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Purpose: This study aimed to investigate the performance, cost-effectiveness and additional findings of combined detailed ultrasound and biochemical screening for risks of major fetal trisomies in the first-trimester. Methods: This is a retrospective analysis study, we estimated the risk of trisomies 21, 18 and 13 based on maternal age, fetal nuchal translucency thickness, nasal bone, ductus venosus pulsatility index velocity, tricuspid regurgitation, fetal heart rate, free beta-human chorionic gonadotropin, and pregnancy-associated plasma protein A in singleton pregnant women, and performed non-invasive prenatal testing for women with risks of trisomy 21 between 1:500 and 1:300. Invasive diagnostic testing was performed for women with positive or failed non-invasive prenatal testing result and in the high-risk group of this screening method. The direct costs were compared between this strategy and the non-invasive prenatal testing which alone used as first-line screening for all pregnant women. Results: Among 25,155 singleton pregnant women who underwent screening, 24,361 were available for analysis, of these, 194 cases underwent non-invasive prenatal testing. Among the 24,361 women, 39, 19, and 7 had trisomies 21, 18 and 13, respectively. The use of this strategy could potentially detect approximately 94.87% of trisomy 21 cases, 100% of trisomy 18 cases, and 100% of trisomy 13 cases, with false-positive rates of 2.49%, 0.41%, and 0.49%, respectively. The overall detection rate and overall false-positive rates were 96.92% and 2.52%, respectively. The detection rate was 100% in the advanced age group and 94.12% in the general age group. Additionally, structural abnormalities were detected in 137 fetuses, and 44 fetuses had other chromosomal abnormalities. The total cost of this strategy was $3,730,843.30, and the cost per person tested was $153.15. The total cost of using non-invasive prenatal testing as the first-line strategy would be $6,813,387.04 and the cost per person tested was $279.68. Conclusions: Our strategy is an efficient and cost-effective approach for detecting major trisomies and identifying more fetuses with a potential abnormality. Therefore, this strategy is a valuable screening method and highly feasible in the clinical setting. [ABSTRACT FROM AUTHOR]

To analyze the reasons for refusal of aneuploidy screening in a multicultural Middle Eastern population. The study included patients delivering in a university hospital, who had refused aneuploidy screening during their pregnancy. We evaluated through a questionnaire submitted during the postpartum period the sociodemographic characteristics, beliefs, attitudes, and the main reason underpinning their choice. Religious, ethical, and financial factors, personal beliefs, medical information, perceived media information, and familial input were assessed through a Likert scale. Our pilot study included 70 patients. The main reason (33 %) was the refusal to terminate pregnancy if the screening tests ultimately led to a diagnosis of aneuploidy. Lack of adequate information on the availability and benefits of this screening method (28 %), religious beliefs (17 %), in addition to other minor reasons such as financial considerations, familial recommendations, late pregnancy follow-ups, and media influence were also identified as contributing factors. Aneuploidy screening is routinely offered to couples, with varying uptake rates observed worldwide. Sufficient information on prenatal screening and diagnosis should be provided to all pregnant women, presenting all available options, thus enabling them to make a free and informed choice during their pregnancy. [ABSTRACT FROM AUTHOR]

The phenotype of SCA patients are diversities, make prenatal counseling and parental decision‐making following the prenatal diagnosis of SCA more complicated and challenging. NIPT has higher sensitivity and specificity in screening trisomy 21 syndrome, but the effectiveness of NIPT in detecting SCA is still controversial. This study is a large‐scale retrospective cohort of positive SCA screened from unselected singleton pregnancies by non‐invasive prenatal testing (NIPT) from a single prenatal center of a tertiary hospital. Clinical information, indications, diagnostic results, ultrasound findings, pregnancy determinations, and follow‐up were reviewed and analyzed. 596 cases of SCA positive were screened out of 122 453, giving a positive detection rate of 0.49%. 510 cases (85.6%) conducted with amniocentesis to detect fetal chromosome, of which 236 were confirmed as true positive of SCA with PPV of 46.3% (236/510). Of the 236 cases confirmed as true positive SCA, 114 cases (48.3%)chose to terminate the pregnancy (93.0%, 65.3%, 15.4% and 10.9% for 45,X, 47,XXY, 47,XXX and 47,XYY, respectively), 122 cases (51.7%) elected to continue the pregnancy. In conclusions, NIPT as a first‐tier routine method for screening autosomal aneuploidies, also could play an important role in screening SCA. Low‐risk pregnant women are the main indication for the detection of SCA as NIPT test provides to non‐selective population. For 47,XXX and 47,XYY with mild phenotype, couples would like to continue the pregnancy. But for 45,X and 47,XXY, parents apt to terminate pregnancy no matter ultrasound abnormalities were found or not. [ABSTRACT FROM AUTHOR]

The use of race in maternal serum screening is problematic because race is a social construct rather than a distinct biological classifier. Nevertheless, laboratories offering this testing are encouraged to use race-specific cutoff values for maternal serum screening biomarkers to determine the risk of fetal abnormalities. Large cohort studies examining racial differences in maternal serum screening biomarker concentrations have yielded conflicting results, which we postulate may be explained by genetic and socioeconomic differences between racial cohorts in different studies. We recommend that the use of race in maternal serum screening should be abandoned. Further research is needed to identify socioeconomic and environmental factors that contribute to differences in maternal serum screening biomarker concentrations observed between races. A better understanding of these factors may facilitate accurate race-agnostic risk estimates for aneuploidy and neural tube defects. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Combined first‐trimester screening (cFTS) for fetal anomalies involves maternal serum screening for biochemical markers and measurement of the nuchal translucency (NT) by ultrasound. Noninvasive prenatal screening (NIPS) analyses cell‐free DNA present in a maternal blood sample for presence of fetal chromosomal aneuploidies. Aims: To compare NIPS with cFTS as frontline screening in a public hospital in Australia. Materials and methods: Women were offered NIPS in addition to the usual cFTS routinely offered to all women at a public hospital in NSW, Australia. The cFTS sample was collected at ten weeks' gestation and the NIPS sample at 12 weeks' gestation at the ultrasound appointment. Results: In a low‐risk population of 997 women, frontline NIPS had a screen‐positive rate of 0.5% (5/997) vs 4.2% (42/997) with cFTS. cFTS correctly identified one trisomy 21 case and one trisomy 18 case; however, there were two trisomy 18 false negatives. Of five positive NIPS calls, four were correctly identified as trisomy 21 (one) and trisomy 18 (three); there were no NIPS false negatives. Overall, the false‐positive rate with NIPS was 0.1% vs 4.0% by cFTS. Conclusions: The lower screen‐positive rate with NIPS for common trisomies was a result of the significantly lower false‐positive rate with NIPS. Consequently, NIPS as first‐line screening, even if funded by the hospital, may provide cost savings. We believe NIPS should be used from ten weeks' gestation in conjunction with morphology ultrasound for routine first‐trimester prenatal management. [ABSTRACT FROM AUTHOR]

Noninvasive prenatal testing (NIPT) for the sex chromosome aneuploidies (45,X, 47,XXY, 47,XXX, and 47,XYY) differs significantly from that for the autosomal aneuploidies (trisomy 13, 18, and 21). As a group, sex chromosome aneuploidies occur more commonly (1/400) than any one isolated autosomal aneuploidy, the phenotypic variation is greater, the role of mosaicism more challenging, and the positive predictive value of a high-risk NIPT result is substantially lower. These considerations should be identified during pretest counseling, the inclusion of sex chromosome testing offered separately, and the differences from autosomal aneuploidy NIPT clearly delineated. [ABSTRACT FROM AUTHOR]

Background: Fetal exposure to maternal anxiety is associated with low birth weight and maternal stress may be led to constriction of uterine arteries. This study compared the relation of anxiety and uterine artery doppler flow indices in pregnant women with the high and low-risk of Down syndrome. Materials and Methods: This prospective cohort study was conducted among pregnant women in the second trimester that were classified as having a high or low risk according to their prenatal aneuploidy screening outcome. The high risk group underwent amniocentesis. Anxiety was initially assessed using the Spielberger State-Anxiety Inventory (STAI) and uterine artery blood flow indices were evaluated 2 times for the both groups. For the high-risk group first: immediately before amniocentesis and second: after two weeks follow up, when receiving the karyotype results and for the low-risk group in the first admission and two weeks later. Results: Totally, 375 pregnant women participated in our study that sorted into 2 risk populations based on the aneuploidy screening test, low-risk=176 and high-risk women=199. The high-risk group for Down syndrome amniocentesis showed abnormal results in the 23 cases (23/199). The mean state (P=0.003) and trait (P=0.033) of the Anxiety Inventory scores were significantly different between the groups. Baseline uterine artery indices were no significant difference between the groups. Baseline Uterine artery indices in the high-risk group was significantly different with follow-up (in both positive-amniocentesis and negative amniocentesis sub-groups) indices. Also, there was a weak and significant correlation in the uterine resistance index and STAI scores (P=0.008, r=0.137) during the follow-up period. Conclusion: All pregnant women experienced high level anxiety, especially in the high-risk group that may reduce after confirmation of prenatal aneuploidy screening test and also affects the Doppler indices. For all pregnant women; Stress management and emotional support training is recommended before and during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Trisomy 13 (T13) and sex chromosome aneuploidies (SCA) are the vital causes of congenital malformations. This study was performed to identify the T13 and SCA with screening tests in the first trimester of pregnancy. Materials and Methods: In this cross-sectional study, first-trimester combined screening was conducted on 2100 pregnant women referred to Narges Genetics Laboratory, Ahvaz, Iran. Evaluating the first trimester screening tests, including nuchal translucency (NT), crown--rump length (CRL) and pregnancy-associated plasma protein-A (PAPP- A), and free beta of human chorionic gonadotropin (fβhCG) was performed. For a definitive diagnosis of T13 and SCA syndrome, fetal karyotype was evaluated. Results: The average NT and CRL in high-risk group for T13 were 5.96 mm and 61.7 mm respectively and in high- risk groups for SCA were 3.7 mm and 75.9 mm, respectively. Significant correlation was observed among NT, CRL and T13, SCA (P<0.05). The average serum fβhCG and PAAP-A levels in high-risk group for T13 were 0.42 and 0.31, respectively. Significant correlation was observed between decrease fβhCG, PAPP-A and T13 levels and increase fβhCG levels and SCA levels (P<0.05). No Significant correlation was observed between PAPP-A levels and SCA levels (P>0.05). Conclusion: Using special software and karyotype testing, the prenatal screening tests based on the maternal age and gestational age in the first trimester of pregnancy may determine the major risk of fetal chromosomal abnormalities. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate fetal ultrasonographic findings and perinatal outcomes in pregnancies with fetal trisomy 18, trisomy 13, and triploidy. Material and Methods: Pregnancies diagnosed as fetal trisomy 18, trisomy 13, and triploidy at a tertiary center between January 2013 and January 2020 were included in the study. Maternal ages, gestational ages at the time of diagnosis, antenatal follow-ups, prenatal fetal ultrasonography reports, perinatal outcomes, whether the pregnancies resulted in live births, and the outcomes of the newborns were obtained. Results: A total of 104 cases (trisomy 18 [n=74, 71.2%], trisomy 13 [n=21, 20.2%], and triploidy [n=9, 8.6%]) were included in the study, and pregnancy was terminated in 79 (76.0%) of the cases. The most common anomaly was cardiac malformations in fetuses with trisomy 18 and triploidy, and central nervous system anomalies in fetuses with trisomy 13. Of 25 patients who preferred to continue the pregnancy, nine (36.0%) resulted in miscarriage and 13 (52.0%) resulted in fetal death. In all three pregnancies that resulted in live births, newborns died in the early neonatal period. Conclusion: Most fetuses with trisomy 18, trisomy 13, and triploidy have severe fetal malformations. In cases where the pregnancy is not terminated, the risk of fetal loss is high. Patients with the expectation of self-termination should be informed that this loss may not occur until the third trimester and that pregnancy may result in a live birth. [ABSTRACT FROM AUTHOR]

Soft markers are sonographic structural, nonspecific signs with little pathological significance, often transient, usually considered as normal variants. However, they may also be associated with chromosomal abnormalities. The most widely examined soft markers include absent or hypoplastic nasal bone (NB), intracardiac echogenic focus (IEF), ventriculomegaly (VM), thickened nuchal fold (NF), choroid plexus cyst (CPC), echogenic bowel, short long bones, and urinary tract dilation (UTD). Although the use of noninvasive prenatal testing (NIPT) has been spreading quickly in maternal–fetal medicine, it is not a diagnostic test and it still remains unavailable or cost-prohibitive for most of the population in many countries. After normal screening test results in the first trimester, there is no uniform consensus regarding the clinical significance of isolated soft markers for aneuploidy. Nowadays, the search for soft markers in an ultrasound is still part of clinical evaluation, and the interpretation of these findings is often a matter of debate. In the present review, we summarize the recent literature about the role of soft markers in the era of NIPT and propose an overview of the different clinical guidelines. [ABSTRACT FROM AUTHOR]

Cell-free DNA is an advancing technology with increasing applications in screening, diagnosis, and treatment for several disease processes. The shared physiologic, genetic, and epigenetic characteristics of placental physiology and tumor development have become apparent to both clinicians and researchers. Maternal malignancy has been reported as a cause of false-positive prenatal cell-free DNA screening results. The detection of multiple aneuploidies or a single autosomal monosomy increases the chance for an underlying maternal malignancy when the result is discordant with fetal diagnostic testing. There is currently no consensus guideline on counseling and evaluation of patients with concern for malignancy from cell-free DNA testing. Furthermore, laboratories differ significantly in reporting policies, terminology, and in reporting strategies and methods used for unexpected or incidental findings. The ordering practitioner is therefore tasked to understand the policies of their laboratory of choice to provide adequate pretest and posttest genetic counseling. In pretest counseling, the potential for incidental or unexpected findings or nonreportable results should be explained. With an abnormal, unanticipated, or nonreportable result, posttest counseling should include a description of possible fetal or maternal diagnoses, including malignancy. Health care professionals should explain options for further evaluation and management, including a recommendation for fetal diagnostic testing. The medical workup recommended by various authors to evaluate cancer risk is based on consensus, experience, and expert opinion. These strategies should incorporate the patient's desire for information, cost, and family and personal medical history. Ongoing research and multi-disciplinary collaboration in this area is critical to identify best practices in management of complex results from this increasingly common screening test. [ABSTRACT FROM AUTHOR]

• Pregnancies with preimplantation genetic testing for aneuploidy (PCT-A) follow standard prenatal screening. • Specificity of the combined screening test decreases in pregnancies conceived through IVF with PGT-A. • Maternal age is the main contributor to risk of trisomy 21 in pregnancies conceived through IVF with PGT-A. How does first-trimester aneuploidy screening perform in pregnancies achieved through IVF with preimplantation genetic testing for aneuploidy (PGT-A) in a medical setting? This retrospective cohort study was undertaken in a single tertiary care centre between January 2013 and June 2022. In total, 20,237 women had prenatal follow-up at the study centre and were included in the study. The women were divided into three groups: singleton pregnancies conceived through the transfer of a PGT-A-screened euploid embryo (n = 510); singleton pregnancies conceived through IVF without PGT-A (n = 3291); and singleton pregnancies conceived naturally (n = 16,436). The conventional combined screening test for pregnancies conceived through IVF with PGT-A had specificity of 91%; sensitivity could not be calculated as there were no cases of fetal aneuploidy in this group. In 89.1% of pregnancies conceived through IVF with PGT-A with high risk for trisomy 21, 18 or 13, the result was related to advanced maternal age (>35 years at time of screening). The current screening strategy for trisomies 21, 18 and 13 can generate unnecessary tests in pregnancies achieved through IVF with PGT-A. A new protocol is needed for these patients, with greater weight given to ultrasound markers. [ABSTRACT FROM AUTHOR]

BACKGROUND: Nuchal translucency (NT) is an important finding of early fetal anatomy scan because of the association with genetic and structural anomalies. Enlarged nuchal translucency can be easily detected even without measurement on fetal anatomy scan as a neck pathology. Because of demanding criteria for measurning NT in established prenatal aneuploidy screening we came with an idea of improvement and simplification with availabe methods. The aim of this study is to compare established screening methods with new model of screening composed of fetal anatomy scan with integrated nuchal translucency and combination of PAPP-A and fβhCG. METHODS: A prospective one center study analyzed a total of 351 pregnancies between January 2017 and December 2020. Sonographic measurement of NT and fetal anatomy scan (FAS) were performend with biochemical testing from blood sample in the first trimester. Combined screening and fetal anatomy scan was performed. Patients with a pathological screening or with structural defects underwent an invasive procedure. In patient with positive screenining who missed the first trimester invasive procedure, amniocentesis was performed. Fetuses were divided into two groups according to positive or negative karyotype and to calculate sensitivity and specificity of screening methods. From statistical methods regression analysis, significance p of individual predictor, sensitivity and specificity with graphic drawing of ROC charts were used. Data were analyzed using statistical tools of Microsoft Excel 365 and BESH stat. RESULTS: Four models for aneuploidy screening were tested. 1) Model of „Age at the time of diagnosis" was slightly significant predictor with insignificant odds ratio (P=0.04, OR=1). 2) Model of„ First trimester biochemical screening" (age, free beta human chorionic gonadotropine -- fβhCG and pregnancy associated plasmatic protein A -- PAPP-A) were significant (P=0.0001; LR=21) with sensitivity of 87.5 % and specificity of 65.7 %. 3) Model of „First trimester combined test“ (age of patients at the time of diagnosis, fβhCG, PAPP-A, NT) was significant (P=7.9 x10-14, LR=67, sensitivity 87 %, specificity 80 %). 4) Model of „Fetal anatomy scan with biochemistry" (structural abnormality finding with combination including age, fβhCG and PAPP-A) was significant (P=4.9x10-18, LR=87, sensitivity 95 %, specificity 80 %). CONCLUSION: Fetal anatomy scan combined with age, fβhCG and PAPP-A has the highest sensitivity and specificity for both, the detection of fetal aneuploidies and structural abnormalities. Our study shows that fetal anatomy scan is the best possible option for first trimester diagnostics (Tab. 4, Fig. 5, Ref. 16). Text in PDF www.elis. sk [ABSTRACT FROM AUTHOR]

Objectives  Our primary objective was to evaluate how prenatal diagnosis of a major fetal structural anomaly and resulting pregnancy outcome affected postpartum depression risk, as assessed by the Edinburgh Postnatal Depression Scale (EPDS). Secondary objectives were to review the rate of mental health follow-up and subsequent diagnosis of postpartum depression in screen-positive women. Study Design  Singleton pregnancies with prenatal diagnosis of one or more major fetal structural anomalies were ascertained from prospectively maintained databases that included perinatal outcomes and subsequent EPDS responses from January 2010 to May 2018. EPDS scores of 13 or higher were considered positive and prompted referral for mental health follow-up, which was verified by medical record review. Statistical analyses were performed using Student's t -test, χ 2 , and odds ratios (ORs) with p  < 0.05 considered significant. Results  A total of 1,306 women had a prenatal diagnosis of one or more major fetal structural anomalies, 896 (68%) also had a postpartum EPDS screening, and 82 (9.2%) screened positive. Positive EPDS screening was more common with anomalies of multiple organ systems (16.5 vs 7.8%, p  = 0.002) and aneuploidy (17.1 vs 9.3%, p  = 0.02). Pregnancies complicated by fetal death, neonatal death, and termination for anomaly were significantly more likely to screen positive than those with neonatal survival to discharge (OR, 3.1 [95% confidence interval [CI], 1.6–6.2], 3.0 [95% CI, 1.5–5.8], and 4.4 [95% CI, 2.1–8.9], respectively, p ≤ 0.002). Of the 35 (43%) screen-positive women who attended follow-up appointments with mental health providers, 18 (51%) were diagnosed with a depressive disorder, accounting overall for 22% of those with a positive EPDS screen. Conclusion  Among women with a prenatal diagnosis of a major fetal structural anomaly, those experiencing a perinatal loss or pregnancy termination have an increased risk of positive EPDS screen result compared with who have a neonate surviving to discharge. A depressive disorder was diagnosed postpartum in 22% of these women with a positive EPDS screen. Our findings highlight the mental health needs in this vulnerable population. Key Points Adverse pregnancy outcome increased positive EPDS screen risk among women with prenatal anomalies. A depressive disorder was diagnosed postpartum in 22% of such women with a positive EPDS screen. Our findings highlight the mental health needs in this vulnerable population. [ABSTRACT FROM AUTHOR]

The American College of Obstetrics & Gynecology (ACOG) recommends offering aneuploidy screening to all pregnant women. Obesity and diabetes are not associated with an increased risk of aneuploidy; however, they can complicate and compromise testing options. As the prevalence of obesity and diabetes, or "diabesity" increases, counseling women regarding potential limitations in testing performance of aneuploidy screening is of paramount importance. This chapter reviews options for aneuploidy screening for women with diabesity including sonography/nuchal translucency, serum analyte screening, and cell-free DNA. Potential challenges associated with diagnostic testing with amniocentesis and chorionic villus sampling in women with obesity are also discussed. [ABSTRACT FROM AUTHOR]

Aim: Analyze if the evaluation of aberrant right subclavian artery in the prenatal echography has improved the detection of chromosomal, genetic and/or morphological abnormalities in our population. Methods: Descriptive, observational, cross‐sectional study of the cases of aberrant right subclavian artery diagnosed in our Prenatal Diagnosis Unit between January of 2011 and December of 2018. Results: Two hundred and fifty‐seven cases of aberrant right subclavian artery were diagnosed and among them, 179 were considered isolated cases and thus were confirmed after birth. The detection of aberrant right subclavian artery did not improve itself neither the diagnosis of trisomy 21 in the second trimester of pregnancy nor other chromosomal or genetic abnormalities, including the not isolated cases. There were two cases of trisomy 21 diagnosed in the second trimester that presented major sonographic disorders and an inadequate examination during the first trimester. When aberrant right subclavian artery was associated with soft markers of aneuploidy in the second trimester, any case was a trisomy 21. Aberrant right subclavian artery seems to be associated with some minor and major heart defects, especially ventriculoseptal defect and aneurismatic ductus, and in some cases, also with clubfeet. Conclusion: When an adequate screening of aneuploidies and a thorough ultrasound have been performed during the first trimester, aberrant right subclavian artery hardly helps to perform other diagnosis in the second trimester. [ABSTRACT FROM AUTHOR]

Down syndrome screening has been available within clinical practice for over 50 years within which time significant innovation and exciting new advances have improved the accuracy, safety, and choice for women who are considering antenatal screening for Down syndrome. The UK National Screening Committee is responsible for setting the national standards regarding screening and it has steadily and consistently directed and facilitated an increase in the detection rate whilst minimising the screen positive rate. This has reduced the number of false positive results and consequently the number of invasive diagnostic procedures and their related miscarriages. Non-invasive pre-natal testing (NIPT) using cell free DNA is a rapidly evolving field and it will soon be incorporated into the existing NHS antenatal screening programme for aneuploidy. It will be offered to women who receive a 'high risk' result following current screening methods (combined test or quadruple test), and will further reduce the number of invasive tests performed, whilst maintaining current detection rates. [ABSTRACT FROM AUTHOR]

Eight years have passed since noninvasive prenatal testing (NIPT) was clinically evaluated and data on NIPT for trisomy 21, 18 and 13 were collected. The data revealed that NIPT is more accurate than conventional first‐trimester screening. However, there is still insufficient data regarding the clinical use of NIPT results in detecting sex chromosome aneuploidies or whole‐genome regions. NIPT is already being used as a clinical screening method globally. However, it is an unconfirmed diagnostic test and the results must be interpreted with caution as they may yield false negatives, false positives or inconclusive results. Therefore, the aim of this review is to highlight the current status of information, including the different methodologies, shortcomings and implications, regarding NIPT after its adoption worldwide. It is important to include genetic counseling when implementing NIPT. Going forward, the knowledge obtained to date, including the associated shortcomings, must be considered in evaluating the effectiveness of NIPT in detecting genetic abnormalities. [ABSTRACT FROM AUTHOR]

Cell‐free DNA screening has quickly become established in Australia as an accurate – albeit costly – prenatal screening test for trisomy 21, 18 and 13. It is also commonly used for the detection of sex chromosome abnormalities. The increasing number of prenatal screening pathways available to women has increased the complexity of pretest counselling. Concurrent advances in diagnostic testing with the widespread use of chromosomal microarrays create further challenges for the continuing education of clinicians and health consumers. This article aims to answer common clinical questions in this rapidly evolving field and complements the recently updated Royal Australian and New Zealand College of Obstetricians and Gynaecologists Statement on Prenatal Screening for Fetal Chromosome and Genetic Conditions. [ABSTRACT FROM AUTHOR]

The discovery of cell free fetal DNA in maternal plasma has stimulated a rapid development of non-invasive prenatal testing. The recent advent of massively parallel sequencing has allowed the analysis of circulating cell-free fetal DNA to be performed with unprecedented sensitivity and precision. It is thus expected that plasma DNA-based non invasive prenatal testing will play an increasingly important role in the future of obstetric care. The present review summarizes recent advances in non invasive prenatal testing using cell free fetal DNA. The importance of genetic counseling, the current guidelines for the use of cffDNA screening in pregnancy, as well as specific maternal conditions that can affect the performance of non invasive prenatal testing are also discussed in this review. [ABSTRACT FROM AUTHOR]

Objective: To describe the changes in women's choices for prenatal testing after the introduction of nationwide health insurance coverage for non-invasive prenatal testing (NIPT) in Switzerland.Methods: The present retrospective study reviewed data from all women with singleton pregnancies who presented at the prenatal unit of Basel University Hospital, Switzerland, for first-trimester screening between July 15, 2014, and December 31, 2015. Women were divided into three categories according to their risk for aneuploidy, and the uptake of NIPT in the period before and after the introduction of the nationwide coverage for NIPT was compared.Results: Overall, 887 women were included in the study: 573 screens were carried out before (group 1) and 314 after (group 2) the introduction of insurance coverage for NIPT. In group 1, 53 (9.2%) had NIPT as compared with 72 (22.9%) in group 2. Among women with intermediate risk for aneuploidies and basic insurance coverage, NIPT increased by 56% (12/88 [14%] vs 32/46 [70%]; P<0.001).Conclusion: There was a notable increase in the uptake of NIPT; uptake was most significant among women with basic health insurance and intermediate risk for aneuploidy. [ABSTRACT FROM AUTHOR]

Single‐nucleotide polymorphism (SNP)‐based non‐invasive prenatal testing (NIPT) can currently predict a subset of submicroscopic abnormalities associated with severe clinical manifestations. We retrospectively analyzed the performance of SNP‐based NIPT in 80 449 referrals for 22q11.2 deletion syndrome and 42 326 referrals for 1p36, cri‐du‐chat, Prader‐Willi, and Angelman microdeletion syndromes over a 1‐year period, and compared the original screening protocol with a revision that reflexively sequenced high‐risk calls at a higher depth of read. The prevalence of these microdeletion syndromes was also estimated in the referral population. The positive predictive value of the original test was 15.7% for 22q11.2 deletion syndrome, and 5.2% for the other 4 disorders combined. With the revised protocol, these values increased to 44.2% for 22q11.2 and 31.7% for the others. The 0.33% false‐positive rate (FPR) for 22q11.2 deletion syndrome decreased to 0.07% with the revised protocol. Similarly, the FPR for the other 4 disorders combined decreased from 0.56% to 0.07%. Minimal prevalences were estimated to be 1 in 1255 for 22q11.2 deletion syndrome and 1 in 1464 for 1p36, cri‐du‐chat, and Angelman syndromes combined. Our results show that these microdeletions are relatively common in the referral population, and that the performance of SNP‐based NIPT is improved with high‐depth resequencing. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to determine whether there is a relationship between first trimester serum pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fβhCG) MoM values and placenta accreta in women who had placenta previa.Study Design: A total of 88 patients with placenta previa who had first trimester aneuploidy screening test results were enrolled in the study. Nineteen of these patients were also diagnosed with placenta accreta. As probable markers of excessive placental invasion, serum PAPP-A and fβhCG MoM values were compared in two groups with and without placenta accreta.Results: Patients with placenta accreta had higher statistically significant serum PAPP-A (1.20 versus 0.865, respectively, p = 0.045) and fβhCG MoM (1.42 versus 0.93, respectively, p = 0.042) values than patients without accreta.Conclusions: Higher first trimester serum PAPP-A and fβhCG MoM values seem to be associated with placenta accreta in women with placenta previa. Further studies are needed to use these promising additional tools for early detection of placenta accreta. [ABSTRACT FROM AUTHOR]

From January 1st 2013 to August 31st 2016, 24408 pregnant women received the first trimester Combined test and contingently offered second trimester maternal serum screening to identify those women who would most benefit from invasive prenatal diagnosis (IPD). The screening was based on first trimester cut-offs of ≥1:30 (IPD indicated), 1:31 to 1:899 (second trimester screening indicated) and ≤1:900 (no further action), and a second trimester cut-off of ≥1:250. From January 2014, analysis of fetal cells from peripheral maternal blood was also offered to women with positive screening results. For fetal Down syndrome, the overall detection rate was 96.8% for a false-positive rate of 2.8% resulting in an odds of being affected given a positive result (OAPR) of 1:11, equivalent to a positive predictive value (PPV) of 8.1%. Additional chromosome abnormalities were also identified resulting in an OAPR for any chromosome abnormality of 1:6.6 (PPV 11.9%). For a sub-set of cases with positive contingent test results, FISH analysis of circulating fetal cells in maternal circulation identified 7 abnormal and 39 as normal cases with 100% specificity and 100% sensitivity. We conclude that contingent screening using conventional Combined and second trimester screening tests is effective but can potentially be considerably enhanced through the addition of fetal cell analysis. [ABSTRACT FROM AUTHOR]

Down screening has been available within clinical practice for over 50 years during which time significant innovation and exciting new advances have improved the accuracy and safety of screening, and improved choice for women who are considering antenatal screening for Down syndrome. The UK National Screening Committee is responsible for setting the national standards regarding screening and it has steadily and consistently directed and facilitated an increase in the detection rate whilst minimising the screen positive rate of Down syndrome screening. This has reduced the number of false positive results and consequently the number of invasive diagnostic procedures and their related miscarriages. Non-invasive pre-natal testing (NIPT) using cell free DNA is a rapidly evolving field and it will soon be incorporated into the existing NHS antenatal screening programme for aneuploidy. It will be offered to women who receive a ‘high risk’ result following current screening methods (combined test or quadruple test), and will further reduce the number of invasive tests performed, whilst maintaining current detection rates. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A meta-analysis published in the November 2022 issue suggests that preimplantation genetic testing for aneuploidies (PGT-A) in in vitro fertilization has beneficial effects on the live-birth rate in women of advanced maternal age.[1] Surprisingly, this finding seems to contradict several previous publications, including a recent Cochrane meta-analysis on the same topic. Preimplantation genetic testing for aneuploidy with comprehensive chromosome screening in patients undergoing in vitro fertilization: a systematic review and meta-analysis. [Extracted from the article]

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. [ABSTRACT FROM PUBLISHER]

Prenatal aneuploidy screening has changed dramatically in recent years with increases in the types of chromosomal abnormalities reliably identified and in the proportion of aneuploid fetuses detected. Initially, screening was available only for trisomies 21 and 18 and was offered only to low-risk pregnancies. Improved detection with the quadruple- and first-trimester multiple marker screens led to the option of aneuploidy screening for women 35 years of age and older. Cell-free DNA tests now screen for common autosomal trisomies and sex chromosome aneuploidies. Cell-free DNA screening is particularly effective in older women because of higher positive predictive values and lower false-positive rates. Integrated first- and second-trimester multiple marker tests provide specific risks for trisomies 21, 18, and possibly 13, and may detect an even wider range of aneuploidies. Given current precision in risk assessment, based on maternal age and preferences for screening or diagnostic tests, counseling has become more complex. This review addresses the benefits and limitations of available aneuploidy screening methods along with counseling considerations when offering them. [ABSTRACT FROM AUTHOR]

Objective: To analyse population-based trends over the entire history of prenatal testing for aneuploidy.Design: Retrospective analysis of state-wide data sets.Setting: Australian state of Victoria with ~70 000 annual births.Population: All pregnant women undergoing invasive prenatal testing at <25 weeks' gestation from 1976 to 2013.Methods: Analysis of three state-wide data sets: (1) Prenatal diagnosis data set of 119 404 amniocenteses and chorionic villus samplings from 1976 to 2013; (2) central serum screening laboratory data set from 1996 to 2013; (3) government birth statistics from 1976 to 2013.Main Outcome Measures: Annual numbers and uptake rates of invasive prenatal tests and serum screening, indications for invasive prenatal testing, prenatal diagnoses of aneuploidy, diagnostic yield of invasive tests.Results: Annual numbers of invasive prenatal tests climbed steadily from 1976, then declined from 2000. In 2013, the number of invasive prenatal tests was the lowest in 25 years, while the number of trisomy 21 diagnoses was the highest ever recorded. Annual uptake of serum screening climbed from 1.6 to 83% over 1996-2013. Results from 2013 showed a high diagnostic yield (15.8%) for a low rate of invasive testing (3.4% of births). Over four decades, the number of invasive procedures performed for each diagnosis of major chromosome abnormality declined from 100 to six.Conclusions: This study demonstrates historic reductions in the proportion of women undergoing invasive testing and dramatic improvements in diagnostic yield. Monitoring the impact of new prenatal technologies on this progress remains an important research priority.Tweetable Abstract: Invasive prenatal testing has reached historic lows due to dramatic improvements in Down syndrome screening. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical performance of non-invasive prenatal testing (NIPT) in detecting fetal copy number variants (CNVs).Methods: NIPT of cell-free fetal DNA was performed retrospectively, using stored maternal plasma, at an average gestational age of 21.1 weeks in 117 pregnant women who had previously undergone invasive prenatal testing for chromosome microarray analysis (CMA). Among the fetal samples tested by CMA, 18 had positive results (CNVs > 1 megabase (Mb)) and 99 had negative results (CNVs < 1 Mb or without CNVs detected). The results of NIPT and CMA were then compared.Results: In the 11 CMA-positive samples with CNVs > 5 Mb, the detection rate of CNVs was 90.9%; the one case missed by NIPT had a fetal fraction of 4.7%. For the other seven CMA-positive samples with CNVs < 5 Mb, the detection rate was 14.3%; only one case with a 2.82-Mb duplication was detected, with a fetal fraction of 26.7%. For 35.7% (5/14) of CNVs detected by both NIPT and CMA, the differences in fragment length were within ± 1 Mb. In this study, the overall sensitivity and specificity of NIPT for detecting CNVs > 1 Mb were 61.1% and 95.0%, respectively, with a false-positive rate of 5.0%.Conclusions: Our results demonstrate that NIPT for common aneuploidies can detect fetal CNVs > 5 Mb with high sensitivity, provided that fetal fraction is high enough, without increasing sequencing depth. The detection power of NIPT is determined mostly by fetal fraction and CNV size. A positive NIPT screening result for CNVs must be interpreted with caution and validated by additional diagnostic study. [ABSTRACT FROM AUTHOR]

Background: Several countries today struggle with suboptimal performances in many aspects of the fetal aneuploidy screening process and consider introducing non-invasive prenatal screening (NIPT) as a solution. In this study, costs and benefits of different scenarios for contingent NIPT screening in Belgium are evaluated with respect to partial redistribution of the national screening budget into quality improving measures for those screening activities that will be maintained when full NIPT screening is implemented.Methods: Data from the Belgian National Institute for Health and Disability Insurance and the Study Centre for Perinatal Epidemiology were used in modeled calculations of medical and economic impact of NIPT after prior conventional screening (1) at thresholds 1:300 and 1:600, and (2) at current and improved screening sensitivity.Results: Contingent NIPT screening under current screening conditions would maintain today's 7.9(0)/000 live birth prevalence of Down syndrome (LBPD) at an 11% reduction of overall short-term costs. Lowering the screening threshold to 1:600 or increasing sensitivity by 10% would reduce LBPD to 7(0)/000 at a maximum 3% increase of overall short-term costs.Conclusion: Today, in Belgium and in many other countries, full NIPT screening is considered too expensive for immediate introduction into the national fetal aneuploidy screening program. Contingent NIPT screening is both clinically and economically beneficial. A temporary contingent NIPT protocol allows for reinvesting economic savings into optimization of those screening aspects, which are to be maintained in parallel to full NIPT screening. [ABSTRACT FROM AUTHOR]

Non-invasive prenatal testing (NIPT) through the analysis of cell free (cf)DNA is revolutionizing prenatal screening for fetal aneuploidy. Current methods used in clinical practice include shotgun massively parallel sequencing (s-MPS); targeted (t-MPS); and an approach that takes advantage of single nucleotide polymorphism (SNP) differences between mother and fetus. Efficacy of cfDNA testing for the common autosomal trisomies far exceeds that of conventional screening. Depending on the methodology used, reasons for discordancy between cfDNA results and fetal karyotype can include true fetal mosaicism, confined placental mosaicism, presence of a maternal karyotype abnormality, insufficient counting due to low fetal fraction, and a vanishing twin. Among the possible cfDNA strategies a Primary test has the highest performance but is expensive, while a Contingent cfDNA test can achieve high performance at a relatively low cost. Practicalities to be considered in the provision of testing include pretest counseling about the scope and accuracy of the testing, the interpretation of results when there is a low fetal fraction and follow-up studies for positive test results. The role of first trimester nuchal translucency measurement and conventional biochemical testing needs to be reassessed in the context of the use of cfDNA. [ABSTRACT FROM AUTHOR]

Background: Despite the non-invasive nature of non-invasive prenatal testing (NIPT), there is still a need for a separate informed consent process before testing. The objectives of this study are to assess (a) knowledge and preferences of Chinese women in a major public hospital in Hong Kong who underwent NIPT, and (b) whether their knowledge and preferences differ depending on womens' characteristics and sources of information. Methods: Setting: prenatal diagnosis and counselling clinic. Between February 2012 and September 2013, a questionnaire survey was distributed to all women who underwent NIPT after positive aneuploidy screening. As a pilot study, ten knowledge questions were designed based on the rapid response statement on Prenatal Detection of Down Syndrome using Massively Parallel Sequencing from the International Society for Prenatal Diagnosis in 2011. The source of women's knowledge and their preferences were also evaluated. While conventional screening was publicly funded, NIPT was not. Differences between subgroups were compared using chi square tests and logistic regression analysis. Results: Of 152 women who underwent NIPT, 135 (88.8 %) completed their questionnaires. More than 90 % of women recognised the possibility of false positive and false negative results. Slightly more than 70 % of women knew the inferior sensitivity of NIPT compared to an invasive test, and the possibility of an uninformative test result, but were not aware of the complicated aspects of NIPT. Pregnant women with an advanced level of education or those who underwent NIPT before 15 weeks provided answers that was more accurate by around 10-20 % in two to three knowledge questions than those without. These associations were confirmed by multivariate logistic regression analysis. The women received information on NIPT largely from their private doctors (47.4 %) and web (41.5 %). In their future pregnancies, more women would opt for NIPT (a self-financed item) after positive screening ('free' in a public hospital) (57.8 %) than as a primary screening (30.4 %). Conclusions: It is feasible to use a questionnaire based on the ISPD statement on NIPT to assess women's knowledge of the test. The Chinese women who underwent NIPT recognised the limitations, but did not understand the complicated aspects. More information should be provided by health care professionals in order to facilitate an informed choice by patients. More women preferred NIPT as a contingent test than as a primary screening probably because of its high cost. [ABSTRACT FROM AUTHOR]

Objective: To evaluate non-invasive prenatal testing (NIPT) of cell-free DNA (cfDNA) as a screening method for major chromosomal anomalies (CA) in a clinical setting. Methods: From January to December 2013, Panorama™ test or Harmony™ prenatal test were offered as advanced NIPT, in addition to first-trimester combined screening in singleton pregnancies. Results: The cohort included 333 pregnant women with a mean maternal age (MA) of 37 years who underwent testing at a mean gestational age of 14.6 weeks. Eighty-four percent were low-risk pregnancies. Results were provided in 97.3% of patients at a mean reporting time of 12.9 calendar days. Repeat sampling was performed in six cases and results were obtained in five of them. No results were provided in four cases. Four cases of Down syndrome were detected and there was one discordant result of Turner syndrome. We found no statistical differences between commercial tests except in reporting time, fetal fraction and MA. The cfDNA fraction was statistically associated with test type, maternal weight, BMI and log βhCG levels. Conclusions: NIPT has the potential to be a highly effective screening method for major CA in a clinical setting. [ABSTRACT FROM AUTHOR]

Background: Non-invasive prenatal testing (NIPT) is currently used as a frontline screening test to identify fetuses with common aneuploidies. Occasionally, incidental NIPT results are conveyed to the clinician suggestive of fetuses with rare chromosome disease syndromes. We describe a child with trisomy 9 (T9) mosaicism where the prenatal history reported a positive NIPT result for T9 that was unconfirmed by conventional prenatal diagnosis. Methods: NIPT was performed by low coverage whole genome plasma DNA sequencing. Karyotyping and fluorescent in situ hybridization (FISH) analysis with chromosome 9p-ter and 9q-ter probes was used to determine the somatic cell level of T9 mosaicism in the fetus and child. Quantitative fluorescent PCR (Q-PCR) of highly polymorphic short tandem repeat (STR) chromosome 9 markers was also performed to investigate the nature of the T9 mosaicism and the parental origin. Results: A 22 month old girl presented with severe developmental delay, congenital cerebral dysplasia and congenital heart disease consistent with phenotypes associated with T9 mosaicism syndrome. Review of the prenatal testing history revealed a positive NIPT result for chromosome T9. However, follow up confirmatory karyotyping and FISH analysis of fetal cells returned a normal karyotype. Post-natal studies of somatic cell T9 mosaicism by FISH detected levels of approximately 20 % in blood and buccal cells. Q-PCR STR analysis of family DNA samples suggested that the T9 mosaicism originated by post-zygotic trisomic rescue of a paternal meiotic II chromosome 9 non-disjunction error resulting in the formation of two distinct somatic cell lines in the proband, one with paternal isodisomy 9 and one with T9. Conclusion: This study shows that NIPT may also be a useful screening technology to increase prenatal detection rates of rare fetal chromosome disease syndromes. [ABSTRACT FROM AUTHOR]

BACKGROUND: We have investigated the efficacy of QF-PCR for the prenatal recognition of common aneuploidy and compared our findings with cytogenetic results in our laboratories. METHODS: A total of 4058 prenatal samples (4031 amniotic fluid and 27 chorionic villous samples) were analyzed by QF-PCR using several selected STR markers together with amelogenin. Results were compared to those obtained by conventional cytogenetic analysis. RESULTS: We detected 139 (3.42%) numerical abnormalities in our subjects by QF-PCR. Concordant QF-PCR and karyotype results were obtained in 4001 (98.59%) of the samples. An abnormal karyotype associated with adverse clinical outcome undetected by QF-PCR was found in 16.66% (n = 28) of samples. Using QF-PCR alone, we were able to detect abnormalities in 98.59% of all referred families; however the karyotyping results improved the detection rate to 99.85% of the referred cases. Individuals with neonatal screening result with 1:10 risk ratio showed 11.29% abnormal karyotype while this number was 2.16% in mothers with risk ratio of 1:250 or less. CONCLUSION: In countries where large scale conventional cytogenetic is hampered by its high cost and lack of technical expertise, QF-PCR may be used as the first line of screening for detection of chromosomal abnormalities. We also recommend QF-PCR for all the families that are seeking prenatal diagnosis of single gene disorders aneuploidies screening to be added to their work up. [ABSTRACT FROM AUTHOR]

Objectives: To investigate how the introduction of noninvasive prenatal testing (NIPT) influenced women's testing choices following a positive Down syndrome screening. Methods: A retrospective study was conducted to compare differences in the uptake rates of invasive prenatal diagnosis (IPD) or no testing in one public hospital 1 year before (pre-NIPT) and 1 and 2 years after the introduction of NIPT in private in August 2011 using descriptive analysis and a χ2 test. Conventional screening was funded publicly, but NIPT was not. Multivariable binary logistic regression was used to determine factors affecting choices. Results: In pre-NIPT and in years 1 and 2 after the introduction of NIPT, 306, 362 and 401 women who screened positive were seen, respectively. In year 1 and year 2, 12.6 and 26.7% of them underwent NIPT while IPD was decreased by 16.3 and 25.6%, respectively (p < 0.001). Both chorionic villus sampling and amniocentesis decreased in year 1, but only the former in year 2. However, the rate of declining further testing was similar before and after NIPT (p = 0.213). In multivariable analysis, first trimester screening, nulliparity and working women were significant predictors of accepting NIPT, while only nulliparity was a predictor of declining IPD (OR = 0.61). Conclusions: Introduction of NIPT resulted in a significant decrease in IPD for 2 consecutive years. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

After numerous clinical validation studies, non-invasive prenatal testing for fetal aneuploidy detection is now a clinical reality. While non-invasive prenatal testing was accepted due to the high accuracy for fetal trisomy (21, 18 and 13) detection, recent research showed that genome-wide analysis is able to detect other fetal and maternal (mosaic) aneuploidies. In the present paper, we discuss the clinical advantages and challenges of genome-wide circulating free fetal deoxyribonucleic acid (DNA) profiling and targeted detection of rare chromosomal anomalies. The use of cell-free DNA tests for sex chromosome aneuploidies and microdeletion syndromes screening cannot be currently recommended without restriction on the basis of the present data. Expanding non-invasive prenatal testing (NIPT)-based prenatal screening to include this anomalies not only raises ethical concerns related to information and counseling challenges but also risks reversing the important reduction in invasive testing achieved with implementation of NIPT for aneuploidy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To estimate performance of a single-nucleotide polymorphism-based noninvasive prenatal screen for fetal aneuploidy in high-risk and low-risk populations on single venopuncture. METHODS: One thousand sixty-four maternal blood samples from 7 weeks of gestation and beyond were included; 1,051 were within specifications and 518 (49.3%) were low risk. Cell-free DNA was amplified, sequenced, and analyzed using the Next-generation Aneuploidy Test Using SNPs algorithm. Samples were called as trisomies 21, 18, 13, or monosomy X, or euploid, and male or female. RESULTS: Nine hundred sixty-six samples (91.9%) successfully generated a cell-free DNA result. Among these, sensitivity was 100% for trisomy 21 (58/58, confidence interval [CI] 93.8-100%), trisomy 13 (12/12, CI 73.5-100%), and fetal sex (358/358 female, CI 99.0-100%; 418/418 male, CI 99.1-100%), 96.0% for trisomy 18 (24/25, CI 79.7-99.9%), and 90% for monosomy X (9/10, CI 55.5-99.8%). Specificity for trisomies 21 and 13 was 100% (905/905, CI 99.6-100%; and 953/953, CI 99.6-100%, respectively) and for trisomy 18 and monosomy X was 99.9% (938/939, CI 99.4-100%; and 953/954, CI 99.4-100%, respectively). However, 16% (20/125) of aneuploid samples did not return a result; 50% (10/20) had a fetal fraction below the 1.5th percentile of euploid pregnancies. Aneuploidy rate was significantly higher in these samples (P<.001, odds ratio 9.2, CI 4.4-19.0). Sensitivity and specificity did not differ in low-risk and high-risk populations. CONCLUSIONS: This noninvasive prenatal screen performed with high sensitivity and specificity in high-risk and low-risk cohorts. Aneuploid samples were significantly more likely to not return a result; the number of aneuploidy samples was especially increased among samples with low fetal fraction. This underscores the importance of redraws or, in rare cases, invasive procedures based on low fetal fraction. [ABSTRACT FROM AUTHOR]

Background: Fetal nasal bone assessment is a non-invasive procedure that helps provide even greater assurance to patients undergoing their first trimester risk assessment for aneuploidies. Absence or presence of this factor is different in some races. Objective: The study was aimed to evaluate nasal bone in the first trimester of pregnancy in the indigenous population of Khuzestan Province, and to monitor its value in the diagnosis of chromosomal abnormalities. Materials and Methods: This study was conducted on 2314 pregnant women between 17-43 years old who referred for first trimester screening for chromosomal abnormalities. Gestational age was between 11-13w + 6 days. Nuchal translucency (NT), fetal heart rate (FHR), crown rump length (CRL), and maternal age and maternal blood serum factors (Free (11 ICG) and pregnancy-associated plasma protein-A (PAPP-A) and nasal bone were assessed. Finally the risk of trisomies was calculated. The statistical tests are based on the relationship between chromosomal abnormality and the presence or absence of the nasal bone. Results: In 114 cases we could not examine the nasal bone. Also, in 20 cases missed abortion happened without knowing the karyotype. 2173 cases were delivered normal baby, and in seven cases chromosomal abnormalities were diagnosed. Nasal bone was absent in all three cases with trisomy 21 and six of 2173 cases with normal phenotype (0.3%). With use of the Fisher exact test (p=0.0001), a significant correlation was found between the absence of the nasal bone and the risk of chromosomal abnormality. Conclusion: Inclusion of the nasal bone in first-trimester combined screening for aneuploidies achieves greater detection rate especially in Down syndrome. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of noninvasive prenatal testing for all fetal chromosomal aneuploidies in an extremely high-risk group undergoing first trimester combined Down syndrome screening. Method: A multicenter cohort prospective study in Taiwan was performed between June and December 2012. Maternal plasma was collected and shotgun massive parallel sequencing was performed on each fetal chromosome. 201 Taiwanese pregnant women at >12 weeks' gestation from 11 medical centers were enrolled in this trial. The extremely high-risk group was defined as a Down syndrome risk cutoff >1:30 or nuchal translucency >3.0 mm (n = 100), while the low-risk group was defined as a Down syndrome cutoff <1:1,500 (n = 101). Amniocentesis confirmation was performed and birth outcome was also recorded. Results: There were 11 cases of trisomy 21, 8 cases of trisomy 18, 3 cases of trisomy 13, 1 case of trisomy 16, 3 cases of 45,X, and 1 case of 47,XYY detected prenatally in 100 extremely high-risk gravidas [n = 27/100 (27%)]. The overall autosomal or sex chromosome aneuploidy detection rate was 96% (27/28) because of an insufficient amount maternal plasma for one fetus with Turner syndrome. In the low-risk group, no chromosomal abnormalities were detected (specificity = 100%). There were no false-positive cases in this study. Conclusions: This first trial in Taiwan shows that noninvasive prenatal testing for whole chromosome aneuploidies can be efficiently applied in extremely high- and low-risk populations. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The authors discuss aspects of the noninvasive prenatal testing for fetal aneuploidy using the cell-free DNA technology in the U.S. They are critical of the measures that the cell-free DNA is a new technology for prenatal testing to benefit pregnant women. They state the importance of developing clinical management guidelines and education related to prenatal testing.

The author discusses non-invasive prenatal testing (NIPT) for fetal aneuploidy with the use of maternal plasma DA sequencing. He mentions the study by G. Ashoor and colleagues, published in the January 2013 issue of the journal, which uses their chromosome-selective technique to trisomy 13. He adds that NIPT can replace ultrasound and maternal serum testing as a basic screening test for all pregnancies.

Objective:In 2009, the California Genetic Disease Branch introduced an aneuploidy screening program allowing Medi-Cal (state insured) patients access to state-sponsored first-trimester screening. The objective of this study was to assess the effect of greater access to prenatal screening on available resources at a single center.Study Design:Data of prenatal screening and diagnostic procedures performed 4 months before the introduction of the program were compared with those of 12 months following the introduction.Result:Between December 2008 and March 2010, 7689 women underwent first trimester screening, 1286 underwent amniocentesis and 398 underwent chorionic villus sampling. When a comparison was made between the 4 months before and the 12 months after the program's introduction, a greater number of nuchal translucency (NT) examinations was seen to have been performed (384 per month vs 513 per month, P=0.001). Prenatal diagnostic procedures did not increase, but a greater proportion was performed for positive screen results.Conclusion:Introduction of the California screening program was associated with increased NT procedures and fewer invasive procedures for advanced maternal age. [ABSTRACT FROM AUTHOR]

The author discusses the diagnosis of spina bifida at the 11-13-week scan by assessing intracranial translucency and the posterior brain region. He examines the rationale for using the mid-sagittal and axial plane for the examination of the posterior brain in early screening for aneuploidies. In addition, he concludes that screening for such an uncommon condition can only be achieved with a simple sign which can be visualized without excessive additional effort.

Background and aims: The obstetric care of a pregnancy, as it is practiced today, includes non-invasive screening approaches as well as invasive procedures for the definitive prenatal diagnosis of fetal disorders correlations between indications for prenatal cytogenetic diagnosis and results of the chromosomal analysis made upon fetal cells. The aim of our study was to evaluate the correlations between the screening test results and results of chromosomal analysis on fetal cells. Methods: Amniotic fluid samples from 1159 pregnant women were studied with the rapid FISH method and the cytogenetic analysis (karyotype). The results from both methods were compared. Results: The indications to perform prenatal cytogenetic diagnosis for numerical chromosomal abnormalities were: abnormal results of double or triple test, advanced maternal age, fetal abnormality detected through ultrasound examination, and positive family history for chromosomal anomalies. In our study we identified 30 cases with abnormal numeric chromosomes (18 cases of trisomy 21, 4 cases of trisomy 18, 3 cases of trisomy X, 1 case of monosomy, 2 cases of trisomy XYY, 1 case of trisomy XXY and 1 case of triploidy). Conclusions: This report confirms the importance of screening and the cytogenetic diagnosis in the identification of the numerical chromosomal abnormalities. [ABSTRACT FROM AUTHOR]

Introduction: To examine the prevalence and outcome of absent ductus venosus (DV) diagnosed at 11-13 weeks' gestation. Method: Prospective screening study for aneuploidies in 65,840 singleton pregnancies, including measurement of nuchal translucency (NT) thickness and examination of the DV. Prenatal findings and outcome of fetuses with absent DV were examined. Results: Absent DV was diagnosed in 26 cases giving a prevalence of 1 in 2,532. In 15 (57.7%) cases the NT was above the 95th centile for crown-rump length. In 11 (42.3%) cases, there was an aneuploidy, mainly Turner syndrome. The incidence of aneuploidies was 66.7% (10 of 15) for those with NT above the 95th centile and 9.1% (1 of 11) in those with normal NT (p = 0.015). In addition to the aneuploidies, there were 3 cases with other abnormalities, including one case each of Ebstein anomaly, Noonan syndrome and Pierre Robin sequence. In 9 of the 11 (81.8%) fetuses with NT below the 95th centile, absent DV was an isolated finding and the pregnancies resulted in healthy live births. Conclusion: The prognosis of fetuses with absent DV depends on the measurement of NT thickness, being poor if the NT is increased and good if the NT is normal. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]