Search

Non-invasive prenatal testing (NIPT) employs ultra-low-pass sequencing of maternal plasma cell-free DNA to detect fetal trisomy. Its global adoption has established NIPT as a large human genetic resource for exploring genetic variations and their associations with phenotypes. Here, we present methods for analyzing large-scale, low-depth NIPT data, including customized algorithms and software for genetic variant detection, genotype imputation, family relatedness, population structure inference, and genome-wide association analysis of maternal genomes. Our results demonstrate accurate allele frequency estimation and high genotype imputation accuracy (R2>0.84) for NIPT sequencing depths from 0.1× to 0.3×. We also achieve effective classification of duplicates and first-degree relatives, along with robust principal-component analysis. Additionally, we obtain an R2>0.81 for estimating genetic effect sizes across genotyping and sequencing platforms with adequate sample sizes. These methods offer a robust theoretical and practical foundation for utilizing NIPT data in medical genetic research.

OBJECTIVE: We report findings from a U.S. mixed-methods pilot study of the Person-Centered Care in Fetal Care Centers (PCC-FCC) Scale. METHODS: Participants, who received care at a U.S. Fetal Care Center (FCC) between 2017 and 2021, completed an online questionnaire providing sociodemographic details, specifics about the care received, qualitative experiences, and scores from the PCC-FCC Scale. RESULTS: Participants (n = 247) PCC-FCC scores and qualitative feedback indicate high perceived person-centered care (PCC), particularly in areas of care coordination, respectful care, and patient education. However, 8% scored below the midpoint, and 38% of comments were negative, especially regarding expectation setting, preparation for post-intervention maternal health, and psychosocial support. Public insurance was associated with higher total PCC-FCC (p = 0.03) and Factor 2 scores (p = 0.02) compared to those with private insurance. The qualitative themes trust, clarity, comprehensive care, compassion, and belonging further elucidate the concept of PCC in FCCs. CONCLUSION: The PCC-FCC Scale pilot study revealed strong overall PCC in FCCs, yet variability in patient experiences suggests areas needing improvement, including expectation setting, preparation for post-intervention maternal health, and psychosocial support. Future research must prioritize diverse samples and continued mixed methodologies to better understand the role of insurance and identify other potential disparities, ensuring comprehensive representation of the FCC patient population.

AimTo develop a non-invasive prenatal test for beta-hemoglobinopathies based on analyzing maternal plasma by using next generation sequencing.MethodsWe applied next generation sequencing (NGS) of maternal plasma to the non-invasive prenatal testing (NIPT) of autosomal recessive diseases, sickle cell disease and beta-thalassemia. Using the Illumina MiSeq, we sequenced plasma libraries obtained via a Twist Bioscience probe capture panel covering 4 Kb of chromosome 11, including the beta-globin (HBB) gene and >450 genomic single-nucleotide polymorphisms (SNPs) used to estimate the fetal fraction (FF). The FF is estimated by counting paternally transmitted allelic sequence reads present in the plasma but absent in the mother. We inferred fetal beta-globin genotypes by comparing the observed mutation (Mut) and reference (Ref) read ratios to those expected for the three possible fetal genotypes (Mut/Mut; Mut/Ref; Ref/Ref), based on the FF.ResultsWe bioinformatically enriched the FF by excluding reads over a specified length via in-silico size selection (ISS), favoring the shorter fetal reads, which increased fetal genotype prediction accuracy. Finally, we determined the parental HBB haplotypes, which allowed us to use the read ratios observed at linked SNPs to help predict the fetal genotype at the mutation site(s). We determined HBB haplotypes via Oxford Nanopore MinION sequencing of a 2.2 kb amplicon and aligned these sequences using Soft Genetics' NextGENe LR software.ConclusionThe combined use of ISS and HBB haplotypes enabled us to correctly predict fetal genotypes in cases where the prediction based on variant read ratios alone was incorrect.

OBJECTIVES: Determine the incremental diagnostic yield of prenatal exome sequencing (pES) over chromosome microarray (CMA) or G-banding karyotype in fetuses with central nervous system (CNS) abnormalities. METHODS: Data were collected via electronic searches from January 2010 to April 2022 in MEDLINE, Cochrane, Web of Science and EMBASE. The NHS England prenatal exome cohort was also included. Incremental yield was calculated as a pooled value using a random-effects model. RESULTS: Thirty studies were included (n = 1583 cases). The incremental yield with pES for any CNS anomaly was 32% [95%CI 27%-36%; I2 = 72%]. Subgroup analysis revealed apparent incremental yields in; (a) isolated CNS anomalies; 27% [95%CI 19%-34%; I2 = 74%]; (b) single CNS anomaly; 16% [95% CI 10%-23%; I2 = 41%]; (c) more than one CNS anomaly; 31% [95% Cl 21%-40%; I2 = 56%]; and (d) the anatomical subtype with the most optimal yield was Type 1 malformation of cortical development, related to abnormal cell proliferation or apoptosis, incorporating microcephalies, megalencephalies and dysplasia; 40% (22%-57%; I2 = 68%). The commonest syndromes in isolated cases were Lissencephaly 3 and X-linked hydrocephalus. CONCLUSIONS: Prenatal exome sequencing provides a high incremental diagnostic yield in fetuses with CNS abnormalities with optimal yields in cases with multiple CNS anomalies, particularly those affecting the midline, posterior fossa and cortex.

OBJECTIVE:  This study aimed to assess factors that influence patients decisions in accepting prenatal diagnostic testing following genetic counseling for increased risk of fetal aneuploidy. METHODS:  This is a retrospective cohort study of women at increased risk of fetal aneuploidy and genetic disorders who had genetic counseling from January 2012 to December 2016 at a single academic center. Demographics, indications for genetic counseling, and rates of diagnostic testing were collected and compared between those who accepted diagnostic testing and those who chose cell free DNA. The variables were analyzed using Chi-square, Fishers exact test, and multiple logistic regression. RESULT:  Of the 2,373 pregnant women who underwent genetic counseling for increased risk of fetal aneuploidy and genetic disorders during the study period, 321 women had diagnostic testing (13.5%). Women at 35 years and older accepted diagnostic testing more than women younger than 35 years (20.7 vs. 11.5%, p

This study reported a large cohort of fetal blood analysis of various hemoglobinopathies.A total of 371 fetal blood specimens were recruited. Complete blood count and hemoglobin (Hb) analysis using capillary electrophoresis were performed. Genotypes were defined by DNA analysis.Among 371 fetuses, 36 were non-thalassemic and 29 thalassemia genotypes were identified in the remaining 335 fetuses. Fetuses with β-thalassemia and Hb E traits, homozygous Hb E, and Hb E-β0-thalassemia had similar hematological parameters as those of non-thalassemic. However, the levels of Hb A in β-thalassemia and Hb E traits were approximately half of that observed in the non-thalassemic fetuses. As for Hb E, fetuses with a single copy of the βE-globin gene in the Hb E trait and Hb E-β0-thalassemia had lower Hb E levels as compared to that of the homozygous Hb E. For α-thalassemia, fetuses with one or two α-globin gene defects had small changes in hematological parameters, but variable Hb Bart’s levels were observed. Fetuses with Hb H and Hb H-CS diseases had moderate anemia, whereas those with homozygous Hb CS and Hb Bart’s hydrops fetalis had severe anemia. Identification of the fetuses with Hb Bart’s hydrops fetalis with various genetic interactions allows the exact re-location of electrophoretic mobilities of various embryonic Hbs.This study confirmed the genetic heterogeneity of hemoglobinopathies among the fetuses and fetal blood analysis are useful for presumptive diagnosis of hemoglobinopathies. The results should facilitate a prevention and control program of hemoglobinopathies in the region. [ABSTRACT FROM AUTHOR]

Objective: This study aims to assess the diagnostic efficacy of a combined approach integrating chromosomal karyotyping, copy number variation sequencing (CNV-seq), and quantitative fluorescence polymerase chain reaction (QF-PCR) in detecting chromosomal abnormalities in high-risk pregnancies. Methods: This retrospective study analyzed 617 high-risk pregnancies undergoing prenatal diagnosis from February 2023 to August 2024, with amniotic fluid samples concurrently analyzed using karyotyping, CNV-seq, and QF-PCR. We evaluated clinical characteristics, diagnostic yields, and inter-method concordance rates. Longitudinal follow-up assessed pregnancy outcomes and neonatal phenotypes, with particular emphasis on cases demonstrating diagnostic discrepancies or variants of uncertain clinical significance. Results: The integrated approach detected chromosomal abnormalities in 12.5% (77/617) of cases, significantly higher than the rates achieved by karyotyping alone (9.7%) and CNV-seq/QF-PCR alone (8.3%) (p < 0.05). Karyotyping showed full concordance with CNV-seq and QF-PCR in detecting major chromosomal aneuploidies, identifying 21 cases of trisomy 21 and 4 cases of trisomy 18. CNV-seq uniquely identified additional pathogenic copy number variations in 2.1% of cases and variants of uncertain significance (VUS) in 3.2% of cases, both undetectable by conventional karyotyping. Subjects with high-risk non-invasive prenatal testing (NIPT) results had the highest abnormality detection rate (57.6%, p < 0.05). Follow-up data revealed pregnancy termination in 44 of 97 cases with chromosomal abnormalities. Notably, neonates carrying pathogenic CNVs inherited from asymptomatic parents demonstrated normal phenotypes. Conclusion: The integration of karyotyping, CNV-seq, and QF-PCR provides superior diagnostic yield compared to individual testing strategies in high-risk pregnancies. Although karyotyping remains the gold standard for detecting major chromosomal aberrations, CNV-seq and QF-PCR enhance diagnostic precision through detection of submicroscopic variations. Multi-center studies with larger cohorts are needed to confirm these findings and clarify the clinical significance of uncertain variants. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical performance of expanded non-invasive prenatal testing (NIPT-plus) and compare its effectiveness in screening for chromosomal aneuploidies with that of NIPT. Methods: Screening results, confirmatory invasive testing results, and follow-up data from pregnant women who underwent either NIPT (6792 cases) or NIPT-Plus (5237 cases) testing at Luohe Central Hospital, China, from January 2019 to June 2023 were collected. The positive predictive value (PPV), sensitivity, specificity, and other indicators for different types of chromosomal abnormalities in NIPT/NIPT-plus screening were calculated. The willingness of pregnant women with various types of abnormalities to undergo confirmatory invasive testing and the proportion of pregnancy terminations were investigated. Results: The average number of unique reads in NIPT-plus samples was 5.26 times greater than that in NIPT samples. There was no significant difference in the PPV or positive rate between NIPT-plus and NIPT for screening chromosomal aneuploidies. Compared with the low-risk group, the high-risk group had a greater PPV; however, in the NIPT-plus group, there was no significant disparity in the PPV between the low-risk and high-risk groups. Compared with rare autosomal aneuploidies (RAAs), pregnant women had a higher rate of confirmatory invasive testing for common trisomies, sex chromosomal abnormalities (SCAs), and copy number variations (CNVs). However, the rate of pregnancy termination for common trisomies, RAAs, and CNVs was higher than that for SCAs. Conclusion: By enhancing sequencing data, NIPT-plus can effectively screen for CNVs as well as chromosomal aneuploidies. However, NIPT-plus does not have an advantage over standard NIPT in screening for chromosomal aneuploidies. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Introduction: Pre-implantation testing (PGT) is often suggested by healthcare professionals (HCP) to parents of children with congenital adrenal hyperplasia (CAH) considering subsequent children. Despite this, some families choose to conceive naturally without genetic testing and intervention. The aims of this study were to explore fertility choices of couples with a child with CAH and the decision making process and perceptions behind these choices, and to explore the families' lived experiences with CAH and the couples' subsequent fertility journey. A better healthcare professional understanding of these experiences may subsequently help guide clinicians to better manage and support families of children with CAH and other autosomal recessive conditions. Methods: All parents of current children of a tertiary service in 2020 with 21-hydroxylase deficient CAH who made an active decision regarding family planning after diagnosis of their index child were invited to participate in a semi-structured interview. Thematic analysis was performed using an inductive, semantic approach. Results: Thirty families (34 children) were identified. Fourteen considered subsequent children and had directed genetic counselling. Eight decided to have additional children of whom seven agreed to participate. Thematic analysis identified six key domains. Psychological impact surrounding the CAH diagnosis was long-lasting, causing symptoms of trauma including depression and anxiety, and influencing a couple's choice to pursue PGT to avoid having another affected child. The perception of the index child having a mild phenotype, and fear of a more severe phenotype, often supported this decision. Conversely, lived experience of CAH and low day-to-day impact, along with a negative experience of PGT, with a greater than anticipated financial, physical, and emotional toll, led some families to subsequently consider natural conception. The role of the healthcare professional (HCP) was important in the CAH and family planning journeys. A perceived poor understanding of CAH, overstating its potential seriousness, contributed to distress. Parents reported feeling pressured to undergo PGT. Peer-support had a universally positive impact on family experience. Discussion/conclusions: This study highlights the complex and dynamic nature of fertility decision-making, and the importance of HCP empathy and open-mindedness. Education of HCP and encouraging peer support may improve the CAH and fertility journey for families. [ABSTRACT FROM AUTHOR]

Background: Amniocentesis is a widely used invasive prenatal diagnostic procedure, recognized for its high sensitivity and low risk of complications. This study aims to evaluate the association between amniocentesis and pregnancy outcomes, such as miscarriage, preterm rupture of membranes (PROM), and preterm birth, as well as perinatal outcomes. Methods: A case-control study was conducted at the Regional Hospital in Kielce, Poland, from 2016 to 2022, involving 1834 patients, 225 of whom underwent amniocentesis, while 1609 did not receive any invasive diagnostics. Data were collected from medical records and included maternal factors such as age, BMI, delivery mode, complications, and newborn condition. Results: The study found no statistically significant differences between the study and the control groups regarding pregnancy or perinatal characteristics. Miscarriage occurred in 1.9% of the patients in the amniocentesis group, with no cases in the control group. Rates of preterm delivery were similar between groups (8.33% in the study group vs. 5.74% in the control group, p > 0.05). Postnatal outcomes, such as birth term, birth weight, and Apgar scores, were comparable across both groups. Fetal growth restriction was slightly more frequent in the study group (2.8% vs. 0.8%). One neonatal death was observed in each group. The relative risk of complications following amniocentesis was 1.69 (CI 0.38–7.24). Conclusions: Amniocentesis is a safe invasive prenatal procedure. It should be offered to every pregnant woman when necessary. Before the procedure, the patient should be clearly informed of the risk related to amniocentesis but at the same time reassured that the complication rate is very low. [ABSTRACT FROM AUTHOR]

Non-invasive prenatal testing (NIPT) has been widely adopted for the screening of chromosomal abnormalities; however, its adoption for monogenic disorders, such as β-thalassaemia, has proven challenging. Haemoglobinopathies are the most common monogenic disorders globally, with β-thalassaemia being particularly prevalent in Cyprus. This study introduces a non-invasive prenatal haplotyping (NIPH) assay for β-thalassaemia, utilizing cell-free DNA (cfDNA) from maternal plasma. The assay determines paternal inheritance by analyzing highly heterozygous single-nucleotide variants (SNVs) in the β-globin gene cluster. To identify highly heterozygous SNVs in the population, 96 randomly selected samples were processed using Illumina DNA-prep NGS chemistry. A custom, high-density NGS genotyping panel, named HAPLONID, was designed with 169 SNVs, including 15 common pathogenic ones. The AmpliSeq for Illumina assay was then applied to cfDNA to evaluate the panel's efficiency in performing NIPT for β-thalassaemia. Analysis revealed 219 highly polymorphic SNVs, and the sequencing of 17 families confirmed successful paternal allele determination. The NIPH assay demonstrated 100% success in diagnostic interpretation. This study achieved the advancement of an integrated NGS-NIPT assay for β-thalassaemia, bringing it one step closer to being a diagnostic assay and thereby enabling a reduction in the number of risky invasive prenatal sampling procedures in Cyprus and elsewhere. [ABSTRACT FROM AUTHOR]

Background: Congenital muscular dystrophies (CMDs) and myopathies (CMYOs) are a clinically and genetically heterogeneous group of neuromuscular disorders that share common features, such as muscle weakness, hypotonia, characteristic changes on muscle biopsy and motor retardation. In this study, we recruited eleven families with early-onset neuromuscular disorders in China, aimed to clarify the underlying genetic etiology. Methods: Essential clinical tests, such as biomedical examination, electromyography and muscle biopsy, were applied to evaluate patient phenotypes. Whole exome sequencing was used to screen for prospective variants responsible for muscular diseases, followed by co-segregation analysis in the families and prenatal diagnosis via Sanger sequencing, if appropriate. Nanopore sequencing and optical genome mapping were applied for detecting complicated genome rearrangements. Results: Fourteen variants in nine genes (ATL1, LMNA, KLHL40, FKRP, DMD, ACTA1, MSTO1, RYR1 and LAMA2) associated with congenital muscular conditions were identified in the ten families mentioned above. Among them, five novel variants, c.1153_1155del in LMNA, c.577 A > G in ACTA1, c.694T > G in MSTO1, c.5938del in LAMA2, and a rare genome fusion ogm[GRCh38] fus(X; X)(p22.31;p21.1) involving DMD, have not been recorded in public databases to the best of our knowledge. Conclusions: CMDs and CMYOs were probably responsible for most of the cases (9/11) of genetic muscular defects in this study. Molecular analysis is highly beneficial for the precise diagnosis, genetic counseling and prenatal diagnosis of families suspected of having genetic muscular disorders. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Objective: Spinal muscular atrophy (SMA) is a motor neuron disorder encompassing 5q and non-5q forms, causing muscle weakness and atrophy due to spinal cord cell degeneration. Understanding its genetic basis is crucial for genetic counseling and personalized treatment options. Methods: This study retrospectively analyzed families of patients suspected of SMA at our institution from February 2006 to March 2024. Various molecular techniques, including multiplex ligation-dependent probe amplification analysis, long-range polymerase chain reaction (PCR) combined with nested PCR, Sanger sequencing, and whole-exome sequencing were employed to establish a thorough genetic variant profile in 680 Chinese pedigrees with clinically suspected SMA. Results: Out of 680 families suspected of having SMA, 675 exhibited mutations in the SMN1 gene, while three families were linked to mutations in the IGHMBP2 gene. One family exhibited a genetic variation in the NEB gene, and another family exhibited a variation in the SCO2 gene. Among the families with mutations in the SMN1 gene, 645 families exhibited either E7‒E8 or E7 homozygous deletion. Some families displayed E7‒8 heterozygous deletions along with other mutations, such as E1 or E1‒6 heterozygote deletion and point mutations. Furthermore, one family demonstrated a compound-heterozygous double mutation, while another carried a type "2 + 0" mutation alongside a point mutation. Conclusions: This study comprehensively analyzed the genetics of suspected familial SMA cases in the Chinese population, providing insights into the molecular genetic mechanisms of SMA and the utility of various detection techniques. The findings revealed important implications for genetic counseling, prenatal diagnosis, and targeted therapies in clinical practice. [ABSTRACT FROM AUTHOR]

In this study, we investigated the factors that influence families’ decision-making processes about whether to carry a pregnancy to term or to terminate it in cases of fetal anomalies. A questionnaire was administered to 25 participants who chose to terminate their pregnancy and 25 participants who chose to carry their pregnancy to term. Among the sociodemographic characteristics investigated, only monthly income significantly differed between the groups (p = .044), being higher in the termination group. The participants in the non-termination group decided to proceed in a shorter time (p = .014). The majority of the participants in this group made this decision for religious reasons (56 percent), while in the other group, the decision was mostly based on baby-centered or parent-centered factors (48 percent and 52 percent, respectively) (p < .001). In the non-termination group, there was a significantly higher number of participants who expressed that their religious beliefs played an influential role in their decision (p = .002). In contrast, in the termination group, higher number of participants indicated that the information provided by their doctor was very effective in shaping their decisions (p < .001). According to the results of our study, social, cultural, and religious reasons seem to be the most important factors affecting participants’ decisions related to pregnancy termination. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of whole exome sequencing (WES) in cases of fetal abnormalities diagnosed by prenatal ultrasound (including structural malformations and soft markers) where chromosome microarray analysis (CMA) failed to clarify the cause. Methods: A total of 81 fetuses were selected from the Department of Ultrasound at the Affiliated Obstetrics and Gynaecology Hospital of Nanjing Medical University, who were diagnosed with fetal abnormalities between January 2022 and January 2024. Following genetic counseling, invasive prenatal diagnoses were chosen, and chorionic villus sampling or amniocentesis was performed for CMA testing, which yielded negative results. WES analysis was then conducted on these samples. The determination of genetic variants was classified according to the guidelines of the American Society for Medical Genetics and Genomics (ACMG). Pathogenic and possibly pathogenic variants were categorized as positive results, while clinical significance unknown, benign, and possibly benign were categorized as negative results. Results: The 81 ultrasound anomalies consisted of 47 (58.02%) monosystemic and 34 (41.98%) multisystemic anomalies. WES detected a total of 14 (17.28% ) positive cases, including 7 cases each of monosystemic and multisystemic anomalies, while the remaining 67 cases (82.72%) were negative. The most common ultrasound abnormalities in positive fetuses were cardiovascular system abnormalities and skeletal system abnormalities, each occurring in 5 cases (35.71%), followed by urinary system abnormalities in 4 cases (28.57%). In addition, 2 fetuses had combined nuchal translucency (NT) thickening at early stage (14.29%), and multiple abnormalities were found by ultrasound at mid⁃trimester. Conclusion: Fetuses with ultrasound anomalies, especially when combined with cardiovascular, skeletal, urinary anomalies or multisystem anomalies, are recommended to undergo WES testing if CMA testing fails to clarify the etiology, which may identify new potential causative genes. [ABSTRACT FROM AUTHOR]

Sonoelastography, a novel ultrasound-based technique, is emerging as a valuable tool in prenatal diagnostics by quantifying tissue elasticity and stiffness in vivo. This narrative review explores the application of sonoelastography in assessing maternal and fetal health, with a focus on cervical, placental, pelvic floor, and fetal tissue evaluations. In the cervix, sonoelastography aids in predicting preterm birth and assessing labor induction success. For the placenta, it provides insights into conditions like preeclampsia and intrauterine growth restriction through elasticity measurements. Assessing fetal tissues, including the lungs, liver, and brain, sonoelastography offers a non-invasive method for evaluating organ maturity and detecting developmental anomalies. Additionally, pelvic floor assessments enable better management of childbirth-related injuries and postpartum recovery. While current studies support its safety when used within established limits, further research is necessary to confirm long-term effects. Future advancements include refining protocols, integrating machine learning, and combining sonoelastography with other diagnostic methods to enhance its predictive power. Sonoelastography holds promise as an impactful adjunct to conventional ultrasound, providing quantitative insights that can improve maternal and fetal outcomes in prenatal care. [ABSTRACT FROM AUTHOR]

Objective Low fetal fraction (FF) on cell-free DNA (cfDNA)-based noninvasive prenatal screening (NIPS) is a common etiology for indeterminate results. As maternal Black race is implicated as a risk factor for low FF and more indeterminate results, we sought to evaluate this association. Study Design This was a single-institution, retrospective cohort study of cfDNA-based NIPS performed between May 2017 and May 2022 with complete clinical data abstraction. We compared FF, indeterminate rates, and total cfDNA concentration among self-reported Black, White, and Other groups from NIPS results from 2017 to 2022 with full clinical data abstraction. Using linear regression and interaction testing, we evaluated associations between self-reported race, FF, indeterminate rate, and total cfDNA concentration. Results In total, 1,591 participants met the inclusion criteria; 70.8% (n = 1,126) self-identified as White, 6.9% (n = 110) as Black, and 22.3% (n = 355) self-identified with another race. Mean FF was not different between the White, Black, or Other groups (11.8 vs. 11.2 vs. 11.7%, respectively, p = 0.52). This remained true after adjusting for body mass index (BMI), gestational age (GA) at draw, and fetal sex (all p > 0.17). Interaction testing for FF and total cfDNA by race with BMI, GA at draw, and fetal sex demonstrated no effect modification. Conclusion In our population, maternal self-identified race, particularly Black race, does not affect FF. Biological plausibility for race-based differences on clinical tests requires ongoing thoughtful consideration. Key Points NIPS is widely used to screen for fetal aneuploidy. FF is an important test metric, and low FF is associated with adverse outcomes, like aneuploidy. In existing studies, Black race is implicated as a risk factor for lower FF. Our study found no differences in FF between groups by self-reported race. Biological plausibility for race-based differences on clinical tests requires ongoing consideration. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine decisional conflict and identify its predictors in Chinese pregnant women who were making decisions about further prenatal testing after receiving a screening result of high-risk for Down syndrome. Method: A cross-sectional study was conducted from September 2020 to July 2021 in Guangzhou, China. Two-hundred and sixty pregnant women receiving a screening result of high-risk for Down syndrome completed a questionnaire comprising the Decisional Conflict Scale, Self‐rating Anxiety Scale, and Social Support Rating Scale. Results: The mean decisional conflict score was 28.8 ± 13.6, representing a moderate level. Advanced age (≥35 years), having a religious belief, not knowing about non-invasive or invasive prenatal testing, choosing NIPT for further prenatal testing, high levels of anxiety, and low levels of social support were significant predictors of decisional conflict, explaining 28.4% of its variance (F = 18.115, p < 0.001). Conclusions: The results highlighted the necessity of assessing patients' decisional conflict and providing adequate interventions along the prenatal care trajectory. The results also showed that providing good support has an essential value for women by relieving their decisional conflict. [ABSTRACT FROM AUTHOR]

Objectives: Reveal developmental alterations in choroid plexus volume (CPV) among fetuses with isolated ventriculomegaly (VM) through neuro-ultrasound. Methods: This prospective study aimed to assess the development of fetal CPV in normal fetuses and those with isolated VM through neuro-ultrasound. The fetuses of isolated VM were categorized into mild, moderate, and severe groups, and subsequently, the lateral ventricle evolution was monitored. The developmental alterations in CPV among fetuses with isolated VM were determined by comparing the CPV z-scores with those of normal fetuses. Receiver operating characteristics curve analysis was used to assess the predictive value of altered CPV in lateral ventricle evolution. Results: A total of 218 normal fetuses and 114 isolated VM fetuses from 22 weeks to 35 weeks of gestation were included. The CPV decreased as the isolated VM was getting worse. Both fetuses with isolated moderate ventriculomegaly and those with isolated severe ventriculomegaly exhibited reduced CPV compared to normal fetuses. The CPV in fetuses with isolated mild ventriculomegaly (IMVM) varied, with some showing a larger CPV compared to normal fetuses, while others exhibited a smaller CPV. The larger CPV in cases of IMVM may serve as a predictive factor for either regression or stability of the lateral ventricle, while reduced CPV in cases of isolated VM may indicate worsening of the lateral ventricle. Conclusion: The growth volume of fetal CP exhibited alterations in fetuses with isolated VM, and these changes were found to be correlated with the evolution of the lateral ventricle. Clinical relevance statement: Neuro-ultrasound revealed varying degrees of alterations in the volume development of the choroid plexus within the fetus with isolated VM. The findings can help predict lateral ventricle prognosis, greatly contributing to prenatal diagnosis strategies for fetuses with isolated VM. Key Points: The volume of choroid plexus growth is altered in fetuses with isolated VM. The altered CPV in isolated VM was associated with lateral ventricle evolution. The findings are useful for prenatal counseling and managing fetuses with isolated VM. [ABSTRACT FROM AUTHOR]

Background: Previous research has linked prenatal maternal infections to later childhood developmental outcomes and socioemotional difficulties. However, existing studies have relied on retrospectively self‐reported survey data, or data on hospital‐recorded infections only, resulting in gaps in data collection. Methods: This study used a large linked administrative health dataset, bringing together data from birth records, hospital records, prescriptions and routine child health reviews for 55,856 children born in Greater Glasgow & Clyde, Scotland, 2011–2015, and their mothers. Logistic regression models examined associations between prenatal infections, measured as both hospital‐diagnosed prenatal infections and receipt of infection‐related prescription(s) during pregnancy, and childhood developmental concern(s) identified by health visitors during 6‐8 week or 27‐30 month health reviews. Secondary analyses examined whether results varied by (a) specific developmental outcome types (gross‐motor‐skills, hearing‐communication, vision‐social‐awareness, personal‐social, emotional‐behavioural‐attention and speech‐language‐communication) and (b) the trimester(s) in which infections occurred. Results: After confounder/covariate adjustment, hospital‐diagnosed infections were associated with increased odds of having at least one developmental concern (OR: 1.30; 95% CI: 1.19–1.42). This was broadly consistent across all developmental outcome types and appeared to be specifically linked to infections occurring in pregnancy trimesters 2 (OR: 1.34; 95% CI: 1.07–1.67) and 3 (OR: 1.33; 95% CI: 1.21–1.47), that is the trimesters in which foetal brain myelination occurs. Infection‐related prescriptions were not associated with any clear increase in odds of having at least one developmental concern after confounder/covariate adjustment (OR: 1.03; 95% CI: 0.98–1.08), but were associated with slightly increased odds of concerns specifically related to personal‐social (OR: 1.12; 95% CI: 1.03–1.22) and emotional‐behavioural‐attention (OR: 1.15; 95% CI: 1.08–1.22) development. Conclusions: Prenatal infections, particularly those which are hospital‐diagnosed (and likely more severe), are associated with early childhood developmental outcomes. Prevention of prenatal infections, and monitoring of support needs of affected children, may improve childhood development, but causality remains to be established. [ABSTRACT FROM AUTHOR]

Introduction: Aim: The aim of the study is to determine the optimal timing for surgery in patients with small bowel duplications. Methods: A retrospective cohort study, including all patients younger than 18 years who were diagnosed with small bowel duplications from 2013 until 2024 in a single tertiary medical center, was performed. Patients' demographics, duplication size and location, pathological results, and clinical outcomes were collected. Results: Sixteen patients (nine boys, seven girls) underwent laparoscopic-assisted resection of small bowel duplication at an average age of 3 years. A prenatal diagnosis was made in 11 patients, 10 (91%) of whom underwent elective surgery at a median age of 1.3 years. Overall, six patients required semi-elective or urgent surgery due to bowel obstruction, abdominal discomfort, or symptomatic anemia, with most (83%) lacking prenatal evaluation. Elective surgery patients had significantly smaller duplications (13 cm3 vs. 135 cm3). Post-operative recovery was satisfactory in all patients, with an average hospital stay of 6 days. Conclusion: In conclusion, asymptomatic, small duplication cysts in the small bowel of pediatric patients can be managed expectantly and can be operated after the first year of age. This approach is safe and allows for laparoscopic exploration in older infants, yielding satisfactory outcomes. [ABSTRACT FROM AUTHOR]

Background: Mucopolysaccharidosis type I (MPS I - IDUA gene) is a rare autosomal recessive lysosomal storage disorder. Clinical symptoms, including visceral overload, are progressive and typically begin postnatally. Descriptions of hepatosplenomegaly associated with lysosomal pathology are uncommon during the prenatal period. The most prevalent etiologies are infections, anemia, and neoplasms. Case presentation: A pregnant woman at 26.5 gestational weeks was referred to our center for fetal ultrasound findings of hepatosplenomegaly, distinct facial features, and liver, spleen and thymus echogenic spots. Whole exome sequencing after amniocentesis identified two likely pathogenic IDUA gene variants (in trans), raising suspicion of a diagnosis of MPS I. MPS I was confirmed by the deficiency of α-L-iduronidase activity in amniotic cells. A medical pregnancy termination was carried out due to the severe prognosis. After termination of pregnancy, external examination of the fetus confirmed hepatosplenomegaly and coarse dysmorphic features. Conclusion: Lysosomal storage diseases (LSD) are a rare cause of prenatal hepatosplenomegaly, but this has not been described in MPS I according to our literature search. The genetic variants identified in this case prompted early diagnosis through genome-wide studies. This rare presentation of MPS I highlights the expanding role of genomic analyses in diagnosing conditions during pregnancy. [ABSTRACT FROM AUTHOR]

Background/Objectives: Cardiac rhabdomyoma (CR), the most frequently occurring fetal cardiac tumor, is often an early marker of tuberous sclerosis complex (TSC). This study evaluates outcomes of fetuses with prenatally diagnosed cardiac tumors managed at a single tertiary center. Methods: Medical records of fetuses diagnosed with cardiac tumors between 2009 and 2024 were retrospectively reviewed. Results: Sixteen cases were identified, with a median follow-up of 6.7 years. TSC was confirmed in 14 cases (88%). Multiple tumors were observed in 13 cases (81%), while 3 cases (19%) had solitary tumors. Both non-TSC cases involved solitary tumors. Cardiac complications (arrhythmias, conduction disorders, and hemodynamic abnormalities) occurred in 38% of cases prenatally and 69% postnatally, with larger tumor diameters significantly associated with complications (p = 0.02). No fetal hydrops or mortality occurred; however, one child died at age five due to a seizure. Postnatal tumor regression occurred in 56% of cases and complete regression in 38% by a median age of 2.3 years (range: 0.6–4.4). One tumor remained stable. Brain MRI revealed TSC-related changes in all TSC-affected patients except one, who had a developmental brain anomaly. Most TSC patients experienced epilepsy (71%) and developmental delays. Conclusion: While CRs are typically benign and regress spontaneously, their strong association with TSC highlights the importance of early diagnosis and family counseling. TSC-related epilepsy and psychomotor delays significantly impair the quality of life. Early mTOR inhibitor therapy offers promise in mitigating TSC-related complications and improving outcomes. [ABSTRACT FROM AUTHOR]

Background and Objectives: Silver–Russell Syndrome (SRS) is a rare genetic disorder characterized by prenatal and postnatal growth restriction, distinctive facial features, and body asymmetry. Early suspicion during the first trimester remains challenging but crucial for optimizing clinical outcomes. This study aims to highlight a diagnostic approach to the early suspicion of SRS. Materials and Methods: A 28-year-old primigravida presented for routine first-trimester prenatal care. An ultrasound revealed asymmetric growth restriction with normal anatomical findings. The first-trimester biochemical markers, including PAPP-A and β-hCG, were within the normal range. A further evaluation, including amniocentesis and genetic testing, was performed. Results: Genetic testing identified hypomethylation at the 11p15 imprinting control region, confirming the diagnosis of SRS. Parental testing excluded the maternal uniparental disomy of chromosome 7, suggesting an epigenetic mechanism. The findings were consistent with a clinical diagnosis of SRS, and appropriate counseling and multidisciplinary management were initiated. Conclusions: This case underscores the importance of the early recognition of atypical growth patterns, the integration of advanced genetic testing, and multidisciplinary counseling to guide parental decision-making and improve outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Abnormal relative positioning of the superior mesenteric artery (SMA) and vein (SMV) can lead to intestinal malrotation that predisposes to midgut volvulus. The aim of this study was to assess the prenatal ultrasound ability to visualize the relative position of SMA and SMV in normal pregnancies. Methods: Prospective cohort study performed in Montpellier University Hospital Centre, including 80 fetuses during routine 3rd trimester ultrasound scan. For each fetus included, the relative position of the vessels on an axial image was defined as SMV on the right, forward, or on the left of SMA. Doppler imaging was additionally used if necessary. Data were compared to the neonatal abdominal scans performed by pediatric radiologist. Results: The superior mesenteric vessels were identified in 79 fetuses. Prenatal findings showed a usual relative position of the vessels, that is, the vein on the right of the artery, in 96.2%. In 2 cases, the vein was strictly in front of the artery, and in 1 case, the vein was on the left side of the artery. Seventy‐four neonates were examined and comparison with prenatal finding showed a perfect agreement (Kappa coefficient of 100%). An intestinal malrotation was postnatally diagnosed corresponding to the case where vein was on the left side of the artery. Conclusion: This study showed that the relative position of the SMA and SMV could be assessed using ultrasound prenatal examination with a perfect agreement with postnatal findings. In case of abnormal vessels positioning more examinations should be promote including prenatal MRI and postnatal conventional radiologic examinations to confirm intestinal malrotation. [ABSTRACT FROM AUTHOR]

Objective: To establish normal values of palatal bone growth in fetuses at different gestational weeks in the early stages of the second trimester and to explore the clinical application value of the four-step ultrasound screening method for fetal cleft lip and palate. Design: A prospective study of prenatal ultrasound screening. Setting: Secondary maternal and child health institutions. Patients: 300 fetuses of 12 to 20 +6 weeks gestation without cleft lip and/or palate; 8538 fetuses at high risk of cleft lip and palate with malformations or karyotypic abnormalities. Interventions: None. Main Outcome Measures: palatomandibular diameter (PMD) and transverse palatal diameter was measured and establish their typical values. Results: (1) There is a typical "superimposed line" sign in the median sagittal section of the typically developing fetal face from 12 to 20+6 weeks of gestation. (2) The PMD and hard palate transverse diameter of fetuses from 12 to 20+6 weeks of gestation increased linearly with time. (3) Among 8538 high-risk fetuses, 21 cases of cleft lip and palate were diagnosed by the four-step ultrasound screening method in the early stages of the second trimester. Conclusions: The median sagittal section of the typically developing fetal face in the early stages of the second trimester presents a typical "superimposed line" sign, and the PMD and transverse palatal diameter increase with time. The four-step ultrasound screening method for fetal cleft lip and palate in the early stages of the second trimester has high clinical application value. [ABSTRACT FROM AUTHOR]

Introduction: Silver-Russell syndrome (SRS) is an imprinting disorder characterized by intrauterine and postnatal growth retardation. The pathogenic alterations and phenotypes are heterogeneous. Methods: Here, we present a rare pedigree of duplications with different methylation patterns in 11p15.5, which caused SRS or a normal phenotype across three generations. Results: Duplications of maternal IC2 (copy number of 3) with enhanced methylation (methylation index of 0.62) resulted in typical SRS. Conclusion: The result added to the complexity of the molecular genetics of SRS. [ABSTRACT FROM AUTHOR]

Background: Prenatal whole exome sequencing (WES) is becoming an increasingly used diagnostic tool for fetuses with structural anomalies. However, the identification of variants of uncertain significance (VUS) in clinically relevant genes can significantly complicate prenatal diagnosis and genetic counseling. Case presentation: A fetus conceived through in vitro fertilization at the third attempt presented with polydactyly and molar tooth sign at 24 + 6 weeks of gestation. Trio-based WES was performed on both parents and the affected fetus, revealing a pair of compound heterozygous CPLANE1 variants (c.4646 A > T/p.Glu1549Val and c.1233 C > A/p.Tyr411*) potentially associated with Joubert syndrome. According to the ACMG guidelines, one of the biallelic variants was classified as VUS, and the other as pathogenic. However, these variants had no allele frequencies in the general population. The p.Tyr411* variant was classified as deleterious, while the p.Glu1549Val variant was located in highly conserved residues, was predicted to be damaging by in silico tools, and altered hydrogen bonding. Furthermore, CPLANE1 expression was highest in the brain during the embryonic and fetal stages. These findings provide additional support for the association between CPLANE1 variants in this fetus and Joubert syndrome. Thus, the most likely diagnosis was Joubert syndrome, and after careful consideration, the couple decided to terminate the pregnancy. Conclusion: The expression patterns of CPLANE1 and the molecular effects of the variants may provide further evidence supporting the potential for prenatal diagnosis of Joubert syndrome in the case of biallelic VUS and pathogenic variant. This study suggests that molecular insights may play a role in interpreting VUS in clinically relevant prenatal genes for prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Objective To observe the results of chromosomal karyotype analysis and chromosomal microarray analysis (CMA) in 1 600 fetuses with abnormal prenatal ultrasonography. Methods A total of 1 600 fetuses exhibiting ultrasonic abnormalities, including 789 cases with structural anomalies and 811 cases with non-structural anomalies, were selected for concurrent chromosomal karyotype analysis and CMA detection. The results and detection rates of the two methods were compared, and the molecular characteristics and ultrasonic findings of 46 cases of pathogenic chromosomal microdeletion/microduplication syndrome identified through CMA were analyzed. Results Among the 1 600 fetuses with abnormal ultrasound findings, 68 cases were identified through chromosomal karyotype analysis, resulting in a detection rate of 4. 25% (68/1600). A total of 147 abnormal cases were identified through CMA, comprising 58 cases of copy number variations of unknown clinical significance (VOUS CNVs) and 89 cases of pathogenic copy number variations (pCNVs), resulting in a detection rate of 9. 19% (147/1600). Significant difference was found in the detection rate between the two methods (P<0. 05). Among the 789 cases exhibiting ultrasonic structural abnormalities, 41 cases were identified through chromosome karyotype analysis, resulting in a detection rate of 5. 20% (41/789) ; among the 811 cases presenting ultrasonic non-structural abnormalities, 27 cases were confirmed via chromosome karyotype analysis, yielding a detection rate of 3. 33% (27/811) ; significant difference was found in the detection rate between the two groups (P<0. 05). Among the 789 cases exhibiting ultrasonic structural abnormalities, 45 cases of pCNV were identified through CMA, resulting in a detection rate of 5. 70% (45/789). Among the 811 cases with ultrasonic non-structural abnormalities, 44 cases of pCNV were detected via CMA, yielding a detection rate of 5. 43% (44/811). No significant difference was found in the detection rate between the two groups (P>0. 05). Two methods were employed to identify 48 cases with identical abnormalities. Karyotype analysis additionally detected 15 cases of balanced structural abnormalities, and CMA additionally detected 39 cases of pCNV. The use of CMA increased the detection rate of pathogenicity by 2. 44% (39/1, 600). A total of 46 instances of pathogenic chromosomal microdeletions and microduplications were identified through CMA, of which 15 cases exhibited fetal ultrasound phenotypes that correlated with the detected pCNVs. Specifically, this included 9 cases of 15q microdeletion/microduplication syndrome, 7 cases of 16p11. 5 microdeletion/microduplication syndrome, 4 cases each of 1q21. 1, 7q11. 23, and 16p13. 11 microdeletion/microduplication syndromes, while the remaining 18 cases were CNVs with a relatively low detection rate. Conclusions The analysis of chromosome karyotype offers advantages in the identification of balanced structural abnormalities and low-proportion chimera abnormalities. Conversely, CMA provides advantages in detecting small structural abnormalities, particularly microdeletions and microduplications, thereby significantly enhancing the detection rate of pCNV and reducing missed diagnoses in prenatal testing. Chromosomal karyotype analysis and CMA can complement each other to provide more precise data for prenatal diagnosis and genetic counseling. [ABSTRACT FROM AUTHOR]

Background: The literature contains exceedingly limited reports on chromosome 10p15.3 microdeletions. In the present study, two cases of fetuses with pure terminal 10p15.3 microdeletion syndrome in a Chinese population were examined, with the objective of enhancing understanding of the genotype-phenotype correlation associated with 10p15.3 microdeletions. Methods: Two fetuses with chromosome 10p15.3 microdeletion were identified from a cohort of 5,258 cases undergoing amniocentesis. Karyotyping and chromosomal microarray analysis (CMA) was conducted to assess chromosomal abnormalities and detect copy number variations (CNVs) within the families, respectively. Results: In Family 1, the fetus exhibited a 556.2-Kb deletion in the 10p15.3 region, encompassing OMIM genes such as DIP2C and ZMYND11, and presented with increased nuchal translucency on prenatal ultrasound examination. Parental CMA analysis revealed that the 10p15.3 microdeletion was inherited from the father, who displayed mild language impairment. In Family 2, a comparable 10p15.3 microdeletion was identified in a fetus presenting with asymmetric butterfly vertebrae at T10 and T12, along with mild scoliosis of the spine. Family 1 elected to terminate the pregnancy, while Family 2 chose to continue. At a follow-up conducted at one year and eight months, the child demonstrated delays in both speech and motor development. Conclusion: The present study is the first to report two cases of pure terminal chromosome 10p15.3 microdeletion syndrome in fetuses, offering valuable insights for the prenatal diagnosis of 10p15.3 microdeletion syndrome. Further, it is the first to describe mild clinical features, specifically limited to language impairment, in a patient with 10p15.3 microdeletion syndrome. [ABSTRACT FROM AUTHOR]

Background: Blake's pouch cyst (BPC) is a midline cystic anomaly of the posterior fossa. BPC has been shown to have a risk of aneuploidy prenatally. Copy number variation (CNV) and/or genetic syndromes have been reported in a few prenatal/postnatal cases with BPC. The purpose of this study is to determine the additional value of CNV analysis for prenatal diagnosis and prognosis evaluation of BPC. Methods: We reviewed the sonographic findings and genetic results of BPC diagnosed within 6 years at our center. Patients were classified into the isolated and non-isolated groups based on the prenatal and postnatal imaging. We analyzed the chromosomal abnormalities by conventional karyotype analysis combined with chromosomal microarray analysis (CMA) or CNV sequencing (CNV-seq). Results: We recruited 467 low-risk fetuses as the control group to establish normal references of vermian area and brainstem-vermis (BV) angle. Prenatal/postnatal MRI or neonatal neurosonography was used as diagnostic criteria. 34 patients were diagnosed as BPC, including 21 (61.8%) patients with non-isolated and 13 (38.2%) with isolated. Twenty-two patients underwent CMA/CNV-seq, among them 14 patients were performed both CMA/CNV-seq and karyotype analysis. Seven (7/22, 31.8%) patients with BPC had chromosomal abnormalities, including 3 (3/22, 13.6%) patients with chromosomal aneuploidy - trisomy 21, 18 and 13, and 4 (4/22, 18.2%) patients had pathogenic CNVs located at 3p, 9p, Xp/Xq and 7p. Anomalies in fetal heart (35.3%), central nervous system (CNS) (26.5%) and limb (14.7%) were the three top anomalies accompanying BPC. Conclusions: CNV analysis could provide some additional information for prenatal diagnosis and prognosis counseling for patients with non-isolated BPC. And, it adds less value for patients with isolated BPC, however, isolated BPC can be a soft marker for aneuploidy. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore variations in prenatal care, delivery methods, influencing factors, and neonatal outcomes among Rh-negative pregnant women, so as to improve pregnancy healthcare for this demographic, raise the quality of maternal–fetal management, and safeguard the health of both mother and infant. Methods: This study included 200 women who received routine prenatal care, exhibited no other pregnancy complications, and were admitted for delivery. They were divided into an observation group (100 Rh-negative blood type) and a control group (100 Rh-positive blood type). The study examined differences in pregnancy management, clinical characteristics and pregnancy outcomes between the two groups. Results: The results indicated that singleton pregnancies in Rh-negative mothers are associated with significantly higher rates of postpartum blood loss (305.1 ± 183.8 vs. 246.1 ± 84.9 mL, P = 0.004), neonatal hyperbilirubinemia (39% vs. 23%, P = 0.014), low birth weight (11% vs. 2%, P = 0.01), and NICU admission (30% vs. 18%, P = 0.046) compared to the control group. Among Rh-negative mothers, subgroup analysis by ethnicity revealed a higher incidence of fetal distress in the other ethnic groups compared to the Han and Zhuang groups (16.7%, 0, 6.5%, respectively, P = 0.025). Subgroup analysis based on ABO blood type within Rh-negative mothers did not show any statistical significance in various outcomes (all P > 0.05). Infants with neonatal hyperbilirubinemia born to Rh-negative mothers experienced a quicker resolution of hyperbilirubinemia compared to those whose mothers did not receive intramuscular anti-D immunoglobulin [1.0 (1.0, 1.5) vs. 5.0 (1.5, 10.0), P = 0.002]. Conclusions: The Rh-negative blood type is linked to higher risks of neonatal hyperbilirubinemia, low birth weight, and increased postpartum hemorrhage, resulting in detrimental pregnancy outcomes. Administering anti-D immunoglobulin speeds up the resolution of neonatal hyperbilirubinemia. Thus, prudent and efficient use of anti-D immunoglobulin can mitigate adverse outcomes for both mothers and newborns. [ABSTRACT FROM AUTHOR]

Single umbilical artery (SUA) is considered an ultrasound marker of anomalies. Although it may be present in about 0.5% to 6% of normal pregnancies, it has been linked with an increased risk of fetal growth restriction (FGR), as well as cardiac, genitourinary and gastrointestinal malformations and chromosomal anomalies such as trisomies 21 and 18. Objectives: This study aims to evaluate whether the presence of isolated SUA (ISUA) is associated with adverse perinatal outcomes. Methods: A descriptive, observational and retrospective study was conducted, analyzing 1234 pregnancies (1157 normal gestations with a three-vessel cord and 77 cases of ISUA). Results: ISUA was associated with a lower gestational age (38 vs. 39 weeks) and a lower birth weight (3013 vs. 3183 g) when performing a univariate analysis. However, after performing a multivariate analysis adjusted for maternal age and BMI, the association between single umbilical artery (SUA) and lower birth weight could not be proven. No significant differences were found in the rate of malformations, genetic disorders, Apgar score, pH at birth or admissions in the neonatal ICU. Conclusions: ISUA is associated with a lower birth weight but does not increase the risk of prematurity or low-birth-weight-related neonatal admissions. Additionally, ISUA is not significantly associated with a lower gestational age, genetic disorders, fetal malformations, worse Apgar scores or lower pH values at birth. [ABSTRACT FROM AUTHOR]

Background: To investigate prenatal ultrasound findings and the chromosomal outcomes of mosaic embryo transfer. Methods: This retrospective study was conducted on pregnant women who underwent mosaic embryo transfer following blastocyst-stage preimplantation genetic testing for aneuploidy (PGT-A) at CHA Gangnam Medical Center from January 2021 to July 2024. Trophectoderm biopsy specimens were collected using standard protocols, and next-generation sequencing profiles were defined as mosaics when displaying copy number counts in the 20–80% range. The results of the PGT-A, the amniocentesis results, the findings of prenatal ultrasounds, and the pregnancy outcomes were analyzed. Results: A total of 88 mosaic embryos were transferred, of which 77 embryos were successfully implanted. Sixty-seven embryo-maintained pregnancies went beyond 11 weeks (87.0%), all among 58 patients with singleton pregnancies. The chaotic subtype showed the lowest ongoing pregnancy rate, and high-level mosaicism was less frequent in the ongoing group, compared to the total study group and the successful implantation group. Amniocentesis was performed on 33 mothers (56.9%), revealing two cases with abnormal findings that did not correlate with the PGT-A results. Two cases showed abnormalities in the second trimester detailed ultrasound, and both subsequently demonstrated normal findings in the third trimester and after birth. The average gestational age at birth was 38.4 weeks, and the average birth weight was 3313 g. No congenital anomalies were detected in 16 postnatal cases. Conclusions: Our study indicated that mosaic embryos can develop into euploid healthy infants with various levels or types of mosaicism, although the postnatal follow-up data are limited. This study is invaluable for counseling clinical results after mosaic embryo transfer, reassuring that, if patients do not have euploid embryos available, mosaic embryos can also be a viable option for transfer. [ABSTRACT FROM AUTHOR]

This study aims to describe the indications, complications, yield, and safety of amniocentesis beyond 24 weeks for prenatal diagnostic procedures along with the associated maternal and fetal outcomes.A retrospective analysis was conducted on 60 pregnant women (with 61 fetuses) who underwent amniocentesis at or beyond 24 weeks from March 2021 to June 2023 at a tertiary care referral center. Data was collected from medical records and individual patient followups. Descriptive data was collected on patient demographics, amniocentesis indications, and the test results. The other outcomes analyzed were the procedure-related complications and pregnancy outcomes.The mean gestational age at time of the procedure was 254/7 (241/7–331/7). The most common indication for late amniocentesis was abnormal sonographic findings (44/61, 72.13 %), with structural anomalies being the commonest (21/61, 34.44 %). There were no complications related to the procedure. Of the 60 women, 88.3 % (53/60) continued their pregnancies, while 11.66 % (7/60) opted for termination of pregnancy, and two patients had intrauterine fetal demise (2/61, 3.27 %). Genetic testing revealed abnormalities in 6.55 % (4/61) of cases. Of the 51 pregnancies, 39 delivered vaginally (76.47 %; 39/51) and 12 (23.52 %; 12/51) required caesarean sections. There were five neonatal and infant deaths due to heart defects (2), metabolic syndrome, congenital diaphragmatic hernia, and non-immune hydrops, respectively.Amniocentesis, done at a later gestation, is a safe and an effective tool for prenatal diagnosis and provides an opportunity to make a genetic diagnosis and further counseling. [ABSTRACT FROM AUTHOR]

Introduction Aims and Approach Conclusion Prenatal multidisciplinary counseling for fetuses with congenital anomalies involves a collaborative approach, integrating expertise from various medical fields.This comprehensive strategy aims to provide expectant parents with accurate information about the diagnosis, potential outcomes, and available interventions. Genetic counselors, obstetricians, neonatologists, and other specialists work together to address medical, psychological, and ethical aspects. The prenatal multidisciplinary counseling approach emphasizes open communication, fostering a supportive environment for the couple to express their concerns and ask questions. In the case of prenatally detected fetal congenital anomalies, several different scenarios can be delineated: (1) detection of surgically correctable congenital anomalies, (2) identification of genetic disease or fetal anomalies likely to result in disabilities, (3) discovery of severe and lethal congenital anomalies, and (4) encountering fetal anomalies that are not well‐defined, leading to an unclear scenario. The process of counseling includes discussing the possibility of pregnancy termination, treatment options, potential challenges, and emotional support, enabling expectant parents to make informed decisions aligned with their values and preferences. Additionally, the counseling process extends beyond the initial diagnosis, providing ongoing support as the pregnancy progresses and helping families to prepare for the difficulties they may face after the birth of the child with congenital anomalies. This collaborative effort not only focuses on the medical aspects but also considers the emotional and ethical dimensions of decision‐making.The multidisciplinary approach enhances the quality of care and empower parents, facilitating a more informed and compassionate journey throughout the prenatal period. [ABSTRACT FROM AUTHOR]

Chromosome microarray analysis (CMA) and whole exome sequencing (WES) are increasingly utilized in prenatal diagnosis of abnormal ultrasound findings, but studies on correlation between pathogenic copy number variations (pCNVs) and single-gene mutations in fetuses with nuchal translucency (NT) thickening/cystic hygroma (CH), and pregnancy outcomes, are rare. This study aimed to investigate clinical value of CMA and WES for NT thickening/CH in fetuses, explore genetic correlation between fetal NT thickening and CH, and analyze pregnancy outcomes. We retrospectively selected 215 pregnant women diagnosed with fetal NT thickening (NT > 95th)/CH who underwent invasive prenatal diagnosis at our hospital from January 2020 to June 2022. With negative chromosomal karyotype analysis (KA) and CMA results, patients voluntarily underwent WES. Patients were grouped by NT thickening/CH, and application value of KA, CMA, and WES examined. Ultrasound findings, pregnancy outcomes, and fetal growth post-birth were followed during mid/late pregnancy and post-delivery. Abnormalities in chromosomal number were detected in 28 of 215 samples, with a detection rate of 13.0%, and pCNVs were detected in 12 cases, with a detection rate of 5.6%. The most common abnormality in fetuses from both groups suggested by CMA was 22q11.21 microdeletion-microduplication syndrome. 35 patients with negative KA and CMA results underwent WES, and single gene variants were detected in 12 fetuses, with an abnormality rate of 34.3%. The incidence of adverse pregnancy outcomes was 28.2% in the NT thickening group and 82.9% in the CH group (P < 0.05). Overall, fetal NT thickening/CH was associated with genetic abnormalities, WES further improved the diagnosis of abnormal fetuses after negative KA and CMA results in both groups, and the incidence of adverse pregnancy outcomes was lower in the NT thickening group than in the CH group. The management of pregnancy outcomes could guide clinical genetic counselling. [ABSTRACT FROM AUTHOR]