Use Of Non-invasive Prenatal Testing Research Articles

Position statement from the International Society for Prenatal Diagnosis on the use of non-invasive prenatal testing for the detection of fetal chromosomal conditions in singleton pregnancies.

n/a This article is protected by copyright. All rights reserved.

Issues associated with possible implementation of Non-Invasive Prenatal Testing (NIPT) in First-Tier Screening: A Rapid Scoping Review.

In recent years, as the implementation and use of NIPT have increased, the cost of the test has been decreasing. The cost of NIPT is expected to fall further in the upcoming years. As a result of the decreasing cost of NIPT, many jurisdictions may change their prenatal screening policies towards abandoning serum-based screening and instead, implement and support NIPT as the first-tier screening for all women. There are several concerns in replacing first-trimester screening with NIPT. In this scoping review, we aimed to map the existing knowledge about possible issues in the systematic implementation of NIPT as the primary method of first-tier screening, and to assess if any jurisdiction has altered its policy and discontinued serum based prenatal screening in exchange for NIPT. The Medline database (Ovid) and Google Scholar was searched and all the studies discussing, investigating, or reporting on the systematic implementation of NIPT as the primary method of first-tier screening were included. All the studies went through a two-stage screening process and included full-text articles were reviewed and charted, and the data is summarized narratively and put in tables. Findings from this scoping review may be informative for stakeholders and policymakers regarding recent changes in NIPT implementation policies around the world and may aid with developing policy for NIPT implementation with a broader perspective. This article is protected by copyright. All rights reserved.

Clinical experience of noninvasive prenatal testing for rare chromosome abnormalities in singleton pregnancies.

Objectives: The study aimed to investigate the clinical use of noninvasive prenatal testing (NIPT) for common fetal aneuploidies as a prenatal screening tool for the detection of rare chromosomal abnormalities (RCAs). Methods: Gravidas with positive NIPT results for RCAs who subsequently underwent amniocentesis for a single nucleotide polymorphism array (SNP array) were recruited. The degrees of concordance between the NIPT and SNP array were classified into full concordance, partial concordance, and discordance. The positive predictive value (PPV) was used to evaluate the performance of NIPT. Results: The screen-positivity rate of NIPT for RCAs was 0.5% (842/158,824). Of the 528 gravidas who underwent amniocentesis, 29.2% (154/528) were confirmed to have positive prenatal SNP array results. PPVs for rare autosomal trisomies (RATs) and segmental imbalances were 6.1% (7/115) and 21.1% (87/413), respectively. Regions of homozygosity/uniparental disomy (ROH/UPD) were identified in 9.5% (50/528) of gravidas. The PPV for clinically significant findings was 8.0% (42/528), including 7 cases with mosaic RATs, 30 with pathogenic/likely pathogenic copy number variants, and 5 with imprinting disorders. Conclusion: NIPT for common fetal aneuploidies yielded low PPVs for RATs, moderate PPVs for segmental imbalances, and incidental findings for ROH/UPD. Due to the low PPV for clinically significant findings, NIPT for common fetal aneuploidies need to be noticed for RCAs.

Role of Sonographic Second Trimester Soft Markers in the Era of Cell-Free DNA Screening Options: A Review

Soft markers are sonographic structural, nonspecific signs with little pathological significance, often transient, usually considered as normal variants. However, they may also be associated with chromosomal abnormalities. The most widely examined soft markers include absent or hypoplastic nasal bone (NB), intracardiac echogenic focus (IEF), ventriculomegaly (VM), thickened nuchal fold (NF), choroid plexus cyst (CPC), echogenic bowel, short long bones, and urinary tract dilation (UTD). Although the use of noninvasive prenatal testing (NIPT) has been spreading quickly in maternal–fetal medicine, it is not a diagnostic test and it still remains unavailable or cost-prohibitive for most of the population in many countries. After normal screening test results in the first trimester, there is no uniform consensus regarding the clinical significance of isolated soft markers for aneuploidy. Nowadays, the search for soft markers in an ultrasound is still part of clinical evaluation, and the interpretation of these findings is often a matter of debate. In the present review, we summarize the recent literature about the role of soft markers in the era of NIPT and propose an overview of the different clinical guidelines.

Insurance and geographic variations in non-invasive prenatal testing.

This article is protected by copyright. All rights reserved.

Non-invasive Prenatal Testing for Fetal Whole Genome Sequencing: An Interpretive Critical Review of the Ethical, Legal, Social, and Policy Implications

Introduction: Non-invasive prenatal testing (NIPT) allows for genetic testing of a fetus through the analysis of cell-free DNA from the mother’s plasma. NIPT is easy and safe for the fetus, since it only requires a blood draw from the mother and therefore holds no risk of miscarriage. It is considered superior to other prenatal screening tests and can also be performed earlier in the pregnancy. NIPT has the future potential for fetal whole genome sequencing (FWGS) for an expanded range of conditions, such as late onset genetic conditions and carrier status. Objective: To review ethical, legal, social, and policy implications of the potential use of non-invasive prenatal testing for FWGS. Methods: This study is a critical interpretive literature review exploring and reporting ethical, legal, social, and policy implications of potential future implementation of NIPT for FWGS, which will be referred to as non-invasive prenatal whole genome sequencing (NIPW). Database and reference list searching was conducted between 2010 and 2019 for terms related to “non-invasive prenatal testing” AND “fetal whole genome sequencing” and derivatives. Results: Following screening, 32 articles were included. Data were grouped into four thematic categories: 1) ethical implications for the future child concerning autonomy and harms, as well as for prospective parents involving autonomy, informed consent concerns, and harms; 2) legal implications including privacy concerns; 3) social implications including changes in family dynamics, altered societal perceptions and disability concerns, justice and equity in accessing the test, and social pressure to use the test; and 4) policy implications including cost and funding concerns, limiting the scope of testing, as well as counseling, education, and support. Discussion: The discussion of results highlights several ethical, legal, social, and policy implications of NIPT use for FWGS. These findings have implications on NIPT implementation for FWGS including how the autonomy of the future child should be balanced with the autonomy of prospective parents, the scope of conditions that should or should not be tested for – and covered or not covered by the healthcare system – and the regulation of FWGS introduction, among others. Further research needs to be performed to address these concerns and hence guide the discussion about the clinical implementation of FWGS through NIPT.

Making use of non-invasive prenatal testing (NIPT): rethinking issues of routinization and pressure.

First mapping the main ethical issues surrounding prenatal testing, we then analyze which concerns are specific to non-invasive methods. Presupposing the privatization premise for reproductive autonomy in fundamentally liberal societies, we go on to specify common concerns about non-invasive prenatal testing (NIPT) covered by the term 'routinization', and conceptually unravel the frequently expressed worry of increasing 'pressure' to test and/or terminate affected pregnancies. We argue that mindful decision-making should be a key educational goal (not only) of NIPT counseling which could be achieved through stepwise disclosure. In addition, we identify indirect social pressure as the most plausible threat to reproductive freedom. While continuous efforts need to be made to prevent such pressure- not least by ensuring balanced availability of options-, restricting testing options, and thus freedom of choice, cannot be the answer to this concern. Lastly, we suggest abandoning the vague term 'routinization' and instead focusing on specified concerns to enable a fruitful debate.

Noninvasive prenatal testing in megacity

Introduction. The article presents an analysis of the use of non-invasive prenatal testing for chromosomal abnormalities in the fetal extracellular DNA in the blood of pregnant women in Moscow. Materials and methods. When processing materials and research results, authors considered all available clinical data: findings of an ultrasound examination, medical history and results of additional laboratory tests. Results. The article presents results of invasive prenatal diagnostics and pregnancy outcomes in patients with high NIPT risks. Discussion. Authors analyzed diagnostic capabilities of NIPT, its limitations, false-positive and false- negative results, and described 3 cases of prenatal diagnosis of fetal aneuploidy identified in patients who are in the «gray zone» of risk based on the results of combined screening of the first trimester of pregnancy. Conclusion. Prenatal diagnosis of the described aneuploidy is difficult due to individual risk of developing chromosomal abnormalities of the fetus based on the results of combined first-trimester screening in the range of 1:101-1: 2500 and lack of indications for invasive prenatal diagnostics.

Pregnancy Loss After Amniocentesis and Chorionic Villus Sampling: Cohort Study.

IntroductionIntroduction: To estimate the procedure-related risks of pregnancy loss following chorionic villus sampling (CVS) and amniocentesis (AC) compared to pregnancies without procedure.MethodsThis cohort study enrolled all women who underwent CVS or AC at the Department of Perinatology, University Medical Centre, Ljubljana, Slovenia (from January 2013 to June 2015). For each group we obtained a maternal age and gestational age (11–14 weeks for CVS and >15 weeks for AC) for a matched control group without invasive procedures from the national database. The data was obtained from hospital records and telephone surveys concerning pregnancy outcomes. Pregnancy loss rates in intervention vs. control groups were compared by generating relative risk (RR) with a 95% confidence interval.ResultsDuring the study period, 828 women underwent CVS and 2,164 women underwent AC. Complete outcome data was available in 2,798 cases (93.5%, 770 CVS, 2,028 AC). Pregnancy loss occurred in 8/770 (1.04%, 95% CI 0.4–2.0%) after CVS vs. 15/1130 (1.33%, 95% CI 0.8–2.2%) in matched control (RR 0.8, 95% CI 0.33–1.8, p=0.6). It occurred in 16/2028 (0.79%, 95% CI 0.5–1.3%) after AC vs. 14/395 (3.29%, 95% CI 2.1–5.8%) in matched control (RR 0.2, 95% CI 0.11–0.45, p<0.0001).ConclusionThe pregnancy loss rates after CVS and AC were comparable to losses in pregnancies without these procedures. With the increasing use of non-invasive prenatal testing, information that the invasive procedures are safe when indicated is essential.

Discussing non-invasive prenatal testing on Reddit: The benefits, the concerns, and the comradery.

As the use of non-invasive prenatal testing (NIPT) increases, its benefits and concerns are being examined through surveys, qualitative studies, and bioethical analysis. However, only scant research has examined public discourse on the topic. This research examined NIPT discussions on the social media platform Reddit. Content and qualitative description analysis was performed on 98 NIPT discussions (2682 comments), obtained by inputting "NIPT" into Reddit's search engine. Detailing of benefits and concerns was found in collaborative and supportive discussions. Overall, NIPT is seen as valuable and desirable. Some concerns focused on cost-related barriers to access, anxiety related to testing, and interpretation of results. NIPT is often portrayed as offering peace of mind and is sometimes described as a means of preparing for possible outcomes. In the discussions analyzed, NIPT is seen, overall, as valuable and greater access to it is desired. Some questions and concerns about NIPT were evident. Reddit stands as a valuable and appreciated tool for individuals wishing to discuss NIPT and to solicit and share information, opinions, and experiences. Health care providers should consider the ways social platforms such as Reddit can be engaged to better inform and educate the public.

Prenatal detection and evaluation of differences of sex development

Differences/disorders of sex development (DSD) can be detected at different ages, including prenatally. The recent implementation of prenatal genetic testing (including cell-free DNA) may affect the frequency and impact of prenatal diagnosis of DSD. Our aims were to(1) describe prenatal detection and evaluation of differences of sex development presenting to a multidisciplinary DSD clinic and (2) explore possible parental distress accompanying this evaluation. A retrospective chart review of mothers presenting prenatally, and patients presenting during infancy, to a multidisciplinary DSD clinic from 2013 to 2017 was conducted. Data extracted included demographics, final diagnoses, prenatal screening, prenatal evaluation, postnatal endocrine, genetic and radiologic testing, and clinician's notes on parent/patient distress. Sixty-seven patients were identified; ten (15%) had prenatal detection of a suspected DSD. Of those, 4/10 were detected prenatally in the last study year alone. Within the prenatal group, 6/10 had cell-free DNA results discordant with ultrasound, 2/10 were detected by atypical genitalia on ultrasound, and 2/10 were detected through karyotyping performed for other indications. After birth, 3/10 patients were found to not have a DSD. Final diagnoses for the full study cohort are shown in the Summary Table, comparing prenatal versus postnatal presentation to our DSD clinic. Clinicians noted distress for most parents during the prenatal evaluation of a possible DSD, including one mother who reported suicidal thoughts. Prenatal suspicion of DSD can occur through discordant prenatal testing and has been observed at our clinic in recent years, in line with other recent studies. Contributing factors to these prenatal presentations could be increased referrals to the clinic, and increased use of non-invasive prenatal testing, which can lead to inaccurate or discordant sex identification. The prenatal suspicion of a potential DSD can be associated with parental distress, underscoring the need for adequate counseling for tests that determine fetal sex, including cell-free DNA.

Noninvasive prenatal testing: from aneuploidy to single genes.

Noninvasive prenatal testing has undergone rapid advances in the last few years. Although researchers have long known about circulating pregnancy-based cell-free fragments of DNA in maternal plasma, it was the introduction of massively parallel sequencing that allowed noninvasive prenatal testing to become a widely used clinical test. This review will begin with an in-depth analysis of the use of noninvasive prenatal testing for aneuploidy, including common causes for inaccurate and/or discordant results. It will also review the ongoing expansion of noninvasive prenatal testing to include copy number variants and select single-gene disorders. Finally, integrated throughout the review is a comparison of noninvasive prenatal testing to more traditional screening methods along with some medical and ethical implications of the widespread use of this new technology.

Noninvasive prenatal testing: the aspects of its introduction into clinical practice

The last couple of years have witnessed the rapid development of prenatal molecular-based screening for fetal aneuploidies that utilizes the analysis of cell-free DNA circulating in the bloodstream of a pregnant woman. The present review looks at the potential and limitations of such testing and the possible causes of false-positive and false-negative results. The review also describes the underlying principles of data acquisition and analysis the testing involves. In addition, we talk about the opinions held by the expert community and some aspects of legislation on the use of noninvasive prenatal testing (NIPT) in clinical practice in the countries where NIPT is much more widespread than in Russia.

EXPERIENCE OF NON-INVASIVE PRENATAL TEST (NIPT) AT FERNANDEZ HOSPITAL.

AIM: Non -Invasive Prenatal Test is the testing for cell free fetal DNA from maternal blood during pregnancy for Trisomy 21, 18,13 and Monosomy 45XO. The aim of our study is to review our institution’s experience in the use of non-invasive prenatal test for aneuploidy screening METHODS: It is a retrospective study of pregnant women who had undergone non-invasive prenatal test between January 2015 and December 2018 at Fernandez Hospital. A detailed Ultrasonogram is done as a mandatory prerequisite before NIPT to rule out major structural anomalies; pre and post- test counselling was done to all pregnant women who underwent non-invasive prenatal test RESULTS: 322 women who had undergone non-invasive prenatal test were included in the study. 32% of the study population were of advanced maternal age. Low fetal fraction was seen in 2.1% of the study population. An abnormal non -invasive prenatal result (aneuploidy detected or inconclusive result) was reported in 36/322(11%).NIPT had a sensitivity of 100% and specificity of 99.6% in our study. Ever since NIPT has been introduced in our clinical practice the rate of invasive tests performed declined and the number of non-invasive prenatal test performed increased yearly CONCLUSION: NIPT is an excellent method for screening for aneuploidy. There is an increasing uptake of NIPT and a decline in the rate of invasive tests performed. The occurrence of false positive results emphasizes that NIPT is a screening test and not to be considered as a replacement for diagnostic tests.

Economic Analysis of The Use of Non-Invasive Prenatal Test (NIPT) For Prenatal Screening of Trisomy 21, 18, 13 In Pregnant Women

Economic Analysis of The Use of Non-Invasive Prenatal Test (NIPT) For Prenatal Screening of Trisomy 21, 18, 13 In Pregnant Women

The use of non-invasive prenatal test in screening for fetal aneuploidies in twin pregnancies with an embryo stopped growing in the first trimester

The use of non-invasive prenatal test in screening for fetal aneuploidies in twin pregnancies with an embryo stopped growing in the first trimester

The value and role of non-invasive prenatal testing in a select South African population.

Concerns have been raised about the injudicious use of non-invasive prenatal testing (NIPT) using cell-free DNA (cfDNA), which often leads to inaccuracies in interpretation of the role and value of cfDNA in prenatal screening. To determine the value and role of NIPT in a select South African (SA) population. A retrospective review of patients who elected to have NIPT between 1 October 2013 and 30 June 2015 at the Morningside Mediclinic Maternal and Fetal Medicine Centre in Johannesburg, SA. Patients had NIPT after either combined first-trimester screening (CFTS) or a second-trimester ultrasound scan. Data were collected on details of the first- and/or second-trimester screening, results of the NIPT, invasive tests done, decisions made in the event of abnormal results, and pregnancy outcomes. Overall, 3473 first- and second-trimester fetal assessments were done at the centre during the study period, and 2.3% of patients (n=82) elected to have NIPT. The majority of these individuals elected to have NIPT on the basis of positive findings on CFTS, or markers of aneuploidy detected on a second-trimester ultrasound scan. Of the tests done, 97.6% produced results. Of those with no results, one did not meet quality metrics and the other had a low fetal fraction of cfDNA. There were two abnormal NIPT results, one indicating a high risk of trisomy 13 and the other a triploidy. Patients who screened negative elected not to have an invasive test. The value of NIPT in this study was that it made it possible to avoid a number of invasive tests. NIPT had a role in contingency screening.

The use of noninvasive prenatal testing in obstetric care: educational resources, practice patterns, and barriers reported by a national sample of clinicians.

The aim of this study was to identify how physicians develop their knowledge base and practice patterns regarding noninvasive prenatal testing (NIPT). A survey was used to assess physicians' informational sources and practice patterns regarding NIPT. While most of the 258 participants acquire knowledge about NIPT from the medical literature or didactic educational programming, 74 (28.7%) cite commercial laboratories as an initial source and 124 (47.8%) as a way to keep current with changes in NIPT. About one-third (n = 94, 36.4%) seek information about ethical issues related to NIPT. Half of the OB/GYN respondents (n = 136, 52.7%) provide pretest counseling; fewer refer to a genetic counselor or maternal fetal medicine specialist (MFM) (n = 94, 34.6%, n = 29, 11.2%, respectively). Pretest counseling content and the comfort with which participants discuss topics pertinent to patients' utilization of NIPT varied between OB/GYNs and MFMs. Advances in cff DNA technology emphasize the need for effective strategies for physicians to develop competency and practice patterns regarding NIPT. Study findings speak to the need for effective educational resources for obstetric providers, not just early adopters of NIPT but also for primary OB/GYNs as they serve in the role of the first point of contact for women considering their prenatal testing options. © 2016 John Wiley & Sons, Ltd.

NIPT and Informed Consent: an Assessment of Patient Understanding of a Negative NIPT Result.

Since becoming clinically available in 2011, the use of noninvasive prenatal testing (NIPT) to screen for fetal aneuploidy has continued to increase. However, it has been questioned whether the education of patients undergoing NIPT consistently meets informed consent standards. We sought to evaluate patients' basic understanding of NIPT, such as conditions assessed and accuracy. In addition, we investigated patient self-assessment of NIPT knowledge and satisfaction with the testing process. We distributed an anonymous paper survey to pregnant women during prenatal visits following a negative NIPT result. The survey assessed patient NIPT knowledge, gathered pregnancy-specific and demographic information, and allowed respondents to rank their basic understanding of NIPT and provide written feedback about the testing process. A total of 95 completed and 3 partially completed surveys were returned. Participants scored lowest on knowledge questions involving whether a negative NIPT result ensures a healthy baby or eliminates the possibility of Down syndrome. Most perceived themselves to have a good basic understanding of NIPT and two-thirds of the written feedback proposed no changes to NIPT administration. Overall, most patients appear satisfied with their understanding of NIPT and the testing process, yet they may not fully appreciate the limitations of this screening method.

A first look at women's perspectives on noninvasive prenatal testing to detect sex chromosome aneuploidies and microdeletion syndromes

The aim of this study is to explore women's opinions about the use of noninvasive prenatal testing (NIPT) to assess the risk of sex chromosome aneuploidies and microdeletion syndromes. Focus groups were conducted with women who were currently pregnant or had recently delivered. Qualitative analysis using interpretive description was used to generate study findings. Thirty-one women (mean age 32.4 years) participated in the focus groups. Participants were unfamiliar with sex chromosome aneuploidies but expressed support for the use of NIPT to detect these conditions. Participants were uncertain about the utility and actionability of receiving information about microdeletion syndromes with variable or unknown phenotypic expression. Participants voiced their desire to be informed of all conditions assessed by NIPT prior to testing. They considered clinicians to be the key provider of such information, although stated that patients have a responsibility to be knowledgeable prior to testing in order to support informed decision making. The use of NIPT to identify sex chromosome aneuploidies and microdeletion syndromes will introduce new challenges for clinicians to ensure pregnant women have the information and resources to make informed choices about NIPT when used for these conditions.