Non-invasive prenatal testing for the diagnosis of congenital abnormalities: Insights from a large multicenter study in southern China

Although non-invasive prenatal testing (NIPT) is widely used to detect fetal abnormalities, the results of NIPT vary by population, and data for the screening efficiency of NIPT positive predictive value (PPV) from different populations is limited. Herein, we retrospectively analyzed the NIPT results in a large multicenter study involving 52,855 pregnant women. Depending on gestational age, amniotic fluid or umbilical cord blood was extracted for karyotype and/or chromosome microarray analysis (CMA) in NIPT-positive patients, and the PPV and follow-up data were evaluated to determine its clinical value. Among the 52,855 cases, 754 were NIPT-positive, with a positivity rate of 1.4%. Karyotype analysis and/or CMA confirmed 323 chromosomal abnormalities, with a PPV of 45.1%. PPV for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosomal aneuploidies (SCAs), and copy number variations (CNVs) were 78.9, 35.3, 22.2, 36.9, and 32.9%, respectively. The PPVs for T21, T18, and T13 increased with age, whereas the PPVs for SCAs and CNVs had little correlation with age. The PPV was significantly higher in patients with advanced age and abnormal ultrasound. The NIPT results are affected by population characteristics. NIPT had a high PPV for T21 and a low PPV for T13 and T18, and screening for SCAs and CNVs showed clinical significance in southern China.

Prenatal Diagnosis of 18q Deletion Syndrome / 中山大学学报(医学科学版)

ObjectiveTo explore the prenatal diagnostic methods of 18q deletion syndrome and improve understanding on the value of non-invasive prenatal testing （NIPT） in prenatal diagnosis of 18q deletion syndrome. Methods18q deletion syndrome was detected by conventional methods such as serological screening， ultrasonic imaging examination， chromosome karyotype analyses of both amniotic fluid cells and parental peripheral blood， and molecular biological techniques including NIPT， chromosomal microarray analysis （CMA） and copy number variation sequencing （CNV-Seq）. Genetic counseling was conducted based on these examination results. ResultsNIPT identified a 24 MB deletion on the chromosome 18 which contained 17 genes including BCL2 by karyotype analysis of amniotic fluid cells and CMA. Further ultrasonic imaging examination confirmed the diagnosis of 18q deletion syndrome and karyotype analysis of parental peripheral blood revealed a de novo deletion mutation. ConclusionsInterventional prenatal diagnosis is an integral standard for the diagnosis of 18q deletion syndrome. NIPT， as an important screening test in middle pregnancy， can indicate the early possible chromosome segment deletion and reduce the time and economic cost when no abnormality is found in ultrasonic imaging.

Knowledge, attitude and practices of obstetricians and gynecologists on non- invasive prenatal testing with cell free fetal DNA in a private tertiary hospital / Philippine Journal of Obstetrics and Gynecology

@#There are a number of novel prenatal cytoogenetic analysis tests for obstetricians and gynecologists on detecting aneuploidies. In the recent years, screening of pregnant patients with non-invasive prenatal testing (NIPT) is one. As the spread of genomic medicine and preventive obstetrics continue, it is prudent for obstetricians and gynecologists to accept and optimize new screening modalities, whenever available. Chromosomal abnormalities are common. Worldwide, one out of 150 live births may involve chromosomal abnormalities. The American College of Obstetrics and Gynecologists (ACOG) and American College of Medical Genetics recommend invasive and non ? invasive prenatal testing (NIPT)3. The invasive testing, however, carries risk for procedure ? related miscarriage. 4This favors NIPT which avoids the risk. The current state of NIPT in the Philippines, is it was only in January 2018, were a NIPT workshop was conducted by the Society of Maternal Fetal Medicine.6 First, due to the minimal studies on personalized and precision medicine on prenatal testing, hence the strong move to conduct this study. In an extensive literature search review in Herdin, a local database and archives of Philippine Obstetrics and Gynecology, none specified researches on non ? invasive prenatal testing. Second, in our country alone, there is no provision for national prenatal tests. In our institution, it was already introduced but with no uptake yet. Because of this gap, scantiness and non - uptake on NIPT locally, hence the conduct of this study. The study aimed to investigate on the obstetricians and gynecologists (OB-GYNs) knowledge, attitude towards and practices (KAP) about NIPT. Majority of the OBGYNs were knowledgeable, had positive attitude and were practicing NIPT. Strikingly, a fourth of the respondents were not comfortable in explaining NIPT. The researcher recommends that there is a need to conduct this study on a larger scale cross - sectional survey and multiple studies due to the paucity of data.

How diseases became "genetic" / Como as doenças se tornaram "genéticas"

Abstract This article examines the origins of the term "genetic disease." In the late 19 and early 20th century, an earlier idea that diseases that occur in families reflect a vague familiar "predisposition" was replaced by the view that such diseases have specific causes, while Mendelian genetics provided then clues to the patterns of their transmission. The genetictisation of inborn pathologies took a decisive turn with the redefinition, in 1959, of Down syndrome as a chromosomal anomaly, then the development of tests for the diagnosis of other hereditary pathologies. At that time, geneticists distinguished "hereditary" diseases that run in families, from "genetic" conditions that are the result of new mutations during the production of egg and sperm cells. In the latter case, the inborn impairment is produced by an anomaly in the genetic material of the cell, but is not hereditary, because it is not transmitted from one or both parents. In the late 20th and early 21st century, new genomic technologies blurred the distinction between hereditary and genetic impairments, extended the concept of genetic disease, and modified the experience of people living with such a disease.

Resumo O presente artigo tem o objetivo de examinar as origens do termo "doença genética. No final do século XIX e início do XX, a vaga ideia que a doença manifesta entre familiares refletia uma "predisposição" familiar, foi substituída pela visão que essas doenças possuem causas específicas, enquanto a genética mendeliana forneceu as pistas para os padrões de transmissão da doença. A genética das patologias congênitas deu uma guinada decisiva, em 1959, com a redefinição da Síndrome de Down como uma anomalia cromossômica e, depois, com o desenvolvimento de testes para o diagnóstico de outras patologias hereditárias. Naquela época, os geneticistas distinguiam doenças "hereditárias" como aquelas que acometiam os elementos de uma família, de condições "genéticas" que são o resultado de novas mutações ocorridas durante a produção dos óvulos e espermatozoides. Neste último caso, a deficiência inata é causada por uma anomalia do material genético da célula, porque não é transmitida por qualquer um ou ambos os pais. No final do século XX e início do XXI, as novas tecnologias genômicas obscureceram a distinção entre deficiências hereditária e a genética, estenderam o conceito da doença genética e modificaram a experiência das pessoas que vivem com esse tipo de doença.

Survey on cognition, attitude, willingness and demand for non-invasive prenatal testing among pregnant women / 上海交通大学学报（医学版）

Objective • To understand the cognition, attitude, willingness and demand for non-invasive prenatal testing (NIPT) of pregnant women. Methods • A total of 852 pregnant women were enrolled, including 318 pregnant women with low risk of Down syndrome screened in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, and 534 pregnant women with high risk of Down syndrome screened in several hospitals in Shanghai who further went to Xinhua Hospital, Shanghai Jiao Tong University School of Medicine for NIPT to confirm the diagnosis of Down syndrome screening. The information about the cognition, attitude, willingness and demand for NIPT was collected by a standard questionnaire. Results • A total of 760 questionnaires were collected, of which 728 ones were valid, with an effective questionnaire rate of 85.45%. The proportion of pregnant women with ideal cognition level was 51.24%. However, 83.10% of pregnant women held a positive attitude towards the promotion of NIPT. There were 79.54% of pregnant women considering it necessary to provide genetic counseling before NIPT. Conclusion • It is of great significance to strengthen the prenatal propaganda and education and pre-test genetic counseling so as to improve the cognitive level of pregnant women and make rational use of NIPT.

Evaluation of preferences of women and healthcare professionals in Singapore for implementation of noninvasive prenatal testing for Down syndrome

<p><b>INTRODUCTION</b>Invasive prenatal diagnosis (IPD) has long been used to prenatally diagnose Down syndrome (DS), but it is associated with a small risk of miscarriage. Noninvasive prenatal testing (NIPT) is a highly sensitive screening test using cell-free DNA in maternal blood for detection of DS without the risk of miscarriage, but it confers a small risk of false-positive and false-negative results. The implementation of these procedures into clinical practice requires an understanding of stakeholder preferences.</p><p><b>METHODS</b>A total of 69 health professionals (HPs) and 301 women took part in a discrete choice experiment (DCE) in which preferences for four prenatal test attributes - accuracy, time of results, risk of miscarriage and amount of information provided - were assessed. Conditional logit regression was used to analyse the data. Data on demographics and ranked preferences for test attributes was collected, and a direct choice question regarding NIPT, IPD or neither test was posed to participants.</p><p><b>RESULTS</b>The women showed a preference for test safety, whereas HPs prioritised test accuracy above all other attributes. When offered a direct choice of NIPT, IPD or neither test, women aged 35 years and older, those with previous miscarriage or who knew a child with DS were more likely to choose NIPT. Chinese women preferred NIPT, whereas Indian women preferred IPD.</p><p><b>CONCLUSION</b>Our data highlights the need for patient-specific counselling, taking into account previous experiences and cultural factors. Since women and HPs prioritise different test attributes, it is essential that HPs recognise these differences in order to provide non-biased counselling.</p>

Diagnóstico prenatal de anomalías cromosómicas: Examen prenatal no invasivo / Prenatal diagnosis of chromosome abnormalities: Noninvasive prenatal testing

El examen prenatal no invasivo es un método de tamizaje para encontrar a aquellas gestantes que tienen un riesgo de aneuploidía alto, específicamente para las trisomías 21, 18 y 13, y anomalías del cromosoma X. Requiere de una muestra de sangre periférica materna, en la que se analiza el ADN fetal libre circulante. En esta revisión detallamos los beneficios, desventajas e indicaciones del estudio.

Non-invasive prenatal test (NIPT) is a screening method that identifies pregnant women with a high aneuploidy risk, specifically for trisomy 21, 18, 13, and chromosome X anomalies. NIPT analyzes free fetal DNA found in maternal blood. In this review, we describe the benefits, disadvantages and study indications.

Noninvasive prenatal test for fetal chromosomal aneuploidies by massively parallel sequencing of cell-free fetal DNA in maternal plasma: The first clinical experience in Korea

PURPOSE: Noninvasive prenatal test (NIPT) by massively parallel sequencing (MPS) of cell-free fetal DNA in maternal plasma marks a significant advancement in prenatal screening, minimizing the need for invasive testing of fetal chromosomal aneuploidies. Here, we report the initial clinical performance of NIPT in Korean pregnant women. MATERIALS AND METHODS: MPS-based NIPT was performed on 910 cases; 5 mL blood samples were collected and sequenced in the Shenzhen BGI Genomic Laboratory to identify aneuploidies. The risk of fetal aneuploidy was determined by L-score and t-score, and classified as high or low. The NIPT results were validated by karyotyping for the high-risk cases and neonatal follow-up for low-risk cases. RESULTS: NIPT was mainly requested for two clinical indications: abnormal biochemical serum-screening result (54.3%) and advanced maternal age (31.4%). Among 494 cases with abnormal biochemical serum-screening results, NIPT detected only 9 (1.8%) high-risk cases. Sixteen cases (1.8%) of 910 had a high risk for aneuploidy: 8 for trisomy 21, 2 for trisomy 18, 1 for trisomy 13, and 5 for sex chromosome abnormalities. Amniocentesis was performed for 7 of these cases (43.8%). In the karyotyping and neonatal data, no false positive or negative results were observed in our study. CONCLUSION: MPS-based NIPT detects fetal chromosomal aneuploidies with high accuracy. Introduction of NIPT as into clinical settings could prevent about 98% of unnecessary invasive diagnostic procedures.