Search Results (383)

Down syndrome (DS), stemming from the triplication of human chromosome 21, results in intellectual disability, with early mid-life onset of Alzheimer’s disease (AD) pathology. Early interventions to reduce cognitive impairments and neuropathology are lacking. One modality, maternal choline supplementation (MCS), has shown beneficial effects on behavior and gene expression in neurodevelopmental and neurodegenerative disorders, including trisomic mice. Loss of basal forebrain cholinergic neurons (BFCNs) and other DS/AD relevant hallmarks were observed in a well-established trisomic model (Ts65Dn, Ts). MCS attenuates these endophenotypes with beneficial behavioral effects in trisomic offspring. We postulate MCS ameliorates dysregulated cellular mechanisms within vulnerable BFCNs, with attenuation driven by novel gene expression. Here, choline acetyltransferase immunohistochemical labeling identified BFCNs in the medial septal/ventral diagonal band nuclei of the basal forebrain in Ts and normal disomic (2N) offspring at ~11 months of age from dams exposed to MCS or normal choline during the perinatal period. BFCNs (~500 per mouse) were microisolated and processed for RNA-sequencing. Bioinformatic assessment elucidated differentially expressed genes (DEGs) and pathway alterations in the context of genotype (Ts, 2N) and maternal diet (MCS, normal choline). MCS attenuated select dysregulated DEGs and relevant pathways in aged BFCNs. Trisomic MCS-responsive improvements included pathways such as cognitive impairment and nicotinamide adenine dinucleotide signaling, among others, indicative of increased behavioral and bioenergetic fitness. Although MCS does not eliminate the DS/AD phenotype, early choline delivery provides long-lasting benefits to aged trisomic BFCNs, indicating that MCS prolongs neuronal health in the context of DS/AD. Full article

Background and Clinical Significance: Brugada syndrome (BrS) is a rare inherited cardiac channelopathy, often associated with SCN5A loss-of-function mutations. Clinical presentations range from asymptomatic to malignant arrhythmias and sudden cardiac death. Physiological and pharmacological stressors affecting sodium channel function—such as pyrexia, certain medications, and possibly pregnancy—may unmask or exacerbate arrhythmic risk. However, there is limited information regarding pregnancy and obstetric outcomes. Obstetric management remains largely informed by isolated case reports and small case series. A literature review was conducted using OVID Medline and Embase, identifying case reports, case series, and one retrospective cohort study reporting clinical presentation, obstetric management, and outcomes in maternal BrS. A case is presented detailing coordinated multidisciplinary input, antenatal surveillance, and intrapartum and postpartum care to contribute to the growing evidence base guiding obstetric care in this complex setting. Case Presentation: A 30-year-old G2P0 woman with asymptomatic BrS (SCN5A-positive) was referred at 31 + 5 weeks’ gestation for multidisciplinary antenatal care. Regular review and collaborative planning involving cardiology, anaesthetics, maternal–fetal medicine, and obstetrics guided a plan for vaginal delivery with continuous cardiac and fetal monitoring. At 38 + 0 weeks, the woman presented with spontaneous rupture of membranes and underwent induction of labour. A normal vaginal delivery was achieved without arrhythmic events. Epidural block with ropivacaine and local anaesthesia with lignocaine were well tolerated, and 24 h postpartum monitoring revealed no abnormalities. Conclusions: This case adds to the limited but growing literature suggesting that with individualised planning and multidisciplinary care, pregnancies in women with BrS can proceed safely and without complication. Ongoing case reporting is essential to inform future guidelines and optimise maternal and fetal outcomes. Full article

Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women may experience two or more consecutive pregnancy losses. Previous studies have investigated risk factors for RPL, including maternal age, uterine pathology, genetic anomalies, infectious agents, endocrine disorders, thrombophilia, and immune dysfunction. However, RPL is a disease caused by a complex interaction of genetic factors, environmental factors (e.g., diet, lifestyle, and stress), epigenetic factors, and the immune system. In addition, due to the lack of research on genetics research related to RPL, the etiology remains unclear in up to 50% of cases. Platelets play a critical role in pregnancy maintenance. This study examined the associations of platelet receptor and ligand gene variants, including integrin subunit beta 3 (ITGB3) rs2317676 A > G, rs3809865 A > T; fibrinogen gamma chain (FGG) rs1049636 T > C, rs2066865 T > C; glycoprotein 1b subunit alpha (GP1BA) rs2243093 T > C, rs6065 C > T; platelet endothelial cell adhesion molecule 1 (PECAM1) rs2812 C > T; and platelet endothelial aggregation receptor 1 (PEAR1) rs822442 C > A, rs12137505 G > A, with RPL prevalence. In total, 389 RPL patients and 375 healthy controls (all Korean women) were enrolled. Genotyping of each single nucleotide polymorphism was performed using polymerase chain reaction–restriction fragment length polymorphism and the TaqMan genotyping assay. All samples were collected with approval from the Institutional Review Board at Bundang CHA Medical Center. The ITGB3 rs3809865 A > T genotype was strongly associated with RPL prevalence (pregnancy loss [PL] ≥ 2: adjusted odds ratio [AOR] = 2.505, 95% confidence interval [CI] = 1.262–4.969, p = 0.009; PL ≥ 3: AOR = 3.255, 95% CI = 1.551–6.830, p = 0.002; PL ≥ 4: AOR = 3.613, 95% CI = 1.403–9.307, p = 0.008). The FGG rs1049636 T > C polymorphism was associated with a decreased risk in women who had three or more pregnancy losses (PL ≥ 3: AOR = 0.673, 95% CI = 0.460–0.987, p = 0.043; PL ≥ 4: AOR = 0.556, 95% CI = 0.310–0.997, p = 0.049). These findings indicate significant associations of the ITGB3 rs3809865 A > T and FGG rs1049636 T > C polymorphisms with RPL, suggesting that platelet function influences RPL in Korean women. Full article

This study evaluated the effects of maternal supplementation with rumen-protected methionine (RPM), alone or combined with rumen-protected choline (RPC) and betaine (RPB), during the periconceptional and prepartum periods on reproductive outcomes and offspring performance in Chios ewes. One hundred synchronized ewes were assigned to three groups—control (no supplementation), M (5.50 g RPM/day), and MCB (3.50 g RPM, 1.60 g RPC, 0.49 g RPB/day)—from day −14 to +14 relative to mating. Blood was collected on days −14, 0, and +14 for ABTS (2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), ferric-reducing ability (FRAP), and malondialdehyde (MDA), on days 18 and 21 for progesterone, and on day 26 for pregnancy-associated glycoprotein (PAG) detection. Thirty days before and up to lambing, the ewes were further divided into C-C, C-M, C-MCB, M-M, M-C, MCB-MCB, and MCB-C subgroups. Embryonic loss did not differ between groups. FRAP was higher (p < 0.001) in MCB ewes, and ABTS was lower (p < 0.05) in M ewes, in the periconceptional period. Offspring in the C-M, C-MCB, M-M, M-C, and MCB-MCB groups had higher birth weights (p < 0.01), along with increased MDA levels (p < 0.05). The results suggest that maternal methyl donor supplementation during early and/or late gestation enhances antioxidant status, supports embryonic development, and increases birth weight. Full article

Maternal and child health during pregnancy is an important issue in global public health, and the classification accuracy of fetal cardiotocography (CTG), as a key tool for monitoring fetal health during pregnancy, is directly related to the effectiveness of early diagnosis and intervention. Due to the serious category imbalance problem of CTG data, traditional models find it challenging to take into account a small number of categories of samples, increasing the risk of leakage and misdiagnosis. To solve this problem, this paper proposes a two-step innovation: firstly, we design a method of adaptive adjustment of misclassification loss function weights (MAAL), which dynamically identifies and increases the focus on misclassified samples based on misclassification rates. Secondly, a primary and secondary correction network model (MAC-NET) is constructed to carry out secondary correction for the misclassified samples of the primary model. Experimental results show that the method proposed in this paper achieves 99.39% accuracy on the UCI publicly available fetal health dataset, and also obtains excellent performance on other domain imbalance datasets. This demonstrates that the model is not only effective in alleviating the problem of category imbalance, but also has very high clinical utility. Full article

Background/Objectives: Overt hypothyroidism during pregnancy has been linked to adverse outcomes, including preterm birth, low birth weight, and impaired fetal neurocognitive development. This study aimed to evaluate pregnancy complications in women with overt hypothyroidism (TSH ≥ 10) through a cross-sectional study. Methods: Data from 259,897 live-birth pregnancies (2013–2022) from Clalit Health Services (CHS) were analyzed. The study included all CHS-insured women aged ≥ 18 years with available TSH results during pregnancy. Overt hypothyroidism was defined as a mean TSH ≥ 10 mIU/L, while the euthyroid reference group had TSH levels < 4 mIU/L and no history of hypothyroidism or levothyroxine use. Cases of overt hypothyroidism were matched with 15 controls using propensity score-based matching. Covariates included maternal age, ethnicity, socioeconomic status, IVF use, recurrent pregnancy loss, and smoking. Pregnancy complications were compared between groups using descriptive statistics and univariate analysis. A quasi-Poisson regression model was used to assess complication risk in overt hypothyroidism versus matched controls. Results: The final analysis included 9125 euthyroid and 611 overt hypothyroid pregnancies, with comparable baseline characteristics between groups. No significant differences were found in maternal age, ethnicity, socioeconomic scores, IVF rates, recurrent pregnancy loss, diabetes, smoking, gestational age at delivery, or rates of preterm birth, pre-eclampsia, gestational diabetes, cesarean section, and intrauterine growth restriction. Overall, overt hypothyroidism was not associated with increased complications. Sensitivity analyses using maximum TSH levels during pregnancy showed a slightly elevated risk for pregnancy complications (IRR 1.1, CI 1.04–1.18; p = 0.002). Conclusions: Overt hypothyroidism was not associated with an increased risk of adverse pregnancy outcomes when adjusted for confounding factors, suggesting that treatment decisions should be made on an individual basis. Full article

Pathogenic variants in the MAP1B gene have been associated with neurological impairment, including intellectual disability, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, brain malformations, cognitive hearing loss, short stature, and dysmorphic features. However, few cases with detailed clinical characterization have been reported. We describe a 12-year-old boy carrying a loss-of-function MAP1B variant, presenting with severe elimination disorders despite normal intelligence. He was referred to the genetics service due to persistent elimination issues, including daytime urinary incontinence, nocturnal enuresis, and fecal incontinence. He had normal motor and cognitive development, with an IQ of 99; however, he also presented with ADHD, short stature, microcephaly, and myopia. Brain MRI revealed bilaterial subependymal periventricular nodular heterotopia (PVNH). Audiometry showed normal bilateral hearing. Testing fragile X syndrome (FXS) and karyotype analyses yielded normal results. Whole exome sequencing (WES) revealed a nonsense pathogenic variant in MAP1B (c.895 C>T; p.Arg299*). No other family members showed a similar phenotype; however, a great-uncle and a great-aunt had a history of nocturnal enuresis until age 10. The patient’s deceased mother had short stature and psychiatric disorders, and a history of consanguinity was reported on the maternal side. This case broadens the phenotypic spectrum associated with MAP1B syndrome, suggesting that elimination disorder, frequently reported in FXS, should also be evaluated in MAP1B pathogenic variant carriers. In addition, the presence of short stature also appears to be part of the syndrome. Full article

Immunological factors have gained growing recognition as key contributors to recurrent pregnancy loss (RPL) after in vitro fertilization (IVF), representing a major challenge in reproductive medicine. RPL affects approximately 1–2% of women trying to conceive naturally and up to 10–15% of those undergoing IVF, where overall success rates remain around 30–40% per cycle. An imbalance in maternal immunological tolerance toward the semi-allogeneic fetus during pregnancy may lead to miscarriage and implantation failure. IVF-related ovarian stimulation and embryo modification offer additional immunological complications that can exacerbate existing immune dysregulation. Recent advances in reproductive immunology have significantly deepened our understanding of the immune mechanisms underlying RPL following IVF, particularly highlighting the roles of regulatory T cells (T regs), natural killer cells, cytokine dysregulation, and disruptions in maternal–fetal immune tolerance. In order to better customize therapies, this evaluation incorporates recently discovered immunological biomarkers and groups patients according to unique immune profiles. Beyond conventional treatments like intralipid therapy and intravenous immunoglobulin, it also examines new immunomodulatory medications that target certain immune pathways, such as precision immunotherapies and novel cytokine modulators. We also discuss the debates over immunological diagnostics and therapies, such as intralipid therapy, intravenous immunoglobulin, corticosteroids, and anticoagulants. The heterogeneity of patient immune profiles combined with a lack of strong evidence highlights the imperative for precision medicine to improve therapeutic consistency. Novel indicators for tailored immunotherapy and emerging treatments that target particular immune pathways have encouraging opportunities to increase pregnancy success rates. Improving management approaches requires that future research prioritize large-scale clinical trials and the development of standardized immunological assessments. This review addresses the immunological factors in RPL during IVF, emphasizing underlying mechanisms, ongoing controversies, and novel therapeutic approaches to inform researchers and clinicians. Full article

Background: Childhood hearing loss is a public health problem of critical importance associated with speech development, academic achievement, and quality of life. Parents’ awareness and knowledge about risk factors contribute to early detection and timely intervention.  Objective: This study aims to examine Jordanian mothers’ knowledge of childhood hearing loss risk factors and investigate the impact of education level and socioeconomic status (SES) on the accuracy and comprehensiveness of this knowledge with the moderating effect of health literacy. Material and Methods: The approach employed an embedded mixed-methods design with a dominant quantitative strand supported by qualitative data, utilizing quantitative surveys (n = 250), analyzed using structural equation modeling (SEM) in SmartPLS, and qualitative interviews (n = 10), analyzed thematically to expand upon the quantitative findings by exploring barriers to awareness and healthcare-seeking behaviors. Results: The accuracy and comprehensiveness of knowledge of hearing loss risk factors were also positively influenced by maternal knowledge of hearing loss risk factors. Maternal knowledge was significantly associated with both education level and socioeconomic status (SES). Furthermore, maternal knowledge and accuracy were significantly moderated by health literacy, such that mothers with higher health literacy exhibited a stronger relationship between knowledge and accuracy. Qualitative findings revealed that individuals encountered barriers to accessing reliable information and comprehending medical advice and faced financial difficulties due to limited options for healthcare services. Conclusions: These results underscore the need for maternal education programs that address specific issues, provide simplified healthcare communication, and enhance access to pediatric audiology services. Future research should explore longitudinal assessments and intervention-based strategies to enhance mothers’ awareness and detect early childhood hearing loss. Full article

Early embryonic loss is a major cause of reproductive inefficiency in cattle, primarily due to premature luteolysis. Interferon tau (IFN-τ), secreted by the trophoblast, plays a critical role in maternal recognition of pregnancy by maintaining corpus luteum function. However, its practical application has been limited by its rapid degradation and short half-life in vivo. Here, we developed a novel formulation of recombinant bovine IFN-τ, combining chitosan-based microencapsulation with starch–chitosan hydrogel delivery, enabling sustained intrauterine release. This dual-delivery strategy offers a significant improvement over conventional IFN-τ administration methods that rely on repeated intrauterine infusions of soluble protein. The rbIFN-τ was expressed in Pichia pastoris, purified to 90.1% homogeneity, and structurally validated via homology modeling and molecular docking, confirming its interaction with type I interferon receptors. The encapsulated formulation retained antiviral activity, stimulated transcription of interferon-stimulated genes (PKR, OAS1, OAS2), and showed sustained release in vitro for up to 26 days. In vivo evaluation demonstrated safety and biological efficacy, with treated cattle showing inhibited luteolysis, sustained serum progesterone levels, and preserved corpus luteum integrity. This formulation represents a promising biotechnological approach to improve reproductive efficiency through a long-acting, species-specific IFN-τ delivery system. Full article

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

Background and Objectives: Calcium is an essential mineral that plays a vital role in fetal development and maternal health during pregnancy. The World Health Organization recommends a daily calcium intake of 1.5–2 g for pregnant adult women. Calcium deficiency during gestation may lead to complications, such as gestational hypertension, preeclampsia, loss of bone mineral density, impaired fetal development, and other adverse pregnancy outcomes. The aim of the present review is to evaluate the current clinical evidence on calcium intake during pregnancy. Methods: The present systematic review was conducted according to the PRISMA 2020 statement by searching two major databases, PubMed and Mendeley. The study protocol was registered in the Open Science Framework (DOI: osf.io/rvj7z). Inclusion criteria were clinical trials on calcium supplementation during pregnancy. Exclusion criteria were clinical guidelines, reviews, case reports, case series, letters, and commentaries. The Newcastle–Ottawa Scale was used to assess the risk of bias in the included studies. Results: Initially, 451 publications were identified, and after removal of duplicates and screening of titles and/or abstracts and/or full texts, 34 studies were included. The number of participants ranged between 30 and 22,000 women. Calcium supplementation was associated with lower incidence of and less severe gestational hypertension and preeclampsia, lower risk of preterm birth, longer pregnancy duration and higher neonatal birth weight, and improved maternal bone mineral density postpartum. When the doses were split up into smaller doses, the benefits were strongest with high-dose regimens (1.5–2 g/day). Conclusions: Calcium supplementation during pregnancy has beneficial effects on maternal and neonatal health, especially in populations with insufficient dietary daily calcium intake and women at high risk of hypertensive disorders. Daily dose may vary according to individual needs, daily dietary calcium intake, and general health status. Further large-scale randomized controlled trials (RCTs) are necessary to confirm these findings. Full article

Background/Objectives: Maternal thrombocytopenia, affecting approximately 10% of pregnancies, may be physiological (e.g., gestational thrombocytopenia) or pathological (e.g., immune thrombocytopenic purpura, aplastic anemia, preeclampsia, systemic lupus erythematosus). While gestational thrombocytopenia is typically benign, its severity and etiology may impact maternal and neonatal outcomes. This study examined the association between severe and moderate thrombocytopenia during pregnancy and perinatal outcomes, focusing on maternal hemorrhage and neonatal thrombocytopenia. Methods: A retrospective analysis was conducted of 182 pregnant women with thrombocytopenia who delivered at Incheon St. Mary’s Hospital and Seoul St. Mary’s Hospital between 2009 and 2019. Participants were classified into two groups: severe thrombocytopenia (platelet count <50 × 10⁹/L) and moderate thrombocytopenia (50–150 × 10⁹/L). Maternal hemorrhagic outcomes, transfusion needs, and neonatal platelet counts were evaluated. Statistical analyses were performed using univariate methods. Results: Severe thrombocytopenia was associated with greater blood loss during delivery, increased transfusion requirements, and elevated neonatal thrombocytopenia rates. Moderate to severe thrombocytopenia was more frequently identified in neonates delivered by mothers with immune thrombocytopenic purpura than in those delivered by mothers with gestational thrombocytopenia. Conclusions: Both the severity and etiology of maternal thrombocytopenia significantly affect the risk of maternal hemorrhage and neonatal thrombocytopenia. Careful prenatal assessment is essential to optimize management and reduce complications. Full article

Background: Preeclampsia (PE) remains a significant cause of maternal and fetal morbidity and mortality, with diagnostic criteria still evolving. Serum albumin, a potential marker of endothelial dysfunction and protein loss, has been proposed as a severity indicator in PE. This study evaluates the clinical utility of serum albumin levels, particularly values below 2 g/dL, in assessing PE severity and predicting maternal–fetal complications. Methods: We conducted a prospective and descriptive study including 59 pregnant women diagnosed with PE. The participants were divided into mild (n = 23) and severe (n = 36) PE groups based on national guidelines. Serum albumin, 24 h proteinuria, renal and hepatic function markers, and fetal outcomes were analyzed. ROC curve analysis was employed to determine albumin’s diagnostic performance. Results: Serum albumin levels were significantly lower in the severe PE group compared to the mild PE group (1.82 ± 0.50 vs. 2.44 ± 0.36 g/dL, p < 0.001). ROC analysis identified a threshold of 2.3 g/dL (sensitivity: 88.9%, specificity: 73.9%) for distinguishing PE severity. A strong association was observed between albumin < 2 g/dL and severe proteinuria (>3 g/24 h), but no significant association emerged with renal or hepatic dysfunction, fetal complications, or birth outcomes. Conclusions: Although serum albumin < 2 g/dL is associated with severe proteinuria, it does not independently correlate with other maternal or fetal complications in PE. These findings suggest that albumin may serve as a complementary, but not a standalone, marker in assessing PE severity. Full article

Background: Preeclampsia (PE) is a deadly obstetric complication in pregnant women leading to escalated rates of maternal and fetal mortality. Current research indicates that inadequate invasion of extravillous trophoblasts (EVTs) is a primary factor associated with the pathogenesis of PE. Insulin-like growth factor binding protein 2 (IGFBP2) plays a significant role in promoting cell migration, invasion, and angiogenesis. Researchers aim to investigate the clinical significance and elucidate the molecular mechanisms of IGFBP2 in the pathogenesis of preeclampsia. Methods: This study included 40 pregnant women categorized into 20 PE patients and 20 healthy controls. Expression levels of the mRNA were quantified using real-time quantitative polymerase chain reaction (qRT-PCR), and protein levels were assessed through Western blotting and immunofluorescence techniques. Moreover, the gain- and loss-of-function assays were conducted in human trophoblast cell line HTR-8/SVneo, and cellular models exhibiting overexpression and the knockdown of IGFBP2 were established. The proliferation, migration, and invasion of HTR-8/Svneo cells were determined using CCK8, wound-healing, and transwell assays, respectively. Results: The IGFBP2 was significantly downregulated, and the EMT was suppressed in the placental tissues of the PE patients. Functional experiments demonstrated that IGFBP2 enhanced the proliferation, invasion, and EMT of trophoblast cells activated through the PI3K/AKT signaling pathway. Conclusion: Our findings indicated that IGFBP2 enhances the proliferation, invasion, and EMT of trophoblast cells by activating the PI3K/AKT signaling pathway, serving as a potential therapeutic target in PE patients. Full article