Objective: To evaluate the clinical and economic impact of adopting noninvasive prenatal testing (NIPT) using circulating cell-free DNA as a first-line screening method for trisomy 21, 18, and 13 in the general pregnancy population. Methods: A decision-analytical model was developed to assess the impact of adopting NIPT as a primary screening test compared to conventional screening methods. The model takes the Belgium perspective and includes only the direct medical cost of screening, diagnosis, and procedure-related complications. NIPT costs are EUR 260. Clinical outcomes and the cost per trisomy detected were assessed. Sensitivity analysis measured the impact of NIPT false-positive rate (FPR) on modelled results. Results: The cost per trisomy detected was EUR 63,016 for conventional screening versus EUR 66,633 for NIPT, with a difference of EUR 3,617. NIPT reduced unnecessary invasive tests by 94.8%, decreased procedure-related miscarriages by 90.8%, and increased trisomies detected by 29.1%. Increasing the FPR of NIPT (from < 0.01 to 1.0%) increased the average number of invasive procedures required to diagnose a trisomy from 2.2 to 4.5, respectively. Conclusion: NIPT first-line screening at a reasonable cost is cost-effective and provides better clinical outcomes. However, modelled results are dependent on the adoption of an NIPT with a low FPR.

Letters to the EditorCell-free DNA testing for prenatal aneuploidy assessment: analysis of professional society statementsWe read the report by Hui et al. 1 'State-wide utilization and performance of traditional and cell-free DNA based prenatal testing pathways: the Victorian Perinatal Record Linkage (PeRL) study' and believe that the study provides valuable information to inform practice recommendations and health policy. We were interested in the global perspective on clinical implementation of prenatal cell-free DNA (cfDNA) testing and reviewed practice guidelines published by international and national professional societies.Guidelines were identified using the Google search engine and the PubMed and EMBASE databases. Search terms included 'non-invasive prenatal testing', 'prenatal cfDNA', 'guidelines', 'society' and 'statement'. We also reviewed the content of the retrieved websites and documents and consulted with professional colleagues to find as many additional guidelines as possible. Searches

Objectives: To estimate the risk of chromosomal abnormalities and explore the application of CMA in fetuses with increased nuchal translucency (NT). Methods: A total of 374 fetuses diagnosed as increased NT from the third affiliated hospital of Guangzhou Medical University were studied retrospectively to analyse the ultrasound and CMA results. Results: Of 374 fetuses with increased NT, 109(29.1%) cases had abnormal CMA findings. All cases were divided into four groups according to the NT measurement. In group NT between 2.5-3.4 mm, 3.5-4.4 mm, 4.5-5.4 mm and NT ≥ 5.5 mm, the number of cases and the number of chromosomal abnormalities cases were 114, 26 (22.8%); 150, 33 (22.0%); 55, 19 (34.5%); 55, 31 (56.4%), respectively. There was significant difference in chromosomal abnormalities among NT groups, and the degree of fetal NT thickness was positively correlated with chromosomal abnormalities (r = 0.208, P < 0.05). There were 64 cases with other ultrasound abnormalities and 39 cases of these presented chromosomal abnormalities (60.9%). Compared the fetal chromosomal abnormalities between the cases with other ultrasound abnormalities and the cases of isolate increased nuchal translucency, the difference was significant (c 2 = 37.794P < 0.001). Conclusions: Fetuses with increased NT have a greater incidence of chromosomal abnormalities, structural malformations, and adverse pregnancy outcomes. The prevalence of chromosomal defects and adverse pregnancy outcomes increases exponentially with NT thickness. The abnormal chromosomal detection rate of fetuses with other ultrasound abnormalities was higher than that with isolate increased nuchal translucency.

Background Non-invasive prenatal testing (NIPT) as a screening method for trisomy 21 and other chromosomal abnormalities has been adopted widely across the globe. However, while many clinical validation studies have been performed, less is known regarding the patient experience with NIPT. This study explored how individuals experience NIPT in a pre- and post-test setting, where NIPT is broadly available as a primary screening method with the option of reporting beyond common trisomies. Methods Participants were recruited using social media with a strategy designed to select individuals who had the option to have NIPT as part of the TRIDENT-2 study (In the Netherlands, NIPT is only available within the TRIDENT studies executed by the NIPT consortium. This research was done independently from the NIPT consortium.) in the Netherlands. The study used online questionnaires and semi-structured interviews. Both were developed around a patient experience framework consisting of seven themes: information, patient as active participant, responsiveness of services, lived experience, continuity of care and relationships, communication, and support. Results Overall, 4539 questionnaire responses were analyzed and 60% of the respondents had experienced NIPT. Of those, 1.7% received a high-risk result for trisomy or another chromosomal copy number variant (referred to as an “additional finding”). Overall, participants felt they had received sufficient information and had control over their decision regarding whether or not to choose NIPT. The vast majority of respondents who had NIPT were positive about their experience and would use it again. Those with results showing an increased probability for trisomy or additional findings were more likely to report negative feelings such as tension and anxiety, and less likely to feel that they had been sufficiently prepared for the implications of their results. Conclusions The patient experience with first-tier NIPT in the Netherlands was largely positive. Areas for improvement included counseling on the implications of screening and the different possible outcomes of NIPT, including additional findings that may be uncovered by expanding NIPT beyond the common trisomies. The experiences reported in this study may be useful for other countries intending to implement NIPT.

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Objectives: To ascertain the performance of non-invasive prenatal screening (NIPS) as a frontline screening option in a population with high body mass index (BMI). Methods: 1,000 women attending a public hospital in Australia were offered NIPS free of charge as part of a study examining the uptake of NIPS in a low socioeconomic population in Australia. Samples were taken at 11-12 weeks of gestation and analysed using Illumina TruSeq v1.2 methodology and interpreted using the SaFER algorithms. Results: The average BMI for our population was 27.8 (range 14.9-57.5). Only 40% of our population had a BMI in the healthy weight range (18.5-24.9). 26% were overweight (BMI 25-29.9), 16% were obese (BMI 30-34.9) and 15% morbidly obese (BMI 35-57.5). Two samples were below 2% fetal fraction (FF) and required recollection (which indicated no aneuploidy) to obtain a successful result. Both had a high BMI (32.6 and 43.3 respectively), the first on medications for hypothyroidism with no major adverse pregnancy outcomes, the second had very low PAPP-A with the pregnancy later being complicated by intrauterine growth restriction (IUGR) and pre-eclampsia. 2.71% had results less than 4% FF and 6.53% of samples had FF equal to 4% or below. Conclusions: NIPS using whole-genome sequencing successfully obtained results for all but two women on first sampling despite the very high BMI of our population (first report failure rate of 1:500 or 0.2%). Other methodologies, not based on whole-genome sequencing, would have resulted in a higher failure to report rates (based on published literature) in our study population. If a fetal fraction requirement of 4% or below is used (as in other methods) between 27-65 samples would have failed, potentially resulting in a higher need for invasive testing and increased anxiety for those patients. Non-invasive prenatal screening can be successfully offered as a first line prenatal screening test in women with very high BMI when using whole-genome sequencing platforms. VP07.02 Cell-free DNA knowledge of the generalist obstetrician

to assess its performance using a clinical database of precisely phenotyped postmortem examinations. Methods: This DSS is knowledge-based and comprises a dedicated thesaurus of 294 syndromes and diseases. It operates by suggesting, at each step of the ultrasound examination, the best next symptom to check for in order to optimise the diagnostic pathway to the smallest number of possible diagnoses. This assistant was tested on a single-centre database of 209 cases of postmortem phenotypes with a definite diagnosis. The primary outcome was a target concordance rate > 90% between the postmortem diagnosis and the top-7 diagnoses given by SONIO when providing the full phenotype as input. Secondary outcomes included concordance for the top-5 and top-3 diagnoses; We also assessed a ''1-by-1'' model, providing only the anomalies sequentially prompted by the system, mimicking the use of the software in a real-life clinical setting. Results:The validation database covered 96 of the 294 (32.65%) syndromes and 79% of their overall prevalence in the SONIO thesaurus. SONIO failed to make the diagnosis on 7/209 cases. On average, each case displayed 6 anomalies, 3 of which were considered atypical for the condition. Using the 'full-phenotype' model, the success rate of the top-7 output of Sonio was 96.7% (202/209). This was 91.9% and 87.1% for the top-5 and top-3 outputs respectively. Using the ''1-by-1'' model, the correct diagnosis was within the top-7, top-5 and top-3 of SONIO's output in 79%, 73% and 68%. Conclusions: Sonio is a robust DSS with a success-rate > 95% for top-7 ranking diagnoses when the full phenotype is provided, using a large database of noisy real data. The success rate of 79% using the '1-by-1' model was understandably lower, given that SONIO's sequential queries may not systematically cover the full phenotype.VP17.

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