Diagnosis Of Chromosomal Abnormalities Research Articles

Prenatal Diagnosis of Chromosome Abnormalities: 21 Years of Experience

Prenatal Diagnosis of Chromosome Abnormalities: 21 Years of Experience

Diagnostic accuracy and value of chromosomal microarray analysis for chromosomal abnormalities in prenatal detection: A prospective clinical study.

Chromosomal microarray analysis (CMA) has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. The aim of this study was to compare the accuracy and value of CMA and karyotyping on diagnosis of chromosomal abnormalities in Fujian province of South China.In the study, 410 clinical samples were collected from pregnant women between March 2015 and December 2016, including 3 villus (0.73%, 3/410), 296 amniotic fluid (72.20%, 296/410), and 111 umbilical cord blood (27.07%, 111/410). All samples were screening for chromosomal abnormalities by both using CMA and karyotyping.The success rate of CMA and karyotyping was 100% (410/410) and 99.27% (407/410), respectively. Sixty-one (14.88%, 61/410) samples were presented with chromosomal abnormalities by using CMA, whereas 47 (11.55%, 47/407) samples were shown with chromosomal abnormalities by using karyotyping. Thirty-one (8.61%, 31/360) samples with normal karyotypes were found to exist chromosomal abnormalities by using CMA. Receiver operating characteristic analysis showed that the area under the curve of karyotyping on the diagnosis of chromosomal abnormalities was 0.90 (95% confidence interval: 0.87–0.93), the sensitivity and specificity was 87.56% and 91.22%, respectively. The area under the curve of CMA on the diagnosis of chromosomal abnormalities was 0.93 (95% confidence interval: 0.90–0.95), with 90.68% sensitivity and 94.40% specificity. Notably, the combination of CMA and karyotyping could improve the diagnosis of chromosomal abnormalities.CMA has a better diagnostic value for screening chromosomal abnormalities, especially for those pregnant women with normal karyotypes. This study has guiding value for prenatal diagnosis in Fujian province of South China.

Application of the BACs-on-Beads assay for the prenatal diagnosis of chromosomal abnormalities in Quanzhou, China

BackgroundAn increasing number of techniques have been used for prenatal diagnosis of genetic abnormalities. Our initial objective was to explore the value of the BACs-on-Beads (BoBs) assay for the prenatal diagnosis of aneuploidies and microdeletion/microduplication syndromes in Quanzhou, Southeast China.MethodsA total of 1409 pregnant women with high-risk factors for chromosomal abnormalities admitted to Quanzhou Women’s and Children’s Hospital were enrolled in this study. BoBs assays and karyotype analyses were conducted for all subjects. Subsequently, chromosome microarray analysis (CMA) or fluorescence in situ hybridization (FISH) was performed to validate the findings.ResultsIn this study, karyotype analysis and BoBs assay failed in 4 cases, and 2 cases, respectively. A total of 1403 cases were successfully analyzed, with success rates of 99.72% (1405/1409) and 99.85% (1407/1409) for karyotype analysis and Bobs assay, respectively. BoBs assay rapidly detected chromosomal aneuploidies in line with the karyotyping data. Additionally, 23 cases of microdeletions/microduplications were detected by BoBs assay but missed by karyotyping, including 22q11.2 microdeletions/microduplications, 5p15.32p15.33 microdeletion, Xp22.31 microdeletions/microduplications, Xq27.3 microdeletion, and Yp11.2 and Yq11.22q11.222 microduplication. In comparison with karyotyping, fewer mosaicisms were identified by BoBs assay. A high detection rate of chromosomal abnormalities was observed in the high-risk group during noninvasive prenatal testing (NIPT) (41.72%) and the abnormal ultrasound group (13.43%).ConclusionsBoBs assay can be used for the rapid and efficient prenatal diagnosis of common aneuploidies and microdeletion/microduplication syndromes. Moreover, the combined use of BoBs assay and karyotyping in prenatal diagnosis may allow for a more effective detection of chromosomal abnormalities.

Phenotypic variance in children with chromosomal aberrations – A cohort study

Background: Chromosomal abnormalities are the result of alterations in the number or structure of chromosomes leading to significant human morbidity and mortality. They are responsible for large proportion of miscarriages, developmental delay, disorders of sexual development, congenital malformations, and mental retardation. Objectives: The objectives of the study were to find the occurrence of chromosomal abnormalities in infants and children with various phenotypic presentations and to analyze the impact of associated risk factors for chromosomal abnormalities in children. Materials and Methods: A retrospective single-center study, based on the outcome data of chromosomal analysis of 112 children admitted to the pediatric department of our hospital over a period of 3 years, was reported. The data were collected from the electronic medical records for analysis, including maternal age, consanguinity, family history of any congenital anomalies and malformations, clinical details, and the results of chromosomal analysis. Results: A statistically significant association between the presence of dysmorphic features and chromosomal abnormalities with 3 times increased risk when compared to children with no dysmorphism (relative risk [RR] 3.06, 95% confidence interval [CI] 1.71–5.50, p=0.0002). Among the congenital anomalies, the presence of congenital heart defects had strong association and was found to be 43% higher in children with chromosomal abnormalities (RR 1.43, 95% CI 1.10–1.86, p=0.0069). Our study demonstrated a strong association for maternal age >35 years and the risk for chromosomal abnormality. It was 1.75 times more than the children born to mothers ?35 years age (RR 1.75, 95% CI 1.29–2.36, p=0.0003). Conclusion: Cytogenetics has a major role in diagnosis of chromosomal abnormalities, especially in children with dysmorphic features and congenital heart defects. The early diagnosis is important for planning and resource allocation of specialized health services directed toward the families and infants.

Committee Opinion No. 406: Prenatal Testing After IVF With Preimplantation Genetic Testing for Aneuploidy.

To review the approach to prenatal genetic screening and diagnosis for chromosomal abnormalities in pregnancies conceived through in vitro fertilization and following preimplantation genetic testing for aneuploidy. General practitioners, family physicians, obstetricians, midwives, nurses, maternal-fetal medicine specialists, fertility specialists, genetic counsellors, geneticists, and other health care providers involved in prenatal screening. All individuals or couples who conceivd through in vitro fertilization and underwent preimplantation genetic testing for aneuploidy. Literature published in or before September 2018 was retrieved through searches of Medline, PubMed, and the Cochrane Library. SUMMARY STATEMENTS.

Молекулярное кариотипирование в практике пренатальной диагностики: опыт, проблемы, перспективы

В последнее время происходит активное внедрение высокоразрешающих методов диагностики для выявления хромосомных аномалий у человека. Так, использование микрочиповой диагностики (aCGH) позволяет выявлять хромосомные аномалии у 6 % плодов с нормальным кариотипом, определённым стандартными цитогенетическими методами. При этом для пренатальной диагностики aCGH используется в значительно меньших объемах. В первую очередь это обусловлено получением большого объема информации и сложностями её интерпретации. В настоящей работе приводятся результаты использования aCGH для пренатальной диагностики в НИИ медицинской генетики Томского НИМЦ. Исследованы 44 образца плодного материала методом aCGH. В 20 случаях (45 %) идентифицирован геномный дисбаланс, сбалансированный кариотип был выявлен в 21 образце (48 %). В трех случаях (7 %) результат не был получен вследствие недостаточного количества или низкого качества биологического материала. Среди 20 случаев с хромосомными аномалиями было 4 образца с анеуплоидиями и 16 образцов с вариациями числа копий ДНК (CNV), из них 13 делеций и 10 дупликаций. Все CNV, выявленные в результате исследования, не представлены или представлены единичными случаями в базе данных DGV. По клинической значимости выявленные CNV распределились следующим образом: 5 аномалий с неясной клинической значимостью, 5 вероятно патогенных и 11 патогенных. Патогенные CNV были представлены 7 делециями и 4 дупликациями, идентифицированными в 10 образцах. Кроме «целевых» патогенных CNV, выявляются и так называемые случайные патогенетически значимые CNV. Случайные находки характерны для всех широкогогеномных и полногеномных исследований и вызывают сложности при медико-генетическом консультировании, связанные с информированием пациентов и возможным прерыванием беременности. В настоящем исследовании было выявлено по пять CNV (24 %), относящихся к группам случайных патогенных и с неясной клинической значимостью. Результаты настоящей работы свидетельствуют о необходимости использования современных молекулярно-цитогенетических методов для пренатальной диагностики хромосомных аномалий. При этом необходимо учитывать возникновение новых методических и этических вопросов, которые наиболее остро стоят при использовании этих методов в пренатальной диагностике. Recently, there has been an active introduction of high-resolution diagnostic methods for detecting chromosomal abnormalities in humans. Thus, the use of microarray diagnostics allows detecting 6% more chromosomal abnormalities in fetuses with a normal karyotype based on the results of standard cytogenetic methods. At the same time, as part of the prenatal diagnosis, aCGH is used in much smaller amounts. This is primarily due to the receipt of a large amount of information and difficulties with its interpretation. This paper presents the results of using the aCGH method in prenatal diagnosis at the Research Institute of Medical Genetics of the Tomsk National Research Medical Center. In the framework of prenatal diagnosis, 44 samples of fetal material were examined using the aCGH method. Prenatal diagnosis using microarray in 20 cases (45%) allowed to identify chromosomal abnormalities, a balanced karyotype was detected in 21 samples (48%). In three cases (7%) the result was not obtained due to insufficient quantity or low quality of the biological material. Among the 20 cases with chromosomal abnormalities, 4 samples with aneuploidy and 16 samples with CNV. In 16 samples of fetal material without aneuploidy, 13 deletions and 10 duplications were identified. All the adjustments included in this list are not represented or represented by isolated cases in the Database of Genomic Variants. When analyzing the clinical significance of the CNV, were identified 11 pathogenic, 5 probably pathogenic and 5 CNV with uncertain significance. Pathogenic rearrangements were represented by 7 deletions and 4 duplications identified in 10 samples. In addition to the “Primary Finding” of pathogenic CNVs, so-called “Incidental Finding” of pathogenetically significant rearrangements are also detected. The identification of “Incidental Finding” is characteristic of all genome-wide studies and leads to the emergence of ethical issues related to informing patients and the possible termination of pregnancy. In the present study, five “Incidental Finding” pathogenic CNVs and five rearrangements with uncertain significance were identified. The results of this work indicate the need to use modern molecular cytogenetic methods for the prenatal diagnosis of chromosomal abnormalities. It is necessary to take into account the emergence of new methodological and ethical issues that are most acute when using these methods in prenatal diagnosis.

Gabapentin Use for Hospitalized Neonates

BackgroundDespite some clinician advocacy for the use of gabapentin to treat neonatal irritability of presumed neurological origin, the extent of gabapentin administration to hospitalized neonates is unknown. We aimed to identify trends in gabapentin utilization among infants hospitalized in neonatal intensive care units (NICUs) across the United States and to evaluate the associations between clinical diagnoses and gabapentin treatment. MethodsWe analyzed neonates admitted to the NICU using the Pediatric Health Information System (2005 to 2016) to measure treatment timing, duration, and frequency. We used modified Poisson regression with a robust between-cluster variance estimator to calculate a probability (adjusted relative risk) for gabapentin administration. ResultsOf 278,403 neonates, 374 were administered gabapentin (0.13%). The median treatment duration was 16 days (25th to 75th percentile: 8; 40). Gabapentin use increased from 0% in 2005 to 0.39% in 2016. Treatment was prescribed to neonates at 31 of 48 studied hospitals; 73% of total treated infants localized to five neonatal intensive care units. Term (0.16%) and ≤28 weeks' gestation preterm infants (0.22%) were most likely to receive gabapentin. Varying by gestational age, a diagnosis of chromosomal abnormalities, severe bronchopulmonary dysplasia, hemorrhagic stroke, and neonatal abstinence syndrome were associated with higher treatment with gabapentin. The majority (88.8%) of treated infants did not have a seizure diagnosis. ConclusionGabapentin use in NICU in the United States increased in recent years and varies markedly between institutions. Term infants, ≤28 weeks' gestation preterm infants, and neonates with chronic genetic, neurological, and gastrointestinal diagnoses were more likely to receive gabapentin.

OP22.05: Changes in the utilisation of prenatal screening and diagnosis of chromosomal abnormalities in the era of cell‐free DNA

OP22.05: Changes in the utilisation of prenatal screening and diagnosis of chromosomal abnormalities in the era of cell‐free DNA

Эффективность пренатальной диагностики синдрома Дауна в шести областях Центрального и Юго-Восточного регионов Украины

Chromosomal aneuploidy (CA), having an incidence rate of 6-8 per 1000 live births, holds a special place in the structure of congenital and hereditary pathology. Among the common CA, trisomy 21 chromosomes (T21) is the most frequently found (its incidence rate in the general population amounts to 1:700–800 live births). The objective: to study the efficiency of prenatal screening of CA (Down’s syndrome, DS) in the areas under the Center’s operational activity in the period of 2010-2015; To estimate the actual prevalence of DS in terms of born and prenatally diagnosed, eliminated fetuses with T21; On the basis of retrospective analysis of indications for prenatal karyotyping, in all detected cases of DS, to specify their structure and incidence rate; Based on data from medical literature, to make a comparative analysis with similar studies in different countries around the world. Patients and methods. Over the six years (2010–2015) we have performed 3,137 invasive prenatal interventions, among which are 720 chorionic villus biopsies, 929 placententesises, and 1,488 amniocentesis of pregnant women having a high risk of CA, who were seeking medical help from our center whose operational activity covers 6 provinces (oblasts). Results. From 3,137 prenatally karyotyped studies, there have been found only 558 cases of fetal CA, including 288 fetuses with T21. A retrospective analysis of the structure of indications for invasive prenatal diagnosis in 288 pregnant women, having fetuses with prenatally detected DS, is presented as follows: – separate: only 40-aged and above mothers – 4 (1.38%); Ultrasound (US)-findings (anomalies and markers of CA) – 192 (69.5%); High biochemical risk of CA – 2 (0.7%). – combined: the mother’s age is 40 and above + US findings – 36 (13%); The mother’s age is 40 and above + US and biochemical (BC) markers – 8 (2.8%); Ultrasound findings + positive BC test – 32 (11.5%). Delivery of the previous child with DS by a pregnant woman under 40 years with no ultrasound and BC markers – 1 (0.34%). In total, ultrasound findings (anomalies and markers of CA) were found in 97.5% of cases of prenatally detected fetuses with DS. The index of prenatal detection of fetuses with Down syndrome of all registered karyotyped cases of T21 (pre- and postnatal) in the Dnepropetrovskaya oblast corresponds to the average European level - 65%, (in the areas of the center’s operational activity – 37.7%). Taking into account 242 cases of DS in fetuses aborted prior 22 weeks of gestation, the actual prevalence of T21 in case of their birth would be 1:766 (13 per 10.000 infants). Conclusions. Prevalence of Down syndrome among newborns in the Dnepropetrovskaya oblast as a result of prenatal diagnosis of chromosomal abnormalities makes 1: 1257, which is 1.8 times lower than the incidence in the average population (1:700); In other areas covered by the center’s consulting and diagnostic activity this rate is 1.1–1.55 times lower than that of the population one. In the absence of the existing system of prenatal diagnosis of Down syndrome, its average prevalence in these provinces would correspond to that of the general population 1:766 newborns. Key words: сhromosomal abnormalities, Down syndrome, prenatal screening strategies, ultrasound diagnosis, invasive prenatal diagnosis, ultrasound markers.

Legitimacy of systematic karyotype evaluation of cattle qualified for reproduction

Cytogenetic studies enable the identification and early elimination from breeding of animals affected by hereditary karyotype defects. These defects cause developmental disorders and a significant decrease of fertility parameters (from a few dozen to 100%) and productivity of breeding herds, and consequently measurable financial losses. Due to the potential possibility of spontaneous occurrence of chromosomal aberrations and rapid spreading of these genetic defects in the population, especially in the conditions of the use of artificial insemination, it is necessary to carry out regular karyotype control of breeding animals. Cytogenetic monitoring of cattle qualified for reproduction guarantees the systematic identification of all karyotype abnormalities carriers, which, causing the decrease of fertility or sterility, determine the low reproductive performance of animals affected by these defects. The cytogenetic control system, implemented by the use of constantly perfected cytomolecular techniques, enables a very precise, reliable evaluation of karyotype and diagnosis of chromosomal abnormalities, as well as formulation of specific recommendations for culling.

Tracheostomy Among Infants With Hypoplastic Left Heart Syndrome Undergoing Cardiac Operations: A Multicenter Analysis

Less than 2.7% of infants undergoing congenital heart disease operations have difficulty weaning from invasive mechanical ventilation. In such instances, clinicians may choose to perform tracheostomy. Limited literature has examined tracheostomy placement specifically in infants with hypoplastic left heart syndrome (HLHS). This study evaluated the risk factors for tracheostomy placement in infants with HLHS and examined the outcomes of these infants before their first hospital discharge. This retrospective analysis of the Pediatric Heath Information System data set included infants with HLHS who underwent stage 1 Norwood operation, a hybrid procedure, or heart transplant from 2004 through2013. We identified 5721 infants with HLHS, and 126 underwent tracheostomy placement. Infants in the tracheostomy group had more morbidities and a higher mortality rate across the study period. Diagnosis of chromosomal abnormalities, anomalies of the trachea and esophagus, larynx, diaphragm and nervous system, bilateral vocal cord paralysis, and necrotizing enterocolitis, and procedures including extracorporeal membrane oxygenation support, cardiac catheterization, and gastrostomy tube were independently associated with tracheostomy placement in the study population. Despite an overall increase in rates of tracheostomy performed in infants with HLHS during the study period, the mortality rate did not improve among tracheostomy patients. Several risk factors were identified in infants with HLHS in whom a tracheostomy was placed during their first hospitalization. Despite an overall increase in rates of tracheostomies during the study period, the mortality rate did not improve among these patients. Appropriate family counseling and thorough preoperative case selection is suggested when discussing possible tracheostomy placement in infants with HLHS.

Invasive Procedures in Monochorionic Twins

ABSTRACT Monochorionic twin pregnancies (MC) are less frequent but they are considered higher risk pregnancies compared to dichorionic pregnancies. As a result, determining the chorionicity of a twin pregnancy is of vital importance for the surveillance and management of the pregnancy. The problem originates from the fact that monochorionic twins have one placenta, and as a result the circulation of the two fetuses is closely related to each other mainly through anastomosis of the placenta. The number and type of anastomosis is of great importance for the course of the pregnancy. Diagnosis of chromosomal abnormalities in such pregnancies requires excellent knowledge of invasive procedures and good clinical skills. Monochorionic twins are at increased risk for unique complications including twin-to-twin transfusion syndrome (TTTS), selective intrauterine growth restriction (sIUGR), and twin-reversed arterial perfusion (TRAP) sequence. Twin-to-twin transfusion syndrome is a very well known and described complication of monochorionic twin pregnancies and must be considered and checked in each monochorionic pregnancy. Selective feticide is not a method used very commonly in MC pregnancies, but may be applied in selected cases. For TTTS laser treatment of the anastomosis is a method of choice, but should be performed in centers with experience. How to cite this article Antsaklis A, Antsaklis P. Invasive Procedures in Monochorionic Twins. Donald School J Ultrasound Obstet Gynecol 2015;9(3):280-292.

The value of microarray-based comparative genomic hybridisation (aCGH) testing in the paediatric clinic

Many human genetic disorders result from an unbalanced chromosomal abnormality in which there is a loss or gain of chromosomal material. Since the 1970s, such imbalances have traditionally been detected...

BACs-on-beads: a new robust and rapid detection method for prenatal diagnosis

Karyotyping, the gold standard used for diagnosis of chromosomal abnormalities, is being progressively replaced by rapid aneuploidy testing (RAT) techniques such as quantitative fluorescence-PCR, FISH and multiplex ligation-dependent probe amplification for diagnosing the common aneuploidies or chromosomal microarray analysis for comprehensive genome-wide testing. However, due to technical limitations, current RATs are confined to the detection of common aneuploidies 13, 18, 21 and sex chromosomes. To overcome the limitations of RATs, a bacterial artificial chromosomes-on-beads (BoBs™) assay technology has been introduced for the detection of the common aneuploidies as well as specific microdeletion syndromes. The BoBs assay is a bead-based multiplex assay using polystyrene beads impregnated with two spectrally distinct infrared fluorochromes to create a liquid array of up to 100 unique spectral signatures that supports the analysis of that scale of simultaneous hybridization assays on a minute DNA sample. This review gives an overview on the collective experiences of BoBs applications in prenatal diagnosis.

Single‐copy gene‐based chromosome painting in cucumber and its application for chromosome rearrangement analysis in Cucumis

Chromosome painting based on fluorescence in situ hybridization (FISH) has played an important role in chromosome identification and research into chromosome rearrangements, diagnosis of chromosome abnormalities and evolution in human and animal species. However, it has not been applied widely in plants due to the large amounts of dispersed repetitive sequences in chromosomes. In the present work, a chromosome painting method for single-copy gene pools in Cucumis sativus was successfully developed. Gene probes with sizes above 2 kb were detected consistently. A cucumber karyotype was constructed based on FISH using a cocktail containing chromosome-specific gene probes. This single-copy gene-based chromosome painting (ScgCP) technique was performed by PCR amplification, purification, pooling, labeling and hybridization onto chromosome spreads. Gene pools containing sequential genes with an interval less than 300 kb yielded painting patterns on pachytene chromosomes. Seven gene pools corresponding to individual chromosomes unambiguously painted each chromosome pair of C. sativus. Three mis-aligned regions on chromosome 4 were identified by the painting patterns. A probe pool comprising 133 genes covering the 8 Mb distal end of chromosome 4 was used to evaluate the potential utility of the ScgCP technique for chromosome rearrangement research through cross-species FISH in the Cucumis genus. Distinct painting patterns of this region were observed in C. sativus, C. melo and C. metuliferus species. A comparative chromosome map of this region was constructed between cucumber and melon. With increasing sequence resources, this ScgCP technique may be applied on any other sequenced species for chromosome painting research.

Prenatal ultrasound screening for external ear abnormality in the fetuses.

Objectives. To investigate the best time of examination and section chosen of routine prenatal ultrasound screening for external ear abnormalities and evaluate the feasibility of examining the fetal external ear with ultrasonography. Methods. From July 2010 until August 2011, 42118 pregnant women with single fetus during 16–40 weeks of pregnancy were enrolled in the study. Fetal auricles and external auditory canal in the second trimester of pregnancy were evaluated by routine color Doppler ultrasound screening and systematic screening. Ultrasound images of fetal external ears were obtained on transverse-incline view at cervical vertebra level and mandible level and on parasagittal view and coronal view at external ear level. Results. Five fetuses had anomalous ears including bilateral malformed auricles with malformed external auditory canal, unilateral deformed external ear, and unilateral microtia. The detection rate of both auricles was negatively correlated with gestational age. Of the 5843 fetuses undergoing a routine ultrasound screening, 5797 (99.21%) had bilateral auricles. Of the 4955 fetuses following systematic screening, all fetuses (100%) had bilateral auricles. The best time for fetal auricles observation with ultrasonography is 20–24 weeks of pregnancy. Conclusions. Detection of external ear abnormalities may assist in the diagnosis of chromosomal abnormalities.

Prevalence of various chromosomal disorders diagnosed in a selected population suspected of having genetic diseases from different regions of the valley of Kashmir, North India

A routine chromosome analysis is being used as a starting point for the diagnosis of chromosomal aberrations by conventional karyotyping. This screening is taken up with an aim to evaluate the prevalence of the patients living with different chromosomal aberrations by conventional karyotyping. A total of 462 suspected cases for different chromosomal abnormalities were included and screened between 2011 and 2013 from the different regions of Kashmir (J & K state, India). Out of the 462 patients, abnormal chromosomes as trisomies, monosomies and translocations were found in 82 (17.75 %) of the cases, whereas 380 (82.25 %) were found to be of normal karyotype. Overall frequency of the various chromosomal disorders found in this investigation was as: Down’s syndrome 11.04 % (51 of 462), Turner’s syndrome 4.11 % (19 of 462), Klinefelter’s syndrome 1.95 % (09 of 462), two Robertsonian translocations t (13:14) 0.43 % (02 of 462) and one triple X with Xp deletion were found in 0.22 % (01 of 462) females who had recurrent missed abortions. Further, out of 24 cases of ambiguous genitalia screened, 12 (50 %) were detected either with 46, XX or 46, XY karyotype. In conclusion we found that people with different genetic disorders particularly chromosomal abnormalities do exist in our population. Among these disorders, Down’s syndrome seems to be occurring at a higher frequency which is possibly due to late marriages with higher maternal age. We also found that interrelation marriages (consanguineous marriages) play an important role in the prevalence of these genetic disorders. The study signifies the importance of karyotyping for the confirmation of clinical diagnosis of chromosomal abnormalities.

Value of detection of cell-free fetal DNA in maternal plasma in the prenatal diagnosis of chromosomal abnormalities

To investigate the value of detection of fetal cell-free fetal DNA (cff-DNA) in maternal plasma in the prenatal diagnosis of chromosomal abnormalities. The plasma from 3200 gravidas (singleton with 20.3 ± 3.8 gestational weeks) was collected from April 1(st) 2011 to May 30(th) 2012. They were divided into 3 groups: (1) To tally 1720 cases were included in the high-risk serological screening group, in which women were younger than 35 years and got high-risk results in serological screening; (2) To tally 1310 cases were included in the advanced age group, in which women's age was more than 35 years; (3) To tally 170 cases were included in the supplementary group, in which women were younger than 35 years and got low-risk results in serological screening, or women who didn't take serological screening tests. All the 3030 gravidas in group 1 and 2 didn't take invasive prenatal diagnosis because of fear of abortion or short of prenatal diagnosis. Cff-DNA were detected by next generation sequencing in Shenzhen BGI Genomics Center for clinical laboratory. Amniocentesis and karyotype analysis were provided to the positive cases and women with negative results were followed-up by telephone. (1) The 3200 cases took cff-DNA detection, and 31 cases got positive results, including 27 cases of trisomy 21 and 4 cases of trisomy 18. Sixteen cases of trisomy 21 and 1 case of trisomy 18 were in the high-risk serological screening group. 7 cases of trisomy 21 and 2 cases of trisomy 18 were in the advanced age group. Four cases of trisomy 21 and 1 case of trisomy 18 were in the supplementary group. (2) And the 84% (26/31) cff-DNA detecting positive cases received amniocentesis. In the 27 trisomy 21 positive cases, 23 received amniocentesis and got karyotype of 47XN, +21, with the diagnostic accordance rate of 100%. In the 4 cases who didn't take karyotype analysis, fetal anomaly (ventricular septal defect, dextrocardia and choroid plexus cyst) was found in 1 case before 20 gestational weeks; intrauterine fetal demise happened in 1 case before getting the result; 2 other cases who already had healthy children took abortion in the local hospital without taking amniocentesis. In the 4 trisomy 18 positive cases, 3 took amniocentesis, 2 of which were trisomy 18 and took abortion, the other was chimera (46, XN/47, XN, +18) with only 2% cells of trisomy 18, with no malformation found after delivery. Hypoevolutism (3 weeks less than gestational week), general hydropsy and intrauterine fetal demise happened before the other case took amniocentesis. (3) Follow up of cff-DNA negative cases:until May 30(th) 2012, no Down's baby was found in the 1230 cases with cff-DNA test negative results. (1) The non-invasive fetal trisomy test (NIFTY) by next generation sequencing is a safe, accurate and high throughput method for the prenatal diagnosis of trisomy-21. (2) Use NIFTY as a further screening for pregnant women with high-risk serological screening results could lower invasive prenatal diagnosis rate. (3) Cases with positive NIFTY test results should receive amniocentesis and karyotype analysis to confirm the diagnosis before abortion.

First trimester prenatal screening among women pregnant after IVF/ICSI

Prenatal screening and diagnosis of chromosomal abnormalities especially Down's syndrome in IVF pregnancies are complicated by higher maternal age, a high multiple pregnancy rate, a high risk of a vanishing twin and an increased risk of chromosomal abnormalities, particularly in pregnancies after ICSI. The aim of the present systematic review was to evaluate the findings of first trimester screening for chromosomal abnormalities in IVF/ICSI singleton and twin pregnancies. A systematic MESH-term search in MEDLINE using PubMed and the Cochrane Library was performed until May 2011, with no earlier date limit. The electronic search retrieved 562 citations, 96 of which were evaluated in detail and 57 were then excluded for not meeting the selection criteria. A total of 61 articles were finally selected for review. Our analysis of the data shows that, for IVF/ICSI singletons, combined first trimester prenatal screening based on maternal age, nuchal translucency scan and biomarkers is appropriate. However, biomarkers seem to be altered, causing a higher false-positive rate, in IVF/ICSI singleton gestations. Correction factors have been developed and should be used when screening for Down's syndrome in singleton pregnancies. With regard to IVF/ICSI twin pregnancies, biomarker values seem to be dependent on chorionicity as well as gestational age. Whether the use of a correction factor for mode of conception in the risk calculations for Down's syndrome in twin pregnancies is valid has not been fully elucidated. In vanishing twin pregnancies with a second gestational sac with a dead fetus, first trimester screening should be based solely on the maternal age and the nuchal translucency scan as biomarkers are significantly altered in these cases. First trimester prenatal screening after IVF/ICSI treatment requires specific precautions in both singleton and twin pregnancies.

Cribado de cromosomopatías fetales en España. Cambios hospitalarios en el periodo 2006–2011

IntroductionThere was no uniform policy for prenatal screening and diagnosis of chromosomal abnormalities in Spain until 2006. The Spanish Society of Obstetrics and Gynaecology (SEGO) recommends rejecting advanced maternal age as the only indication for invasive procedure, and proposes the first trimester combined test. ObjectiveTo determine the level of implementation of the SEGO recommendations and the changes in hospital screening practice in Spain. MethodsA total of 54 Hospitals, that had attended to 149,320 pregnant women, and 53 hospitals with147,195 pregnancies, responded to an e-mail survey, in the year 2007 and 2011, respectively. The McNemar test was used to compare the results. ResultsA total 26 hospital centres performed invasive procedures for advanced maternal age only in 2007, and 11 in 2011 (P=.01); 31 had chorionic villus sampling (CVS) available in 2007, and 33 in 2011 (P=.005); in 42 implemented first trimester combined screening in 2007, and 50 in 2011 (p=ns); in 30 hospitals the only ultrasound marker was Nuchal translucency in 2007, and in 36 in 2011 (p=ns); 26 did not know the type of analyser used for determining biochemical markers in 2007, and 17 in 2011 (P<.01); and 34 the laboratory performed risk calculation in 2007 and 36 in 2011 (p=ns). ConclusionFirst trimester combined screening test is widely available across Spanish hospitals, and most centres, do not consider advanced maternal age as the only indication for the invasive procedure, have CVS available, perform combined first trimester test only with nuchal translucency as an ultrasound marker, do not know the analyser used for measure biochemical markers, and that the laboratory provide risk calculations.