 per 100 000 47,XYY (5% of expected) SCAs, with an overall detection rate of 27%. Compared with controls, all four SCA groups showed significantly higher NT and lower PAPP-A compared with controls (all P < 0.01) and similar to DS. The legal abortion rate was high for all four syndromes (47,XXX: 24%; 47,XYY: 29%; Klinefelter syndrome: 48%, TS: 84%). For SCA fetuses carried to term, only TS fetuses had consistently lower birthweights and placenta weights than non-SCA controls (both P = 0.0001). A few SCA cases localized in DCCR could not be found in DFMD (n = 16).Limitations, Reason For Caution: Controls were matched on sex of the fetus of cases, meaning that all electively aborted fetuses (before week 12) were excluded, possibly reducing the diversity in the control group. We were not able to localize all diagnosed cases of SCA and DS in DFMD. Although these cases were present in DCCR, we were not able to account for the discrepancy. In addition, we suspect that several SCA children have not been diagnosed yet and future post-natal diagnosis of these cases would reduce the diagnostic yield reported here even further.Wider Implications Of the Findings: The prenatal detection rate is below 50% for all SCAs. The approach used for detecting DS cannot be extended to also include SCAs. In addition, all SCAs have low PAPP-A and increased NT, thus probably reflecting an abnormal embryogenesis. Growth retardation of TS fetuses is if anything more pronounced than previously reported, both when evaluating fetus and placenta.Study Funding/competing Interests: This study received support from Aarhus University and the Novo Nordisk Foundation. The authors have no competing interests that may be relevant to the study. [ABSTRACT FROM AUTHOR]

Objective: To analyze the most relevant anomalies, seen in a sequential segmental transverse views approach to imaging the fetal heart, that provide clues to the diagnosis of complete transposition of the great arteries (TGA). Methods: We reviewed retrospectively all the cases of isolated TGA diagnosed in our center or submitted for a second opinion through the spatio-temporal image correlation (STIC) telemedicine (TELE-STIC) program. Only transverse cardiac sweeps were obtained. Digital video clips and STIC volumes were reviewed. The abnormal features on four-chamber, five-chamber, three-vessel (3V) and three vessels and trachea (3VT) views were analyzed. Results: The study population consisted of eight fetuses with TGA with normal extracardiac anatomy. The gestational age ranged from 13 to 32 (mean, 23) weeks. The maternal age ranged from 25 to 42 (mean, 32) years. A normal four-chamber view was seen in seven cases. Only one case demonstrated a significant ventricular septal defect. At the level of the five-chamber view a straight course arterial vessel arose from the left ventricle with lateral branches in all fetuses. In the 3V view, the ascending aorta was seen reaching more anteriorly than was the pulmonary artery in six cases. At the level of the 3VT view, two vessels (transverse aortic arch and superior vena cava) rather than three were seen in all cases. Conclusion: Our proposed sequential segmental approach to imaging the fetal heart apparently allows, in five-chamber and 3VT views, clear and confident signs to be detected that aid diagnosis of TGA. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether training and experience in performing ultrasound examinations are factors that influence the prenatal detection of congenital heart defects (CHDs) in a non-selected population, in order to evaluate and improve the current training program. Methods: All pregnant women who received a routine second-trimester ultrasound scan by a sonographer/midwife and delivered at our hospital between February 1991 and December 2001 were registered prospectively. Less experienced sonographer/midwives who had performed between 200 and 2000 routine examinations were compared with experienced sonographer/midwives who had carried out more than 2000 examinations. During the first 5 years of the study the heart structures obtained were registered in detail. Results: Of 29,035 fetuses, 35/82 (43%) major CHDs were prenatally detected at the routine examination. The experienced sonographer/midwives obtained both the four-chamber view and the great arteries in 75%; the figure for the less experienced sonographer/midwives was 36% (P < 0.001). The differences in detecting major heart defects were 22/42 (52%) and 13/40 (32.5%), isolated CHDs 8/18 (44%) and 6/22 (27%) and CHDs with associated malformations 14/24 (58%) and 7/18 (39%), respectively. In both groups some CHDs with an abnormal four-chamber view were missed, although the experienced sonographer/midwives recognized significantly more of the abnormal views than did the less experienced sonographer/midwives (P = 0.002). Conclusions: Experience has a significant impact on the examination of the fetal heart and the prenatal detection rate of major CHDs. To avoid a relatively long learning curve, ultrasound education needs to intensify the teaching of the basic four-chamber view. The great arteries should be included after additional training. Those basic views of the fetal heart must be mastered before new views and advanced technology are added to the fetal heart examination. [ABSTRACT FROM AUTHOR]

Comments on the second trimester ultrasound markers (STUM) for the detection of Down's syndrome. Overview of STUM; Advantage and disadvantage of STUM; Prenatal screening for Down's syndrome; Background of studies on Down's syndrome.