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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.

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

The accurate prenatal diagnosis of skeletal anomaly (SKA) using prenatal imaging alone remains challenging. We aimed to investigate the efficacy of whole-exome sequencing (WES) in the prenatal molecular genetic diagnosis of skeletal system abnormalities, with or without additional ultrasound anomalies. All fetuses with SKA were subjected to sequential genetic tests, and after excluding fetal chromosomal abnormalities and clinically significant copy number variations (CNVs) consistent with the observed phenotype, the affected fetuses were further subjected to WES. The clinical features of fetal SKA were collected, and the results of molecular genetic testing and perinatal outcomes were analyzed. Following negative routine genetic test results of the 78 fetuses, trio-WES was conducted for 73 fetuses, and fetus-only WES (single WES) was performed for five fetuses due to parental refusal. Fetal skeletal system abnormalities in our cohort were subdivided into seven groups: 39 (50%) had short long bones, 14 (17.9%) had abnormal limb morphology, 4 (5.1%) had polydactyly, 4 (5.1%) had the absence of the radius tibia or tibiofibula, 5 (6.4%) had spine anomalies, 6 (7.7%) had strephenopodia, and 6 (7.7%) had multiple deformities. In total, we identified the molecular diagnoses for 32/78 fetuses with SKAs, and confirmed 41 pathogenic/likely pathogenic variants in 28 genes, including nine novel variants in our cohort. The overall diagnostic rate was 41% (32/78). Our findings demonstrate that WES can greatly improve the genetic diagnostic rate of fetal SKAs following routine genetic testing, which can comprehensively guide perinatal management and help assess the risk of recurrence in future pregnancies. Our data also provide a basis for the association between the SKA phenotype and related genotypes and expand the spectrum of fetal SKA phenotypes and related genes. [ABSTRACT FROM AUTHOR]

Objective: Analyze the ultrasound findings, single nucleotide polymorphism array (SNP-array) results, and pregnancy outcomes of fetuses with 7q11.23 deletions and duplications in the second and third trimesters. Investigate the prenatal ultrasound characteristics and follow up information of these fetuses. Methods: Seven fetuses were diagnosed with 7q11.23 deletion and six with 7q11.23 duplication via SNP-array at the prenatal diagnosis center of a single Chinese tertiary medical center from January 2017 to May 2024. Maternal demographics, ultrasound findings, SNP-array results, pregnancy outcomes, and follow-up information were comprehensively reviewed and analyzed. Results: The copy number variations (CNVs) ranged from 1.43 Mb to 1.78 Mb in cases of 7q11.23 deletions and from 1.42 Mb to 1.68 Mb in cases of 7q11.23 duplications. These CNVs encompassed 29 OMIM-listed genes, including ELN, DNAJC30, GTF2IRD1, and GTF2I. Among the seven cases of 7q11.23 deletion syndrome, six exhibited ultrasound abnormalities. The main clinical phenotypes included three cases of intrauterine growth restriction and four cases of cardiovascular system abnormalities, specifically two cases with ventricular septal defects, one case with aortic narrowing, and one case with supravalvular pulmonary stenosis. One case was particularly notable, exhibiting complex multi-organ structural malformations. Out of six cases of 7q11.23 duplication syndrome, five exhibited ultrasound abnormalities. These included two cases of cardiovascular abnormalities: one case with a widened left ventricle and another case with a shortened fetal humerus length. One case revealed complex multi-organ structural malformations, including hydronephrosis, a microgallbladder, and a cleft lip and palate. All seven cases of 7q11.23 deletions and three cases of 7q11.23 duplications opted for termination of the pregnancy. The remaining three cases of 7q11.23 duplications chose to continue the pregnancy. One case underwent surgical treatment for a ventricular septal defect after birth, and the prognosis was favorable. Another case involved a full-term delivery, this child was followed up at the age of 4 and exhibited a phenotype of poor language expression ability. Conclusion: Our study broadened the clinical phenotype spectrum of fetuses with 7q11.23 deletions and duplications. Additionally, it conducted a preliminary evaluation of prenatal ultrasound findings and postnatal clinical phenotypes in follow-up cases. The clinical phenotype of fetuses with 7q11.23 deletion and duplication syndromes involves multiple systems and is relatively complex. Cardiovascular abnormalities and intrauterine growth restriction are the most common clinical manifestations observed in prenatal 7q11.23 deletion syndrome. Fetuses with 7q11.23 duplications exhibit a wide range of clinical phenotypes that lack specificity. [ABSTRACT FROM AUTHOR]

Genome-Wide Non-Invasive Prenatal Testing (GW-NIPT) can provide positive results not only for common autosomal aneuploidies but also for rare autosomal trisomies (RATs) and structural chromosomal abnormalities (StrCAs). Due to their rarity, there is currently insufficient information on positive predictive value PPV of RAT and StrCA-positive cases in the literature. In this study, the screening accuracy and pregnancy outcomes of cases positive for rare chromosomal abnormalities were examined based on publications in which GW-NIPT testing was performed. True positive cases were determined using two different methodologies. One was a confirmed methodology, where only cases validated by genetic testing were considered true positives with a definite diagnosis, and the other was an extended methodology, where, in addition to cases confirmed by genetic testing, intrauterine fetal death and termination of pregnancy due to an abnormality confirmed by ultrasound examination were also considered true positives, where no diagnosis had been made but the fetus was probably affected. Seventeen studies were analyzed, with a total GW-NIPT population of 740,076. Of these, 1,738 were RAT positive. Using the confirmed method, we found the highest rates of true positives in T16, followed by T22, and T2, using the extended method, the highest rate of true positives in T15, T16 and T22. This is the first meta-analysis to determine the frequency of rare chromosomal abnormalities, test-positive rates, and the PPV of each chromosomal abnormality with high precision. Our results could aid pre- and post-test genetic counselling and help patients and clinicians in their decision-making. [ABSTRACT FROM AUTHOR]

To estimate the number of pregnancies complicated by vasa previa annually in nine developed countries, and the potential preventable stillbirths associated with undiagnosed cases. We also assessed the potential impact of universal screening for vasa previa on reducing stillbirth rates. We utilized nationally-reported birth and stillbirth data from public databases in the United States, United Kingdom, Canada, Germany, Ireland, Greece, Sweden, Portugal, and Australia. Using the annual number of births and the number and rate of stillbirths in each country, and the published incidence of vasa previa and stillbirth rates associated with the condition, we estimated the expected annual number of cases of vasa previa, those that would result in a livebirth, and the potential preventable stillbirths with and without prenatal diagnosis. There were 6,099,118 total annual births with 32,550 stillbirths, corresponding to a summary stillbirth rate of 5.34 per 1,000 pregnancies. The total expected vasa previa cases was estimated to be 5,007 (95 % CI: 3,208–7,201). The estimated number of livebirths would be 4,937 (95 % CI: 3,163–7,100) and 3,610 (95 % CI: 2,313–5,192) in pregnancies with and without a prenatal diagnosis of VP. This implies that prenatal diagnosis would potentially prevent 1,327 (95 % CI: 850–1,908) stillbirths in these countries, corresponding to a potential reduction in stillbirth rate by 4.72 % (95 % CI: 3.80–5.74) if routine screening for vasa previa was performed. Our study highlights the importance of universal screening for vasa previa and suggests that prenatal diagnosis of prevention could potentially reduce 4–5 % of stillbirths. [ABSTRACT FROM AUTHOR]

Background: Split hand/foot malformation (SHFM) is a congenital limb deficiency characterized by missing or shortened central digits. Several gene loci have been associated with SHFM. Identifying microduplications at the single-cell level is challenging in clinical practice, and traditional detection methods may lead to misdiagnoses in embryos and pregnant women. Results: In this research, we utilized a low cell count and whole-genome amplification products to employ single nucleotide polymorphism arrays, next-generation sequencing, and third-generation sequencing methods to detect copy number variants of microduplications in a SHFM3 case with limited DNA. Additionally, Karyomapping and combined linkage analysis were conducted to validate the results. Conclusions: This study establishes a new strategy for identifying microduplications or microdeletions at the single-cell level in clinical preimplantation genetic testing, enhancing the efficiency and accuracy of diagnosing microduplication or microdeletion diseases during IVF-PGT and prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To identify prenatal predictors of poor perinatal outcome in fetuses with isolated sacrococcygeal teratoma (SCT). Methods: This was a retrospective study of fetuses with isolated (non‐syndromic) SCT managed at one of five pediatric surgery and/or fetal medicine centers between January 2007 and December 2017. The primary outcome was the occurrence of poor perinatal outcome, defined as prenatal death (including termination), or neonatal death or severe compromise (hemorrhagic shock). Data regarding prenatal diagnosis (sonographic features both at referral and at the last ultrasound examination before pregnancy outcome, assessment of SCT growth velocity), perinatal complications and outcome, and neonatal course were analyzed to determine prenatal SCT characteristics associated with adverse perinatal outcome. Results: Fifty‐five fetuses were included, diagnosed with isolated SCT at a median gestational age of 22 (interquartile range, 18–23) weeks. There was a poor perinatal outcome in 31% (n = 17) of these cases, including intrauterine fetal demise (4%, n = 2), pregnancy termination (13%, n = 7) and neonatal severe compromise (15%, n = 8), leading to neonatal death in five cases. The overall survival rate after prenatal diagnosis of isolated SCT was 75% (n = 41 of 55). Earlier gestational age at diagnosis (P = 0.02), large tumor volume at referral (P < 0.001), presence of one or more hemodynamic complications (P = 0.02), fast tumor growth velocity (P < 0.001) and high tumor grade (highest tumor grade ≥ 3) (P = 0.049) were associated with poor perinatal outcome on univariate analysis. On stepwise logistic regression analysis, tumor growth velocity was the only remaining independent factor associated with poor perinatal outcome (odds ratio (OR) (per 1‐mm/week increase), 1.48 (95% CI, 1.22–1.97), P = 0.001). The best predictive cut‐off of tumor growth velocity for poor perinatal outcome was 7 mm/week (OR, 25.7 (95% CI, 5.6–191.3), P < 0.001), yielding a sensitivity of 88% and a specificity of 77%. Conclusions: Approximately 30% of fetuses with a diagnosis of isolated SCT have poor perinatal outcome. Tumor growth velocity ≥ 7 mm/week appears to be an appropriate discriminative cut‐off for poor perinatal outcome. These results could help to inform prenatal management and counseling of parents with an affected pregnancy. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Parental counseling for fetal malformations of cortical development (MCD) is based on data from studies in children and adults undergoing imaging investigation for abnormal neurodevelopment. However, such postnatal findings may not be applicable to prenatally diagnosed cases. The aim of this study was to review the existing data on postnatal neurodevelopmental outcome for fetuses diagnosed with MCD. Methods: A literature search was conducted in PubMed, Web of Science and EMBASE for articles published between 2013 and 2023, using standardized keywords to describe fetal cortical malformations. Full‐text articles were accessed for the retrieved citations and data on participant characteristics, imaging findings, and pregnancy and neonatal outcomes were extracted. Fetal MCD was defined as either complex or isolated, according to the presence or absence, respectively, of additional brain or extracranial defects. Results: Overall, 30 articles including 371 cases of fetal MCD were reviewed. The cases were classified as complex (n = 324), isolated (n = 21) or unknown (n = 26). There were 144 terminations and four stillbirths, with pregnancy outcome unreported in 149 cases. A total of 108 cases had postnatal magnetic resonance imaging or postmortem examination data available. In nine of these cases, a diagnosis of complex fetal MCD was changed to isolated MCD after birth, and one case was found not to have MCD. There were 74 live births, for which postnatal neurodevelopment data were available in only 30 cases. Normal neurodevelopmental outcome was reported in seven (23.3% (95% CI, 9.9–42.2%)) infants, with the remaining 23 exhibiting various levels of neurodevelopmental delay (three mild, seven moderate and 13 severe) from 6 months to 7 years of age. Conclusions: Most reviewed cases of fetal MCD were complex in nature and underwent termination of pregnancy. There is a paucity of data on postnatal neurological development in fetuses diagnosed with MCD. The available data suggest antenatal overdiagnosis of case severity in about 5% of cases with known outcome, and either normal neurodevelopment or mild neurodevelopmental delay in approximately one‐third of liveborn cases with neurological follow‐up. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to investigate the clinical outcomes of fetuses diagnosed with isolated mega cisterna magna in utero. Methods: A multicenter retrospective cohort study was conducted across 18 university hospitals from 2010 to 2019. Cases diagnosed with isolated mega cisterna magna, defined as a cisterna magna >10 mm with a normal cerebellar vermis and no cystic dilation of the fourth ventricle, were included. Cases with other central nervous system (CNS) anomalies, extra–central nervous system anomalies, chromosomal abnormalities, or congenital infections were excluded. Maternal demographics, prenatal findings, delivery outcomes, and postnatal outcomes were analyzed. Results: The mean gestational age at initial diagnosis was 28.6 ± 3.9 weeks, and the mean anteroposterior diameter of the cisterna magna was 12.5 ± 3.2 mm. Of the 71 cases initially assessed, 48 (67.6%) showed self-regression in utero. Postnatally, 13 cases (18.3%) had persistent isolated mega cisterna magna, whereas 10 cases (14.1%) were diagnosed with other central nervous system anomalies. Among the persistent isolated mega cisterna magna cases, one child exhibited delayed neurodevelopment. There was a higher incidence of isolated mega cisterna magna in male fetuses, which exhibited a significantly larger mean cisterna magna diameter compared with female fetuses (P =.045). Conclusion: Male fetuses exhibited a higher incidence of isolated mega cisterna magna compared with female fetuses and had larger anteroposterior diameters of the cisterna magna. The study demonstrated favorable neurodevelopmental outcomes associated with isolated mega cisterna magna, with self-regression observed in two-thirds of the cases. However, consecutive prenatal and postnatal evaluations for additional central nervous system or extra–central nervous system malformations need to be performed, considering the differences between prenatal and postnatal diagnoses. [ABSTRACT FROM AUTHOR]

Objective Fetal diagnosis of coarctation of the aorta (CoA) is currently associated with a high false-positive rate. Many predictive markers may be gestational age (GA)-specific. We sought to establish GA-specific traditional and speckle-tracking fetal echocardiography (STE) markers predictive of true CoA in neonates with prenatal suspicion. Study Design This is a retrospective case–control study. We compared the fetal ventricular and arch dimensions, as well as the deformation parameters by STE, of infants who required a postnatal intervention for their CoA with those who did not. Cohort was stratified based on GA before or after 30 weeks. Data extractors were masked to the outcome. The first fetal echocardiogram available was used. Results Seventy-five newborns with a fetal echocardiography performed between October 2013 and May 2022 for an antenatal suspicion of CoA were included, of which 59 (79%) had an aortic arch with nonsignificant obstruction upon ductal closure, and 16 (21%) underwent a neonatal intervention for a confirmed CoA. Before 30 weeks' GA, the right ventricular to left ventricular (RV/LV) end-diastolic width and end-diastolic area (EDA) ratios were most associated with postnatal CoA confirmation (area under the curve [AUCs] = 0.96 and 0.92). After 30 weeks' GA, the RV/LV end-diastolic width ratio (AUC = 0.95), the Z-score for the ascending aorta (AUC = 0.93), and the LV end-diastolic width Z-score (AUC = 0.91) performed the best. A decreased RV peak longitudinal strain was observed in those who developed true CoA and performed well by receiver operating characteristic analysis after 30 weeks (AUC = 0.85). In the overall cohort, the RV/LV EDA ratio was the most sensitive predictor of CoA and identified all cases with CoA. Indeed, a cutoff > 1.24 had a specificity of 69.5% and a sensitivity of 100% (receiver operating characteristic curve with an AUC of 0.88). Conclusion We outlined sensitive and specific fetal markers associated with postnatal CoA based on GA at suspicion. Key Points Fetal ventricular disproportion predicts postnatal coarctation. A decreased right ventircular contraction was observed in those with coarctation. Fetal markers differ based on gestational age at fetal evaluation. [ABSTRACT FROM AUTHOR]

• Massive parallel sequencing-based NIPT has the capacity to identify aberrations beyond identification of common trisomies. • Complex structural rearrangements are not detected with NIPT as the algorithm is specific to copy gains or losses. • Low grade mosaicism of chromosome 13 has the possibility to be detected with NIPT by massive parallel sequencing. We report data of non-invasive prenatal testing (NIPT) at Uppsala University Hospital between 2017–2022. Furthermore, we illustrate the potential capacity of massive parallel sequencing-based NIPT beyond identification of common trisomies. Maternal blood samples were analyzed using the Verifi NIPT or VeriSeq NIPT assays. Diagnostic testing, performed on amniotic fluid samples, included QF-PCR, microarray (SNP-array) and metaphase FISH. Among 4532 NIPT tests performed between 2017–2022, 125 samples (2.76%) showed increased risk for trisomies 13, 18, 21 and sex chromosome aneuploidy. For three patients with normal NIPT result further microarray indicated other types of chromosomal rearrangement which were not analyzed by NIPT. For another patient (case 1) the Verifi NIPT indicated trisomy 13. Fetal fraction (FF) was estimated to be 10%. Confirmatory microarray detected a segmental duplication on chromosome 13, as well as a terminal duplication and a terminal deletion on chromosome 10. A complex karyotype was observed in the fetus with metaphase FISH. In the second case the VeriSeq NIPT indicated trisomy 13. FF was estimated to be 11%. Confirmatory microarray detected a mosaicism of trisomy 13 in 30 % of cells. This study illustrates detection of peculiar abnormalities of chromosome 13 and supports potential to screen copy number variations with genome-wide NIPT. [ABSTRACT FROM AUTHOR]

While non-invasive prenatal testing (NIPT) has been widely adopted throughout Europe, Australia, and the USA, population level access to NIPT varies considerably. Ireland has no national screening programme for fetal anomalies, although NIPT is available from out-of-country providers. We aimed to describe the availability of NIPT in Ireland and the quality of information available online from NIPT providers. Information available online from NIPT providers in the Republic of Ireland was analysed by examining all healthcare facilities websites and reviewing private health insurance directories. Data on information provided by NIPT providers was collected by two independent researchers from April to May 2023. Four of the 19 maternity hospitals/units in Ireland had information on NIPT on their websites, with three including an explanation of NIPT, testing accuracy, and associated fees (€380-480). Twenty private clinics led by obstetric consultants advertised NIPT online, of which seventeen clinics included an explanation of NIPT, testing accuracy, and associated fees (€380-€650). Twenty-nine other providers, which included ultrasound clinics, direct-to-consumer laboratory testing, and General Practitioners, advertised NIPT with 18 of these providers including an explanation of NIPT, testing accuracy, and associated fees (€179-€630). While there is apparent demand for NIPT and it is available in Ireland, there is disparity between providers on the type and quality of information available. Difficulty obtaining accessible information, the associated financial costs and location of providers advertising NIPT are likely to be barriers to accessing NIPT. A national screening programme for aneuploidy should be considered to ensure both equitable access to and reliable information about prenatal screening. [ABSTRACT FROM AUTHOR]

Purpose: To assess the value of routine mid-trimester fetal ultrasound scans in detecting FCs, as well as the related ultrasound and clinical follow-up outcomes. Methods: A retrospective analysis was conducted on 1064 fetuses who underwent standardized ultrasound screening during the mid-trimester. During the examination, high-frequency ultrasound was used to examine the fetal spine. Different frequency ultrasound probes were used to compare and analyze the detection rates of FCs. We conducted follow-up ultrasound observations on all FCs and conducted long-term follow-up observations in terms of the motor function of the children after birth. Results: Among 1064 fetuses detected by ultrasound, a total of 910 fetuses were completely evaluated using high-frequency and low-frequency ultrasound, and 24 FCs were found. In all 24 cases of FCs, 7 cases were detected using low-frequency ultrasound, while high-frequency ultrasound detected all cases. There was a significant difference in the detection rates between the two groups (χ2 = 26.323, P = 0.000). Of all the 24 FCs, 21 cysts disappeared spontaneously (87.5%); one fetus was induced for abortion due to a concurrent cleft lip; after multiple ultrasound examinations, it was found that the cyst persisted in one fetus; one case was not followed up by ultrasound. There was no statistically significant difference in the start of sitting and crawling time between the control group and the FCs group. Conclusion: Routine mid-trimester fetal ultrasound scan detect FCs, particularly when high-frequency ultrasound probes were routinely applied. Most FCs detected by prenatal ultrasound spontaneously disappear and have no impact on the motor function of the fetus after birth (with the conus medullaris located at or above the L3 level). The shortest time interval from the detection to the disappearance of the cyst was 11 days. [ABSTRACT FROM AUTHOR]

Introduction: The evaluation of the performance of new methods, expected to provide cheaper and faster results than existing (reference) methods in the health field, is based on comparing the results obtained with this new method to those obtained with the existing method. The primary aim of this study is to examine the correlational and absolute agreement between measurement methods in clinical studies using Bland–Altman analysis and methodological (Ordinary Least Squares, Weighted Ordinary Least Squares, Deming, Weighted Deming, Passing–Bablok, Theil-Sen, and Passing–Bablok for Large Data Sets.) methods, and the secondary aim is to compare the accuracy and precision of Hadlock (I–V) formulas used for fetal weight estimation. Materials and methods: The study was conducted on singleton pregnancies examined in the Prenatal Diagnosis and Treatment Unit of the Department of Obstetrics and Gynecology at Inonu University Faculty of Medicine and who gave birth in the Obstetrics Unit between 01.01.2020 and 01.09.2023, whose gestational ages were confirmed by first-trimester ultrasonography. Estimated fetal weights were calculated using Hadlock (I–V) formulas, and the agreement of these weights with birth weight was evaluated with Bland–Altman method. Results: The comparison of estimated fetal weights calculated using Hadlock formulas with birth weight was analyzed using Bland–Altman analysis, ICC, and CCC values along with regression analyses. According to the mean difference values obtained by Bland–Altman analysis, the estimated fetal birth weights obtained by the Hadlock IV formula were most consistent with the actual birth weights. Conclusions: The estimated fetal weights obtained using the Hadlock IV formula resulted in the closest measurements to the birth weight. This study showcases the efficacy of a new web-based software, Method Comparison Software (MCS), which can be utilized for evaluating the agreement between different methods in clinical measurements. [ABSTRACT FROM AUTHOR]

The article focuses on using deep learning to accurately identify fetal head positions during the second stage of labor through transperineal ultrasound imaging. It highlights how an artificial intelligence model demonstrated a high accuracy rate of 94.5 percent in detecting various fetal positions, which is crucial for preventing complications such as prolonged labor and operative deliveries.

15q24.1 microdeletion syndrome is a recently described condition often resulting from non‐allelic homologous recombination (NAHR). Typical clinical features include pre and post‐natal growth retardation, facial dysmorphism, developmental delay and intellectual disability. Nonspecific urogenital, skeletal, and digit abnormalities may be present, although other congenital malformations are less frequent. Consequently, only one case was reported prenatally, complicating the genotype–phenotype correlation and the genetic counseling. We identified prenatally a second case, presenting with cerebral abnormalities including hydrocephaly, macrocephaly, cerebellum hypoplasia, vermis hypoplasia, rhombencephalosynapsis, right kidney agenesis with left kidney duplication and micropenis. Genome‐wide aCGH assay allowed a diagnosis at 26 weeks of amenorrhea revealing a 1.6 Mb interstitial deletion on the long arm of chromosome 15 at 15q24.1‐q24.2 (arr[GRCh37] 15q24.1q24.2(74,399,112_76,019,966)x1). A deep review of the literature was undertaken to further delineate the prenatal clinical features and the candidate genes involved in the phenotype. Cerebral malformations are typically nonspecific, but microcephaly appears to be the most frequent in postnatal cases. Our case is the first reported with a frank cerebellar involvement. [ABSTRACT FROM AUTHOR]

Hemoglobinopathies are a group of autosomal recessive disorders characterized by either a reduced synthesis of one or more normal globin chains or the synthesis of a structurally abnormal globin chain or, in a few cases, by both that is, the reduced synthesis of a haemoglobin (Hb) variant. Depending on the mutations, these patients may exhibit distorted Hb patterns along with altered red cell indices, both of which can be used to support identification by diagnostic tools. The approach in the diagnosis of hemoglobinopathies and thalassemia depends upon the target geographical population and aim of testing. Red cell indices, Hb pattern analysis on high-performance liquid chromatography, and Hb capillary-zone electrophoresis are the first-line screening tests, and molecular testing helps confirm the diagnosis and is also useful in prenatal and preimplantation genetic diagnosis. Thalassemia patients need lifelong medical care, receiving trasfusions and supplemental therapies, and therefore, timely diagnosis and screening is essential. In the present paper, we review the potential pitfalls and interfering factors in their diagnosis. [ABSTRACT FROM AUTHOR]

The fetal venous system begins developing around the sixth week of gestation, with three paired veins: the umbilical, vitelline, and cardinal veins. These veins are essential for transporting blood from the placenta to the heart. As the liver matures, connections between the liver and these veins form a complex venous system. Disruptions in this process can lead to various fetal venous anomalies, arising from abnormalities in the formation or regression of these veins. Common anomalies include ductus venosus agenesis, persistent right umbilical vein, umbilical vein varix, agenesis of the portal system, and IVC interruptions. Ductus venosus agenesis can cause compensatory blood flow changes, while a persistent right umbilical vein occurs when the left vein regresses. Umbilical vein varix is a dilation of the umbilical vein, and agenesis of the portal system disrupts normal liver blood flow. IVC interruptions affect systemic venous return to the heart. Diagnosing these anomalies requires detailed ultrasound evaluation, including Doppler studies, and prenatal monitoring to assess potential complications and guide appropriate clinical management. In evaluating complex communication pathways, the first step is to examine how that structure is organized. The categorized segmentation of the venous system leads to a wider horizon of vision and higher perception. In this pictorial essay article, the fetal venous system and its anomalies are classified according to their primary origin. Special attention to depicting normal anatomy and anomalies using color schematic images and real two-dimensional and color ultrasound images together play an important role in promoting spatial perception and simplifying the categorized approach to fetal venous system anomalies. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the use of two‐dimensional (2D) ultrasound combined with high‐definition flow (HD‐flow) render mode and spatiotemporal image correlation (STIC) in diagnosing and classifying fetal persistent left superior vena cava (PLSVC). Methods: Overall, 114 cases of fetal PLSVC were diagnosed using 2D ultrasound combined with STIC, and 114 normal fetuses of the same gestational week were selected. These cases were retrospectively analyzed to evaluate the effectiveness of the diagnostic approach. Results: All 114 PLSVC cases were diagnosed using 2D ultrasound combined with STIC. Although the diagnostic coincidence rate of PLSVC in the HD‐flow combined with STIC was similar to that in the 2D ultrasound combined with HD‐flow (96.8 vs 96.2%), 2D ultrasound with STIC enabled dynamic visualization of the PLSVC, furthering prenatal diagnosis. These cases were classified as type I PLSVC: 80 cases of type Ia, 29 cases of type Ib, and 5 cases of type Ic. Seventy isolated PLSVC cases (61.4%) were noted, whereas 44 cases (35.6%) were associated with concomitant structural abnormalities. Intracardiac structural malformations accounted for the highest proportion (n = 53, 58.89%), followed by single umbilical artery and facial/bodily abnormalities (n = 10, 11.11%). Conclusion: Combining HD‐flow and STIC complements 2D ultrasound in diagnosing and classifying fetal PLSVC, demonstrating significant clinical relevance. [ABSTRACT FROM AUTHOR]

Purpose: Alimentary tract duplications (ATDs) are rare congenital lesions often associated with anomalies such as spinal, urinary and GI tract malformations. The purpose of this study was to report the experience of a single center with ATDs in children, focusing on the natural history, associated malformations, and their impact on patient management. Methods: We performed a retrospective analysis over 14 years, collecting prenatal, clinical, surgical, and follow-up data. We focus on associated anomalies prenatal and postnatal management, and outcomes. Results: Sixty-three patients with ATD (thirty-six females, twenty-seven males, aged 1 day to 14 years) were enrolled in this study. Prenatal diagnosis was made in 22 patients (35%), of whom 8 showed compression signs. Elective surgery was performed at a mean age of 1.5 years in prenatally diagnosed cases. The others presented symptoms at a mean age of 5.2 years (55.5%) or were detected incidentally (9.5%) at a mean age of 10.7 years. In four patients (6.3%), we identified multiple duplications, and ten cases (15.8%) were found with associated anomalies. Conclusion: The wide spectrum of clinical appearance of ATDs and a comprehensive knowledge of human embryology might define surgical management, which should always be patient-tailored and respectful of the child's development. [ABSTRACT FROM AUTHOR]

The innovation in ultrasound has greatly promoted the prenatal diagnosis of ventricular septal defect. As a minor lesion of congenital heart disease, the prenatal genetic counseling of isolated ventricular septal defect faces some challenges, including the true genetic correlationship, selection of appropriated testing methods to identify deleterious mutations, and avoidance of overdiagnosis and overintervention. Researchers have explored the prenatal diagnosis efficiency of commonly used cytogenetic and molecular genetic technologies. Small insertions/deletions and monogenic variants with phenotypic heterogeneity play important role and contribute to the comprehend of pathogenesis. Isolated ventricular septal defect fetuses without genetic finding and extracardiac structural abnormality generally have good pregnancy outcome. Long-term follow-up data is needed to describe the comprehensive map, such as the potential missed diagnosis especially late-onset syndromes, the impact on the quality of life and life expectancy. When conducting prenatal genetic counseling, strict adherence to ethical principles is needed to ensure that the rights of all parties involved are fully protected. Clinicians should carefully evaluate the risks and benefits and provide parents with sufficient information and advice to enable them to make informed decisions. [ABSTRACT FROM AUTHOR]

Background: The clinical phenotypes of 16p13.11 microduplication syndrome have been extensively reported in previous studies, mostly about adults and children, with limited information available on fetal cases. This study aims to explore the genotype-phenotype correlation of fetuses with 16p13.11 microduplication syndrome and analyze the characteristics of prenatal diagnosis indications and provide clinical information for prenatal and postnatal genetic counseling. Methods: We conducted a retrospective analysis of 3,451 pregnant women who underwent invasive prenatal diagnosis for SNP array between January 2018 and December 2022 at the Jinan Maternal and Child Health Hospital. Descriptive statistical analysis was performed on the prenatal diagnosis indications, pedigree analysis, pregnancy outcomes and postnatal follow-up of 15 fetuses with 16p13.11 microduplication syndrome. Results: SNP array revealed that 15 fetuses had duplications in the 16p13.11 region with varying prenatal diagnosis indications. Among the cases, 6/15 exhibited ultrasound abnormalities, 5/15 had abnormal chromosomal copy number variations as indicated by non-invasive prenatal testing (NIPT), one case involved advanced maternal age, and 3/15 had other abnormalities. 16p13.11 microduplication syndrome was closely related to ultrasound abnormalities, especially structural abnormalities and soft marker anomalies (abnormal ultrasonic soft indicators), while the indication of NIPT could improve the detection rate of copy number variations (CNVs) in this region. Only 7/15 fetuses underwent pedigree verification, with one case of de novo 16p13.11 microduplication, and the others inherited from one parent. Pregnancy was terminated in 2/15 cases and the outcome of one case is unknown due to loss to follow-up. Among the remaining cases, only one case exhibited a ventricular septal defect, while another presented with omphalocele. No other obvious abnormalities were reported postnatally. Conclusion: The prenatal phenotypes of fetuses with 16p13.11 microduplication were highly associated with ultrasound abnormalities but lacked specificity. Comprehensive genetic tracing, outcome analysis, and follow-up are essential for providing accurate prenatal and postnatal genetic counseling. [ABSTRACT FROM AUTHOR]

Aim: This study was aimed at comparing the positive predictive value of a high‐risk cell‐free fetal DNA test result for sex chromosome aneuploidies (45,X0, 47,XXX, 47,XXY, and 47,XYY) and autosomal trisomies (T21, T18, and T13) with confirmatory tests in singleton pregnancies. Additionally, we identify the main reason for discordant and inconclusive results. Methods: PubMed, Web of Science, and Scopus were searched from 2017 for primary research articles on cell‐free fetal DNA testing of autosomal trisomies and sex chromosome aneuploidies in singleton pregnancies. The methodological characteristics and the statistical results of the studies were collected, and the risk of bias was assessed. Results: Fourteen studies were included. Among the autosomal trisomies, T21 had the highest, whereas T13 showed the lowest positive predictive values. As for the sex chromosome aneuploidies, the lowest values were found with 45,X0. Although discordant and inconclusive results were reported inconsistently, false positives were mainly caused by mosaicism, and inconclusive results were mostly secondary to a low fetal DNA fraction. Conclusion: Cell‐free fetal DNA is a reliable screening tool for autosomal trisomies. It is also useful for sex chromosome aneuploidies, although the positive predictive values are lower. A positive screening result should be followed with a confirmatory test. [ABSTRACT FROM AUTHOR]

Background: In order to attain the ambitious 95-95-95 UNAIDS goals, HIV testing serves as the pivotal starting point and plays a crucial role in preventing, treating, and managing HIV. Equal access to HIV testing is crucial to stop the spread of the virus. Measuring healthcare disparities is vital for promoting fairness in health services and achieving global goals for HIV prevention and treatment. Ethiopia is actively engaged in efforts to achieve these goals and is dedicated to combating HIV/AIDS. To the best of our knowledge, no previous systematic review or meta-analysis has been conducted on sociodemographic inequalities in prenatal HIV testing in Ethiopia. Hence, this study aims to assess sociodemographic inequalities in prenatal HIV testing in Ethiopia. Methods: We conducted an extensive search across various databases, such as PubMed, Scopus, Google Scholar, and Embase, to collect articles and reports. The data we gathered was then exported to R software for further analysis. Our analysis involved performing a meta-analysis of proportions using a random effect model. To assess the variability among the included studies, we used statistical measures such as I2 statistics and the Cochran's Q test. The results of the pooled prenatal HIV testing, along with its corresponding 95% confidence interval, were presented using a forest plot. Results: A comprehensive analysis of 20 research papers on prenatal HIV testing in Ethiopia revealed that the overall pooled prevalence of testing was 69% (95% CI [60.0–80.0]). Factors such as higher education, urban residence, income, a positive attitude towards testing, marriage, and discussions about testing during antenatal care (ANC) were found to positively influence testing rates. Conclusion: The prevalence of prenatal HIV testing among antenatal care attendees in Ethiopia falls short of the UNAIDS target. In order to enhance the testing rates, it is advised to implement targeted initiatives within Ethiopia's public health programs. To ensure effectiveness, these initiatives should adopt a sustainable and customized approach that takes into account the specific needs and circumstances of women, particularly those who are economically disadvantaged. Ethiopia can make significant strides in enhancing the prenatal HIV testing landscape by effectively implementing policies and programs that prioritize the welfare of the less privileged. Limitations: As limitation this systematic review did not include longitudinal and qualitative studies that might have provided different results. Clinical trial registration: Trial registration in PROSPERO with ID: CRD42024550564. [ABSTRACT FROM AUTHOR]

Background: X-linked recessive chondrodysplasia punctata 1 (CDPX1) is a rare congenital skeletal dysplasia characterized by stippled epiphyses, nasal hypoplasia, and brachytelephalangy. ARSL (formerly known as ARSE), a member of the sulfatase gene family located on Xp22.3, has been identified as the causative gene for CDPX1. The high clinical and genetic heterogeneity of CDPX1 presents a challenge to prenatal diagnosis. Case presentation: A G1P0 woman in her 30s with an unremarkable prenatal course presented in the second trimester. Maternal diseases, tobacco, alcohol, and drug history during pregnancy were denied. Obstetrical ultrasound examination revealed a flattened nose and a flattened midface with echogenic alterations of lumbar spinous process in the fetus. Amniocentesis was performed for genetic testing. A normal karyotype and a negative result of CNV-seq were obtained. However, Whole exome sequencing (WES) in trios revealed a hemizygous ARSL variant [NM_000047.3:c.1108del p.(Trp370Glyfs*35)] in the fetus, which was maternally inherited as confirmed by Sanger sequencing. This variant was absent from the genomAD and HGMD databases. According to the ACMG guidelines, this variant was interpreted as likely pathogenic (PVS1 + PM2_Supporting). The couple decided to terminate the pregnancy. After induction of labour, a severe nasal hypoplasia was noted; and brachytelephalangy was not remarkable. Postmortem digital X-ray imaging revealed symmetrical stippled epiphyses of the vertebrae in all spine regions and enlargement of spinous process of L1-L4 vertebrae. Conclusion: A novel frameshift deletion variant of ARSL and the associated fetal phenotype have been identified. This study provides useful information for prenatal diagnosis and genetic counseling of CDPX1. [ABSTRACT FROM AUTHOR]

AbstractObjectivesMethodsResultsConclusionsTo examine the knowledge, confidence and practice of motor neuron disease (MND) clinicians toward discussing reproductive options with people who carry a causal variant in an MND gene (both clinically affected and asymptomatic).An online cross-sectional survey was distributed nationwide to UK MND clinicians and clinical geneticists and genetic counselors. The survey assessed respondents’ understanding on reproductive medicine techniques; their confidence in discussing reproductive medicine options and their access to information resources.Seventy six clinicians responded to the online survey (45 neurology clinicians and 31 clinical geneticists). MND clinicians had limited knowledge and low confidence in discussing reproductive medicine options. Geneticists were more likely to carry out reproductive genetic counseling with very few MND clinicians reporting undertaking these discussions. Further, 57% of the 45 MND clinicians surveyed reported to have never made a referral for reproductive genetic counseling. Multiple barriers to offering reproductive counseling or referral were identified including a lack of knowledge, lack of awareness of the different options, lack of clinic time and uncertainty around issues such as funding for PGT and whose responsibility it comes under.There is a need for training and education on reproductive options and referral for these options needs to be integrated within the health system. Developing more resources for both clinicians and patients is required as MND clinicians reported a lack of resources. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to investigate the application value of Chromosomal microarray analysis (CMA) in prenatal diagnosis of nuchal translucency (NT) thickening and nasal bone dyscalcification. Methods The fetuses diagnosed with NT thickening and nasal bone dyscalcification at the Prenatal Diagnosis Center of Meizhou People's Hospital from September 2022 to April 2024, who underwent CMA and karyotype analysis were collected to analyze the relationship between NT thickening and nasal bone dyscalcification and chromosome abnormalities. The detection of chromosomal abnormalities in fetuses with NT thickening, nasal bone dyscalcification and the value of ultrasound combined with CMA in prenatal diagnosis were analyzed. Results In 75 fetuses with NT thickening and/or nasal bone dyscalcification, 11 cases of chromosome aneuploidy were detected by karyotype analysis, and 5 cases of pathogenic copy number variations (CNV) were detected by CMA, with an additional detection rate of 6.7%. The additional diagnosis rates of CMA were 6.0% and 5.0% in fetuses with simple NT thickening and nasal bone dyscalcification, respectively. Conclusion CMA technique is of high value in prenatal diagnosis of fetuses with NT thickening and nasal bone dyscalcification, it can improve the detection rate of fetal chromosomal abnormalities, and the combined application of multiple techniques can provide a more comprehensive evaluation of the fetuses. [ABSTRACT FROM AUTHOR]

Adnexal masses are uncommon in children but are increasingly recognized due to advancements in diagnostic facilities. Such masses in the pediatric population often raise concerns about malignancy. Typically, these masses are small and can resolve spontaneously; however, larger ones can pose a diagnostic dilemma due to their signs and symptoms, requiring clinicians to be particularly vigilant. Simple ovarian cysts are seen in 1 in 2500 live births. They are commonly diagnosed prenatally as intra-abdominal masses by ultrasonography. While there are no established guidelines for management, larger cysts are generally managed surgically (either open or laparoscopic) with the aim of protecting the ovaries and ensuring future fertility. Herein, we present a case of an unusually large congenital ovarian cyst in a newborn that mimicked an abdominal mass, leading to respiratory compromise. [ABSTRACT FROM AUTHOR]

Many people living with a rare disease (RD) face challenges accessing timely diagnosis and disease-specific specialist care. Early health-care challenges for people living with Epidermolysis Bullosa (EB), a rare genetic disease affecting 1:20,000 individuals, can begin in the antenatal period. People living with EB in Australia have access to a government funded disease specific antenatal education and support program through the National Epidermolysis Bullosa Dressing scheme (NEBDS). This article discusses two births involving families living with EB Simplex (EBS) in regional Australia. The education and support structures implemented by the NEBDS and clinical teams are discussed in line with the Australian National Strategic Action Plan for rare diseases, and includes access to genetic diagnosis, EB education, and complex care coordination. [ABSTRACT FROM AUTHOR]

Background: Prenatal ultrasound findings of fetal bilateral echogenic kidneys accompanied by oligohydramnios can be highly stressful for both pregnant women and physicians. The diversity of underlying causes makes it challenging to confirm a prenatal diagnosis, predict postnatal outcomes, and counsel regarding recurrence risks in future pregnancies. Case Presentation: We report two cases of abnormal fetal echogenic kidneys with oligohydramnios detected in the early third trimester. Autosomal recessive polycystic kidney disease (ARPKD), a rare genetic syndrome, was initially suspected in both cases. However, postnatal diagnoses differed: the first case was confirmed as glomerulocystic kidney disease (GCKD) through renal pathology, while the second case was diagnosed as ARPKD with a compound heterozygous likely pathogenic PKHD1 mutation. Conclusion: Prenatal diagnosis of fetal echogenic kidneys with oligohydramnios should prioritize accurate diagnosis. Given the differences in the clinical spectrum, GCKD should be considered a differential diagnosis for this condition, particularly ARPKD. This study highlights the importance and benefits of molecular diagnosis and postnatal renal pathology for precise diagnosis and effective counseling. [ABSTRACT FROM AUTHOR]

Preconception and prenatal genetic counseling is a well-established means of risk assessment in many parts of the world, and in recent years, an emerging concept in India. Likelihood of an offspring having autosomal recessive disorder increases based on the degree of consanguinity. Hence, genetic testing of the couple for the identification of carrier status for disease-causing variants is crucial. The purpose of this study is to understand the frequency of genetic abnormalities in consanguineous marriages by using a comprehensive genetic testing algorithm where in karyotyping, FISH, exome sequencing and microarray are used sequentially to determine the genetic etiology based on the clinical presentation and to evaluate the need and benefits of preconceptional and prenatal genetic counseling. This retrospective study includes 66 couples having consanguinity referred for genetic counseling and testing. Of the 66 couples, 58 underwent comprehensive genetic testing which included Karyotyping, Fluorescence in Situ Hybridization (FISH), Microarray and Exome sequencing based on their clinical presentation. The analyses revealed a genetic abnormality in approximately 31% and chromosomal polymorphic variations & variants of uncertain significance in 17% of the couples. Counseling in these couples helped in identifying the carrier status and enabled them to take an informed decision in subsequent pregnancies. These findings reiterate the acute need for preconception and prenatal genetic counseling services in India. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to explore parents' experiences of their relationships and interactions with healthcare professionals (HCPs) during care related to prenatal diagnosis and termination of pregnancy for foetal anomaly (TOPFA). Methods: A qualitative approach was used. Participants included 33 parents (23 women and 10 men) from Northern Ireland (n = 11) and Ireland (n = 22) who had a TOPFA. Data collection methods included semi‐structured interviews and written narrative accounts. Data were analysed using thematic analysis. Results: Findings confirmed that TOPFA was a traumatic, life‐altering experience for parents, impacting their health and well‐being. The actions, behaviours and words of HCPs impacted how parents perceived and interpreted their healthcare experiences and their access to services and supports. In relation to this, five themes are presented: (1) the importance of compassionate and non‐judgemental care, (2) the value of effective information and communication, (3) the desire for compassionate care for baby and facilitation of memory making, (4) the need for continuity of care and (5) parents' experiences of healthcare relationships during times of legislative change. Conclusion: This research reveals the important role HCPs play in helping parents cope with prenatal testing and TOPFA. Parents who had a positive relationship with an HCP, in which information was communicated effectively and compassionate and non‐judgmental care was provided, felt more supported and more able to accept and adapt to their loss. Patient and Public Contribution: An advisory group composed of parents who had experienced TOPFA and HCPs with experience in caring for such families were involved in the study from the outset, contributing to the design and development of data collection materials, interpretation of the findings and design of dissemination materials. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical value of whole‐exome sequencing (WES) in the diagnosis of foetuses with central nervous system (CNS) abnormalities but having a normal karyotyping and chromosomal microarray result. Method: During the period of 2016–2022, there were a total of 149 foetuses with CNS abnormalities but having negative karyotyping and chromosomal microarray analysis results; WES was performed on these foetuses and their parents. Variants were classified according to ACMG guidelines, and the association of pathogenic variants with specific types of CNS abnormalities was explored. Results: Among these 149 foetuses, three categories of abnormalities, namely, single CNS abnormality, multiple CNS abnormalities, CNS abnormalities along with other organ system abnormalities were identified, for which the detection rate of P/LP variants is 17.4% (12/69), 28.6% (14/49) and 54.8% (17/31), respectively. Conclusion: WES brought about an increase of 28.9% in diagnostic yield in the prenatal evaluation of foetuses with CNS abnormalities but having negative karyotyping and chromosome array results. WES may also be of benefit for the diagnosis of foetuses with isolated CNS abnormalities, as well as for making more informed interpretations of imaging findings and for providing better genetic counselling. [ABSTRACT FROM AUTHOR]

Background: Arising in the late 1990s, when a promising role in prenatal diagnostics was first delineated for circulating fetal DNA, non-invasive prenatal tests (NIPTs) have been increasingly used with more frequency and popularity. These exams have been used as a prenatal screening tests for genetic diseases. Initially, they were developed for the investigation of the main fetal chromosomal aneuploidies, but lately they have also been used to rule out genomic microrearrangements and monogenic conditions. However, along with great opportunities and potential, the tests can show inconclusive or unexpected results. Several studies have shown that the current pre-test counseling is often insufficient, and more oriented at providing pieces of information about the identifiable diseases rather than providing extensive information on all possible scenarios which may affect both the fetus and the pregnant mother, especially in the case of an invasive test for the pregnant mother. Methods and Results: We have gathered from the literature on NIPT the main pitfalls, imperfections, and particular cases associated with this innovative diagnostic procedure. Conclusions: In view of further improvements in the methods that can limit the inconclusive or unexpected results, this paper aims to reinforce the importance of more accurate pre-test counseling with comprehensive information about the above-mentioned questions, as well as ultrasound use and also the creation of an international consensus statement concerning these topics. [ABSTRACT FROM AUTHOR]

Problem: Preeclampsia is a heterogeneous syndrome of diverse etiologies and molecular pathways leading to distinct clinical subtypes. Herein, we aimed to characterize the extracellular vesicle (EV)‐associated and soluble fractions of the maternal plasma proteome in patients with preeclampsia and to assess their value for disease prediction. Method of Study: This case–control study included 24 women with term preeclampsia, 23 women with preterm preeclampsia, and 94 healthy pregnant controls. Blood samples were collected from cases on average 7 weeks before the diagnosis of preeclampsia and were matched to control samples. Soluble and EV fractions were separated from maternal plasma; EVs were confirmed by cryo‐EM, NanoSight, and flow cytometry; and 82 proteins were analyzed with bead‐based, multiplexed immunoassays. Quantile regression analysis and random forest models were implemented to evaluate protein concentration differences and their predictive accuracy. Preeclampsia subgroups defined by molecular profiles were identified by hierarchical cluster analysis. Significance was set at p < 0.05 or false discovery rate‐adjusted q < 0.1. Results: In preterm preeclampsia, PlGF, PTX3, and VEGFR‐1 displayed differential abundance in both soluble and EV fractions, whereas angiogenin, CD40L, endoglin, galectin‐1, IL‐27, CCL19, and TIMP1 were changed only in the soluble fraction (q < 0.1). The direction of changes in the EV fraction was consistent with that in the soluble fraction for nine proteins. In term preeclampsia, CCL3 had increased abundance in both fractions (q < 0.1). The combined EV and soluble fraction proteomic profiles predicted preterm and term preeclampsia with an AUC of 78% (95% CI, 66%–90%) and 68% (95% CI, 56%–80%), respectively. Three clusters of preeclampsia featuring distinct clinical characteristics and placental pathology were identified based on combined protein data. Conclusions: Our findings reveal distinct alterations of the maternal EV‐associated and soluble plasma proteome in preterm and term preeclampsia and identify molecular subgroups of patients with distinct clinical and placental histopathologic features. [ABSTRACT FROM AUTHOR]

Background: Genetic sonography following first-trimester combined screening appears to increase substantially detection rates for Down syndrome, but it relies on the unproved assumption of independence between these tests. Aim and Objective: To detect nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities. Method: This study was performed on pregnant women with a gestational age of 11 weeks and 13 weeks (6 days) at the department of radiology, VIMS, Gajraula, UP, India. Pregnant women undergone screening are followed up till delivery and assessment of congenital anomalies done. The subjects are followed up till the pregnancy outcome. The clinical assessment of the newborn baby was done to look for any congenital anomalies. The statistical analysis was done by using the chi-square test. p < 0.05 is considered to be significant. Results: An increase in NT is associated with congenital abnormalities. Increased NT is more likely to have anomalies compared with normal NT. Conclusion: Nuchal translucency is a strong predictor of congenital and chromosomal anomalies. [ABSTRACT FROM AUTHOR]

Background: Tetralogy of Fallot with an absent pulmonary valve is a very rare variant of tetralogy. It is characterized by absent valve tissue, severe pulmonary regurgitation, and secondary aneurysmal dilatation of the pulmonary arteries. Aim: In this study, we aim to investigate the clinical presentations, management strategies, and outcomes of patients with tetralogy of Fallot and absent pulmonary valve. Methodology: We retrospectively reviewed the charts of all patients who presented to the American University of Beirut Medical Center between January 2010 and December 2020 and who were diagnosed with this anomaly. Results: A total of 300 cases of tetralogy of Fallot were identified, of which 18 patients had absent pulmonary valves. They were followed up for an average of 8.2 years. Prenatal diagnoses were made in four patients, while 13 patients were identified in the neonatal period, with an average age of 4.5 days. Genetic testing confirmed DiGeorge syndrome in one patient. Five patients underwent surgical intervention in the neonatal period, while the remaining patients were operated on during their early childhood. While overall there were no surgical mortalities nor any need for reinterventions, a variety of morbidities were encountered. Conclusion: This study provides an overview of this rare anomaly and its management in a developing country. [ABSTRACT FROM AUTHOR]

This was a study of 12 cerebellar cortical dysplasias (CCDs) fetuses, these cases were characterized by a disorder of cerebellar fissures. Historically, CCD diagnosis was primarily performed using postnatal imaging. Unique to this study was the case series of CCD for prenatal diagnosis using prenatal ultrasound, as well as we found that AXIN1 and FOXC1 mutations may be related to CCD. [ABSTRACT FROM AUTHOR]

Background • Copy number variants (CNVs) contribute significantly to normal and pathogenic genomic variations. Chromosome 17q12 microdeletion is implicated in structural or functional kidney and urethral abnormalities, MODY5 (type 5 diabetes), and neurodevelopmental or neuropsychiatric disorders. Conversely, microduplication of 17q12, though rare, elevates the risk of epilepsy and mental retardation. Case Presentation • This study focuses on a 33-year-old woman (gravida 1, para 0) who underwent amniocentesis at 22 weeks gestation due to bilateral hyperechogenic kidneys observed on prenatal ultrasound. Results • Chromosomal microarray analysis (CMA) unveiled a 1.46-Mb microdeletion on chromosome 17q12 in the fetus, spanning positions 35,802,057 to 37,261,945 (hg19). Trio whole-exome sequencing (WES) revealed 17q12 microdeletion in the fetus and 17q12 microduplication in the father. Notably, at the 3-year follow-up, the baby exhibited a normal phenotype. Conclusions • This research provides a comprehensive description of the phenotype in a rare family featuring 17q12 microdeletion and microduplication. Employing a combination of karyotype analysis, CMA, WES, prenatal ultrasound, and genetic counseling proves helpful in the prenatal diagnosis of chromosomal microdeletions/ microduplications. [ABSTRACT FROM AUTHOR]

Background: Brain anomalies (BAs) have been the focus of research, as they have a high impact on fetal health but therapeutic and diagnostic approaches are limited. Objectives: In this study, the application and efficiency of exome sequencing (ES) in detecting different cases of BAs in fetuses were evaluated and compared with chromosomal microarray analysis (CMA). Search strategy: To conduct this study, three databases including PubMed, Web of Science and Embase were utilised with the keywords 'prenatal', 'diagnoses', 'brain anomalies' and 'exome sequencing'. Selection criteria: Studies were included based on the STARD checklist, for which the ES and CMA diagnostic yields were calculated. Data collection and analysis: Meta‐analysis was performed on the included studies using a random‐effects model and subgroup analysis to define the risk difference between them. Main results: We included 11 studies representing 779 fetuses that implemented ES along with imaging techniques. The pooled ES diagnostic yield in fetuses with BAs detected through magnetic resonance imaging (MRI) and ultrasonography was 26.53%, compared with 3.46% for CMA. The risk difference between ES and CMA for complex BAs was 0.36 [95% confidence interval (CI) 0.24–0.47], which was higher than for single BAs (0.22; 95% CI 0.18–0.25]. Conclusions: ES is a useful method with a significantly higher diagnostic yield than CMA for genetic assessment of fetuses with complex BAs detected by imaging techniques. Moreover, ES could be applied to suspected fetuses with related family histories to predict congenital diseases with high efficiency. [ABSTRACT FROM AUTHOR]

Objective: A late mid-trimester fetal organ scan (lMTS) is recommended between 18 and 22 weeks of pregnancy. Evidence has been accumulating on the effectiveness of first-trimester anatomy scans. Early mid-trimester fetal scans (eMTSs; 14–17 weeks) may have the advantage of visualization of most organs, hence allowing earlier genetic assessment and decision making. Our aim is to examine the effectiveness of eMTSs in identifying fetal anomalies compared to lMTSs. Methods: A retrospective study was conducted based on data from the multidisciplinary prenatal diagnosis clinic in a tertiary center. During the study period (2011–2021), an out-of-pocket eMTS in a community setting was offered routinely to the general population. Women who had previously undergone an eMTS and were later assessed due to a fetal anomaly in our clinic were included in the study. The cohort was divided into two groups according to whether the anomaly had been detected during the eMTS. We then compared the groups for factors that may be associated with anomaly detection in eMTSs. We used t-tests and chi-square tests, for quantitative and qualitative variables, respectively, to determine variables related to eMTS anomaly detection, and logistic regression for multivariate analysis. Results: Of 1525 women assessed in our multidisciplinary clinic, 340 were included in the study. The anomaly detection rate of the eMTS compared to the lMTS was 59.1% The eMTS detection rates for specific organ systems were as follows: skeletal, 57%; cardiac, 52%; congenital anomalies of the kidneys and urinary tract (CAKUT), 44%; central nervous system, 32.4%; chest, 33%; and abdominal, 28%. In multivariate analysis, abnormal first-trimester screening (aOR 3.2; 95%CI 1.26–8.08) and multiple anomalies (aOR 1.86; 95%CI 1.02–3.37) were found to be associated with eMTS anomaly detection. Conclusions: The eMTS detection rate was nearly 60% and was most accurate in detecting skeletal, cardiac, and CAKUT anomalies. Since the eMTS was community-based, this rate likely reflects a "real-world" scenario. Our findings support consideration of performing an eMTS or first-trimester scan routinely for earlier diagnosis and decision making, as an adjunctive to lMTSs. Future studies will examine the cost-effectiveness of early scans. [ABSTRACT FROM AUTHOR]

Noonan syndro me is a rare autosomal dominant congenital abnormality associated with a gene defect located on the short arm of chromosome 12. It is characterized by dysmorphic facies, webbed neck, short stature, lymphatic obstruction, cardiac anomalies, and intellectual disability. Prenatal diagnosis of Noonan syndrome is rare because there are no pathognomonic sonographic signs. Studies on the prenatal sonographic features of Noonan syndrome have been reported in very limited numbers. This case series of severe fetal Noonan syndrome, together with a literature review, was conducted to establish prenatal sonographic features highly suggestive of Noonan syndrome to facilitate early detection by clinicians. This study reveals that Noonan syndrome has a relatively specific pattern, which facilitates prenatal molecular genetic diagnosis. Increased nuchal translucency (NT) in the late first trimester and fluid collection in the early second trimester could be warning signs for follow-up, prompting further investigation to detect late-onset features and leading to molecular genetic confirmation. Most structural abnormalities appear in the second trimester, with progressive changes noted throughout gestation. This review better characterizes the sonographic features of fetal Noonan syndrome based on a larger sample size, illustrating a wider spectrum of prenatal phenotypes, including lymphatic drainage disorders, cardiac abnormalities, polyhydramnios, and absent ductus venosus. [ABSTRACT FROM AUTHOR]

Malformative uropathy in children is one of the most common pathological conditions, with an incidence of 5–14% in newborns. Recent research shows that even in the current conditions, they are often diagnosed only in the advanced stages, when Chronic Kidney Disease is already affirming. This study's objective is to identify urinary tract anomalies, including malformative uropathies in the prenatal stage, using imaging techniques, namely ultrasound of the pregnant uterus. Using prenatal ultrasonography of the pregnant uterus and postnatal clinical and paraclinical examination, we prospectively evaluated a cohort of fifty children with pyelectasia. We describe the demographic and pathological characteristics of patients diagnosed with renal–urinary abnormalities, as well as their postnatal management. A prenatal diagnosis made during the first 15 to 22 weeks of pregnancy enables the evaluation of early malformative uropathies and the determination of the best time to operate in order to minimize complications. When prenatal ultrasonography, fetal karyotype, tissue sample, and embryonic appendages work together, problems may be partially or entirely revealed by these methods due to mistakes made in imaging examinations. In the case of a pregnancy with an antenatal malformation detected, it is necessary for the delivery to take place in a clinic that can provide favorable services for the survival and investigation of the child born with malformative abnormalities. [ABSTRACT FROM AUTHOR]

Introduction: Invasive prenatal testing with chromosomal microarray analysis after first-trimester screening is a relevant option but there is still debate regarding the indications. Therefore, we evaluated the prevalence of numerical chromosomal aberrations detected by classic karyotype and clinically relevant copy number variants (CNVs) in prenatal samples using array comparative genomic hybridization (aCGH) stratified to NT thickness: 4.5 mm, and by the presence/absence of associated structural anomalies detected by ultrasonography. Materials and Methods: Retrospective cohort study carried out at two tertiary Polish centers for prenatal diagnosis (national healthcare system) in central and south regions from January 2018 to December 2021. A total of 1746 prenatal samples were received. Indications for invasive prenatal testing included high risk of Down syndrome in the first-trimester combined test (n = 1484) and advanced maternal age (n = 69), and, in 193 cases, other reasons, such as parental request, family history of congenital defects, and genetic mutation carrier, were given. DNA was extracted directly from amniotic fluid (n = 1582) cells and chorionic villus samples (n = 164), and examined with classic karyotype and aCGH. Results: Of the entire cohort of 1746 fetuses, classical karyotype revealed numerical chromosomal aberrations in 334 fetuses (19.1%), and aCGH detected CNV in 5% (n = 87). The frequency of numerical chromosomal aberrations increased with NT thickness from 5.9% for fetuses with NT < p95th to 43.3% for those with NT > 4.5 mm. The highest rate of numerical aberrations was observed in fetuses with NT > 4.5 mm having at least one structural anomaly (50.2%). CNVs stratified by NT thickness were detected in 2.9%, 2.9%, 3.5%, 4.3%, 12.2%, and 9.0% of fetuses with NT < 95th percentile, 95th percentile–2.9 mm, 3.0–3.4 mm, 3.5–3.9 mm, 4.0–4.5 mm, and >4.5 mm, respectively. After exclusion of fetuses with structural anomalies and numerical aberrations, aCGH revealed CNVs in 2.0% of fetuses with NT < 95th percentile, 1.5% with NTp95–2.9 mm, 1.3% with NT 3.0–3.4 mm, 5.4% with NT 3.5–3.9 mm, 19.0% with NT 4.0–4.5 mm, and 14.8% with NT > 4.5 mm. Conclusions: In conclusion, our study indicates that performing aCGH in samples referred to invasive prenatal testing after first-trimester screening provides additional clinically valuable information over conventional karyotyping, even in cases with normal NT and anatomy. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of ductus venosus agenesis (ADV) in singleton pregnancies ranges from 0.04% to 0.15%, while its prevalence in twins remains largely unknown. To our knowledge, in the literature, there is only a single case report of a monochorionic diamniotic (MCDA) pregnancy complicated by ADV. Fetuses with ADV are at increased risk for congenital cardiac disease, heart failure, and fetal growth restriction (FGR). Consequently, these pregnancies have a heightened risk of experiencing an adverse outcome, like stillbirth and neonatal or infant death. Closer antenatal monitoring is warranted when ADV is suspected. Currently, there are no guidelines regarding the standard of care in cases of ADV and no recommendations for the timing of delivery in either singleton or twin pregnancies. Cases: This study aims to provide a comprehensive overview of the management of twin pregnancies complicated by ADV, featuring two cases of MC twins with concurrent sFGR and ADV in one twin. Discussion: These pregnancies experienced completely different outcomes, underscoring the necessity for personalized management tailored to the specific risk factors present in each pregnancy. Typically, in MCDA pregnancies with severe sFGR (type II and III), delivery represents the most reasonable option when venous Doppler abnormalities are identified. However, the absence of the DV complicates the management and the process of decision-making regarding the timing of delivery in cases of sFGR and ADV. We emphasize that effective decision-making should be guided by the presence of additional risk factors, including velamentous insertion, significant estimated fetal weight discordance, and progressive deterioration of the Doppler over time. Conclusions: Our experience suggests that these factors are strongly correlated with poorer outcomes. Given this context, could it be acceptable, in the case of MC pregnancy complicated by severe sFGR and ADV, with worsening findings and additional risk factors (e.g., velamentous insertion, severe birth weight discrepancy), to anticipate the time of delivery starting from 30 weeks of gestational age? [ABSTRACT FROM AUTHOR]

Background: Micrognathia can be diagnosed in utero with ultrasound by measuring the jaw index and/or inferior facial angle, though it can be challenging due to fetal positioning. The jaw index can be measured with magnetic resonance imaging (MRI) using the masseter muscle, but indistinct margins can lead to inaccuracy; the easily visualized posterior teeth buds may be a better landmark. Objective: We aimed to evaluate inter-reader variability, agreement with ultrasound, and association with postnatal outcomes using MRI to measure the inferior facial angle, jaw index by masseter muscle, and jaw index by posterior teeth buds. Materials and methods: A single-institution retrospective review was performed of singleton pregnancies with prenatally diagnosed micrognathia by ultrasound or MRI from September 2013-June 2022. Ultrasound measurements were obtained by a maternal–fetal medicine specialist and MRI measurements by two radiologists to evaluate inter-reader variability. Intraclass correlation coefficients (ICC) and Bland–Altman analysis were used to assess agreement between imaging methods and logistic regressions and ROC curves to assess associations with postnatal outcomes. Results: Forty-three fetuses (median gestational age 26 weeks (IQR 22–31); 47% male (20/43)) were included. Ultrasound measurements could not be obtained for jaw index in 15/43 (35%) fetuses and inferior facial angle in 11/43 (26%); MRI measurements were obtained by at least one reader in all cases. Jaw index by teeth buds demonstrated lowest inter-reader variability (ICC = 0.82, P < 0.001) and highest agreement with ultrasound (bias -0.23, 95% CI -2.8–2.2). All MRI measurements, but not ultrasound, predicted need for mandibular distraction (inferior facial angle P = 0.02, jaw index by masseter muscle P = 0.04, jaw index by teeth buds P = 0.01). Conclusion: Fetal MRI measurements, particularly jaw index measured by posterior teeth buds, demonstrate low inter-reader variability and high agreement with ultrasound, and may predict need for mandibular distraction postnatally. [ABSTRACT FROM AUTHOR]

There are limited data on how neighborhood-level risk factors affect the likelihood of having prenatal diagnosis. Neighborhood social vulnerability can be quantified and ranked using the social vulnerability index (SVI), a tool that measures the cumulative effect of external stressors in the local environment that may affect health outcomes. The objective of the study was to determine the relationship between SVI and prenatal diagnosis among pregnant patients who received genetic counseling. Retrospective cohort study of all pregnant patients who had genetic counseling at two hospitals in New York between January 2019 and December 2022. For each patient, the address of residence was linked to an SVI score (primary exposure) based on census tract. SVI scores were subdivided into fifths and analyzed categorically. The primary outcome was prenatal diagnosis (yes/no). Multivariable logistic regression was performed. A total of 5,935 patients were included for analysis and 231 (3.9 %) had prenatal diagnosis. On regression analysis, no association between SVI and prenatal diagnosis was observed. Patients who had a diagnostic procedure were more likely to be English speaking (aOR 1.80; 95 % CI 1.13–2.87), carriers of a genetic disorder (aOR 1.94; 95 % CI 1.32–2.86), had increased NT (aOR 6.89; 95 % CI 3.65–13.00), abnormal NIPS (aOR 9.58; 95 % CI 5.81–15.80), or had fetal structural anomalies (aOR 10.60; 95 % CI 6.62–16.96). No differences were seen based on race and ethnicity group, insurance type, or marital status. SVI score does not affect rate of prenatal diagnosis. Findings may differ in other geographic regions and populations. [ABSTRACT FROM AUTHOR]

Objectives: To transform the standardized descriptions of the ultrasound characteristics of endometrial and intrauterine lesions devised by the International Endometrial Tumor Analysis (IETA) group into a practical scoring method and to investigate whether application of this method enhances the diagnostic accuracy of ultrasound radiologists with different levels of experience in detecting malignancy compared with subjective assessment. Methods: This was a retrospective study of 855 patients with endometrial and/or intrauterine lesions, who were divided into a training (n = 600) and a validation (n = 255) set. Ultrasound radiologists with varying levels of experience (expert, intermediate and junior) evaluated all lesions by subjective assessment and according to IETA rules. Using IETA rules, the experts identified signs of malignancy in the training set, assigned scores for each indicator and validated the scoring method in the validation set. The intermediate‐level and junior ultrasound radiologists reassessed the malignancy of the lesions using the IETA scoring method and compared their classifications with those made previously by subjective assessment. Postsurgical pathological evaluation was used as the reference standard. Results: Using subjective assessment, the experts demonstrated the highest level of diagnostic accuracy, with a sensitivity of 85.0%, specificity of 94.3% and an area under the receiver‐operating‐characteristics curve (AUC) of 0.897. Applying the IETA scoring method (comprising eight ultrasound characteristics that contributed to the total score) with a threshold of > 25 points for the diagnosis of malignancy achieved a sensitivity of 84.7%, specificity of 94.7% and AUC of 0.9533 in the training set, with similar performance in the validation set, when performed by experts. Using the IETA scoring method, both junior and intermediate ultrasound radiologists showed improvement in sensitivity (from 55.5% to 74.8% and from 70.2% to 77.1%, respectively), specificity (from 88.4% to 91.5% and from 87.4% to 92.2%, respectively) and AUC (from 0.704 to 0.827 and from 0.793 to 0.841, respectively) for diagnosing malignant lesions. Conclusions: The IETA scoring method exhibits high diagnostic efficacy for malignant endometrial and intrauterine lesions. This method compensates for the lack of experience among junior and intermediate‐level ultrasound radiologists, enhancing their diagnostic skill to a level nearing that of experienced senior ultrasound radiologists. Further research is essential to validate the practicality of implementing this method and to confirm its clinical value. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]