Prenatal Screening For Fetal Aneuploidy Research Articles

Economic evaluation of prenatal screening for fetal aneuploidies in Thailand.

Historically, there has been a lack of cost-effectiveness data regarding the inclusion of universal non-invasive prenatal testing (NIPT) for trisomy 21, 18, and 13 in the benefit package of the Universal Health Coverage (UHC) in Thailand. Therefore, this study aimed to perform the cost-benefit analysis of prenatal screening tests and calculate the budget impact that would result from the implementation of a universal NIPT program. A decision-tree model was employed to evaluate cost and benefit of different prenatal chromosomal abnormalities screenings: 1) first-trimester screening (FTS), 2) NIPT, and 3) definitive diagnostic (amniocentesis). The comparison was made between these screenings and no screening in three groups of pregnant women: all ages, < 35 years, and ≥ 35 years. The analysis was conducted from societal and governmental perspectives. The costs comprised direct medical, direct non-medical, and indirect costs, while the benefit was cost-avoidance associated with caring for children with trisomy and the loss of productivity for caregivers. Parameter uncertainties were evaluated through one-way and probabilistic sensitivity analyses. From a governmental perspective, all three methods were found to be cost-beneficial. Among them, FTS was identified as the most cost-beneficial, especially for pregnant women aged ≥ 35 years. From a societal perspective, the definitive diagnostic test was not cost-effective, but the other two screening tests were. The most sensitive parameters for FTS and NIPT strategies were the productivity loss of caregivers and the incidence of trisomy 21. Our study suggested that NIPT was the most cost-effective strategy in Thailand, if the cost was reduced to 47 USD. This evidence-based information can serve as a crucial resource for policymakers when making informed decisions regarding the allocation of resources for prenatal care in Thailand and similar context.

Cost-effectiveness of ultrasound before non-invasive prenatal screening for fetal aneuploidy.

To determine the cost-effectiveness of first-trimester ultrasound before fetal aneuploidy screening with cell-free DNA (cfDNA) compared with screening by cfDNA alone. A decision analytic model was constructed for 400 000 pregnant individuals with advanced maternal age who desired first-trimester aneuploidy screening with cfDNA in the USA, to compare two screening strategies: (1) cfDNA only and (2) ultrasound performed within 4 weeks before cfDNA. Input parameters included probability of fetal aneuploidy, cfDNA performance, desire for diagnostic testing, pregnancy outcomes, and pregnancy and lifetime costs and utilities. The primary outcome measure was the incremental cost-effectiveness ratio (ICER), in terms of cost in 2020 US dollars (USD) per quality-adjusted life year (QALY) gained. Secondary outcomes included procedure-related loss, pregnancy termination, live birth with aneuploidy, live birth with structural anomaly and stillbirth. Discounting was performed at 3% per year with an estimated maternal lifespan of 81 years starting at the age of 35 years. One-way, multiway and Monte Carlo probabilistic sensitivity analyses were performed. All base-case estimates and ranges of uncertainty were derived from the literature. The willingness-to-pay threshold was set at 100 000 USD per QALY. In the base-case analysis, ultrasound before cfDNA screening was more cost-effective than cfDNA screening without pretest ultrasound, with an ICER of 12 588 USD and higher net monetary benefit (24 241 vs 20 466). The strategy involving ultrasound before cfDNA was more costly by 544 USD but also more effective (by 0.04 QALY) compared with cfDNA alone. Base-case results were robust in sensitivity analyses with the strategy involving ultrasound before cfDNA always remaining the most cost-effective approach with the highest net monetary benefit. First-trimester ultrasound before cfDNA is a more cost-effective strategy for non-invasive prenatal aneuploidy screening compared with cfDNA alone. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Non-invasive prenatal testing for everybody or contingent screening?

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: Current Perspectives and Future Challenges.

Fetal aneuploidies are among the most common causes of miscarriages, perinatal mortality and neurodevelopmental impairment. During the last 70 years, many efforts have been made in order to improve prenatal diagnosis and prenatal screening of these conditions. Recently, the use of cell-free fetal DNA (cff-DNA) testing has been increasingly used in different countries, representing an opportunity for non-invasive prenatal screening of pregnant women. The aim of this narrative review is to describe the state of the art and the main strengths and limitations of this test for prenatal screening of fetal aneuploidies.

Применение неинвазивного пренатального ДНК-скрининга анеуплоидий при оказании акушерско-гинекологической помощи

Используемый в настоящее время в России пренатальный скрининг хромосомной патологии основан на косвенных маркерах и имеет ограничение по чувствительности и специфичности. Поэтому более перспективным является применение неинвазивного пренатального ДНК-скрининга анеуплоидий (НИПС). Целью данной работы являлась оценка возможности применения полногеномного НИПС при оказании акушерско-гинекологической помощи. Проведена валидация ДНК-скрининга на образцах с известными результатами пренатальной инвазивной диагностики (N=1134). Доказана возможность транспортировки и хранения образцов (N=477). Проведено отсроченное исследование аликвот плазмы через год после первоначального исследования (N=70). Оценены факторы, которые могут влиять на результаты НИПС - доля плодовой ДНК, индекс массы тела (ИМТ), срок беременности, мозаицизм и другие. Widely performed in Russia prenatally first-trimester screening is based on secondary markers of pathology and has limited sensitivity and specificity. The most promising alternative is the use of noninvasive prenatal screening for fetal aneuploidy (NIPS). This study aims to validate the possibility of NIPS usage for obstetric and gynecological care. DNA screening was validated on samples with known results of invasive prenatal diagnostics (N=1134). It was proven that it is possible to store and transport the samples (N=477). We studied plasma aliquot samples after one year of storage (N=70). Factors that can influence the NIPS results were also evaluated: the proportion of fetal DNA, body mass index (BMI), gestational age, mosaicism, and others.

1057: Noninvasive prenatal screening for fetal aneuploidy in twin pregnancies: A clinical laboratory experience

1057: Noninvasive prenatal screening for fetal aneuploidy in twin pregnancies: A clinical laboratory experience

The association of HBB-related significant hemoglobinopathies and low fetal fraction on noninvasive prenatal screening for fetal aneuploidy

Objectives HBB-related significant hemoglobinopathies have been anecdotally associated with low fetal fraction on noninvasive prenatal screening (NIPS). We sought to compare the difference in fetal fraction using NIPS in women with HBB-related significant hemoglobinopathies (HSH) and women with normal hemoglobin. Study design This is a retrospective case-control study. Cases were women with a diagnosis of HSH using NIPS from a commercial laboratory. The comparison group was women with hemoglobin AA from a tertiary care center database. We tested for differences in median fetal fraction using quantile regression analysis, adjusting for maternal body weight and gestational age. Results This study includes 35 women with clinically significant HSH and a comparison group of 636 women with hemoglobin AA. Adjusting for gestational age and body weight, the median fetal fraction was 4.1 point lower in the HSH than in the comparison group (β − 4.1; 95% −5.7 to −2.5, p < .05). The rate of no-calls due to low fetal fraction was significantly higher in the clinically significant HSH group than in the comparison group [HSH: n = 9/35, 25.7% versus comparison: n = 32/636, 5.0% (p < .001)]. Conclusion Women with HSH were more likely to have a lower fetal fraction and ultimately a five-fold higher no-call rate. What’s already known about this topic? Low fetal fraction is one of the most common causes of no-call result in noninvasive prenatal screening High maternal weight, early gestational age and fetal aneuploidies are associated with low fetal fraction What does this study add? HBB-related significant hemoglobinopathies are associated with low fetal fraction Reduction in fetal fraction due to HBB-related significant hemoglobinopathies may also result in higher no-call rate

A two-year experience of non-invasive prenatal testing (NIPT) at an urban tertiary medical center in South Korea

ObjectiveTo report our experience of implementing non-invasive prenatal testing (NIPT) in a tertiary urban academic medical center in South Korea. Materials and methodsAn observational retrospective study of singleton and twin pregnancies that underwent prenatal screening for fetal aneuploidy from July 2016 to April 2018 was conducted. Demographics of the study population electing NIPT versus those opting the integrated test were compared. We also assessed clinical significant factors influencing cfDNA fetal fraction in NIPT. ResultsAmong the 817 women who underwent serum screening tests during the study period, 490 women (60.0%) chose the integrated test while 327 women (40.0%) chose NIPT. Compared to the integrated test group, women in the NIPT group were older (mean age 34.7 ± 3.7 vs. 32.6 ± 3.4; p-value < 0.01), multiparous (47.1% vs. 39.8%; p-value = 0.046), and had higher rate of previous abortion history (28.4% vs. 21.6%; p-value = 0.033). A significant decrease in the number of invasive diagnostic tests was observed since the adoption of NIPT. The screen negative and positive rates of the integrated test group for fetal aneuploidy were 95.3% and 4.7%, respectively while those of the NIPT group were 95.9% and 1.2%, respectively. The rate of inadequate cfDNA fetal fraction was 3.0%. Low fetal fraction was associated with higher maternal age, body weight and BMI. ConclusionsThe implementation of NIPT has significantly affected the practice pattern of prenatal aneuploidy screening by replacing the integrated test and decreasing invasive diagnostic tests.

Korean physicians’ attitudes toward the prenatal screening for fetal aneuploidy and implementation of non-invasive prenatal testing with cell-free fetal DNA

Korean physicians’ attitudes toward the prenatal screening for fetal aneuploidy and implementation of non-invasive prenatal testing with cell-free fetal DNA

Non-invasive prenatal screening for fetal aneuploidy in twin pregnancies by cell-free DNA analysis

Objective: To evaluate the efficacy of Cell-free DNA (cfDNA) based non-invasive prenatal testing (NIPS) in detecting fetal chromosomal aneuploidies among twin pregnancies. Materials and Methods:&nbsp;A cohort of 384 women with twin pregnancies were recruited for chromosomal aneuploidies testing through NIPS. cfDNA was extracted from maternal blood serum and sequenced by massively parallel sequencing (MPS). Result: Two cases of trisomy 21 (T21), one case of trisomy 13 (T13), and two cases of sex chromosomal aneuploidies (SCA) in twin pregnancies were correctly identified through MPS and confirmed their discordant fetal karyotypes (one normal and the other trisomy) by karyotyping; 378 twin pregnancies cases with negative NIPS results were confirmed through postnatal phone follow-up. NIPS detection rate and positive predictive value for T21, T13, and SCA were 100%, respectively, in twin pregnancies; sensitivity and specificity towards T21 and T13 in twin pregnancies were both 100%. Conclusion: cfDNA based NIPS for fetal chromosomal aneuploidy have shown a satisfactory clinical performance in twin pregnancies.

Midwifery education from perspective of the WHO

Situational factors of prenatal screening have changed in recent decades. To explore the effect of a changing context on women's decision making, differences and similarities in the decision-making process of pregnant women regarding prenatal screening for fetal aneuploidy between two periods in time were studied.A qualitative comparison was made between a dataset of 22 semi-structured interviews with pregnant women from 2003 and a newly collected dataset with 19 semi-structured interviews from 2016.Overall, women reported similar considerations in their decision-making process in 2003 and 2016, suggesting that decision making has not essentially changed. In 2016, women were still making a deliberate decision, however for some women costs and societal views as to what is acceptable did appear to impact the decision-making process. Moreover, new screening possibilities (e.g. improved test characteristics and including more conditions to be screened) seemed to impact the decision outcome.Since most women based their decisions mainly on their personal values and personal experiences rather than on situational factors, the results suggest that the changing context with regard to prenatal screening had no major effect on women's decision making. It therefore seems unlikely that future changes in the field of prenatal screening will drastically change the decision-making process of pregnant women as long as informed and deliberate decision making is safeguarded.

Women's decision making regarding prenatal screening for fetal aneuploidy: A qualitative comparison between 2003 and 2016

ObjectiveSituational factors of prenatal screening have changed in recent decades. To explore the effect of a changing context on women's decision making, differences and similarities in the decision-making process of pregnant women regarding prenatal screening for fetal aneuploidy between two periods in time were studied. DesignA qualitative comparison was made between a dataset of 22 semi-structured interviews with pregnant women from 2003 and a newly collected dataset with 19 semi-structured interviews from 2016. FindingsOverall, women reported similar considerations in their decision-making process in 2003 and 2016, suggesting that decision making has not essentially changed. In 2016, women were still making a deliberate decision, however for some women costs and societal views as to what is acceptable did appear to impact the decision-making process. Moreover, new screening possibilities (e.g. improved test characteristics and including more conditions to be screened) seemed to impact the decision outcome. ConclusionsSince most women based their decisions mainly on their personal values and personal experiences rather than on situational factors, the results suggest that the changing context with regard to prenatal screening had no major effect on women's decision making. It therefore seems unlikely that future changes in the field of prenatal screening will drastically change the decision-making process of pregnant women as long as informed and deliberate decision making is safeguarded.

A National Referral Laboratory\u2019s Experience with the Implementation of SNP-Based Non-invasive Prenatal Screening for Fetal Aneuploidy and Select Microdeletion Syndromes

To retrospectively evaluate the successful test rate and performance of non-invasive prenatal screening (NIPS) for aneuploidies and microdeletions with international transportation of samples. Blood samples from Iberian women with singleton pregnancies were sent to a US laboratory for NIPS for aneuploidy and microdeletion syndromes (22q11.2, 1p36, Cri-du-chat, Prader Willi and Angelman). The NIPS methodology involved the analysis of single nucleotide polymorphisms in cell-free DNA in maternal plasma. Women with high-risk results were offered karyotyping and/or microarray confirmatory studies. Based on 14,175 women with successful testing (98.76% of all referrals), the overall test positive rate was 2.37% (1.9% for aneuploidy and 0.47% for microdeletion syndromes). Based on cases with known outcome, the positive predictive values (PPVs) were: for trisomy 21, 98.6%; trisomy 18, 85.7%; trisomy 13, 71.4%; monosomy-X, 87.5%; other sex chromosome aneuploidies, 100%; 22q11.2 deletion, 15.4%; and other microdeletions combined, 20%. With a protocol change that involved selective use of resequencing at a higher depth of read, the PPV for 22q11.2 deletion increased to 33.3 and 75% for the other microdeletions. Effective NIPS for both aneuploidies and select microdeletion syndromes can be provided even when this involves international transportation of blood specimens.

Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women.

Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women.

Pride of my inner lioness

Situational factors of prenatal screening have changed in recent decades. To explore the effect of a changing context on women's decision making, differences and similarities in the decision-making process of pregnant women regarding prenatal screening for fetal aneuploidy between two periods in time were studied.A qualitative comparison was made between a dataset of 22 semi-structured interviews with pregnant women from 2003 and a newly collected dataset with 19 semi-structured interviews from 2016.Overall, women reported similar considerations in their decision-making process in 2003 and 2016, suggesting that decision making has not essentially changed. In 2016, women were still making a deliberate decision, however for some women costs and societal views as to what is acceptable did appear to impact the decision-making process. Moreover, new screening possibilities (e.g. improved test characteristics and including more conditions to be screened) seemed to impact the decision outcome.Since most women based their decisions mainly on their personal values and personal experiences rather than on situational factors, the results suggest that the changing context with regard to prenatal screening had no major effect on women's decision making. It therefore seems unlikely that future changes in the field of prenatal screening will drastically change the decision-making process of pregnant women as long as informed and deliberate decision making is safeguarded.

No. 348-Joint SOGC-CCMG Guideline: Update on Prenatal Screening for Fetal Aneuploidy, Fetal Anomalies, and Adverse Pregnancy Outcomes.

To review the available prenatal screening options in light of the recent technical advances and to provide an update of previous guidelines in the field of prenatal screening. Health care providers involved in prenatal screening, including general practitioners, obstetricians, midwives, maternal fetal medicine specialists, geneticists, and radiologists. All pregnant women receiving counselling and providing informed consent for prenatal screening. Published literature was retrieved through searches of Medline, PubMed, and the Cochrane Library in and prior to March 2016 using an appropriate controlled vocabulary (prenatal diagnosis, amniocentesis, chorionic villi sampling, non-invasive prenatal screening) and key words (prenatal screening, prenatal genetic counselling). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies written in English and published from January 1985 to May 2016. Searches were updated on a regular basis and incorporated in the guideline. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical speciality societies. Evidence will be reviewed 5 years after publication to determine whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations.

Performance of non-invasive prenatal screening for fetal aneuploidy in twin pregnancies: a meta-analysis.

The objectives of this study were to review the published studies of non-invasive prenatal screening (NIPS) in twin pregnancies and to evaluate the performance for screening fetal trisomies 21, 18, and 13 in twin pregnancies. Ten eligible studies were included in this meta-analysis. Data analysis, heterogeneity exploring, meta-regression, and subgroup analysis were all conducted with Meta-DiSc 1.4. Quality assessments were carried out with the Quality Assessment Tool for Diagnostic Accuracy Studies. Non-invasive prenatal screening for trisomy 21 screening in twin pregnancies showed a pooled sensitivity of 0.99 (95% CI, 0.92-1.00), a specificity of 1.00 (95% CI, 0.99-1.00), a positive likelihood ratio (LR) of 116.46 (95% CI, 53.84-251.92), a negative LR of 0.11 (95% CI, 0.06-0.22), and a diagnostic odds ratio of 1297.73 (95% CI, 438.06-3844.42). But the difference of detection rates between monozygotic and dichorionic twin pregnancies was uncertain for only a very small number of monochorionic twins available. For trisomy 18 screening, the pooled sensitivity, specificity, positive LR, negative LR, and diagnostic odds ratio were 0.85 (95% CI, 0.55-0.98), 1.00 (95% CI, 0.99-1.00), 86.11 (95% CI, 32.45-228.47), 0.25 (95% CI, 0.11-0.56), and 333.90 (95% CI, 35.15-3171.78), respectively. For trisomy 13 screening, three cases in three studies were all detected accurately. The meta-analysis results from 10 eligible studies demonstrated that NIPS has both high sensitivity and specificity for trisomy 21 screening in twin pregnancies. The results for trisomy 18 screening are less satisfactory than those for trisomy 21. The performance for trisomy 13 screening could not be determined as only three cases were identified. © 2017 John Wiley & Sons, Ltd.

Prenatal Screening for Fetal Aneuploidy

Prenatal genetic aneuploidy screening approaches are designed to identify pregnant patients at increased risk of having a fetus affected. Conventional prenatal screening has consisted in providing women a risk estimate of having a pregnancy affected with trisomy 21 or trisomy 18 based on maternal age and analysis of serum markers and ultrasound nuchal translucency (NT) measurement. In 2011, the introduction of cell-free DNA (cfDNA) based screening into clinical practice has provided new options for aneuploidy screening programs. Different protocols are currently in use, some that perform screening in the first trimester (combined first trimester screening), some in the second trimester (QUAD), some that integrate first and second trimester (serum integrated screening, integrated screening, sequential, or contingent screening). cfDNA screening can be implemented as a second tier / contingent screen or as a first tier screen and has the ability to detect chromosomal anomalies other than the common aneuploidies screened for by conventional screening. The choice of protocol will be based on local expertise and resources. Aneuploidy screening should also be offered to pregnant women with twin gestation although fewer validation studies in twins of the test being offered are available compared to studies done in singleton gestations. Professional societies and expert groups emphasize the need for pre-test and post-test counselling to ensure that women are making an informed decision. The general counselling points to be covered are similar regardless of the type of prenatal screening being offered. Prenatal screening programs should be implemented with resources that support patient and health care provider education, quality assurance of laboratory and NT services, access to genetic counselling services and diagnostic testing. The rapid pace of new developments in cfDNA screening for chromosomal anomalies brings new opportunities to enhance the performance of the screening but at the same time, challenges as the test menus are expanded and data is lacking as to the cost-effectiveness and clinical utility of implementing expanded panels.

The application of next generation sequencing on non-invasive prenatal testing: today and tomorrow

Next-generation sequencing has boosted the development and application of non-invasive prenatal testing. Non-invasive prenatal screening of fetal aneuploidies (T21/T18/T13) has been widely applied around the world as the well-recognized best screening method because of its high sensitivity, low false-positive rate and false-negative rate. Non-invasive prenatal testing of fetal sex chromosome aneuploidies, common chromosome deletion-duplication syndromes and several monogenic disorders has also become technically feasible. It can be expected that primary challenges in the future would be the issues of clinical services and proper managements.(Chin J Lab Med, 2017, 40: 489-491) Key words: High-throughput nucleotide sequencing; Prenatal diagnosis

The Significance of Test Failures in Noninvasive Prenatal Screening for Fetal Aneuploidy Using Cell-free DNA

AbstractNoninvasive prenatal screening (NIPS) for fetal aneuploidy is less effective when there is a small fraction of fetal cell-free DNA in the maternal plasma. In this study, modeling was used to assess the impact of a low fetal fraction (FF) in NIPS when (a) FF is not measured; (b) low FF cases receive invasive testing; (c) low FF cases receive the combined test; (d) low FF cases receive the quadruple test. Modeling was based on expected performance of NIPS, invasive testing, and conventional screening. NIPS failure rates of 0–6% due to low FF were considered under the assumption that aneuploidy rates were the same in successful and unsuccessful cases. In a secondary analysis, the effect of higher rates of aneuploidy in failed cases was assessed. Failure to measure FF can result in lower detection rates. Providing invasive tests to all women with low FF restores a high level of detection but at the expense of many unnecessary invasive tests. Utilization of conventional screening results in only a modest loss in detection and limited deterioration in the false-positive rate. These trends are more apparent when higher rates of fetal aneuploidy are present in low FF women. Recognizing those cases where an NIPS result is invalid due to low FF is important from both the individual patient and overall population screening perspectives. When there is a NIPS test failure due to low FF, utilization of conventional maternal serum marker screening and ultrasound should be considered for women who have previously not received conventional screening.