Search Results (140)

Molar pregnancy (MP) is a gestational disorder resulting from abnormal fertilization, leading to atypical trophoblastic proliferation and the formation of a complete or partial hydatidiform mole. This condition represents the most common form of gestational trophoblastic disease (GTD) and carries a significant risk of progression to gestational trophoblastic neoplasia (GTN). Although rare in high-income countries, MP remains up to ten times more prevalent in low-income and developing countries, contributing to preventable maternal morbidity and mortality. This narrative review provides an updated, practical overview of the clinical presentation, diagnosis, treatment, and follow-up of MP. A key focus is the challenge of early diagnosis, particularly given the increasing frequency of first-trimester detection, where classical histopathological criteria may be subtle, leading to diagnostic errors. The review innovates by integrating advanced diagnostic methods—combining histopathology, immunohistochemistry using p57Kip2, Ki-67, and p53 markers, along with cytogenetic analysis—to improve diagnostic accuracy in early gestation. The central role of referral centers is also emphasized, not only in facilitating timely treatment and access to chemotherapy, but also in implementing standardized post-molar follow-up protocols that reduce progression to GTN and maternal mortality. By focusing on both advanced diagnostic strategies and the organization of care through referral centers, this review offers a comprehensive, practice-oriented perspective to optimize patient outcomes in GTD and address persistent care gaps in high-burden regions. Full article

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare, often fatal congenital disorder characterized by severe neonatal respiratory distress and associated with complex multisystem malformations. In approximately 90% of cases, the condition is linked to deletions or mutations affecting the FOXF1 gene or its upstream enhancer region on chromosome 16q24.1. This review analyzes reported prenatal cases with 16q24.1 deletion involving FOXF1, aiming to identify recurrent sonographic features and elucidate the underlying genomic and epigenetic mechanisms. We reviewed prenatal cases reported in the literature involving deletions of the 16q24.1 region, including the FOXF1 gene. Here, we expand the case series by reporting a fetus with increased nuchal translucency measuring 8 mm and a de novo 16q24.1 deletion. We identified nine prenatal cases with a 16q24.1 deletion, all involving the FOXF1 gene or its enhancer region. The main ultrasound findings included increased nuchal translucency and cystic hygroma during the first trimester, and cardiac, renal, and intestinal malformations from 20 weeks of gestation onward. Prenatal diagnosis of ACDMPV based solely on ultrasound findings is challenging. In most reported cases, the pregnancy was carried to term, with the diagnosis being confirmed by post-mortem histopathological examination. In the only case in which the pregnancy was terminated at 14 weeks’ gestation, histological examination of the fetal lungs, despite them being in the early stages of development, revealed misaligned pulmonary veins in close proximity to the pulmonary arteries and bronchioles. Evidence highlights the significance of non-coding regulatory regions in the regulation of FOXF1 expression. Differential methylation patterns, and possible contributions of parental imprinting, highlight the complexity of FOXF1 regulation. Early detection through array comparative genomic hybridization (array CGH) or next-generation sequencing to identify point mutations in the FOXF1 gene, combined with increased awareness of ultrasound markers suggestive of the condition, could improve the accuracy of prenatal diagnosis and genetic counseling. Further research into the epigenetic regulation of FOXF1 is crucial for refining recurrence risk estimates and improving genetic counseling practices. Full article

To assess the association between known (PlGF, sFlt-1, betaHCG, PAPPA) and novel (cell-free DNA, cfDNA, and total endothelial and platelet microvesicles, MVs) maternal blood biomarkers measured at the first trimester with the later development of preeclampsia (PE) and PE-related severe adverse events (SAE), we conducted a retrospective case–control study including women with an established diagnosis of preeclampsia (cases) and healthy pregnant women (controls). Biomarkers were measured from first-trimester blood samples stored in a hospital biobank. A total of 89 women, 54 women with PE and 35 controls were included. PlGF showed good performance for diagnosing overall preeclampsia (AUC: 0.71; 95% CI 0.59–0.82), early-onset preeclampsia (AUC 0.80; 95% CI 0.68–0.9) and fetal-neonatal SAEs (AUC: 0.73; 95% CI 0.63–0.84). Multivariate models including clinical variables, PlGF and other biomarkers showed good to very good discrimination for the development of PE, early-onset PE and fetal-neonatal SAEs (AUCs of 0.87, 0.89 and 0.79, respectively). Platelet-derived MVs were the best isolated biomarker for late-onset PE and, combined with systolic blood pressure, showed good discrimination (AUC: 0.81; 95% CI 0.71–0.92). For maternal SAEs, a model incorporating cfDNA and sFlt-1 provided excellent discrimination (AUC 0.92; 95% CI 0.82–1.00). Our findings suggest that multivariate models incorporating both clinical variables and first-trimester biomarkers may improve risk stratification for PE, especially for late-onset PE and for identifying women at risk of severe maternal or fetal complications. Notably, the inclusion of novel biomarkers such as cfDNA and MVs added value in clinical scenarios where the predictive performance of existing tools remains suboptimal. Full article

Recurrent pregnancy loss (RPL) is a multifactorial condition affecting 1–5% of couples, often with unclear etiology. Idiopathic pregnancy losses (iPLs) are particularly challenging due to unknown molecular mechanisms. This study investigates the transcriptomic profiles of first-trimester products of conception (POC) from iPLs to uncover underlying molecular pathways. We performed RNA-sequencing on nine POC samples, identifying two distinct clusters enriched in trophoblast and decidual cells. Deconvolution analysis revealed reduced syncytiotrophoblast (STB) cells, with increased cytotrophoblast (CTB) and extravillous trophoblast (EVT) cells in iPLs. Gene Set Enrichment Analysis highlighted immune pathways enrichment in both villous trophoblasts and decidua. Gene ontology (GO) analysis of downregulated genes implicated hormonal and endocrine processes, consistent with STB reduction, while upregulated genes were associated with MHC protein complex and immune system processes, aligning with EVT increases. Histological analysis showed chronic histiocytic intervillositis (CHI) in iPL samples, supporting maternal immune dysregulation in unexplained RPL. Together, transcriptomic and histological analyses indicate that immune signaling dysregulation and impaired trophoblast differentiation may underlie unexplained iPLs. These findings bridge molecular and histopathological evidence, underscoring the interplay between trophoblast dysfunction and immune imbalance. Our results provide insights into iPL pathogenesis, highlighting potential biomarkers that may contribute to improved diagnosis and future research. Full article

Placenta accreta spectrum (PAS) and placenta previa (PP) are severe obstetric disorders associated with high maternal and perinatal morbidity. Early diagnosis of both conditions remains challenging, particularly in cases with subtle imaging findings. This study was aimed to evaluate the diagnostic value of first-trimester maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta subunit of human chorionic gonadotropin (β-hCG) in predicting PAS and PP. In this retrospective case–control study, a total of 100 pregnant women were included: 36 with PAS, 32 with PP, and 32 healthy controls. Serum levels were measured at 11–13⁶ weeks of gestation. Both biomarkers were significantly altered in pathological groups compared to controls: PAPP-A was lower in PP (3.04 [1.42–4.52] IU/L) and PAS (3.63 [2.51–5.39] IU/L) vs. controls (5.34 [3.72–8.41] IU/L; p < 0.001), while β-hCG was higher in PP (45.4 [40.1–54.9] IU/L) and PAS (51.4 [32.3–74.8] IU/L) vs. controls (33.5 [22.7–54.1] IU/L; p = 0.044 and p < 0.001, respectively). ROC analysis demonstrated that combined biomarker modeling improved diagnostic accuracy over single-marker use, with AUCs reaching 0.85 (sensitivity 85.2%, specificity 72%) for PAS and 0.88 (sensitivity 100%, specificity 72%) for PP. These findings support the integration of biochemical screening into first-trimester risk assessment protocols. Incorporating maternal serum biomarkers may enhance early identification of high-risk pregnancies, allow timely referral to specialized care, and reduce adverse outcomes. Further prospective studies are warranted to validate the utility of this dual-marker approach across diverse populations and clinical settings. Full article

Objective: This study aimed to investigate the prognostic value of two novel systemic inflammatory indices—the Aggregate Systemic Inflammation Index (AISI) and the Systemic Inflammatory Response Index (SIRI)—in predicting preterm delivery and associated neonatal outcomes. Methods: A retrospective, descriptive, cross-sectional study was conducted using the electronic health records of 1056 pregnant women admitted to a tertiary university hospital between 2020 and 2025. Pregnancies were classified into preterm (n = 528) and term (n = 528) groups. Demographic, obstetric, neonatal, and laboratory data were analyzed. Results: The AISI and SIRI values in the first trimester and at admission were significantly higher in the preterm delivery group than in the term delivery group (p < 0.001). Elevated AISI and SIRI levels correlated with lower 1st- and 5th-minute APGAR scores (p < 0.001) and higher neonatal intensive care unit (NICU) admission rates (35.8% vs. 4.5%; p < 0.001). The AISI cut-offs were 399.2 for preterm delivery (59.7% sensitivity, 59.8% specificity), 558.8 for NICU admission (79.3% sensitivity, 79.2% specificity), 694.0 for RDS (87.8% sensitivity, 87.8% specificity), 602.1 for sepsis (79.6% sensitivity, 79.2% specificity), and 753.8 for congenital pneumonia (81.6% sensitivity, 81.9% specificity). The SIRI cut-offs were 1.7 for preterm delivery (59.1% sensitivity, 58.9% specificity), 2.4 for NICU admission (81.7% sensitivity, 81.6% specificity), 3.1 for RDS (89.0% sensitivity, 89.5% specificity), 3.0 for sepsis (85.8% sensitivity, 85.7% specificity), and 3.4 for congenital pneumonia (85.7% sensitivity, 83.8% specificity). Conclusions: The AISI and SIRI showed significant predictive utility for neonatal morbidity in preterm delivery. The use of these markers in clinical practice may improve neonatal outcomes by enhancing the early diagnosis and management of high-risk pregnancies. Full article

Background and Clinical Significance: Implantation of an embryo in the cervical canal is the rarest location of ectopic pregnancy, as it occurs between 1 in 1000 and 1 in 18,000 pregnancies. Dilation and curettage in previous pregnancies have been identified as risk factors in most cases. Other predisposing factors include pelvic inflammatory disease (PID), prior tubal surgeries, assisted reproductive technologies, as well as the presence of fibroids and intrauterine. Importantly, ectopic pregnancies are the main cause of maternal morbidity and mortality in the first trimester. Given the rarity of cervical ectopic pregnancies (CEPs) and the lack of specific recommendations, clinical data supporting current evidence is of utmost significance. Case Presentation: A 29-year-old nulliparous woman presented with spotting from the genital tract and lower abdominal pain persisting for four days. Pregnancy could not be ruled out based on the patient’s medical history. The level of β-Human chorionic gonadotropin (β-HCG) on admission was 1487.99 mIU/mL. The first ultrasonography examination revealed a non-specific imaging appearance suggestive of the presence of cervical mucus. Targeted examination with visualization of the cervical canal revealed a gestational sac measuring 4–5 mm in diameter, containing an embryonic echo. The patient was treated with 84 mg of methotrexate (MTX) i.v. in a 1, 3, 5, 7 scheme along with 0.1 mg/kg calcium folinate i.m. in a 2, 4, 6, 8 scheme prior to curettage. Conclusions: A diagnosis of cervical pregnancy cannot be excluded even in the absence of prior risk factors. Methotrexate should be considered a safe and efficient option in the management of CEP. As shown in our case, early detection of CEP is of utmost significance. Full article

Congenital Rubella Syndrome (CRS) results from maternal infection with the rubella virus during pregnancy, particularly in the first trimester, when the risk of vertical transmission and severe fetal damage is highest. CRS is characterized by a broad spectrum of congenital anomalies, including sensorineural hearing loss, congenital heart defects, cataracts, neurodevelopmental delay, and behavioral disorders. Despite the absence of specific antiviral therapies, active immunization remains the only effective strategy to prevent rubella infection and its congenital consequences. Global immunization efforts, particularly in the Americas, have led to the elimination of rubella and CRS in several countries. However, challenges persist in the post-elimination era, including declining vaccine coverage, vaccine hesitancy, and setbacks caused by the COVID-19 pandemic. Diagnosis relies on maternal serology, fetal imaging, postnatal antibody testing, and molecular techniques. Management requires long-term, multidisciplinary follow-up due to the complex and lifelong sequelae affecting sensory, motor, and cognitive development. This review highlights the clinical, epidemiological, and pathophysiological aspects of CRS, while emphasizing the urgent need to maintain high vaccination coverage and strengthen surveillance systems. Sustained public health commitment is essential to prevent the reemergence of rubella and protect future generations from this preventable syndrome. 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

The relevance of O₃ exposure in critical congenital heart disease (CCHD) remains uncertain and requires further investigation. The present study aims at quantitatively assessing the association between ambient O₃ exposure during the early pregnancy period with fetal CCHD and identifying possible susceptible exposure windows. A retrospective cohort study involving 24,516 pregnant women was conducted using data from the Maternal–Fetal Medicine Consultation Network, which encompassed 1313 medical centers across China from 2013 to 2021. We extracted daily O₃ concentrations from a validated grid dataset with a spatial resolution of 0.1° at each participant’s residential county to assess ambient O₃ exposure, followed by calculating the average exposure levels in the periconceptional period, embryonic period, first trimester, and preconception period. The diagnosis of CCHD was based on fetal echocardiography. Exposure–response analyses were carried out using logistic regression models. During the study period, a total of 1541 (17.4%) subjects were diagnosed with fetal CCHD. Each 10 µg/m³ increase in ambient O₃ exposure in the periconceptional period was associated with a 26.0% increase in the odds of CCHD (odds ratio [OR]: 1.260, 95% confidence interval [CI]: 1.189, 1.335; p < 0.001). Importantly, the association was not modified by factors including maternal age and occupation status, paternal age and smoking status, conception mode, and the presence of risk factors. In the sensitivity analysis, significant associations were observed between O₃ exposure and CCHD in the embryonic period, first trimester, and preconception period, which was consistent with the results of the main analyses. These findings suggest that lowering ambient O₃ exposure in the preconception and early pregnancy periods may be beneficial in reducing the risk of fetal CCHD, especially in regions with elevated O₃ levels. Full article

The aim of the study was to determine the prevalence rates of respiratory pathogens using syndromic tests and also to show which respiratory viruses were detected in suspected cases, especially during and after the pandemic period. A total of 1984 different respiratory tract samples from various departments were included and studied with the QIAstat-Dx device in 2021–2023. The samples were studied with the QIAstat-Dx1 Respiratory SARS-CoV-2 Panel. The kit used was a fully automated, multiplex syndromic test that detected SARS-CoV-2 and 21 other respiratory tract pathogens. As a result of the study, the prevalence of Rhinovirus/Enterovirus (RV/EV) (18.59%), RV/EV-SARS-CoV-2 (42.74%), SARS-CoV-2 (5.04%), and Influenza A Virus (IAV) (5.59%) agents was found to be higher than other agents during the period investigated. Among the 1984 patients examined, 959 (48.33%) had a single viral agent, 156 (7.86%) had double coinfection, 11 (0.55%) had triple coinfection and 1 patient had quadruple coinfection. Nearly half of the patients had a straightforward infection, which helps clinicians in directing specific treatment methods. The study results demonstrate that during the pandemic period, the detection of respiratory pathogens such as SARS-CoV-2 and RV/EV was not only critical for accurate diagnosis but also served as an important indicator of the broader epidemiological trends in respiratory infections. The seasonal distribution showed that while RV/EV was frequently present, its coinfection with SARS-CoV-2 was notably observed only in the first trimester. In light of our findings showing high rates of SARS-CoV-2 and RV/EV detection, along with diverse patterns of coinfection in clinical samples, such comprehensive testing not only assists in rapid diagnosis but also informs public health strategies by reflecting the evolving landscape of respiratory infections in the pandemic and post-pandemic era. Full article

The incidence of malignancies diagnosed during pregnancy is estimated at 1 in 1000 pregnancies, with cervical cancer being the most common gynecological malignancy in this population. The increasing maternal age and widespread use of prenatal screening contribute to the rising detection rates. Early symptoms of cervical cancer, such as vaginal bleeding or discharge, often mimic normal pregnancy changes, leading to potential delays in diagnosis. Cervical dysplasia, a known precursor of cervical cancer, is closely associated with high-risk HPV infection, which affects approximately 25% of women of reproductive age. Screening using cytology and HPV testing is considered safe and effective during pregnancy in early detection. Colposcopy remains the gold standard in further diagnostics, with targeted biopsy indicated in selected cases. In cases of high-grade lesions (CIN II/III), conservative management is often preferred, as more than 60% of lesions regress postpartum. Invasive cervical cancer diagnosed during pregnancy is rare, with an estimated incidence of 1.4–4.6 per 100,000 pregnancies. Management decisions depend on gestational age, cancer stage, and the patient’s reproductive preference. Chemotherapy can be administered after the first trimester with acceptable maternal and fetal safety profiles. This review presents current evidence on screening, diagnostic pathways, and treatment strategies. It emphasizes the importance of individualized care, multidisciplinary collaboration, and shared decision-making to optimize outcomes for both mother and fetus. Full article

Introduction: Molybdenum cofactor deficiency (MoCD) is a rare, lethal disorder characterized by early-onset encephalopathy and seizures. In 2021, fosdenopterin (Nulibry^TM) became the first FDA-approved treatment for MoCD type A (MoCD-A). Case Presentation: A G3P2 woman with a prior affected child underwent prenatal diagnosis of MoCD-A at 16 weeks via amniocentesis. Fetal Magnetic Resonance Imaging (MRI) at 22 weeks was normal but showed a mega cisterna magna by 28 weeks. Concerns of ongoing brain damage led to a cesarean section at 32 weeks 6 days estimated gestational age (EGA). Intravenous fosdenopterin was administered within 10 min of birth. Seizures started around 12 h and escalated to status epilepticus by 24 h but resolved by 60 h with treatment. Early MRI demonstrated acute injury without chronic changes. The infant was discharged on day 37 and diagnosed with spastic quadriplegic cerebral palsy at 6 months, with cognition relatively spared. At 24 months, the child remains seizure-free with moderate motor impairment. Conclusions: This case highlights that brain injury in MoCD-A may commence in utero during the second trimester. Early delivery combined with immediate neonatal fosdenopterin treatment controlled seizures and halted progression, but residual injury suggests that prenatal interventions are necessary to optimize outcomes. Full article

Background/Objectives: Over the years, the potential of the first-trimester (FT) ultrasound in the detection of fetal structural defects has increased. The main objectives of the first-trimester fetal screening evaluation are the detection of major structural anomalies and the diagnosis of additional sonographic markers for chromosomal disorders. When a fetal anomaly is diagnosed, patients have the right to be informed about the risks, necessary interventions, or alternatives. Depending on the severity of the anomalies and the pregnancy period, the legality of the pregnancy termination was evaluated. The aim of this study was to assess the impact of the first-trimester morphological screening of the fetus using an ultrasound protocol according to the latest international protocols (the ISUOG protocol). Methods: Between 1 January 2024 and 31 December 2024, 854 pregnancies with gestational ages between 11 weeks and 13 weeks + 6 days were morphologically evaluated during the nuchal scan in the Obstetrics and Gynecology Department of the Emergency County Hospital from Craiova. Both transabdominal and transvaginal ultrasound in 2D and in a color Doppler mode were used in the scanning technique. The ultrasound findings were correlated with the genetic testing results and pregnancy outcome. The medical law implications were related to the cases where the ultrasound was performed at about 13 weeks of gestation, and the screening genetic results showed an increased pregnancy risk, which arose during the FT. In these cases, we performed amniocentesis at about 16–17 weeks of gestation, and especially, the Non-Invasive Prenatal Testing (NIPT)-positive cases were confirmed by karyotyping. Still, at this gestational age of diagnosis, the Romanian law would not allow abortions. Results: By using this extended FT ultrasound protocol, we detected 58 cases with fetal structural anomalies. Eighteen cases were also associated with genetic syndromes after performing chorionic villous sampling (CVS). Three cases detected with minor structural anomalies (two cases with club foot and one case with a cleft upper lip) were lost to follow-up. Conclusions: Fetal morphological ultrasound evaluation is feasible in the late first trimester. By using an extended ultrasound protocol, we can detect most of the fetal structural anomalies and contribute to better medical counseling and improve pregnancy outcomes. Full article

Background/Objectives: The main goal of this study was to determine whether ductal constriction in the third trimester of a pregnancy during fetal echocardiography examination has an impact on the neonatal clinical condition during the first days after birth. Methods: A retrospective study was based on 348 newborns who were examined during their fetal life in the third trimester of a pregnancy in our fetal cardiology center. They were divided into two groups: the study group (n = 49): neonates with “normal heart anatomy” (NHA), assessed by fetal echocardiography (ECHO) examination and prenatally diagnosed ductal constriction (NHA-DC); and the control group (n = 299): NHA neonates without DC (NHA-NDC). Results: Prenatally, DC was associated with other functional abnormalities, such as myocardial hypertrophy, cardiomegaly, tricuspid regurgitation, pericardial effusion and abnormal flow through foramen ovale. Neonates with prenatally diagnosed DC in 43% of cases presented with elevated neonatal bilirubin levels requiring phototherapy treatment (p < 0.006). In the study group 27% of neonates showed signs of breathing difficulties in the first hours of life (p < 0.001). Neonates with a prenatal diagnosis of DC were hospitalized longer than neonates with a normal heart study (NHS) (p < 0.001). Conclusions: Neonates with a prenatal diagnosis of ductal constriction are prone to having transient respiratory problems (up to 27%) and mild neonatal hyperbilirubinemia (in presented series up to 43%). Gestational diabetes can be associated with ductal constriction. Full article