Prenatal Testing For Fetal Aneuploidy Research Articles

Understanding knowledge, perception, and willingness of non-invasive prenatal testing for fetal aneuploidy: a survey among Chinese high-risk pregnant women.

Non-invasive prenatal testing (NIPT) is utilized for screening the likelihood of fetal aneuploidy, presenting the benefits of non-invasiveness, high sensitivity, and specificity. Its application in prenatal screening has become ubiquitous. The inquiry into how pregnant women comprehend and determine NIPT screening strategies is paramount. Regrettably, there has been a dearth of research on this subject in China. Consequently, this study scrutinizes pregnant women's cognizance and perspectives concerning NIPT, furnishing a foundation for advancing its judicious implementation. From February 2021 to December 2022, a questionnaire survey was conducted among pregnant women receiving prenatal care and screening at the Women's Hospital, School of Medicine, Zhejiang University, who were randomly selected from a pool of individuals exhibiting a high risk of fetal aneuploidy on serological screening. The survey aimed to gather data on participant characteristics, knowledge, perception, and willingness concerning NIPT. The study employed chi-square and Kruskal Wallis tests to analyze subgroup differences. A total of 226 valid questionnaires were obtained. 83.2% of women pregnant women identified as high risk by serological screening would opt for NIPT, with 66.4% indicating that they would prefer NIPT for fetal aneuploidy screening in future pregnancies. These findings suggest a notable willingness among pregnant women to undergo NIPT. Additionally, the results suggest that various factors, including place of residence, educational level, family income, causes of abortion, and conception method, influence pregnant women's knowledge about NIPT Accordingly, the level of NIPT knowledge varies among pregnant women. The survey generally revealed that pregnant women were strongly inclined to select NIPT; however, expectant Chinese mothers possess limited knowledge and perception regarding this screening method for fetal aneuploidy. Therefore, the government must implement effective measures to augment public awareness of fetal aneuploidy screening and encourage the judicious utilization of NIPT.

NanoNIPT: Short-fragment nanopore sequencing of cell-free DNA for non-invasive prenatal testing of fetal aneuploidies and sex chromosome aberrations.

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Performance of expanded non-invasive prenatal testing for fetal aneuploidies and copy number variations: A prospective study from a single center in Jiangxi province, China.

To evaluate the performance of expanded non-invasive prenatal testing (expanded noninvasive prenatal testing, NIPT-Plus) in screening for fetal chromosomal abnormalities includes aneuploidies and copy number variations, a total of 23,116 pregnant women with a singleton pregnancy were recruited for NIPT-Plus. Screening positive results were verified by karyotype analysis and chromosomal microarray analysis after amniocentesis. A total of 264 pregnancies (1.14%) were positive results as predicted by NIPT-Plus, including 233 aneuploidies and 31 copy number variations. Following genetic counseling, 233 (88.26%) pregnant women underwent invasive prenatal diagnosis and 136 were verified as true positives, comprising 72 common trisomies (T21, T18, T13), 47 sex chromosomal abnormalities two rare autosomal aneuploidies (RATs) and 15 copy number variations The positive predictive value for common trisomies, SCAs, RATs and CNVs were 68.57%, 68.12%, 6.67% and 51.72%, respectively. Pregnant women with screen-positive results for common trisomies have higher rates of invasive prenatal diagnosis and pregnancy termination than those with positive results for SCAs, RATs, and CNVs. NIPT-Plus showed a good performance in detecting common trisomies, SCAs and also contributed to detecting pathogenic CNVs, but higher accuracy was required in the detection of RATs. In summary, this study provides a reference for the clinical application of NIPT-Plus for screening fetal chromosomal abnormalities in this region. Therefore, we suggest that NIPT-Plus could be widely used in clinical screening for fetal chromosomal abnormalities in combination with prenatal diagnosis and genetic counseling.

Prenatal Diagnosis of Congenital Heart Diseases and Associations with Serum Biomarkers of Aneuploidy: A Multicenter Prospective Cohort Study.

PurposeWe assessed prenatal detection rates of congenital heart disease (CHD) and associations between maternal serum biomarkers and non-chromosomal CHD in singleton pregnancies.Materials and MethodsThis study was conducted as a secondary analysis of data obtained during a multicenter prospective cohort study that investigated the cost-effectiveness of prenatal testing for fetal aneuploidy. We analyzed the prenatal detection rate and accuracy for CHD screening via ultrasound during the second trimester, as well as associations between serum biomarkers and CHDs, in singleton newborns without chromosomal abnormalities.ResultsAmong 6715 women, 142 (2.1%) newborns were born with CHDs, of which 67 (1.0%) newborns had major CHDs. The prenatal detection rate for all CHDs and major CHDs were 34.5% and 58.2%, respectively. After excluding isolated ventricular septal defects, the detection rate for critical CHDs was 85.9%. Women with low pregnancy-associated plasma protein A (PAPP-A) (<0.4 multiples of the median, MOM) face increased risks of non-chromosomal CHDs [adjusted odds ratio (aOR) 2.76; 95% confidence interval (CI) 1.36–5.13] and major CHDs (aOR 7.30; 95% CI 3.18–15.59), compared to those without CHDs. A higher inhibin A level (≥2.5 MOM; aOR 4.84; 95% CI 1.42–12.46) was associated with non-chromosomal major CHDs.ConclusionUltrasonography performed during the second trimester by obstetricians detected over 85% of critical CHDs. Low maternal serum PAPP-A or high inhibin-A was associated with non-chromosomal CHDs. These results may contribute to an improvement in prenatal diagnosis of CHDs.

Prenatal Testing – What Is It Good For? A Review and Critique

The goals of prenatal testing remain controversial and reflect competing interests of public health, patient rights, disability activists, scholars, feminist critics, commercial laboratories, judiciary/legislative trends, and medical science. This paper reviews and critiques the most common justifications of prenatal testing for fetal aneuploidy that have been put forth over the half century of its existence: reducing the medical and economic burden to society of genetic disease through selective abortion, allowing parents to avoid raising a child with disabilities, preventing the suffering associated with chromosomal and genetic disorders, emotional reassurance about the health of the baby, and medical and emotional preparation for the birth of a baby with a disability. Each of these goals has problematic aspects, as do some of the criticisms of these goals. The most striking shortcoming of the justifications for prenatal testing is a dearth of research about potential medical, psychological, or adaptational benefits of prenatal testing, especially for aneuploidy, for babies and families, beyond the option of pregnancy termination.

Expanded noninvasive prenatal testing for fetal aneuploidy and copy number variations and parental willingness for invasive diagnosis in a cohort of 18,516 cases

BackgroundNoninvasive prenatal testing (NIPT) has been wildly used to screen for common aneuplodies. In recent years, the test has been expanded to detect rare autosomal aneuploidies (RATs) and copy number variations (CNVs). This study was performed to investigate the performance of expanded noninvasive prenatal testing (expanded NIPT) in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RATs), and copy number variations (CNVs) and parental willingness for invasive prenatal diagnosis in a Chinese prenatal diagnosis center.MethodsA total of 24,702 pregnant women were retrospectively analyzed at the Women and Children’s Hospital from January 2013 to April 2019, among which expanded NIPT had been successfully conducted in 24,702 pregnant women. The high-risk expanded NIPT results were validated by karyotype analysis and chromosomal microarray analysis. All the tested pregnant women were followed up for pregnancy outcomes.ResultsOf the 24,702 cases, successful follow-up was conducted in 98.77% (401/446) of cases with common trisomies and SCAs, 91.95% (80/87) of RAT and CNV cases, and 76.25% (18,429/24,169) of cases with low-risk screening results. The sensitivity of expanded NIPT was 100% (95% confidence interval[CI], 97.38–100%), 96.67%(95%CI, 82.78–99.92%), and 100%(95%CI, 66.37–100.00%), and the specificity was 99.92%(95%CI, 99.87–99.96%), 99.96%(95%CI, 99.91–99.98%), and 99.88% (95%CI, 99.82–99.93%) for the detection of trisomies 21, 18, and 13, respectively. Expanded NIPT detected 45,X, 47,XXX, 47,XXY, XYY syndrome, RATs, and CNVs with positive predictive values of 25.49%, 75%, 94.12%, 76.19%, 6.45%, and 50%, respectively. The women carrying fetuses with Trisomy 21/Trisomy 18/Trisomy 13 underwent invasive prenatal diagnosis and terminated their pregnancies at higher rates than those at high risk for SCAs, RATs, and CNVs.ConclusionsOur study demonstrates that the expanded NIPT detects fetal trisomies 21, 18, and 13 with high sensitivity and specificity. The accuracy of detecting SCAs, RATs, and CNVs is still relatively poor and needs to be improved. With a high-risk expanded NIPT result, the women at high risk for common trisomies are more likely to undergo invasive prenatal diagnosis procedures and terminate their pregnancies than those with unusual chromosome abnormalities.

VP29.11: High‐positive predictive values across maternal ages in non‐invasive prenatal testing for fetal aneuploidy

VP29.11: High‐positive predictive values across maternal ages in non‐invasive prenatal testing for fetal aneuploidy

Implementing Publicly Funded Noninvasive Prenatal Testing for Fetal Aneuploidy in Ontario, Canada: Clinician Experiences With a Disruptive Technology.

The last decade has experienced unprecedented uptake of noninvasive prenatal testing (NIPT), creating significant changes in the way prenatal clinicians provide services. Through the lens of social shaping of technology, we examine the effects of the introduction of this technology on the health care system in Ontario, Canada. Using a qualitative descriptive approach, we conducted a cross-sectional study investigating clinicians' perspectives of NIPT in 2014, 2016, and 2018. Through in-depth interviews (n = 37), we explored their perspectives on the impact of NIPT on their referral practices, workload, coordination of testing modalities, education and counseling, and elicited their views on recent expansions of the test. Findings suggest that the introduction of NIPT has created unintended consequences with respect to clinician workload and wellness, clinician education, equity of access, and public system resources. Responsiveness from decision makers is key to ensuring the responsible use of NIPT in the health care system.

Implementation challenges for an ethical introduction of noninvasive prenatal testing: a qualitative study of healthcare professionals\u2019 views from Lebanon and Quebec

BackgroundThe clinical introduction of non-invasive prenatal testing for fetal aneuploidies is currently transforming the landscape of prenatal screening in many countries. Since it is noninvasive, safe and allows the early detection of abnormalities, NIPT expanded rapidly and the test is currently commercially available in most of the world. As NIPT is being introduced globally, its clinical implementation should consider various challenges, including the role of the surrounding social and cultural contexts. We conducted a qualitative study with healthcare professionals in Lebanon and Quebec as case studies, to highlight the relevance of cultural contexts and to explore the concerns that should be taken into account for an ethical implementation of NIPT.MethodsWe conducted semi-structured interviews with 20 healthcare professionals (HCPs), 10 from each country, practicing in the field of prenatal screening and follow up diagnostic testing, including obstetricians and gynecologists, nurses, medical geneticists and, genetic counselors. We aimed to 1) explore HCPs’ perceptions and views regarding issues raised by NIPT and 2) to shed light on ways in which the introduction of the same technology (NIPT) in two different contexts (Lebanon and Quebec) raises common and different challenges that are influenced by the cultural norms and legal policies in place.ResultsWe identified challenges to the ethical implementation of NIPT. Some are common to both contexts, including financial/economic, social, and organizational/ educational challenges. Others are specific to each context. For example, challenges for Lebanon include abortion policy and financial profit, and in Quebec challenges include lobbying by Disability rights associations and geographical access to NIPT.ConclusionsOur findings highlight the need to consider specific issues related to various cultural contexts when developing frameworks that can guide an ethically sound implementation of NIPT. Further, they show that healthcare professional education and training remain paramount in order to provide NIPT counseling in a way that supports pregnant women and couples’ choice.

Combining the use of a fetal fraction-based risk algorithm and probability of an informative redraw in noninvasive prenatal testing for fetal aneuploidy.

Some women undergoing noninvasive prenatal testing (NIPT) do not receive an informative result due to low fetal fraction (FF). A proportion of these are at increased risk for fetal trisomy 13, 18, or triploidy, while others have no change from their prior risk. Women with an initial uninformative NIPT need to be counseled about any such change in their risk for fetal abnormality and also the probability that a redraw will be informative. To help in the decision making, we reviewed a dataset of single nucleotide polymorphism‐based NIPT with uninformative results where a redraw was received. Risk for trisomy 13, 18, or triploidy was evaluated using a fetal fraction‐based risk (FFBR) algorithm. Risk‐unchanged women were further analyzed using a regression model to determine the likelihood of an informative redraw. Of 2,644 women with an uninformative NIPT and a redraw, 1,147 (43.4%) were high risk for trisomy 13, 18, or triploidy. 1,497 (56.6%) were risk unchanged and, of these, 975 (65.1%) cases had an informative redraw (i.e., risks were available for 2,122 (80%) of those initially classified as uninformative). The regression model for the risk‐unchanged cases provided a new table for predicting an informative redraw. Likelihood of a successful redraw was significantly (p < .001) dependent on the initial FF, maternal weight, and time between blood draws. We conclude that the FFBR algorithm and the predictive model for an informative redraw provide complementary additions in the management of women presented with an initially uninformative SNP‐based NIPT due to low FF. We suggest approaches for the counseling and follow‐up testing for women with an initially uninformative NIPT.

High risk-What's next? A survey study on decisional conflict, regret, and satisfaction among high-risk pregnant women making choices about further prenatal testing for fetal aneuploidy.

To investigate decision making among pregnant women when choosing between noninvasive prenatal testing, invasive testing, or no further testing. Women with a high-risk result from the first trimester screening were invited to fill in two online questionnaires at gestational age 12 to 14 (Q1) and 24 weeks (Q2). The scales used were Decisional Conflict and Regret Scales, Satisfaction with genetic Counselling Scale, and Health-Relevant Personality Inventory. Three hundred thirty-nine women agreed to participate, and the response rates were 76% on Q1 and 88% on Q2. A percentage of 75.4% chose an invasive test, 23.8% chose noninvasive prenatal testing (NIPT), 0.4% chose no further testing, and 0.4% had both NIPT and invasive testing. Among all participants, 13.3% had a high level of decisional conflict. We found that choosing NIPT was associated with a high decisional conflict (p = 0.013), receiving genetic counselling the same day was associated with a high decisional conflict (p = 0.039), and a high satisfaction with the genetic counselling was associated with low decisional conflict (p < 0.001). Furthermore, the personality subtrait "alexithymia" was associated with low decisional conflict (p = 0.043). There was a significant association between high decisional conflict and later decisional regret (p = 0.008). We present evidence that satisfaction with and timing of counselling are important factors to limit decisional conflict. Interestingly, women choosing NIPT had more decisional conflict than women choosing invasive testing.

Sequencing shorter cfDNA fragments improves the fetal DNA fraction in noninvasive prenatal testing

Sequencing cell-free DNA in maternal plasma is an effective noninvasive prenatal testing technique that has been used in fetal aneuploidy screening worldwide. However, its clinical application is limited by the low fetal fraction (<4%) of cell-free DNA in many singleton pregnancies, which usually results in screen failures or no calls. In addition, dizygotic twin contributions of cell-free DNA into the maternal circulation can vary by 2-fold, complicating the quantitative diagnosis of fetal aneuploidy. We performed semiconductor sequencing of shorter fragments (107-145 bp) of circulating cell-free DNA to improve the fetal DNA fraction at lower uniquely mapped reads (1-8.5 MB) to reduce the probability of no calls. We identified 2903 plasma samples from pregnant women, including 86 dizygotic twin pregnancy, that were collected at a single prenatal diagnostic center between October 2015 and July 2018. Size-selection noninvasive prenatal testing for fetal aneuploidy was applied to 2817 plasma samples (1409 male and 1408 female fetuses) and 86 dizygotic twins using noninvasive prenatal testing with and without size selection. Shorter fragment size was the key factor affecting fetal fraction in multivariable linear regression models as well as to validate the accuracy of the size selection for noninvasive prenatal testing. Analysis of 1409 male fetuses by multivariable linear regression showed that maternal age, body mass index, number of pregnancies, average cell-free DNA size, maternal plasma cell-free DNA concentration, library concentration, and multiple gestation were negatively correlated with fetal fraction. Conversely, gestational age and uniquely mapped reads were positively correlated with fetal fraction. Compared with ≤120 bp cell-free DNA fragments, mean fetal fraction differences were -3.57% (95% confidence interval, -5.95% to -1.19%), for 121-130 bp, -9.52% (95% confidence interval, -11.89% to -7.14%) for 131-140 bp, and -14.47% (95% confidence interval, -18.37% to -10.58%) for ≥141 bp (Ptrend < .0001). These results were statistically significant after multivariable adjustments in models for fetal fraction. Meanwhile, results from 86 dizygotic twins showed that the size selection increased the fetal fraction by ∼3.2-fold, with 98.8% of samples reaching a fetal fraction >10%. Improved detection accuracy was also achieved. Sequencing shorter cell-free DNA fragments is a reasonable strategy to reduce the probability of no calls results because of low fetal fraction and should be recommended to pregnant subjects.

Validation of Noninvasive Prenatal Testing for Fetal Aneuploidies and Microdeletions Down to 2% Fetal Fraction [20O

INTRODUCTION: Noninvasive prenatal testing (NIPT) by massively parallel sequencing of cell-free DNA in maternal plasma detects fetal aneuploidies with high sensitivity and specificity. However, accurate detection of fetal aneuploidies in samples with low fetal fraction remains challenging. METHODS: We have developed an NIPT pipeline that utilizes a statistical model-based counting algorithm to (1) calculate the representation of genomic regions of interest; (2) estimate the fetal fraction; (3) assess the fetal sex by Y chromosome representation; (4) determine the risk of fetal aneuploidies and microdeletions. The training set was modeled using 2,813 euploid samples (1,673 male and 1,140 female fetuses). For intermediate result calls, assessment incorporated likelihood ratios. Sensitivities and specificities were dynamically calculated in relation to both sequencing read depth and fetal fraction to set reporting thresholds. RESULTS: This clinical pipeline tested with 2,253 samples including 98 known positive samples for aneuploidies of chromosomes 21, 18, 13, 16, 22, 15, X and Y as well as microdeletions of subchromosomal regions (22q11.2, 1p36, 15q11.2-q13, 4p16, 5p15, 11q23, and 8q24). Results were called with both sensitivity and specificity &gt;99% for common aneuploidies. The observed normalized chromosome values closely fit the statistical model's estimation, indicating accurate aneuploidy calls down to 2% fetal fraction. CONCLUSION: In this study, we present a validation model for an NIPT pipeline utilizing a statistical model-based counting algorithm that can accurately detect the fetal aneuploidies and microdeletions down to low fetal fraction.

Australian laboratory experience of the PPV of non-invasive prenatal testing for fetal Aneuploidy

Australian laboratory experience of the PPV of non-invasive prenatal testing for fetal Aneuploidy

Accuracy and Clinical Value of Maternal Incidental Findings During Noninvasive Prenatal Testing for Fetal Aneuploidies

(Abstracted from Genet Med 2017;19(3):306–313) Genome-wide shotgun sequencing of cell-free (cf)DNA from the serum of pregnant women can identify chromosomal imbalances in an unborn fetus. Although initially developed to screen for fetal trisomies 21, 18, and 13, several studies have now demonstrated that genome-wide analysis can also detect other fetal aneuploidies, segmental imbalances, and even submicroscopic copy-number variations (CNVs).

Validation of a method for noninvasive prenatal testing for fetal aneuploidies risk and considerations for its introduction in the Public Health System

Objective: The aim of this study was to validate noninvasive prenatal testing (NIPT) for fetal aneuploidies by whole-genome massively parallel sequencing (MPS).Methods: MPS was performed on cell-free DNA (cfDNA) isolated from maternal plasma in two groups: a first set of 186 euploid samples and a second set of 195 samples enriched of aneuploid cases (n = 69); digital PCR for fetal fraction (FF) assessment was performed on 178/381 samples. Cases with <10 × 106 reads (n = 54) were excluded for downstream data analysis. Follow-up data (invasive testing results or neonatal information) were available for all samples. Performances in terms of specificity/sensitivity and Z-score distributions were evaluated.Results: All positive samples for trisomy 21 (T21) (n = 43), trisomy 18 (T18) (n = 6) and trisomy 13 (T13) (n = 7) were correctly identified (sensitivity: 99.9%); 5 false positive results were reported: 3 for T21 (specificity = 98.9%) and 2 for T13 (specificity = 99.4%). Besides FF, total cfDNA concentration seems another important parameter for MPS, since it influences the number of reads.Conclusions: The overall test accuracy allowed us introducing NIPT for T21, T18 and T13 as a clinical service for pregnant women after 10 + 4 weeks of gestation. Sex chromosome aneuploidy assessment needs further validation due to the limited number of aneuploid cases in this study.

Ethical Concerns in the Implementation of DNA Sequencing-Based Noninvasive Prenatal Testing for Fetal Aneuploidy Among Obstetric Professionals in Hong Kong

Background: Cell-free fetal DNA-sequencing-based noninvasive prenatal testing (NIPT) for fetal aneuploidy was introduced in late 2011 in Hong Kong. While the clinical benefits of NIPT as an easy, accurate, and procedurally risk-free test at an early gestational stage are recognized, little is known about its ethical implications in antenatal care. This study aimed to assess obstetric professionals’ views of NIPT. Methods: Surveys containing closed-ended questions about knowledge and attitudes toward NIPT and views on selected ethical issues associated with it were distributed to obstetricians, nurses, and midwives practicing in both the public and private sectors in Hong Kong between October 2013 and January 2014. Results: Of the 327 respondents, 123 (38%) were NIPT providers, 138 (42%) were knowledgeable about the test but did not provide it (“nonproviders”), and 20% (66/327) had no knowledge of NIPT (“NIPT unaware”). Forty-three percent of NIPT providers and nonproviders (111/261) regarded NIPT as a primary screening test, and 27% regarded it as diagnostic test. NIPT providers were more likely than nonproviders to obtain NIPT information from university and hospital websites (p = .03), scientific reports (p < .001), or pregnant women's media (p = 001). The greatest ethical concerns among respondents were patients undertaking multiple screening tests, unequal access due to high cost, and patients’ inadequate knowledge. The social implications of possible increased rates of pregnancy terminations and increased discrimination of individuals with Down syndrome were found to be the ethical issues of least concern, but nonproviders regarded these issues as raising more ethical concerns than providers. Conclusion: Consistent with earlier research, this study found that health care providers who are familiar with NIPT see this technology as having some clinical utility while raising a number of ethical issues. Educational and informational materials should be developed to support those who deliver this service.

Accurate Fetal Chromosome Dosage Determination by Shotgun Sequencing of Maternal Plasma DNA without PCR Amplification during Library Preparation

To the Editor: Nextgen sequencing technologies have enabled noninvasive prenatal testing of fetal aneuploidies by shotgun sequencing of maternal plasma DNA during pregnancy (1). A statistically significant change (e.g., using z -score statistics) in the number of reads mapped to a chromosome of interest (such as chromosome 21) is used to identify fetal aneuploidy. The accuracy of the test is largely dependent on 2 factors: the variability (SD) of the percentage of reads mapped to the chromosome of interest among euploidy samples and the absolute difference between the sample being tested and the mean of the euploidy samples. We speculated that the PCR enrichment step in the library preparation before cluster generation and sequencing contributes to the variation in chromosome dosage determination. Additionally, with 3 ng of DNA (typically obtainable from about 2 mL of maternal plasma) at an average size of 150 bp per DNA fragment, around 20 billion DNA fragments were available for sequencing, suggesting PCR amplification may not be necessary. We thus modified the current protocol for library preparation from maternal plasma DNA by removing the PCR enrichment step. Maternal plasma samples of about 2.5–3.2 mL were obtained with informed consent. DNA preparation and sequencing library preparation were performed as previously described (2), up to the step for adaptor ligation and purification. The purified ligation products were then equally divided into 2 …

Noninvasive Prenatal Testing for Fetal Aneuploidy

ABSTRACT After decades of research with a wide range of putative methodologies, at last a commercially viable technique has emerged for the noninvasive prenatal testing (NIPT) for the most common fetal aneuploidies, the massively parallel shotgun sequencing (MPSS). Recently, a number of groups have validated this technology to accurately detect most common trisomies as early as the 10th week of pregnancy with results available 1 to 2 weeks after maternal sampling. Several molecular techniques have been proposed for the detection of trisomies 21, 18 and 13, mainly by two different approaches in analyzing the cell-free fetal (cff) DNA: quantitative and singlenucleotide polymorphism (SNP)-based methods. Among them and to address some of the limitations of counting techniques, a new method called NATUS algorithm (Next-generation Aneuploidy Testing Using SNPs) has been recently introduced. This approach, as a targeted and noncounting technique, offers numerous advantages, although more evidence is needed from large prospective studies. Published studies have demonstrated that diagnostic parameters of NIPT are better than those of the current first trimester prenatal screening risk assessment for fetal trisomy 21. NIPT of trisomy 21 by MPS with or without preselection of chromosomes is promising and likely to replace the prenatal serum screening test that is currently combined with nuchal translucency measurement in the first trimester of pregnancy. However, before NIPT can be introduced as a screening test, more evidence is needed from large prospective diagnostic accuracy studies in first trimester pregnancies. How to cite this article Gabriel CC, Echevarria M, Rodríguez M, Serra B. Noninvasive Prenatal Testing for Fetal Aneuploidy. Donald School J Ultrasound Obstet Gynecol 2013;7(4):443-452.

Motivations for undertaking DNA sequencing-based non-invasive prenatal testing for fetal aneuploidy: a qualitative study with early adopter patients in Hong Kong.

BackgroundA newly introduced cell-free fetal DNA sequencing based non-invasive prenatal testing (DNA-NIPT) detects Down syndrome with sensitivity of 99% at early gestational stage without risk of miscarriage. Attention has been given to its public health implications; little is known from consumer perspectives. This qualitative study aimed to explore women’s motivations for using, and perceptions of, DNA-NIPT in Hong Kong. Methods and FindingsIn-depth interviews were conducted with 45 women who had undertaken DNA-NIPT recruited by purposive sampling based on socio-demographic and clinical characteristics. The sample included 31 women identified as high-risk from serum and ultrasound based Down syndrome screening (SU-DSS). Thematic narrative analysis examined informed-decision making of the test and identified the benefits and needs. Women outlined a number of reasons for accessing DNA-NIPT: reducing the uncertainty associated with risk probability-based results from SU-DSS, undertaking DNA-NIPT as a comprehensive measure to counteract risk from childbearing especially at advanced age, perceived predictive accuracy and absence of risk of harm to fetus. Accounts of women deemed high-risk or not high-risk are distinctive in a number of respects. High-risk women accessed DNA-NIPT to get a clearer idea of their risk. This group perceived SU-DSS as an unnecessary and confusing procedure because of its varying, protocol-dependent detection rates. Those women not deemed high-risk, in contrast, undertook DNA-NIPT for psychological assurance and to reduce anxiety even after receiving the negative result from SU-DSS. ConclusionsDNA-NIPT was regarded positively by women who chose this method of screening over the routine, less expensive testing options. Given its perceived utility, health providers need to consider whether DNA-NIPT should be offered as part of universal routine care to women at high-risk for fetal aneuploidy. If this is the case, then further development of guidelines and quality assurance will be needed to provide a service suited to patients’ needs.