Search Results (667)

Background: Monozygotic twin pregnancies are at increased risk of congenital abnormalities compared to singletons. In 20% of cases, both fetuses are affected (concordance), while in 80% of cases, only one fetus is affected (discordance). This study examines the prevalence of discordance for structural defects in monochorionic (MC) twins, with normal aCGH comparative genomic hybridization (aCGH), reporting the types of detected abnormalities and their possible impact on perinatal outcomes, including the rate of single and double fetal loss before 24 weeks’ gestation and the rate of preterm birth (PB) before 32 weeks’ gestation. Methods: This was a retrospective study of discordant structural fetal anomalies in MC twin pregnancies detected at first-trimester scanning in three fetal medicine centers in Poland. Results: In the study population of 381 monochorionic twin pregnancies examined at 11–13 weeks’ gestation, 21 (5.5%) pregnancies showed discordant structural defects with normal aCGH result. The most common were cardiac defects (n = 8), followed by central nervous system (CNS) (n = 6) defects and facial anomalies (n = 3). Single or double fetal loss before 28 weeks occurred in four (19%) and two (9%) cases, respectively, and was associated with intertwin crown–rump length (CRL) discordance greater than 20% (p = 0.046). PB before 32 weeks’ gestation occurred in nine cases (47%) and was strongly associated with polyhydramnios (p = 0.001), which occurred mainly in CNS and facial defects. Conclusions: The prevalence of discordant structural defects with normal aCGH results among monochorionic twins is approximately 5%. In pregnancies with discordant defects, cardiac defects are the most common. Intertwin discordance greater than than 20% is associated with an increased risk of fetal demise. Full article

Background/Objectives: Maternal immune activation (MIA) increases the risk of Autism Spectrum Disorders (ASD). Experimental models demonstrate that maternal exposure to bacterial endotoxin or the viral mimic polyinosinic:polycytidylic acid [poly (I:C)] reliably recapitulates ASD-like behavioral abnormalities in offspring, yet the underlying neurobiological mechanisms linking MIA to altered neurodevelopment remain incompletely understood. Increasing evidence highlights the placenta as a critical mediator in shaping fetal brain development through immunological and hormonal regulation. Likewise, disruption of placental regulatory functions upon MIA may therefore represent a mechanistic pathway. Here, we investigated how alterations in placental cytokine profiles, innate immune cell composition, and endocrine outputs relate to neuroinflammation and neurogenesis in the offspring. Methods: Pregnant mice at gestational day 12.5 received a single intraperitoneal injection of poly (I:C). Placental macrophages, neutrophils, inflammatory cytokines, and nerve growth factor (NGF) expression were examined 72 h later. Neurodevelopmental outcomes, including microglial activity and neurogenic markers, were evaluated in mouse offspring at postnatal day (P) 1 and 6. Results: MIA induced a significant accumulation of monocytes and neutrophils in the placenta, which was associated with elevated levels of a broad spectrum of inflammatory mediators, including Th17-biased proinflammatory cytokines, chemokines, and adhesion proteins, in the placenta and amniotic fluid. In contrast, the placenta-derived NGF levels were significantly reduced. MIA induced strong and sustained microglial activation in the fetal and neonatal brain. This inflammatory milieu was accompanied by disrupted cortical neurogenesis, characterized by a marked increase in Ki67+ neuronal progenitor cells (NPCs) in the subventricular zone (SVZ), overproduction of early-born Tbr1+ neurons at P1, later-born Satb2+ neurons at P6. Conclusions: Collectively, these findings suggest that heightened Th17 inflammatory signaling, coupled with impaired placental endocrine function, contributes to dysregulated cortical neurogenesis in the offspring. Full article

Background: Congenital cytomegalovirus (cCMV) infection is a leading cause of neonatal morbidity. This retrospective study aimed to evaluate the efficacy of valacyclovir in reducing vertical transmission after primary maternal CMV infection and to assess the diagnostic performance of amniocentesis and prenatal imaging. Methods: Eighty-two pregnant women with confirmed primary CMV infection were included. Maternal CMV serology and viral DNA were assessed in blood and urine, with standardized prenatal care including serial ultrasound examinations and fetal MRI when indicated. Amniocentesis was offered to confirm fetal infection. Valacyclovir (8 g/day) was administered before 24 weeks’ gestation, and neonatal infection was diagnosed by CMV DNA detection in urine at birth. Statistical analyses were performed using SPSS version 27.0. Results: Most infections (62.2%) were diagnosed in the first trimester. Valacyclovir was administered in 97.6% of cases, and amniocentesis was performed in 81.7%, with CMV DNA detected in 19.4%. Among 74 live births, 23% of neonates were CMV-positive and 6.8% symptomatic. Seven infected neonates had negative amniocentesis (false-negative rate, 13.2%). Prenatal ultrasound and MRI failed to detect abnormalities in symptomatic cases. Conclusions: Valacyclovir may reduce, but does not eliminate, the risk of cCMV transmission. Negative amniocentesis does not fully exclude fetal infection, highlighting postnatal follow-up. Full article

Background: Fetal growth restriction (FGR) is a significant obstetric complication associated with increased perinatal morbidity and long-term developmental risks. Despite advances in prenatal diagnosis, the genetic etiology of isolated FGR remains incompletely characterized, complicating genetic counseling and clinical management. Objective: This study aimed to systematically evaluate the genetic causes of isolated FGR by integrating karyotyping, chromosomal microarray analysis (CMA), and trio-based whole exome sequencing (trio-WES) and to assess the incremental diagnostic yield of this sequential approach. Methods: A retrospective cohort of 153 fetuses with isolated FGR (diagnosed by ultrasound between February 2018 and July 2024) underwent karyotyping and CMA. Cases with normal results from both tests (n = 50) were subsequently analyzed by trio-WES. Results: Karyotyping identified chromosomal abnormalities in three cases (2.0%). CMA detected pathogenic/likely pathogenic copy number variations (CNVs) or uniparental disomy (UPD) in twelve cases (7.8%), including the three karyotypic abnormalities and nine additional cases (5.9% incremental yield). Trio-WES performed on 50 CMA-negative cases identified pathogenic or likely pathogenic variants in 12 cases (24%). Among these, seven cases (14% of the WES subgroup) harbored variants directly causative of FGR, including one case of UPD(6) missed by CMA alone. Additionally, trio-WES revealed seven incidental pathogenic/likely pathogenic variants not directly linked to FGR and identified one case in which FGR was attributed to maternal hyperphenylalaninemia. Conclusions: The sequential application of CMA and trio-WES significantly improves the diagnostic yield for isolated FGR. Trio-WES proved particularly valuable in detecting UPD and single-gene variants missed by CMA alone and in revealing contributory maternal genetic conditions. These findings support the integration of advanced genetic testing into the diagnostic workup for isolated FGR to enhance etiological diagnosis, facilitate comprehensive genetic counseling, and inform multidisciplinary management. Full article

Doppler assessment of fetal cerebral circulation has become a cornerstone of modern fetal medicine. It is used to evaluate cerebral vascular malformations, brain anomalies, fetal growth restriction due to placental insufficiency, fetal anemia, and hemodynamic complications arising from placental vascular anastomoses in monochorionic pregnancies. Emerging research also explores the predictive value of Doppler parameters for perinatal outcomes and long-term neurodevelopment. To review the anatomy and physiology of fetal cerebral vessels accessible to Doppler evaluation, outline key technical aspects, and summarize current obstetric applications. A PubMed search identified 113 relevant publications, published between 1984 and 2025. Three book chapters by authors recognized internationally within the scientific community were included. A total of 116 publications were critically analyzed in this narrative review. Strong evidence supports the use of Doppler ultrasound in obstetrics, particularly for evaluating fetal cerebral hemodynamics, where it contributes to reducing fetal morbidity and mortality. Doppler assessment of fetal brain circulation is a valuable tool for evaluating brain vascular malformations, other structural abnormalities, and for assessing fetuses with growth restriction, anemia, and twin-to-twin transfusion syndrome. It allows targeted fetal monitoring and timely interventions, providing critical prognostic information and aiding parental counseling. Ongoing advances in Doppler technology and understanding of fetal brain physiology are likely to broaden its clinical uses, improving both perinatal outcomes and long-term neurological health. Full article

Peters-Plus syndrome is a rare autosomal recessive disorder caused by biallelic pathogenic variants in the B3GLCT gene and characterized by multisystem involvement. Fewer than 100 cases have been reported to date, and only a limited number have been diagnosed prenatally. Prenatal identification is challenging due to the variable and non-specific nature of fetal findings and the frequent absence of detectable ocular anomalies during routine ultrasound. We report a prenatal diagnosis of Peters-Plus syndrome in a monochorionic diamniotic twin pregnancy, based on the progressive identification of early-onset intrauterine growth restriction, rhizomelic limb shortening, craniofacial dysmorphism, and mild central nervous system abnormalities. Standard cytogenetic and chromosomal microarray analyses were normal, prompting extended genetic testing. Prenatal exome sequencing identified a homozygous pathogenic splice-site variant (c.660+1G>A) in B3GLCT in both fetuses, confirming the diagnosis. This case highlights the importance of recognizing suggestive multisystem prenatal findings and the crucial role of advanced genetic testing in achieving an accurate prenatal diagnosis. Early molecular confirmation enables appropriate parental counseling regarding prognosis, recurrence risk, and future reproductive options. Full article

Background/Objectives: Our aim was to investigate the diagnostic accuracy of prenatal ultrasound (US) in fetal limb abnormalities. As a secondary target, we wanted to correlate various predictors for the diagnosis accuracy. Methods: We prospectively enrolled cases with routine prenatal US performed in five participating centers. Subsequently, we selected and processed all cases with limb abnormalities: suspected, diagnosed, and missed on the prenatal diagnosis scans. We collected data on the type of anomaly, the US equipment and probes used, the operator’s expertise, the gestational age at the diagnosis, the length of the examination, and the use of US reporting form. SPSS 22.0 software was applied to perform the analyses using non-parametric statistical methods. Associations between categorical variables were evaluated using Fisher’s exact test and Chi-square tests. For correlations between the gestational age and the anomaly severity, we used Spearman’s rank-order correlation. Predictive performance of operator- and scan-related variables for diagnostic accuracy was assessed using receiver operating characteristic (ROC) curve analysis, with area under the curve (AUC) estimates, standard errors (SE), confidence intervals (95% CI), and p-values reported. Results: Our data showed that most US examinations were performed as part of routine screening (79.7%), and the most frequent anomaly diagnosed was clubfoot. Operators’ expertise demonstrated the highest predictive performance, while technical parameters—scan duration (AUC = 0.20, p = 0.1188) and US equipment (AUC = 0.30, p = 0.3478)—did not significantly predict diagnostic accuracy. Conclusions: The overall diagnostic accuracy of prenatal US was 85.5%. Our findings indicate that diagnostic performance is driven primarily by operator expertise and training, rather than by gestational age at scan and technical parameters. Full article

Sjögren’s disease (SjD), which is also known as Sjögren’s syndrome (SS), is a chronic autoimmune disease characterized by dysfunction of exocrine glands, such as the salivary and lacrimal glands, resulting in xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). Mice in which the SATB1 gene is conditionally deleted in hematopoietic cells (SATB1cKO mice) develop SS as early as 4 weeks of age; however, the etiology of the disease remains to be elucidated. Here, we found that the frequency of abnormally appearing CD4⁺CD8⁺ double positive (DP) T cells in the periphery of SATB1cKO mice was higher in the salivary glands than that in the spleen, suggesting a possible involvement of DP T cells in the pathogenesis of SS in SATB1cKO mice. To investigate the nature of DP T cells, we established DP T cell hybridomas by fusing T cells from the cervical lymph nodes of SATB1cKO mice with the BW5147 thymoma cell line. Among six DP hybridoma clones, the TCRβ gene from five clones exhibited a fetal or immature phenotype. In addition, four out of five clones exhibited upregulated transcription of IL-2 in the salivary glands of T/B cell-deficient RAG2^−/− mice, suggesting that autoreactive T cells were enriched in the DP T cell population of SATB1cKO mice. These results suggest that unusual DP T cells in SATB1cKO mice may be involved in autoimmune pathogenesis in SATB1cKO mice. Full article

Background/Objectives: Intrauterine growth restriction (IUGR) is a condition in which a fetus does not reach its normal growth potential and is associated with increased neonatal morbidity. Surveillance relies on cardiotocography, a biophysical ultrasound, and a Doppler assessment, but placental pathology remains insufficiently integrated into clinical evaluations. This study aimed to compare placentas from IUGR and normal pregnancies. Methods: This cohort included 34 pregnancies (16 IUGR, 18 controls) managed at Hunedoara County Hospital (Romania). The ultrasound and Doppler parameters were documented. The placentas were collected after delivery, fixed in formalin, and processed using standard histopathological protocols. The villous morphology and maternal vascular malperfusion features were assessed on H&E sections, focusing on syncytial knots, villous caliber reduction, stromal fibrosis, fibrin deposition, and infarctions. Immunohistochemistry for CD34, cytokeratin 7 (CK7), CD68, vascular endothelial growth factor (VEGF), and Hypoxian inducible factor 1 (HIF-1α)was performed using a semi-quantitative 0–3 scoring system. A statistical analysis was performed using chi-squared testing for categorical variables and t-tests for continuous variables. Results: The ultrasound evaluation showed an estimated fetal weight below the 10th percentile and abnormal Doppler indices in the IUGR group. The histopathology demonstrated a strong association between IUGR and villous abnormalities, including an increased number of syncytial knots, stromal fibrosis, a reduced villous caliber, and placental infarctions. The immunohistochemistry showed a marked overexpression of VEGF and HIF-1α and increased CD68-positive Hofbauer cells in IUGR placentas (p < 0.0001), while CD34 and CK7 displayed preserved strong staining in both groups. Conclusions: Placentas from IUGR pregnancies exhibited advanced maternal vascular malperfusion with consistent hypoxic and inflammatory changes, correlating with Doppler alterations. These findings highlight the diagnostic relevance of placental pathology in pregnancies with IUGR. Full article

Background/Objectives: The antenatal management of Down syndrome (DS) is difficult as it is associated with a high risk for in utero fetal demise (IUFD) with a paucity of literature to guide antenatal surveillance. Avoidance of preterm delivery in the DS fetus, so commonly affected by anomalies, compounds the dichotomy of achieving term delivery while balancing against the risk for IUFD as gestational age advances. Higher-performing tests are needed to predict, and, thus, hopefully prevent, both preterm delivery and fetal mortality. Our study was undertaken to evaluate the performance metrics of current antenatal surveillance parameters that might suggest an increased risk for IUFD. Methods: We studied a retrospective cohort of all continuing pregnancies with a cytogenetically confirmed DS fetus between 2009 and 2019 at a single institution. Cases were investigated for abnormalities in fetal growth, anatomy, UA Doppler, and amniotic fluid volume to analyze their interrelationships and their association with the primary outcome, IUFD. Nonstress testing (NST) and biophysical profile data as available were also reviewed for analysis on each case. Maternal demographic data were also collected. Results: A total of 41 DS pregnancies at >20 weeks gestation were included. Eight (19.5%) resulted in IUFD, while thirty-three (80.5%) resulted in live birth. Between these groups, there was no significant difference in the incidence of fetal structural anomalies. FGR was present in 8/41 fetuses or 19.5% of all cases. FGR was present in 1 of 8 (12.5%) IUFD cases and 7 of 33 (21.2%) live births (p = 0.50). Thus, notably, 87.5% (7/8) of the IUFDs occurred in the absence of FGR. Furthermore, 1/8 (12.5%) FGR cases resulted in IUFD vs. 7/33 (21.2%) of non-FGR cases (p = 0.50). In DS fetuses after 24 weeks gestation, UA Doppler abnormalities developed in 75% of FGR cases (6/8) and in 64.5% of normally grown cases (20/31) (p = 0.33). Abnormal UA Dopplers were noted in 83.3% of IUFD and in 84.8% of liveborn cases (p = 0.34). Eleven of thirty-three live births, however, underwent iatrogenic delivery secondary to worsening fetal surveillance, including ten with worsening UA Doppler indices. There was an increased frequency of abnormal NST in the IUFD group (66.7% vs. 23.8%), although this difference did not reach statistical significance. Polyhydramnios was more frequent in the IUFD group (62.5% vs. 16.1%, p = 0.04). Conclusions: Aside from polyhydramnios, no fetal surveillance parameter demonstrated an association with IUFD that reached statistical significance. A majority of fetuses with DS are normally grown and demonstrate abnormal UA Doppler indices in the absence of FGR. Within our cohort, a substantial number of liveborn deliveries were prompted following worsening UA Dopplers. Both polyhydramnios and UA Doppler indices are worthy of further investigation to inform clinically useful fetal surveillance strategies in DS. Full article

Inferior vena cava (IVC) disruption with continuation of the azygos is a rare congenital vascular abnormality that can be detected prenatally via high-resolution ultrasound. We present a case of isolated discontinuation of IVC, diagnosed during a routine abnormal scan of the second trimester, confirmed by fetal echocardiography, with an uneventful neonatal outcome. In accordance with the literature, we discuss the diagnostic approach, clinical significance and long-term implications of this vascular variant. We want to emphasize the importance of recognizing this anomaly and differentiating isolated cases from those associated with other congenital malformations. Full article

Introduction: Primary Cytomegalovirus (CMV) infection occurs in 0.7–4.1% of all pregnancies. Our study aims to analyze the incidence rate of ultrasound anomalies, as well as CMV PCR analysis of the amniotic fluid sample obtained from amniocentesis in CMV-infected pregnancies, as well as the outcome of the pregnancies and neonatal follow-up. Methods: We analyzed cases of recent maternal CMV infections confirmed by serological testing at the Department of Obstetrics and Gynecology, Semmelweis University, between 2001 and 2023. In cases of primary CMV infection confirmed by serological testing during pregnancy, we offered amniocentesis at the genetic counseling, which was performed at the 20–21 weeks stage of the pregnancy. Results: In 130 cases of recent maternal CMV infection confirmed by serological testing, amniocentesis was performed, and a total of 11 cases (8.46%) were found to have CMV DNA in the amniotic fluid. Based on the neonatological follow-up examinations in 116 deliveries, 18 newborns had complications (15.52%); however, some cases were associated with multiple complications, resulting in a total of 33 types of complications being identified (28.45%). Among the 11 neurological complications (9.48%), we found 1 case each (0.86%) of severe inoperable intracranial space occupation, hydrocephalus, balance disorder, sleep disorder–sleep apnea, and speech development disorder. Two cases (1.72%) were found to have rigid muscles, epilepsy, and hypotonic muscles. Ophthalmological complications occurred in five cases (4.31%), such as enophthalmos, cataract, and retinopathy of prematurity (ROP), one case each, and two cases of strabism. Other complications were detected in 17 cases (14.66%). Conclusions: Because of the high incidence rate of recent CMV infection, serological testing is recommended following fetal abnormality detected by ultrasound. If a serologically confirmed new infection is diagnosed, the affected couple should be offered amniocentesis. Full article

Fetal ventriculomegaly (VM) is a condition characterized by abnormal enlargement of the cerebral ventricles of the fetus brain that often causes developmental disorders in children. Manual segmentation and classification of ventricular structures from brain MRI scans are time-consuming and require clinical expertise. To address this challenge, we develop an automated pipeline for ventricle segmentation, ventricular width estimation, and VM severity classification using a publicly available dataset. An adaptive slice selection strategy converts 3D MRI volumes into the most informative 2D slices, which are then segmented to isolate the lateral ventricles and deep gray matter. Ventricular width is automatically estimated to assign severity levels based on clinical thresholds, generating labeled data for training a deep learning classifier. Finally, an explainability module using a large language model integrates the MRI slices, segmentation masks, and predicted severity to provide interpretable clinical reasoning. Experimental results demonstrate that the proposed decision support system delivers robust performance, achieving dice scores of 89% and 87.5% for the 2D and 3D segmentation models, respectively. Also, the classification network attains an accuracy of 86% and an F1-score of 0.84 in VM analysis. Full article

During fetal life, the hepatic artery (HA) is responsible for a small contribution to the total hepatic blood inflow; however, it plays a key role in maintaining liver perfusion and reflects fetal hemodynamic adaptation. With advances in ultrasonography, HA Doppler assessment has emerged as a potential tool for evaluating fetal well-being. This review aims to synthesize current knowledge on the embryology, anatomy, physiology, and Doppler assessment of the fetal hepatic artery, highlighting its diagnostic and clinical significance. A prenatal hepatic arterial buffer response (HABR), analogous to that in postnatal life, allows for compensatory vasodilatation when umbilical or portal venous inflow decreases. Doppler studies demonstrate that a reduced pulsatility index (PI) and resistance index (RI) and an increased peak systolic velocity (PSV) correspond to enhanced arterial flow and decreased vascular resistance. These patterns have been observed in fetal growth restriction (FGR) and certain chromosomal abnormalities. Fetal hepatic artery Doppler assessment contributes to the understanding of fetal adaptation to hypoxia and has a promising role in fetal well-being evaluation. As of now, there are no established reference curves, and it has not yet been incorporated into routine obstetric screening; future research should focus on standardizing measurement techniques and validating its prognostic value. Full article

Placenta Accreta Spectrum (PAS) disorders, including placenta accreta, increta, and percreta, are serious obstetric conditions characterized by abnormal placental adherence to the uterine wall. With increasing incidence, PAS poses significant risks, primarily through massive hemorrhage during or after delivery, often necessitating hysterectomy. Key risk factors include prior cesarean sections, uterine surgery, and placenta previa diagnosis. In this review, we will examine the pathophysiology of PAS, with a focus on the mechanisms underlying abnormal trophoblast invasion and defective decidualization. We will highlight the role of uterine scarring, extracellular matrix remodeling, dysregulated signaling pathways, and immune and vascular alterations in disrupting the maternal-fetal interface, ultimately predisposing to morbid placentation and delivery complications. We will also discuss the life-threatening complications of PAS, such as shock and multi-organ failure, which require urgent multidisciplinary intensive care, as well as the optimization of management through preoperative planning and intraoperative blood loss control to reduce maternal morbidity and mortality. Full article