Search Results (498)

Background: Preterm birth, the leading cause of neonatal mortality, is associated with reduced nephron endowment and an increased risk of kidney disease in later life. In preterm infants, the interruption of nephrogenesis leads to a lower nephron number and structural abnormalities. Prenatal factors such as intrauterine growth restriction, and postnatal factors including nephrotoxic medications, patent ductus arteriosus, perinatal asphyxia, and infections contribute to this deficit. Ultrasound is a key tool for assessing renal volume at birth and can, when indexed to body weight, be used to estimate nephron endowment, which is known to vary widely among individuals. Methods: This study analyzed 52 preterm infants with birth weight < 1000 g, assessing combined renal volume (sum of right and left kidney volumes) indexed to body weight. Results: The mean combined kidney volume-to-body weight ratio was 12.12 (SD = 2.03). Values below the 10th percentile (9.46) or more than one standard deviation below the mean (10.11) may indicate nephron deficiency at birth. Conclusions: Standardized ultrasound-based parameters enable the early identification of neonates at risk for nephron deficit, supporting targeted preventive strategies. Long-term follow-up is essential to detect early renal functional impairment and reduce the risk of chronic kidney disease. Full article

Kidney development in the first 1000 days of life is vulnerable to numerous prenatal, perinatal, and congenital factors. This review aims to analyze the main determinants of early kidney development and to highlight the role of pediatricians in identifying at-risk infants and implementing preventive strategies to reduce the risk of chronic kidney disease (CKD). For at-risk newborns, early assessment of kidney size and function is essential for the timely detection of functional decline. Key risk factors include prenatal exposures, perinatal complications, genetic conditions, and postnatal factors. Early, tailored nephrological follow-up is crucial for preventing CKD and its complications. Determining optimal monitoring intervals through clinical, laboratory, and ultrasound evaluations enables risk stratification, ensuring closer surveillance for the most vulnerable infants during this critical window. This review integrates evidence from experimental, epidemiological, and clinical studies and highlights the importance of early-life interventions in shaping renal health across the lifespan. Full article

Objective: Increased nuchal translucency (NT) thickness at 10–14 weeks’ gestation is a well-established marker of chromosomal abnormalities, foetal structural defects, genetic syndromes, and foetal death; however, its association with foetal central nervous system (CNS) abnormalities has not been systematically evaluated. This study aimed to review and synthesise existing evidence on the relationship between first-trimester increased NT and prenatal ultrasound–detected foetal CNS abnormalities. Methods: A systematic literature search of MEDLINE, Embase, and CINAHL was conducted in accordance with PRISMA guidelines and registered in PROSPERO. Studies reporting increased NT in singleton pregnancies and structural abnormalities of the foetal CNS identified on prenatal ultrasound were included. Study selection, data extraction, and quality assessment were performed independently by two reviewers. Results: Twenty-three studies, including 15,592 euploid pregnancies with increased NT, met the inclusion criteria. Definitions of increased NT varied across studies, most commonly >95th centile or ≥3.5 mm. The pooled prevalence of CNS anomalies was 1.16% (95% CI 0.68–1.95; I² = 80%). In three comparative studies including 6040 pregnancies with increased NT and 152,682 with normal NT, increased NT was associated with higher odds of CNS anomalies (OR 3.22, 95% CI 1.52–6.80; I² = 74.1%). Conclusions: These findings suggest that euploid foetuses with increased NT may have a higher risk of CNS abnormalities. Full article

Objective: We aimed to determine the ability of prenatal ultrasound to detect velamentous cord insertion (VCI) in twin pregnancies and identify factors influencing diagnostic sensitivity. Methods: This single-center retrospective study included twins delivered between April 2018 and March 2024. We excluded monochorionic monoamniotic twins, those without chorionicity or umbilical cord insertion data, and fetuses that died in utero. Umbilical cord insertion sites assessed by second-trimester transabdominal ultrasound (16 + 0 to 21 + 6 weeks of gestation) using color Doppler imaging were classified as normal, marginal, or velamentous. The results of postnatal macroscopic examinations served as reference standards. We calculated accuracy, sensitivity, specificity, positive (PPV) and negative (NPV) predictive values. The effects of examiner expertise, chorionicity, placental location, ultrasound device, and maternal body mass index (BMI) on diagnostic sensitivity were analyzed in subgroups. Results: We confirmed VCI in 45 (8.8%) of 514 delivered fetuses. Prenatal ultrasound correctly identified 14 VCI cases. Sensitivity, specificity, PPV, and NPV were 31.1% (14/45), 98.9% (464/469), 73.7% (14/19), and 93.7% (464/495), respectively. The overall accuracy was 93.0% (478/514). Sensitivity was significantly higher when ultrasound specialists conducted examinations compared with non-specialists and when twins were monochorionic diamniotic twins than dichorionic. Anterior placental location and high-performance ultrasound equipment were also associated with increased sensitivity, but were not statistically significant. Maternal BMI did not affect diagnostic sensitivity. Conclusions: Prenatal ultrasonographic detection of VCI in twin pregnancies has high specificity but limited sensitivity. Diagnostic performance was influenced by examiners’ experience and chorionicity. Routine assessment of cord insertion sites and targeted training might improve detection and support the optimized perinatal management of twin pregnancies. Full article

Prenatal whole-genome sequencing (WGS) is a comprehensive genetic test for fetal anomalies, enabling simultaneous detection of aneuploidies, copy number variants (CNVs), single-nucleotide variants (SNVs), small insertions/deletions, structural variants, and regions of absence of heterozygosity. However, its clinical performance, optimal sequencing strategies, and implementation challenges remain incompletely defined. We conducted a narrative review of PubMed-indexed studies (1966–December 2025) evaluating prenatal WGS in fetuses with structural anomalies. Across 29 studies, diagnostic yield ranged from approximately 20% to 40%, influenced by phenotype complexity, sequencing depth, and study design. Low-coverage WGS (≤5×) reliably detected large chromosomal abnormalities with a performance comparable to chromosomal microarray analysis. Moderate-coverage WGS (20–40×) additionally enabled detection of SNVs and structural variants, providing up to 30% incremental diagnostic yield after uninformative standard testing. Turnaround times were typically 14–21 days. Higher sequencing depth increases detection of variants of uncertain significance (0.6% to 35.7%) and secondary/incidental findings (1.6–30.8%). Prenatal WGS offers meaningful diagnostic value but requires careful patient selection, multidisciplinary expertise, and structured pre- and post-test genetic counseling to ensure responsible integration into routine clinical practice, with careful consideration of clinical benefit and economic feasibility. Full article

Preeclampsia (PE), pregnancy-associated high blood pressure linked to organ damage, affects 3–8% of all pregnancies and results worldwide in 70,000 maternal and 500,000 perinatal deaths each year. Untreated PE may progress to eclampsia with long-term health implications for both mother and child. Non-invasive prenatal diagnosis or screening applies cell-free DNA approaches and offers a less invasive and more economical method for early diagnosis and prediction of various pregnancy complications. Recently, cell-free assays, particularly blood-based cell-free DNA and RNA analysis, have shown great potential in early PE prediction and diagnosis. Here, we provide an updated review of the current understanding and discoveries of PE, focusing on recent publications (1 January 2019–30 December 2025) of liquid biopsy-derived circulating fetal cells (circulating trophoblasts and fetal nucleated red blood cells), cell-free DNA, cell-free RNA and small extracellular vesicles (i.e., exosomes). We aim to discuss the conceptual framework and technical evolution of liquid biopsy applications in preeclampsia pathogenesis, prediction and diagnosis. Progressing novel screening and diagnostic molecular biomarkers have high potential to facilitate early detection for patients at risk of PE. Liquid biopsy-based screening strategies may aid in providing timely intervention and treatment. Full article

Introduction: Cystic fibrosis (CF) frequently presents prenatally with meconium ileus (MI), a condition associated with significant neonatal morbidity and long-term gastrointestinal complications. The advent of highly effective CFTR modulators, particularly elexacaftor/tezacaftor/ivacaftor (ETI), during pregnancy remains off-label, and their role as in utero therapy for affected fetuses of carrier mothers is still emerging. Methods: We conducted a narrative literature review using PubMed, Embase, and Scopus to identify published reports of in utero CFTR modulator therapy for MI between 2022 and 2026. Seven relevant studies were identified and qualitatively synthesized. Their findings were interpreted in comparison with the present case. Results: We describe the first Italian case of prenatal ETI therapy for fetal CF. At 32 weeks’ gestation, ultrasound (US) findings were suggestive of evolving MI. Both parents were carriers of F508del CFTR and subsequent testing confirmed fetal homozygosity. Following urgent multidisciplinary consultation and ethics committee approval, maternal ETI therapy was initiated at 33 weeks’ gestation. After 21 days of treatment, follow-up fetal US demonstrated improvement in bowel dilatation and hyperchogenity. The infant was delivered at 36 + 2, passed meconium spontaneously, and required no surgical intervention. Pharmacokinetic assessment showed substantial transplacental transfer of all three ETI components, with cord-to-maternal plasma ratios of 0.34 (elexacaftor), 2.48 (tezacaftor), and 0.58 (ivacaftor), and detectable concentrations in amniotic fluid. Postnatally, sweat chloride was elevated, and pancreatic function transitioned from initially preserved to pancreatic insufficiency within the first month of life. Conclusions: This case and literature review suggest that prenatal CFTR modulation may influence the early trajectory of CF, potentially by preventing MI and potentially delaying the progression to pancreatic insufficiency and potentially reducing later gastrointestinal complications. While evidence remains limited, these findings highlight a potential therapeutic window during fetal life and underscore the need for prospective data collection, structured registries, and harmonized clinical guidance in this evolving field. Full article

Ultra-high-field (UHF) magnetic resonance imaging, defined as imaging at field strengths of 7 Tesla (7T) and above, represents a frontier technology in neuroimaging with emerging applications in prenatal brain research. This narrative review examines the current evidence on the potential benefits of UHF-MRI for investigating embryonic and fetal brain development. Through analysis of 97 studies identified across multiple databases, we find that UHF-MRI offers substantial advantages in spatial resolution, tissue contrast, and anatomical detail compared to conventional clinical field strengths (1.5T and 3T). The primary applications to date have been in ex vivo imaging of post-mortem fetal specimens and preclinical animal models, where UHF-MRI has enabled unprecedented visualization of laminar cortical organization, early sulcation patterns, microstructural development, and subtle anatomical features critical for understanding normal and abnormal neurodevelopment. Key benefits include enhanced delineation of transient developmental zones, improved characterization of cortical folding, superior detection of subtle malformations, and the ability to create high-resolution three-dimensional atlases of fetal brain development. However, significant technical and safety challenges currently limit in utero human applications, including concerns about specific absorption rate, acoustic noise, and fetal motion artifacts. This review identifies critical knowledge gaps and future directions for translating UHF-MRI technology to clinical prenatal diagnostics. Full article

Comparative evaluations of different serological methods for the diagnosis of toxoplasmosis in pregnant women remain limited, and the performance of indirect immunofluorescence assay (IFA), modified agglutination test (MAT), and chemiluminescent microparticle immunoassay (CMIA) has not been previously assessed simultaneously in this population. This study aimed to compare the performance of these three serological methods for the detection of Toxoplasma gondii antibodies in pregnant women. A total of 469 serum samples were collected from pregnant women receiving prenatal care through the Brazilian public healthcare system. Samples were tested using IFA, MAT, and CMIA for the detection of IgG and IgM antibodies. Statistical analyses included McNemar’s χ² test, Kappa agreement, and Pearson and Spearman correlation coefficients. IFA and MAT showed higher IgG seropositivity rates (53.1% and 51.2%, respectively) compared to CMIA (46.7% and 48.6%). Agreement between CMIA and IFA was moderate for IgG (Kappa = 0.51) and very strong for IgM (Kappa = 0.89). Pearson’s correlation for IgG between CMIA and IFA was moderate (r = 0.678), while Spearman’s correlation for IgM was weak. IFA and MAT demonstrated greater sensitivity for IgG detection than CMIA, while CMIA and IFA performed similarly for IgM. Conventional methods may complement automated systems to improve diagnostic accuracy in prenatal screening. Full article

Therapeutic termination of pregnancy (TToP) represents an intervention that is performed for medical reasons, such as risks to maternal health or severe fetal anomalies. Advances in prenatal screening and diagnostic tools—including serum markers, ultrasound, cell-free fetal DNA, chorionic villus sampling and amniocentesis—have significantly improved early detection and clinical decision-making. This narrative review synthesizes current knowledge on the genetic, environmental and psychosocial determinants that influence the decision of the patients to pursue TToP. The literature search was performed primarily using PubMed database, while Scopus and Google Scholar were used to identify additional relevant studies. Some of the selected studies, as well as certain sections of this review, address both therapeutic and voluntary termination of pregnancy, whereas others focus exclusively on TToP. Moreover, this review describes the types of abortion (medical or surgical/aspiration) along with their management strategies to prevent or address potential complications. It is well known that demographic, cultural and socio-economic factors continue to influence the access to TToP, as well as the perceptions of it. Psychiatric comorbidities (such as anxiety, affective and psychotic disorders) are observed with a higher prevalence among women undergoing TToP and may influence both the decision and psychological outcomes post-procedure. While most women report emotional relief after TToP, some of them experience depression, post-traumatic stress disorder or substance misuse. Legal and ethical considerations further complicate access to safe abortion, leading to situations where patients may resort to unsafe procedures, which result in higher rates of morbidity and mortality. Data from the EUROCAT network show rising trends in congenital anomalies like trisomy 13, trisomy 18 and caudal regression syndrome (conditions commonly associated with TToP). Therefore, it is mandatory to form a multidisciplinary team in these cases, integrating medical, psychological and ethical dimensions. Ensuring safe, evidence-based and compassionate access to TToP remains a critical component of reproductive healthcare. Full article

Maternal Smoking During Pregnancy (MSDP) remains a major source of fetal toxicant exposure. We applied adductomics to profile reactive adducts at the human serum albumin cysteine-34 (HSA-Cys³⁴) locus, which integrates longer-term exposures. HSA-Cys³⁴ adducts formed by acrylonitrile and ethylene oxide, two tobacco-related toxicants previously linked to smoking in adults, were quantified and compared with cotinine and MSDP status. Their relationships with other reactive adducts were also examined. Neonatal dried blood spots (DBS) from 110 children were analyzed. Cotinine and 55 Cys³⁴ adducts were measured by Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS). Associations were evaluated using linear regression, chi-square tests, and principal component analysis. Eighteen adducts differed significantly by MSDP status after Bonferroni correction (p ≤ 9.1 × 10⁻⁴). S-acrylonitrile was markedly elevated in exposed newborns, including those whose mothers reported smoking cessation after early pregnancy (p < 0.001). S-acrylonitrile correlated with 31 adducts related to oxidative stress and thiol metabolism, whereas cotinine correlated with eight. S-ethylene oxide, though detectable in DBS, showed no consistent association with MSDP. Adductomics analysis of newborn DBS sensitively captures molecular signatures of prenatal tobacco exposure and related oxidative stress. Acrylonitrile adducts appear to better reflect cumulative MSDP exposure than cotinine, highlighting the utility of adductomics for improved exposure assessment and mechanistic insight. Full article

Tubulinopathies are severe, non-progressive neurodevelopmental disorders caused by mutations in tubulin genes, leading to profound intellectual disability, drug-resistant epilepsy, motor impairment, and lifelong dependence on care. While historically diagnosed postnatally, advances in prenatal neurosonography now allow for the suspicion of this pathology in utero during routine second and early third-trimester anomaly scans. This narrative review synthesizes key findings from the literature published between 2019 and 2025 regarding prenatal ultrasonographic signs of tubulinopathies. Recognition of specific red-flag patterns should prompt dedicated neurosonography and targeted genetic testing. Early pregnancy detection is crucial for parental counseling and evidence-based decisions regarding pregnancy continuation. Full article

Myasthenia gravis (MG) is a prevalent autoimmune disorder affecting neuromuscular junctions, typically characterized by muscle weakness due to autoantibodies targeting acetylcholine receptors (AChR) or muscle-specific kinase (MuSK). Generalized MG is a more severe form of the condition than ocular MG. Although MG can strike at any age, young adult women are typically affected, especially in their reproductive years. MG is rare during pregnancy, with the first trimester and the postpartum period being the most common times for exacerbations. The influence of MG on pregnancy outcomes remains ambiguous, with some studies finding larger prevalence of issues such as preterm birth and small-for-gestational-age babies, while others indicate results similar to the general population. Management of MG during pregnancy necessitates careful monitoring and drug adjustments. Teratogenic concerns make several immunosuppressive drugs, such mycophenolate mofetil and methotrexate, contraindicated. In contrast, medications like prednisolone and pyridostigmine are generally recognized as safe. Women with MG may have flare-ups after giving birth, and infants may have transient neonatal myasthenia gravis. Comprehensive prenatal treatment and multidisciplinary assistance are crucial for promoting maternal and fetal health during pregnancy in women with MG. This paper examines the relevance of immunological biomarkers, RNAs, and other novel biomarkers in myasthenia gravis (MG). It emphasizes the need for more investigation to determine their role in the pathogenesis of MG, evaluate biomarker profiles across subgroups, and look at changes after treatment. The study also underlines the significance of high-throughput investigations to detect new biomarkers and reveal genetic variables impacting MG pathogenesis. Full article

Background/Objectives: Chlorpyrifos (CPF), a widely used organophosphate pesticide, has been associated with oxidative stress-mediated renal injury. Prenatal exposure may pose a risk for developmental nephrotoxicity; however, data regarding protective natural agents remain limited. This study evaluated the protective effects of Ganoderma lucidum (GNL) against CPF-induced renal alterations in rat offspring. Methods: Pregnant rats received CPF (5 mg/kg) and/or GNL (400 mg/kg) orally throughout gestation. On postnatal day 28, blood and kidney tissues from male offspring were collected for biochemical, ELISA, histopathological, immunohistochemical, and stereological analyses. Results: Prenatal CPF exposure significantly elevated serum urea and creatinine levels and induced oxidative stress, evidenced by increased malondialdehyde (MDA) and nitric oxide (NO) levels and decreased antioxidant enzyme activities (Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH)) (all p < 0.05). Renal TNF-α and IL-6 levels were significantly increased, indicating inflammatory activation. Apoptotic signaling was enhanced, demonstrated by elevated cleaved caspase-3 levels and an altered Bax/Bcl-2 ratio. Tubular injury biomarkers, kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), were markedly increased. Histopathological findings revealed tubular degeneration, while stereological analysis confirmed significant increases in cortical and glomerular volumes. GNL co-treatment attenuated oxidative stress, suppressed inflammatory cytokines, reduced caspase-3 activation, lowered KIM-1 and NGAL levels, and preserved renal structure. Conclusions: Prenatal CPF exposure induces developmental nephrotoxicity through interconnected oxidative, inflammatory, and apoptotic mechanisms. Ganoderma lucidum mitigates these alterations by restoring antioxidant defense systems, modulating the Bax/Bcl-2 apoptotic balance, suppressing pro-inflammatory cytokine production, reducing tubular injury markers, and normalizing stereologically detected renal structural changes. Full article

Background/Objectives: This study assesses the genetic basis of fetal congenital heart disease (CHD), which exhibits a complex etiology, by using chromosomal microarray analysis (CMA); it also elucidates perinatal outcomes and postnatal development to support prenatal diagnosis and genetic counseling. Methods: Pregnant women (n = 1195) who were diagnosed with fetal CHD based on echocardiography were selected along with those having an interventional prenatal diagnosis, all of whom underwent CMA. Depending on the gestational age, amniotic fluid or umbilical cord blood samples were collected. Patients were included if they were diagnosed with fetal CHD based on echocardiography. Those who could not consent to amniocentesis or umbilical vein puncture or who had contraindications for amniocentesis or umbilical vein puncture were excluded. Patients were studied until May 2025. Results: Of the 1195 fetuses with CHD, 140 had pathogenic copy number variation (pCNV). The pCNV detection rate in cases with a single CHD was 3.17%, whereas it was 13.51% in the group with multiple CHDs. The detection rate for pCNVs in patients with extracardiac abnormalities was 28.62%. The fetal and postnatal mortality rates were highest for fetuses with multiple CHDs. The survival rate was highest for fetuses with a single CHD. Early detection of CHD and timely genetic testing can inform clinical management of CHD-affected pregnancies; however, larger prospective studies are needed to establish their impact on perinatal outcomes. Conclusions: CMA provides valuable information for genetic counselling, as it identifies pathogenic variants associated with CHD. However, prognostic predictions should consider multiple clinical factors. Full article