Fetal Chromosomal Abnormalities Research Articles

Retrospective study revealed integration of CNV-seq and karyotype analysis is an effective strategy for prenatal diagnosis of chromosomal abnormalities

Fetal chromosomal abnormalities are the main cause of adverse pregnancy outcomes and are the focus of invasive prenatal diagnosis. Recent studies have demonstrated that various techniques have distinct advantages. Achieving high-resolution and effective prenatal chromosomal abnormality diagnosis requires a multi-technology integration strategy. Based on retrospective samples from a single center, we propose that integrating CNV-seq and karyotype analysis is an effective strategy for prenatal diagnosis of chromosomal abnormalities. In this study, 13.80% of the pregnant women (347/2514) were found to have likely pathogenic or pathogenic fetal chromosomal abnormalities using this integrated approach. Among these cases, 53.89% (187/347) had consistent chromosomal abnormalities detected by both CNV-seq and karyotyping analysis, while 19.02% (66/347) and 27.09% (94/347) of cases were diagnosed solely by CNV-seq or karyotyping, respectively. Fetal chromosomal abnormalities were identified in 18.39% of samples with abnormal ultrasound, which was significantly higher than the percentage found in samples with normal ultrasound (p < 0.001). Samples with multiple ultrasound abnormalities and single-indicator ultrasound abnormalities such as nasal bone dysplasia, renal dysplasia, or echogenic fetal bowel also had higher rates of chromosomal abnormalities (p < 0.05) compared to normal samples. Analyzing samples with Trio family data (N = 521) revealed that about 94% of variants of uncertain significance were inherited from parents and were non-pathogenic. Overall, integrating CNV-seq and karyotype analysis is an effective strategy for prenatal diagnosis of chromosomal abnormalities. This study provides valuable insights for correlating prenatal screening indicators with chromosomal abnormalities.

Prenatal Screening and Diagnosis: Time for a Paradigm Shift.

Recent advances in genetics and imaging have ushered in substantial breakthroughs in screening and diagnosis for chromosomal and structural abnormalities. Thus, it is imperative that healthcare providers caring for pregnant individuals should re-examine established practices in prenatal screening and diagnosis. In the past, screening for chromosomal abnormalities was based almost entirely on Down syndrome. Pregnant individuals aged > 35 were considered at "high risk" or of "advanced maternal age" based on age alone; however, the advent of tests with high sensitivity for prenatal detection of chromosomal abnormalities should lead to abandoning that concept, at least from the perspective of chromosomal abnormalities. Given that first-trimester and second-trimester screening will fail to detect between 5 and 20% of Down syndrome, in most situations, non-invasive testing with cell-free DNA should be the first-line screen for Down syndrome. The fact that over 99% of fetuses with Down syndrome will be detected prenatally with cell-free DNA gives other fetal chromosomal and structural abnormalities increasing prominence. Chromosomal microarray analysis (CMA) permits prenatal detection of several clinically important chromosomal aberrations that cannot be detected by karyotype and may exist in structurally normal fetuses with low-risk cell-free DNA screening. As such, CMA should be more readily conducted when invasive testing is performed, regardless of the presence of a structural abnormality. Isolated sonographic "soft markers" have no clinical significance in patients who have normal cell-free DNA screening, can cause unwarranted anxiety and a negative impact on pregnancy, and perhaps it is time to stop discussing them. Detailed first-trimester ultrasound allows early detection of several severe fetal anomalies, and therefore in settings with adequately trained personnel and resources, should be used more frequently. This Opinion traces the evolution of prenatal screening and diagnosis and advocates for a paradigm shift that aligns with recent developments in prenatal screening and diagnostic capabilities.

Prenatal diagnosis of fetal microdeletion and microduplication syndromes among pregnant women with advanced maternal ages

To assess the value of combined chromosomal karyotyping and chromosomal microarray analysis (CMA) and/or copy number variation sequencing (CNV-seq) for the prenatal diagnosis for women with advanced maternal ages, and to explore the challenges of prenatal genetic counseling brought by the types of fetal CNVs and uncertainty of related phenotypes. A retrospective analysis was carried out on 1 841 women with advanced maternal age who underwent interventional prenatal diagnosis at the Prenatal Diagnosis Center of Xiamen University Affiliated Women and Children's Hospital from January 2017 to December 2020. Routine chromosomal karyotyping analysis and CMA/CNV-seq detection were carried out. CMA/CNV-seq had detected pathogenic variants in 2 cases which had failed karyotyping analysis. Two hundred and twenty one fetal chromosomal abnormalities were detected by karyotyping analysis, among which 187 were detected by CMA/CNV-seq. CMA/CNV-seq analysis of 23 cases with balanced chromosome structural aberrations and 10 cases with low proportion mosaicisms (including a marker chromosome) had yielded a negative result. In addition, 26 cases (26/1 841, 1.4%) with pathogenic CNVs were discovered among those with a normal karyotype, of which 13 (50.0%) were recurrent CNVs associated with neurocognitive impairment, with 22q11.21 microdeletions and microduplications being the most common types (26.92%). The combination of karyotyping analysis and CMA/CNV-seq not only increased the rate of prenatal diagnosis, but also complemented with each other, which has facilitated genetic counseling and formulation of prenatal diagnosis strategy for the affected families.

Associations between genomic aberrations, increased nuchal translucency, and pregnancy outcomes: a comprehensive analysis of 2,272 singleton pregnancies in women under 35.

Regarding increased nuchal translucency (NT), the cutoff values used are heterogeneous in clinical practice, this study aims to assess the efficacy of prenatal detection for chromosomal abnormalities and pregnancy outcomes in fetuses with varying NT thicknesses, in order to provide data that supports informed prenatal diagnosis and genetic counseling for such cases. We included 2,272 pregnant women under 35 with singleton pregnancies who underwent invasive prenatal diagnosis between 2014 and 2022. The cohort comprised 2,010 fetuses with increased NT (≥2.5 mm) and 262 fetuses with normal NT but exhibiting a single soft marker. Prenatal diagnoses were supported by chromosomal microarray (CMA) and copy number variation sequencing (CNV-seq) analyses. The detection rates of numerical chromosomal abnormalities were 15.4% (309/2,010) and 17.3% (297/1,717) in the NT ≥2.5 and ≥ 3.0 groups, respectively. Pathogenic/likely pathogenic CNV incidence increased with NT thickness (χ2 = 8.60, p < 0.05), peaking at 8.7% (22/254) in the NT 4.5-5.4 mm group. Structural defects were found in 18.4% of fetuses with NT values between 2.5 mm and 2.9 mm. Chromosomal abnormality rates in the isolated increased NT groups of 2.5-2.9 mm and 3.0-3.4 mm were 6.7% (16/239) and 10.0% (47/470), respectively, with no statistical significance (χ2 = 2.14, p > 0.05). Fetuses with NT thickness between 2.5 and 2.9 mm combined with the presence of soft markers or non-lethal structural abnormalities exhibited a significantly higher chromosomal abnormality risk (19.0%) compared to fetuses with isolated increased NT ranging from 3.5 to 4.4 mm (13.0%). Pregnancy termination rates increased with NT thickness (χ2 = 435.18, p < 0.0001), ranging from 12.0% (30/249) in the NT 2.5-2.9 mm group to 87.0% (141/162) in the NT ≥ 6.5 mm group. CMA or CNV-seq exhibited good performance in identifying genomic aberrations in pregnancies with increased NT thickness. NT ranging from 2.5 mm to 2.9 mm elevated the risk of fetal chromosomal abnormalities, particularly when combined with other soft markers.

Approach and Management of Pregnancies with Risk Identified by Non-Invasive Prenatal Testing.

This study represents our second investigation into NIPT, involving a more extensive patient cohort with a specific emphasis on the high-risk group. The high-risk group was subsequently divided into two further groups to compare confirmed cases versus unconfirmed via direct methods. The methodology encompassed the analysis of 1400 consecutive cases from a single genetic center in western Romania, where NIPT was used to assess the risk of specific fetal chromosomal abnormalities. All high-risk cases underwent validation through direct analysis of fetal cells obtained via invasive methods, including chorionic villus sampling and amniocentesis. The confirmation process utilized QF-PCR, karyotyping, and SNP-Array methods customized to each case. Results: A high risk of aneuploidy at NIPT was identified in 36 out of 1400 (2.57%) cases and confirmed in 28 cases. The study also detected an increased risk for copy number variations (CNVs) in 1% of cases, confirmed in two instances involving one large microdeletion and one large microduplication. Trisomy 21 was the exclusive anomaly where NIPT confirmed all cases with identified risk. High-risk NIPT results which were not validated by invasive methods, were classified as false positives; parents in these cases determined to continue the pregnancy. In conclusion, NIPT can serve as a screening method for all pregnancies; however, in high-risk cases, an invasive confirmation test is strongly recommended.

A rapid PCR-free next-generation sequencing method for comprehensive diagnosis of chromosome disease syndromes in prenatal samples.

The aim of this study is to investigate the application performance of rapid copy number variation sequencing (rCNV-seq) technology for the detection of chromosomal abnormalities during prenatal diagnosis. Samples were collected from 424 pregnant women who were at high-risk for noninvasive prenatal screening in Kunming Maternal and Child Care Hospital from January 2018 to May 2022. rCNV-seq technique was used to detect fetal chromosome abnormalities and compare the results with that of chromosomal karyotype analysis. The Result showed that 330 (77.83%, 330/424) cases indicated chromosomal abnormalities among 424 high-risk pregnant women who underwent rCNV-seq. Moreover, 94 (22.17%, 94/424) cases were discovered to have copy number variations. Among the 330 fetuses with chromosomal abnormalities, common autosomal aneuploidy was observed in 203 cases (47.87%, 203/424) and sex chromosome aneuploidy was observed in 91 cases (21.46%, 91/424). Moreover, the abnormalities in multiple chromosomes were discovered in 33 cases (7.78%, 33/424), and the rare autosomal aneuploidy was observed in 3 cases (0.71%, 3/424). There were 63 fetuses (14.86%, 63/424) with pathogenic CNVs among the 94 fetuses with variable copy numbers. Of the 245 pregnant women who voluntarily selected G-band karyotyping, 1 fetus with copy number variation had normal karyotype results, and the remaining women were consistent with rCNV-seq. Our study revealed that rCNV-seq has higher accuracy in detecting common trisomy and can also detect chromosomal microdeletions or microduplications that cannot be detected by G-banding karyotype analysis. There is no effective treatment for chromosomal diseases, so it is particularly important to prevent chromosomal diseases through genetic counseling and prenatal diagnosis of chromosomal diseases.

The homozygous pathogenic variant of the POMGNT1 gene identified using whole-exome sequencing in Iranian family with congenital hydrocephalus

BackgroundHydrocephalus is one of the most common pathophysiological disabilities with a high mortality rate, which occurs both congenitally and acquired. It is estimated that genetic components are the etiology for up to 40% of hydrocephalus cases; however, causal mutations identified until now could only explain approximately 20% of congenital hydrocephalus (CH) patients, and most potential hydrocephalus-associated genes have yet to be determined. This study sought to find causal variations in a consanguineous family with four affected children diagnosed with hydrocephalus.Material and methodsIn this study, we evaluated twenty-five members of an extended family consisting of a nuclear family with four affected children resulting from a consanguineous couple and eighteen of their relatives, including one hydrocephalus case. The mother of this family was experiencing her 15th week of pregnancy, and cytogenetic evaluation was performed using amniocentesis to identify fetal chromosomal abnormalities. We conducted whole-exome sequencing (WES) on the genomic DNA of the proband to detect the CH-causing variants, followed by confirmation and segregation analysis of the detected variant in the proband, fetus, and family members through Sanger sequencing.ResultsFollowing the bioinformatic analysis and data filtering, we found a homozygous variant [NM_001243766.2:c.74G>A:p.W25X] within the protein O-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) gene confirmed by Sanger sequencing in the proband and segregated with the hydrocephalus in the family. The variant was described as pathogenic and regarded as a nonsense-mediated mRNA decay (NMD) due to the premature stop codon, which results in a truncated protein.ConclusionThe results of the current study broadened the mutational gene spectrum of CH and our knowledge of the hydrocephalus etiology by introducing a novel homozygous variant within the POMGNT1 gene, which had never been previously reported solitary in these patients.

Public Opinions and Attitudes toward Noninvasive Prenatal Testing on Reddit: Content and Sentiment Analysis

Introduction: Noninvasive prenatal testing (NIPT) can be used to detect fetal chromosomal abnormalities early in pregnancy. As eligibility criteria broaden and screening targets expand, gauging public acceptability of NIPT becomes increasingly important. Leveraging social media as a rich source of public discourse, the purpose of this study was to understand public opinions and attitudes toward NIPT on the social media platform Reddit. Methods: We applied content and natural language processing techniques (i.e., sentiment analysis) to textual data collected from 4 Reddit communities focusing on the NIPT content posted from September 2012 to September 2022 (367 posts and 7,822 comments in total). Results: Content analysis findings indicated that social media users consider NIPT to be worthwhile. Reasons NIPT was perceived to be not worthwhile related to unwanted anxiety, and the fact that NIPT results would not change anything about their approach to pregnancy were also expressed. The sentiment analysis identified more positive than negative emotions; the mean sentiment scores ranged from 0.48 to 1.22, depending on the specific Lexicon used. Specific emotions (i.e., trust, fear) were also identified. Conclusion: Our novel approach to understanding public perception and attitudes toward NIPT yielded results that are consistent with conventional patient-oriented research methods. These findings may not only contribute to ongoing improvements in prenatal patient care, research, and policy but also indicate that sentiment analysis applied to social media data can serve as a suitable means to assess public acceptability of NIPT, particularly as public dialogue on this topic increases over time.

Ultrasound signs of fetal chromosomal abnormalities at 11–14 weeks of pregnancy and its value in the era of modern genetic testing

A steady increase in average maternity age at the time of first childbirth lead to a higher risk of fetal chromosomal abnormalities. The Order No. 1130n of the Ministry of Health of the Russian Federation establish the screening protocol at 11–14 weeks of gestation with assessing the followed criteria of fetal chromosomal pathology: the nuchal translucency thickness, nasal bone measurement, ductus venosus pulsatility index, tricuspid regurgitation, and heart rate. The value of non-invasive prenatal testing (NIPT) in the early prenatal diagnosis of the most common chromosomal abnormalities, as the trisomies 21, 18, 13, and monosomy X is also increasing. Additionally, numerous other fetal karyotype abnormalities can also be suspected at 11–14 weeks of gestation by revealing a number of other ultrasound signs. The article presents the literature review on additional ultrasound signs of various, both more and less common, chromosomal abnormalities. Pathological signs, abnormalities of fetal anatomy and extrafetal structures in the first trimester, which could be used as additional ultrasound signs of chromosomal pathology of various organs and systems (central nervous system and head, heart and blood vessels, urinary system, abdominal organs, fetal skeleton, as well as the placenta, umbilical cord, amniotic membranes) are described in the article. Despite the use of NIPT, including its extended panels, there remains a need to use ultrasound to detect the signs of rarer, but no less significant chromosomal pathologies, such as triploidies, mosaic trisomies, rare autosomal trisomies, duplications, and deletions.

Perinatal characteristics and pregnancy outcomes of advanced maternal age women with gestational diabetes mellitus: A retrospective cohort study.

The prevalence of gestational diabetes mellitus (GDM) continues to increase, and the phenomenon of women giving birth at an older age is becoming more common worldwide. Less is known abouts the impact of GDM combined with advanced maternal age (AMA) on pregnancy outcomes. To explore the impact of AMA complicated with GDM on pregnancy outcomes. This study included 34,602 pregnancies between 2018 and 2020 in Hangzhou, China. The pregnant women were divided into four groups according to advanced age (≥35 years) and GDM as follows: AMA women without GDM (non-AGDM) group (n = 2614), young pregnant women with GDM (YGDM) group (n = 4016), AMA women with GDM (AGDM) group (n = 850), and young pregnant women without GDM (non-YGDM) group (n = 27,122). Univariate analysis was carried out by Mann-Whitney U test or Pearson's χ 2 test. Multivariate logistic regression analysis was used to investigate the effect of AMA and GDM on pregnancy outcomes. Multivariate logistic regression analysis showed that in the comparison against non-YGDM garoup, the ORs of fetal chromosome abnormality, parity, urgent cesarean section, gravidity, scheduled cesarean section, body mass index (BMI) ≥30 kg/m2, pre-eclampsia, thrombocytopenia, hyperlipidemia, BMI 25-29.9 kg/m2, blood urea nitrogen, fasting blood glucose, and creatinine in AGDM group were 16.044, 4.284, 3.530, 3.284, 3.257, 2.049, 1.935, 1.898, 1.690, 1.471, 1.304, 1.216, and 1.026 (all p < 0.05). The prevalence of pregnant women with AGDM was 2.46% in Hang Zhou, China. The increasing gravidity of AMA women was related to a greater risk of GDM. The AGDM group associated with a greater risks of chromosomal abnormality in offspring and cesarean section, especially urgent cesarean section.

Immunological effects of human decidual mesenchymal stem cells in spontaneous and recurrent abortions

The aim of this study was to evaluate the immunological activities of human decidual mesenchymal stem cells (MSCs) on proliferation, apoptosis and percentage of regulatory T cells (Treg) in abortions and to investigate whether these activities differ in spontaneous abortions (SA) and recurrent abortions (RA). This prospective cohort study included women who had a first-trimester abortion between 2019 and 2022. Women with uterine anomaly, endocrinological disease, known autoimmune or thrombophilic disease, and fetal chromosomal abnormality in abortion material were excluded. Decidual MSCs isolated from abortion materials were classified as spontaneous abortion-MSCs (SA-MSCs) and recurrent abortion-MSCs (RA-MSCs). Peripheral blood mononuclear cells were isolated from venous blood and co-cultured with SA-MSCs and RA-MSCs. The effects of MSCs on proliferation and apoptosis of lymphocytes, and Tregs levels were compared between SA-MSCs and RA-MSCs groups. Thirty cases (15 SA-MSCs and 15 RA-MSCs) were included in the study. The presence of MSC in co-cultures increased percentage of Treg cells while reducing proliferation and apoptosis compared to those without MSCs (p < 0.0001, p < 0.0001 and p < 0.0001). The increase in percentage of Treg cells and the reduction in apoptosis were significantly lower in the RA-MSCs group compared to the SA-MSCs group (p < 0.0001 and p < 0.001, respectively). Although the proliferation reducing effect of the presence of MSCs was lower in the RA-MSCs group compared to the SA-MSCs group, the difference was not significant (p = 0.07). MSCs contribute to maternal immunotolerance to semi-allogeneic fetus by suppressing proliferation and apoptosis, and increasing percentage of Treg cells. However, the immunoregulatory effects of MSCs are lower in RA compared to SA.

Molecular cytogenetic analysis of multi-miscarriage products of conception in clinical cases from Al-Anbar Governorate, west of Iraq

Most clinical miscarriages often occur throughout the first trimester of pregnancy, with fetal chromosomal abnormalities being identified as the primary reason for such occurrences. The objective is to analyze the fetal chromosomal aberrations in the product of conception among Iraqi patients suffering from recurrent miscarriages. The cross-sectional study was performed on 60 cases of products of conception in women suffering from multiple miscarriages, obtained from Department of Obstetrics and Gynecology is located in Ramadi Teaching Hospital for Child and Maternity, as well as other Private Clinics in the Ramadi City. Long-term culture of conventional cytogenetic analysis using the G-banding technique was employed to determine the chromosomal disorder of fetal tissue part or villus samples. Fetal chromosomal abnormalities were detected in 86.7 %. Numerical chromosomal abnormalities were revealed in 98.1 %, while structural abnormalities were detected in 1.9 %. Additionally, the commonest gestation loss occurs in parents under 35 years in the first trimester (92.3 %). Trisomy 21 was the most frequent (46.2 %) in gestational loss. Fetal chromosomal abnormalities have been linked with gestational loss in Iraqi couples. Therefore, it is recommended that cytogenetic analysis should be performed to identify the genetic cause of recurrent miscarriage. This is important for providing appropriate genetic counseling and educating couples about the risk of future pregnancies.

Clinical value of screening prenatal ultrasound combined with chromosomal microarrays in prenatal diagnosis of chromosomal abnormalities

Objective To evaluate the clinical value of ultrasound findings in the screening of fetal chromosomal abnormalities and the analysis of risk factors for chromosome microarray analysis (CMA) abnormalities. Methods We retrospectively analyzed the datasets of 15,899 pregnant women who underwent prenatal evaluations at Affiliated Maternity and Child Health Care Hospital of Nantong University between August 2018 and December 2022. Everyone underwent ultrasound screening, and those with abnormal findings underwent CMA to identify chromosomal abnormalities. Results The detection rates for isolated ultrasound anomalies and combined ultrasound and CMA anomalies were 11.81% (1877/15,899) and 2.40% (381/15,899), respectively. Among all ultrasound abnormalities, detection rates for isolated ultrasound soft marker anomalies, isolated structural abnormalities, and both ultrasound soft marker anomalies with structural abnormalities were 82.91% (1872/2258), 15.99% (361/2258), and 1.11% (25/2258), respectively. The detection rate of abnormal chromosomes in pregnant women with abnormal ultrasound results was 16.87% (381/2258). The detection rates were 13.33% in cases with two or more ultrasound soft markers anomalies, 47.37% for two or more structural anomalies, and 48.00% for concomitant ultrasound soft marker and structural anomalies. Conclusions Enhanced detection rates of chromosomal anomalies in fetal malformations are achieved with specific ultrasound findings (NT thickening, cardiovascular abnormalities, and multiple soft markers) or when combined with high-risk factors (advanced maternal age, familial history, parental chromosomal anomalies, etc.). When the maternal age is over 35 and with ≥2 ultrasound soft marker anomalies accompanied with any high-risk factors, CMA testing can aid in the diagnosis of prenatal chromosomal abnormalities.

The detection efficacy of noninvasive prenatal genetic testing (NIPT) for sex chromosome abnormalities and copy number variation and its differentiation in pregnant women of different ages

ObjectiveTo analyze the efficacy of noninvasive prenatal genetic testing (NIPT) in detecting fetal sex chromosome abnormalities and copy number variation (CNV), compare the efficacy between NIPT and serological screening alone, and further analyze the fetal sex chromosome abnormalities and CNV differentiation in pregnant women of different ages, so as to provide a reference for the prevention and control of fetal birth defects. MethodsClinical data from 22,692 pregnant women admitted to our hospital from January 2013 to December 2022 were retrospectively analyzed. All participants underwent serological screening and NIPT screening to compare fetal chromosomal abnormalities between the two screening modalities. 145 women whose fetus were diagnosed as sex chromosome abnormalities and 36 women whose fetus were diagnosed as CNV abnormalities based on NIPT screening were selected for prenatal diagnosis by amniocentesis or karyotyping. Taking prenatal diagnosis as the standard, the four-grid table method was used to detect the positive predictive value of NIPT screening for fetal sex chromosomal abnormalities and CNV. According to the age, pregnant women were divided into 18–30 years old (n = 9844), 31–35 years old (n = 7612), >35 years old (n = 5236), and then the detection rates of sexual fetal chromosomal abnormalities, CNV and total chromosomal abnormalities were compared in pregnant women. ResultsAmong the 22,692 pregnant women in this study, the high-risk proportion of serologic screening with 4.38% was higher than that of NIPT screening with 1.93% (P < 0.05). Among the 145 women with fetal sex chromosome abnormalities screened by NIPT, 122 cases of fetal sex chromosome abnormalities were diagnosed prenatally, including 45, X/47, XXX/47, XYY/47, XXY. The positive predictive values of NIPT screening were 25.00%, 58.82%, 85.71%, and 85.71%, respectively, with an overall predictive value of 44.26%. The positive predictive value of fetal sex chromosome abnormalities in NIPT screening was higher than that of serological screening (P < 0.05). Among the 36 pregnant women with fetal CNV, NIPT screening showed that CNVs≤10 Mb and CNVs>10 Mb were 33.33% and 66.67%, respectively. There were 12 cases of prenatal diagnosis of fetal CNV, among which the NIPT-screened positive predictive values of fetal copy number deletion, duplicate, deletion and duplicate were 50.00%, 57.14% and 100.00%, respectively, with an overall predictive value of 58.33%. The positive predictive value of CNV in NIPT screening was higher than that of serological screening without statistically significant difference (P > 0.05). The results of NIPT screening showed that the detection rate of fetal sex chromosome abnormalities and total abnormalities of pregnant women over 35 years of age was significantly higher than that of pregnant women aged 18–30 and 31–35 years (P < 0.05). ConclusionNIPT screening could greatly improve the detection efficacy of fetal sex chromosome abnormalities, CNV and other chromosome abnormalities, and decline the false positive rate. However, the positive predictive value of NIPT screening was relatively low, and further prenatal testing and genetic counseling are still required. In addition, NIPT screening for fetal sex chromosome abnormalities, and the detection rate of total abnormalities in pregnant women older than 35 years old were increased significantly, and pregnancy at an advanced age may be one of the risk factors for fetal chromosomal abnormalities.

Study of biochemical markers during the first trimester of pregnancy among women of Almaty city

One of actual problems is the birth of children with genetic diseases, such as Down syndrome, Edwards syndrome, Patau syndrome, Shereshevsky-Turner syndrome. Study of level of biochemical markers of the first trimester of pregnancy for diagnose of chromosomal abnormalities in fetus was the purpose and objectives of this research. A risk group was identified, including 684 women on the base of results of studies of biochemical markers of the 1-st trimester of pregnancy – PAPP-A and β-hCG. In these pregnant women, PAPP-A and β-hCG concentrations were higher or lower than normal values. It has been shown that decrease in PAPP-A levels and increase or decrease in β-hCG in the 1-st trimester of pregnancy may indicate the presence of a chromosomal abnormality in the fetus. Next, a pattern has been identified that with increasing women age, the risk of having children with chromosomal abnormalities increases. During the study, it was found that PAPP-A levels are reduced at Down and Edwards syndromes and slightly reduced at Shereshevsky-Turner syndrome. Level of β-hCG is significantly higher at Down syndrome, while at Edwards syndrome, on the contrary, it has reduced values; and at Shereshevsky-Turner syndrome the level of β-hCG has a normal value. Changes in levels of these indicators from norm do not always indicate a fetal pathology, but they are grounds for further medical examination.

From sensing interactions to controlling the interactions: a novel approach to obtain biological transistors for specific and label-free immunosensing.

Antibody-antigen interactions are shaped by the solution pH level, ionic strength, and electric fields, if present. In biological field-effect transistors (BioFETs), the interactions take place at the sensing area in which the pH level, ionic strength and electric fields are determined by the Poisson-Boltzmann equation and the boundary conditions at the solid-solution interface and the potential applied at the solution electrode. The present study demonstrates how a BioFET solution electrode potential affects the sensing area double layer pH level, ionic strength, and electric fields and in this way shapes the biological interactions at the sensing area. We refer to this as 'active sensing'. To this end, we employed the meta-nano-channel (MNC) BioFET and demonstrate how the solution electrode can determine the antibody-antigen equilibrium constant and allows the control and tuning of the sensing performance in terms of the dynamic range and limit-of-detection. In the current work, we employed this method to demonstrate the specific and label-free sensing of Alpha-Fetoprotein (AFP) molecules from 0.5 μL drops of 1 : 100 diluted serum. AFP was measured during pregnancy as part of the prenatal screening program for fetal anomalies, chromosomal abnormalities, and abnormal placentation. We demonstrate AFP sensing with a limit-of-detection of 10.5 aM and a dynamic range of 6 orders of magnitude in concentration. Extensive control measurements are reported.

Non-invasive prediction of preeclampsia using the maternal plasma cell-free DNA profile and clinical risk factors.

Preeclampsia (PE) is a pregnancy complication defined by new onset hypertension and proteinuria or other maternal organ damage after 20 weeks of gestation. Although non-invasive prenatal testing (NIPT) has been widely used to detect fetal chromosomal abnormalities during pregnancy, its performance in combination with maternal risk factors to screen for PE has not been extensively validated. Our aim was to develop and validate classifiers that predict early- or late-onset PE using the maternal plasma cell-free DNA (cfDNA) profile and clinical risk factors. We retrospectively collected and analyzed NIPT data of 2,727 pregnant women aged 24-45 years from four hospitals in China, which had previously been used to screen for fetal aneuploidy at 12 + 0 ~ 22 + 6 weeks of gestation. According to the diagnostic criteria for PE and the time of diagnosis (34 weeks of gestation), a total of 143 early-, 580 late-onset PE samples and 2,004 healthy controls were included. The wilcoxon rank sum test was used to identify the cfDNA profile for PE prediction. The Fisher's exact test and Mann-Whitney U-test were used to compare categorical and continuous variables of clinical risk factors between PE samples and healthy controls, respectively. Machine learning methods were performed to develop and validate PE classifiers based on the cfDNA profile and clinical risk factors. By using NIPT data to analyze cfDNA coverages in promoter regions, we found the cfDNA profile, which was differential cfDNA coverages in gene promoter regions between PE and healthy controls, could be used to predict early- and late-onset PE. Maternal age, body mass index, parity, past medical histories and method of conception were significantly differential between PE and healthy pregnant women. With a false positive rate of 10%, the classifiers based on the combination of the cfDNA profile and clinical risk factors predicted early- and late-onset PE in four datasets with an average accuracy of 89 and 80% and an average sensitivity of 63 and 48%, respectively. Incorporating cfDNA profiles in classifiers might reduce performance variations in PE models based only on clinical risk factors, potentially expanding the application of NIPT in PE screening in the future.

Результати комплексних пренатальних обстежень за наявності дисбалансу хромосоми 21 у плода

Purpose - to characterize the cases of chromosome 21 imbalance in fetuses of high-risk pregnant women, to describe prenatal cytogenetic diagnosis and associated ultrasound findings - structural anomalies and soft markers. Materials and methods. The results of complex prenatal examination of high-risk pregnant women in the Department of Fetal Medicine of the SI “Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine” during 5 years period were analyzed: results of ultrasound and cytogenetic exams of 200 cases of chromosome 21 imbalance in the fetus. Results. Among 4,748 prenatal cytogenetic testing of fetuses of high-risk women abnormal karyotypes with an imbalance of chromosome 21 were found in 200 (4.21%) cases. In the majority of cases Down's syndrome (DS) was diagnosed (n=199; 99.5%), in 1 (0.2%) case - deletion of chromosome 21. In DS, regular trisomy of chromosome 21 was found in 191 (95.97%) cases, translocant forms - in 5 (2.51%) cases, in 1 (0.5%) case there was there was an additional sex chromosome, and in 1 (0.5%) - a variant with two cell lines. In 1 (0.5%) case limited placental mosaicism was present, with a false negative result that required verification by the analysis of fetal lymphocytes obtained during cordocentesis. Advanced maternal age (≥35 years) was registered in less than half of fetal DS cases (n=92/199, 46.2%). The main indications for invasive procedures and their types are described. It was demonstrated that ultrasound findings (structural anomalies and/or “soft” markers for chromosomal pathology) were present in 78% of fetal chromosome 21 imbalance; nevertheless in 22% ultrasound findings were absent, and the indication for invasive procedures were advanced maternal age or isolated changes of biochemical markers. Conclusions. Chromosome 21 imbalance in fetuses is mainly represented by trisomy, cases of chromosome 21 deletion are extremely rare. Targeted ultrasound examination is important for screening and diagnosis of fetal chromosomal abnormalities. High-risk pregnant women shouldn’t be reassured in case of “normal” ultrasound exam results. Under certain conditions, it is advisable to perform placental biopsy in the II trimester of pregnancy, but only in specialized tertiary centers or departments. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

CLINICAL, ULTRASOUND AND CYTOGENETIC CHARACTERISTICS OF FETUSES WITH INCREASED NUCHAL TRANSLUCENCY THICKNESS IN THE FIRST TRIMESTER OF PREGNANCY

Background: Improving programs for early prenatal detection of congenital malformations remains a relevant scientific and practical problem. The prevalence of congenital anomalies in Ukraine is 23.7:1000 among live-born babies, and there is no significant decrease in it. The aim of this study was to compare clinical, ultrasound and cytogenetic data in swollen fetuses with increased nuchal translucency (NT) thicknesses from the group of pregnant women in the first trimester at high genetic risk to optimize the algorithm of prenatal diagnostics.&#x0D; Materials and Methods: Clinical examinations, ultrasound diagnostics, invasive methods of prenatal diagnostics (chorion biopsy, amniocentesis), genetic testing techniques, such as karyotyping and FISH, genetic counseling and statistical analysis were carried out. The results of complex examinations of 127 fetuses with an increased NT thickness from the group of pregnant women were analyzed. Fetuses were divided into two groups with an NT thickness of 2.5–3.5 mm (group 1) (38 cases) and with an NT above 3.5 mm (group 2)(89 cases).&#x0D; Results: Among pregnancies with fetuses with an increased NT thickness, there were 65.4% cases of adverse outcomes with chromosomal pathology (69.9%), congenital malformations of non-chromosomal etiology (25.3%) and pregnancy loss (4.8%). The frequency of chromosomal abnormalities in fetuses of group 1 was 55.3% and 41.6% in group 2. Congenital malformations of various systems and organs in fetuses, the most frequent of which were cardiac defects, were diagnosed. The ratio of congenital heart defects in the fetuses of groups 1 and 2 was 23.7% and 43.8%, respectively (p=0.03; OR=0.40).&#x0D; Conclusion: There is no significant difference between the frequency of chromosomal abnormalities in the fetuses of group 1 compared to group 2, which indicates a high informative value of an increased NT thickness, including the thickness of 2.5–3.5 mm in fetuses in the first trimester as a marker of chromosomal pathology. A significantly higher incidence of congenital malformations of non-chromosomal etiology was found in fetuses with venous duct pathology and NT thickness over 3.5 mm compared to fetuses with the same pathology and NT thickness of 2.5–3.5 mm. Proposed changes to the management algorithm for pregnant women with swollen fetuses include mandatory congenital heart defects screening in the first trimester.

Evaluation of Hypertension and Renal Function in Preeclamptic Women: A Follow-Up Study at 6th Week of Postpartum

OBJECTIVES: Chronic hypertension stands as the primary contributing factor for cardiovascular ailments among women who have experienced preeclampsia. The purpose of this research is to examine how often preeclamptic symptoms persist at the postpartum 6th week. STUDY DESIGN: The study included 50 singleton pregnant women in the third trimester who were diagnosed with preeclampsia according to ACOG criteria, were older than 18 years, had no known hypertension before the 20th gestational week, had no additional systemic disease, did not use medication, had no fetal chromosomal or structural abnormalities and delivered within 24-48 hours of hospitalization. RESULTS: The mean age of preeclamptic pregnant patients was 29.26±7.15 years, the mean gestational week was 35.6±2.8, and the mean BMI was 31.3±4.9. Twenty (40%) of 50 preeclamptic patients had severe preeclampsia. The mean decrease in systolic blood pressure was 34.6±15.2 mmHg, while the mean decrease in diastolic blood pressure was 22.88±11.68 mmHg (p&lt;0.001). The decrease in systolic and diastolic blood pressure at postpartum 6th week was statistically significant. The mean change in 24-hour urine protein value at postpartum 6th week was 2313.52 ± 2696.48 and the difference was statistically significant (p&lt;0.001). There were 14 patients (28%) with persistent hypertension and 19 patients (38%) with persistent proteinuria. CONCLUSIONS: Although preeclampsia is considered a complication of pregnancy, persistent hypertension, and proteinuria after delivery show us that preeclampsia is a disease that threatens maternal health even after delivery. These women should be followed up long-term period.