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(1) Background: To examine the incidence of the prenatal diagnosis of the renal double-collecting system (rDCS) and describe its clinical outcome and associated genetic abnormalities. (2) Methods: This retrospective study included women who attended the obstetric clinic for early fetal anatomic sonography with findings of a renal DCS. Diagnosis was conducted by an expert sonographer using defined criteria. (3) Results: In total, 29,268 women underwent early ultrasound anatomical screening at 14–16 weeks, and 383 cases of rDCS were diagnosed (prevalence: 1:76). Associated abnormalities were diagnosed in eleven pregnancies; four had chromosomal aberrations. No chromosomal abnormalities were reported in isolated cases. Ectopic uretrocele and dysplastic kidney were diagnosed in 6 (1.5%) and 5 (1.3%) fetuses, respectively. One girl was diagnosed with vesicoureteral reflux and recurrent UTIs, and two boys were diagnosed with undescended testis. The recurrence rate of rDCS was 8% in subsequent pregnancies. (4) Conclusions: In light of its benign nature, we speculate that isolated rDCS may be considered a benign anatomic variant, but a repeat examination in the third trimester is recommended to assess hydronephrosis. [ABSTRACT FROM AUTHOR]

Simple Summary: This study focused on the ultrasound diagnosis of twins in canine and feline species. Prenatal diagnosis is becoming increasingly important even in small animals to assess foetal morphology and identify any eventual abnormalities. In canine and feline species, which are typically polytocous species, only monochorionic twins, i.e., sharing at least the same placenta, can be termed, using ultrasound, as twins. In this study, seven cases of monochorionic twins were reported with a prevalence of under 1%. The clinical relevance of such a diagnosis is to prevent complications during pregnancy and, especially, delivery. Prenatal diagnosis comprises a set of investigations, both instrumental and laboratory-based, which aim to monitor the health of the foetus during pregnancy, from the early stages of embryonic development to the moments preceding delivery. A growing interest is emerging for the preterm ultrasound morphological screening of embryos and foetuses, aimed at assessing the integrity and viability of the conceptus, as well as the early diagnosis of anomalies which can cause complications. This study is a retrospective study of the ultrasonographic findings of twins in the authors' clinical activity from 2016 to 2022. Only seven cases of monochorionic twins were recorded, out of the whole number of evaluations performed on 3120 foetuses, with a prevalence of 0.6% and 0.2% in feline and canine foetuses. All the twins had their own amniotic sac and umbilical cord but presented a single placenta and a single allantoic sac. Unfortunately, the three feline cases were not more recognizable at term. In the four canine cases, three were of opposite sex and then necessarily dizygotic. Twins may have an impact on the success of a pregnancy due to the risk of dystocia, as observed in some of the reported cases. Prenatal ultrasound allows early recognition of twins in dogs and cats. [ABSTRACT FROM AUTHOR]

Fetal development is a critical phase in prenatal care, demanding the timely identification of anomalies in ultrasound images to safeguard the well-being of both the unborn child and the mother. Medical imaging has played a pivotal role in detecting fetal abnormalities and malformations. However, despite significant advances in ultrasound technology, the accurate identification of irregularities in prenatal images continues to pose considerable challenges, often necessitating substantial time and expertise from medical professionals. In this review, we go through recent developments in machine learning (ML) methods applied to fetal ultrasound images. Specifically, we focus on a range of ML algorithms employed in the context of fetal ultrasound, encompassing tasks such as image classification, object recognition, and segmentation. We highlight how these innovative approaches can enhance ultrasound-based fetal anomaly detection and provide insights for future research and clinical implementations. Furthermore, we emphasize the need for further research in this domain where future investigations can contribute to more effective ultrasound-based fetal anomaly detection. [ABSTRACT FROM AUTHOR]

(1) Purpose: Retrospective back-to-back comparisons were performed to evaluate the accuracy, effectiveness, and incremental yield of chromosome microarray analysis (CMA) and exome sequencing (ES) analysis in fetuses with digestive system malformations (DSMs). (2) Methods: In total, 595 women with fetal DSMs who underwent prenatal diagnosis were enrolled. We analyzed the diagnostic yields of CMA and ES and evaluated pregnancy outcomes. Copy number variants (CNVs) were classified according to the American College of Medical Genetics and Genomics guidelines. (3) Results: Pathogenic CNVs were detected in 11/517 (2.12%) fetuses, and variants of unknown significance (VUS) were identified in 69 (13.35%) fetuses using CMA. ES detected 29 pathogenic/likely pathogenic variants in 23/143 (16.08%) fetuses and 26/143 (18.2%) VUS. In those with other ultrasound abnormalities, the detection rate of multiple system structural malformations was 41.2%, followed by skeletal (33.3%), cardiovascular (25.4%), and central nervous system (18.6%) malformations. Of the 391 surviving children, 40 (10.2%) exhibited varying degrees of mental retardation. (4) Conclusion: A correlation exists between DSMs and chromosomal abnormalities. When combined with other systemic abnormalities, the incidence of chromosomal abnormalities increases significantly. Patients with congenital DSM are at risk of developing neurodevelopmental disorders. Combined CMA and ES detection of fetal DSM has good clinical application potential. [ABSTRACT FROM AUTHOR]

Prenatal ultrasonography is the most crucial imaging modality during pregnancy. However, problems such as high fetal mobility, excessive maternal abdominal wall thickness, and inter-observer variability limit the development of traditional ultrasound in clinical applications. The combination of artificial intelligence (AI) and obstetric ultrasound may help optimize fetal ultrasound examination by shortening the examination time, reducing the physician's workload, and improving diagnostic accuracy. AI has been successfully applied to automatic fetal ultrasound standard plane detection, biometric parameter measurement, and disease diagnosis to facilitate conventional imaging approaches. In this review, we attempt to thoroughly review the applications and advantages of AI in prenatal fetal ultrasound and discuss the challenges and promises of this new field. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the potential of the first-trimester ultrasound (US) features for the detection of central nervous system (CNS) anomalies. Methods/Methodology: This is a prospective one-center three-year study. Unselected singleton pregnant women were examined using an extended first-trimester anomaly scan (FTAS) that included the CNS assessment: the calvaria shape, the septum (falx cerebri), the aspect of the lateral ventricles, the presence of the third ventricle and aqueduct of Sylvius (AS) and the posterior brain morphometry: the fourth ventricle, namely intracranial translucency (IT), brain stem/brain stem–occipital bone ratio (BS/BSOB) and cisterna magna (CM). The spine and underlying skin were also evaluated. The cases were also followed during the second and third trimesters of pregnancy and at delivery. FTAS efficiency to detect major CNS abnormalities was calculated. Results: We detected 17 cases with CNS major abnormalities in a population of 1943 first-trimester (FT) fetuses, including spina bifida with myelomeningocele, exencephaly-anencephaly, holoprosencephaly, hydrocephaly, cephalocele and Dandy-Walker malformation. The CNS features in the abnormal group are presented. In the second trimester (ST), we further diagnosed cases of corpus callosum agenesis, cerebellar hypoplasia, vein of Galen aneurysm and fetal infection features (ventriculomegaly, intraventricular bands, intraventricular cyst and hyperechoic foci), all declared normal at the FTAS. During the third trimester (TT) scan we identified a massive fetal cerebral haemorrhage absent at previous investigations. We report a detection rate of 72.7% of fetal brain anomalies in the FT using the proposed CNS parameters. The sensitivity of the examination protocol was 72.7%, and the specificity was 100%. Conclusion: A detailed FT CNS scan is feasible and efficient. The majority of cases of major CNS abnormalities can be detected early in pregnancy. The visualization rates of the CNS parameters in the FT are great with short, if any, additional investigation time. FT cerebral disorders such as haemorrhage or infections were missed in the FT even when an extended evaluation protocol was used. [ABSTRACT FROM AUTHOR]

Objective: SHOX haploinsufficiency have been commonly found in isolated short stature (ISS) and Léri–Weill dyschondrosteosis (LWD) patients. However, few publications have described the genetic analysis and clinical characteristics of fetuses with SHOX haploinsufficiency. Methods: Chromosomal microarray (CMA) were applied in 14,051 fetuses and sequentially whole exome sequence (WES) in 1340 fetuses who underwent prenatal diagnosis during 2016–2021. The analysis and summary of molecular genetics, sonographic characteristics, and follow-up results were performed in fetuses with SHOX haploinsufficiency without other genetic etiologies. A comparison was made between three groups according to prenatal diagnostic indications. Results: 8 (0.06%) fetuses of SHOX haploinsufficiency were all detected by CMA, of which 5 (62.5%) were detected with short long bones by ultrasound scan, and 4 were inherited from their previously undiagnosed parents. No pathogenic SHOX variants were found by WES. The detection rate of SHOX haploinsufficiency was obviously higher in the short long bone group (2.6%, 5/191) than the other abnormality group (0.03%, 1/3919) or no ultrasound abnormality group (0.02%, 2/9941). Three of the fetuses were liveborn with normal growth up to the age of four and four were terminated. Conclusion: The phenotype of fetuses with SHOX haploinsufficiency is highly varied. Over 1/3 of the cases exhibited no phenotype and nearly 2/3 with short long bones, in the absence of Madelung deformity during fetal development. SHOX haploinsufficiency should be considered in all antenatal presentations, especially in the case of isolated short long bones. CMA can provide effective detection. [ABSTRACT FROM AUTHOR]

Background: There are few studies on the detection rate by chromosomal microarray analysis (CMA) of the prenatal diagnosis of talipes equinovarus (TE) compared to conventional karyotyping. We aimed to explore the molecular etiology of fetal TE and examine the detection rate by CMA, which provides more information for the clinical screening and genetic counseling of TE. Methods: In this retrospective study, pregnancies diagnosed with fetal TE were enrolled and clinical data for all cases were retrieved from our medical record database, including demographic data for pregnancies, ultrasound findings, karyotype/CMA results, and pregnant and perinatal outcomes. Results: Among the 164 patients, 17 (10.4%) clinically significant variants were detected by CMA. In 148 singleton pregnancies, the diagnostic rate of clinically significant variants was significantly higher in the non-isolated TE group than in the isolated TE group (10/37, 27.0% vs. 6/111, 5.4%, P < 0.001). In twin pregnancies, 1 (6.3%) pathogenic copy number variant was present in the other 16 twin pregnancies. Conclusions: This study demonstrates that CMA is useful for the prenatal genetic diagnosis of fetal TE. Fetal TE with the associated structural malformation correlates with a higher probability of clinically significant variants. This data may aid prenatal diagnosis and genetic counseling for fetal TE. [ABSTRACT FROM AUTHOR]

Congenital malformations diagnosed by ultrasound screening complicate 3–5% of pregnancies and many of these have an underlying genetic cause. Approximately 40% of prenatally diagnosed fetal malformations are associated with aneuploidy or copy number variants, detected by conventional karyotyping, QF-PCR and microarray techniques, however monogenic disorders are not diagnosed by these tests. Next generation sequencing as a secondary prenatal genetic test offers additional diagnostic yield for congenital abnormalities deemed to be potentially associated with an underlying genetic aetiology, as demonstrated by two large cohorts: the 'Prenatal assessment of genomes and exomes' (PAGE) study and 'Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study' performed at Columbia University in the US. These were large and prospective studies but relatively 'unselected' congenital malformations, with little Clinical Genetics input to the pre-test selection process. This review focuses on the incremental yield of next generation sequencing in single system congenital malformations, using evidence from the PAGE, Columbia and subsequent cohorts, with particularly high yields in those fetuses with cardiac and neurological anomalies, large nuchal translucency and non-immune fetal hydrops (of unknown aetiology). The total additional yield gained by exome sequencing in congenital heart disease was 12.7%, for neurological malformations 13.8%, 13.1% in increased nuchal translucency and 29% in non-immune fetal hydrops. This demonstrates significant incremental yield with exome sequencing in single-system anomalies and supports next generation sequencing as a secondary genetic test in routine clinical care of fetuses with congenital abnormalities. [ABSTRACT FROM AUTHOR]

Fetal magnetic resonance imaging (MRI) has become a widely used tool in clinical practice, providing increased accuracy in prenatal diagnoses of congenital abnormalities of the brain, allowing for more accurate prenatal counseling, optimization of perinatal management, and in some cases fetal intervention. In this article, a brief description of how fetal ultrasound (US) and fetal MRI are used in clinical practice will be followed by an overview of the most common reasons for referral for fetal MRI of the brain, including ventriculomegaly, absence of the cavum septi pellucidi (CSP) and posterior fossa anomalies. [ABSTRACT FROM AUTHOR]

Cri-du-Chat syndrome (CdCS) is a rare but serious genetic disorder. Most cases occur de novo, without specific risk factors as an indication of invasive prenatal diagnosis. Moreover, no specific ultrasound findings have been reported to facilitate early detection. This study presents a case of CdCS with fetal ultrasound findings of cerebellar hypoplasia and peri-membranous ventricular septal defect (VSD), which are consistent with previous reports, as well as coarctation of the aorta and hypercoiling cord, which have never been described in CdCS before. Additionally, we performed an analytical literature review to identify the sonographic pattern facilitating prenatal diagnosis. Based on the review of 47 reported cases, most CdCS fetuses (87.2%) had ultrasound characteristics: cerebellar hypoplasia (29.8%), followed by cardiac abnormalities (19.1%), hydrops fetalis/fluid collection (17.0%), ventriculomegaly (14.9%), choroid plexus cyst (12.8%) and nasal bone hypoplasia (12.8%). Increased nuchal translucency/nuchal fold thickness was also common. This is the first study providing a fetal sonographic pattern of CdCS that may facilitate early diagnosis. [ABSTRACT FROM AUTHOR]

Umbilical cord abnormalities are not rare, and are often associated with structural or chromosomal abnormalities, fetal intrauterine growth restriction, and poor pregnancy outcomes; the latter can be a result of prematurity, placentation deficiency or, implicitly, an increased index of cesarean delivery due to the presence of fetal distress, higher admission to neonatal intensive care, and increased prenatal mortality rates. Even if the incidence of velamentous insertion, vasa praevia and umbilical knots is low, these pathologies increase the fetal morbidity and mortality prenatally and intrapartum. There is a vast heterogeneity among societies' guidelines regarding the umbilical cord examination. We consider the mandatory introduction of placental cord insertion examination in the first and second trimester to practice guidelines for fetal ultrasound scans. Moreover, during the mid-trimester scan, we recommend a transvaginal ultrasound and color Doppler assessment of the internal cervical os for low-lying placentas, marginal or velamentous cord insertion, and the evaluation of umbilical cord entanglement between the insertion sites whenever it is incidentally found. Based on the pathological description and the neonatal outcome reported for each entity, we conclude our descriptive review by establishing a new, clinically relevant classification of these umbilical cord anomalies. [ABSTRACT FROM AUTHOR]

Background: Noninvasive prenatal genetic testing (NIPT) has been adopted as the first choice for aneuploidy screening. The purposes of this study were to investigate the accuracy of Vanadis® NIPT (hereafter CRITO-NIPT) in order to gain a deeper insight into the reasons for discrepancies, as well as to discuss the role of fetal ultrasound. Methods: Between 2019 and 2020, CRITO-NIPT was performed in 1218 cases of patients who underwent CVS or amniocentesis after a detailed fetal ultrasound exam and genetic counseling. The CRITO-NIPT results were compared with the genetic results. In cases of test discrepancies, the placentae were collected for detailed genetic research, and the pre-procedure fetal ultrasound findings were referred to. Results: The positive predictive value of T21, T18, and T13 was 93.55%, 88.46%, and 100%, respectively. In 90% of the of false positive (FP) cases, the placentae were examined. In 75% of the CRITO FP-T21 cases, placental mosaicism, or a demised twin's T21, were confirmed. There were complicated mosaic cases, including tetrasomy 21/trisomy7 and monosomy 21/trisomy21 cases. In one of three no-call cases, an intermediate deletion of chromosome 13 was detected. Conclusions: The CRITO study investigated the mechanism of false positives, and the detailed mechanisms in mosaic and no-call cases. There have hitherto been no reports that have provided insight by partitioning the placenta to compare the NIPT and invasive test results, nor that have provided detailed ultrasound findings in the cases of discordant results, revealing the demonstrated importance of, and necessity for, detailed ultrasonography. This article describes the potential of rolling-circle replication as a powerful biosensing platform, as well as the importance of examining the fetus in detail with ultrasound. However, we should remember that the potential applications raise ethical and social concerns that go beyond aneuploidy and its methodology. [ABSTRACT FROM AUTHOR]

The greater omentum is an apron-like peritoneal mesothelial sheet that was described by ultrasound as a floating fluid-filled viscus in ascites during the fetal period. To examine the association between the etiology of fetal ascites and ultrasound findings of the greater omentum, a retrospective study was conducted. Ultrasound findings of fetal omentum were defined as follows: (1) a cyst-like shape with a thin membrane observed as wavy in the ascites, (2) beside the stomach and below the liver, and (3) no blood flow noted on color Doppler. Eleven pregnancies had fetal ascites. A fetal greater omentum was confirmed in eight cases in which ascites were caused by non-peritonitis: fetal hydrops (n = 4), congenital cytomegalovirus infection (n = 2), idiopathic chylous ascites (n = 1), and unknown cause (n = 1). Of these eight cases, no abdominal surgical management was required in three live babies. However, a fetal greater omentum was not confirmed in all three cases of meconium peritonitis. It was suggested that the finding of the greater omentum can be an important clue for estimating the pathophysiological etiology of fetal ascites and helping with postnatal management. It should be reasonable to add the finding of the greater omentum to the detailed ultrasound examination checklist. [ABSTRACT FROM AUTHOR]

Chromosomal microarray analysis (CMA), recently introduced following conventional cytogenetic technology, can detect submicroscopic copy-number variations (CNVs) in cases previously diagnosed as "cytogenetically benign". At present, rapid and accurate chromosomal analysis is required in prenatal diagnostics, but prenatal CMA is not widely used due to its high price and long turnaround time. We introduced a new prenatal screening method named digital karyotyping (D-karyo), which utilizes a preimplantation genetic test for the aneuploidy (PGT-A) platform. First, we conducted a preliminary experiment to compare the original PGT-A method to our modified method. Based on the preliminary results, we decided to implement the modified strategy without whole-genome amplification (WGA) and combined it with three analytical software packages. Next, we conducted a prospective study with 824 samples. According to the indication for invasive tests, the D-karyo positive rates were 2.5% and 5.0%, respectively, in the screening positive group with NT ≥ 3.5 mm and the group with fetal abnormalities by ultrasound. D-karyo is a breakthrough modality that can detect submicroscopic CNVs ≥ 1.0 Mb accurately in only 10.5 h for 24 samples at a low cost. Implementing D-karyo as a prenatal rapid screening test will reduce unnecessary CMA and achieve more accurate prenatal genetic testing than G-banding. [ABSTRACT FROM AUTHOR]

The routine assessment to determine the genetic etiology for fetal ultrasound anomalies follows a sequential approach, which usually takes about 6–8 weeks turnaround time (TAT). We evaluated the clinical utility of simultaneous detection of copy number variations (CNVs) and single nucleotide variants (SNVs)/small insertion-deletions (indels) in fetuses with a normal karyotype with ultrasound anomalies. We performed CNV detection by chromosomal microarray analysis (CMA) or low pass CNV-sequencing (CNV-seq), and in parallel SNVs/indels detection by trio-based clinical exome sequencing (CES) or whole exome sequencing (WES). Eight-three singleton pregnancies with a normal fetal karyotype were enrolled in this prospective observational study. Pathogenic or likely pathogenic variations were identified in 30 cases (CNVs in 3 cases, SNVs/indels in 27 cases), indicating an overall molecular diagnostic rate of 36.1% (30/83). Two cases had both a CNV of uncertain significance (VOUS) and likely pathogenic SNV, and one case carried both a VOUS CNV and an SNV. We demonstrated that simultaneous analysis of CNVs and SNVs/indels can improve the diagnostic yield of prenatal diagnosis with shortened reporting time, namely, 2–3 weeks. Due to the relatively long TAT for sequential procedure for prenatal genetic diagnosis, as well as recent sequencing technology advancements, it is clinically necessary to consider the simultaneous evaluation of CNVs and SNVs/indels to enhance the diagnostic yield and timely TAT, especially for cases in the late second trimester or third trimester. [ABSTRACT FROM AUTHOR]

Background: Ultrasound is operator-dependent, and its value and efficacy in fetal morphology assessment in a low-resource setting is poorly understood. We assessed the value and efficacy of fetal morphology ultrasound assessment in a Nigerian setting. Materials and Methods: We surveyed fetal morphology ultrasound performed across five facilities and followed-up each fetus to ascertain the outcome. Fetuses were surveyed in the second trimester (18th–22nd weeks) using the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) guideline. Clinical and surgical reports were used as references to assess the diagnostic efficacy of ultrasound in livebirths, and autopsy reports to confirm anomalies in terminated pregnancies, spontaneous abortions, intrauterine fetal deaths, and still births. We calculated sensitivity, specificity, positive and negative predictive values, Area under the curve (AUC), Youden index, likelihood ratios, and post-test probabilities. Results: In total, 6520 fetuses of women aged 15–46 years (mean = 31.7 years) were surveyed. The overall sensitivity, specificity, and AUC were 77.1 (95% CI: 68–84.6), 99.5 (95% CI: 99.3–99.7), and 88.3 (95% CI: 83.7–92.2), respectively. Other performance metrics were: positive predictive value, 72.4 (95% CI: 64.7–79.0), negative predictive value, 99.6 (95% CI: 99.5–99.7), and Youden index (77.1%). Abnormality prevalence was 1.67% (95% CI: 1.37–2.01), and the positive and negative likelihood ratios were 254 (95% CI: 107.7–221.4) and 0.23 (95% CI: 0.16–0.33), respectively. The post-test probability for positive test was 72% (95% CI: 65–79). Conclusion: Fetal morphology assessment is valuable in a poor economics setting, however, the variation in the diagnostic efficacy across facilities and the limitations associated with the detection of circulatory system anomalies need to be addressed. [ABSTRACT FROM AUTHOR]