Search Results (82)

Background/Objectives: Preterm birth (PTB), defined as birth before 37 completed weeks of gestation, is a major global health challenge and a leading cause of neonatal mortality. PTB is broadly classified into spontaneous and medically indicated (iatrogenic), which have distinct etiologies. While prediction is key to improving outcomes, there is a lack of models that specifically differentiate between spontaneous and iatrogenic PTB subtypes. This study aimed to develop and validate predictive models for the prediction of spontaneous and iatrogenic PTB at <32, <34, and <37 weeks’ gestation using medical history and readily available second-trimester data. Methods: This was a retrospective cohort study on singleton pregnancies from a single tertiary institution (2012–2025). Predictor variables included maternal characteristics, obstetric history, and second-trimester ultrasound markers. Four algorithms, including multivariable Logistic Regression and three machine learning methods (Random Forest, XGBoost, and a Neural Network), were trained and evaluated on a held-out test set (20% of the data). Model performance was primarily assessed by the Area Under the Curve (AUC). Results: In total, 9805 singleton pregnancies were included. The models performed significantly better for iatrogenic PTB than for spontaneous PTB. For delivery <37 weeks, the highest AUC for iatrogenic PTB was 0.764 (Random Forest), while for spontaneous PTB it was 0.609 (Neural Network). Predictive accuracy improved for earlier gestations; for delivery <32 weeks, the best model for iatrogenic PTB achieved an AUC of 0.862 (Neural Network), and the best model for spontaneous PTB achieved an AUC of 0.749 (Random Forest). Model interpretation revealed that iatrogenic PTB was primarily driven by markers of placental dysfunction, such as estimated fetal weight by ultrasound scan and uterine artery pulsatility index, while spontaneous PTB was most associated with a history of PTB and a short cervical length. Conclusions: Models using routine mid-gestation data demonstrate effective prediction for iatrogenic PTB, with accuracy improving for earlier, more severe cases. In contrast, performance for spontaneous PTB was modest. Traditional Logistic Regression performed comparably to complex machine learning algorithms, highlighting that the clinical value is rooted in the subtype-specific modeling approach rather than in algorithmic complexity. Full article

Background/Objectives: The primary aim of this study was to describe all cases of fetal hemivertebrae diagnosed prenatally at the Hospital Clínico Universitario de Salamanca over the last 15 years. Additionally, the presence of associated malformations was assessed, pregnancy outcomes were evaluated, and child development results were analyzed in affected cases. Methods: We undertook a prospective observational analysis of all cases (N = 10) of prenatally diagnosed hemivertebrae at our hospital between 2007 and 2022. Postnatal follow-up was performed through telephone interviews and reviewing medical records. Results: Most cases were diagnosed during the second-trimester ultrasound, with the lumbar region being the most frequently affected site (60%). Multiple hemivertebrae were detected in 4 of 10 cases. One case of Marfan syndrome and two cases of VACTERL association (vertebral defects, anal atresia, tracheoesophageal fistula, renal dysplasia, and limb abnormalities) were documented. Six cases presented with additional malformations. Cases involving multiple hemivertebrae (40%) were more likely to be associated with other anomalies and poorer prognoses, while isolated single hemivertebra showed favorable outcomes, with normal development during childhood. Vaginal delivery occurred in six cases, while cesarean sections were performed for standard obstetric indications unrelated to the hemivertebra diagnosis. Conclusions: Prenatal diagnosis of hemivertebra is achievable and holds critical neonatal and postnatal relevance. Hemivertebrae are often linked to additional disorders, including genetic syndromes, and carry significant prognostic implications depending on the associated anomalies and the extent of vertebral involvement. Full article

Background: A short cervix in the second trimester significantly increases preterm birth risk, yet no reliable first-trimester prediction method exists. Current guidelines lack consensus on which women should undergo transvaginal ultrasound (TVUS) screening for cost-effective prevention. Therefore, it is vital to establish a highly accurate and economical method for use in the early stages of pregnancy to predict short cervix in mid-pregnancy. Methods: A total of 1480 pregnant women with singleton pregnancies and at least one risk factor for spontaneous preterm birth (<37 weeks) were recruited from January 2020 to December 2020 at the Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine. Cervical length was assessed at 20–24 weeks of gestation, with a short cervix defined as <25 mm. Feature selection employed tree models, regularization, and recursive feature elimination (RFE). Seven machine learning models (logistic regression, linear discriminant analysis, k-nearest neighbors, support vector machine, decision tree, random forest, XGBoost) were trained to predict mid-trimester short cervix. The XGBoost model—an ensemble method leveraging sequential decision trees—was analyzed using Shapley Additive Explanation (SHAP) values to assess feature importance, revealing consistent associations between clinical predictors and outcomes that align with known clinical patterns. Results: Among 1480 participants, 376 (25.4%) developed mid-trimester short cervix. The XGBoost-based prediction model demonstrated high predictive performance in the training set (Recall = 0.838, F1 score = 0.848), test set (Recall = 0.850, F1 score = 0.910), and an independent dataset collected in January 2025 (Recall = 0.708, F1 score = 0.791), with SHAP analysis revealing pre-pregnancy BMI as the strongest predictor, followed by second-trimester pregnancy loss history, peripheral blood leukocyte count (WBC), and positive vaginal microbiological culture results (≥10⁵ CFU/mL, measured between 11⁺⁰ and 13⁺⁶ weeks). Conclusions: The XGBoost model accurately predicts mid-trimester short cervix using first-trimester clinical data, providing a 6-week window for targeted interventions before the 20–24-week gestational assessment. This early prediction could help guide timely preventive measures, potentially reducing the risk of spontaneous preterm birth (sPTB). Full article

Background/Objectives: Cystic hygroma is a congenital lymphatic malformation often identified during early pregnancy and frequently associated with chromosomal abnormalities and adverse outcomes. We aimed to appraise the genetic and clinical characteristics of fetuses diagnosed with cystic hygroma in the first/early second trimester, assess the resolution patterns in chromosomally normal cases, and provide insights into prognosis—based on data collected over a 30-year period. Methods: A retrospective cohort study was conducted on 405 consecutive fetuses diagnosed with nuchal cystic hygroma between 8.0 and 14.0 weeks of gestation from 1993 to 2023 at two tertiary care centers. Diagnoses were established using high-resolution transabdominal and transvaginal 3D/4D ultrasonography. All cases underwent prenatal cytogenetic analysis, including karyotyping. Fetuses with a normal karyotype were observed through serial ultrasounds through the remainder of the pregnancy to verify the eventual resolution of hygromas. Both descriptive and inferential statistical methods were used, with p < 0.05 as a cut-off (two-tailed). Results: Of the 405 fetuses, 210 (51.9%) had chromosomal abnormalities, most commonly trisomy 21, while 195 (48.1%) had a normal karyotype. A significantly higher frequency of trisomy 21 was observed compared to other identified chromosomal abnormalities (p < 0.001). In the chromosomally normal group, 85 (43.6%) showed spontaneous resolution of the hygroma within four weeks, and these pregnancies resulted in phenotypically normal live births. Septated hygromas were significantly more frequent in the abnormal karyotype group (71.4%). Conclusions: The finding and diagnosis of cystic hygroma in first trimester and early second-trimester pregnancy represent a strong predictor of chromosomal aneuploidy and warrant comprehensive prenatal genetic testing and close follow-up. However, in the absence of genetic abnormalities and additional malformations, spontaneous resolution is common, and neonatal outcomes are generally favorable. Health systems should provide equitable access to genetic testing and fetal imaging to support accurate diagnosis and informed decisions. Full article

Objective: To describe first-trimester maternal, biochemical, biophysical, and ultrasound characteristics in women with recurrent pregnancy loss (RPL) compared to women without RPL. Methods: This was a retrospective cohort study analyzing data from 4440 pregnant women, including 142 women with previous RPL. Maternal and pregnancy characteristics, first-trimester biochemical markers, biophysical assessments, early-onset preeclampsia (EOPE) risk, and perinatal outcomes were compared. Results: Women with RPL were older (37.8 vs. 34.0 years, p < 0.001) and had higher rates of antiphospholipid syndrome (4.9% vs. 0.9%, p < 0.001), other thrombophilias (5.6% vs. 0.8%, p < 0.001), and thyroid disorders (14% vs. 7.5%, p = 0.010) than women without RPL. First-trimester uterine artery pulsatility index (UtA-PI) values, pregnancy-associated plasma protein-A (PAPP-A) levels, mean arterial pressure, and final risk for EOPE were comparable between groups. However, the RPL group had higher rates of very high risk for PE (10.6 vs. 5.1, p = 0.011). Likewise, second-trimester UtA-PI was higher in this group (1.10 vs. 1.01, p = 0.045). Aspirin and low molecular weight heparin prophylaxis were more frequent in women with RPL (23.8% vs. 9.6%, p < 0.001; 14.7% vs. 0.1%, p < 0.001). Regarding perinatal outcomes, we found a higher incidence of second-trimester intrauterine demise in the RPL group (6.4% vs. 1.4%, p = 0.011), with no other differences observed in the remaining outcomes. Conclusions: Women with RPL exhibit distinct maternal characteristics and worse pregnancy outcomes, although first-trimester markers do not seem to significantly differ from findings in women without RPL. These findings underscore the importance of tailored screening and intervention protocols to improve perinatal outcomes in this high-risk population. Full article

Background and Objectives: Congenital abnormalities are a leading cause of neonatal morbidity and mortality and are frequently detectable through prenatal ultrasound. While widely implemented in high-income countries, such screening remains inconsistently applied in low- and middle-income regions. This study aimed to estimate the prevalence of congenital abnormalities identified via prenatal ultrasound in Lebanon and to explore associated maternal, obstetric, and psychosocial factors. Methods: A multicenter retrospective observational study, supplemented by follow-up interviews, was conducted in five Order of Malta medical centers. Pregnant women in their second trimester underwent an obstetric ultrasound, and data were collected through structured questionnaires and follow-up phone interviews. Variables included maternal demographics, obstetric history, anxiety levels (GAD-7 scores), and ultrasound findings. Results: A total of 426 pregnant women were enrolled (mean age: 28.8 ± 5.9 years). The overall prevalence of congenital abnormalities was 13.1%. Growth abnormalities were observed in 8.5% of fetuses and were significantly associated with obstetric complications and the presence of multiple abnormalities. Morphological malformations were found in 10.1% of cases and were more common among women of advanced maternal age, those with a history of anomalies, and those reporting elevated anxiety scores. Combined abnormalities, as well as growth and morphological malformations, were significantly associated with higher parity, prior anomalies, and current pregnancy complications. Conclusions: Prenatal ultrasound is essential for early detection of congenital abnormalities, facilitating timely intervention and improved neonatal outcomes. These findings emphasize the need to integrate systematic screening into prenatal care in Lebanon and for ongoing research to identify context-specific risk factors. Full article

Introduction: Gestational diabetes mellitus (GDM) is a form of hyperglycemia that develops during pregnancy and poses risks to both the mother and fetus. In other words, it is a glucose intolerance disorder first recognized during pregnancy, specifically in the second and third trimesters, with approximately 7–14% of pregnancies worldwide being affected. Methodology: A systematic literature search was conducted across three major well-established databases; PubMed, Scopus, and ScienceDirect. The search was conducted with the aim of identifying the most suitable studies for the evaluation of fetal cardiac function using Doppler ultrasound techniques in pregnancies affected by GDM. Results: Following a comprehensive full-text assessment, 186 papers were excluded, mainly due to discrepancies in the population, unsuitable study design, publishing type, or unavailability of full-text access. Ultimately, 12 studies met all the inclusion criteria and were incorporated into the scoping review. From the studies included it was found that the conventional pulsed-wave Doppler was the most frequently used modality, assessing parameters such as the E/A ratios, myocardial performance index (MPI), and the isovolumic relaxation time (IVRT). The advanced techniques of choice included tissue Doppler imaging (TDI), speckle-tracking echocardiography (STE), dual-gate Doppler, and automated MPI. Conclusions: Doppler ultrasound techniques, particularly the advanced modalities like TDI and STE, provide valuable insights into fetal cardiac function in GDM pregnancies. Their integration into routine prenatal surveillance may enhance the early detection of cardiac dysfunction and inform timely clinical interventions. Full article

This study applies Computational Fluid Dynamics (CFD) and mathematical modeling to examine uterine and umbilical arterial blood flow during pregnancy, providing a more detailed understanding of hemodynamic changes across gestation. Statistical analysis of Doppler ultrasound data from a large cohort of more than 200 pregnant women (in the second and third trimesters) reveals significant increases in the umbilical arterial peak systolic velocity ($PSV$) between the 22nd and 30th weeks, while uterine artery velocities remain relatively stable, suggesting adaptations in vascular resistance during pregnancy. By combining the Navier–Stokes equations with Doppler ultrasound-derived inlet velocity profiles, we quantify several key fluid dynamics parameters, including time-averaged wall shear stress ($TAWSS$), oscillatory shear index ($OSI$), relative residence time ($RRT$), Reynolds number ($Re$), and Dean number ($De$), evaluating laminar flow stability in the uterine artery and secondary flow patterns in the umbilical artery. Since blood exhibits shear-dependent viscosity and complex rheological behavior, modeling it as a non-Newtonian fluid is essential to accurately capture pulsatile flow dynamics and wall shear stresses in these vessels. Unlike conventional imaging techniques, CFD offers enhanced visualization of blood flow characteristics such as streamlines, velocity distributions, and instantaneous particle motion, providing insights that are not easily captured by Doppler ultrasound alone. Specifically, CFD reveals secondary flow patterns in the umbilical artery, which interact with the primary flow, a phenomenon that is challenging to observe with ultrasound. These findings refine existing hemodynamic models, provide population-specific reference values for clinical assessments, and improve our understanding of the relationship between umbilical arterial flow dynamics and fetal growth restriction, with important implications for maternal and fetal health monitoring. Full article

Objectives: To evaluate the association between late CVS (placental biopsy, later than 13 weeks of gestations) and complications between sampling and delivery in 8599 cases in the Department of Obstetrics and Gynecology of a private hospital Podobnik, Zagreb, Croatia. Methods: Late chorionic villus sampling under ultrasound guidance was carried out in prospective monocentric cohort study of 7859 (91.4%) cases in the second trimester and 700 (8.6%) cases in the third trimester of pregnancy. Out of 8599 late CVS cases, 1476 (17.2%) were performed because of suspicious ultrasonographic findings. Results: In 43 patients (0.50%), complications were found between sampling and delivery. There were only 12 (0.15%) spontaneous abortions four to six weeks after late CVS (before 28 weeks). We found 190 (2.3%) chromosomal abnormalities. In the group with suspicious ultrasonographic findings, comparing 1476 cases, we found significant oligohydramnios in 375 (25.4%), significant polyhydramnios in 197 (13.3%) and chromosomal abnormalities in 125 (8.5%) cases. Among the 190 patients with chromosomal abnormalities, ultrasonographic findings were detected in 98 (49.2%) after the 22th week of pregnancy. Conclusions: Late CVS is a safe method of invasive prenatal diagnosis with lower spontaneous abortions rate (0.15%). This method, applicable after 13 weeks of gestation, offers a more flexible approach to invasive prenatal diagnosis of chromosome abnormalities, in very specialized fetal-maternal centres for this method. Full article

Background: Physical exercise during pregnancy is strongly recommended due to its well-established benefits for both mother and child. However, its impact on the pelvic floor remains insufficiently studied. This study aimed to evaluate pelvic floor adaptations to a structured prenatal exercise program using transperineal ultrasound, and to assess associations with the duration of the second stage of labor and mode of delivery. Methods: This is a planned secondary analysis of a randomized controlled clinical trial (RCT) (NCT04563065) including women with singleton pregnancies at 12–14 weeks of gestation. Participants were randomized to either an exercise group, which followed a supervised physical exercise program three times per week, or a control group, which received standard antenatal care. Transperineal ultrasound was used at the second trimester of pregnancy and six months postpartum to measure urogenital hiatus dimensions at rest, during maximal pelvic floor contraction, and during the Valsalva maneuver, to calculate hiatal contractility and distensibility and to evaluate levator ani muscle insertion. Regression analyses were performed to assess the relationship between urogenital hiatus measurements and both duration of the second stage of labor and mode of delivery. Results: A total of 78 participants were included in the final analysis: 41 in the control group and 37 in the exercise group. The anteroposterior diameter of the urogenital hiatus at rest was significantly smaller in the exercise group compared to controls (4.60 mm [SD 0.62] vs. 4.91 mm [SD 0.76]; p = 0.049). No other statistically significant differences were observed in static measurements. However, contractility was significantly reduced in the exercise group for both the latero-lateral diameter (8.54% vs. 4.04%; p = 0.012) and hiatus area (20.15% vs. 12.55%; p = 0.020). Distensibility was similar between groups. There were no significant differences in the duration of the second stage of labor or mode of delivery. Six months after delivery, there was an absolute risk reduction of 32.5% of levator ani muscle avulsion in the exercise group compared to the control group (53.3% and 20.8%, respectively; p = 0.009). Conclusions: A supervised exercise program during pregnancy appears to modify pelvic floor morphology and function, reducing the incidence of levator ani muscle avulsion without affecting the type or duration of delivery. These findings support the safety and potential protective role of prenatal exercise in maintaining pelvic floor integrity. Full article

Background: Hydatid disease, caused by the larval form of Echinococcus granulosus, is a rare but potentially life-threatening condition during pregnancy, with an estimated incidence of 1 in 20,000 to 30,000 gestations. Physiological immunosuppression and increased placental steroid levels during pregnancy may promote cyst growth, elevating the risk of rupture, which can result in anaphylactic shock, sepsis, or widespread peritoneal dissemination. Diagnostic imaging, particularly ultrasonography, plays a central role in detection, while treatment decisions are complicated by the lack of standardized guidelines and the need to balance maternal–fetal safety. Methods: This case report describes a 29-year-old pregnant woman at 22 weeks’ gestation who was incidentally diagnosed with two large hepatic hydatid cysts during a routine ultrasound. Results: Given the high rupture risk, she underwent successful laparoscopic surgery in the second trimester, followed by careful monitoring and elective cesarean delivery at term. A third retroperitoneal cyst, initially managed conservatively, was excised postpartum. Conclusions: This case highlights the critical importance of individualized, multidisciplinary management in achieving favorable maternal and neonatal outcomes in complex presentations of hydatid disease during pregnancy. Full article

Background and clinical significance: Ectopic ureters are a rare urinary tract malformation, typically diagnosed in childhood and infrequently in adulthood. The prenatal detection by ultrasound and magnetic resonance imaging (MRI) of this clinical entity has scarcely been reported. Careful foetal scanning during the late second and third trimester might provide clues and lead to prenatal detection. However, even the postnatal diagnosis is challenging, and often delayed towards adulthood, since the condition may present with nonspecific symptoms, leading to underdiagnosis or misdiagnosis. In female patients, approximately 25% of ectopic ureters open into the vagina. Due to the high risk of recurrent urinary tract infections and the potential development of uretero-hydronephrosis, timely diagnosis is essential, and prompt surgical correction is mandated. Case presentation: We report the case of a 33-year-old GII PI patient diagnosed with cystic dysplasia of the left foetal kidney at the 16 WG (weeks of gestation) scan. The malformation was consistent at 21 WG when karyotyping by amniocentesis identified a normal female molecular karyotype. MRI performed at 28 weeks confirmed the left renal dysplasia and raised the suspicion of an abnormal insertion of the left ureter into the vagina. After delivery, the vaginal ureteral ectopy was confirmed at 3 weeks postpartum via cystoscopy. Postpartum whole exome sequencing identified a variant of uncertain significance (VUS) mutation in the SOX 13 gene (SRY-box transcription factor 13). Renal scintigraphy performed 7 months postnatally identified a hypo/afunctional left kidney which led to the indication of nephrectomy by the paediatric urologist. The surgical intervention was performed at 8 months postpartum with a favourable outcome. Conclusions: Ectopic ureters are a pathology generating life-long morbidity and discomfort of the offspring and young adult. Awareness to this pathology must be raised among clinicians, especially regarding the potential detection by minute prenatal ultrasound examinations, followed by MRI to refine diagnosis. Postnatally, the persistence of suspicious yet unspecific symptoms, in both males and females, must trigger thorough imaging/cystoscopic examination to reach diagnosis and provide correct management. Full article

Background and Clinical Significance: Prader–Willi syndrome (PWS) is a rare genetic disease caused by imprinted gene dysfunction, typically involving deletion of the chromosome 15q11.2-q13 region, balanced translocation, or related gene mutations in this region. PWS presents with complex and varied clinical manifestations. Abnormalities can be observed from the fetal stage and change with age, resulting in growth, developmental, and metabolic issues throughout different life stages. Case Presentation: We report the prenatal characteristics observed from the second to third trimester of pregnancy in a neonate with PWS. Prenatal ultrasound findings included a single umbilical artery, poor abdominal circumference growth from 26 weeks, normal head circumference and femur length growth, increased amniotic fluid volume after 30 weeks, undescended fetal testicles in the third trimester, small kidneys, and reduced fetal movement. The male infant was born at 38 weeks of gestation with a birth weight of 2580 g. He had a weak cry; severe hypotonia; small eyelid clefts; bilateral cryptorchidism; low responsiveness to medical procedures such as blood drawing; and poor sucking, necessitating tube feeding. Blood methylation-specific multiple ligation-dependent probe amplification (MS-MLPA) showed paternal deletion PWS. Notably, this case revealed two previously unreported prenatal features in PWS: a single umbilical artery and small kidneys. Conclusions: Through literature review and our case presentation, we suggest that a combination of specific sonographic features, including these newly identified markers, may aid clinicians in the early diagnosis of PWS. Full article

Background and Objectives: Pregnancies resulting from assisted reproductive technology (ART) have been associated with placenta-related adverse outcomes. Uterine artery Doppler pulsatility index (UtA-PI) reflects placental function. This study aimed to examine whether second-trimester UtA-PI differs according to the conception method after adjusting for potential confounding factors. Materials and Methods: In this retrospective cohort study, we included data from February 2015 to August 2024, at the third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece, on singleton pregnancies presenting for their routine antenatal care, including a second-trimester anomaly scan. Pregnancies conceived via ART, including those conceived via ovulation induction/intrauterine insemination (OI/IUI) or in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), were compared to those conceived spontaneously. Multiple linear regression was employed to investigate the association between the mode of conception and log₁₀ UtA-PI values, adjusting for various confounders, including gestational age at the time of the scan, maternal weight, height, age, parity, mode of delivery, smoking status, pre-existing diabetes mellitus (type I or II), and pre-existing thyroid disease. Results: The study included 15,552 singleton pregnancies, of which 82 (0.5%) were conceived via OI/IUI and 690 (4.4%) were conceived via IVF/ICSI. The median UtA-PI values were 0.99 (IQR: 0.85–1.17) for spontaneous conception (SC), 1.00 (IQR: 0.86–1.16) for OI/IUI, and 0.90 (IQR: 0.76–1.12) for IVF/ICSI. The Kruskal–Wallis test indicated a statistically significant difference among these groups (p < 0.001). Pairwise comparisons using the Wilcoxon rank-sum test with Bonferroni correction revealed that UtA-PI values in IVF/ICSI pregnancies were significantly lower compared to both SC and OI/IUI pregnancies (p < 0.001 for both). No significant difference was observed between the SC and OI/IUI groups. In the multivariable linear regression model, IVF/ICSI conception was independently associated with lower log₁₀ UtA-PI values (estimate = −0.076, 95% CI: −0.096, −0.056) while no association was found for OI/IUI conception. Conclusions: Although ART has been associated with placental-related complications, mid-trimester UtA flow was found to be lower in IVF/ICSI pregnancies, suggesting better utero-placental flow in ART pregnancies and other possible mechanisms in the maternal–placental interplay for the development of pregnancy complications. Full article

Background: Noonan syndrome (NS) is a relatively common RASopathy that can be associated with a variety of phenotypic and genotypic variations and potential long-term health consequences. Its most described prenatal ultrasound features in the first trimester are thickened nuchal translucency (NT) and dilated jugular sacs; while heart defects, polyhydramnios and facial dysmorphisms are its known manifestations in the second and third trimesters. Methods: We present two cases of NS with the prenatal ultrasound diagnosis of external hydrocephalus (EH) in the second trimester. Results: Case 1 had a normal first trimester scan and showed mild polyhydramnios, an echogenic intracardiac focus (EIF) in the left ventricle and pyelectasis in the second trimester in association with the EH. The whole exome sequencing (WES) confirmed a pathogenic variant in the SOS1 gene. Case 2 showed increased NT, agenesis of the ductus venosus (DV), single umbilical artery (SUA), an EIF in the right ventricle and an abnormal prefrontal space ratio (PSFR). By the 19th gestational week, EH appeared. The ambient and quadrigeminal cisterns were also slightly widened. The WES revealed a PTPN11 gene variant. Conclusions: The most reported sonographic features of NS are either non-specific or difficult to integrate into routine screening, requiring substantial experience. In our two cases, we detected EH in the second trimester, which is rarely described as a prenatal ultrasound diagnosis. To our current knowledge, this is the first case reported of EH in NS caused by an SOS1 gene variant and these are the first cases reported with the prenatal sonographic diagnosis of EH in NS. Full article