Non-Invasive Prenatal Testing in the Kingdom of Saudi Arabia: Current Status of Adoption and Roadmap for the Future

Objective To evaluate the value of non-invasive prenatal testing (NIPT) in pregnancies with anomaly in prenatal screening. Methods This was a retrospective study of 2 837 singleton pregnancies who performed NIPT indicated by isolated anomaly in prenatal screening at Guangdong Women and Children Hospital between November 2014 and August 2016. All pregnancies were divided into 3 groups by single indication: advanced maternal age ( AMA, ≥35), abnormal multiples of the median (MoM) in standard screening, increased nuchal translucency thickness (NT, 2.5-3.0 mm). High risk results were verified by prenatal diagnosis. Low risk cases were followed by a 22-26 week anatomical ultrasound examination. All of the cases were followed up and the performance of NIPT for every single indication was evaluated. Results There were total of 2 837 pregnant women who underwent NIPT. Twenty-five of 2 448 pregnancies indicated by AMA had high risk results, among which 17 were confirmed by invasive genetic testing, except 1 case rejecting prenatal diagnosis. In 351 pregnant women with abnormal MoM, NIPT found 3 cases of sex chromosome aneuploidies (SCA) and 2 of them were validated by invasive prenatal diagnosis. Increased NT group included 38 cases, NIPT found 1 case of trisomy 21 which was consistent with karyotype analysis. For common aneuploidies and SCA, the performance of NIPT in the pregnant women who indicated by AMA, abnormal MoM and increased NT were as the follows: the sensitivity were 17/17, 2/2 and 1/1 respectively, the specificity were 99.7% (2 423/2 431), 99.7% (348/349) and 100%(37/37), the positive predictive value were 68% (17/25), 2/3 and 1/1, the negative predictive value were 100% (2 423/2 423), 100% (348/348) and 100% (38/38), respectively. By follow-up survey, a total of 8 cases of abnormal fetus were recorded in NIPT low-risk women, including 5 cases of termination of pregnancy due to abnormal ultrasound findings, 2 cases of abortion as a result of severe obstetric complications and 1 case of stillbirth. Conclusions To the pregnant women who indicated by advanced maternal age, abnormal MoM and increased NT (2.5-3.0 mm), NIPT had satisfactory performance for common aneuploidies, and also had potential value for SCA, resulting in a significant reduction in diagnostic procedures. However, for NIPT low-risk pregnancies, routine antenatal examination and anatomical ultrasound detection would be highly necessary to avoid missing abnormal fetuses.(Chin J Lab Med, 2018, 41: 509-513) Key words: Aneuploidy; Prenatal diagnosis; Genetic testing; Nuchal translucency measurement

To compare the advantages and disadvantages of two main implementation strategies for non-invasive prenatal testing (NIPT) for the detection of trisomies 21, 13 and 18 in public healthcare settings. These concern NIPT as a first-tier screening test for all pregnant women, or NIPT contingent on an increased risk first-trimester combined test (FCT) result. Comparison based on (un)published data and literature. Despite the lower prevalence of trisomies in the low-risk population, data show that the positive predictive value (PPV) and detection-miscarriage ratio of first-tier NIPT are comparable to NIPT used as contingency test. Advantages of NIPT as a first-tier test compared to FCT with contingent NIPT are that there is no time-window for testing, sensitivity is higher, fewer women need follow-up testing (PPV of NIPT is higher than PPV of FCT), less anxiety for pregnant women and partners. When given the choice, pregnant women prefer first-tier NIPT. Although contingency testing still seems to be the cheaper option, the differences in costs are becoming increasingly smaller and might soon disappear. We argue that NIPT should preferably be offered as a first-tier test for the detection of fetal aneuploidies for all pregnant women, provided that women are supported to make informed decisions. This article is protected by copyright. All rights reserved.

Non‐invasive prenatal testing for fetal aneuploidy: charting the course from clinical validity to clinical utility

ACOG approves new trisomy screen for high‐risk pregnancies

Objective To grasp the situation of chromosome abnormalities of pregnant women with high-risk in noninvasive prenatal testing (NIPT) in Inner Mongolia Autonomous Region and the application of NIPT in this region. Methods From March 2013 to July 2017, a total of 82 pregnant women with high-risk in NIPT and then received amniocentesis in the Affiliate Hospital of Inner Mongolia Medical University were collected as research subjects. They were divided into indication group (n=68) and non-indication group (n=14) according to whether they were combined with prenatal diagnosis indications of amniocentesis or not before receiving NIPT. Retrospective analysis was conducted to collect clinical data of these 82 pregnant women, including origin areas of pregnant women, prenatal diagnosis indications of amniocentesis before receiving NIPT, fetal chromosomes abnormalities diagnosed by NIPT and amniocentesis, and statistical analysis was performed. Chi-square test was used to compare the detection rates of fetal chromosome abnormalities between two groups. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Affiliate Hospital of Inner Mongolia Medical University. Informed consent was obtained from each participant before amniocentesis. There were no statistical differences between two groups in the aspects of age, gestational age, and so on (P>0.05). Results ①Among 82 pregnant women with high-risk in NIPT in this study, 78.0% (64/82) of them were from three major cities in the Inner Mongolia Autonomous Region which were Hohhot (58.5%, 48/82), Ordos (11.0%, 9/82), and Baotou City (8.5%, 7/82). ②Among those 82 pregnant women with high-risk in NIPT in this study, 82.9% (68/82) pregnant women were combined with prenatal diagnosis indications of amniocentesis before receiving NIPT, including advanced age (≥35 years old) (36.6%, 30/82), high risk in maternal serum screening (30.5%, 25/82), abnormal results of prenatal ultrasonography (15.8%, 13/82); and 17.1% (14/82) of them were not combined with prenatal diagnosis indications of amniocentesis before receiving NIPT. ③Among those 82 pregnant women with high-risk in NIPT in this study, a total of 52 cases of fetal chromosomes abnormalities were detected by amniocentesis, and the detection rate of fetal chromosome abnormalities was 63.4% (52/82). The detection rate of NIPT for fetal autosomes abnormalities (21-, 18-, and 13-trisomy) was 85.7% (36/42), and the detection rate of NIPT for fetal sex chromosome abnormalities was 45.7% (16/35). ④The detection rate of fetal chromosome abnormalities in indication group was 73.5% (50/68), which was significantly higher than that in non-indication group 14.3% (2/14), and the difference was statistically significant (χ2=17.563, P<0.001). Conclusions The application of NIPT technology in Inner Mongolia Autonomous Region has improved the deficiency of prenatal aneuploid screening in this region. However, there is still a lack of consensus in clinical practice so far in the indications of NIPT screening. And the false positive rate of NIPT screening for chromosomal abnormalities in our hospital is significantly higher than that in other regions. In addition, using the prenatal screening methods common in current clinical trials for initial prenatal screening could effectively improve the positive detection rate of NIPT. Key words: Prenatal diagnosis; Chromosome aberrations; Noninvasive prenatal testing; False positive rate; Pregnant women

Expanded indications for noninvasive prenatal genetic testing: Implications for the individual and the public

Prenatal screening for chromosomal abnormalities has two components i.e. prenatal screening (maternal serum screening and cell-free fetal DNA screening) and prenatal diagnosis (chorionic villus sampling, amniocentesis, and cordocentesis). Prenatal testing in the past decade is evolving towards non-invasive methods to determine the chromosome abnormality disorders in the fetus without incurring the risk of miscarriage. Conventional tools for prenatal screening included maternal age, maternal serum markers, ultrasound marker (nuchal thickness), and their combinations. With the increased risk of screening test patients were offered diagnostic tests (chorionic villus sampling, amniocentesis, and cordocentesis). After the availability of noninvasive prenatal tests for commercial use in 2011, a great marketing drive is there to establish it as a master tool for prenatal testing. However various society guidelines i.e. ACOG, RCOG, and ISUOG have clearly stated that cell-free fetal DNA based noninvasive prenatal tests is a screening test, not a diagnostic test. In the succeeding paragraph, we will review current trends in the field of cell-free fetal DNA noninvasive prenatal tests and the relevance of invasive testing in the context of noninvasive prenatal tests. Noninvasive prenatal tests does not entirely replace invasive prenatal testing procedures. Positive noninvasive prenatal tests findings must be confirmed by diagnostic tests based on an invasive sample source, mainly chorionic villus sampling or amniocentesis due to false positive and false negative reports of cell-free fetal DNA based tests. Continuing research and development efforts are focused on overriding noninvasive prenatal tests limitations. Recent studies show that procedure-associated risks in the case of prenatal invasive testing are very low as compared to previous studies. Prenatal invasive testing will remain as the backbone of prenatal diagnostic testing until the limitation of noninvasive prenatal tests is overcome.

Informed decisions concerning non-invasive prenatal testing (NIPT) seem contingent on health professionals and expectant parents (1) having access to multifaceted information about the procedure of NIPT and the subsequent choices; and (2) actively reflecting about what prenatal screening means beyond the medical level (including personal values and beliefs). International studies show that many pregnant women do not make informed decisions about prenatal testing (Beulen et al. 2016). Interviews we conducted with various stakeholders in Belgium show similar tendencies.Based on transdisciplinary research (Dehens et al. 2017)—which included stakeholder interviews, and a review of academic literature, current prenatal screening guidelines, and good practices—we propose three initiatives that can help stimulate informed choices. The initiatives are: (1) a decision aid that encourages expectant parents to think about NIPT, its possible outcomes, and the conditions NIPT screens for (see e.g. Smith et al. 2018; Carslon et al. 2019); (2) the creation of a nation-wide protocol (draaiboek) for prenatal screening outlining what information should be provided at what point during a pregnancy, in what way, and by whom (see for instance the Draaiboek Prenatale screening down-, edwards- en patausyndroom en structureel echoscopisch onderzoek versie 9.0 in the Netherlands); and (3) an online platform featuring a balanced representation of testimonials about various experiences with the main conditions NIPT screens for taking Braverman (2008) as a starting point. These initiatives were discussed (conceptually) at a round table discussion with a broad range of stakeholders (May 8, 2019). A concluding poll showed &lt;target target-type="page-num" id="p-20"/&gt;a strong consensus concerning the need to develop a prenatal screening protocol and a decision aid in order to help health professionals and expectant parents, navigate through prenatal screening programs in Belgium. Anticipating the widening scope of genetic tests, a general plan of action is necessary to ensure counseling possibilities and informed decisions.

A new comprehensive paradigm for prenatal diagnosis: seeing the forest through the trees.

Since April 2013, Hokkaido University Hospital (HUH) has participated in a multicenter clinical trial in which non-invasive prenatal testing (NIPT) for fetal trisomies 21, 18 and 13, using fetal cell-free DNA from maternal plasma, has been provided for women at increased risk of trisomy. It was expected that the number of pregnant women seeking NIPT would be high, because of both the presence of numerous reports in the Japanese media prior to commencement of the clinical trial and the knowledge that NIPT, in addition to being non-invasive, is a procedure with high sensitivity and low false-negative rates among women at higher risk of fetal aneuploidy1. We did not expect that there would be a corresponding increase in the number of women undergoing invasive confirmatory tests, such as chorionic villus sampling (CVS) and amniocentesis. However, as of yet no data have been published regarding changes in the number of women seeking prenatal screening, including the combined test2, first-trimester ultrasound examination3, quad screen4 and NIPT, or in the number undergoing invasive confirmatory tests following the introduction of NIPT in Japan. During the 2 years preceding the clinical introduction of NIPT at HUH, 75 and 144 women underwent at least one prenatal screening test in the Japanese fiscal years beginning in 2011 and 2012, respectively. This increased markedly to 369 women after the introduction of NIPT in 2013 (Table 1). This change was due entirely to the number of women undergoing NIPT, accounting for 70.7% (261/369) of all women who had at least one prenatal screening test in 2013. However, there was no corresponding increase in the number of women undergoing invasive confirmatory tests, such as CVS or amniocentesis. In 2011, 18 of 75 (24.0%) women who underwent prenatal screening subsequently underwent further invasive confirmatory tests, as did 28 of 144 (19.4%) women in 2012. This decreased to 18 (4.9%) of 369 women in 2013 after the introduction of NIPT (Table 1). In the 3-year study period, 61 (18.7%) of 327 women who underwent prenatal screening other than NIPT alone underwent invasive confirmatory tests, while only three (1.1%) of 261 women who underwent NIPT underwent such tests (Figure 1) (P < 0.0001, Fisher's exact test). Among 237 women with negative results for prenatal screening other than NIPT, 12 (5.1%) underwent CVS or amniocentesis for confirmation, while no one with negative NIPT results underwent these tests. This suggests that women who underwent NIPT accepted the results of the technique as reliable. In Japan, the number of pregnant women undergoing prenatal screening has been traditionally lower than that in some European countries and the USA5. However, with the introduction of NIPT, the number of women seeking prenatal screening has increased markedly, suggesting a potential need for prenatal diagnosis that had been hidden because sufficient information regarding prenatal screening was absent and because there was concern among pregnant Japanese women about the risk of adverse events associated with CVS and amniocentesis. NIPT may become accepted in Japan, which could lead to a reduction in the number of invasive procedures for detection of fetal trisomies in the near future. R. Akaishi, T. Yamada*, S. Kawaguchi, T. Kojima, T. Koyama, T. Umazume, M. Morikawa, K. Cho and H. Minakami Department of Obstetrics, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan *Correspondence. (e-mail: [email protected])

Public funding for non-invasive prenatal testing for fetal aneuploidy - It's time.

BackgroundHealthcare professionals have ethical duties to provide information according to conceptions of the doctor-patient relationship, and one way this responsibility is established in practice is by UK guidance on shared decision making. Non-invasive prenatal testing (NIPT) is a relatively new prenatal screening test offered by the UK National Health Service (NHS) since 2021. Since NIPT has different characteristics when compared to other prenatal screens and tests—such as the combined test and amniocentesis—it is not clear how information should be offered in a pre-test consultation. Key to answering this question is to understand more about the HCP-patient relational dynamics surrounding the offer of NIPT. Previous studies have focused on the woman’s role in this; the views and attitudes of pregnant women about decision making in the offer of NIPT has been interrogated elsewhere. However, little attention has been given to the views and attitudes of healthcare professionals (HCPs) and how those views might shape the dynamics of how NIPT is offered and how the decision-making process goes.MethodsThis study carried out qualitative interviews with 20 UK HCPs who offered NIPT and/or provided counselling for NIPT. Findings from the interviews were analysed and themes were developed about how HCPs reported they offered NIPT and their reasons for this.ResultsHCPs say they conveyed information about the nature of NIPT to women when offering the test. This includes how HCPs say they described the risks of NIPT, their views about clarifying the non-diagnostic nature of NIPT, how they explained NIPT accuracy to women, and how they stressed that decisions about test options were up to the patient. HCPs also reported how they distinguished NIPT from other screens and tests and described NIPT as a different category of screening test. Furthermore, many HCPs say they either provided predetermined information to patients or reported being patient-led in the offer.ConclusionsThis study explores how HCPs reported the offer of NIPT and also how they thought the offer should go, by giving their reasons for what they report. This indicates their normative sense of which information ought to be given (that is, what they believed was critical to provide for decision making). It also indicates which aspects within the offer they believed should be emphasised or played down. The accounts reported here of HCPs’ experiences raise questions about how information should be provided to women in the offer of NIPT. This might help us establish better practices of informing women who use NIPT. Results of this study have a number of implications for the ethics of prenatal testing in practice. Firstly, they indicate a need for better guidance and education about how to discuss certain informational aspects within the offer such as NIPT characteristics and statistics. Secondly, they show that aspects of the current offer may be value-laden, and the way HCPs counsel patients about NIPT may be insufficiently patient-led. More research in this area might tell us whether different guidance or educational opportunities ought to be developed to help HCPs discuss NIPT and its characteristics.Clinical trial numberNot applicable.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12910-025-01227-z.

In Denmark, non-invasive prenatal testing (NIPT) has been used since 2013. We aimed to evaluate the early clinical use of NIPT in Danish public and private healthcare settings before NIPT became an integrated part of the national guidelines on prenatal screening and diagnosis in 2017. NIPT data were collected between March 2013 and June 2017 from national public registries and private providers. Results from follow-up samples (chorionic villi, amniotic fluid, postnatal blood or fetal tissue) were included from The Danish Cytogenetics Central Registry and indications and outcome from The Danish Fetal Medicine Database. A total of 3936 NIPT results were included in the study from public hospitals (n=3463, 88.0%) and private clinics (n=473, 12.0%). The total number of prenatal tests was 19713 during the study period: 20% were NIPT analyses (n=3936) and 80% invasive procedures (n=15777). Twenty-five percent of NIPTs in the private clinics were performed before gestational week 11+0 , whereas NIPT in public settings was used only after combined first trimester screening (P< .001). Regardless of indication, the national public sensitivity was 96.9% (95% CI 82.0%-99.8%) for trisomy 21, 100% (95% CI 46.3%-100%) for trisomy 18, 100% (95% CI 5.5%-100%) for trisomy 13, and 87.0% (95% CI 74.5%-92.4%) for any fetal chromosomal aberration. Forty-seven true-positive NIPT results included cases of common aneuplodies (trisomy 21, n=31; trisomy 18, n=5; and trisomy 13, n=1), sex chromosomal aberrations (n=7) and atypical chromosomal aberrations (n=3). One false-negative NIPT result occurred (trisomy 21). Of 47 cases, 21 (45%) cases with a true-positive NIPT result resulted in live births by choice; 11 of these children had Down and 4 had Edwards syndrome. The total number of NIPT analyses was low compared with the number of invasive procedures in the implementation period. In contrast to the generally high termination rate after a positive result following invasive testing in Denmark, a high proportion of true-positive NIPT results from the public setting resulted in live births. NIPT may be an important risk-free alternative to invasive testing for a minority of women in the public setting who wish to use prenatal genetic testing for information only and not for reproductive decision-making.

Noninvasive prenatal testing (NIPT) using cell-free fetal DNA has increasingly been adopted as a screening tool for fetal aneuploidies. Several studies have discussed benefits and limitations of NIPT compared with both ultrasound and invasive procedures, but in spite of some shortcomings NIPT has become extensively used within the last 5years. This study aims to describe the current use of NIPT in Europe, Australia and the USA. We conducted a survey to describe the current use of NIPT. Colleagues filled in a simple email-based questionnaire on NIPT in their own country, providing information on (a) access to NIPT, (b) NIPT's chromosomal coverage, (c) financial coverage of NIPT for the patient and (d) the proportion of women using NIPT in pregnancy. Some data are best clinical estimates, due to a lack of national data. In Europe, 14 countries have adopted NIPT into a national policy/program. Two countries (Belgium and the Netherlands) offer NIPT for all pregnant women, whereas most other European countries have implemented NIPT as an offer for higher risk women after first trimester screening. In Australia, either combined first trimester screening (cFTS) or NIPT is used as a primary prenatal screening test. In the USA, there are no national consensus policies on the use of NIPT; however, NIPT is widely implemented. In most European countries offering NIPT, the proportion of women using NIPT is well below 25%. In the Netherlands, Austria, Italy, Spain and most Australian and American States, 25%-50% of women have NIPT performed and in Belgium testing is above 75%. In most countries, NIPT reports on trisomy 13, 18 and 21, and often also on sex chromosome aneuploidies. Only in Belgium, the Netherlands, Lithuania, Greece, Cyprus and Italy is NIPT offered predominantly as a genome-wide test (including some microdeletions or a whole genome coverage). Noninvasive prenatal testing has been widely adopted throughout Europe, Australia and the USA, but only a few countries/states have a national policy on the use of NIPT. The variation in NIPT utilization is considerable.

BackgroundNoninvasive prenatal testing (NIPT) is a screening tool for chromosomal aneuploidies. Prior knowledge of NIPT is an inherent factor in the decision‐making process. We assessed the knowledge and attitude of pregnant women related to prenatal testing with a particular focus on NIPT.MethodsA prospective cross‐sectional study, using a culturally validated questionnaire, was conducted with 342 pregnant women of whom 74.9% consented for prenatal screening. Mean age and gestational weeks ± standard deviation was 31 ± 5 and 26 ± 11, respectively.ResultsA positive/very positive attitude was observed to ultrasound, followed by FCT, NIPT, and lastly to CVS. More than half of the participants (56.1%) had no previous knowledge of NIPT. A reaching significance association was detected between education and knowledge of NIPT. Significant association was detected between risk for aneuploidy and knowledge of NIPT. The majority (74%) indicated their willingness to perform the test. The effect and value of society on the pregnant women to make a decision regarding NIPT was negligible.ConclusionThe pregnant women in the current study displayed a lack of knowledge and awareness regarding prenatal screening, particularly the NIPT. We recommend that pregnant women receive adequate counseling regarding prenatal screening to increase their awareness and knowledge of prenatal testing, including NIPT.