Current practice of first-trimester ultrasound screening for structural fetal anomalies in developed countries

Objectives: First-trimester ultrasound screening is increasingly performed to detect fetal anomalies early in pregnancy, aiming to enhance reproductive autonomy for future parents. This study aims to display the current practice of first-trimester ultrasound screening in developed countries. Method: An online survey among 47 prenatal screening experts in developed countries. Results: First-trimester structural anomaly screening is available in 30 of the 33 countries and is mostly offered to all women with generally high uptakes. National protocols are available in 23/30 (76.7%) countries, but the extent of anatomy assessment varies. Monitoring of scan quality occurs in 43.3% of the countries. 23/43 (53.5%) of the respondents considered the quality of first-trimester ultrasound screening unequal in different regions of their country. Conclusions: First-trimester screening for structural fetal anomalies is widely offered in developed countries, but large differences are reported in availability and use of screening protocols, the extent of anatomy assessment, training and experience of sonographers and quality monitoring systems. Consequently, this results in an unequal offer to parents in developed countries, sometimes even within the same country. Furthermore, as offer and execution differ widely, this has to be taken into account when results of screening policies are scientifically published or compared.</p

Is there still a role for nuchal translucency measurement in the changing paradigm of first trimester screening?

Objectives: To give an overview of the genetic and structural abnormalities occurring in fetuses with nuchal translucency (NT) measurement exceeding the 95th percentile at first-trimester screening and to investigate which of these abnormalities would be missed if cell-free fetal DNA (cfDNA) were used as a first-tier screening test for chromosomal abnormalities. Methods: This is a national study including 1901 pregnancies with NT≥95th percentile referred to seven university hospitals in the Netherlands between 1 January 2010 and 1 January 2016. All cases with unknown pregnancy outcome were excluded. Results of detailed ultrasound examinations, karyotyping, genotyping, pregnancy and neonatal outcomes, investigation by a clinical geneticist and post-mortem investigations were collected. Results: In total, 821 (43%) pregnancies had at least one abnormality. The rate of abnormalities was 21% for fetuses with NT between 95th and 99th percentile and 62% for fetuses with NT≥99th percentile. Prevalence of single-gene disorders, submicroscopic, chromosomal and structural abnormalities was 2%, 2%, 30% and 9%, respectively. Conclusion: Although cfDNA is superior to the combined test, especially for the detection of trisomy 21, 34% of the congenital abnormalities occurring in fetuses with increased NT may remain undetected in the first trimester of pregnancy, unless cfDNA is used in combination with fetal sonographic assessment, including NT measurement

Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging

Objective: The purpose of this study was to explore the diagnostic yield and clinical utility of trio-based rapid whole exome sequencing (rWES) in pregnancies of fetuses with a wide range of congenital anomalies detected by ultrasound imaging. Methods: In this observational study, we analyzed the first 54 cases referred to our laboratory for prenatal rWES to support clinical decision making, after the sonographic detection of fetal congenital anomalies. The most common identified congenital anomalies were skeletal dysplasia (n = 20), multiple major fetal congenital anomalies (n = 17) and intracerebral structural anomalies (n = 7). Results: A conclusive diagnosis was identified in 18 of the 54 cases (33%). Pathogenic variants were detected most often in fetuses with skeletal dysplasia (n = 11) followed by fetuses with multiple major fetal congenital anomalies (n = 4) and intracerebral structural anomalies (n = 3). A survey, completed by the physicians for 37 of 54 cases, indicated that the rWES results impacted clinical decision making in 68% of cases. Conclusions: These results suggest that rWES improves prenatal diagnosis of fetuses with congenital anomalies, and has an important impact on prenatal and peripartum parental and clinical decision making

Placental Vessel Segmentation Using Pix2pix Compared to U-Net

Computer-assisted technologies have made significant progress in fetoscopic laser surgery, including placental vessel segmentation. However, the intra- and inter-procedure variabilities in the state-of-the-art segmentation methods remain a significant hurdle. To address this, we investigated the use of conditional generative adversarial networks (cGANs) for fetoscopic image segmentation and compared their performance with the benchmark U-Net technique for placental vessel segmentation. Two deep-learning models, U-Net and pix2pix (a popular cGAN model), were trained and evaluated using a publicly available dataset and an internal validation set. The overall results showed that the pix2pix model outperformed the U-Net model, with a Dice score of 0.80 [0.70; 0.86] versus 0.75 [0.0.60; 0.84] (p-value &lt; 0.01) and an Intersection over Union (IoU) score of 0.70 [0.61; 0.77] compared to 0.66 [0.53; 0.75] (p-value &lt; 0.01), respectively. The internal validation dataset further validated the superiority of the pix2pix model, achieving Dice and IoU scores of 0.68 [0.53; 0.79] and 0.59 [0.49; 0.69] (p-value &lt; 0.01), respectively, while the U-Net model obtained scores of 0.53 [0.49; 0.64] and 0.49 [0.17; 0.56], respectively. This study successfully compared U-Net and pix2pix models for placental vessel segmentation in fetoscopic images, demonstrating improved results with the cGAN-based approach. However, the challenge of achieving generalizability still needs to be addressed

Computer-assisted fetal laser surgery in the treatment of twin-to-twin transfusion syndrome:Recent trends and prospects

Fetal laser surgery has emerged as the preferred treatment of twin-to-twin transfusion syndrome (TTTS). However, the limited field of view of the fetoscope and the complexity of the procedure make the treatment challenging. Therefore, preoperative planning and intraoperative guidance solutions have been proposed to cope with these challenges. This review uncovers the literature on computer-assisted software solutions focused on TTTS. These solutions are classified by the pre- or intraoperative phase of the procedure and further categorized by discussed hardware and software approaches. In addition, it evaluates the current maturity of technologies by the technology readiness level and enumerates the necessary aspects to bring these new technologies to clinical practice

Informed choice and routinization of the second-trimester anomaly scan: a national cohort study in the Netherlands

Abstract Background Since 2007 all pregnant women in the Netherlands are offered the second-trimester anomaly scan (SAS) in a nationwide prenatal screening program. This study aims to assess the level of informed choice of women opting for the SAS and to evaluate the presence of routinization 16 years after its implementation. It further explores decisional conflict and women’s decision making. Methods This prospective national survey study consisted of an online questionnaire which was completed after prenatal counseling and before undergoing the SAS. Informed choice was measured by the adapted multidimensional measure of informed choice (MMIC) and was defined in case women were classified as value-consistent, if their decision for the SAS was deliberated and made with sufficient knowledge. Results A total of 894/1167 (76.6%) women completed the questionnaire. Overall, 54.8% made an informed choice, 89.6% had good knowledge, 59.8% had deliberated their choice and 92.7% held a positive attitude towards the SAS. Women with low educational attainment (p=0.004) or respondents of non-Western descent (p=0.038) were less likely to make an informed choice. Decisional conflict was low, with a significantly lower decisional conflict score in women that made an informed choice (p<0.001). Most respondents (97.9%) did not perceive pressure to undergo the SAS. Conclusions Our study showed a relatively low rate of informed choice for the SAS, due to absence of deliberation. Therefore, some routinization seem to be present in the Netherlands. However, most women had sufficient knowledge, did not perceive pressure and experienced low decisional conflict

Factors associated with poor outcome in fetuses prenatally diagnosed with sacrococcygeal teratoma

Aim of the study: Outcome of fetuses, prenatally diagnosed with sacrococcygeal teratoma (SCT), is still poorly documented. This study assesses the incidence and prenatal predictors of outcome in all fetuses prenatally diagnosed with SCT. Methods: This is a retrospective study on all fetuses prenatally diagnosed with SCT from 1998 to 2018 in the Netherlands. Poor outcome was defined as terminations of pregnancy (TOP) because of expected unfavorable outcome, intrauterine fetal death, or early neonatal death. Potential risk factors for poor outcome were analyzed. Main results: Eighty-four fetuses were included. Sixteen (19.0%) TOPs were excluded from statistical analysis. Eleven of the remaining 68 fetuses had poor outcome. Overall mortality was 32.1%, with a mortality excluding TOPs of 13.1%. Thirteen fetal interventions were performed in 11 (13.1%) fetuses. Potential risk factors for poor outcome were the presence of fetal hydrops (OR: 21.0, CI: 2.6–275.1, p = 0.012) and cardiomegaly (OR: 10.3, CI: 1.9–55.8, p = 0.011). Conclusions: The overall mortality of fetuses prenatally diagnosed with SCTs including tTOP was 32.1%. This high mortality rate was mainly due to termination of pregnancy. Mortality excluding TOP was 13.1%. Potential risk factors for poor outcome were fetal hydrops and cardiomegaly.</p

Additional file 1 of Informed choice and routinization of the second-trimester anomaly scan: a national cohort study in the Netherlands

Additional file 1

Survival in very preterm infants with congenital diaphragmatic hernia and association with prenatal imaging markers: A retrospective cohort study

Objectives: To describe the outcomes of preterm born infants with congenital diaphragmatic hernia (CDH; ≤32.0 weeks of gestation) and the associations between prenatal imaging markers and survival. Design: Retrospective cohort study. Setting: Multicentre study in large referral centres. Population: Infants with an isolated unilateral CDH, live born at 32.0 weeks or less of gestation, between January 2009 and January 2020. Methods: Neonatal outcomes were evaluated for infants that were expectantly managed during pregnancy and infants that underwent fetoscopic endoluminal tracheal occlusion (FETO) therapy, separately. We evaluated the association between prenatal imaging markers and survival to discharge. Prenatal imaging markers included observed to expected lung-to-head ratio (o/e LHR), side of the defect, liver position, stomach position grade, and observed to expected total fetal lung volume (o/e TFLV). Main Outcome Measure: Survival to discharge. Results: We included 53 infants born at 30 +4 (interquartile range 29 +1–31 +2) weeks. Survival in fetuses expectantly managed during pregnancy was 48% (13/27) in left-sided CDH and 33% (2/6) in right-sided CDH. Survival in fetuses that underwent FETO therapy was 50% (6/12) in left-sided CDH and 25% (2/8) in right-sided CDH. The o/e LHR at baseline was positively associated with survival in cases expectantly managed during pregnancy (odds ratio [OR] 1.20, 95% CI 1.07–1.42, p < 0.01), but not in cases that received FETO therapy (OR 1.01, 95% CI 0.88–1.15, p = 0.87). Stomach position grade (p = 0.03) and o/e TFLV were associated with survival (p = 0.02); liver position was not (p = 0.13). Conclusions: In infants with CDH born at or before 32 weeks of gestation, prenatal imaging markers of disease severity were associated with postnatal survival

Implementing NIPT as part of a national prenatal screening program: The Dutch TRIDENT studies

Objectives: In most countries, non-invasive prenatal testing (NIPT) has been introduced commercially without any governmental guidance. In the Netherlands, prenatal screening for fetal anomaly is subject to a governmental license. NIPT has been implemented as part of the TRIDENT studies (Trial by Dutch laboratories for Evaluation of NIPT). TRIDENT-2 aims at offering NIPT to all pregnant women (∼174,000 women/year) within the national prenatal screening program. Since April 2017, women can choose NIPT as a contingent test after first-trimester combined testing (FCT), but may also choose NIPT as first-tier screening test. TheTRIDENT studies evaluate implementation and women's perspectives. Methods: All pregnant women in the Netherlands are offered prenatal screening and are counselled by certified counselors, generally midwives. A first-tier NIPT costs women € 175, comparable to the costs of FCT (∼€ 168). NIPT is performed by three Dutch university clinical genetic laboratories using an in-house validated test. Women can choose to have analysis of chromosomes 21, 18, and 13 without or with a report of incidental findings (findings other than trisomy 21, 13, 18) on the remaining autosomes, respectively, using the 'targeted' or 'whole genome' WISECONDOR pipeline. Sex chromosomes are not analyzed. Results: After 8 months of study, 48,234 tests have been performed (nationwide uptake of prenatal screening by NIPT as first-tier test was 40%), and 98.3% reports successfully issued. Failure rate was less than 2%. Mean turnaround time was 7 working days. 80% of women chose to have all autosomes analyzed. A total of 152 cases of T21 (0.3%), 32 cases of T18 (0.1%), 41 cases of T13 (0.1%), and 158 (0.3%) other chromosomal aberrations were found. First year results (and available follow-up) will be presented at the meeting. Conclusions: The Netherlands are the first country where NIPT is incorporated as a first-line test into a governmentally supported and health care funded prenatal aneuploidy screening program. The incorporation of the test in a university hospital laboratory and clinical service guarantees appropriate counselling and allows for proper follow-up. This 3-year study aims to provide all necessary information for a successful introduction of NIPT within the Dutch National prenatal screening program