Disparities in the acceptance of chromosomal microarray at the time of prenatal genetic diagnosis.

OBJECTIVE: Chromosomal microarray (CMA) increases the diagnostic yield of prenatal genetic diagnostic testing but is not universally performed. Our objective was to identify provider and patient characteristics associated with the acceptance of CMA at the time of prenatal genetic diagnostic testing. METHODS: Retrospective cohort study of patients undergoing prenatal genetic diagnostic testing (chorionic villus sampling or amniocentesis) at a single institution between 2014 and 2020. Primary outcome was the acceptance of CMA based on the genetic counselor ,GC who saw the patient. Secondary analyses assessed patient characteristics associated with the acceptance of CMA. RESULTS: 2372 participants were included. Fifty-eight percent of participants accepted CMA. Acceptance of CMA varied significantly by GC, ranging from 31% to 90%. Patients with public insurance and those who identified as Black or Hispanic/Latina were less likely to have CMA performed (aOR 0.24, 95% CI 0.20-0.30, and 0.68, 95% CI 0.50-0.92). Even among those with a structural anomaly present, public insurance was associated with significantly lower odds of CMA being performed (aOR 0.39, 95% CI 0.25-0.61). CONCLUSIONS: Acceptance of CMA at the time of prenatal genetic diagnostic testing varied based on the GC performing the counseling. Public insurance was associated with lower frequency of accepting CMA.

Consensus on Training and Assessment of Competence in Performing Chorionic Villus Sampling and Amniocentesis: An International Delphi Survey.

INTRODUCTION: The aim of this study was to obtain expert consensus on the content of a curriculum for learning chorionic villus sampling (CVS) and amniocentesis (AC) and the items of an assessment tool to evaluate CVS and AC competence. METHODS: We used a 3-round iterative Delphi process. A steering committee supervised all processes. Seven international collaborators were identified to expand the breadth of the study internationally. The collaborators invited fetal medicine experts to participate as panelists. In the first round, the panelists suggested content for a CVS/AC curriculum and an assessment tool. The steering committee organized and condensed the suggested items and presented them to the panelists in round 2. In the second round, the panelists rated and commented on the suggested items. The results were processed by the steering committee and presented to the panelists in the third round, where final consensus was obtained. Consensus was defined as support by more than 80% of the panelists for an item. RESULTS: Eighty-six experts agreed to participate in the study. The panelists represented 16 countries across 4 continents. The final list of curricular content included 12 theoretical and practical items. The final assessment tool included 11 items, systematically divided into 5 categories: pre-procedure, procedure, post-procedure, nontechnical skills, and overall performance. These items were provided with behavioral scale anchors to rate performance, and an entrustment scale was used for the final overall assessment. CONCLUSION: We established consensus among international fetal medicine experts on content to be included in a CVS/AC curriculum and on an assessment tool to evaluate CVS/AC skills. These results are important to help transition current training and assessment methods from a time- and volume-based approach to a competency-based approach which is a key step in improving patient safety and outcomes for the 2 most common invasive procedures in fetal medicine.

Assessment of an intervention to optimise antenatal management of women admitted with preterm labour and intact membranes using amniocentesis-based predictive risk models: study protocol for a randomised controlled trial (OPTIM-PTL Study).

INTRODUCTION: The majority of women admitted with threatened preterm labour (PTL) do not delivery prematurely. While those with microbial invasion of the amniotic cavity (MIAC) represent the highest risk group, this is a condition that is not routinely ruled out since it requires amniocentesis. Identification of low-risk or high-risk cases might allow individualisation of care, that is, reducing overtreatment with corticosteroids and shorten hospital stay in low-risk women, while allowing early antibiotic therapy in those with MIAC. Benefits versus risks of amniocentesis-based predictor models of spontaneous delivery within 7 days and/or MIAC have not been evaluated. METHODS AND ANALYSIS: This will be a Spanish randomised, multicentre clinical trial in singleton pregnancies (23.0-34.6 weeks) with PTL, conducted in 13 tertiary centres. The intervention arm will consist in the use of amniocentesis-based predictor models: if low risk, hospital discharge within 24 hours of results with no further medication will be recommended. If high risk, antibiotics will be added to standard management. The control group will be managed according to standard institutional protocols, without performing amniocentesis for this indication. The primary outcome will be total antenatal doses of corticosteroids, and secondary outcomes will be days of maternal stay and the occurrence of clinical chorioamnionitis. A cost analysis will be undertaken. To observe a reduction from 90% to 70% in corticosteroid doses, a reduction in 1 day of hospital stay (SD of 2) and a reduction from 24% to 12% of clinical chorioamnionitis, a total of 340 eligible patients randomised 1 to 1 to each study arm is required (power of 80%, with type I error α=0.05 and two-sided test, considering a dropout rate of 20%). Randomisation will be stratified by gestational age and centre. ETHICS AND DISSEMINATION: Prior to receiving approval from the Ethics Committee (HCB/2020/1356) and the Spanish Agency of Medicines and Medical Devices (AEMPS) (identification number: 2020-005-202-26), the trial was registered in the European Union Drug Regulating Authorities Clinical Trials database (2020-005202-26). AEMPS approved the trial as a low-intervention trial. All participants will be required to provide written informed consent. Findings will be disseminated through workshops, peer-reviewed publications and national/international conferences. PROTOCOL VERSION: V.4 10 May 2021. TRIAL REGISTRATION NUMBERS: NCT04831086 and Eudract number 2020-005202-26.

Fetal lung maturity assessment: A historic perspective and Non - invasive assessment using an automatic quantitative ultrasound analysis (a potentially useful clinical tool).

Immature fetal lung is associated with many adverse outcomes including respiratory distress syndrome and transient tachypnoea of the newborn. Several methods/tools have been used over several decades to assess fetal lung maturity prior to delivery. Some of the methods that have been used to assess fetal lung maturity include amniocentesis for the biochemical markers, lecithin and sphingomyelin, lamellar body counts, gray scale ultrasound scan and magnetic resonance imaging. Amniocentesis an invasive procedure which carries a small risk of miscarriage has almost become obsolete. Magnetic resonance imaging on the other hand is expensive and not very practical. Quantitative ultrasound fetal lung maturity (quantusFLM) assessment is a new technique aimed at assessing fetal lung texture using ultrasound. The technique depends on visualization of fetal lungs at the level of the 4- chamber view. Images obtained are then uploaded via a web page application and these are analyzed remotely and results generated in minutes. The analysis depends on studying changes in the texture of lung images that depend on changes at histological level especially of collagen, fat and water. These changes are undetectable to the human eye. Randomized clinical trials have shown this technique to be accurate, reproducible, and completely non - invasive. The aim of this review was to take a historic look at methods/tools for assessing fetal lug maturity and discuss further advances and a potential non-invasive tool/method especially the non-invasive assessment that combines ultrasound scan and machine learning to accurately assess lung maturity.

Amniocentesis learning curve using a low-cost simulation model to teach maternal-fetal medicine fellows.

OBJECTIVE: To describe the learning curve for amniocentesis among Maternal-Fetal Medicine (MFM) fellows using a low-cost simulation model in Mexico. METHODS: Fourteen first- and second-year MFM fellows with no previous experience in amniocentesis participated in this single-center prospective study from March to June of 2019. The study was approved by the Institutional Review Board at the Instituto Nacional de Perinatologia and written informed consent was obtained from all participants. After an introductory course based on a standardized technique for amniocentesis, each fellow performed this procedure using a low-cost simulation model; experienced operators supervised the procedures. Learning curves were then created using cumulative sum analysis. Thresholds for acceptable and unacceptable failure rates were defined as 10% and 25%, respectively. RESULTS: Experienced MFM specialists evaluated 3675 procedures. On average, MFM fellows performed 263 ± 53 procedures. The mean number to achieve competence was 255 ± 53. The overall failure rate among the trainees was 16%. CONCLUSION: We describe individual learning curves for amniocentesis among MFM fellows using a low-cost simulation model. This approach allows direct assessment of proficiency in amniocentesis before clinical practice.

Optimizing Fetal Aneuploidy Screening in an Austere Military Clinical Environment: A Prenatal Cost Comparison.

INTRODUCTION: Austere clinical settings, including remote military installations, face unique challenges in screening pregnant women for aneuploidy. The objective of this study was to compare the direct and indirect prenatal costs of traditional 2-part serum-based screening to cell-free DNA (cfDNA) for detection of trisomies 18 and 21 for a military treatment facility with limited in-house perinatal resources. MATERIALS AND METHODS: We identified Naval Hospital Guantanamo Bay as a surrogate for an austere clinical environment. A prenatal cost of care analysis incorporating direct and indirect expenses was performed to compare the 2 aneuploidy screening strategies for a theoretical cohort of 100 patients for detection of trisomies 18 and 21. The baseline aneuploidy uptake rate was determined using a historical cohort. Test performance characteristics were obtained from the contracting laboratory. Aneuploidy rates and costs were calculated using previously published data. RESULTS: Assuming a baseline screen uptake rate of 87%, initial screening using the traditional approach would directly cost $8,285.01 versus $44,140.32 with cfDNA. Considering indirect costs such as travel, consultative services, evaluation and follow-up testing of an abnormal screen result, and lost productivity, the cost difference narrows to $14,458.25 over a 5- to 6-year period. Cost equivalence is achieved when cfDNA is priced at $341.17 per test. CONCLUSION: Cell-free DNA as an initial screening strategy offers enhanced detection rates for trisomies 18 and 21 but remains more costly than traditional screening when incorporating direct and indirect expenses. In a low volume setting with limited resources, the added cost may be justified given the implications of unrecognized aneuploidy.

DORSCON Orange: An Approach to Challenges in a Busy Antenatal Diagnostic Centre in the Midst of a Global Pandemic.

The WHO declared the coronavirus disease 2019 (COVID-19) a global pandemic on 11 March 2020. Lessons from SARS epidemic led Singapore to develop stringent infection control protocols in preparation for future pandemics. However, unlike SARS, COVID-19 appears to be more transmissible and is predicted to continue for longer. As of 14 June 2020, there have been 40,197 positive cases with 26 deaths in Singapore, and KK Women's and Children's Hospital (KKH) has managed a total of 73 cases. Obstetrics ultrasound is an indispensable medical service and must continue to operate during a pandemic. A key balance must be struck between keeping patients and healthcare workers safe while being able to provide quality and prompt obstetric care. Our Antenatal Diagnostic Centre (ADC) in KKH developed new strategies to adapt to the pandemic when the national Disease Outbreak Response System Condition (DORSCON) was raised from yellow to orange on 7 February 2020. In this paper, we discuss our clinical workflow to reduce the risk of transmission amongst patients and staff while minimising disruption to our services.

Prenatal diagnosis of BACs-on-Beads assay in 1520 cases from Fujian Province, China.

BACKGROUND: The aim of this study was to evaluate the application of BACs-on-Beads (BoBs™) assay for rapid detection of chromosomal abnormalities for prenatal diagnosis (PND). METHODS: A total of 1520 samples, including seven chorionic villi biopsy samples, 1328 amniotic fluid samples, and 185 umbilical cord samples from pregnant women were collected to detect the chromosomal abnormalities using BoBs™ assay and karyotyping. Furthermore, abnormal specimens were verified by chromosome microarray analysis (CMA) and fluorescence in situ hybridization (FISH). RESULTS: The results demonstrated that the success rate of karyotyping and BoBs™ assay in PND was 98.09% and 100%, respectively. BoBs™ assay was concordant with karyotyping for Trisomy 21, Trisomy 18, and Trisomy 13, sex chromosomal aneuploidy, Wolf-Hirschhorn syndrome, and mosaicism. BoBs™ assay also detected Smith-Magenis syndrome, Williams-Beuren syndrome, DiGeorge syndrome, Miller-Dieker syndrome, Prader-Willi syndrome, Xp22.31 microdeletions, 22q11.2, and 17p11.2 microduplications. However, karyotyping failed to show these chromosomal abnormalities. A case of 8q21.2q23.3 duplication which was found by karyotyping was not detected by BoBs™ assay. Furthermore, all these chromosomal abnormalities were consistent with CMA and FISH verifications. According to the reports, we estimated that the detection rates of karyotyping, BoBs™, and CMA in the present study were 4.28%, 4.93%, and 5%, respectively, which is consistent with the results of a previous study. The respective costs for the three methods were about $135-145, $270-290, and $540-580. CONCLUSION: BoBs™ assay is considered a reliable, rapid test for use in PND. A variety of comprehensive technological applications can complement each other in PND, in order to maximize the diagnosis rate and reduce the occurrence of birth defects.

Cell-free DNA for Down syndrome screening in obese women: Is it a cost-effective strategy?

OBJECTIVE: Determine cost differences between cell-free DNA (cfDNA) and serum integrated screening (INT) in obese women given the limitations of aneuploidy screening in this population. METHODS: Using a decision-analytic model, we estimated the cost-effectiveness of trisomy 21 screening in class III obese women using cfDNA compared with INT. Primary outcomes of the model were cost, number of unnecessary invasive tests, procedure-related fetal losses, and missed cases of trisomy 21. RESULTS: In base case, the mean cost of cfDNA was $498 greater than INT ($1399 vs $901). cfDNA resulted in lower probabilities of unnecessary invasive testing (2.9% vs 3.5%), procedure-related loss (0.015% vs 0.019%), and missed cases of T21 (0.00013% vs 0.02%). cfDNA cost $87 485 per unnecessary invasive test avoided, $11 million per procedure-related fetal loss avoided, and $2.2 million per missed case of T21 avoided. In sensitivity analysis, when the probability of insufficient fetal fraction is assumed to be >25%, cfDNA is both costlier than INT and results in more unnecessary invasive testing (a dominated strategy). CONCLUSION: When the probability of insufficient fetal fraction more than 25% (a maternal weight of ≥300 lbs), cfDNA is costlier and results in more unnecessary invasive testing than INT.

An economic analysis of chromosome testing in couples with children who have structural chromosome abnormalities.

BACKGROUND: Structural chromosome abnormalities can cause significant negative reproductive outcomes as they typically result in morbidity and mortality of newborns. The prevalence of structural chromosomal abnormalities in live births is at least 0.05%, of which many of them have parental origins. It is uncommon to predict structural chromosome abnormalities at birth in the first child but it is possible to prevent repeated abnormalities through screening and diagnostic programmes. This study will provide an economic analysis of the prenatal detection of these abnormalities. METHODS: A cost-benefit analysis using a decision analytic model was employed to compare the status quo (doing nothing) with two interventional strategies. The first strategy (Strategy I) is preconceptional screening plus amniocentesis, and the second strategy (Strategy II) is amniocentesis alone. The monetary values in Thai baht (THB) were adjusted to international dollars (I$) using purchasing power parity (PPP) (I$1 = THB 17.60 for the year 2013). The robustness of the results was tested by applying a probabilistic sensitivity analysis. RESULTS: Both diagnostic strategies can reduce approximately 10.7-11.1 births with abnormal chromosomes per 1,000 diagnosed couples. The benefit cost ratios were 1.62 for Strategy I and 1.24 for Strategy II. Net present values per 1,000 diagnoses in couples were I$464,000 for Strategy I and I$267,000 for Strategy II. The probabilistic sensitivity analysis suggested that the cost-benefit analysis was sufficiently robust, confirming that both strategies provided higher benefits than costs. CONCLUSIONS: Since the benefits of both diagnostic strategies exceeded their costs, both strategies are economical-with Strategy I being more economically attractive. Strategy I is superior to Strategy II because it decreases the risk of normal children potentially dying from the amniocentesis process.

Cortisol, cortisone, and BDNF in amniotic fluid in the second trimester of pregnancy: Effect of early life and current maternal stress and socioeconomic status.

The prenatal environment shapes the offspring's phenotype; moreover, transgenerational stress and stress during pregnancy may play a role. Brain-derived neurotrophic factor (BDNF) and glucocorticoids influence neurodevelopment during pregnancy, and there is evidence that BDNF in amniotic fluid is mainly of fetal origin, while the source of glucocorticoids is maternal. We tested the hypothesis that maternal early life stress, psychiatric diagnoses, anxiety, perceived stress, and socioeconomic status influence BDNF and glucocorticoid concentrations in amniotic fluid in the second trimester. We studied 79 pregnant women who underwent amniocentesis in the early second trimester and analyzed BDNF, cortisol, and cortisone concentrations in amniotic fluid. The endocrine data were related to maternal early life adversities (Childhood Trauma Questionaire), perceived stress (Perceived Stress Scale), anxiety, socioeconomic status (family income), and the presence of psychiatric diseases. We found BDNF in amniotic fluid to be positively related to maternal early adversity (Childhood Trauma Questionaire). Low family income (socioeconomic status) was related to high amniotic fluid glucocorticoid concentrations. Neither glucocorticoid concentrations nor hydroxy steroid dehydrogenase (HSD2) activity could be related to BDNF concentrations in amniotic fluid. Early maternal adverse events may be reflected in the fetal BDNF regulation, and it should be tested whether this relates to differences in neurodevelopment.

Assessing the cost of implementing the 2011 Society of Obstetricians and Gynecologists of Canada and Canadian College of Medical Genetics practice guidelines on the detection of fetal aneuploidies.

BACKGROUND: The Society of Obstetricians and Gynecologists of Canada and the Canadian College of Medical Genetics published guidelines, in 2011, recommending replacement of karyotype with quantitative fluorescent polymerase chain reaction when prenatal testing is performed because of an increased risk of a common aneuploidy. STUDY OBJECTIVE: This study's objective is to perform a cost analysis following the implementation of quantitative fluorescent polymerase chain reaction as a stand-alone test. RESULTS: A total of 658 samples were received between 1 April 2014 and 31 August 2015: 576 amniocentesis samples and 82 chorionic villi sampling. A chromosome abnormality was identified in 14% (93/658) of the prenatal samples tested. The implementation of the 2011 Society of Obstetricians and Gynecologists of Canada and the Canadian College of Medical Genetics guidelines in Edmonton and Northern Alberta resulted in a cost savings of $46 295.80. The replacement of karyotype with chromosomal microarray for some indications would be associated with additional costs. CONCLUSION: The implementation of new test methods may provide cost savings or added costs. Cost analysis is important to consider during the implementation of new guidelines or technologies. © 2017 John Wiley & Sons, Ltd.

Management of suspected primary Toxoplasma gondii infection in pregnant women in Norway: twenty years of experience of amniocentesis in a low-prevalence population.

BACKGROUND: Primary infection with Toxoplasma gondii during pregnancy may pose a threat to the fetus. Women infected prior to conception are unlikely to transmit the parasite to the fetus. If maternal serology indicates a possible primary infection, amniocentesis for toxoplasma PCR analysis is performed and antiparasitic treatment given. However, discriminating between primary and latent infection is challenging and unnecessary amniocenteses may occur. Procedure-related fetal loss after amniocentesis is of concern. The aim of the present study was to determine whether amniocentesis is performed on the correct patients and whether the procedure is safe for this indication. METHODS: Retrospective study analysing data from all singleton pregnancies (n = 346) at Oslo University Hospital undergoing amniocentesis due to suspected maternal primary toxoplasma infection during 1993-2013. Maternal, neonatal and infant data were obtained from clinical hospital records, laboratory records and pregnancy charts. All serum samples were analysed at the Norwegian Institute of Public Health or at the Toxoplasma Reference Laboratory at Oslo University Hospital. The amniocenteses were performed at Oslo University Hospital by experienced personnel. Time of maternal infection was evaluated retrospectively based on serology results. RESULTS: 50% (173) of the women were infected before pregnancy, 23% (80) possibly in pregnancy and 27% (93) were certainly infected during pregnancy. Forty-nine (14%) women seroconverted, 42 (12%) had IgG antibody increase and 255 (74%) women had IgM positivity and low IgG avidity/high dye test titre. Fifteen offspring were infected with toxoplasma, one of them with negative PCR in the amniotic fluid. Median gestational age at amniocentesis was 16.7 gestational weeks (GWs) (Q1 = 15, Q3 = 22), with median sample volume 4 ml (Q1 = 3, Q3 = 7). Two miscarriages occurred 4 weeks after the procedure, both performed in GW 13. One of these had severe fetal toxoplasma infection. CONCLUSIONS: Half of our study population were infected before pregnancy. In order to reduce the unnecessary amniocenteses we advise confirmatory serology 3 weeks after a suspect result and suggest that the serology is interpreted by dedicated multidisciplinary staff. Amniocentesis is safe and useful as a diagnostic procedure in diagnosing congenital toxoplasma infection when performed after 15 GW.

Prenatal screening costs at a large military treatment facility.

OBJECTIVE: Prenatal screening with cell-free DNA (cfDNA) offers improved detection of Down syndrome (T21) compared to conventional screening. These tests are expensive and have fewer detectable anomalies. Our objective was to investigate potential costs and test performance of screening algorithms when accounting for detectable aneuploidies. METHODS: This is a cost analysis for a large military treatment facility. Using a theoretical delivery cohort and published performance data, universal screening with cfDNA was compared to sequential screening, comparing T21 to all detectable aneuploidies. Predicted test performance and costs were calculated. RESULTS: A cohort of 3000 deliveries was used. For T21, universal cfDNA is more expensive ($1,346,064) than sequential screening ($244,885), but has a lower false positive rate and avoids 101 invasive diagnostic tests. An additional case of T21 is detected with a marginal cost of $1,101,179. For all detectable aneuploidies, cfDNA is more expensive ($1,353,660) than sequential screening ($239,189), and 59 invasive diagnostic tests are avoided. Sequential screening detects an additional case of aneuploidy, with a cost savings of $1,114,471. CONCLUSIONS: Although cfDNA is superior in detecting T21 cases, sequential screening is superior when considering all aneuploidies detectable. The cost increase with universal cfDNA is significant, and is not justified with small improvements in the performance.

The impact of financing of screening tests on utilization and outcomes: The case of amniocentesis.

We use a 1993 policy change in Israel's public healthcare system that lowered the eligibility age for amniocentesis to 35 to study the effects of financing of screening tests. Financing is found to have increased amniocentesis testing by about 35%. At ages above the eligibility threshold, utilization rates rose to roughly 33%, reflection nearly full takeup among prospective users of amniocentesis. Additionally, whereas below the age-35 threshold amniocentesis utilization rates increase with maternal age, this relation is muted above this age. Finally, no evidence is found that financing affects outcomes such as pregnancy terminations and births of children with Down syndrome. These results support the view that women above the eligibility threshold tend to refrain from acquiring inexpensive information about their degree of risk that absent the financing they would acquire, and instead, undergo the accurate and costly test regardless of additional information that noninvasive screening would provide.

Non-invasive prenatal diagnosis (NIPD) for single gene disorders: cost analysis of NIPD and invasive testing pathways.

OBJECTIVE: Evaluate the costs of offering non-invasive prenatal diagnosis (NIPD) for single gene disorders compared to traditional invasive testing to inform NIPD implementation into clinical practice. METHOD: Total costs of diagnosis using NIPD or invasive testing pathways were compared for a representative set of single gene disorders. RESULTS: For autosomal dominant conditions, where NIPD molecular techniques are straightforward, NIPD cost £314 less than invasive testing. NIPD for autosomal recessive and X-linked conditions requires more complicated technical approaches and total costs were more than invasive testing, e.g. NIPD for spinal muscular atrophy was £1090 more than invasive testing. Impact of test uptake on costs was assessed using sickle cell disorder as an example. Anticipated high uptake of NIPD resulted in an incremental cost of NIPD over invasive testing of £48 635 per 100 pregnancies at risk of sickle cell disorder. CONCLUSION: Total costs of NIPD are dependent upon the complexity of the testing technique required. Anticipated increased demand for testing may have economic implications for prenatal diagnostic services. Ethical issues requiring further consideration are highlighted including directing resources to NIPD when used for information only and restricting access to safe tests if it is not cost-effective to develop NIPD for rare conditions. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

The choice of amniotic fluid in metabolomics for the monitoring of fetus health.

Amniotic fluid (AF) is a biological fluid in which metabolite transport is regulated by the placenta, the permeable skin, fetal lung egress and gastric fluid. During pregnancy, the composition of AF changes from similar to the interstitial fluid of the mother, to a more complex system, influenced by the fetus's urine. Since AF reflects the mother's and the fetus's health status at the same time, it may be an important diagnostic tool for a wider spectrum of clinical conditions. Indeed, the metabolic characterization of AF in relation to pathological occurrences may lead to the discovery of new biomarkers for a better clinical practice. For this reason, metabolomics may be the most suitable strategy for this task. In this review, research works on metabolomic AF analysis are discussed according to the morbidity of interest, being preterm birth/labor, gestational age and diabetes and fetal malformations, along with a number of other important studies.

Uptake of non-invasive prenatal testing in Chinese women: money matters.

OBJECTIVE: To determine the influence of free invasive prenatal testing on the uptake of non-invasive prenatal testing (NIPT). STUDY DESIGN: Over a 2-year period at a Chinese tertiary prenatal diagnostic unit, women at risk of fetal trisomy were given the option of NIPT or invasive prenatal testing. Invasive prenatal testing was offered free of charge to women with a local Hukou (household registration); however, women without a local Hukou were charged for invasive prenatal testing. Both women with and without a local Hukou were charged for NIPT. RESULTS: During the first year, 2647 women with a positive trisomy 21 screening test were referred (474 women with a local Hukou and 2173 women without a local Hukou). Only 1.6% of the women with a local Hukou underwent NIPT, while this proportion was 20.6% in the women without a local Hukou. During the second year, the price of NIPT was reduced. The total number of women referred was 3047 (502 women with a local Hukou and 2545 women without a local Hukou). The uptake of NIPT in women without a local Hukou doubled, but the uptake of NIPT remained stable in women with a local Hukou. CONCLUSION: The financial impact on the uptake of NIPT should not be underestimated.

National decline in invasive prenatal diagnostic procedures in association with uptake of combined first trimester and cell-free DNA aneuploidy screening.

In late 2012, a new screening test for fetal aneuploidy based on circulating cell-free DNA (cfDNA) became available to Australian women. The introduction of this technology in the United States has led to a reduction in invasive diagnostic procedures. Analysis of the number of amniocentesis and chorionic villus sampling (CVS) procedures performed in Australia from 1994 to 2014 shows that the introduction of cfDNA testing has been associated with the most rapid decline in invasive procedures in the last 20 years. This change has important implications for training in, and maintenance of, the procedural skills of amniocentesis and CVS.