Search Results (650)

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

Aortic coarctation (CoA) comprises local narrowing of the aortic lumen, which is located at the level of the isthmus in 95% of patients and accounts for 5 to 8% of live births with congenital heart disease. It can be associated with other congenital defects, such as a bicuspid aortic valve (BAV), and in adulthood should be considered a secondary cause of hypertension in patients younger than 40 years, particularly in the presence of severe or resistant hypertension, in accordance with current hypertension guidelines. A correct diagnosis is necessary for the proper assessment and management of these patients. A multimodality imaging approach using ultrasound, computed tomography (CT), and MRI allows for accurate and effective diagnosis. The purpose of this review is to describe different non-invasive imaging techniques and highlight their advantages and disadvantages, aiming to provide a guide to clinicians and cardiovascular imaging specialists in choosing the best imaging tools to use in adults with native CoA. Full article

The post-implantation phase of mammalian development is crucial yet challenging to study due to ethical and technical constraints, particularly in humans. Recent revolutionary advances in extended in vitro culture systems for mammalian embryos now offer unprecedented windows into this developmental “black box”. This review synthesizes how these platforms, alongside stem cell-derived embryo models, are transforming our ability to model early human development in a dish. We detail the technological evolution from two-dimensional (2D) to three-dimensional (3D) cultures that support mouse, non-human primate, and human embryos through key stages of implantation and gastrulation, recapitulating events like lineage specification and axial patterning. Furthermore, we explore how these models serve as powerful tools for investigating the etiology of early pregnancy failure, screening for developmental toxicity of pharmaceuticals, and deciphering the molecular pathogenesis of birth defects. By bridging fundamental embryology with clinical and pharmacological applications, these innovative models herald a new era in biomedical research, holding significant promise for advancing reproductive medicine and regenerative strategies. Full article

Vision is fundamental to the acquisition of motor, cognitive, and social skills, playing a crucial role in typical development. Early visual impairments are associated with various neurodevelopmental conditions, including Autism Spectrum Disorder (ASD). The (Brain-specific serine/threonine-protein kinase 2, BRSK2) gene has been identified as a high-risk gene for ASD. This study aims to investigate the role of brsk2 in retinal photoreceptor development and visual function in zebrafish. Using behavioral assays, histological analysis, and transcriptomic profiling, we assessed the impact of brsk2 deletion on retinal structure and function. The results showed that brsk2ab^−/− zebrafish larvae exhibited significantly enhanced light perception compared to wild-type (WT) controls. Structural analysis of the retina revealed disruptions in the layered organization, along with up-regulated rhodopsin expression in retinal cells. Additionally, transcriptomic analysis indicated that key opsins and genes involved in visual development and phototransduction pathways were markedly up-regulated following brsk2 deletion. This research highlights the importance of brsk2 in early retinal circuit development and its potential implications for understanding sensory processing deficits in neurodevelopmental disorders. By linking BRSK2 to specific sensory phenotypes, this study addresses a critical gap in knowledge regarding the mechanisms underlying sensory abnormalities in ASD and related conditions. Full article

For decades, cervical insufficiency (CI) has been framed predominantly as a mechanical failure of the cervix resulting in painless mid-trimester dilatation. This disease-centered paradigm, reinforced by clinical teaching and administrative coding, does not fully capture the dynamic and biologically integrated nature of cervical remodeling. Accumulating evidence suggests that cervical change is governed by coordinated mechanical, inflammatory, and immunologic interactions rather than by a purely anatomic defect. To outline a process-oriented conceptual framework that situates CI within the broader preterm-birth continuum, this perspective aims to integrate biomechanical, inflammatory, and immunologic dimensions of cervical remodeling and to emphasize that infection- and inflammation-related changes represent dynamic, potentially modifiable elements that may inform more individualized, biology-guided clinical decision-making. This Perspective traces the evolution from a traditional “disease entity” interpretation of CI toward a more integrated view of cervical remodeling as a dynamic, biology-responsive process. Emerging data suggest that when intra-amniotic infection or inflammation is appropriately managed, cervical competence may be partially restored, and mechanical support can be applied more safely in selected patients. Clinical observations indicate that infection-controlled cerclage is associated with meaningful prolongation of gestation. Earlier reports describing double-level mechanical reinforcement techniques conceptually align with contemporary interpretations of infection-controlled emergent cerclage by linking surgical timing with the underlying biology of cervical change. Rather than proposing a prescriptive management pathway, this framework highlights how mechanical, inflammatory, and immunologic factors may interact across heterogeneous CI etiologies and how individualized intervention may be guided by biologic context. Understanding CI as a dynamic rather than a fixed condition provides a framework that integrates its mechanical, inflammatory, and immunologic dimensions within the preterm birth continuum. Such a perspective encourages individualized, biology-informed interpretation of cervical change and supports more context-specific use of established interventions such as cerclage. By emphasizing developmental processes rather than a static defect, this approach seeks to bridge classical clinical practice with contemporary insights into cervical remodeling. Full article

Introduction: To explore whether antenatal and preoperative factors predict disability-free survival of preterm newborns with biventricular complex congenital heart defects (CHD). Methods: Retrospective cohort study, using the prospectively designed database of Complex Pediatric Therapies Follow Up Program and a chart review of mother–newborn dyads, born under 37 weeks’ gestation with biventricular complex CHD, between 1997 and 2019, who had open heart surgery up to 6 weeks corrected age. Surviving children had neurodevelopmental assessments between 18 and 24 months corrected age. Bayley Scales of Infant Development, 2nd edition, and Bayley Scales of Infant and Toddler Development, 3rd edition, assessed cognitive, language, and motor skills; Adaptive Behavior Assessment System, 3rd edition, assessed adaptive skills. Univariate and multivariate analyses assessed predictors of mortality, disability (cerebral palsy, visual impairment, permanent hearing loss), and neurodevelopmental delay. Results: Of 84 preterm newborns (34.6 ± 2.1 weeks’ gestation, 2321 ± 609 g, 57% males), 8 (9.5%) died by 2 years of age; 69 (91%) survived without and 7 (9%) with disability. Chorioamnionitis was associated with death [Hazard ratio 7.92 (95% CI 1.3, 33.3), p = 0.025]; prolonged rupture of membranes was associated with disability [Odds Ratio 9.7 (95% CI 1.99, 46.9), p = 0.005]. Maternal diabetes, antenatal diagnosis of CCHD, birth head circumference, cardiopulmonary resuscitation, and chromosomal anomalies were associated with adverse neurodevelopment. Conclusions: Chorioamnionitis and prolonged rupture of membranes are associated with worse outcomes in preterm newborns with biventricular complex CHD up to 2 years of age. Adverse neurodevelopmental outcomes are associated with maternal diabetes and antenatal diagnosis of CCHD. Prospective studies are needed to confirm these results. Full article

Background: Folic acid supplementation (FAS) before and in early pregnancy prevents neural tube defects, but the benefits of extending FAS to late pregnancy on pregnancy outcomes remain unclear. We aimed to investigate the associations between duration of FAS and a spectrum of pregnancy outcomes, and to determine whether the associations were modified by maternal age or pre-pregnancy body mass index (BMI). Methods: This prospective multicenter study included 15,694 singleton pregnancies. We used mixed-effects log-binomial regression models to estimate the adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) for gestational diabetes mellitus (GDM), gestational hypertensive disorders (GHDs), pre-eclampsia, preterm birth, macrosomia, small (SGA) and large for gestational age (LGA), and the interaction effects of advanced maternal age and pre-pregnancy BMI. Results: Of 15,694 women, 4523 (28.8%) did not take FAS before or during pregnancy, 2854 (18.2%) took FAS only during peri-pregnancy, 921 (5.9%) took FAS from peri- to mid-pregnancy, and 7396 (47.1%) took it through late pregnancy. Compared with women without FAS, those supplemented until mid-pregnancy were associated with lower risks of GHDs (aRR 0.84, 95% CI 0.74, 0.96) and pre-eclampsia (aRR 0.81, 95% CI 0.67, 0.97). Supplementation until late pregnancy was associated with lower risks of preterm birth (aRR 0.67, 95% CI 0.59, 0.76), SGA (aRR 0.74, 95% CI 0.63, 0.87), and LGA (aRR 0.88, 95% CI 0.79, 0.97). Among women of advanced maternal age or with overweight/obesity, supplementation until mid-pregnancy was associated with higher risk of GDM. Conclusions: Extending FAS until mid-pregnancy is associated with lower risks of GHDs and preeclampsia, and extending it until late pregnancy is associated with lower risks of preterm birth, SGA, and LGA. However, women of advanced maternal age or with overweight/obesity should be cautious about prolonging FAS. Full article

Background: Molar–Incisor Hypomineralization (MIH) represents a developmental enamel defect of systemic origin, typically affecting the first permanent molars and often the incisors. Within the limitations of this study, several associations were observed between perinatal factors and MIH-related outcomes. However, most of these connections were not retained in adjusted analyses. Febrile illness during the first year of life showed a significant association with hypersensitivity. Methods: A structured 30-item questionnaire was distributed to mothers of 50 children diagnosed with MIH between February and March 2024. Data was analyzed using chi-square tests, with p < 0.05 considered significant, and univariate and multivariate logistic regressions at 95% confidence interval. Clinical diagnosis followed the Weerheijm (EAPD) criteria. Results: Maternal medication during pregnancy (antibiotics, antiepileptics, asthma drugs) was significantly associated with preterm birth (p = 0.01). Low birth weight correlated with tooth eruption disorders (p = 0.009) and perinatal complications such as hypoxia and respiratory distress (p = 0.0001). Fluoride application demonstrated a protective effect against discolorations (p = 0.005), caries (p = 0.002), and hypersensitivity (p = 0.01). In the multivariate model, febrile illness during the first year of life may be associated with hypersensitivity in MIH-affected teeth (aOR = 5.71, 95% CI: 1.01–32.27, p = 0.049). Conclusions: Maternal medication and perinatal complications, particularly low birth weight, were associated with MIH occurrence. Preventive strategies emphasizing maternal health, early screening, and remineralization-based therapies can mitigate long-term oral health impacts. Full article

Male reproductive disorders and declining fertility rates play an important role in birth rates, and their impact on future populations makes them one of the most serious public health issues of this century. Defects in spermatogenesis are the most common manifestation of male infertility, and exposure to environmental pollutants has been suggested as a potential cause. Nanomaterials, due to their unique physicochemical properties and widespread application, have raised growing concerns about their potential reproductive toxicity. Studies have shown that nickel nanoparticles (Ni NPs) have reproductive toxicity in male rats and mice, especially sperm damage. This study aimed to explore the male reproductive toxicity of Ni NPs and the role of mitochondrial fission in mouse spermatocytes (GC-2). Our results showed that Ni NPs induced the damage of mitochondrial structure and function in GC-2 cells and disrupted intramitochondrial homeostasis, thereby resulting in enhanced Dynamin-related protein 1(Drp1)-mediated mitochondrial fission and cell apoptosis, along with aggravated cytotoxicity and obvious reproductive toxicity. The mitochondrial division inhibitor 1(Mdivi-1) and lentiviral-transfected low expression of Dnm1l can significantly alleviate the germ cell toxicity caused by Ni NPs, suggesting a certain therapeutic effect. The novelty of this study lies in its systematic demonstration that Drp1-mediated mitochondrial division is a core pathogenic mechanism of Ni NP-induced male reproductive toxicity, and the validation of both pharmacological inhibition and genetic silencing as effective intervention strategies. Therefore, this study offers a reference for expanding the reproductive toxicity effect of Ni NPs and potential molecular mechanisms and provides an important basis for finding potential targets and treatment of Ni NPs. Full article

Adverse pregnancy outcomes (APOs) such as prematurity, low birth weight, stillbirth, and birth defects remain significant global health challenges. While many risk factors are known, APOs encompass a wide range of outcomes with diverse, sometimes poorly understood etiologies. Pregnancy-related acute kidney injury (PR-AKI) and liver injury are particularly associated with increased maternal and fetal mortality. This study investigated the association between hematological parameters, kidney and liver injury markers and adverse pregnancy outcomes. This cross-sectional study involved 714 pregnant women aged 18–40 years, conducted between August 2021 and August 2022. Maternal blood samples were collected before and after delivery to compare hematological parameters. Kidney and liver injury markers were measured using standard methods. The study analysed the association of these parameters with adverse pregnancy outcomes. The median age of participants was 24 years (Q1, Q3: 21, 26). Women with adverse pregnancy outcomes had statistically significant serum creatinine levels [0.52 mg/dL (0.45, 0.58)] compared to those without [0.50 mg/dL (0.44, 0.56)], although the difference was not clinically significant. Elevated Aspartate Transaminase (AST) levels (>90th percentile) were statistically associated with adverse pregnancy outcomes. Pairwise comparisons with Bonferroni corrections revealed significant differences in Hemoglobin (Hb), White Blood Cell (WBC), Red Blood Cell (RBC), platelet, and Packed Cell Volume (PCV) levels before and after delivery (p < 0.05) in both groups. Elevated AST levels, but not other hematological or biochemical parameters, were independently associated with adverse pregnancy outcomes, whereas creatinine differences lacked clinical impact. Full article

Copper (Cu), zinc (Zn), and selenium (Se) play a pivotal role in pregnancy. Both a deficiency and an excess of Cu, Zn, and Se have deleterious consequences for the outcome of pregnancy. Accordingly, maintaining optimal levels of circulating Cu, Zn, and Se is critical for proper fetal growth and development. However, to our knowledge, this is the first narrative global review that not only summarizes Cu, Zn, and Se levels in maternal and cord blood but also examines their associations with multiple adverse pregnancy outcomes. Thus, this up-to-date review seeks to address these key questions. To achieve these goals, literature was collected from the past several decades from three relevant databases (PubMed, Scopus, and Cochrane Library), and rigorous exclusion and inclusion criteria were set for peer-reviewed studies that met the requirements for a final inclusion in the review analysis. In this study, data is presented on the levels of Cu, Zn, and Se in maternal and cord blood across the globe (herein used to suggest optimal maternal levels for Cu, Zn, and Se during a normal, healthy pregnancy), elemental differences between maternal and cord blood, and the fluctuations of their blood levels depending on the trimester of pregnancy. In addition, the review presents findings on the effects of Cu, Zn, and Se on birth weight and anthropometric parameters of newborns, as well as on preterm birth, preeclampsia, gestational diabetes mellitus, neural tube defects, and congenital heart defects. Full article

Selective laser melting (SLM) is a 3D printing technology for precision manufacturing. Owing to its high forming accuracy, parts fabricated by SLM can often be used directly without secondary machining. Consequently, the stress field in the structure, especially local stress concentration in small regions, is of great importance. Building on our previous work, this study proposes an accurate and efficient thermo-mechanical analysis method that combines a computational fluid dynamics (CFD) model and a finite element method (FEM) model for stress prediction in micrometer-scale SLM. Compared with the conventional element birth–death method, the present model more faithfully reproduces the SLM process and the post-solidification morphology and stress distribution. Numerical simulation of a single-track TC4 scan shows that pronounced surface undulations and lack-of-fusion regions exhibit significant stress concentration: the local residual stress can reach approximately 900 MPa, whereas regions with relatively smooth surface geometry exhibit stresses of about 650 MPa. This indicates a clear positive correlation between surface quality and stress concentration. The results provide a new theoretical basis for understanding defect formation mechanisms, spatial stress distribution, and scan-path optimization in SLM components. Full article

Solitary Median Maxillary Central Incisor Syndrome is unique congenital developmental defect affecting midline structures of the head and the body. The prevalent symptom is a solitary median incisor of the maxilla in primary and secondary dentition, which is positioned exactly in the midline of the alveolus. Other abnormalities that are characteristic of the syndrome include holoprosencephaly, nasal cavity anomalies, cleft palate–lip, hypotelorism, and microcephaly. It is estimated to occur in 1:50,000 live births, with female gender predilection. The cause of the syndrome is related to midline defects in the migration and connection of the prechordal mesoderm between the 35th and 38th days post-conception. Early diagnosis of SMMCI is important for practicing orthodontists, as it may be a symptom of other developmental abnormalities. The aim of this study is to report a case of SMMCI syndrome in a patient treated in the Department of Orthodontics and Facial Malformation of the University of Medical Sciences in Poznan. Full article

Diabetic retinopathy (DR), a leading cause of vision loss in diabetic patients, involves complex pathological mechanisms including neurodegeneration, microvascular damage, inflammation, and oxidative stress. Recent studies have identified ferroptosis—a ferrodependent cell death mechanism—as playing a pivotal role in DR development. Existing evidence indicates that oxidative stress and mitochondrial dysfunction induced by hyperglycemia may contribute to retinal damage through the ferroptosis pathway in DR. Ferroptosis inhibitors such as Ferostatin-1 have demonstrated protective effects against DR in animal models. The core mechanisms of ferroptosis involve iron homeostasis imbalance and lipid peroxidation, with key regulatory pathways including GPX4-dependent and non-dependent mechanisms (such as FSP1-CoQ10). Within the signaling network, Nrf2 inhibits ferroptosis, p53 promotes it, while Hippo/YAP functions are environment-dependent. Non-coding RNAs and epigenetic modifications (e.g., DNA methylation and histone modifications) also participate in regulation. In DR, iron overload, GPX4 dysfunction, and p53 upregulation collectively induce ferroptosis in various types of retinal cells, making these pathways potential therapeutic targets. This review not only elaborates the role of iron metabolism imbalance and ferroptosis pathway in the occurrence and development of DR but also summarizes the new therapeutic approaches of DR targeting ferroptosis pathway. Investigating the relationship between ferroptosis and DR not only helps unravel its core pathophysiological mechanisms but also provides theoretical foundations for developing novel therapeutic approaches. Full article

Molar incisor hypomineralisation (MIH) is a developmental defect affecting permanent first molars and often the incisors too. Hypomineralised second primary molars (HSPM) have been proposed as potential early indicators of MIH. Aim: The aim was to identify potential aetiological factors associated with MIH and assess their relationship with HSPM in a pilot study. Methods: A cross-sectional case–control study was conducted with 120 patients (60 cases and 60 controls), aged 7–15 years, from the Paediatric Dentistry Postgraduate Programme. MIH was diagnosed following European Academy of Paediatric Dentistry (EAPD) guidelines. Parents completed a structured questionnaire on potential aetiological factors. Results: MIH was significantly associated with maternal smoking during pregnancy (p = 0.013), birth hypoxia (p = 0.013) and the use of amoxicillin and inhalation therapy during infancy (p < 0.001). It was also associated with tonsillitis (p = 0.022), bronchiolitis (p = 0.005) and other respiratory disorders (p = 0.049). HSPM was associated with anaemia and hypotension during pregnancy (p = 0.001), bottle-feeding (p = 0.044) and urinary tract infections (p = 0.003). No statistically significant association was found between MIH and HSPM. Conclusions: This pilot study has identified specific prenatal, perinatal, and postnatal factors associated with MIH and HSPM. The findings emphasise the clinical relevance for early diagnosis and management and highlight the need for studies with larger sample sizes to validate these associations. Full article