Detection Of Fetal Chromosomal Abnormalities Research Articles

Overview of Noninvasive Prenatal Testing (NIPT) for the Detection of Fetal Chromosome Abnormalities; Differences in Laboratory Methods and Scope of Testing.

Although nearly all noninvasive prenatal testing is currently based on analyzing circulating maternal cell-free DNA, the technical methods usedvary considerably. We review the different methods. Based on validation trials and clinical experience, there are mostly relatively small differences in screening performance for trisomies 21, 18, and 13 in singleton pregnancies. Recent reports show low no-call rates for all methods, diminishing its importance when choosing a laboratory. However, method can be an important consideration for twin pregnancies, screening for sex chromosome abnormalities, microdeletion syndromes, triploidy, molar pregnancies, rare autosomal trisomies, and segmental imbalances, and detecting maternal chromosome abnormalities.

Trophoblast retrieval from the cervical canal to predict abnormal pregnancy early in gestation: a pilot study

BackgroundThe current detection of fetal chromosomal abnormalities by non-invasive prenatal testing (NIPT) mainly relies on the cell free DNA(cfDNA) in the maternal blood. However, a gestational age of less than 12 weeks or a high maternal BMI affects cfDNA fetal fraction and further the detection by NIPT negatively. In this study, we aim to retrieve the trophoblast cells from the maternal cervix to develop a new sampling method for NIPT enabling an earlier use of NIPT.MethodsWe enrolled three patients who wanted to undergo induced abortion at Beijing Hospital between January 2022 and March 2022. Peripheral blood, cervix specimen, and the abortion tissue were collected and processed for each patient. Allele frequencies of the mutated gene loci of the maternal blood and the cervix sample were compared and the Sex Determining Region Y (SRY) gene was tested.ResultsThe allele frequencies of the mutated gene loci showed no significant difference between the maternal blood and the cervix sample. But we successfully detected signal of the SRY gene in the cervix sample of the only patient carrying a male fetus.ConclusionsThe detection of the SRY gene in a cervix sample indicated a successful retrieval of trophoblast cells from the cervix canal. Further study needs to be conducted to verify our finding before its application to the clinical settings.

Cell-free DNA versus sequential screening for fetal chromosomal abnormalities varied by age: a cost-effectiveness analysis

Cell-free DNA (cfDNA) and sequential screening (SS) are frequently used for prenatal genetic screening. Though cfDNA has higher detection rates for common aneuploidies, SS may better identify risk for other nontargeted aneuploidies. We compared the cost-effectiveness of cfDNA versus SS for detection of fetal chromosome abnormalities across varied age cohorts. A decision-analytic model compared cfDNA versus SS for diagnosis of chromosomal abnormalities across different maternal age cohorts stratified by 5-year increments of < 20, 20-24, 25-29, 30-34, 35-39, 40-44, and >45 years. Chromosomal abnormalities included trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), 45X syndrome, sex chromosome abnormalities (SCA), and other nontargeted chromosomal abnormalities . Probabilities, costs, and utilities were derived from literature and varied in sensitivity analysis. The primary outcome was incremental cost per quality-adjusted life year (QALY). We also considered affected neonates, missed prenatal diagnoses, procedure-related loss (PRL), pregnancy termination (TOP), stillbirth, and neonatal death (NND). The cost-effectiveness threshold was $100,000/QALY. SS was cost-effective for detection of all fetal chromosome abnormalities until age 39. Cell-free DNA was only cost-effective starting at age 40, with an Incremental Cost Effectiveness Ratio (ICER) of $51,919/QALY (40-44 years) and ICER $16,830/QALY ( >44 years). In all maternal age cohorts, cfDNA led to more frequent identification of T21, T18, T13, 45X and SCA but fewer other nontargeted chromosomal abnormalities. cfDNA was associated with more terminations and fewer stillbirths, NND, and PRL. The model was sensitive to the prevalence of T21. When varying the prevalence of T21 in the age 35-39 cohort cfDNA was cost effective when the prevalence of T21 was greater than 0.017 which corresponds with the prevalence of T21 at a maternal age of 39. Compared to cfDNA, SS is a cost-effective screening method for fetal chromosome abnormalities for pregnant persons under the age of 40 at a population-based level.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Clinical Experience With Non-invasive Prenatal Screening for Single-Gene Disorders

(Abstracted from Ultrasound Obstet Gynecol 2022;59:33–39) First described in 1997, the presence of cell-free fetal DNA in maternal plasma has been increasingly used in the last decade for cell-free DNA (cfDNA)–based noninvasive prenatal testing (NIPT) thanks to advances in molecular genetic technology. This method, now commonly used in the detection of fetal chromosomal abnormalities, can test for a variety of conditions.

Application of CNV-seq and chromosomal karyotyping in the prenatal diagnosis for carriers of balanced translocations

To assess the value of copy number variation sequencing (CNV-seq) and karyotyping in the prenatal diagnosis for carriers of balanced translocations. Clinical records of 135 amniocentesis samples of balanced translocation carriers undergoing simultaneous CNV-seq and karyotyping were analyzed. Chromosomal aberrations were defined as those can definitely lead to birth defects definitely, which included chromosomal numerical abnormality, large deletion/duplication and pathogenic copy number variations (pCNVs). The detection rates for karyotyping and CNV-seq were 4.44% (6/135) and 5.93% (8/135) respectively, and the latter had a detection rate of 1.48(2/135) higher than the former. A total of 68 fetal chromosomal translocations were detected by karyotying analysis. For couples carrying a balanced translocation, simultaneous CNV-seq and karyotyping is conducive to the detection of fetal chromosomal abnormalities and genetic counseling.

Noninvasive Prenatal Testing Using Next Generation Sequencing: Pilot Experience of the D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology

In recent years, noninvasive prenatal testing (NIPT) for fetal chromosomal abnormalities has come into wide use. NIPT allows detection of fetal chromosomal abnormalities without invasive sampling of fetal material: by analyzing cell-free fetal DNA in maternal blood. Here, we report on the pilot results of using NIPT at the D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology (St. Petersburg, Russia). The results obtained in 149 blood samples from pregnant women proved the clinical value of NIPT for detection of fetal trisomies 21, 18, and 13. Aneuploidy was detected in 20 out of 149 samples. Among these 20 aneuploid cases, trisomy 21 amounted to 60%, trisomy 18 – to 25%, and trisomy 13 to 5% of cases. In one sample, double aneuploidy involving chromosomes 13 and 21 was detected, and in one case, trisomy X was identified. In 100% of cases, aneuploidies were confirmed by prenatal karyotyping advocating for the absence of false positive NIPT results. The observed high specificity was consistent with the declared test specificity level of >99.9%. The sensitivity of the method was 100%. To summarize, NIPT is a new reliable technique that will probably soon replace the conventional first trimester combined screening. The only disadvantages of implementing NIPT in Russia are its relatively high cost and the lack of coverage by insurance companies. NGS-based NIPT is suitable for clinical practice and will be widely deployed due to a further cost decrease.

Application of chromosomal microarray analysis in prenatal diagnosis for fetal abnormalities detected by ultrasonography

To analyze the outcome of chromosomal microarray analysis (CMA) in prenatal diagnosis for fetal abnormalities detected by ultrasonography. Amniotic fluid samples from 477 pregnancies with abnormal ultrasound findings but without common aneuploidies were detected by CMA with Affymetrix CytoScan 750K arrays. The results were analyzed with ChAS v3.0 software. Among the 477 samples, 24 (5.03%) were detected with pathogenic copy number variations (pCNVs) by CMA. Six (9.68%) among 62 cases with structural fetal abnormalities in multiple organ systems were detected with pCNVs, 11 (7.48%) among 147 cases with a single structural anomaly were detected with pCNVs, and 7 (2.61%) among 268 cases with a soft marker were detected with pCNVs. CMA has offered a clear advantage over conventional karyotyping for the detection of fetal chromosomal abnormalities, and can provide an effective diagnostic tool for those with one or more structural abnormalities detected by ultrasound.

Clinical Significance of Conventional Karyotype and QF-PCR in Detection of Fetal Chromosomal Abnormalities

AbstractThis study aims to compare the advantages of two widely used methods for fetal chromosomal detection, karyotyping and QF-PCR, together with the indications for invasive prenatal diagnosis. We retrospectively investigated 888 amniocenteses analyzed by karyotyping only or karyotyping combined with QF-PCR. We assessed the results of each method and compared them to the indications for prenatal testing including maternal age, fetal ultrasound findings, and serum screening. We found 39 (4.4%) abnormalities, where 59% of those abnormalities were numerical and 41% were structural abnormalities undetectable by QF-PCR methods. Many structural abnormalities do not have clinical significance and we found that 23% of found structural abnormalities were clinically significant but undetectable by QF-PCR (0.3% of all amniocentesis analyzed). Additional 23% of found structural abnormalities were balanced translocations which can have rare clinically significant consequences. In total, 46% of found structural abnormalities had possible clinical consequences, which were undetectable by QF-PCR, or by noninvasive prenatal testing for five common aneuploidies. Thus, QF-PCR is a reliable method to detect most common fetal aneuploidies, but karyotyping should be used if any other chromosomal abnormalities are suspected. Even though QF-PCR is a fast and reliable method, physicians should be aware of the limitations of various methodologies for detection of fetal abnormalities and assign the proper method to the indication for amniocentesis.

Cell-Free DNA vs Sequential Screening for the Detection of Fetal Chromosomal Abnormalities

(Abstracted from Am J Obstet Gynecol 2016;214:727.e1–727.e6) Cell-free DNA (cfDNA) screening has shown high sensitivities and specificities for trisomy 21 and other common aneuploidies, thereby leading to a consideration for its use as a primary screening test. However, it has limitations, including the limited range of targeted aneuploidies and the failure to always provide a result.

Cell-free DNA vs sequential screening for the detection of fetal chromosomal abnormalities

Sequential and cell-free DNA (cfDNA) screening are both tests for the common aneuploidies. Although cfDNA has a greater detection rate (DR) for trisomy 21, sequential screening also can identify risk for other aneuploidies. The comparative DR for all chromosomal abnormalities is unknown. To compare sequential and cfDNA screening for detection of fetal chromosomal abnormalities in a general prenatal cohort. The performance of sequential screening for the detection of chromosome abnormalities in a cohort of patients screened through the California Prenatal Screening Program with estimated due dates between August 2009 and December 2012 was compared with the estimated DRs and false-positive rates (FPRs) of cfDNA screening if used as primary screening in this same cohort. DR and FPR for cfDNA screening were abstracted from the published literature, as were the rates of "no results" in euploid and aneuploid cases. Chromosome abnormalities in the entire cohort were categorized as detectable (trisomies 13, 18, and 21, and sex chromosome aneuploidy), or not detectable (other chromosome abnormalities) by cfDNA screening. DR and FPR were compared for individual and all chromosome abnormalities. DR and FPR for the cohort were compared if "no results" cases were considered "screen negative" or "screen positive" for aneuploidy. DR and FPR rates were compared by use of the Fisher exact test. Of 452,901 women who underwent sequential screening during the time period of the study, 2575 (0.57%) had a fetal chromosomal abnormality; 2101 were detected for a DR of 81.6%, and 19,929 euploid fetuses had positive sequential screening for an FPR rate of 4.5%. If no results cases were presumed normal, cfDNA screening would have detected 1820 chromosome abnormalities (70.7%) with an FPR of 0.7%. If no results cases were considered screen positive, 1985 (77.1%) cases would be detected at a total screen positive rate of 3.7%. In either case, the detection rate of sequential screening for all aneuploidies in the cohort was greater than cfDNA (P<.0001). For primary population screening, cfDNA provides lower DR than sequential screening if considering detection of all chromosomal abnormalities. Assuming that no results cfDNA cases are high-risk improves cfDNA detection but with a greater FPR. cfDNA should not be adopted as primary screening without further evaluation of the implications for detection of all chromosomal abnormalities and how to best evaluate no results cases.

Optimal Detection of Fetal Chromosomal Abnormalities by Massively Parallel DNA Sequencing of Cell-Free Fetal DNA from Maternal Blood

Massively parallel DNA sequencing of cell-free fetal DNA from maternal blood can detect fetal chromosomal abnormalities. Although existing algorithms focus on the detection of fetal trisomy 21 (T21), these same algorithms have difficulty detecting trisomy 18 (T18). Blood samples were collected from 1014 patients at 13 US clinic locations before they underwent an invasive prenatal procedure. All samples were processed to plasma, and the DNA extracted from 119 samples underwent massively parallel DNA sequencing. Fifty-three sequenced samples came from women with an abnormal fetal karyotype. To minimize the intra- and interrun sequencing variation, we developed an optimized algorithm by using normalized chromosome values (NCVs) from the sequencing data on a training set of 71 samples with 26 abnormal karyotypes. The classification process was then evaluated on an independent test set of 48 samples with 27 abnormal karyotypes. Mapped sites for chromosomes of interest in the sequencing data from the training set were normalized individually by calculating the ratio of the number of sites on the specified chromosome to the number of sites observed on an optimized normalizing chromosome (or chromosome set). Threshold values for trisomy or sex chromosome classification were then established for all chromosomes of interest, and a classification schema was defined. Sequencing of the independent test set led to 100% correct classification of T21 (13 of 13) and T18 (8 of 8) samples. Other chromosomal abnormalities were also identified. Massively parallel sequencing is capable of detecting multiple fetal chromosomal abnormalities from maternal plasma when an optimized algorithm is used.

Second‐trimester genetic sonogram for detection of fetal chromosomal abnormalities in a community‐based antenatal testing unit

To evaluate the efficacy of the second-trimester genetic sonogram for the detection of Down syndrome and other chromosomal abnormalities in a community-based antenatal testing unit. This was a retrospective study using data from two community hospital antenatal ultrasound units. Six hundred and sixty fetal ultrasound examinations in both at-risk (n = 581) and low-risk (n = 79) pregnancies were performed from 15 + 0 to 22 + 6 weeks' gestation and all cases were verified for outcome data. The sonographic detection of a major congenital anomaly or a sonographic marker (increased nuchal skinfold, short humerus, short femur, echogenic bowel, pyelectasis, echogenic intracardiac focus, absence or hypoplasia of fifth mid phalanx or choroid plexus cyst) was recorded. The entire group of 660 ultrasound examinations as well as subgroups with and without non-ultrasound risk factors for a fetal chromosomal abnormality were analyzed to determine the sensitivity, specificity, positive and negative predictive values and positive likelihood ratio for the detection of Down syndrome and other fetal chromosomal abnormalities. There were 32 (4.85%) chromosomal abnormalities in our study population. Twelve (3.75%) of these were Down syndrome, of which eight (66.6%) had a positive ultrasound examination in the second trimester. Six of seven (85.7%) of the trisomy 18 fetuses, 2/2 of the trisomy 13 fetuses and 2/3 of the non-mosaic 45,X fetuses had positive sonograms. The overall detection rate for chromosomal abnormalities was 20/32 (sensitivity, 62.5%; specificity, 80.7%; negative predictive value, 97.7%; positive predictive value, 14.2%; positive likelihood ratio, 3.24). Major structural defects and sonographic markers, excluding hypoplastic fifth digit and choroid plexus cyst, occurred significantly more frequently in Down syndrome cases compared with normal ones. In a community-based antenatal testing unit we have demonstrated a detection rate for fetal Down syndrome with the second-trimester genetic sonogram that is comparable to the range of sensitivities reported by larger centers involving primarily high-risk patients. However, only 12 of the 32 fetal chromosomal abnormalities that we encountered were Down syndrome.

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

Objective. The study aimed to estimate the incidence of increased nuchal translucency in the first trimester ultrasound scan results (cut-off limit 2.5 mm) and to evaluate the predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities.Methods. We used the ultrasound scan results of nuchal translucency evaluation and the results of chromosomal analysis of the invasive prenatal control performed as a result of increased nuchal translucency.Results. We collected 2183 nuchal translucency ultrasound scans in which we detected 21 embryos with a pathologic value (0.96%). We collected the data of 168 cases of invasive prenatal control due to increased nuchal translucency from which 122 cases were found. A total of 122 cases of pregnant women undergone an invasive prenatal diagnostic method due to increased nuchal translucency, of which 11 fetuses were found with trisomy 21 (Down syndrome) (9%), 3 fetuses with trisomy 13 (Patau syndrome) (2.45%), 3 fetuses with monosomy 45XO (Turner syndrome) (2.45%) and 1 fetus with translocation (0.8%).Conclusions. The positive predictive value of the increased fetal nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities based on the results of the chromosomal-genetic analysis of the invasive prenatal diagnostic procedures is 14.8%.

Invasive Pränataldiagnostik im Umbruch

Die Indikationsstellung zur invasiven pränatalen Diagnostik (PND) fetaler chromosomaler Störungen hat sich im letzten Jahrzehnt verändert. Die Altersindikation (Alter der Schwangeren ≥ 35 Jahren) verliert zugunsten einer individuellen Indikationsstellung unter Berücksichtigung des maternalen Alters und der detaillierten Sonographie inklusive fetaler Echokardiographie zunehmend an Bedeutung. Durch den Einsatz von hochauflösenden Ultraschallsonden und der Vaginalsonographie können Auffälligkeiten beim Feten (z. B. strukturelle Fehlbildungen, wie Omphalozele, Herzfehler, ZNS-Fehlbildungen, Megazystis und Extremitätenfehlbildungen, und „Marker“, wie verdickte Nackentransparenz, Hygroma colli und Hydrops fetalis), die mit einer chromosomalen Fehlverteilung oder auch nicht chromosomal bedingten Syndromen assoziiert sind, häufig bereits im 1. Trimenon erkannt werden. Die frühe Diagnose solcher struktureller Fehlbildungen und Marker ermöglicht es, den Paaren nach individueller, ausführlicher Beratung eine invasive Diagnostik zur Bestimmung des fetalen Karyotyps anzubieten. Die Entwicklungen der nicht invasiven Verfahren der pränatalen Diagnostik resultierten in einem Rückgang der invasiven pränatalen diagnostischen Eingriffe (Amniozentese [AC], Chorionzottenbiopsie [CVS]) bei gleichzeitigem Anstieg des Anteils von auffälligen Chromosomenbefunden in den letzten 15 Jahren im Bereich der Pränatalmedizin der Frauenklinik und dem Institut für Humangenetik der Universität zu Lübeck.

Prenatal Diagnosis of Chromosomal Abnormalities through Amniocentesis

The incidence of major chromosome abnormalities in newborns is about 0.7 percent and increases with maternal age. Amniocentesis is the most common invasive prenatal procedure for the detection of fetal chromosomal abnormalities. Amniocentesis is a relatively safe procedure and fetal loss related to amniocentesis is about 0.5%. An advanced maternal age is the most common reason for using amniocentesis. The use of amniocentesis because of abnormal fetal ultrasound findings has increased recently. Fluorescence in situ hybridization (FISH) is currently a powerful tool in the area of prenatal cytogenetics. The number of amniocentesis procedures in Japan is about ten thousand per year and it is generally recognized to be a great benefit for pregnant women who have a risk of fetal chromosomal abnormalities.

Increased Nuchal Translucency, Hydrops fetalis or Hygroma colli

Objectives: Nuchal translucency measurement of 3 mm or more (≧95th centile for gestation age), hydrops fetalis or hygroma colli between the 11th and 14th weeks of gestation is associated with a higher risk of fetal Down syndrome and other aneuploidies. So far, chromosome preparation of chorionic villi samplings (CVS) after short-term (or direct) culture is the only valid, reliable and rapid method of choice for the early detection of chromosomal aberrations. However, because of the placental mosaicisms detected after short-term culture, CVS has to be confirmed by a second method. Moreover, short-term villi preparation does not always provide a sufficient quantity and quality of metaphases to enable cytogenetic analysis. Unfortunately, a predicative cytogenetic result will be available only after long-term cultivation (usually after 1–2 weeks). An alternative rapid method, inexpensive and suitable for diagnosing autosomal trisomies, is the quantitative fluorescence polymerase reaction (QF-PCR) using different polymorphic small tandem repeats (STRs) on CVS-DNA. Therefore, it was the aim of the study to evaluate whether a new CVS test strategy could be employed in early pregnancies at high risk after the rapid detection of fetal chromosomal abnormalities by QF-PCR for chromosomes 13, 18 or 21 and sexing in conjunction with short-term chromosome analysis. Materials: Nineteen CVS were chosen for QF-PCR detection of trisomy 21, 18 or 13 after an increased nuchal translucency measurement (≧95th centile for gestation age), a hydrops fetalis or a hygroma colli. The amelogenin locus of chromosomes X and Y (AMXY) were used for sexing. The QF-PCR results were compared with routine karyotyping after short- and/or long-term cultivation of CVS cells. Results: An informative result was demonstrated in all analysed specimens. Nine CVS were diagnosed as a QF-PCR trisomy either for chromosome 21, 18 and 13. The pathological samples also included 4 cases of mosaicism where the normal cell line was not identified by QF-PCR. In 1 additional case with a normal QF-PCR result, short-term CVS chromosome analysis showed a mosaic trisomy 13, whereas longterm CVS culture revealed a normal karyotype. The malformed aborted fetus showed no clinical signs of trisomy 13, confirming the normal results obtained by QF-PCR and long-term CVS chromosome analysis. One pregnancy with a Turner syndrome was not identified by molecular analysis. Conclusions: This study showed that all early pregnancies with a clinically relevant autosomal trisomy could be detected prenatally in routine practice by QF-PCR. The combined use of both rapid methods – QF-PCR and short-term chromosome analysis – optimise the results by minimising the possibility of false-positive or false-negative findings. We believe that after verification of a pathological result obtained by two independent methods (QF-PCR and short-term CVS chromosome analysis), long-term villi cultivation is no longer necessary. However, in all cases with discrepancies, especially in samples with mosaic findings at short-term CVS cultivation, further studies are still necessary.

Efficacy of Maternal Serum Screening in the Prenatal Detection of Fetal Chromosome Abnormalities in Japanese Women

Objective: This prospective study assesses the efficacy of maternal serum screening for use in prenatal diagnosis of fetal anomaly and chromosome imbalance in Japanese women. Methods: Maternal serum α-fetoprotein, human chorionic gonadotropin, and unconjugated estriol were measured in 1,055 singleton pregnant women between 14 and 20 weeks of gestation. A calculated risk for trisomy 21 of ≥1/299 or α-fetoprotein ≥2.5 multiples of the median was adopted as positive. Results: Three hundred and seventy-eight of the 1, 055 women screened (35.8%) were identified as positive. Sensitivity, false-positive rate, and positive predictive value in women aged <35 years were 60.0, 10.6, and 6.8%, respectively, and these values were 87.5, 49.3, and 4.2%, respectively, in women aged ≥35 years. The false-positive rate in women aged <35 years was significantly lower than that for women aged ≥35 years (p < 0.001). Chromosomal abnormalities were identified in 21 cases, including 10 with trisomy 21, 5 with trisomy 18, 2 with trisomy 13, and 4 with other chromosomal disorders. Seventeen of the 21 cases (81.0%) showed screen-positive results, and among these all 10 cases with trisomy 21 were detectable. Two cases with trisomy 18, 1 with trisomy 13 and 1 with isochromosome X showed extremely low human chorionic gonadotropin levels (0.4 ± 0.1 multiples of the median, mean ± SE), although they were screen negative. Of the 264 women who did not undergo amniocentesis, none had any clinical findings consistent with aneuploidy after birth. Conclusions: Our results suggest that the evaluation of each serum marker, as well as of the calculated risk, was significantly important in the prenatal detection of fetal aneuploidy.

Direct analysis of uncultured cytotrophoblastic cells from second- and third-trimester placentas: An accurate and rapid method for detection of fetal chromosome abnormalities

Abstract Transabdominal chorionic villus sampling can be readily used for detection of fetal chromosome abnormalities in the second and third trimesters of pregnancy. Although culture of chorionic villi offers little advantage over cultured amniotic fluid cells with respect to time required to obtain results, cytogenetic analysis of chorionic villi by direct analysis of uncultured cytotrophoblastic cells offers clear advantages because of the very short time required to obtain results. To determine whether direct analysis of uncultured cytotrophoblastic cells from second- and third-trimester placentas can routinely provide rapid and accurate assessment of fetal status, we evaluated chorionic villus specimens obtained from 57 placentas; 49 placentas were sampled in the second trimester whereas eight were sampled in the third trimester. Direct preparations yielded karyotypes in 56 (98.2%) preparations; all results of direct analyses were available within 72 hours and, when requested, within 12 hours. All results were confirmed by chromosome analysis of cultured mesenchymal core cells or cultured fetal tissue. We conclude that direct analysis of cytotrophoblastic cells from second- and third-trimester placentas is a very rapid and accurate method for determining fetal chromosome status that is comparable with, if not superior to, percutaneous umbilical blood sampling. (AM J OesTET GYNECOL 1990;163:1606-9.)

Direct analysis of uncultured cytotrophoblastic cells from second- and third-trimester placentas: An accurate and rapid method for detection of fetal chromosome abnormalities

Transabdominal chorionic villus sampling can be readily used for detection of fetal chromosome abnormalities in the second and third trimesters of pregnancy. Although culture of chorionic villi offers little advantage over cultured amniotic fluid cells with respect to time required to obtain results, cytogenetic analysis of chorionic villi by direct analysis of uncultured cytotrophoblastic cells offers clear advantages because of the very short time required to obtain results. To determine whether direct analysis of uncultured cytotrophoblastic cells from second- and third-trimester placentas can routinely provide rapid and accurate assessment of fetal status, we evaluated chorionic villus specimens obtained from 57 placentas; 49 placentas were sampled in the second trimester whereas eight were sampled in the third trimester. Direct preparations yielded karyotypes in 56 (98.2%) preparations; all results of direct analyses were available within 72 hours and, when requested, within 12 hours. All results were confirmed by chromosome analysis of cultured mesenchymal core cells or cultured fetal tissue. We conclude that direct analysis of cytotrophoblastic cells from second- and third-trimester placentas is a very rapid and accurate method for determining fetal chromosome status that is comparable with, if not superior to, percutaneous umbilical blood sampling. (AM J OesTET GYNECOL 1990;163:1606-9.)