Prenatal testing technologies in Australia: Unintended clinical and emotional complexities in underprepared systems.

The past decade has seen technological advances in prenatal screening technologies rapidly integrated into clinical practice. These technologies have revolutionised healthcare and raised complex socio-ethical issues such as equitable access, medical commercialisation, and new eugenics. However, the important issue of the impact of these technologies on healthcare professionals is receiving less attention. Exploring this issue in the Australian context, we conducted a survey from August to November 2022, targeting health and allied health professionals who work with parents in the perinatal period who have received a fetal diagnosis. We received 75 substantive responses from a diversity of professionals, including sonographers, midwives, genetic counsellors and medical providers. In this article, we consider the unintended impacts of prenatal screening technologies on healthcare workers, drawing from Ziebland et al., 's 2021 unintended consequences framework. Our reflexive thematic analysis produced three key themes: "Unintended Clinical Complexities", "Adapting Work Practices to Keep Up in Systems that Lack", and "Unintended Intensification of Emotional Labour". Prenatal testing technologies have intentionally increased early testing and fetal information, offering veiled promises of increased certainty in pregnancy. However, our analysis highlights that these advancing technologies also generate more ambiguous results, creating unintended clinical and emotional complexities for healthcare providers. Workers must manage increased clinical uncertainty and constant change, creating intensified emotional labour in under-prepared systems. We conclude by identifying the need to recognise the impacts of advancing prenatal screening technologies on healthcare workers and for targeted professional training to prepare healthcare professionals for the complexities introduced by these new technologies.

The efficacy of expanded non-invasive prenatal testing (NIPT) in a high-risk twin pregnancies cohort.

INTRODUCTION: Our objective was to evaluate the efficacy of expanded non-invasive prenatal testing (NIPT) that includes both trisomies and copy number variants (CNVs) in high-risk twin pregnancies. MATERIAL AND METHODS: A prospective, double-blinded cohort study was conducted, enrolling 73 high-risk twin pregnancies characterized by increased risk of genetic disorders due to factors such as increased nuchal translucency, structural anomalies, fetal growth restriction, and other factors associated with chromosomal abnormality. Participants underwent invasive karyotyping and chromosomal microarray analysis, alongside separate expanded NIPT for research purposes. The sensitivity, specificity, positive predictive value, and negative predictive value of expanded NIPT were calculated. RESULTS: The cohort included 24 monochorionic and 49 dichorionic twin pregnancies. The median cell-free fetal DNA concentration in expanded NIPT was 16.7% (range 3.86%-49.1%), with a test failure rate of 1.4% (1/73). High-risk findings for trisomy 21/13/18 were identified in five cases (6.8%), Turner syndrome in one case (1.4%), and CNVs indicative of high risk for clinically significant microdeletion/microduplication syndromes (MMS) in ten cases (13.7%). Of these, 56 cases (76.7%) tested NIPT negative, revealing one false-negative for 45, X and five false-negatives for CNVs. Expanded NIPT achieved a detection rate of 100% (5/5) for trisomy 21/13/18 with a false-positive rate of 0% (0/5), a detection rate of 33.3% (1/3) for sex chromosome abnormalities with a false-positive rate of 0% (0/3), and a detection rate of 66.7% (4/6) for MMS with a false-positive rate of 3.0% (2/67). The positive predictive values for trisomy T21/13/18, sex chromosome abnormalities, and known MMS were 100% (5/5), 100% (1/1), and 66.7% (4/6) in the expanded NIPT, respectively. CONCLUSIONS: The expanded NIPT demonstrated high detection rates for common trisomies and moderate detection rates for prenatal MMS in high-risk twin pregnancies. Further studies with large sample sizes in low-risk populations are needed.

Prenatal detection of copy number variants.

Prenatal detection of copy number variants (CNVs) plays an important role in the diagnosis of fetal genetic abnormalities. Understanding the methods used for prenatal CNV detection and their clinical significance contributes to the implementation of advanced genetic screening techniques in prenatal care; facilitating early identification and management of genetic disorders in fetuses. Some CNVs impose significant genetic counselling challenges; especially those which are associated with uncertain clinical significance, in the context of variable penetrance and/or expressivity or when identified incidentally. This chapter focuses on the different techniques used for detecting CNVs, including Single Nucleotide Polymorphism (SNP) arrays, comparative genomic hybridization (CGH) arrays, Non-Invasive Prenatal Testing (NIPT), Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS) as well as their advantages and limitations. The tools needed for the classification of CNVs and their clinical relevance are also explored, emphasising the importance of accurate interpretation for appropriate clinical management and genetic counselling.

An Auto-Reading probe system for detecting deletion mutations In liquid biopsy with direct quantification of mutation abundance.

Background: Deletion mutations have been confirmed to be closely related to the occurrence and progression of different hereditary diseases and tumors. Specifically, the deletion of a small number of bases is more challenging to be captured and differentiated. In non-invasive prenatal testing (NIPT) and liquid biopsy targeting circulating tumor DNA, obtaining accurate mutation abundance in targeted DNA is a crucial step in the detection process. However, the quantification of mutation abundance with existing methods is not accurate enough. Results: Herein, we developed the " Auto-Reading" probe detection system based on our previous work. Through theoretical modeling and experimental calculations, we verified the successful application of our system in NIPT and early cancer diagnosis, enabling effective discrimination of different mutant abundances. Significance: Our method overcomes the interference of reaction concentrations on signal detection, allowing direct quantification of mutation abundance without the need for purification of PCR products. The detection system is cost-effective and feasible for laboratory use. We believe the system will facilitate broad applications in mutation detection.

Implementing non-invasive prenatal testing in a national screening program: Lessons learned from the TRIDENT studies.

The Dutch NIPT Consortium, a multidisciplinary collaboration of stakeholders in prenatal care initiated and launched the TRIDENT studies. The goal of the TRIDENT studies was to implement non-invasive prenatal testing (NIPT), first as a contingent (second-tier) and later as a first-tier test, and to evaluate this implementation. This paper describes how NIPT can be successfully implemented in a country or state. Important factors include the significance of forming a consortium and encouraging cooperation among relevant stakeholders, appropriate training for obstetric care professionals, and taking into account the perspectives of pregnant women when implementing prenatal tests. We describe the advantages of high sensitivity and specificity when comparing contingent NIPT with first-tier NIPT. This paper emphasizes the value of pre- and post-test counselling and the requirement for a standardized method of information delivery and value clarification, to assist couples in decision making for prenatal screening.

Genetic counseling of mosaic and non-mosaic tetrasomy 9p at prenatal diagnosis.

Genetic counseling of mosaic and non-mosaic tetrasomy 9p remains difficult because of the possible associated congenital abnormalities, cytogenetic discrepancy in various tissues, true-positive and false-positive diagnosis in non-invasive prenatal testing (NIPT), uniparental disomy (UPD) 9, tissue-limited mosaicism, perinatal progressive decrease of the aneuploid cell line, phenotypic normal carriers and possible favorable fetal outcome in the cases with mosaic tetrasomy 9p at amniocentesis. This article presents a comprehensive review of various counseling issues concerning mosaic and non-mosaic tetrasomy 9p at prenatal diagnosis, and the information provided is very useful for genetic counseling under such circumstances.

GWAS shows the genetics behind cell-free DNA and highlights the importance of p.Arg206Cys in DNASE1L3 for non-invasive testing.

The properties of cell-free DNA (cfDNA) are intensely studied for their potential as non-invasive biomarkers. We explored the effect of common genetic variants on the concentration and fragmentation properties of cfDNA using a genome-wide association study (GWAS) based on low-coverage whole-genome sequencing data of 140,000 Dutch non-invasive prenatal tests (NIPTs). Our GWAS detects many genome-wide significant loci, functional enrichments for phagocytes, liver, adipose tissue, and macrophages, and genetic correlations with autoimmune and cardiovascular disease. A common (7%) missense variant in DNASE1L3 (p.Arg206Cys) strongly affects all cfDNA properties. It increases the size of fragments, lowers cfDNA concentrations, affects the distribution of cleave-site motifs, and increases the fraction of circulating fetal DNA during pregnancy. For the application of NIPT, and potentially other cfDNA-based tests, this variant has direct clinical consequences, as it increases the odds of inconclusive results and impairs the sensitivity of NIPT by causing predictors to overestimate the fetal fraction.

Impact of the new government-involved noninvasive prenatal testing certification system on the awareness of pregnant women about noninvasive prenatal testing in Japan.

AIM: In Japan, noninvasive prenatal testing (NIPT) has been performed by facilities accredited by the Japanese Society of Obstetrics and Gynecology since 2013. However, since 2016, with the implementation of NIPT, which can only be performed by blood sampling, non-obstetricians have been involved in prenatal testing. Therefore, in July 2022, a new government-involved NIPT certification system based on Health Sciences Council guidelines was introduced to ensure access to prenatal testing information for pregnant women. METHODS: This survey was conducted in February 2023 and was the first survey after the certification system implementation. We conducted a web-based survey of 1227 pregnant women and nursing mothers who underwent NIPT after July 2022 to evaluate their experiences. RESULTS: Respondents were categorized by certification status as certified (C: 56%), non-certified (non-C: 23%), or uncertain (Q: 20%). The C group with a higher mean age at examination (35.0 ± 4.5 years) paid lower examination fees, received longer pre- and post-examination explanations, and underwent more weekday examinations (80%) than the other groups. Most respondents, 67%, 48%, and 53% in the C, non-C, and Q groups, respectively (p < 0.0001), stated that "NIPT needs to be regulated by the government or academic societies." The non-C group was more likely to say, "Insufficient post-test explanations at the laboratory made me more anxious," than the other groups when the testing results were non-negative (p = 0.015). CONCLUSIONS: Despite government regulation, some pregnant women choose convenience over certified facilities, risking inadequate care. The government should ensure that NIPT is a safe option for all pregnant women.

The role of patient-reported experiences in disclosing genetic prenatal testing: Findings from a large-scale survey on pregnant women.

Introduction: Pregnant women can choose from different prenatal genetic tests throughout their maternity journey. We aim to investigate the clinical, societal, and economic determinants influencing the selection of different options (non-invasive, invasive, or both). Methods: A systematic survey focusing on maternity pathways was launched by the Region of Tuscany, Italy, to collect data on pregnant women's experience, outcomes and satisfaction levels. Drawing from this survey, we retrospectively analyzed data on women who filled out the second-trimester questionnaire between March 2019 and February 2023 (n = 27,337), providing complete data on relevant variables. Logistic regression models were applied to identify the factors contributing to a higher likelihood of opting for non-invasive prenatal testing (NIPT) and invasive testing. Results: Among the participants, 42.7 % chose only NIPT, 3.8 % opted for invasive tests exclusively, 1.3 % underwent both tests, and 52.2 % did not pursue any genetic testing. NIPT was more often chosen by older, Italian, highly educated, nulliparous women, who perceived better health, were employed (versus unemployed), had higher economic status, planned pregnancy, received hospital-based care (versus counseling center), under gynecologist supervision (versus midwife), not opted for combined testing and received pregnancy vaccinations. Conversely, invasive testing was more prevalent among older women but less common among those who were nulliparous, had Italian nationality, and had a perceived better health status. This group also tended to experience unplanned and high-risk pregnancy, did not take folate during pregnancy, received public hospital-based assistance, less frequently chose combined tests or NIPT, and had frequent delays in examinations. Conclusions: Various factors beyond clinical considerations influence the selection of a prenatal test. Therefore, NIPT pathways should include balanced, high-quality information about benefits and limitations, ensuring laboratory specialists' active and integrated involvement in decision-making.

The use of free DNA for fetal RHD genotyping in the Rh negative pregnant patient-the time has come.

Cell-free DNA to determine the fetal RHD genotype from the maternal circulation was first described in 1993. High throughput assays using polymerase chain reaction technology were introduced in Europe and gained widespread acceptance in the management of the Rhesus alloimmunized pregnancy. The specificity and sensitivity of these assays approached 99%. As confidence was gained with these results, Scandinavian countries began to employ cell-free DNA for fetal RHD typing as an integral component of their introduction of antenatal Rhesus immune globulin in non-alloimmunized pregnancies. Since 40% of RhD-negative pregnant women will carry an RhD-negative fetus, doses of Rhesus immune globulin were conserved. Recently 2 U.S. companies have introduced cell-free DNA assays for RHD as part of their noninvasive prenatal testing assays. Both utilize next generation sequencing and have developed methodologies to detect the aberrant RHD pseudogene and the hybrid RHD-CE-Ds genotype. In addition, excellent correlation studies with either neonatal genotyping or serology have been reported. The manufacturer of RhoGAM has recently announced a national shortage. Given the current availability of reliable cell-free DNA assays for determining the RHD status of the fetus, the time has come to implement this strategy to triage the antenatal use of Rhesus immune globulin in the U.S.

Impact of Structural Differences on the Modeled Cost-Effectiveness of Noninvasive Prenatal Testing.

BACKGROUND: Noninvasive prenatal testing (NIPT) was developed to improve the accuracy of prenatal screening to detect chromosomal abnormalities. Published economic analyses have yielded different incremental cost-effective ratios (ICERs), leading to conclusions of NIPT being dominant, cost-effective, and cost-ineffective. These analyses have used different model structures, and the extent to which these structural variations have contributed to differences in ICERs is unclear. AIM: To assess the impact of different model structures on the cost-effectiveness of NIPT for the detection of trisomy 21 (T21; Down syndrome). METHODS: A systematic review identified economic models comparing NIPT to conventional screening. The key variations in identified model structures were the number of health states and modeling approach. New models with different structures were developed in TreeAge and populated with consistent parameters to enable a comparison of the impact of selected structural variations on results. RESULTS: The review identified 34 economic models. Based on these findings, demonstration models were developed: 1) a decision tree with 3 health states, 2) a decision tree with 5 health states, 3) a microsimulation with 3 health states, and 4) a microsimulation with 5 health states. The base-case ICER from each model was 1) USD$34,474 (2023)/quality-adjusted life-year (QALY), 2) USD$14,990 (2023)/QALY, (3) USD$54,983 (2023)/QALY, and (4) NIPT was dominated. CONCLUSION: Model-structuring choices can have a large impact on the ICER and conclusions regarding cost-effectiveness, which may inadvertently affect policy decisions to support or not support funding for NIPT. The use of reference models could improve international consistency in health policy decision making for prenatal screening. HIGHLIGHTS: NIPT is a clinical area in which a variety of modeling approaches have been published, with wide variation in reported cost-effectiveness.This study shows that when broader contextual factors are held constant, varying the model structure yields results that range from NIPT being less effective and more expensive than conventional screening (i.e., NIPT was dominated) through to NIPT being more effective and more expensive than conventional screening with an ICER of USD$54,983 (2023)/QALY.Model-structuring choices may inadvertently affect policy decisions to support or not support funding of NIPT. Reference models could improve international consistency in health policy decision making for prenatal screening.

Uterine fibroids and non-informative cell-free DNA screening results.

OBJECTIVE: Uterine fibroids are monoclonal tumors, which are often genetically abnormal and associated with false-positive genome-wide cell-free DNA (cfDNA) screening results, particularly when large. It is plausible that fibroids may also increase the risk of cfDNA failure by affecting fetal fraction or due to their genetic anomalies confounding cfDNA algorithms. We aimed to investigate a possible association between fibroids and cfDNA non-informative results. METHODS: This was a retrospective cohort study of women undergoing cfDNA screening for fetal chromosomal abnormalities between 2013 and 2020, comparing pregnancies with vs without uterine fibroids recorded on any obstetric ultrasound before 24 weeks' gestation. Univariable and multivariable logistic regression models were used to investigate the association between fibroids and cfDNA failure, adjusting for gestational age, maternal age, weight and height at blood sampling, mode of conception, multiple gestation and test platform (chromosome-selective or genome-wide). Analyses were stratified according to the number of fibroids and total fibroid volume. The impact of fibroids on fetal fraction was assessed using linear regression, adjusting for the same covariates. RESULTS: Among 19 818 pregnancies undergoing cfDNA screening, fibroids were reported in 2038 (10.28%) and cfDNA failure at the first screening attempt occurred in 228 (1.15%) pregnancies. Non-informative results occurred in 1.96% of pregnancies with fibroids and 1.06% of pregnancies without fibroids (adjusted odds ratio (aOR), 2.40 (95% CI, 1.65-3.48)). The risk of failure in the first screening attempt increased progressively with the number of fibroids (aOR, 5.05 (95% CI, 2.29-11.13) in women with four or more fibroids) and total fibroid volume, with greater than a 5-fold and 14-fold increase in risk among women with fibroid volumes of 100.1-400 mL (aOR, 5.52 (95% CI, 2.30-13.25)) and > 400 mL (aOR, 14.80 (95% CI, 4.50-48.69)), respectively. Although test failure was more common with chromosome-selective than genome-wide screening, fibroids similarly increased the risk of failure of both screening platforms. Compared to pregnancies without fibroids, those with fibroids had a fetal fraction on average 0.61% lower (adjusted mean difference, -0.61% (95% CI, -0.77% to -0.45%)). CONCLUSION: Uterine fibroids are associated with lower fetal fraction and an increased risk of cfDNA screening failure. The strength of this association increases with increasing fibroid number and volume. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Clinical Applications of Fetal Cell-Free DNA: State of the Science.

Advances in technology have correlated with expanding prenatal genetic testing options for pregnant people. Leading medical organizations recommend cell-free DNA as the most sensitive screening test for trisomies 13, 18, and 21, as well as for fetal sex chromosome aneuploidies. The commercially available testing options go beyond these recommended tests, and prenatal care professionals should be familiar with the tests that their patients may choose despite being beyond the scope of current medical recommendations. This article explains updates in cell-free DNA technology and clinical considerations for prenatal care professionals, recognizing that this is a rapidly changing field of science and health care.

Early Non-Invasive Prenatal Testing at 6-9 Weeks of Gestation.

Non-invasive prenatal testing (NIPT) is usually performed beyond 10 weeks of gestation, because earlier in pregnancy, the fetal fraction is low, resulting in failure to obtain reliable results. This study aimed to evaluate the clinical performance of NIPT earlier in pregnancy using a method for cell-free DNA (cfDNA) analysis that eliminates the need for polymerase chain reaction (PCR), DNA sequencing, or microarrays (Vanadis® system, PerkinElmer, Waltham, MA, USA). Cell-free DNA was extracted from the maternal plasma of 30 singleton pregnancies at 6-9 weeks of gestation (group 1) and at 11-14 weeks of gestation of the same patients (group 2). The mean crown-rump length (CRL) and gestational age in group A was 16.12 mm and that in group B was 61.45 mm. In group A, results were obtained in all, but one, cases (97%). From the remaining pregnancies, one miscarried at 8 weeks and, therefore, the follow-up NIPT at 12 weeks could not be performed. The fetal sex was diagnosed correctly in the 28 cases that had a successful early test, and the results were in accordance with the examination at 12 weeks. There were no cases of aneuploidies and disomy was diagnosed correctly in all. The "Vanadis" prenatal NIPT assay can successfully be used early during the first trimester at 6-9 weeks of gestation (early NIPT) to identify the fetal sex. Further studies are needed to explore the diagnostic potential for aneuploidies.

The Impact of Chromosomal Mosaicisms on Prenatal Diagnosis and Genetic Counseling-A Narrative Review.

Genetic disorders represent a high-impact diagnosis for both patients and their families. Prenatal screening methods and, when recommended, genetic testing allow parents to make informed decisions about the course a pregnancy is going to take. Although offering certainty about the potential evolution and prognosis of the pregnancy, and then the newborn, is usually not possible, genetic counseling can offer valuable insights into genetic disorders. Chromosomal mosaicisms are genetic anomalies that affect only some cell lines in either the fetus or the placenta or both. They can affect autosomal or heterosomal chromosomes, and they can be either numerical or structural. The prognosis seems to be more severe if the genetic alterations are accompanied by malformations visible in ultrasounds. Several genetic techniques can be used to diagnose certain mosaicisms, depending on their nature. A novel approach in prenatal care is non-invasive prenatal screening (NIPS), also known as non-invasive prenatal testing (NIPT), which, although it does not always have diagnostic value, can provide valuable information about potential genetic anomalies, especially numerical, with high sensitivity (Se).

Performance of Massive Parallel Sequencing-Based Cell-Free DNA Testing in Compromised Pregnancies.

Background/Objectives: Non-Invasive prenatal test (NIPT) is used as a universal or contingent test after prior risk assessment. Screening is mainly performed for common trisomies (T21, T13, T18), although other chromosomal anomalies may be detected. Our objective was to study the performance of GWNIPT in the detection of chromosomal abnormalities in pregnancies in which an invasive prenatal study was performed and in early pregnancy losses, in comparison with the reference test. Method: VeriSeqTM NIPT Solution v2, a genome-wide NIPT (GWNIPT), was performed prior to invasive testing in fetal diagnostic study cases (FDS, n = 155) and in early pregnancy losses (EPL, n = 68). Results: In the FDS group, the diagnostic test (QFPCR, array and karyotype) detected anomalies in 32 pregnancies (21%), in twenty of them (61%) also detected by GWNIPT. Eleven of the twelve cases undetected by GWNIPT were balanced translocations (n = 4) or deletions/duplications <7 Mb (n = 7). In the EPL group, GWNIPT detected anomalies in 46% of cases (31/68) but comparison with reference test (QFPCR and karyotype) in products of conception (POC) was only possible in 18 cases. Concordant results between POC and GWNIPT test were obtained in 16 of the 18 cases. In EPL, with GWNIPT testing, common trisomies accounted for 25.8% of cases (8/31), rare trisomies 54.8% (17/31) and microdeletions/duplications 16.1% (5/31). Conclusions: The GWNIPT test may be useful in clinical practice in prenatal and in EPL's genetic diagnosis when the appropriate sample is not available.

Low fetal fraction and adverse pregnancy outcomes- systematic review of the literature and metanalysis.

PURPOSE: While cell-free DNA (cfDNA) screening has emerged as a screening modality for common aneuploidies, further research and several publications over the past decade suggested some correlation between the low concentrations of cfDNA and a number of pregnancy-related complications. The primary goal of this systematic review and meta-analysis was to assess the potential value of low-ff levels in the prediction of subsequent PE/PIH, GDM, SGA/FGR, and PTB. The meta-analysis results aim at summarizing the currently available literature data and determining the clinical relevance of this biochemical marker and the potential necessity for additional investigation of its utility in complications other than the detection of common aneuploidies. METHODS: This systematic review and meta-analysis was designed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. It included all observational studies that reported low -ff levels after the performance of non-invasive prenatal testing (NIPT) as part of the screening for chromosomal abnormalities and their association with adverse pregnancy outcomes, namely the subsequent development of hypertensive disorders of pregnancy, gestational diabetes, preterm birth, and the detection of small for gestational age fetuses or growth-restricted fetuses. The Medline (1966-2041), Scopus (2004-2024), Clinicaltrials.gov (2008-2024), EMBASE (1980-2024), Cochrane Central Register of Controlled Trials CENTRAL (1999-2024) and Google Scholar (2004-2024) databases were used in our primary search along with the reference lists of electronically retrieved full-text papers. The date of our last search was set at February 29, 2024. RESULTS: Our search identified 128 potentially relevant studies and,overall, 8 studies were included in the present systematic review that enrolled a total of 72,507 patients. Low ff of cfDNA cfDNA was positively associated with HDP (OR 1.66, 95% CI 1.34, 2.06, I-square test: 56%). Low ff of cfDNA was positively associated with GDM (OR 1.27, 95% CI 1.03, 1.56, I-square test: 76%). Furthermore, low ff levels were positively associated with SGA/FGR (OR 1.63, 95% CI 1.32, 2.03, I-square test: 0%). Low ff levels were positively correlated with the risk for PTB but the association did not manage to reach a statistical significant level (OR 1.22, 95% CI 0.89, 1.67, I-square test: 66%). CONCLUSION: Our study suggests that low ff is associated with increased risk of adverse perinatal outcomes, including PE/PIH, GDM, and SGA/FGR. However, the relationship between ff and PTB remains unclear due to conflicting evidence. It should be emphasized that further research is needed to reveal the underlying mechanisms behind the association of low ff with adverse pregnancy outcomes and explore its potential role in an overall prenatal screening, which could potentially not be limited to detecting aneuploidies.

Advancements of non-invasive prenatal testing: the role of obstetricians.

Since its debut in 2011, Non-Invasive Prenatal Testing (NIPT) has continually demonstrated its effectiveness in detecting an expanding number of diseases. NIPT offers a less invasive approach to prenatal chromosomal disease screening, providing prospective parents with vital information to better prepare for their potential pregnancy outcomes. NIPT was primarily designed for screening trisomy 13, 18, and 21. However, its scope has since broadened to encompass microdeletions and autosomal dominant monogenic diseases. Conversely, the normalization of NIPT can have unintended consequences. Some patients opt for NIPT without any medical indications, driven by a desire to remain cautious. This over-screening for chromosomal abnormalities can exacerbate pregnancy-related anxiety, as individuals might feel pressured into taking the test unnecessarily. While NIPT can be highly successful when conducted correctly, it is not infallible, and obstetricians play a crucial role in managing patient expectations. This includes providing genetic counseling to individuals with relevant genetic information regarding their personal and family histories. In the context of NIPT, a bioinformatics analysis is performed on a cell-free DNA (cfDNA) sample extracted from the mother's placenta to determine the fetal fraction (FF). This FF measurement is vital for quality control and ensuring statistical confidence in the test results. Raising awareness among clinicians about the significance of FF enhances patient care and alleviate concerns about the possibility of failed NIPT. This paper aims to explore the ongoing debates and more specifically the significance and pitfalls of NIPT on a psychosocial and ethical scale, all while highlighting the importance of genetic counseling.

Confined placental mosaicism: Distribution of chromosomally abnormal cells over the term placenta.

OBJECTIVE: Non-invasive prenatal testing (NIPT) investigates placental DNA and may detect confined placental mosaicism (CPM). The aim of this study was to confirm CPM in the term placenta in cases with abnormal NIPT but normal follow-up cytogenetic studies of fetus and mother. Additionally we examined the distribution of abnormal cells over the placenta. METHODS: Four chorionic villus (CV) biopsies from four placental quadrants were requested in cases where CPM was assumed. Both cell lineages of the CV, cytotrophoblast (CTB) and mesenchymal core (MC), were analyzed separately with SNP array. RESULTS: The chromosome aberration was confirmed in 67 % of the placentas. Three quarters of the CTB and MC biopsies from these mosaic placentas were uniformly normal (57 %) or abnormal (20 %), and a minority showed mosaicism. Among 16 cases of CPM where first trimester CV were examined as well, 11 had chromosomally normal results during pregnancy. DISCUSSION: Cytogenetic investigations of term placental biopsies suspected to be affected with CPM did not reveal the chromosome aberration in one third of the placentas. This is caused by the patchy pattern in which chromosomally abnormal cells are distributed over the placenta with the majority of the biopsies being uniformly normal. Further CPM research, including its clinical impact, requires the analysis of more than four biopsies to get insight into the extent of the affected part. Moreover, a subset of CPM type 1 and 3 seems to be only detectable with NIPT and not with first trimester CVS.

Acceptability of Prenatal Screening Tests Among Expectant Mothers in India: Insights and Implications for Public Health.

INTRODUCTION: Prenatal screening tests are essential for preventing common genetic disorders, yet their acceptability among pregnant women in India remains unexplored. This study aims to investigate the acceptability of prenatal screening tests and their correlation with demographic characteristics among pregnant women in India. METHODS: A cross-sectional study was conducted at a tertiary care, public hospital, involving 200 pregnant women. Data were collected through a self-administered questionnaire assessing demographic information and the acceptability of prenatal screening tests. Statistical analysis included chi-square tests and logistic regression. RESULTS: Most participants demonstrated adequate acceptability toward prenatal screening tests, with 73% scoring above the threshold. Factors associated with higher acceptability included younger maternal age, second-trimester gestational age, higher education, salaried employment, and urban residence. However, factors such as parity, consanguinity, mode of conception, and family history of genetic disease showed no significant associations. CONCLUSION: The study highlights positive attitudes toward prenatal screening tests among pregnant women in India, particularly among younger, more educated, and urban populations. These findings emphasize the need for targeted interventions to enhance awareness and accessibility of prenatal screening, ultimately contributing to the reduction of the genetic disorder burden in India.