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At least 19 recordsLinked to original sources
PubMed2025

Visualization using NIPTviewer support the clinical interpretation of noninvasive prenatal testing results.

BACKGROUND: Noninvasive prenatal testing (NIPT) is increasingly used to screen for fetal chromosomal aneuploidy by analyzing cell-free DNA (cfDNA) in peripheral maternal blood. The method provides an opportunity for early detection of large genetic abnormalities without an increased risk of miscarriage due to invasive procedures. Commercial applications for use at clinical laboratories often take advantage of DNA sequencing technologies and include the bioinformatic workup of the sequence data. The interpretation of the test results and the clinical report writing, however, remains the responsibility of the diagnostic laboratory. In order to facilitate this step, we developed NIPTviewer, a web-based application to visualize and guide the interpretation of NIPT data results. RESULTS: NIPTviewer has a database functionality to store the NIPT results and a web interface for user interaction and visualization. The application has been implemented as part of a novel analysis pipeline for NIPT in a diagnostic laboratory at Uppsala University Hospital. The validation data set included 84 previously analyzed plasma samples with known results regarding chromosomes 13, 18, 21, X and Y. They were sequenced in six different experiments, uploaded to NIPTviewer and assigned to a clinical laboratory geneticist for interpretation. The results of all previously analyzed samples were replicated. CONCLUSION: NIPTviewer facilitates NIPT results interpretation and has been implemented as part of a NIPT analysis routine that was accredited by the national accreditation body for Sweden (Swedac).

Humans↗
PubMed1994

[Noninvasive serum test for prenatal detection of Down syndrome, other chromosome abnormalities and open neural tube defects--a prospective study].

Between September 1st 1990 and Juli 31st 1993, 5071 pregnant women were screened prospectively by the "triple-test", including maternal serum alpha-fetoprotein, human chorionic gonadotropin and unconjugated oestriol in order to detect chromosomal anomalies and open neural tube defects. The serum samples were collected in collaboration with the obstetricians of the region of West-Mecklenburg and North-West-Brandenburg. Laboratory testing using radioimmunoassays was performed between weeks 15 and 20 of gestation, all serum specimens being investigated in only one institution. The original alpha-software from Wald et al. was the basis for calculating the statistical risk for Down's syndrome. Pregnant women with a high risk for Down's syndrome (cutoff > or = 1:250) were taken care of in a special outpatient clinic including procedures like amniocentesis and fetal blood sampling. Amongst 5071 pregnant women, 21 fetal anomalies were seen. Five cases of Down's syndrome, three of trisomy 18, one trisomy 13, two cases of triploidy and four cases of open neural tube defects, one 46 xy/45 x mosaic karyotype and one case of gastroschisis could be diagnosed correctly. One case of trisomy 21, one case of trisomy 18 and two open neural tube defects showed false negative results. Using the cutoff of 1:250 for prenatal detection of Down's syndrome and performing ultrasound routinely to determine gestational age, the sensitivity of the "triple-test" was 83.33% having a specificity of 92.68%. The predictive value of a positive test for prenatal diagnosis of Down's syndrome was 1.33%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2026

Novel and High-Throughput Method of Isolating Single Fetal Cells Using FACS for NIPT.

OBJECTIVE: To evaluate fluorescence activated cell sorting (FACS) as a method of single-cell isolation of rare circulating fetal cells from maternal blood for use in cell-based non-invasive prenatal testing (cbNIPT). METHOD: Blood samples (30 mL) were collected from 75 'low-risk' pregnant women (gestational age 10-15 weeks). Fetal cells were enriched and stained using magnetic activated cell sorting. Following enrichment, single fetal cells were sorted in individual PCR tubes by FACS. After cell lysis, verification of fetal cell origin was performed using short tandem repeat (STR) analysis with the GlobalFiler PCR Amplification kit. RESULTS: An average of 13.7 cells were sorted using FACS. STR analysis identified 8.2 fetal cells on average, representing 60.2% of the sorted cells. The four-step single-cell isolation procedure facilitated an overall enrichment of approximately 16-million-fold. One sample did not render any fetal cell, corresponding to 1.3% of the samples. CONCLUSION: FACS, which is typically used for segregation of large populations of cells, can be used for single-cell isolation of rare fetal cells in an automated setup. This not only helps in making cell isolation faster and high throughput but also provides fetal cells for a more comprehensive genetic analysis of the fetus.

Humans↗
PubMed1993

Nuchal-fold thickening in Down syndrome fetuses: transient appearance and spontaneous resolution in the second trimester.

To elucidate the cause of the wide variation of sensitivity of the nuchal-fold thickness (NFT) for a noninvasive prenatal screening test for fetal Down syndrome, we consecutively measured the NFT throughout pregnancy in eight fetuses with Down syndrome and 100 normal fetuses (negative controls) using video-recorded ultrasonography. When 6 mm was set as the cutoff value, 6/8 Down syndrome fetuses showed a NFT above this value at least once during pregnancy. However, the thickening was transient in 5 of them and resolved spontaneously during the second trimester. Persistent thickening of nuchal-fold was only observed in one fetus. From the results of the present study, we recommend that the NFT be measured repetitively during the first and second trimesters as a noninvasive prenatal screening test for Down syndrome.

Down Syndrome↗
PubMed1996

Prenatal diagnosis using fetal cells isolated from maternal peripheral blood: a review.

Many questions remain about the feasibility of using fetal cells from maternal blood for prenatal diagnosis. Although recently there has been more focus on clinically relevant methods, many studies have been performed using blood drawn after invasive procedures, and over a wide range of gestational ages. For methods to be applicable to clinical use, more work is needed on isolating cells early in pregnancy, when termination is still an option for parents who are found to have an affected pregnancy. It is generally agreed that fetal nucleated erythrocytes are the most efficacious cell type for prenatal diagnosis, but it has not yet been shown definitively whether there is an ideal gestational age for sampling, whether ABO incompatibility might limit availability of fetal cells, or whether the number of cells present might be different in normal versus abnormal pregnancies. PCR has been shown to be a powerful tool in allowing amplification and identification of very small amounts of fetal DNA. However, this is limited to cases in which a specific and unique gene from the father is sought. This means that there is the potential to diagnose many paternally inherited autosomal dominant diseases and some autosomal recessive diseases, in which the parents have different and identifiable mutations. However, when parents are both carriers of the same autosomal recessive mutations, or when the disease is X linked, PCR will not aid in prenatal diagnosis. Cytogenetic analysis of fetal cells by FISH after cell sorting is another potentially useful method of prenatal diagnosis, but requires relatively pure samples of fetal cells or an independent marker that allows easy microscopic identification. The latter might be accomplished by identifying fetal cells through their expression of embryonic hemoglobins or because they contain HLA-G mRNA. In addition, current techniques of cell sorting must be improved so that a higher percentage of fetal cells can be isolated. Currently, the best cell sorting techniques usually produce a maximum purity of 10% fetal cells. Commonly, in normal pregnancies, fewer than 0.1% of the cells isolated after sorting are fetal in origin. Improving the concentration and quantity of fetal cells will improve the accuracy of FISH. Methods such as immunophenotyping that allow the selective identification of fetal cells by microscopy, and can be used in conjunction with FISH, may be extremely valuable because they may allow the genetic analysis of only the few fetal cells within a background preponderance of maternal cells. Although the retrieval of fetal cells from maternal blood is an attractive concept, it must be clearly stated that presently it is only in the investigational phase because of the low sensitivity and specificity. There is no current application for these methods in clinical practice. It remains to be determined whether testing maternal blood for fetal cells or DNA will be used as a screening tool, similar to the maternal serum screening currently in use, or whether the accuracy can be improved to a level such that the techniques can be used diagnostically. Although there are many questions that remain unanswered at this time, the outlook for noninvasive prenatal genetic testing in the future is optimistic.

Erythrocytes↗
PubMed1996

Fetal RhD genotyping in fetal cells flow sorted from maternal blood.

OBJECTIVE: The aim of this study was to determine the accuracy of noninvasive fetal RhD genotyping by fetal cell isolation from maternal blood. STUDY DESIGN: Candidate fetal cells from 18 pregnant women (one twin gestation) were flow-sorted. Polymerase chain reaction amplification of a 261 bp fragment of the RhD gene was performed on sorted fetal cells. The presence of amplified product was considered predictive of the Rhd-positive genotype in the fetus. RESULTS: Sixteen of the 19 fetal RhD genotypes were correctly predicted in fetal cells isolated from maternal blood (10 were Rh positive, 6 were Rh negative). In 3 cases no amplification products were detected in RhD-positive fetuses. The association between presence of the fragment and RhD-positive genotype was significant (p=0.003, Fisher's exact test). CONCLUSIONS: Noninvasive prenatal diagnosis of the fetal RhD genotype is feasible. Absence of amplification products in the reaction requires confirmation that fetal material is present. Improvements in fetal cell purity and yield should increase diagnostic accuracy, although the current protocol has a positive predictive value of 100% and a negative predictive value of 67%.

Base Sequence↗
PubMed2026

A Simplified Workflow for the Prediction of Putative Viral Reads Using NIPT Data.

OBJECTIVE: Non-invasive prenatal testing (NIPT) identifies fetal chromosomal abnormalities by sequencing cell-free fetal DNA (cffDNA). Recent studies suggest the prediction of viral sequences from NIPT data, but current methods lack cost-effectiveness for routine use. This study develops a straightforward workflow to investigate potential viral signatures in pregnant women using NIPT data from 888 Iranian participants. METHOD: Two bioinformatic workflows were compared for predicting viral reads: the traditional method involved mapping reads to the human genome, followed by mapping unmapped reads to viral references, and a direct mapping approach to viral genomes, as proposed in this research. RESULTS: While maintaining reproducibility comparable to the conventional method, the proposed workflow minimizes computational complexity and time usage for data processing. Ultimately, this analysis suggested viral DNA in 24.2% of samples, encompassing 29 distinct species, implying the diversity of the maternal virome. CONCLUSION: This study presents a computationally efficient workflow for the in silico prediction of viral-like sequences from routine NIPT data. Further experimental validation is essential to verify the presence, viability, or clinical relevance of these sequences.

Humans↗
PubMed2026

Non-invasive embryo assessment: Cell-free DNA-based genetic testing and amino acid metabolomics in relation to morphology: A case-control study.

BACKGROUND: Cell-free DNA (cfDNA) in spent culture medium (SCM) offers a non-invasive option for preimplantation genetic testing, but its low concentration and fragmentation reduce clinical reliability. Combining genetic assessment with metabolomic profiling may provide complementary information about embryo competence. OBJECTIVE: This study assessed pre-analytical cfDNA processing workflows and examined whether SCM amino acid metabolic patterns could act as practical markers of embryo quality. MATERIALS AND METHODS: In this case-control study (2021-2023), 90 embryos were evaluated using fluorescence in situ hybridization or array comparative genomic hybridization. SCM samples underwent rapid boiling, silica-based purification, or whole-genome amplification (WGA). Sex determination was performed using quantitative polymerase chain reaction (qPCR). For cfDNA quality control and aneuploidy screening, the multiplex IRFiling kit and quantitative fluorescent polymerase chain reaction (QF-PCR) were used. Amino acid profiles across embryonic developmental stages and quality grades were quantified via liquid chromatography-tandem mass spectrometry. RESULTS: Rapid boiling resulted in complete failure of DNA amplification. Conversely, silica-based purification yielded 70.0% concordance for qPCR-based sexing and 56.7% for QF-PCR. WGA achieved the highest efficacy (73.3% qPCR and 56.7% QF-PCR concordance), although quality control checks flagged occasional misclassifications. LC-MS/MS profiling revealed significantly elevated alanine and arginine levels in tripronuclear embryos. Furthermore, high-quality blastocysts exhibited elevated glutamic acid levels alongside a pronounced overall depletion of extracellular amino acids compared to low-quality counterparts and controls. CONCLUSION: WGA improves cfDNA detectability and qPCR accuracy compared with boiling or purification, but remains inadequate as a standalone screening approach. SCM amino acid profiling provides informative, complementary metabolic signatures of developmental competence, supporting a multimodal strategy for non-invasive embryo assessment.

Amino acid metabolism↗
PubMed2025

Identification of maternal Gγ(Aγδβ)0 thalassemia through retrospective reanalysis of prenatal cfDNA sequencing data.

OBJECTIVE: Non-invasive prenatal screening (NIPS) is widely used to detect chromosomal abnormalities such as trisomies 21, 13, and 18 and is also effective in screening for copy number variations (CNVs). However, the routine application of NIPS to detect smaller CNVs within the HBB gene, specifically Gγ(Aγδβ)0 thalassemia, has yet to be well documented. This study aims to evaluate the efficacy of cfDNA-based maternal carrier screening in routine screening for Gγ(Aγδβ)0 thalassemia. METHODS: We performed a retrospective analysis of 107,300 pregnant women who underwent NIPS at Longgang Maternal and Child Healthcare Hospital in Shenzhen from December 2017 to May 2022. Using an improved algorithm, we reanalyzed NIPS data to identify maternal Gγ(Aγδβ)0 thalassemia. Positive cases were confirmed by multiplex ligation-dependent probe amplification (MLPA) using peripheral blood leukocytes. RESULTS: Among the 107,300 NIPS analyses, 38 maternal deletion CNVs within the HBB gene were identified using the improved algorithm, with a prevalence of 0.035% (38/107,300). MLPA confirmed that all detected deletions were consistent with Gγ(Aγδβ)0 thalassemia. The positive predictive value (PPV) for detecting Gγ(Aγδβ)0 thalassemia by cfDNA-based maternal carrier screening was 100%. Among the 38 Gγ(Aγδβ)0 cases, 9 were also associated with α-thalassemia deletions, including 4 cases with -SEA/αα, 4 with -α3.7/αα, and 1 with -α4.2/αα. No cases of homozygosity or compound HBB gene variants were observed. CONCLUSIONS: Gγ(Aγδβ)0 thalassemia is not uncommon in China, and repurposed NIPS methodology for maternal genomic analysis in detecting HBB gene deletions is a reliable method for identifying maternal carriers of this disease.

Humans↗
PubMed2026

Identification of rare maternal copy number variants by genome-wide analysis of noninvasive prenatal screening data in 113,017 pregnant women.

OBJECTIVES: Knowledge of copy number variants (CNVs) is relevant to maternal and fetal health and can be obtained from noninvasive prenatal screening (NIPS) of pregnancy. However, genome-wide analysis of maternal CNVs using NIPS data has not been conducted in large populations. METHODS: For CNV analysis, the human genome was segmented into 10 kilobase pairs (Kb) bins, and the relative sequencing depth of each bin was calculated. The circular binary segmentation algorithm was used to estimate CNVs. Detected CNVs from two pregnancies of the same participant were compared to validate the reproducibility. All CNVs were merged into CNV regions (CNVRs) to evaluate their frequency, distributions, and relationship with disease-related genes and regions. RESULTS: In this study, 113,017 pregnant women were recruited. A total of 363,886 CNVs larger than 50 Kb were detected in 101,779 individuals and merged into 43,005 CNVRs. For evaluating the reproducibility of CNVs, 90.18% of deletions and 88.07% of duplications were consistent. In general, 78.13% of individuals carried CNVRs that overlapped protein-coding genes, while 14.76% overlapped OMIM genes. We detected 246 novel CNVRs, 134 (54.47%) involving protein-coding genes. For the perspective of maternal-fetal health, we identified 4,984 (4.41%) individuals as carriers of 5,243 CNVs containing known pathogenic or likely pathogenic regions, including 22q11.2 region and DMD gene.. CONCLUSIONS: NIPS sequencing data is a reliable source for maternal CNV detection. These CNVs constitute an integrate component in maternal-fetal health management.

Humans↗
PubMed2026

Trophoblast Enrichment by Maternal Immune-Cell Depletion Using CD45 and CD56 Surface Markers in Trophoblast Retrieval and Isolation from the Cervix (TRIC).

Background: Trophoblast retrieval and isolation from the cervix (TRIC) has emerged as a promising alternative to invasive prenatal diagnostic procedures. However, contamination by maternal immune cells remains a major challenge that may compromise trophoblast purity and the reliability of downstream fetal genetic analyses. Methods: Maternal immune cells were selectively depleted by immunomagnetic sorting using antibodies targeting CD45 or CD56. The remaining cells were subsequently enriched for HLA-G-positive trophoblasts and characterized by immunofluorescence and gene-expression analyses using CD45, CD56, HLA-G, cytokeratin 7 (CK7), and β-human chorionic gonadotropin (β-hCG). Results: Compared with CD45-mediated depletion, CD56-mediated depletion demonstrated more efficient removal of maternal immune cells, as indicated by significantly reduced CD56 expression. CK7 expression showed an increasing trend following CD56 depletion, whereas β-hCG expression remained largely unchanged. Immunofluorescence analysis further demonstrated a significant increase in the proportion of CK7+/β-hCG+ trophoblast cells after CD56 depletion. Conclusions: Among the evaluated depletion strategies, CD56-mediated depletion demonstrated a more favorable profile for trophoblast-associated characteristics than CD45-mediated depletion, suggesting its potential contribution to further methodological optimization of trophoblast isolation in TRIC-based noninvasive prenatal genetic testing.

maternal immune cell↗
PubMed1993

Prenatal diagnosis using fetal cells from the maternal circulation.

All current methods of fetal karyotyping are invasive and carry a definite, albeit small, procedure-related risk. Because of this and testing costs, only women older than 35 years who have a greater risk for fetal aneuploidy are currently offered prenatal testing. But this detects only 20% to 25% of fetuses with Down syndrome. It would be a tremendous advance to find a noninvasive technique for prenatal diagnosis that carries no procedure-related risk and could be offered to all pregnant women. We describe a possible technique for noninvasive prenatal diagnosis that aims to identify fetal cells in the peripheral maternal circulation and successfully garner them for prenatal testing. Early attempts at fetal karyotyping were hampered by inaccurate diagnostic methods and cumbersome cell-counting techniques. Today, improved capabilities of identifying and enriching for fetal cells, coupled with sensitive methods of analysis such as the polymerase chain reaction, bring renewed enthusiasm to this task. Many technical issues, as well as serious questions regarding the test's utility, still exist, however, and must be explored and answered before the capture of fetal cells in the maternal circulation translates into reality for noninvasive prenatal diagnosis.

Antibodies, Monoclonal↗
PubMed1994

[The triple test].

Until the late 80s advanced maternal age was the main indication for prenatal chromosomal diagnosis. The triple test has introduced a noninvasive method for all women to determine the risk of chromosomal abnormality. Not only women aged over 35 years, but also those less than 35 years of age may benefit from the triple test. An exactly performed triple test will allow a diagnosis in 70% of all cases with trisomy 21. Additionally, a positive triple test will be found in 9% of all screened women. 1-2% of the women with a positive triple test will exhibit a fetus with trisomy 21. A false-negative result will be found in 0.1%. Beside trisomy 21, the triple test allows also the diagnosis of pregnancies with a high risk of trisomy 18 and Turner syndrome. The value of the triple test is mainly determined by the quality of the laboratory and the exactness of the determination of the gestational age, which is done mainly by means of ultrasound. Ultrasound investigation also provides information about structural abnormalities. In future the triple test will increase in accuracy and it will be performed in the first trimester.

Chromosome Aberrations↗
PubMed1991

The search for fetal cells in the maternal circulation.

Currently, all methods of prenatal diagnosis require an invasive approach. The next step in the continuing challenge to make prenatal diagnosis more accessible is the development of a noninvasive test. The presence of fetal cells in the maternal circulation has been debated for several decades, but traditional attempts to identify the rare fetal cell within the pool of maternal cells have met with partial success at best. Today, with the aid of highly sensitive and specific techniques such as fluorescent activated cell sorting, polymerase chain reaction, and in-situ hybridization, the task of finding the "on-in-a-million" fetal cell is moving from the realm of the imagination into that of reality.

Blood Cells↗
PubMedDate not supplied

Ionizing radiation and the developing brain.

The unique susceptibility of the central nervous system to radiation exposure is attributable to its extensive period of development, the vulnerability of its neuronal cells, the migratory activity of many of its cells, its inability to replace mature neurons, and the complexity of the system itself. Radiation effects may be due to glial or neuronal cell death, interruption of migratory activity, impaired capacity to establish correct connections among cells, and/or alterations in dendritic development. These structural changes are often manifested as behavioral alterations later in life. Sensitivity to radiation (dose-response) is markedly similar among all mammalian species when developmental periods are compared. This review compares and contrasts human and animal behavioral data. Neonatal and postnatal adult behavioral tests have been shown to be sensitive, noninvasive measures of prenatal radiation exposure, although currently their predictive validity for humans is uncertain. Additional research is needed to determine the presence and significance of postnatal morphologic and functional alterations due to prenatal exposure to low levels of ionizing radiation.

Animals↗
PubMed1994

Peroxisomal disorders.

Disorders of peroxisome function result in severe and progressive neurologic deficits. Knowledge of these disorders and their role in neurodegenerative disorders has been growing rapidly over the last 40 years. Noninvasive diagnostic tests can identify all of the peroxisomal disorders, many of them prenatally. The genetic basis of some of these peroxisomal disorders is being established, which will advance understanding of their pathobiology and provide clues for therapeutic interventions.

Adolescent↗
PubMed1993

Prenatal diagnosis and fetal therapy.

The protective effect of folic acid supplementation has been demonstrated in patients at risk of neural tube defects by a large, randomized double-blind study. The feasibility of second-trimester screening for Down syndrome, based on the combination of maternal and biochemical markers on maternal blood, has also been verified in two large series from both the United Kingdom and the United States. These results represent major advances in the field of prenatal diagnosis, which, in the future, is likely to rely more and more on better selection by noninvasive testing of high-risk patients. The emphasis has moved away from very early invasive testing due to concerns related to the safety of both early chorionic villus sampling and amniocentesis. Evaluation of renal damage in fetuses with obstructive uropathy by analysis of urinary biochemistry may constitute the basis for more efficient selection of cases amenable to antenatal treatment. Twin-to-twin transfusion syndrome remains a challenge for the future.

Congenital Abnormalities↗
PubMed1995

Contemporary approaches to prenatal diagnosis.

A variety of options for prenatal diagnosis are available to the pregnant woman. Maternal serum analyte analysis, performed between 15 and 20 weeks' gestation, provides a screening test for fetal neural tube defects and aneuploidy in low-risk pregnancies. Fetal ultrasound examination is of benefit in high-risk pregnancies. The necessity of prenatal screening in the low-risk patient with an established date of last menstrual period is more controversial. Ultrasound examination can establish gestational age, assess fetal number and position, determine placental location and amniotic fluid volume, and rule out major structural anomalies. Invasive fetal testing, including amniocentesis and chorionic villus sampling, should be offered to women who are 35 years of age or older or who have had abnormal results on noninvasive prenatal screening and in cases in which the parents are carriers of genetic conditions that are amenable to prenatal diagnosis.

Amniocentesis↗