Prenatal diagnosis using fetal cells in the maternal circulation

Since the introduction of ultrasound into obstetrics during the 1960s, there has been rapid progress in the detection of genetic and nongenetic defects in utero. With the development of sampling procedures like amniocentesis, chorionic villus sampling (CVS) and fetal blood sampling, the obstetrician has been able to obtain fetal tissue and the parallel improvement in laboratory techniques has allowed the diagnosis of chromosomal anomalies and single gene defects from fetal cells. Amniocentesis and CVS have become well established techniques for routine prenatal diagnosis of chromosomal and metabolic disorders and fetal tissue is now accessible throughout all three trimesters.

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Noninvasive Prenatal Diagnosis from Maternal Blood: Finally Available after 20 Years of Research

Donald School Journal of Ultrasound in Obstetrics & Gynecology ◽

10.5005/jp-journals-10009-1315 ◽

2013 ◽

Vol 7 (4) ◽

pp. 440-442

Author(s):

Wolfgang Holzgreve

Keyword(s):

Prenatal Diagnosis ◽

Single Gene ◽

Chorionic Villus ◽

Maternal Blood ◽

Chorionic Villus Sampling ◽

Clinical Use ◽

Maternal Circulation ◽

Isolated Cells ◽

Noninvasive Prenatal Diagnosis ◽

Cell Free Fetal Dna

ABSTRACT Since all prenatal invasive procedures, such as amniocentesis and chorionic villus sampling carry a small risk for the pregnant woman and a risk to induce the loss of a pregnancy of up to 1%, there have been efforts now for at least a quarter of a century to develop a noninvasive method from the blood of pregnant women. First there was a considerable effort to isolate fetal cells from maternal circulation, and these techniques were carefully evaluated in a NIH-sponsored study of a few US American centers and ours in Basel/Switzerland. It turned out; however, that interphase fluorescence to identify fetal aneuploidies from these isolated cells was not reliable enough for clinical use. The breakthrough came with the recognition of the group by D Lo et al; who showed for the first time that cell-free fetal DNA in maternal plasma and serum can be used reliably for prenatal diagnosis. One of the first successful applications was the detection of the fetal Rhesus factor around 11 weeks of gestation in pregnancies of Rhesus-negative mothers. The Sequenom Company in San Diego, USA, which acquired the patent of D Lo et al on the use of cell free DNA and ours on size separation of fetal vs maternal DNA subsequently showed in large series that the noninvasive prenatal diagnosis of fetal trisomy 21 from maternal blood by massive parallel sequencing has an accuracy around 99%, and currently up to 100,000 cases have been investigated already in different laboratories. Also the noninvasive prenatal diagnosis of trisomies 18 and 13 is possible, and an increasing amount of single gene anomalies will be diagnosable in the future noninvasively. The whole development of noninvasive prenatal diagnosis is appositive example that long-term research pays-off to bring a concept from the first steps finally into clinical use. How to cite this article Holzgreve W. Noninvasive Prenatal Diagnosis from Maternal Blood: Finally Available after 20 Years of Research. Donald School J Ultrasound Obstet Gynecol 2013;7(4):440-442.

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Prenatal diagnosis of familial lethal hypophosphatasia using imaging, blood enzyme levels, chorionic villus sampling and archived fetal tissue

Journal of Obstetrics and Gynaecology Research ◽

10.1111/j.1447-0756.2011.01526.x ◽

2011 ◽

Vol 37 (10) ◽

pp. 1470-1473 ◽

Cited By ~ 5

Author(s):

Nobuhiro Suzumori ◽

Etienne Mornet ◽

Eita Mizutani ◽

Shintaro Obayashi ◽

Yasuhiko Ozaki ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Chorionic Villus ◽

Fetal Tissue ◽

Chorionic Villus Sampling

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Basic Diploma in International Ultrasound for Prenatal Diagnosis and Therapy

Donald School Journal of Ultrasound in Obstetrics & Gynecology ◽

10.5005/jp-journals-10009-1304 ◽

2013 ◽

Vol 7 (3) ◽

pp. 346-348

Author(s):

Maria Angelica Zoppi

Keyword(s):

Prenatal Diagnosis ◽

Chorionic Villus ◽

Diagnostic Procedures ◽

Beta Thalassemia ◽

Chorionic Villus Sampling ◽

Diagnosis And Therapy ◽

Fetal Blood Sampling ◽

Chain Analysis ◽

Invasive Techniques ◽

Chromosomal Diseases

ABSTRACT In the Microcitemico Hospital the first prenatal diagnosis in Europe of beta-thalassemia was performed in 1977 using fetal blood sampling and globin chain analysis at 20th week of gestation. Since then, more than 55,000 prenatal invasive procedures were performed in our center for several genetic and chromosomal diseases. In 2011, our department has been introduced as a center for teaching invasive diagnostic procedures under the umbrella of the Ian Donald International University School of Medical Ultrasound. After a period of tutoring for 2 or more weeks, fellow doctors who intend to learn invasive techniques for prenatal diagnosis under the direct supervision of a senior tutor (G. Monni) can receive the basic diploma in invasive prenatal procedures (Fig. 1). In the following study, we describe the training process of the invasive prenatal procedure performed by transabdominal chorionic villus sampling (TA-CVS). How to cite this article Monni G, Zoppi MA, Iuculano A. Basic Diploma in International Ultrasound for Prenatal Diagnosis and Therapy. Donald School J Ultrasound Obstet Gynecol 2013;7(3):346-348.

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Prenatal Diagnosis for Pediatricians

PEDIATRICS ◽

10.1542/peds.84.4.741 ◽

1989 ◽

Vol 84 (4) ◽

pp. 741-744

Author(s):

Keyword(s):

Prenatal Diagnosis ◽

Genetic Disorder ◽

Chorionic Villus ◽

Fetal Tissue ◽

Maternal Serum ◽

Family Counseling ◽

Current Status ◽

Chorionic Villus Sampling ◽

Tissue Sampling ◽

Umbilical Blood

This statement is for the pediatrician who may be called upon to care for the child with a birth defect or genetic disorder. The involved family may wish to know and may benefit from methods that convert probability statements about recurrence risks into facts about the fetus. Many families will find knowledge and choice better than chance. Rapid advances in technology have prompted the Committee on Genetics to retire the June 1980 statement and to prepare a new one. The purpose of this revised statement is to inform the pediatrician about the current status of antenatal diagnosis as it relates to genetic and family counseling in clinical practice. The pediatrician may be called upon to help address questions about the natural history of the disorder under consideration and the possibility of intrauterine treatment. Prenatal diagnosis can give information that may improve the outcome of pregnancy and can be helpful to the obstetrician in the management of labor and delivery. The availability of prenatal diagnosis gives couples options they might not otherwise have, including termination of an affected pregnancy or preparation for the birth of an abnormal child. This enables many couples to have children, when without this information they would have chosen to be childless. The techniques currently in use or under investigation for prenatal diagnosis include (1) fetal tissue sampling: amniocentesis, chorionic villus sampling, percutaneous umbilical blood sampling, precutaneous skin biopsy, and other organ biopsies; (2) fetal visualization: ultrasound, fetoscopy, magnetic resonance imaging, and radiography; and (3) maternal serum α-fetoprotein screening. INDICATIONS FOR FETAL TISSUE SAMPLING

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Invasive Prenatal Diagnosis: Chorionic Villus Sampling

Donald School Journal of Ultrasound in Obstetrics & Gynecology ◽

10.5005/jp-journals-10009-1416 ◽

2015 ◽

Vol 9 (3) ◽

pp. 293-306

Author(s):

Panos Antsaklis ◽

Aris Antsaklis ◽

Michael Sindos ◽

Fotodotis M Malamas

Keyword(s):

Prenatal Diagnosis ◽

Obstet Gynecol ◽

Genetic Material ◽

Chorionic Villus ◽

First Trimester ◽

Chorionic Villus Sampling ◽

Maternal Circulation ◽

Maternal Cell ◽

Non Invasive ◽

Limb Reduction

ABSTRACT Chorionic villus sampling (CVS) is the method of choice for first trimester invasive prenatal diagnosis. In expert hands, it is nowadays considered as safe as amniocentesis and has the advantage of an earlier diagnosis. In this review, we describe the technique of the procedure, its indications and contraindications and the requirements concerning adequate training and optimum clinical practice. We also discuss issues concerning the safety of the procedure in singleton and multiple pregnancies, other complications and controversies, such as the association with limb reduction defects and pre-eclampsia, as well as diagnostic problems and dilemmas, such as maternal cell contamination and confined placental mosaicism. We also describe new and promising methods of non-invasive diagnosis, based on the isolation and analysis of fetal cells or cell-free fetal genetic material from the maternal circulation, that aim to replace the invasive methods of prenatal diagnosis in the future. How to cite this article Sindos M, Malamas FM, Antsaklis P, Antsaklis A. Invasive Prenatal Diagnosis: Chorionic Villus Sampling. Donald School J Ultrasound Obstet Gynecol 2015; 9(3):293-306.

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Diagnostic Prenatal Invasive Procedures in Obstetrics

Donald School Journal of Ultrasound in Obstetrics & Gynecology ◽

10.5005/jp-journals-10009-1313 ◽

2013 ◽

Vol 7 (4) ◽

pp. 426-428 ◽

Cited By ~ 1

Author(s):

Maria Angelica Zoppi

Keyword(s):

Single Gene ◽

Chorionic Villus ◽

Genetic Diagnosis ◽

Beta Thalassemia ◽

Pcr Analysis ◽

Comparative Genomic ◽

Chorionic Villus Sampling ◽

Invasive Procedures ◽

Diagnostic Prénatal ◽

Fetal Blood Sampling

ABSTRACT In 1977, we performed in Cagliari the first invasive prenatal diagnosis for beta-thalassemia in Europe, using fetal blood sampling by placentacentesis and chain globins analysis at 20th week of gestation. Since then we have performed more than 8,000 fetal diagnoses for beta-thalassemia using placentacentesis, fetoscopy, cordocentesis, cardiocentesis, amniocentesis, transcervical-chorionic villus sampling (TC-CVS), transabdominal (TA-CVS) and preimplantation genetic diagnosis (PGD) by embryo biopsy. Since 1986 we have been using for the beta-thalassemia and other single gene diseases only TA-CVS and PGD and DNA polymerase chain reaction (PCR) analysis. For karyotype we have been using mostly TA-CVS and amniocentesis and traditional cytogenetic analysis, in several cases also fluorescent in situ hybridization (FISH) and comparative genomic hybridization (CGH) array. How to cite this article Monni G, Zoppi MA, Iuculano A. Diagnostic Prenatal Invasive Procedures in Obstetrics. Donald School J Ultrasound Obstet Gynecol 2013;7(4):426-428.

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Dual and multiple trisomies: analysis of 38 cases from 13 thousand karyotyped embryos and fetuses

HEALTH OF WOMAN ◽

10.15574/hw.2017.117.109 ◽

2017 ◽

pp. 109-115

Author(s):

N.P. Veropotvelyan ◽

Keyword(s):

Prenatal Diagnosis ◽

High Risk ◽

Pregnant Women ◽

Maternal Age ◽

Chromosomal Abnormalities ◽

Chorionic Villus ◽

Primary Group ◽

Chorionic Villus Sampling ◽

Missed Abortion ◽

Reproductive Losses

The study presents data of different authors, as well as its own data on the frequency of multiple trisomies among the early reproductive losses in the I trimester of pregnancy and live fetuses in pregnant women at high risk of chromosomal abnormalities (CA) in I and II trimesters of gestation. The objective: determining the frequency of occurrence of double (DT) and multiple trisomies (MT) among the early reproductive losses in the I trimester of pregnancy and live fetuses in pregnant women at high risk of occurrence of HA in I and II trimesters of gestation; establishment of the most common combinations of diesel fuel and the timing of their deaths compared with single regular trisomy; comparative assessment materinskogo age with single, double and multiple trisomies. Patients and methods. During the period from 1997 to 2016, the first (primary) group of products in 1808 the concept of missed abortion (ST) of I trimester was formed from women who live in Dnepropetrovsk, Zaporozhye, Kirovograd, Cherkasy, Kherson, Mykolaiv regions. The average term of the ST was 8±3 weeks. The average age of women was 29±2 years. The second group (control) consisted of 1572 sample product concepts received during medical abortion in women (mostly residents of Krivoy Rog) in the period of 5-11 weeks of pregnancy, the average age was 32 years. The third group was made prenatally karyotyped fruits (n = 9689) pregnant women with high risk of HA of the above regions of Ukraine, directed the Centre to invasive prenatal diagnosis for individual indications: maternal age, changes in the fetus by ultrasound (characteristic malformations and echo markers HA) and high risk of HA on the results of the combined prenatal screening I and II trimesters. From 11 th to 14 th week of pregnancy, chorionic villus sampling was performed (n=1329), with the 16th week – platsentotsentez (n=2240), 18 th and 24 th week – amniocentesis (n=6120). Results. A comparative evaluation of maternal age and the prevalence anembriony among multiple trisomies. Analyzed 13,069 karyotyped embryonic and fetal I-II trimester of which have found 40 cases of multiple trisomies – 31 cases in the group in 1808 missed abortion (2.84% of total HA), 3 cases including 1 572 induced medabortov and 7 cases during 9689 prenatal research (0.51% of HA). Determined to share the double trisomies preembrionalny, fetal, early, middle and late periods of fetal development. Conclusion. There were no significant differences either in terms of destruction of single and multiple trisomies or in maternal age or in fractions anembrionalnyh pregnancies in these groups. Key words: multiple trisomies, double trisomy, missed abortion, prenatal diagnosis.

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Early ultrasound prenatal diagnosis of the Meckel — Gruber syndrome in combination with 47,XYY

10.21516/2413-1458-2018-17-1-62-67 ◽

2018 ◽

Author(s):

N.P. Veropotvelyan , E.S. Savarovskaya , T.V. Usenko

Keyword(s):

Prenatal Diagnosis ◽

Chorionic Villus ◽

Autosomal Recessive Disorder ◽

Chorionic Villus Sampling ◽

Previous Pregnancy ◽

Cystic Kidneys ◽

Occipital Encephalocele ◽

Posterior Fossa Cyst ◽

The Family ◽

Hands And Feet

Meckel — Gruber syndrome (MGS) is a rare lethal autosomal recessive disorder characterised by occipital encephalocele, polydactyly and bilateral dysplastic cystic kidneys. A case of prenatal diagnosis of MGS at 12 weeks of gestation is described. The previous pregnancy was terminated at 20 weeks due to polycystic kidneys of the fetus. The transabdominal scan of the present pregnancy revealed occipital encephalocele of the fetus. There was no oligohydramnios, but the fetal urinary bladder was not visualised and both kidneys were enlarged. The transvaginal sonogram demonstrated intracranial space dilatation (6 mm) and encepalocele with posterior fossa cyst, protrunding from the occipital bone deffect. The kidneys had the polycystic structure suggesting cystic dysplasia and there was no evidence of the hands and feet polydactyly. Based on these findings the diagnosis of the MGS was made. Chorionic villus sampling revealed 47,XYY. The family elected to terminate pregnancy and the diagnosis was confirmed by autopsy.

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