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Search Results (332)

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23 pages, 1417 KB  
Article
Beyond the Curtains: Identification of the Genetic Cause of Foetal Developmental Abnormalities Through the Application of Molecular Autopsy
by Beatrice Spedicati, Giulia Pianigiani, Aurora Santin, Vanessa Rebecca Gasparini, Ilaria Falcomer, Agnese Feresin, Maria Teresa Bonati, Daniela Mazzà, Elisa Paccagnella, Domizia Pasquetti, Elisa Rubinato, Claudio Granata, Flora Maria Murru, Maurizio Pinamonti, Rossana Bussani, Ilaria Fantasia, Tamara Stampalija, Paolo Gasparini, Stefania Zampieri and Giorgia Girotto
Genes 2025, 16(10), 1167; https://doi.org/10.3390/genes16101167 - 2 Oct 2025
Viewed by 382
Abstract
Background: Foetal structural abnormalities can be detected in approximately 3% of all pregnancies and frequently remain without a genetic diagnosis. This study aims to apply an integrated approach with the final goal of providing a molecular diagnosis in the challenging Italian setting [...] Read more.
Background: Foetal structural abnormalities can be detected in approximately 3% of all pregnancies and frequently remain without a genetic diagnosis. This study aims to apply an integrated approach with the final goal of providing a molecular diagnosis in the challenging Italian setting of early termination of pregnancy. Methods: In a cohort of 86 foetuses, post-mortem dysmorphological examination, radiological assessments, and molecular autopsy through Whole-Exome Sequencing—WES—analysis were performed. Results: Forty-two foetuses were phenotypically classified as presenting a single major malformation (i.e., central nervous system, skeletal, urogenital, or cardiac anomalies, or fluid accumulation), while 44 foetuses presented multiple malformations and/or dysmorphic features. Overall, WES provided a diagnostic yield of 26.7%; additionally, seven Variants of Uncertain Significance (VUS) potentially liked to the foetal phenotype were identified. The highest detection rate was achieved for foetuses presenting a single major urogenital (50%) or skeletal (42.9%) malformation, followed by foetuses presenting multiple malformations (27.3%). Peculiar results of particular interest were (1) the identification of two splicing variants (within the INPPL1 and RHOA genes), functionally characterised through minigene assay, which contributed to evaluate their pathogenicity, and (2) the identification of a novel de novo missense ZNF292 variant (NM_015021.3:c.6325A>C p.(Ser2109Arg)) in a foetus affected by corpus callosum hypoplasia. The ZNF292 gene is associated with the Intellectual developmental disorder, autosomal dominant 64 and this finding represents the first report of prenatally detected anomalies of the central nervous system in a foetus carrying a ZNF292 variant. Conclusions: This study underlines the diagnostic utility of an integrated approach to achieve a precise genetic diagnosis for structural foetal abnormalities, thus providing families with precise recurrence risk estimations and detailed options about future pregnancies. Additionally, a systematic implementation of this strategy could be crucial to better characterise new variants and discover new genes involved in embryonic and foetal development. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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15 pages, 1137 KB  
Review
The Pathophysiology of Wharton’s Jelly and Its Impact on Fetal and Neonatal Outcomes: A Comprehensive Literature Review
by Tudor-Andrei Butureanu
Med. Sci. 2025, 13(4), 215; https://doi.org/10.3390/medsci13040215 - 2 Oct 2025
Viewed by 681
Abstract
Wharton’s jelly (WJ), the mucoid connective tissue of the umbilical cord, provides essential protection to the umbilical vessels against mechanical stress. While research into WJ-derived stem cells for regenerative medicine has surged, the clinical significance of its in utero pathologies remains less explored. [...] Read more.
Wharton’s jelly (WJ), the mucoid connective tissue of the umbilical cord, provides essential protection to the umbilical vessels against mechanical stress. While research into WJ-derived stem cells for regenerative medicine has surged, the clinical significance of its in utero pathologies remains less explored. This review synthesizes the current literature on the pathophysiology of WJ abnormalities and their direct impact on fetal and neonatal outcomes. Pathologies are broadly categorized as quantitative (absence/reduction or excess/edema) and structural (pseudocysts, mucoid degeneration). A reduction or segmental absence of WJ critically compromises cord integrity, leading to vascular compression and is a direct cause of stillbirth, fetal growth restriction (FGR), and intrapartum distress. Conversely, excessive WJ or edema is associated with maternal diabetes and fetal hydrops and can also impair hemodynamics. Umbilical cord pseudocysts, arising from focal WJ degeneration, are significant markers for severe chromosomal abnormalities, particularly Trisomy 18 and 13, and other structural defects, especially when persistent or multiple. Sonographic measurement of WJ area shows promise as a surrogate for placental function, with decreased area correlating with placental pathology and FGR. However, significant diagnostic challenges persist, particularly the prenatal detection of segmental WJ absence, a “silent” pathology often discovered only after a catastrophic event. This review highlights the critical role of WJ integrity in determining perinatal outcomes and underscores the urgent need for improved diagnostic modalities and standardized management protocols to mitigate associated risks. Full article
(This article belongs to the Section Gynecology)
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13 pages, 4125 KB  
Case Report
The Baffling Diagnosis of a Rare Case of Polypoid Endometriosis: Neoplasm Mimicking in a Young Pregnant Woman—A Case Report and Literature Review
by Nicolae Gică, Ioana-Stefania Bostan, George-Dumitru Gheoca, Raluca Chirculescu, Alexandru-Gabriel Bran, Anca Maria Panaitescu and Claudia Mehedințu
Diagnostics 2025, 15(19), 2460; https://doi.org/10.3390/diagnostics15192460 - 26 Sep 2025
Viewed by 338
Abstract
Background: Polypoid endometriosis is a rare variant of endometriosis that presents as a tumorous mass, making it difficult to differentiate it from a malignant tumor. It usually occurs in perimenopausal women or those undergoing hormone therapy, and its presence in a young [...] Read more.
Background: Polypoid endometriosis is a rare variant of endometriosis that presents as a tumorous mass, making it difficult to differentiate it from a malignant tumor. It usually occurs in perimenopausal women or those undergoing hormone therapy, and its presence in a young pregnant woman is extremely uncommon. Case Presentation: This article describes a rare instance of polypoid ovarian endometriosis in a pregnant woman, a condition with few documented cases in the medical literature. An adnexal mass was discovered incidentally during a routine prenatal ultrasound, with imaging features that raised the suspicion of a neoplastic process and prompted surgery to exclude malignancy. However, histopathological examination of the excised lesion confirmed features compatible with polypoid endometriosis, without revealing evidence of cancer. This case highlights the diagnostic challenges of differentiating polypoid endometriosis from ovarian neoplasms, especially during gestation, where imaging findings can be ambiguous. In addition, the hormonal environment inherent in pregnancy may exacerbate the proliferative behavior of endometriotic lesions, thus complicating clinical evaluations. The presence of an adnexal mass in such a setting often requires careful evaluation to balance the risks of surgery with the potential consequences of delayed diagnosis. The data presented emphasize the importance of an accurate diagnosis. In conclusion, a well-coordinated approach ensures the protection of maternal and fetal health. Conclusions: By prioritizing accurate diagnosis and personalized treatment plans, physicians can minimize complications and improve outcomes for both mother and child. Full article
(This article belongs to the Special Issue Imaging for the Diagnosis of Obstetric and Gynecological Diseases)
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13 pages, 903 KB  
Article
A Validation Approach for Determining Fetal Blood Groups Non-Invasively by High-Sensitive Next-Generation Sequencing
by Sandra Wienzek-Lischka, Marion Soelter, Annika Froelich, Marion Ernst-Schlegel, Stefan Gattenloehner, Andreas Braeuninger and Ulrich J. Sachs
J. Clin. Med. 2025, 14(19), 6812; https://doi.org/10.3390/jcm14196812 - 26 Sep 2025
Viewed by 239
Abstract
Introduction: For pregnant women with a history of fetal and neonatal alloimmune thrombocytopenia (FNAIT) or hemolytic disease of the fetus and newborn (HDFN), prenatal intervention in subsequent pregnancies may be necessary to prevent complications for the fetus. A non-invasive prenatal diagnostic procedure (NIPD) [...] Read more.
Introduction: For pregnant women with a history of fetal and neonatal alloimmune thrombocytopenia (FNAIT) or hemolytic disease of the fetus and newborn (HDFN), prenatal intervention in subsequent pregnancies may be necessary to prevent complications for the fetus. A non-invasive prenatal diagnostic procedure (NIPD) is recommended for fetal blood group genotyping. RT-PCR is used for fetal RHD determination as a reliable screening method with high sensitivity and specificity. For other antigens with variants involving single-base substitutions, droplet digital PCR (ddPCR) and next-generation sequencing (NGS) are recommended to reduce the risk of false-negative results. Only NGS offers the possibility of determining the cell-free fetal DNA (cffDNA) fraction in maternal plasma by sequencing additional gene fragments in parallel, but no standard exists for assay validation. Material and Methods: A custom-made primer panel was designed to target the common platelet and red cell antigens involved in fetal red cell and platelet incompatibilities, as well as additional anonymous single-nucleotide polymorphism (SNP) targets for use as an internal control. Amplicon-based NGS was carried out using semiconductor sequencing. For HPA-1a (HPA*1A, ITGB3) and K (KEL*01.01, KEL) assay validation, the limit of detection (LOD) and limit of quantification (LOQ) were estimated, as were false-positive antithetic alleles, linearity, and inter-assay variation, using cell-free DNA (cfDNA) extracted from the blood samples of healthy blood donors. An additional analysis was performed using 23 diagnostic samples from 21 pregnant women. Results: Regression analysis of dilution series using HPA-1a- and K-positive cell-free plasma samples in antigen-negative donor plasma showed that recovery is definitely feasible up to an HPA*1A and KEL*01.01 allele frequency of 1%. Base calls of false-positive antithetic alleles were detected with a maximum of 0.25% using 21 healthy blood donors. The LOD was estimated to be 0.2057% (mean + 3 SD) for HPA*1A with a LOQ of 0.6298% (mean + 10 SD). For KEL*01.01, the LOD was 0.1706% (mean + 3 SD) and the LOQ was 0.5314% (mean + 10 SD). The analysis of 15 of 21 cases with diagnostic samples from pregnant women with neonatal blood available for confirmatory testing resulted in 100% concordant results. The fetal fraction of these samples was calculated with a median of 11.03% (95% CI: 8.89, 13.20). Conclusions: NGS for non-invasive fetal blood group genotyping is an accurate and reliable method. In-house validation of the used assays can be performed using healthy donors to determine the LOD, LOQ and sensitivity. The threshold for paternally inherited fetal HPA*1A and KEL*01.01 alleles could be set at 1% (i.e., 2% fetal fraction) to obtain reliable test results. Internal controls for assessing the fetal fraction are essential to avoid false-negative test results. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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25 pages, 1711 KB  
Review
The Role of Prenatal Care in Fetal and Infant Development in Brazil: A Narrative Review
by Amanda Maieski da Silva, Caroline Stadler, Luiz Gustavo Gusson de Camargo, Paula Rothbarth Silva, Nathalia Marçallo Peixoto Souza, Mateus Santana Lopes, Fabiane Gomes de Moraes Rego, Juliana Sartori Bonini, Roberta Fabbri, Jéssica Brandão Reolon, Luana Mota Ferreira and Marcel Henrique Marcondes Sari
Healthcare 2025, 13(19), 2414; https://doi.org/10.3390/healthcare13192414 - 24 Sep 2025
Viewed by 756
Abstract
Background/Objectives: In Brazil, nearly universal access to prenatal care coexists with ongoing negative fetal and infant outcomes. This review explores how the adequacy of prenatal care affects maternal, fetal, and child health, and highlights recurring gaps in service delivery. Methods: A narrative review [...] Read more.
Background/Objectives: In Brazil, nearly universal access to prenatal care coexists with ongoing negative fetal and infant outcomes. This review explores how the adequacy of prenatal care affects maternal, fetal, and child health, and highlights recurring gaps in service delivery. Methods: A narrative review of Brazilian studies published between 2018 and 2024 was conducted through the Virtual Health Library and PubMed. The initial search (July 2024) was updated in February 2025, and two reviewers independently screened and extracted data, synthesizing clinical outcomes from the findings. Results: A total of thirty-six studies were included in the review. Inadequate prenatal care was consistently linked to higher rates of infant and neonatal mortality, prematurity, low birth weight, congenital syphilis, and neonatal near misses. The studies indicated that counting visits alone does not adequately reflect the quality of care: when evaluated against the Prenatal and Birth Humanization Program (PHPN), most studies met only one of the eight minimum criteria. Common shortcomings included late initiation of care, incomplete diagnostic testing, fragmented follow-up, and insufficient treatment for partners regarding sexually transmitted infections. Conclusions: Adverse outcomes persist in Brazil not due to a lack of access, but rather due to deficiencies in the content and continuity of prenatal care. To improve perinatal outcomes, it is essential to strengthen care through standardized, multidimensional indicators and integrated strategies that combine clinical, educational, and psychosocial support. Full article
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15 pages, 561 KB  
Article
Diagnostic Impact of Fetal MRI in 556 Fetuses: Where It Adds Value Beyond Ultrasound
by Zübeyde Emiralioğlu Çakır, Hakan Golbasi, Raziye Torun, Ceren Sağlam, İlayda Gercik Arzık, Hale Ankara Aktaş, Sevim Tuncer Can, İlknur Toka, İlker Uçar, Fatma Ceren Sarıoğlu and Atalay Ekin
J. Clin. Med. 2025, 14(19), 6690; https://doi.org/10.3390/jcm14196690 - 23 Sep 2025
Viewed by 297
Abstract
Objectives: This study aimed to assess the diagnostic contribution of fetal MRI across different anatomical systems and evaluate its added value beyond prenatal ultrasonography. Methods: This retrospective cohort included 556 fetuses who underwent both prenatal ultrasound and fetal MRI in a [...] Read more.
Objectives: This study aimed to assess the diagnostic contribution of fetal MRI across different anatomical systems and evaluate its added value beyond prenatal ultrasonography. Methods: This retrospective cohort included 556 fetuses who underwent both prenatal ultrasound and fetal MRI in a single tertiary center. Cases were classified by anatomical system. The concordance between ultrasound and MRI findings, as well as additional or ruled-out findings identified by MRI, was analyzed. Statistical significance and clinical relevance were also evaluated. Results: Among the 556 cases, complete concordance between ultrasound and MRI findings was observed in 48.9%. MRI ruled out the initial diagnosis in 20.1% and revealed additional findings in 32% of cases. A total of 192 additional findings were identified, while 115 previously suspected anomalies were ruled out. The highest diagnostic contribution was observed in central nervous system (CNS) and gastrointestinal system (GIS) anomalies. Posterior fossa abnormalities and cystic or mass lesions were frequently detected as additional findings on MRI. In contrast, ultrasound alone was generally sufficient for evaluating genitourinary (GUS), thoracic, and vertebral anomalies. The overall diagnostic yield of MRI was higher in anatomically complex or sonographically ambiguous cases. Conclusions: Fetal MRI provides significant additional diagnostic value, particularly in CNS and GIS anomalies, by detecting additional findings, clarifying uncertain diagnoses, or excluding suspected anomalies. Its selective use may enhance both prenatal counseling and postnatal management. Full article
(This article belongs to the Section Clinical Pediatrics)
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21 pages, 412 KB  
Article
Unveiling the Hemostatic Signature of Prematurity: A Prospective Rotational Thromboelastometry-Based Analysis
by Martha Theodoraki, Alexia Eleftheria Palioura, Aikaterini-Pothiti Palioura, Abraham Pouliakis, Zoi Iliodromiti, Theodora Boutsikou, Nicoletta Iacovidou and Rozeta Sokou
Medicina 2025, 61(9), 1718; https://doi.org/10.3390/medicina61091718 - 21 Sep 2025
Viewed by 544
Abstract
Background and Objectives: The evaluation of the haemostatic mechanism in premature neonates remains particularly challenging, due to their immature haemostatic system, the influence of inflammation and the variety of clinical factors. This prospective study aimed at (a) assessing the haemostatic profile of [...] Read more.
Background and Objectives: The evaluation of the haemostatic mechanism in premature neonates remains particularly challenging, due to their immature haemostatic system, the influence of inflammation and the variety of clinical factors. This prospective study aimed at (a) assessing the haemostatic profile of clinically stable preterm neonates by Rotational Thromboelastometry [ROTEM; (EXTEM, INTEM, FIBTEM assays)], (b) establishing reference ranges, and (c) investigating potential differences in comparison to healthy term neonates. We also evaluated the impact of clinical and perinatal factors on the haemostatic status of this vulnerable population. Materials and Methods: 69 premature neonates with no underlying morbidity and 226 healthy term neonates were the study subjects. In term neonates, blood was collected on the 2nd-3rd day of life, if sampling was required for any other reason (hyperbilirubinemia, ABO blood group incompatibility screening, maternal thyroid antibodies, or insufficient prenatal care), whereas in premature neonates, blood was collected between the 4nd-10th day after stabilisation. The parameters measured for each ROTEM assay included Clotting Time (CT), Clot Formation Time (CFT), Alpha angle (α, degrees), Clot Amplitude at 5 and 10 min (A5, A10), Maximal Clot Firmness (MCF), and Lysis Index at 30, 45 and 60 min (Li30, Li45, and Li60 respectively). Results: The data analysis demonstrated a prothrombotic profile in preterm neonates, characterized by increased values of A5, A10, (MCF), and α-angle, and shortened CT and CFT across all assays (EXTEM, INTEM, FIBTEM), when compared to term neonates. A statistically significant inverse correlation was observed between gestational age and clot lysis parameters (INTEM Li45, Li60). Additionally, hematocrit levels were negatively correlated with clot amplitude and kinetics of clot development, while platelet count was positively associated with clot firmness parameters (A5, A10, MCF) and α-angle. Mode of delivery and the presence of gestational diabetes did not significantly affect ROTEM assay values. Preterm neonates with a history of respiratory distress syndrome (RDS) exhibited a more pronounced hypercoagulable profile compared to those without RDS, as reflected by the enhanced clot strength and reduced CT, findings that may be attributed to postnatal pulmonary inflammation and its systemic effects on coagulation. Conclusions: This study introduces for the first time reference values for the parameters of ROTEM assays (EXTEM, INTEM, FIBTEM) in clinically stable preterm neonates—a highly vulnerable patient group with a distinct need for accurate and individualized monitoring of their haemostatic status. The combined assessment of these assays enhances diagnostic precision, and offers a more comprehensive evaluation of neonatal haemostasis. By defining reference ranges in whole blood, this work provides novel data that support the integration of ROTEM into clinical transfusion algorithms. Full article
(This article belongs to the Special Issue From Conception to Birth: Embryonic Development and Disease)
15 pages, 310 KB  
Review
Prognostic Significance of Serial Ultrasonography in Placenta Accreta Spectrum and Its Impact on Perinatal Outcomes
by Antonia Varthaliti, Alexandros Psarris, Pelopidas Koutroumanis, Giwrgos Gkiaourakis, Maria Anastasia Daskalaki, Panos Antsaklis, George Daskalakis and Marianna Theodora
Medicina 2025, 61(9), 1612; https://doi.org/10.3390/medicina61091612 - 5 Sep 2025
Viewed by 653
Abstract
Placenta accreta spectrum (PAS) disorders remain a major cause of maternal morbidity and adverse perinatal outcomes due to abnormal placental adherence and invasion. Early and accurate prenatal diagnosis is essential to optimize surgical planning and reduce complications. Although ultrasound is well established as [...] Read more.
Placenta accreta spectrum (PAS) disorders remain a major cause of maternal morbidity and adverse perinatal outcomes due to abnormal placental adherence and invasion. Early and accurate prenatal diagnosis is essential to optimize surgical planning and reduce complications. Although ultrasound is well established as the cornerstone for PAS detection, the potential role of serial ultrasonography in refining risk assessment and predicting outcomes is increasingly being explored. Monitoring with serial ultrasonographic imaging may offer valuable insights into the progression of sonographic features, such as placental lacunae, myometrial thinning, placental bulge, and bladder wall disruption, which can predict surgical complexity and perinatal risk and influence decision-making and management. However, there is still limited evidence about the prognostic value of serial scans, and the variability in interpreting ultrasound markers continues, presenting challenges. While scoring systems incorporating ultrasound features show promise for risk stratification, further validation in larger studies is needed. Future research should focus on standardizing ultrasound protocols, validating predictive models, and exploring technological innovations, including artificial intelligence, to enhance diagnostic precision. Incorporating serial ultrasound assessments thoughtfully into clinical practice may improve individualized care and outcomes for women affected by PAS, but more studies are required. Full article
35 pages, 1322 KB  
Review
Congenital Cytomegalovirus Infection: From Silent Threat to Vaccine Horizon
by Rafaela Anna Moutsopoulou, Aikaterini Markou, Alexandra Lianou, Konstantina Leontari, Zoi Iliodromiti, Theodora Boutsikou, Georgios Kafalidis, Styliani Paliatsiou, Paraskevi Volaki, Nicoletta Iacovidou, Andreas G. Tsantes and Rozeta Sokou
Vaccines 2025, 13(9), 929; https://doi.org/10.3390/vaccines13090929 - 30 Aug 2025
Viewed by 1123
Abstract
Congenital cytomegalovirus (cCMV) infection is the most prevalent congenital infection, affecting approximately 0.5–2% of newborns, and is the leading non-genetic cause of sensorineural hearing loss and neurological impairment. The most severe outcome occurs following primary maternal infection during the first trimester of pregnancy, [...] Read more.
Congenital cytomegalovirus (cCMV) infection is the most prevalent congenital infection, affecting approximately 0.5–2% of newborns, and is the leading non-genetic cause of sensorineural hearing loss and neurological impairment. The most severe outcome occurs following primary maternal infection during the first trimester of pregnancy, and up to 40–50% of affected fetuses sustain permanent damage. Diagnosis relies on early prenatal screening through maternal serum testing, optimally performed in the first trimester, followed by confirmatory amniocentesis after 17 weeks’ gestation. Prenatal imaging with ultrasound and magnetic resonance imaging (MRI) plays a critical role in the identification of fetal brain abnormalities. Prevention strategies emphasize hygiene measures aimed at reducing maternal exposure to bodily fluids of young children, particularly prior to conception and during early pregnancy. Despite progress in vaccine development, currently available ones demonstrate modest efficacy. This review presents a comprehensive summary of congenital CMV infection, addressing its epidemiology, pathogenesis, diagnostic approaches, clinical presentation, and preventive measures, with a focus on recent advances in vaccine research. Full article
(This article belongs to the Special Issue Maternal Vaccination and Vaccines)
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10 pages, 1271 KB  
Article
More than a Diagnosis: How Prenatal Identification of Cantú Syndrome Transformed a Family’s Medical Narrative
by Isidoro Narbona-Arias, Marta Blasco-Alonso, Susana Monís-Rodriguez, Cristina Gómez Muñoz, Ernesto González-Mesa, Daniel María Lubián-López and Jesús Jiménez-López
J. Clin. Med. 2025, 14(17), 6017; https://doi.org/10.3390/jcm14176017 - 26 Aug 2025
Viewed by 993
Abstract
Background/Objectives: Cantú syndrome is a rare autosomal dominant genetic disorder caused by gain-of-function variants in the ABCC9 or KCNJ8 genes. Although its phenotypic expression is variable and can go unnoticed postnatally, certain ultrasound findings may raise suspicion during pregnancy. This article presents a [...] Read more.
Background/Objectives: Cantú syndrome is a rare autosomal dominant genetic disorder caused by gain-of-function variants in the ABCC9 or KCNJ8 genes. Although its phenotypic expression is variable and can go unnoticed postnatally, certain ultrasound findings may raise suspicion during pregnancy. This article presents a case of prenatal diagnosis through exome sequencing, which also enabled retrospective diagnosis in the mother and a previously undiagnosed child, highlighting the clinical and emotional value of diagnostic certainty in fetal medicine. Methods: We conducted a descriptive observational study based on a case identified at the Fetal Medicine Unit of the Regional University Hospital of Málaga. The patient underwent high-resolution ultrasound and trio-based exome sequencing (fetus and both parents). Results: Prenatal exome sequencing revealed a heterozygous pathogenic variant in ABCC9, consistent with Cantú syndrome, identified simultaneously in the fetus and the mother as part of a trio-based analysis, confirming maternal inheritance. The same variant was later detected in the patient’s older daughter, who had been under pediatric evaluation for a suggestive phenotype but had not received a genetic diagnosis until this study. The prenatal diagnosis allowed for obstetric and neonatal planning, genetic counselling, and a reinterpretation of the clinical and emotional meaning of previous pregnancies. Conclusions: Prenatal diagnosis of Cantú syndrome enables anticipation of perinatal complications, planned clinical interventions, and also provides emotional relief and a coherent narrative for families. In scenarios of variable phenotypic expressivity, fetal medicine may represent a gateway to family diagnosis, with significant clinical and psychosocial implications. Full article
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13 pages, 545 KB  
Article
The Diagnostic Utility of Prenatal Microarray in High-Risk Pregnancies: A Single-Center Experience in Enhancing Reproductive Care and Risk Stratification
by Abdullatif Bakır, Mustafa Tarık Alay, Umut Can Tekbaş, Sadun Sucu, İrem Kalay and Hanife Saat
Diagnostics 2025, 15(17), 2129; https://doi.org/10.3390/diagnostics15172129 - 23 Aug 2025
Viewed by 638
Abstract
Background/Objective: Prenatal cytogenetic testing is essential for pregnant women who are at high risk of having a child with a chromosomal abnormality. While conventional karyotyping detects large aneuploidies and structural rearrangements (>5–10 Mb), chromosomal microarray analysis (CMA) identifies smaller copy number variants (CNVs), [...] Read more.
Background/Objective: Prenatal cytogenetic testing is essential for pregnant women who are at high risk of having a child with a chromosomal abnormality. While conventional karyotyping detects large aneuploidies and structural rearrangements (>5–10 Mb), chromosomal microarray analysis (CMA) identifies smaller copy number variants (CNVs), increasing the diagnostic yield by approximately 5%. CMA is now recommended as the first-line test for evaluating fetal structural anomalies that are detected by ultrasound. Method: From March 2023 to September 2024, we analyzed 344 prenatal samples using conventional karyotyping and SNP-based CMA. Karyotyping was performed via flask culture, and CMA was conducted using the Infinium Global Screening Array Cyto (GSA-Cyto) on the Illumina iScan platform. We interpreted the CNVs using NxClinical v6.0 and curated databases including ClinVar, DECIPHER, OMIM, and ClinGen, among others. Our results aligned with the GRCh37/hg19 reference genome. Results: Chromosomal abnormalities were identified in 57/344 cases (16.5%). Of these, 39 cases were numerical chromosomal anomalies, and 18 cases were pathogenic or likely pathogenic CNVs. Notably, 11 CNVs (3.2%) were undetectable by conventional karyotyping, emphasizing the added value of CMA. Conclusions: CMA enhances the prenatal diagnostic accuracy by detecting submicroscopic CNVs that are not visible with conventional methods, supporting the routine use of this analysis in prenatal genetic evaluation. Full article
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21 pages, 410 KB  
Systematic Review
Parental Psychological Response to Prenatal Congenital Heart Defect Diagnosis
by Cristina Tecar, Lacramioara Eliza Chiperi and Dafin Fior Muresanu
Children 2025, 12(8), 1095; https://doi.org/10.3390/children12081095 - 20 Aug 2025
Viewed by 585
Abstract
Background: This systematic review aims to summarize the most recent data from the literature on the psychological aspects of parents of children prenatally diagnosed with congenital heart defects (CHDs). Methods: A comprehensive literature search was conducted to identify relevant studies on the psychological [...] Read more.
Background: This systematic review aims to summarize the most recent data from the literature on the psychological aspects of parents of children prenatally diagnosed with congenital heart defects (CHDs). Methods: A comprehensive literature search was conducted to identify relevant studies on the psychological issues faced by parents of children prenatally diagnosed with CHD. Searches were performed in multiple scientific databases, including PubMed, Science direct, Embase, Scopus, Medline, Clarivate, to ensure the broad coverage of the literature. The search was limited to studies published up until February 2025. The search strategy included the following terms and combinations: “congenital heart defect” OR “CHD” AND “prenatal diagnosis” AND “psychological impact” OR “parental distress” OR “coping”. Results: Eighteen studies involving the 673 parents of fetuses diagnosed with congenital heart defects were included. Studies spanned four continents and employed both qualitative (n = 14) and quantitative (n = 4) designs. Key psychological outcomes reported were anxiety, depression, stress, post-traumatic stress, coping strategies, maternal–fetal attachment, and life satisfaction. Anxiety and depression were the most frequent issues, with maternal anxiety reaching 65% and depression up to 45.7%. Stress related to diagnostic uncertainty was common. While some parents used adaptive coping (social support, emotional regulation), others experienced maladaptive patterns such as avoidance. One study reported increased maternal–fetal attachment following prenatal CHD diagnosis. Predictors of psychological distress included time of diagnosis, parental gender, education level, social support, and severity of the defect. Recommended interventions included early psychological screening, empathetic communication, structured counseling, and long-term emotional support. Despite heterogeneity in design and moderate overall bias, findings highlight a consistent psychological burden among parents, underscoring the need for integrated psychosocial care following a prenatal CHD diagnosis. Conclusions: Parents whose children have been prenatally diagnosed with a congenital heart defect are at an increased risk for psychological distress. To improve the quality of care, a multidisciplinary team is needed to provide parents with the necessary information on diagnosis, interventions, and potential outcomes. Full article
(This article belongs to the Section Pediatric Cardiology)
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21 pages, 563 KB  
Review
Addressing Patient–Provider Communication Gaps in Vanishing Twin Syndrome: Implications for Patient Care and Clinical Guidelines
by Nichole M. Cubbage, Samantha L. P. Schilit, Allison Groff, Stephanie Ernst and Marc A. Nascarella
Healthcare 2025, 13(16), 2048; https://doi.org/10.3390/healthcare13162048 - 19 Aug 2025
Viewed by 2040
Abstract
Background: Vanishing twin syndrome (VTS) represents a complex and under-recognized phenomenon in multifetal pregnancies, associated with both clinical uncertainty and significant psychosocial impact. Despite its frequency, gaps remain in diagnostic clarity, international guidelines, and communication strategies with patients and families. Materials and [...] Read more.
Background: Vanishing twin syndrome (VTS) represents a complex and under-recognized phenomenon in multifetal pregnancies, associated with both clinical uncertainty and significant psychosocial impact. Despite its frequency, gaps remain in diagnostic clarity, international guidelines, and communication strategies with patients and families. Materials and Methods: This hybrid review integrates narrative and systematic elements to assess the diagnostic, clinical, and psychosocial gaps in VTS. A systematic literature search was conducted across Medline/PubMed, CINAHL, PsycINFO, EBM Reviews, and Scopus using terms such as “vanishing twin syndrome,” “patient-provider communicat*,” and “bereave* care.” Sources included systematic reviews, randomized controlled trials, cohort studies, and qualitative studies. Exclusion criteria were outdated publications (>10 years old). Results: Evidence revealed multiple domains of concern. Clinical risks and diagnostics remain poorly defined, with inconsistent recognition of maternal and neonatal complications. Psychosocial impacts were prominent, encompassing grief, identity disruption, and unmet support needs. Patient–provider communication was frequently inadequate, with insufficient training and lack of standardized language. International guidelines varied widely in scope, with only a few of them providing clear recommendations for bereavement care in multifetal loss contexts. Discussion: Emerging discourse highlights the limitations of the traditional fission model and alternative conceptual frameworks, such as Herranz’s model, for understanding VTS. These theoretical differences underscore the need for precise terminology and consistent diagnostic practices. Clinical implications extend to prenatal screening, obstetric management, and the integration of psychosocial support. Patient-centered communication and structured support initiatives (e.g., the Butterfly Project) demonstrate the potential to bridge communication gaps and improve care experiences. Conclusions: VTS requires recognition as both a medical and psychosocial condition. Improved clinical definitions, harmonized international guidelines, and emphasis on empathetic communication are essential to address the current gaps. Integrating these elements into practice may enhance patient outcomes and provide families with validation and support following multifetal loss. Full article
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25 pages, 906 KB  
Review
Evolution and Prognostic Variables of Cystic Fibrosis in Children and Young Adults: A Narrative Review
by Mădălina Andreea Donos, Elena Țarcă, Elena Cojocaru, Viorel Țarcă, Lăcrămioara Ionela Butnariu, Valentin Bernic, Paula Popovici, Solange Tamara Roșu, Mihaela Camelia Tîrnovanu, Nicolae Sebastian Ionescu and Laura Mihaela Trandafir
Diagnostics 2025, 15(15), 1940; https://doi.org/10.3390/diagnostics15151940 - 2 Aug 2025
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Abstract
Introduction: Cystic fibrosis (CF) is a genetic condition affecting several organs and systems, including the pancreas, colon, respiratory system, and reproductive system. The detection of a growing number of CFTR variants and genotypes has contributed to an increase in the CF population which, [...] Read more.
Introduction: Cystic fibrosis (CF) is a genetic condition affecting several organs and systems, including the pancreas, colon, respiratory system, and reproductive system. The detection of a growing number of CFTR variants and genotypes has contributed to an increase in the CF population which, in turn, has had an impact on the overall statistics regarding the prognosis and outcome of the condition. Given the increase in life expectancy, it is critical to better predict outcomes and prognosticate in CF. Thus, each person’s choice to aggressively treat specific disease components can be more appropriate and tailored, further increasing survival. The objective of our narrative review is to summarize the most recent information concerning the value and significance of clinical parameters in predicting outcomes, such as gender, diabetes, liver and pancreatic status, lung function, radiography, bacteriology, and blood and sputum biomarkers of inflammation and disease, and how variations in these parameters affect prognosis from the prenatal stage to maturity. Materials and methods: A methodological search of the available data was performed with regard to prognostic factors in the evolution of CF in children and young adults. We evaluated articles from the PubMed academic search engine using the following search terms: prognostic factors AND children AND cystic fibrosis OR mucoviscidosis. Results: We found that it is crucial to customize CF patients’ care based on their unique clinical and biological parameters, genetics, and related comorbidities. Conclusions: The predictive significance of more dynamic clinical condition markers provides more realistic future objectives to center treatment and targets for each patient. Over the past ten years, improvements in care, diagnostics, and treatment have impacted the prognosis for CF. Although genotyping offers a way to categorize CF to direct research and treatment, it is crucial to understand that a variety of other factors, such as epigenetics, genetic modifiers, environmental factors, and socioeconomic status, can affect CF outcomes. The long-term management of this complicated multisystem condition has been made easier for patients, their families, and physicians by earlier and more accurate identification techniques, evidence-based research, and centralized expert multidisciplinary care. Full article
(This article belongs to the Special Issue Advances in the Diagnosis of Inherited/Genetic Diseases)
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24 pages, 624 KB  
Review
Integrating Artificial Intelligence into Perinatal Care Pathways: A Scoping Review of Reviews of Applications, Outcomes, and Equity
by Rabie Adel El Arab, Omayma Abdulaziz Al Moosa, Zahraa Albahrani, Israa Alkhalil, Joel Somerville and Fuad Abuadas
Nurs. Rep. 2025, 15(8), 281; https://doi.org/10.3390/nursrep15080281 - 31 Jul 2025
Cited by 1 | Viewed by 1715
Abstract
Background: Artificial intelligence (AI) and machine learning (ML) have been reshaping maternal, fetal, neonatal, and reproductive healthcare by enhancing risk prediction, diagnostic accuracy, and operational efficiency across the perinatal continuum. However, no comprehensive synthesis has yet been published. Objective: To conduct a scoping [...] Read more.
Background: Artificial intelligence (AI) and machine learning (ML) have been reshaping maternal, fetal, neonatal, and reproductive healthcare by enhancing risk prediction, diagnostic accuracy, and operational efficiency across the perinatal continuum. However, no comprehensive synthesis has yet been published. Objective: To conduct a scoping review of reviews of AI/ML applications spanning reproductive, prenatal, postpartum, neonatal, and early child-development care. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus through April 2025. Two reviewers independently screened records, extracted data, and assessed methodological quality using AMSTAR 2 for systematic reviews, ROBIS for bias assessment, SANRA for narrative reviews, and JBI guidance for scoping reviews. Results: Thirty-nine reviews met our inclusion criteria. In preconception and fertility treatment, convolutional neural network-based platforms can identify viable embryos and key sperm parameters with over 90 percent accuracy, and machine-learning models can personalize follicle-stimulating hormone regimens to boost mature oocyte yield while reducing overall medication use. Digital sexual-health chatbots have enhanced patient education, pre-exposure prophylaxis adherence, and safer sexual behaviors, although data-privacy safeguards and bias mitigation remain priorities. During pregnancy, advanced deep-learning models can segment fetal anatomy on ultrasound images with more than 90 percent overlap compared to expert annotations and can detect anomalies with sensitivity exceeding 93 percent. Predictive biometric tools can estimate gestational age within one week with accuracy and fetal weight within approximately 190 g. In the postpartum period, AI-driven decision-support systems and conversational agents can facilitate early screening for depression and can guide follow-up care. Wearable sensors enable remote monitoring of maternal blood pressure and heart rate to support timely clinical intervention. Within neonatal care, the Heart Rate Observation (HeRO) system has reduced mortality among very low-birth-weight infants by roughly 20 percent, and additional AI models can predict neonatal sepsis, retinopathy of prematurity, and necrotizing enterocolitis with area-under-the-curve values above 0.80. From an operational standpoint, automated ultrasound workflows deliver biometric measurements at about 14 milliseconds per frame, and dynamic scheduling in IVF laboratories lowers staff workload and per-cycle costs. Home-monitoring platforms for pregnant women are associated with 7–11 percent reductions in maternal mortality and preeclampsia incidence. Despite these advances, most evidence derives from retrospective, single-center studies with limited external validation. Low-resource settings, especially in Sub-Saharan Africa, remain under-represented, and few AI solutions are fully embedded in electronic health records. Conclusions: AI holds transformative promise for perinatal care but will require prospective multicenter validation, equity-centered design, robust governance, transparent fairness audits, and seamless electronic health record integration to translate these innovations into routine practice and improve maternal and neonatal outcomes. Full article
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