First-trimester ultrasound has evolved to incorporate a detailed fetal anatomy scan (FAS) with nuchal translucency (NT) screening. Many institutions use a 2-visit protocol: NT followed by detailed FAS at 14-16 weeks. We aimed to evaluate whether integrating detailed FAS into the NT window (12 + 5 to 13 + 6 weeks) is non-inferior in diagnostic yield to the 2-visit protocol. We enrolled 755 mixed high- and low-risk pregnant women with singleton gestations into either integrated NT + FAS group (n = 243, 12 + 5 to 13 + 6 weeks) or 2-visit group (n = 512, 14-16 weeks). All underwent follow-up at 20-24 weeks. Scans followed ISUOG guidelines; the primary outcome was detection of fetal anomalies during detailed early scans. Non-inferiority was defined as a margin of ≤6% difference in detection rates. Study groups were similar except in parity (mean 2.6 [0-9] vs. 3.1 [0-10], P = .0081 in FAS + NT and 2-visit group, respectively). Anomalies were identified in 16 fetuses (7.5%) in the NT + FAS group and 16 (3%) in the 2-visit group (P = .033). Additional anomalies were detected at mid-trimester in 2/227 (0.9%) NT + FAS and 4/496 (0.8%) 2-visit group fetuses (P = 1.0). The integrated approach met non-inferiority criteria. Detailed FAS during the final NT window week is non-inferior to the 2-visit approach. This integrated protocol offers earlier reassurance without compromising diagnostic accuracy.

To share our experience of ultrasonographic evaluation of fetal anatomy in the first trimester and pregnancy follow-up in a tertiary center. This retrospective study was conducted in the Acıbadem University Atakent Hospital and Acıbadem University Bakırköy Hospital Prenatal Diagnosis Units between April 2015 and December 2019. The study group included pregnant women referred for first-trimester aneuploidy screening and anomaly survey. The mean maternal age was 31.28±4.43 years and ranged from 20-49 years. The median gestational week at which first-trimester evaluation was made was 12.4 weeks. Of 3254 cases, 55 (1.69%) had pathologic ultrasound findings in the first-trimester anomaly scan, including increased nuchal translucency (NT) value over 95th percentile in 34 fetuses (52.3%) with structural anomaly. Median (range) crown-rump length was 58.69 (45-83) mm, and the median NT value was 3,5 (1.5-12) mm for fetuses with abnormal sonographic findings. The total detection rate for sonographic anomalies in the first-trimester scan was 60.43%. Of note, 27.3% of fetuses with detected anomalies had multiple congenital anomalies. Twenty-four new cases were diagnosed in the second trimester, and 11 new cases were detected in the last trimester from the same cohort. Screening between 11-14 weeks of pregnancy may be an opportunity to evaluate maternal health and detect severe fetal anomalies. The family should be counseled about structural anomalies that may be detected later, especially in the second and third trimesters, the limitations of the technique, and the ongoing progress of fetal development.

To expand the clinical phenotype spectrum and improve the understanding of prenatal ultrasound manifestations and fetal prognosis of 16p13.11 deletion/duplication syndrome in the East Asian population. We conducted a comprehensive ultrasound phenotypic analysis, pedigree analysis and long-term postnatal outcome follow-up on 201 fetuses with 16p13.11 deletion/duplication, as well as on the phenotypic manifestations of 14 patients who underwent chromosomal microarray analysis between April 2013 and July 2024. Descriptive statistical analysis was used. The detection rates were 0.08% and 0.18%, the frequencies of de novo occurrence were 26.9% and 14.5%, and the rates of abnormal postnatal phenotypes were 25% and 17.5% in our prenatal cohort of deletion and duplication, respectively. Overall, 28.6% of deletions and 15.9% of duplications exhibited abnormal postnatal phenotypes even if they were inherited from a phenotypically normal parent. Developmental delay was the most common clinical abnormality. Immune disorders, torticollis, concealed penis and cryptorchidism were closely related phenotypes that had previously gone unnoticed. Copy number variations extending to intervals I + II or II + III appeared to be associated with a broader range of phenotypes. Isolated choroid plexus cysts may be the most relevant ultrasound soft marker for deletion, whereas isolated thickened nuchal translucency appears to be more closely associated with duplication. Cardiovascular and urinary malformations were the most frequently detected ultrasound structural abnormalities. The large East Asian prenatal cohort is conducive to enhancing genetic counseling for 16p13.11 deletion/duplication syndrome by facilitating a more accurate prediction of fetal prognosis and developmental potential.

ObjectiveThe purpose of this study was to explore the detection rate of chromosomal copy number variants (CNVs) in fetuses with isolated and non-isolated increased nuchal translucency (NT) by chromosomal microarray analysis (CMA).MethodsA retrospective study was conducted on 211 fetuses with increased NT diagnosed prenatally at Meizhou People’s Hospital from November 2022 to June 2025. Interventional prenatal CMA testing was conducted on these fetuses. The detection rates of chromosomal abnormalities in fetuses with isolated and non-isolated increased NT, and fetuses with different NT thicknesses (2.5-3.4, 3.5-4.4, and ≥4.5 mm) were analyzed.ResultsAmong the fetuses, hromosomal aneuploidy, pathogenic or likely pathogenic (P/LP) CNVs, and variants of uncertain significance (VOUS) were detected in 23, 14, and 26 fetuses respectively, with a total detection rate of 29.9%. A total of 151 fetuses (71.6%) had increased NT, and 60 fetuses (28.4%) had non-isolated increased NT. There was a statistically significant difference in the detection rate of chromosomal abnormalities between the two groups (23.2% vs. 46.7%, χ2=11.311, p=0.001). In fetuses with isolated increased NT, with the increase of NT thickening, the rate of chromosomal aneuploidy shows an increasing trend. And there was statistically significant difference in detection rate of chromosomal aneuploidy in fetuses with different NT thicknesses (p=0.045).ConclusionsA notable difference existed in the detection rate of chromosomal abnormalities between fetuses with isolated and non-isolated increased NT. For those with isolated increased NT, chromosomal aneuploidy rates tended to rise with increasing NT thickness, while this trend was not observed for P/LP CNVs.

We aimed to characterize the fetal features across gestation and describe genotype-phenotype correlations for pregnancies with fetal RASopathies that were more severely affected as they presented with at least one abnormal fluid collection. Retrospective cohort study of pregnancies with a fetal RASopathy and one or more abnormal fluid collections. Ultrasound and clinic databases were searched at six institutions to identify pathogenic or likely pathogenic variants indicating a fetal RASopathy. Phenotypic features were organized by gestational age to evaluate their evolution, and chi-square and Fisher exact proportions were compared. Forty-six pregnancies were included. Pleural effusions, skin edema, ascites, and cardiac abnormalities presented across gestation. Cystic hygroma and jugular sacs presented in the first trimester and persisted into the second trimester. Hepatomegaly, polyhydramnios, small or absent stomach, and contractures were more frequent in the second and third trimesters. Contractures were more likely with HRAS variants (63% vs. 24%, p=0.044) and increased nuchal translucency or cystic hygroma were more common with SOS1 variants (100% vs. 44%, p=0.049). These data provide insight into genotype-phenotype correlations and the course of fetal RASopathies that present with at least one abnormal fluid collection. Timing of these phenotypes is important to consider for future research on targeted in utero approaches to management.

ABSTRACT Objective To investigate the additional clinical value of nuchal translucency (NT) measurement at the first‐trimester anomaly scan (FTAS) in a setting with first‐tier non‐invasive prenatal testing (NIPT). Method This nationwide prospective cohort study, part of the IMITAS study on FTAS implementation, included all pregnancies with increased NT (≥ 3.5 mm) at FTAS, subsequently referred for detailed diagnostic scans at eight Dutch tertiary centers (Nov 2021–Nov 2022). Women with abnormal dating scans, abnormal NIPT before FTAS, or high‐risk for fetal anomalies were not eligible for FTAS and received diagnostic ultrasound directly. The primary outcome was prenatal diagnosis of structural or genetic anomalies based on pre‐ and postnatal findings. Results FTAS was performed in 129,704 pregnancies, of which 230 (0.18%) had an increased NT. Anomalies were detected in 33.9% of these cases. Genetic anomalies included 76.8% aneuploidies, 14.3% SNVs, 8.9% CNVs; 39.3% beyond NIPT's detection scope. Trisomy 21/18 was diagnosed in 29.3% referred for increased NT without prior NIPT; 73.5% of these opted for termination. Anomaly prevalence increased with greater NT thickness. Conclusion NT measurement adds value in a national screening program including FTAS and NIPT. Prenatal counseling should address trisomies and other genetic abnormalities as a potential result of an abnormal FTAS, particularly when NIPT is declined.

Objectives: To evaluate the diagnostic and descriptive role of first-trimester ultrasound (FTU) in early pregnancy at a tertiary healthcare center. Methods: A retrospective observational study was conducted in which 120 pregnant women who underwent FTU (≤12 weeks gestation) between March 2024 and February 2025. Archived imaging and hospital records were reviewed to analyze obstetric and ultrasound data. Outcomes assessed included gestational age confirmation, detection of fetal cardiac activity, yolk sac evaluation, and diagnosis of early pregnancy complications. Statistical analysis was performed using the Statistical Package for the Social Sciences v23.0. Results: Of the 120 cases, 77.5% were viable singleton intrauterine pregnancies. Multifetal gestation was identified in 5.8% with chorionicity assessment possible in all twin pregnancies. Ectopic pregnancies and anembryonic gestations were each diagnosed in 5% of cases. Embryonic cardiac activity was present in 83.3% and yolk sac abnormalities were noted in 11.6%. The nuchal translucency was measured in 16.6% of cases (Mean NT 1.34±0.29 mm). Additional findings included subchorionic hematomas (3.3%) and adnexal masses (4.2%). Crown-rump length-based gestational dating closely agreed with last menstrual period-based estimates. Conclusion: FTU plays an important role in early pregnancy care by ensuring early diagnosis of both normal as well as abnormal pregnancies. It improves obstetric decision-making through accurate dating, identification of viability, and early detection of complications.

Objectives: To evaluate the diagnostic and descriptive role of first-trimester ultrasound (FTU) in early pregnancy at a tertiary healthcare center. Methods: A retrospective observational study was conducted in which 120 pregnant women who underwent FTU (≤12 weeks gestation) between March 2024 and February 2025. Archived imaging and hospital records were reviewed to analyze obstetric and ultrasound data. Outcomes assessed included gestational age confirmation, detection of fetal cardiac activity, yolk sac evaluation, and diagnosis of early pregnancy complications. Statistical analysis was performed using the Statistical Package for the Social Sciences v23.0. Results: Of the 120 cases, 77.5% were viable singleton intrauterine pregnancies. Multifetal gestation was identified in 5.8% with chorionicity assessment possible in all twin pregnancies. Ectopic pregnancies and anembryonic gestations were each diagnosed in 5% of cases. Embryonic cardiac activity was present in 83.3% and yolk sac abnormalities were noted in 11.6%. The nuchal translucency was measured in 16.6% of cases (Mean NT 1.34±0.29 mm). Additional findings included subchorionic hematomas (3.3%) and adnexal masses (4.2%). Crown-rump length-based gestational dating closely agreed with last menstrual period-based estimates. Conclusion: FTU plays an important role in early pregnancy care by ensuring early diagnosis of both normal as well as abnormal pregnancies. It improves obstetric decision-making through accurate dating, identification of viability, and early detection of complications.

Background:Nuchal translucency (NT) measurement by ultrasound is used in the first trimester as a screening tool for genetic, chromosomal, and structural anomalies. As the NT measurement increases, the risk of an underlying abnormality also rises. This study aims to evaluate the significance of increased NT measurements within a local cohort, examining their associations with adverse pregnancy outcomes and their potential role in guiding clinical interventions.Methods:Pregnancies with first-trimester fetal NT measurements greater than 2.5 mm were included. Participants were categorized into five groups based on NT measurements: ≤3.4 mm, 3.5–4.4 mm, 4.5–5.4 mm, 5.5–6.4 mm and ≥6.5 mm. The outcomes evaluated included chromosomal anomalies confirmed by invasive testing (such as Trisomy 21), major congenital anomalies involving any major organ system, and miscarriage or termination of pregnancy before 24 weeks of gestation. Gestational age at delivery, birthweight, small-for-dates (SFD) status, and admission to the neonatal intensive care unit (NICU) were evaluated for infants born after 24 weeks of gestation without congenital anomalies.Results:The median NT measurement among the 290 women in the study was 3.7 mm, ranging from 2.9 mm (25th centile) to 7.4 mm (75th centile). Overall, 43.5% of the participants were in the lowest NT category, while 15.9% were in the highest category. Maternal age, body mass index, and nationality were comparable between the groups. The odds of chromosomal anomalies increased with higher NT measurements, with odds ratio (OR) ranging from 2.50 to 4.02 (p < 0.05), compared to the lowest NT group. Similarly, the odds of major congenital anomalies (OR: 2.20–4.20; p < 0.05), multiple anomalies (OR: 5.61–8.19 in the highest three categories; p < 0.005), and miscarriages (OR: 5.04–14.9 in the highest three categories; p < 0.001) all increased with rising NT measurements. The odds of most chromosomal anomalies increased with NT, except for Trisomy 21, which was similar across the groups. Participants in the two lowest NT groups had 12.7- and 7.5-fold higher odds (both p < 0.001) of achieving a pregnancy beyond 24 weeks without anomalies compared to those in the highest NT group. Among pregnancies resulting in viable non-anomalous deliveries, there were no significant differences in the gestational age at delivery, birthweight, incidence of SFD, or NICU admission.Conclusion:Adverse outcomes, including chromosomal and congenital anomalies, increased with higher NT measurements, with a significant difference observed beyond 3.4 mm. These findings highlight the importance of early NT screening and targeted interventions to improve perinatal outcomes.

Abstract Objective To evaluate the technical feasibility of isolating fetal trophoblasts and detecting fetal chromosomal anomalies (trisomy 21 and XY chromosomes) using cervical smear samples obtained during routine prenatal care, and to explore the potential of this approach as a preliminary step towards a cost-effective alternative to current non-invasive prenatal testing methods. Study design Prospective cohort study with fluorescence in situ hybridization (FISH) analysis of cervical smear samples for chromosomal screening. Place and duration Department of Obstetrics and Gynecology, Caspian International Hospital, Azerbaijan, conducted in 2024. Methods Fifty pregnant women between 5 and 15 gestational weeks underwent cervical smear collection via cytobrush during routine prenatal visits. Samples were processed for the isolation of extravillous trophoblasts (EVTs). Successful isolation of EVTs was confirmed by morphological assessment and the presence of HLA-G markers. Samples were then analyzed using FISH methodology with probes specific for chromosomes 21, X, and Y. Ultrasound confirmation of fetal sex and nuchal translucency measurements was performed for initial correlation (Interim Correlation Standard). Automated scanning systems and manual verification were employed for accurate chromosomal analysis. Results Extravillous trophoblasts were successfully isolated in all 50 samples (100% success rate (95% CI: 92.9%-100%)). XY chromosomes were detected in 17 cases (34%), with ultrasound confirming male sex in 6 of 7 eligible cases (85.7% concordance). XX chromosomes were identified in 33 cases (66%), with ultrasound confirming female sex in 12 of 14 cases (85.7% concordance). No trisomy 21 cases were detected in this cohort, precluding the calculation of sensitivity for Trisomy 21 detection. One case presented with nuchal translucency ≥ 3 mm and was referred for amniocentesis, with subsequent normal karyotype confirmed by amniocentesis. FISH analysis demonstrated 100% specificity for chromosomal detection with no false-positive results for the sex chromosomes when correlated with the interim ultrasound standard. Conclusion Cervical smear-based FISH analysis represents a promising non-invasive, cost-effective approach for early fetal chromosomal screening that leverages existing clinical infrastructure. While demonstrating excellent specificity for sex chromosome determination, and technical feasibility of EVT isolation, the absence of Trisomy 21 cases in this pilot cohort limits the assessment of sensitivity for aneuploidy detection. A key limitation of this feasibility study is the use of ultrasound as an interim standard for sex determination; we lacked definitive postnatal follow-up data. Definitive validation will require a subsequent publication with full newborn follow-up data. Larger multicenter studies with known aneuploidy cases are essential to validate sensitivity for trisomy 21 detection and establish clinical implementation protocols. This methodology offers potential advantages in resource-limited settings and could complement current prenatal screening strategies as a preliminary screening tool.

Integrative review of intelligent nuchal translucency for genetic disorder.

ABSTRACTBackgroundTo evaluate the utility of prenatal whole exome sequencing (WES) in cases of isolated increased nuchal translucency (NT).MethodsRetrospective analysis of the prenatal WES results in fetuses with increased NT (≥ 3.0 mm) and normal fetal anatomy, normal karyotype, and chromosomal microarray analysis (CMA). Subgroup analysis was performed based on NT measurements.ResultsDiagnostic variants were identified in 3 of 118 fetuses (2.5%) with isolated increased NT (≥ 3.0 mm). The distribution of positive findings was as follows: NT 3.0–3.4 mm group (n = 13): 1 case (7.7%) with diagnostic genetic variants; NT ≥ 3.5 mm group (n = 105): 2 cases (1.9%) with diagnostic genetic variants (both in the NT 5.0–6.4 mm subgroup). Fisher's exact test (two‐tailed) showed no statistically significant differences in diagnostic yield between: NT 3.0–3.4 mm versus NT ≥ 3.5 mm (p = 0.298); NT 3.0–3.4 mm versus NT 5.0–6.4 mm (p = 1.000); NT ≥ 3.0 mm versus NT ≥ 3.5 mm (p = 1.000).ConclusionOur analysis revealed a low diagnostic yield (2.5%) for prenatal WES in cases of isolated increased NT ≥ 3.0 mm. Our findings provide valuable evidence for clinical counseling, particularly when patients inquire about the likelihood of isolated findings. These data offer meaningful guidance for their decision‐making process regarding further testing options.

PurposeThis study aimed to evaluate the performance of the first-trimester Fetal Medicine Foundation (FMF) algorithm in predicting monosomy X and compare it with a Thai NT-based model using nuchal translucency (NT) alone or combined with maternal serum markers.Patients and MethodsThis retrospective study analyzed 6,860 singleton pregnancies screened at 11–13+6 weeks. Monosomy X risk was estimated based on the trisomy 21 risk calculated by the FMF algorithm and Thai logistic regression models based on NT alone, NT with pregnancy-associated plasma protein A (PAPP-A), and NT with PAPP-A and beta-human chorionic gonadotropin (β-hCG).ResultsThirty cases of monosomy X were identified (0.4%), all of which were confirmed prenatally by invasive diagnostic procedures, including amniocentesis, chorionic villus sampling, or cordocentesis. The Thai model using NT and PAPP-A had the highest area under the receiver operating characteristic curve (AUC) of 0.953, with a sensitivity of 86.7% and a specificity of 94.1%. NT alone also showed strong performance (sensitivity 83.3%, specificity 94.4%). The FMF algorithm achieved the highest specificity (97.9%) but lower sensitivity (53.3%). Adding β-hCG did not improve performance.ConclusionNT alone or combined with PAPP-A outperformed the FMF algorithm for monosomy X screening, with NT alone being particularly useful in settings without biochemical testing. The FMF algorithm, while primarily designed for trisomy 21 risk estimation, can also provide monosomy X risk within the same report at no additional cost, which is especially valuable in resource-limited settings where biochemical testing or NIPT is not widely accessible.

FAM20B encodes glycosaminoglycan xylosylkinase, a key enzyme in proteoglycan biosynthesis. Biallelic pathogenic variants have only recently been linked to skeletal dysplasia. We report two pregnancies from one couple, resulting in three fetuses (twin sibs and younger sib) with severe skeletal anomalies. Prenatal findings included enlarged nuchal translucency, short bowed and dislocated limbs, intrauterine growth restriction, and multiple malformations. Intra-uterine fetal death occurred in Probands 1 and 2, and neonatal death of Proband 3. Postnatally, all three probands showed limb shortening with joint (sub)luxations and contractures, and craniofacial dysmorphisms. SNP-array and exome analysis revealed compound heterozygosity for two novel FAM20B variants: a paternal ~8 kb deletion encompassing the terminal exon and a maternal missense variant (p.Arg290Cys) at an evolutionary conserved position. The same amino acid residue was previously affected in a child with a milder phenotype. In silico modeling supports a destabilizing effect of the missense change on protein structure, especially due to the loss of a salt bridge essential for catalytic function. This report describes the prenatal phenotype of FAM20B-related dysplasia and can help establish the phenotypic spectrum of the disorder. It further supports the essential role of FAM20B in early skeletal development.

To present prenatal sonographic features, genomic results of chromosomal microarray analysis (CMA) and exome sequencing (ES), and pregnancy outcomes of fetuses with Sotos syndrome, and to provide genetic counseling for at-risk pregnancies. This retrospective study analyzed 13 cases of prenatally diagnosed Sotos syndrome from January 2016 to March 2025. We collected and compared ultrasound findings, CMA and ES results, and pregnancy outcomes with the literature. All 13 cases exhibited de novo abnormalities in the NSD1 gene, with nine deletions identified through CMA and four pathogenic/likely pathogenic variants detected via ES, two of which were novel. The observed phenotypes included increased nuchal translucency (NT) (5/13), central nervous system (CNS) anomalies (6/13), and growth abnormalities (2/13). Additionally, polyhydramnios, cardiac anomalies, and renal anomalies were also noted. All pregnancies resulted in termination. Sotos syndrome presents with nonspecific symptoms during the early stages of gestation, except for increased NT. However, CNS anomalies begin to appear during the second and third trimesters. Furthermore, polyhydramnios should be noted. A comprehensive prenatal diagnosis of Sotos syndrome can be made through ultrasound and genetic testing.

ObjectiveFetal cleft lip and palate (CLP) is among the most common congenital craniofacial anomalies, posing significant physical and psychological burdens on affected families and contributing to increased societal and healthcare costs. We aimed to develop an individualized nomogram model incorporating fetal nuchal translucency thickness (NT), crown-rump length (CRL), and facial profile markers for predicting CLP in the first trimester of pregnancy.MethodsSingleton pregnancies undergoing first-trimester screening (11+0 to 13+6 weeks) were enrolled. Fetal NT, CRL, and ultrasonographic facial markers, including the frontomaxillary facial angle (FMFA) and inferior facial angle (IFA), were measured. Feature selection was performed using the least absolute shrinkage and selection operator algorithm, followed by multivariable analysis to establish a nomogram model. The model’s diagnostic performance was assessed through receiver operating characteristic (ROC) and precision-recall (PR) curves, calculating the area under the ROC curve (AUC) and area under the PR curve (AUPRC). Calibration curve analysis and decision curve analysis (DCA) were used to evaluate model calibration and clinical utility. Performance was compared with individual ultrasonographic facial markers.ResultsA total of 764 fetuses were included, comprising 732 normal and 32 CLP cases. The nomogram demonstrated excellent predictive performance with an AUC of 0.847 (95% CI: 0.751-0.944) and AUPRC of 0.689. The model achieved an accuracy of 0.977, F1-score of 0.640, sensitivity of 0.482, specificity of 0.999, positive predictive value of 0.955, and negative predictive value of 0.978. Compared to FMFA (AUC = 0.757), IFA (AUC = 0.708), NT (AUC = 0.714), and CRL (AUC = 0.592), the nomogram demonstrated significantly improved diagnostic performance (both P < 0.05). DCA confirmed the net clinical benefit of the model, and the calibration curve demonstrated good agreement between predicted and observed outcomes.ConclusionThe nomogram model integrating NT ≥ 2.5 mm, FMFA, CRL, and IFA demonstrates superior diagnostic performance for the first-trimester predicting of CLP compared with individual markers. Given its reliance on routinely measured parameters and ease of use, this model offers a practical, non-invasive, and efficient tool that may facilitate early detection of CLP in the first trimester of pregnancy.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12884-025-08274-9.

We describe a series of pregnancies with autosomal dominant lymphedema and generalized lymphatic dysplasia in the fetus diagnosed with prenatal exome or genome sequencing. We focus on specific syndromes, fetal features, and parental symptoms to deepen our understanding of congenital lymphatic anomalies. Pregnancies with one or more fetal effusions were prospectively enrolled from 2017 to 2024 and underwent exome or genome sequencing. Fetal effusions included increased nuchal translucency ≥3.5mm, cystic hygroma, pleural effusion, pericardial effusion, ascites, and/or skin edema. Records were reviewed to extract personal and family history, ultrasound findings, and pregnancy outcomes. Among 303 pregnancies with one or more fetal effusions, eight (3%) had a molecular diagnosis of autosomal dominant lymphedema or generalized lymphatic dysplasia. Gestational age at detection of fetal effusion(s) ranged from the first through third trimesters. Four fetuses inherited the genetic variant(s) from a biological parent. Of these, one parent was asymptomatic, and three had largely milder symptoms than their fetus. Perinatal outcomes were more favorable for fetuses with heterozygous PIEZO1 variants. Autosomal dominant lymphedema and generalized lymphatic dysplasia can present with a breadth of fetal effusions from the first through third trimesters and are frequently inherited from a biological parent with less severe symptoms. These data provide a deeper understanding of how congenital lymphatic anomalies manifest in utero and inform expectations about recurrence risk in future pregnancies.

Clinical and molecular analysis of seventy-one fetal cases with RASopathies.

Developing a transfer learning model for the prediction of Down syndrome from first-trimester ultrasound images.

ABSTRACTPurposeTo investigate the association between increased fetal nuchal translucency (NT) and maternal folate receptor alpha autoantibodies (FRAA) positivity, and to evaluate the subsequent risk of non‐syndromic autism spectrum disorder (ASD) in offspring.MethodsA total of 3600 first‐trimester ultrasounds were screened at a fetal medicine center. Among these, 27 fetuses with markedly increased NT (≥ 3.5 mm) underwent invasive prenatal diagnosis, including karyotyping, CGH array, and postnatally whole‐exome sequencing (WES) when standard tests were negative. Maternal serum samples were tested for FRAA using ELISA. Eleven pregnancies with negative genetic testing were followed longitudinally, and neurodevelopmental outcomes in children were assessed up to 36 months using ADOS‐2 and DSM‐5 criteria.FindingsAmong the 11 fetuses with negative genetic outcomes, 4 mothers tested positive for FRAA. All four FRAA‐positive offspring were later diagnosed with ASD, while only one of the seven FRAA‐negative offspring received an ASD diagnosis. FRAA‐positive cases exhibited markedly increased NT (≥ 3.5 mm) but no pathogenic genetic variants, suggesting an immune‐mediated etiology. FRAA levels persisted in maternal and neonatal serum, implying ongoing exposure during gestation.ConclusionFRAA positivity in pregnancies with isolated markedly increased NT may serve as an early biomarker of increased ASD risk in offspring. These findings support the hypothesis of an immune‐metabolic mechanism contributing to ASD and suggest potential preventive interventions such as folinic acid supplementation.