Prenatal Testing Research Articles

The clinical value of optical genome mapping in the rapid characterization of RB1 duplication and 15q23q24.2 triplication, for more appropriate prenatal genetic counselling.

Despite recent advances in prenatal genetic diagnosis, medical geneticists still face considerable difficulty in interpreting the clinical outcome of copy-number-variant duplications and defining the mechanisms underlying the formation of certain chromosomal rearrangements. Optical genome mapping (OGM) is an emerging cytogenomic tool with proved ability to identify the full spectrum of cytogenetic aberrations. Here, we report on the use of OGM in a prenatal diagnosis setting. Detailed breakpoint mapping was used to determine the relative orientations of triplicated and duplicated segments in two unrelated foetuses harbouring chromosomal aberrations: a de novo 15q23q24.2 triplication and a paternally inherited 13q14.2 duplication that overlapped partially with the RB1 gene. OGM enabled us to suggest a plausible mechanism for the triplication and confirmed that the RB1 duplication was direct oriented and in tandem. This enabled us to predict the pathogenic consequences, refine the prognosis and adapt the follow-up and familial screening appropriately. Along with an increase in diagnostic rates, OGM can rapidly highlight genotype-phenotype correlations, improve genetic counselling and significantly influence prenatal management.

Hepatitis B virus infection on Kwajalein Atoll, Marshall Islands: a seroprevalence, knowledge and attitudes study.

A study was conducted to determine the seroprevalence of chronic hepatitis B virus (HBV) infection among children and their mothers on Kwajalein Atoll in the Marshall Islands two decades after routine vaccination was introduced in the 1990s. Mothers' knowledge and attitudes towards HBV disease and vaccination were also assessed. Results of a national seroprevalence survey conducted in 2016-2017 and antenatal records were used to determine the prevalence of HBV seropositivity in children aged 6-8years and their biological mothers. The associations between demographic, social and vaccination-related factors and seropositivity were explored using Fisher's exact tests. HBV seroprevalence was 0.3% in children and 6.8% in their mothers (during pregnancy). Coverage of timely HBV vaccination was 90.3% for the birth dose and was significantly associated with factors related to place of residence (P<0.001), place of birth (P<0.001) and number of antenatal visits (P<0.001). Maternal attitudes towards infant vaccination and antenatal screening were largely positive (95.8% and 96.7%, respectively) despite low vaccination rates (20.9%) among mothers. Knowledge levels were low for disease complications, treatment and transmission. Prevalence of HBV in children and mothers residing on Kwajalein Atoll in 2016-2017 was lower than the national average for the Marshall Islands. Timely birth dose administration appears to have been effective in preventing mother-to-child transmission of HBV in this setting and should be promoted in remote settings where antiviral therapy is not available. Provision of out-of-cold-chain HBV vaccines should be considered to improve access in remote settings.

Does siPantau Bumil GIS-Based Able to Increase K6 Visits and Reduce Complication for High-Risk Pregnant Women?

K6 visits and obstetric complications scope is one indicator of maternal health program services. Scarcely have these indicator’s achievements met the expected targets so innovation is needed to improve them. The method that can be used to increase the accomplishment is digitalization, through the use of applications to provide and improve the health services quality in monitoring pregnant women. The objective is to design and investigate the GIS (Geographical Information System) influence on pregnancy monitoring practice, especially on K6 visits and pregnant women’s high-risk obstetric complications in Pekalongan City. This research uses the Research and Development (R&amp;D) method with a quasi-experimental research design and posttest control group design. The population is pregnant women with high-risk factors at 32 weeks gestation in Pekalongan City. The total sample is 60 people, who were divided into two groups, namely 30 respondents in the intervention group and 30 respondents in the control group. In the intervention group, pregnant women were given monitoring through the Sipantau Bumil application and K6 visit notifications, while in the control group, the K6 visit schedule was written in the KIA book. Moreover, the data analysis used the Chi-Square test. The result is the siPantau Bumil application has increased K6 visits with a significance value of p-value=0.012 (p&lt;0.005). In addition, it also reduces obstetric complications with a significance value of p-value=0.002 (p&lt;0.005). The conclusion is the GIS-based pregnancy monitoring application can increase K6 visits and reduce obstetric complications.

Where is the “counseling” in prenatal genetic counseling?

ObjectivePrenatal genetic testing is routinely offered to all pregnant patients in the United States and is variably offered to certain pregnant populations globally [1]. To achieve value-based, informed decision-making, we argue for a shift away from the predominant “teaching” model of genetic counseling practice that prioritizes information and counselor dominance, toward a “counseling” model of practice that prioritizes the patient’s narrative, values and beliefs. DiscussionSince prenatal testing began, genetic counseling has aimed to facilitate informed decision-making. Many patients are not familiar with the conditions which can be screened for prenatally or the quality of life of affected children. This lack of understanding can leave expectant parents unprepared to make informed decisions about prenatal testing. As the number of prenatal genetic tests expands, genetic counselors and all healthcare providers who discuss prenatal testing face a growing amount of information that is not feasible to explain to patients in a routine appointment. Research demonstrates that the common approach to genetic counseling, including in the prenatal setting, is the provision of biomedical information. Yet, genetic counseling outcome studies suggest that attending to the relational aspects of genetic counseling are associated with more positive patient outcomes, including enhanced knowledge, informed decision-making and greater patient satisfaction [2,3]. Through case vignettes, we illustrate the application of a counseling model of practice using Accreditation Council for Genetic Counseling (ACGC) practice-based competencies in the domain of “Interpersonal, Psychosocial and Counseling Skills” [4]. Finally, we propose changes across the genetic counseling profession to move clinical practice toward a more relational model of care. Practice implicationsA counseling model of genetic counseling practice leads to more positive patient outcomes [2,3]. Genetic counselors and other prenatal healthcare providers can leverage existing counseling and communication skills to support clients in value-based, informed decision-making in prenatal genetic counseling practice.

Navigating Uncertain Waters: First-Trimester Screening's Role in Identifying Neonatal Complications.

Background: Contemporary diagnostic methods aimed at assessing neonatal outcomes predominantly rely on the medical history of pregnant women. Ideally, universal biomarkers indicating an increased risk of delivering infants in poor clinical condition, with a heightened likelihood of requiring hospitalization in a Neonatal Intensive Care Unit (NICU), would be beneficial for appropriately stratifying pregnant women into a high-risk category. Our study evaluated whether biochemical and ultrasonographical markers universally used in first-trimester screenings for non-heritable chromosomal aberrations could serve this purpose. Methods: This study encompassed 1164 patients who underwent first-trimester screening, including patient history, ultrasound examinations, and biochemical tests for pregnancy-associated plasma protein-A (PAPP-A) and the free beta-HCG subunit (fbHCG), from January 2019 to December 2021. The research concentrated on the correlation between these prenatal test results and neonatal outcomes, particularly Apgar scores, umbilical blood pH levels, and the necessity for NICU admission. Results: In our cohort, neonates scoring lower than 8 on the Apgar scale at birth exhibited lower concentrations of PAPP-A in the first trimester, both in raw and normalized values (PAPP-A MoM 0.93 vs. 1.027, p = 0.032). We also observed a higher pulsatility index in the venous duct in the first trimester in full-term neonates born with <8 points on the Apgar scale. Additionally, newborns born with an umbilical blood pH < 7.2 had lower normalized first-trimester PAPP-A concentrations (0.69 vs. 1.01 MoM, p = 0.04). We also noted that neonates requiring NICU hospitalization post-delivery had lower first-trimester bHCG concentrations (0.93 MoM vs. 1.11 MoM, p = 0.03). However, none of the correlations in our study translated into a robust prognostic ability for predicting dichotomous outcomes. All areas under the curve achieved a value < 0.7. Conclusions: Low concentrations of PAPP-A and free bHCG subunit in the first trimester may be associated with poorer clinical and biochemical conditions in neonates post-delivery. However, the relationship is weak and has limited predictive capability. Further research evaluating these relationships is necessary for the appropriate stratification of pregnant women into high-risk categories for neonatological complications.

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 Novel Transfer Learning Approach to Improve Breast Cancer Diagnosing on Screening Mammography

Segmentation is a technique for separating an image into discrete areas in order to separate objects of interest from their surroundings. In image analysis, segmentation—which encompasses detection, feature extraction, classification, and treatment—is crucial. In order to plan treatments, segmentation aids doctors in measuring the amount of tissue in the breast. Categorizing the input data into two groups that are mutually exclusive is the aim of a binary classification problem. In this case, the training data is labeled in a binary format based on the problem being solved. Identifying breast lumps accurately in mammography pictures is essential for the purpose of prenatal testing for breast cancer. The proposed TLA (Transfer Learning Approach) based CNN (Convolution Neural Network) –TLA based CNN aims to offer binary classification for rapid and precise breast cancer diagnosis (benign and malignant). In order to predict the sub-type of cancer, this exploration as used Deep Learning techniques on the Histogram of Oriented Gradient (HOG) - Feature extraction technique that creates a local histogram of the image to extract features from each place in the image with CNN classifier. This research work employs two well-known pre-trained models, ResNet-50 and VGG16, to extract characteristics from mammography images. The high-level features from the Mammogram dataset are extracted using a transfer learning model based on Visual Geometry Group (VGG) with 16-layer and Residual Neural Network with 50-layers deep model architecture (ResNet-50). The proposed model TLA based CNN has achieved 96.49% and 95.48% accuracy as compared to ResNet50 and VGG16 in the breast cancer classification and segmentation.

Urban Green Space and Perinatal Health Inequities in the United States: A Literature Review.

Access to urban green space has been linked to positive health outcomes including enhanced perinatal health. The purpose of this article was to review, summarize, and synthesize what is known about the relationship between urban green space and perinatal health and outline implications for practice, policy, education, and research. Nineteen articles were included in this state-of-the-science review. Overall, it was found that limited access to green space is significantly related to adverse birth outcomes. These findings present an important opportunity for childbirth educators and other clinicians involved in the provision of prenatal and reproductive health care. Through education and intervention, poor perinatal outcomes may be mitigated. Clinical screening and education about the importance of access to and use of urban green space during pregnancy should be an essential component of preconception counseling and antenatal screening for at-risk populations. Policy makers should be made aware of these findings so that impactful change can be made in order to reduce disparities and promote health equity.

Understanding the Awareness of Prenatal Genetic Screening Tests Among Pregnant Women in India: A Cross-Sectional Study.

Introduction Genetic disorders pose a significant health challenge in India, with chromosomal abnormalities ranking second only to congenital anomalies in terms of disease burden. Prenatal testing offers a crucial strategy for identifying and managing these disorders. However, the awareness and understanding of prenatal screening tests among pregnant women in India remain understudied. This study aims to fill this gap by investigating the awareness quotient of prenatal screening tests for genetic disorders among pregnant women in India. Methods A hospital-based cross-sectional study was conducted at the Genetics Unit, Department of Anatomy, and Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Mangalagiri. Ethical clearance was obtained, and data were collected using a self-administered questionnaire covering demographic characteristics and awareness assessment. Descriptive statistics, chi-square tests, and logistic regression analysis were employed for data analysis. Results Among the 200 pregnant women surveyed, the majority demonstrated inadequate awareness of prenatal screening tests for genetic disorders, with only 36.5% possessing adequate knowledge. Significant associations were found between awareness levels and factors such as age, trimester of pregnancy, and education level. Notably, awareness about non-invasive prenatal testing (NIPT) was notably low at 7%, indicating a need for targeted educational interventions. Comparison with international studies revealed varying levels of awareness across different populations, highlighting the influence of socio-cultural factors and healthcare systems. Conclusion This study underscores the need for improved awareness of prenatal screening tests among pregnant women in India. Addressing disparities in awareness, particularly among younger age groups and those with lower education levels, is crucial for informed decision-making in prenatal care. Targeted educational interventions can empower pregnant women to make informed choices, ultimately contributing to better maternal and child health outcomes. Further research should explore the effectiveness of such interventions in diverse settings to enhance prenatal care delivery.

Ultrasonographic Fetal Nuchal Translucency Measurements and Cytogenetic Outcomes

Ultrasonographic measurement of fetal nuchal translucency is used in prenatal screening for trisomies 21 and 18 and other conditions. A cutoff of 3.5 mm or greater is commonly used to offer follow-up investigations, such as prenatal cell-free DNA (cfDNA) screening or cytogenetic testing. Recent studies showed a possible association with chromosomal anomalies for levels less than 3.5 mm, but extant evidence has limitations. To evaluate the association between different nuchal translucency measurements and cytogenetic outcomes on a population level. This population-based retrospective cohort study used data from the Better Outcomes Registry & Network, the perinatal registry for Ontario, Canada. All singleton pregnancies with an estimated date of delivery from September 1, 2016, to March 31, 2021, were included. Data were analyzed from March 17 to August 14, 2023. Nuchal translucency measurements were identified through multiple-marker screening results. Chromosomal anomalies were identified through all Ontario laboratory-generated prenatal and postnatal cytogenetic tests. Cytogenetic testing results, supplemented with information from cfDNA screening and clinical examination at birth, were used to identify pregnancies without chromosomal anomalies. Multivariable modified Poisson regression with robust variance estimation and adjustment for gestational age was used to compare cytogenetic outcomes for pregnancies with varying nuchal translucency measurement categories and a reference group with nuchal translucency less than 2.0 mm. Of 414 268 pregnancies included in the study (mean [SD] maternal age at estimated delivery date, 31.5 [4.7] years), 359 807 (86.9%) had a nuchal translucency less than 2.0 mm; the prevalence of chromosomal anomalies in this group was 0.5%. An increased risk of chromosomal anomalies was associated with increasing nuchal translucency measurements, with an adjusted risk ratio (ARR) of 20.33 (95% CI, 17.58-23.52) and adjusted risk difference (ARD) of 9.94% (95% CI, 8.49%-11.39%) for pregnancies with measurements of 3.0 to less than 3.5 mm. The ARR was 4.97 (95% CI, 3.45-7.17) and the ARD was 1.40% (95% CI, 0.77%-2.04%) when restricted to chromosomal anomalies beyond the commonly screened aneuploidies (excluding trisomies 21, 18, and 13 and sex chromosome aneuploidies). In this cohort study of 414 268 singleton pregnancies, those with nuchal translucency measurements less than 2.0 mm were at the lowest risk of chromosomal anomalies. Risk increased with increasing measurements, including measurements less than 3.5 mm and anomalies not routinely screened by many prenatal genetic screening programs.

Clinical Effectiveness of Continuous Glucose Monitoring in Pregnancies Affected by Type 1 Diabetes.

Background: Continuous glucose monitoring (CGM) improves neonatal outcomes in type 1 diabetes pregnancies; however, its effectiveness has not been assessed in a real-world setting in the United States. Objective: The Triple C Study aimed to examine the clinical effectiveness, assessed through maternal glucose control and gestational health outcomes, of CGM use compared with self-monitoring of blood glucose (SMBG) in pregnancies associated with type 1 diabetes in a real-world setting. Research Design and Methods: We retrospectively identified 160 type 1 diabetes pregnancies at the Barbara Davis Center for Diabetes managed with CGM therapy (n = 109) or SMBG (n = 51) over a 6.5-year period (2014-2020). Obstetric care was provided at multiple practices. CGM use was defined as ≥60% wear in the second and third trimesters of pregnancy. Data were obtained from the electronic medical record system, hospital records, and vital statistics departments (Colorado and Wyoming). We used Student's t-test for continuous variables and chi-square test for categorical variables to compare outcomes between groups. Results: The CGM group had more participants meeting trimester-specific hemoglobin A1C (HbA1c) goals throughout pregnancy and postpartum (P < 0.01 in each time period). The CGM group had fewer participants never meeting HbA1c goals in any trimester than the SMBG group (P < 0.001). There were no significant differences in neonatal outcomes between groups, other than for macrosomia (12.8% CGM vs. 29.4% SMBG, P = 0.01). Infants of CGM users required a neonatal intensive care unit admission less often (52.9% CGM vs. 68.3% SMBG, P = 0.0989). Conclusions: CGM use was associated with improved maternal glucose levels in a diverse real-world cohort.

From Conception to Revelation: Non-Invasive Prenatal Testing Explored

Prenatal testing plays a crucial role in addressing the inherent unpredictability of genetic disorders that can affect unborn children. Non-Invasive Prenatal Testing (NIPT) has emerged as a groundbreaking tool in the realm of prenatal care, enabling the early detection of chromosomal abnormalities. By examining fetal DNA present in the mother's bloodstream, NIPT has achieved remarkable accuracy rates, surpassing invasive techniques that carry inherent risks. However, with these advancements come ethical considerations. The results of NIPT can significantly influence a mother's decision regarding the continuation or termination of pregnancy. This decision can be further complicated by religious beliefs, which often play a pivotal role in guiding choices related to pregnancy. Moreover, receiving a positive result from NIPT can subject expectant mothers to profound emotional stress, highlighting the need for comprehensive counseling and support services. In addition to these ethical concerns, practical limitations persist. The cost of NIPT remains a substantial barrier for many families, potentially limiting its accessibility. Furthermore, NIPT's accuracy can be influenced by factors such as gestational age, with tests often yielding inconclusive results when fetal fractions are low. Despite these challenges, technological innovations, including microarrays and Next Generation Sequencing (NGS), have bolstered the capabilities of NIPT. These advancements enable a more comprehensive assessment of fetal DNA, enhancing the overall quality of prenatal care. As NIPT continues to evolve and integrate with broader genomic technologies, society must engage in thoughtful reflection on its implications. The potential normalization of pregnancy terminations based on genetic information underscores the importance of ethical and societal discussions surrounding the use of NIPT, with a focus on preserving informed patient choices and ensuring comprehensive support for expectant parents facing difficult decisions.

Fraccaro Syndrome (49,XXXXY): Case study in antenatal and postnatal from South Indian patients, an awareness to the human society

Aim: 49, XXXXY syndrome is a rare chromosomal abnormality with an approximate incidence of 1:85000 – 1:100000. Early diagnosis is important to improve the quality of life of patient. This study was carried out to assess the chromosomal abberations in prenatal and postnatal sample of patients through cytogenetics study. Methodology: Sex chromosomal aneuplodies were performed in both amniotic fluid and peripheral venous blood samples. Cytogenetic studies such as Karyotyping was done in in-vitro culture cells by GTG banded metaphase slides. FISH test was conducted in raw sample to rule out low grade mosaicism and DNA isolated from both the samples to rule out the gain and loss of genes by Chromosomal microarray technique. Results: The two cases performed showed aneuploidy with pentasomy sex chromosomes in Karyotyping in all the metaphase analysed and FISH test resulted with five signals in sex chromosome with four copies of X chromosomes and one copy of Y chromosome in all the cells. There was no loss of genes and only gain of genes in X chromosomes as identified in Chromosomal microarray. Interpretation: Based on the findings, antenatal screening is essential and should not be avoided for any USG findings and biochemical screening. The test should not be limited only to trisomy studies. Extensive studies should be performed to rule out the genetic disorders. Chromosomal aneuploidies can be identified by cytogenetic studies like Karyotyping, FISH and Chromosomal microarray technique. Key words: Aneuploidy, Chromosomal microarray analysis, Cytogenetics, Fraccaro syndrome, Karyotyping, Pentasomy sex chromosome

Use of cell-free non-invasive prenatal testing in pregnancies affected by placental mosaicism.

To evaluate cell-free non-invasive prenatal testing (cfNIPT) in pregnancies affected by mosaicism. We assessed paired cfNIPT and chorionic villus sample (CVS) results from the same pregnancies in a case series of mosaicism detected in Central and North Denmark Regions from April 2014 to September 2018. Indications for the clinically obtained CVS, pregnancy markers and outcome were retrieved from The Danish Fetal Medicine Database. Mosaicisms in CVS involved common aneuploidy, n=14; sex chromosomal aneuploidies, n=14; rare autosomal trisomies (RATs), n=16 and copy number variants (CNVs) >5Mb, n=9. Overall, 24/53 (45.3%; CI 95%: 31.8%-59.4%) of cases with mosaicism were detected by cfNIPT; highest for RATs (56%) and lowest for CNVs (22%). CfNIPT more commonly detected high-level than low-level mosaic cases (p=0.000). CfNIPT detected 7/16 (43.8%; CI 95%: 21%-69%) clinically significant mosaic cases, either true fetal mosaicism or confined placental mosaicisms with adverse pregnancy outcome. There was a trend toward a higher risk for adverse outcome in pregnancies where mosaicism was detected by cfNIPT compared to pregnancies where mosaicism was not detected by cfNIPT (p=0.31). CfNIPT has a low detection rate of mosaicism, including pregnancies with clinically significant mosaicism. However, abnormal cfNIPT results may be a predictor of adverse pregnancy outcomes.

Prospective Investigation of Optical Genome Mapping for Prenatal Genetic Diagnosis.

Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.

Prevalence of HTLV-1/2 infection in pregnant women in Central and South America and the Caribbean: a systematic review and meta-analysis

BackgroundHuman T-lymphotropic viruses (HTLV)-1 infection is endemic in many countries of Central and South America and Caribbean (CSA&C). Neither screening nor surveillance programs exist for HTLV-1/2 infection among pregnant women in this region. Neither in Western nations with large migrant flows from HTLV-1/2 endemic regions. MethodsSystematic review and meta-analysis of the prevalence of HTLV-1/2 infection among CSA&C pregnant women. We included studies searching EMBASE, PubMed/MEDLINE, Scopus, and Web of Science from inception to February 15, 2023. This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. ResultsWe identified a total of 620 studies. Only 41 were finally included in the meta-analysis. Most studies (61.0%) were from Brazil and Peru (14.6%). The total number of participants was 343,707. The pooled prevalence of HTLV-1/2 infection among CSA&C pregnant women was 1.30% (95% CI: 0.96-1.69) using anti-HTLV-1/2 antibody screening tests. There was a high heterogeneity (I2 = 98.6%). Confirmatory tests gave an HTLV-1 infection rate of 1.02% (95% CI: 0.75-1.33). ConclusionsThe prevalence of HTLV-1/2 infection among CSA&C pregnant women is 1.3%, most cases being HTLV-1. This rate is greater than for other microbial agents regularly checked as part of antenatal screening (such as HIV, hepatitis B, or syphilis). Thus, HTLV-1/2 antenatal testing should be mandatory among CSA&C pregnant women everywhere.

Supporting patient decision-making in non-invasive prenatal testing: a comparative study of professional values and practices in England and France

BackgroundNon-invasive prenatal testing (NIPT), which can screen for aneuploidies such as trisomy 21, is being implemented in several public healthcare systems across Europe. Comprehensive communication and information have been highlighted in the literature as important elements in supporting women’s reproductive decision-making and addressing relevant ethical concerns such as routinisation. Countries such as England and France are adopting broadly similar implementation models, offering NIPT for pregnancies with high aneuploidy probability. However, we do not have a deeper understanding of how professionals’ counselling values and practices may differ between these contexts.MethodsIn this paper, we explore how professionals in England and France support patient decision-making in the provision of NIPT and critically compare professional practices and values. We draw on data from semi-structured interviews with healthcare professionals.ResultsBoth English and French professionals emphasised values relating to patient choice and consent. However, understandings and application of these values into the practice of NIPT provision differed. English interviewees placed a stronger emphasis on interpreting and describing the process of counselling patients and clinical care through a “principle” lens. Their focus was on non-directiveness, standardisation, and the healthcare professional as “decision-facilitator” for patients. French interviewees described their approach through a “procedural” lens. Their focus was on formal consent, information, and the healthcare professional as “information-giver”. Both English and French professionals indicated that insufficient resources were a key barrier in effectively translating their values into practice.ConclusionOur findings illustrate that supporting patient choice in the provision of NIPT may be held as an important value in common on a surface level, but can be understood and translated into practice in different ways. Our findings can guide further research and beneficially inform practice and policy around NIPT provision.

A noninvasive prenatal test pipeline with a well-generalized machine-learning approach for accurate fetal trisomy detection using low-depth short sequence data

Noninvasive prenatal test (NIPT) reduces the associated risk of procedure-related miscarriage. However, due to accuracy, special fetuses, economic and policy gaps, NIPT still cannot replace traditional surgical methods. Developing a pipeline with low cost, low technical difficulty, stability and high accuracy is a major challenge for NIPT to be widely used. This study proposes a new pipeline for the detection of fetal trisomy which includes 3 steps: 1. 40 bp single-end sequencing, 2. PchrN calculations, and 3. logisticregression (LR) models. Part of the public dataset (100 out of 144 samples) was used to train models and select features in the machine learning pipeline. 314 samples from different sources were used for independent testing. We compare the performance of our method with the bioinformatics method widely used today. Our model shows high robustness to data from different sources. The final best model achieved an AUC of 99.85 % in predicting T21 using chr21 features which are the DNA fragment concentrations. The AUC is 99.50 %, and 97.70 % in predicting T18 and T13 with all features from 24 chromosomes. The PPV of T21, T18 and T13 was predicted to be 91.67 %, 93.33 % and 83.33 %, respectively, which was higher than that obtained by standard bioinformatics methods. The NPV to identify T21, T18, and T13 were 100 %, 99.33 %, and 98.70 %, respectively. Our approach does not need to calculate fetal fraction (FF) and can handle samples from a wide range of gestational ages (GA), twin pregnancies and fetal mosaicism. Our approach can achieve comparable accuracy with the current standard bioinformatics analysis in low-depth sequencing data. This convenient pipeline can be used independently of traditional bioinformatics methods, and its performance has been tested in real clinical practice. Our pipeline can be an important aid for the detection of fetal trisomy in clinical NIPT, which will help further popularize NIPT.

Analysis of Factors Affecting Fetal Fraction in Cell-Free DNA Test

Background: Noninvasive prenatal testing (NIPT) serves as a screening method to assess the risk of chromosomal abnormalities in the fetus, including trisomy 18, 21, and 13. The reliability and success of this test are influenced by the proportion of circulating cell-free DNA obtained from the feto-placental unit, known as the fetal fraction (FF). Objectives: Our study aims to investigate the fetal and maternal factors affecting FF. Methods: Our research involved 1 150 patients referred for NIPT due to various reasons such as maternal age over 35, high-risk screening tests in the first or second trimester, history of trisomy in previous pregnancies, or patient request. Patients completed a questionnaire providing variables including maternal and fetal age, body mass index (BMI), smoking status, multiple pregnancies, and medication use such as Heparin or enoxaparin. Noninvasive prenatal testing was conducted on blood samples using Ion proton technology by Premaitha of the UK. The results, including fetal sex, trisomy risk, fetal fraction, and abnormal sex chromosomes, were analyzed using IBM SPSS 27 to assess the relationship between FF percentage and other variables. Results: The study included 1150 NIPT cases, with maternal ages ranging from 13 to 48 years, BMI from 15 to 70, and gestational age from 10 to 27 weeks. Among these, 96.4% were singleton pregnancies and 3.6% were twin pregnancies. Spontaneous pregnancies accounted for 88.9%, while 9.2% were IVF and 1.2% were IUI. Fetal sex distribution was 45.9% female and 54.1% male. FF ranged from 4% to 20.7%, with a mean FF of 11.07. No significant correlation was found between maternal age, fetal age, maternal BMI, trisomies, and FF. Conclusions: We can see that maternal age has no significant correlation with the fetal fraction. Although fetal age increases, the fetal fraction does too, but this increase was not significant. Body mass index, the route of pregnancy, and the sex of the fetus had no effect on FF. Despite NIPS being safer and yielding better results, other factors can still influence the outcomes of NIPS. Therefore, this test remains a screening tool, and clinical counseling should be conducted both before and after the test.

Isolated fetal umbilical vein varix and the association with intrauterine fetal death and fetal growth restriction: A systematic review, meta-analysis, and nested retrospective cohort study.

To assess the risk of intrauterine fetal death (IUFD) and fetal growth restriction (FGR) in fetuses with an isolated fetal intra-abdominal umbilical vein varix (i-FIUVV). A retrospective cohort study combined with a systematic review and meta-analysis of the literature was performed. In the retrospective cohort study, all singleton fetuses with an i-FIUVV in the fetal medicine units of the Amsterdam UMC (between 2007 and 2023) were analyzed. The primary outcome measures were IUFD and FGR. The sample proportions of IUFD and FGR were depicted as risk percentages. The IUFD proportion was compared to the regional reference population and the FGR proportion was compared to the reported proportions in Europe. The secondary outcome measures were gestational age at diagnosis, initial and maximal FIUVV diameter, fetal monitoring in pregnancy, turbulent flow in the varix, thrombus formation in the varix, induction of labor, gestational age at birth, and birthweight centile. The proportion of fetuses with a birthweight below the 10th centile was compared with that of the regional reference population. The systematic review included all cases from eligible literature published between 2007 and 2023 supplemented by the data of our retrospective cohort study. In the systematic review and meta-analysis, the pooled proportions of IUFD and FGR were assessed in fetuses with i-FIUVV. The retrospective cohort included 43 singletons with an i-FIUVV. The IUFD risk was 0% [Confidence Interval, CI: 0%-8.2%], which did not differ significantly from 0.3% in the reference population, p=1.0. The risk of FGR was 16.3% [CI: 6.8%-30.7%] in the studied population, which is higher than the reported incidence of FGR in Europe ranging from 5%-10%. The proportion of fetuses with birthweights below the 10th centile was higher in our cohort compared with the reference population (23.3 vs. 9.9%, p<0.01). The systematic review included 12 articles, three abstracts, and our current cohort. In total, 513 cases with an i-FIUVV were included. The pooled risk was 0.4% [CI: 0.1%-1.7%] for IUFD and 5.2% [CI: 1.1%-21.3%] for FGR. The mean gestational age at birth did not exceed 39weeks in neither the cohort (38.7weeks) nor the pooled literature (37.6weeks). An i-FIUVV in singletons is not associated with an increased IUFD risk up to 39weeks of gestation but is possibly associated with FGR. The incidence of FGR in our cohort was higher than in the pooled literature (16.3% vs. 5%) but FGR definitions in the included studies varied. The proportion of birthweights below the 10th percentile in our cohort was significantly higher than in the reference group. Thus, based on these findings, we suggest conducting sonographic growth assessments while simultaneously assessing the i-FIUVV. No further monitoring and follow-up are indicated up to 39weeks of gestation. After 39weeks of gestation, data on fetuses with i-FIUVV and their outcomes are lacking.