Prenatal screening for fetal aneuploidies with cell-free DNA in the general pregnancy population: a cost-effectiveness analysis

Objective: To estimate the cost-effectiveness of fetal aneuploidy screening in the general pregnancy population using non-invasive prenatal testing (NIPT) as compared to first trimester combined screening (FTS) with serum markers and NT ultrasound.

Methods: Using a decision-analytic model, we estimated the number of fetal T21, T18, and T13 cases identified prenatally, the number of invasive procedures performed, corresponding normal fetus losses, and costs of screening using FTS or NIPT with cell-free DNA (cfDNA). Modeling was based on a 4 million pregnant women cohort, which represents annual births in the U.S.

Results: For the general pregnancy population, NIPT identified 15% more trisomy cases, reduced invasive procedures by 88%, and reduced iatrogenic fetal loss by 94% as compared to FTS. The cost per trisomy case identified with FTS was $497?909. At a NIPT unit, cost of $453 and below, there were cost savings as compared to FTS. Accounting for additional trisomy cases identified by NIPT, a NIPT unit cost of $665 provided the same per trisomy cost as that of FTS.

Conclusions: NIPT in the general pregnancy population leads to more prenatal identification of fetal trisomy cases as compared to FTS and is more economical at a NIPT unit cost of $453.     

Cell-Free DNA–Based Non-invasive Prenatal Screening for Common Aneuploidies in a Canadian Province: A Cost-Effectiveness Analysis

Objective

Yearly, 450?000 pregnant Canadians are eligible for voluntary prenatal screening for trisomy 21. Different screening strategies select approximately 4% of women for invasive fetal chromosome testing. Non-invasive prenatal testing (NIPT) using maternal blood cell-free DNA could reduce those invasive procedures but is expensive. This study evaluated the cost-effectiveness of NIPT strategies compared with conventional strategies.

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

Objective: The aim of this study was to validate noninvasive prenatal testing (NIPT) for fetal aneuploidies by whole-genome massively parallel sequencing (MPS).

Methods: MPS was performed on cell-free DNA (cfDNA) isolated from maternal plasma in two groups: a first set of 186 euploid samples and a second set of 195 samples enriched of aneuploid cases (n?=?69); digital PCR for fetal fraction (FF) assessment was performed on 178/381 samples. Cases with?<10?×?10⁶ reads (n?=?54) were excluded for downstream data analysis. Follow-up data (invasive testing results or neonatal information) were available for all samples. Performances in terms of specificity/sensitivity and Z-score distributions were evaluated.

Results: All positive samples for trisomy 21 (T21) (n?=?43), trisomy 18 (T18) (n?=?6) and trisomy 13 (T13) (n?=?7) were correctly identified (sensitivity: 99.9%); 5 false positive results were reported: 3 for T21 (specificity?=?98.9%) and 2 for T13 (specificity?=?99.4%). Besides FF, total cfDNA concentration seems another important parameter for MPS, since it influences the number of reads.

Conclusions: The overall test accuracy allowed us introducing NIPT for T21, T18 and T13 as a clinical service for pregnant women after 10?+?4 weeks of gestation. Sex chromosome aneuploidy assessment needs further validation due to the limited number of aneuploid cases in this study.     

Fetal aneuploidy screening with cell-free DNA in late gestation

Objective: The aim of this study was to evaluate clinical use of NIPT at gestational ages of 23 weeks and above.

Methods: A cohort of 5579 clinical patients with singleton gestations of 23 weeks or greater submitting a blood sample for NIPT in an 18-month period were selected for this study. Clinical outcomes were requested for samples with NIPT results indicating fetal aneuploidy and compared with NIPT findings to confirm concordance or discordance.

Results: A review of clinical indications revealed that a significantly (p?Conclusions: NIPT is a highly accurate prenatal screening option for women after 23 weeks of gestation. Women who presented for NIPT in the latter stages of pregnancy more frequently specified clinical indications of abnormal ultrasound findings than women who entered screening earlier in pregnancy.     

无创产前检测进行染色体缺失或重复检测的临床应用价值

目的:探讨无创产前检测(NIPT)进行染色体缺失或重复检测的临床应用价值。方法:对传统产前筛查异常、既往有唐氏儿分娩史及高龄孕妇等3500例孕妇采集外周血,采用Illumina测序技术检测母体血浆胎儿游离DNA(cff DNA),分析胎儿性染色体及除21、13、18号染色体以外的其他常染色体信息,对NIPT阳性的孕妇进行遗传咨询,对其中自愿进行介入性产前诊断的,行染色体核型分析及染色体微阵列分析(CMA)进行验证。结果:3500例接受NIPT的病例中,检出32例常染色体异常(除外21、13、18号),其中有11例接受介入性产前诊断,染色体核型分析及CMA检测分别提示3例异常,符合率27.3%(3/11)。检出45例性染色体异常,其中有23例接受介入性产前诊断,染色体核型分析及CMA检测分别确诊12例异常,符合率52.2%(12/45)。结论:NIPT在预测胎儿性染色体异常及常染色体(除外21、13、18号)异常方面有一定的参考价值,但需要进行染色体核型分析和(或)CMA检测进行验证。     

Predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities

Objective.?The study aimed to estimate the incidence of increased nuchal translucency in the first trimester ultrasound scan results (cut-off limit 2.5 mm) and to evaluate the predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities.

Methods.?We used the ultrasound scan results of nuchal translucency evaluation and the results of chromosomal analysis of the invasive prenatal control performed as a result of increased nuchal translucency.

Results.?We collected 2183 nuchal translucency ultrasound scans in which we detected 21 embryos with a pathologic value (0.96%). We collected the data of 168 cases of invasive prenatal control due to increased nuchal translucency from which 122 cases were found. A total of 122 cases of pregnant women undergone an invasive prenatal diagnostic method due to increased nuchal translucency, of which 11 fetuses were found with trisomy 21 (Down syndrome) (9%), 3 fetuses with trisomy 13 (Patau syndrome) (2.45%), 3 fetuses with monosomy 45XO (Turner syndrome) (2.45%) and 1 fetus with translocation (0.8%).

Conclusions.?The positive predictive value of the increased fetal nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities based on the results of the chromosomal-genetic analysis of the invasive prenatal diagnostic procedures is 14.8%.     

Non-invasive prenatal testing: impact on invasive prenatal diagnosis at a mainland Chinese tertiary medical center

Objective: We describe the changes over a 4-year period in the number of diagnostic testing after the introduction of non-invasive prenatal testing (NIPT).

Methods: The rate of NIPT as an indication in women who received amniocentesis, and the number of amniocentesis required for detection of one case with major aneuploidy were compared between a 1-year baseline period before the introduction of NIPT, and the 3 years following NIPT introduction.

Results: A total of 7536 amniocentesis procedures were performed over the 4-year study period. During the baseline period of the year 2011, the number of invasive testing required for detection of one common trisomy was 57. During the first 2 years that NIPT was offered, NIPT averaged 1.7 percent of the total indications for amniocentesis, and the required number of invasive testing decreased to 30. With the increase of the percentage of NIPT during the 3rd year, the required number of invasive testing further decreased to 26.

Conclusion: After the clinical introduction of NIPT, invasive prenatal diagnostic testing had not decreased at a Chinese prenatal diagnostic unit, but a remarkably improved detection rate of major aneuploidies in diagnostic procedures was observed.     

Noninvasive prenatal testing (NIPT) detects variant of Turner syndrome not detectable by fluorescent in situ hybridization

Abstract

Introduction: Noninvasive prenatal testing (NIPT) is a reliable screening method for fetal aneuploidy detection of trisomy 18, 13, 21 along with few sex chromosome abnormalities monosomy X, XXX, XXY (Klinefelter), XYY (Jacob) syndromes and certain microdeletions which include cri-du-chat, DiGeorge, 1p36, Angelman, and Prader-Willi syndromes in comparison to the available screening methods. Prenatal screening of Turners syndrome is possible by ultrasound in certain conditions only. Recently benefits of early detection and treatment of Turners syndrome has been emphasized, enforcing on accurate and early screening prenatally.

Case details: The current case emphasizes on the reliability of NIPT testing which comes with an advantage of early screening. A 24-year-old primi gravida was referred for NIPT as she tested for high risk on biochemical screening. The Panorama? NIPT results showed low risk for trisomies, 21, 18, and 13 but high risk of monosomy X and was advised confirmatory amniocentesis. The fluorescence in situ hybridization (FISH) report revealed no numerical abnormality detected for any of the five chromosomes tested. On receiving this discordant report, the sample was rerun for NIPT, to rule out any laboratory-related issues. The result obtained on a rerun was consistent with the first report and showed monosomy X again. The karyotype report was available three weeks later and a rare variant of Turners syndrome was identified.

Discussion: Panorama? NIPT considers single nucleotide polymorphisms spread across the chromosomes for analysis, different variants of aneuploidy can be picked up in comparison to FISH, similar to the current case wherein it could not as it was a centromeric probe. Reported first case of X chromosome variant detected by NIPT confirmed by karyotyping, missed by FISH.     

Establishing and validating noninvasive prenatal testing procedure for fetal aneuploidies in Vietnam

Abstract

Objective: Noninvasive prenatal testing (NIPT) for fetal aneuploidies has been widely adopted in developed countries. Despite the sharp decrease in the cost of massively parallel sequencing, the technical know-how and skilled personnel are still one of the major limiting factors for applying this technology to NIPT in low-income settings. Here, we present the establishment and validation of our NIPT procedure called triSure for detection of fetal aneuploidies.

Methods: We established the triSure algorithm based on the difference in proportion of fetal and maternal fragments from the target chromosome to all chromosomes. Our algorithm was validated using a published data set and an in-house data set obtained from high-risk pregnant women in Vietnam who have undergone amniotic testing. Several other aneuploidy calling methods were also applied to the same data set to benchmark triSure performance.

Results: The triSure algorithm showed similar accuracy to size-based method when comparing them using published data set. Using our in-house data set from 130 consecutive samples, we showed that triSure correctly identified the most samples (overall sensitivity and specificity of 0.983 and 0.986, respectively) compared to other methods tested including count-based, sized-based, RAPIDR and NIPTeR.

Conclusions: We have demonstrated that our triSure NIPT procedure can be applied to pregnant women in low-income settings such as Vietnam, providing low-risk screening option to reduce the need for invasive diagnostic tests.     

First trimester combined screening for Trisomy 21 in Hong Kong: outcome of the first 10,000 cases

Objective.?To examine the effectiveness of first trimester fetal Trisomy 21 (T21) screening using a combination of maternal age, nuchal translucency, maternal serum levels of free β-hCG and PAPP-A in a predominantly Chinese population in Hong Kong.

Methods.?Consecutive women who underwent the combined screening for T21 between 11 and 13 + 6 weeks of gestation between 2003 and 2007 were recruited. Risk of T21 was calculated using Fetal Medicine Foundation algorithm and karyotyping was advised when the risk was 1:300 or above. All women were followed up for pregnancy and fetal outcome.

Results.?10,363 fetuses underwent screening. 99% of the women were Chinese and 27.4% were at or above 35 years old. 618 fetuses were screened positive (5.9%), which included 31 cases of T21, 14 cases of T18, 7 cases of T13, 10 cases of 45XO and 7 cases of other chromosomal abnormalities. Among the 9745 screened negative fetuses all but 50 (0.5%) had a known outcome, which included three T21 and four other chromosomal abnormalities. All were subsequently identified at the morphology scan except for one case of T21. The detection rate and false positive rates for T21 were 91.2% and 5.4%, respectively and the positive predictive value for all chromosomal abnormalities was 1 in 9.

Conclusions.?Combined screening for T21 is highly effective among Chinese women. Training, quality control, regular auditing and follow up are essential to maintain screening standards.     

Noninvasive Prenatal Testing for Trisomies 21, 18, and 13, Sex Chromosome Aneuploidies,and Microdeletions in Average-Risk Pregnancies: A Cost-Effectiveness Analysis

ObjectiveThe cost effectiveness of noninvasive prenatal testing (NIPT) has been established for high-risk pregnancies but remains unclear for pregnancies at other risk levels. The aim was to assess the cost effectiveness of NIPT in average-risk pregnancies from the perspective of a provincial public payer in Canada.MethodsA model was developed to compare traditional prenatal screening (TPS), NIPT as a second-tier test (performed only after a positive TPS result), and NIPT as a first-tier test (performed instead of TPS) for trisomies 21, 18, and 13; sex chromosome aneuploidies; and microdeletions in a hypothetical annual population cohort of average-risk pregnancies (142 000 to 148,000) in Ontario, Canada. A probabilistic analysis was conducted with 5000 repetitions.ResultsCompared with TPS, NIPT as a second-tier test detected more affected fetuses with trisomies 21, 18, and 13 (188 vs. 158), substantially reduced the number of diagnostic tests (i.e., chorionic villus sampling and amniocentesis) performed (660 vs. 3107), and reduced the cost of prenatal screening ($26.7 million vs. $27.6 million) annually. Compared with second-tier NIPT, first-tier NIPT detected an additional 80 cases of trisomies 21, 18, and 13 at an additional cost of $33 million. The incremental cost per additional affected fetus detected was $412 411. Extending first-tier NIPT to include testing for sex chromosome aneuploidies and 22q11.2 deletion would increase the total screening cost.ConclusionsNIPT as a second-tier test is cost-saving compared with TPS alone. Compared with second-tier NIPT, first-tier NIPT detects more cases of chromosomal anomalies but at a substantially higher cost.     

Next-generation sequencing: a follow-up of 36,913 singleton pregnancies with noninvasive prenatal testing in central China

PurposeTo evaluate the noninvasive prenatal testing (NIPT) results of 36,913 cases in Jiangxi province of central China and explore its application value in prenatal screening and diagnosis.MethodsThis retrospective analysis included 36,913 singleton pregnant women who underwent NIPT because of moderate-/high-risk pregnancy or voluntary requirements between January 2017 and December 2019 in our hospital. Chromosomal abnormalities such as trisomies 21, 18, and 13 (T21, T18, T13) and sex chromosome aneuploidies (SCAs) were judged by standard Z-score analysis. Positive NIPT results were confirmed by amniocentesis and karyotyping. Pregnancy outcomes were followed up via telephone interview.ResultsA total of 1.01% (371/36,913) positive cases were detected by NIPT, comprising 137, 46, 31, and 157 cases of T21, T18, T13, and SCAs, respectively. A total of 116 of T21, 27 of T18, 13 of T13, and 51 of SCAs were confirmed to be true positive; all normal cases that had been followed up were verified to be true negative. The NIPT sensitivity in T21, T18, T13, and SCAs was 100.00% individually, whereas the specificity was 99.94% (36,488/36,509), 99.95% (36,579/36,598), 99.95% (36,594/36,612), and 99.72% (36,472/36,574), respectively. Furthermore, the negative predictive values of T21, T18, T13, and SCAs were all 100%, while the positive predictive values were 84.67%, 58.70%, 41.94%, and 33.33%, respectively.ConclusionNIPT is highly sensitive and has a low false positive rate in testing clinically significant fetal aneuploidies of general reproductive women. However, this technique cannot substitute for amniocentesis and karyotyping, and detailed genetic counseling is also essential for the high-risk group of NIPT.     

Nichtinvasive Pränataltestung (NIPT)

Non-invasive prenatal testing (NIPT) using cell-free fetal DNA (cff-DNA) in maternal blood has the potential to dramatically alter the way prenatal screening and diagnosis is delivered. Before NIPT can be implemented into routine practice, information is required on its costs and benefits. The best performing screening tests are able to identify more than 90?% of trisomy 21 cases with a 5?% rate of false positives but positive screening results require confirmation with diagnostic testing, such as amniocentesis or chorionic villus sampling (CVS). However, both sampling procedures are invasive, and are associated with significant risks to the fetus and mother, including the potential loss of a healthy fetus. For this reason invasive prenatal diagnosis tests are currently performed only in high-risk pregnancies or in pregnancies with increased maternal age and/or a family history of inherited disease. Therefore, developing a reliable method for NIPD for fetal trisomy 21 is of critical importance in prenatal care and NIPT is able to identify 99?% of trisomy 21 cases with a 0.1?% rate of false positives. As first-line testing NIPT detects more Down’s syndrome cases, results in fewer procedure-related miscarriages and is more expensive than current screening. When NIPT uptake increases, NIPT will detect more trisomy 21 cases with a small increase in procedure-related miscarriages and costs. As first-line testing NIPT is likely to produce more favorable outcomes but at greater cost. Further research is needed to evaluate NIPT under real world conditions.     

MicroRNAs as potential biomarkers for noninvasive detection of fetal trisomy 21

Purpose

The objective of this study was to discover a panel of microRNAs (miRNAs) as potential biomarkers for noninvasive prenatal testing (NIPT) of trisomy 21 (T21) and to predict the biological functions of identified biomarkers using bioinformatics tools.

Methods

Using microarray-based genome-wide expression profiling, we compared the expression levels of miRNAs in whole blood samples from non-pregnant women, whole blood samples from pregnant women with euploid or T21 fetuses, and placenta samples from euploid or T21 fetuses. We analyzed the differentially expressed miRNAs according to disease and tissue type (P value <0.05 and two-fold expression change). To predict functions of target genes of miRNAs, the functional annotation tools were used.

Results

We identified 299 miRNAs which reasonably separate the whole blood from the placenta. Among the identified miRNAs, 150 miRNAs were up-regulated in the placenta, and 149 miRNAs were down-regulated. Most of the up-regulated miRNAs in the placenta were members of the mir-498, mir-379, and mir-127 clusters. Among the up-regulated miRNAs in the placenta, mir-1973 and mir-3196 were expressed at higher levels in the T21 placenta than in the euploid placenta. The two miRNAs potentially regulate 203 target genes that are involved in development of brain, central nervous system, and nervous system. The genes are significantly associated with T21-related disorder such as congenital abnormalities, mental disorders, and nervous system diseases.

Conclusions

Our study indicates placenta-specific miRNAs that may be potential biomarkers for NIPT of fetal T21 and provides new insights into the molecular mechanisms of T21 via regulation of miRNAs.     

Prenatal diagnosis versus first-trimester screening of trisomy 21 among pregnant women aged 35 or more

Objective: To compare the policy of prenatal diagnosis versus first trimester screening of trisomy 21 among pregnant women of advanced age.

Methods: A retrospective study was conducted on patients aged ≥35 divided in two groups: patients who requested first trimester combined test and only in case of screen-positive result underwent invasive testing (group A); patients undergoing chorionic villous sampling or amniocentesis as first investigation (group B). The following outcome variables were compared: antenatal detection of trisomy 21, occurrence of trisomy 21 at birth, miscarriage rate, hospitals' costs.

Results: 4527 women were included. Of these, 534 (11.80%) underwent T21 screening whereas 3993 (88.20%) requested primary invasive testing. In group A, 64 combined test were positive (11.99%) and 8 trisomy 21 cases were diagnosed (1.50%); the loss of euploid fetuses after invasive procedure was 4.55% (2/44). No false-negative case was observed. In group B 57 cases of trisomy 21 were diagnosed (1.43%), and pregnancy loss rate of chromosomally normal fetuses was 0.45% (17/3806). The estimated cost was, respectively, 67.720€ for the primary screening versus 1.996.500€ for direct prenatal diagnosis.

Conclusion: First trimester screening of trisomy 21 is highly accurate and cost saving among women ≥35.     

Canadian women’s attitudes toward noninvasive prenatal testing of fetal DNA in maternal plasma*

Objective: To determine the perceptions and attitudes of Canadian women to Noninvasive Prenatal Testing of fetal DNA.

Study design: A designed questionnaire was administered to women attending the outpatient antenatal clinic at a tertiary urban hospital. Attitudes to current and new prenatal screening modalities were assessed using a five-point Likert scale. Bowker’s test of symmetry was used to compare individual responses regarding the two screening modalities. Changes in women’s responses pre- and post-delivery were also compared.

Results: One hundred and twenty-nine women were enrolled in this study. 88% of women state that they would perform prenatal screening via fetal DNA in the maternal plasma if available. When compared to conventional screening, significantly less women believe that the NIPT should be available upon request for non-medical traits (36.4% versus 60.4%, p?<?0.001). When compared to their answer before delivery, more women agreed that screening with fetal DNA in maternal plasma could be used in a negative way to select for desired non-medical traits such as gender.

Conclusions: The use of fetal DNA in the maternal plasma is widely accepted in our Canadian population as a future method of noninvasive prenatal screening despite recognition of certain ethical concerns. This information can be used when implementing new genetic screening programs.     

Psychological factors influencing choice of prenatal diagnosis in Chinese multiparous women with advanced maternal age

Objectives: To investigate the psychological predictors in Chinese multiparous pregnant women of advanced maternal age (AMA) for choosing aneuploidy screening or diagnostic testing.

Methods: A total of 84 pregnant women of AMA were consecutively enrolled from Renming Hospital, Wuhan University. All participants completed three questionnaires: Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating Depression Scale (SDS), and Pregnancy Stress Rating Scale (PSRS). Demographic information and the choice of noninvasive prenatal testing (NIPT) versus invasive prenatal diagnosis (PND) were also collected.

Results: Thirty-seven chose to have invasive PND, and 47 chose NIPT. Choosing invasive PND, as opposed to NIPT, was associated with lower educational background (χ²?=??2.269, p?=?.023), higher SAS scores (47.62?±?7.96 versus 44.21?±?6.10, p?=?.029), and higher SDS scores (50.41?±?9.80 versus 45.96?±?11.05, p?=?.058). Logistic regression analysis further showed that the decisive predictors for invasive PND are SAS (OR =1.106, p?=?.008) scores, scores of factor 3 in PSRS and the stress from changes of shape and motility (OR =0.471, p?=?.038). Subgroup analysis showed that women with previous negative pregnancy experience had higher scores in factor 2-stress (guarantee of maternal-fetal safety: 1.96?±?0.63 versus 2.49?±?0.65, p?=?.004) and total PSRS scores (1.60?±?0.4 versus 1.83?±?0.31, p?=?.044) than those without. Additionally, unemployment post pregnancy was associated with marginally significant higher PSRS scores (p?=?.083).

Conclusions: The decision for invasive PND might be swayed by anxiety and attenuated by pregnancy stress originating from worry about changes in fetal shape and motility (measured by SAS and factor 3 score of PSRS, respectively).     

无创DNA检测在诊断高龄孕妇胎儿非整倍体中的应用

目的:探讨高龄妊娠胎儿染色体异常的风险以及无创DNA产前检测(NIPT)在诊断高龄孕妇胎儿非整倍体染色体病中的应用价值。方法:选择≥35岁的高龄孕妇2714例,按年龄分为35~39岁,≥40岁两组,采用NIPT高通量测序检测孕妇血浆游离DNA,并对检测结果提示21-三体、18-三体、13-三体及性染色体高风险者行羊膜腔穿刺术及胎儿染色体核型分析,对检测结果阴性者通过电话随访进行验证。计算NIPT检测的敏感度、特异度、阳性预测值、阴性预测值及Youden指数。结果:2714例高龄孕妇NIPT检测结果提示胎儿非整倍体染色体异常高风险47例,6例高风险孕妇拒绝侵入性产前诊断,余41例高风险孕妇行羊膜腔穿刺术及羊水细胞染色体核型分析,结果显示21-三体19例,18-三体1例,13-三体2例,性染色体异常7例。与现有的金标准羊膜腔穿刺术核型分析相比较,NIPT对高龄孕妇除外性染色体异常的胎儿非整倍体染色体异常检出敏感度为100.00%,特异度为99.93%,阳性预测值为90.91%,阴性预测值为100.00%,Youden指数为0.99。进一步通过年龄分组发现,40岁及以上年龄组异常率显著高于35~39岁年龄组(P=0.011)。结论:高龄孕妇可通过NIPT快速、安全地筛查出胎儿非整倍体染色体异常,减少侵入性产前检测比例,降低胎儿出生缺陷率。     

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.     

Prenatal invasive testing: a 13-year single institution experience

Abstract

Objectives: To analyze trends in screening and invasive prenatal diagnosis over a 13-year period in relation to changes in the national prenatal screening policy.

Methods: Fetal karyotypes obtained following 11?045 prenatal invasive procedures between January 1999 and December 2011 were retrospectively reviewed. Referral indications were classified as medical and non-medical (anxiety). The number of tests per relevant chromosomal abnormalities (CA) detected in both groups adjusted for indication was calculated.

Results: A total of 414 CA were detected (3.8%), 355 of which were considered clinically significant. The percentage of invasive procedures has declined from 49% to 12%, although cases referred by anxiety have increased from 22% to 55%. A total of 3129 invasive procedures did not have any medical indication (28%) and 13 relevant CA (0.42%) were found in this group. In this low-risk series, the index “number of invasive testing needed to detect 1 relevant CA” adjusted for indication was 241.

Conclusions: Changes in our national prenatal policy through this 13-year period show an increasing efficiency of prenatal detection of CA. However, despite the intensifying screening policies, low-risk pregnant women show a growing demand for prenatal invasive testing and a baseline risk for cytogenetic abnormality of 1/241.