Search Results (8,914)

Background: Prenatal vitamin D exposure has been proposed as a potential determinant of immune development and subsequent allergic disease risk in offspring; however, long-term cohort data remain inconsistent. Methods: We analyzed data from the KLOTHO birth cohort, including 98 adolescents with available allergic outcome assessment. A maternal–neonatal sub-cohort of mother–child pairs with available maternal and neonatal serum total 25-hydroxyvitamin D₃ [25(OH)D] measurements at delivery was used for vitamin D analyses. Allergic outcomes included asthma, allergic rhinitis, and eczema in offspring. Associations were evaluated using descriptive statistics, Spearman correlation analyses, and logistic regression models. Results: Maternal 25(OH)D concentrations were not significantly associated with asthma (ρ = 0.075, p = 0.652), allergic rhinitis (ρ = 0.100, p = 0.556), or eczema (ρ = 0.131, p = 0.426). In crude logistic regression models, vitamin D concentrations were not associated with asthma (odds ratio (OR) per 10 nmol/L: 1.07, 95% confidence interval (CI): 0.78–1.48, p = 0.67), allergic rhinitis (OR: 1.05, 95% CI: 0.76–1.45, p = 0.77), or eczema (OR: 1.17, 95% CI: 0.86–1.60, p = 0.31). Adjusted models including maternal age, pre-pregnancy body mass index (BMI), season of delivery, and ultraviolet exposure yielded similar non-significant findings, although analyses were limited by a reduced complete-case sample size. Conclusions: In this prospective cohort with follow-up into early adolescence, vitamin D status at delivery was not associated with asthma, allergic rhinitis, or eczema in offspring. These findings support a lack of statistically significant association; however, potential non-linear relationships should be interpreted cautiously, given the modest sample size. Full article

Therapeutic playgroups have shown promise in enhancing caregiver–infant mental health outcomes, yet tailored approaches for families following neonatal intensive care unit (NICU) admission remain limited. In this brief report on Quality Improvement, we evaluate key strategies and challenges in implementing an adapted therapeutic playgroup intervention designed for caregivers and infants with a history of NICU hospitalization at University of California, San Francisco and Zuckerberg San Francisco (UCSF) Zuckerberg San Francisco General Hospital (ZSFG) We conducted semi-structured interviews with NICU psychologists to assess local feasibility, barriers, and facilitators to implementation. Implementation science frameworks—the Consolidated Framework for Implementation Research (CFIR) and Proctor et al.’s implementation outcomes framework (acceptability, adoption, appropriateness, feasibility, and sustainability)—were used to guide data organization and interpretation. Qualitative reporting guidelines were followed to enhance transparency in describing interviews and analytic procedures. The psychologists emphasized the importance of embedding therapeutic playgroups within existing clinical workflows, providing flexible delivery models, and customizing curricula to meet cultural and family-specific needs. Multidisciplinary collaboration enhanced feasibility and parent engagement. Barriers included organizational constraints and variability in caregiver readiness. These findings inform local program development and highlight considerations for integrating dyadic mental health support into post-NICU care. Future work should incorporate caregiver perspectives and explore effective interventions across diverse settings. Full article

Selenium (Se) is an essential trace element. The bioactivity of Se arises from its incorporation into the 21st amino acid, selenocysteine (Sec). Twenty-five human genes have been identified that encode selenoproteins, each of which contains at least one Sec residue. Selenoprotein functions include antioxidant responses, thyroid hormone synthesis, and maintenance of cellular redox homeostasis. Due to its role in critical cellular functions, Se deficiency is associated with morbidities of the cardiovascular system and connective tissue in regions of countries with low soil Se content. While these morbidities are geography-specific and have been mitigated in adults through public health interventions, preterm infants remain susceptible to Se deficiency worldwide. Infants born preterm are deprived of fetal Se accrual in the 3rd trimester of pregnancy, a deficiency compounded by higher Se needs than term infants and older infants and dependence on parenteral nutrition (PN) and fortification. In addition, the composition of selenoproteins and selenometabolites in human milk is different from that in formula and PN, yet little is known about the biological impact of these differences. The knowledge gap in optimal Se supplementation is reflected in discrepant guidelines between North American and European/Chinese nutrition societies, whose recommended Se supplementation in preterm infants differs by more than 2-fold. In this review, we describe the biosynthesis, metabolism, and maternal-fetal transfer of Se. In addition, we address how developmentally regulated aspects of metabolism may impact how preterm infants respond to supplementation with different forms of Se. Lastly, we highlight current challenges and recommendations for optimizing Se levels in neonates based on available data. Full article

The microbiota–gut–brain axis (MGBA) is a complex bidirectional communication network integrating neural, endocrine, immune, and metabolic pathways linking intestinal microbiota to central nervous system function. Increasing evidence indicates that microbiota-derived signals are critical regulators of neurodevelopment and may contribute to vulnerability to neurodegenerative disorders across the lifespan. In this narrative review, we synthesize experimental and clinical evidence to define the key biological mechanisms underlying microbiota–brain interactions. Converging data indicate that immune activation, barrier dysfunction, and microbial metabolites, particularly short-chain fatty acids and tryptophan-derived compounds, represent central mediators linking gut dysbiosis to neuroinflammatory and neurodegenerative processes. Early-life microbial perturbations, driven by factors such as antibiotic exposure, diet, and psychosocial stress, appear to induce long-term immunometabolic programming that may increase susceptibility to neurological disorders later in life. Clinical studies consistently associate dysbiosis with neurodevelopmental conditions and major neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease; however, causal relationships remain incompletely defined due to heterogeneity and the predominance of observational data. Overall, the available evidence supports a lifespan model in which microbiota-driven immune and metabolic dysregulation contributes to both early neurodevelopmental trajectories and late-life neurodegeneration. While microbiome-based biomarkers and therapeutic strategies show promise, their clinical translation requires validation in longitudinal and interventional studies. Full article

Background: Preeclampsia is a heterogeneous multisystem disorder characterized by endothelial dysfunction and angiogenic imbalance. While the sFlt-1/PlGF ratio is widely used for diagnostic purposes, its role in defining biological phenotypes of preeclampsia remains insufficiently explored. This study aimed to investigate whether angiogenic imbalance is associated with distinct multisystem phenotypes of preeclampsia and with perinatal outcomes. Methods: We conducted a retrospective cohort study including 320 pregnant women, of whom 68 were diagnosed with preeclampsia. Multisystem phenotypes were defined using laboratory markers reflecting renal, hepatic, and hematologic involvement. The sFlt-1/PlGF ratio was compared across phenotypes. Associations with gestational age at delivery, birth weight, Apgar score, and neonatal intensive care unit (NICU) admission were evaluated. Receiver operating characteristic (ROC) analysis assessed the discriminatory performance of the sFlt-1/PlGF ratio for identifying the renal-dominant phenotype. Results: The mean sFlt-1/PlGF ratio was higher in preeclampsia compared to normotensive pregnancies (58.5 ± 20.3 vs. 34.6 ± 15.9). Within preeclampsia, the renal-dominant phenotype showed the highest ratio (66.0 ± 22.5), followed by hepatic (55.9 ± 18.2) and hematologic phenotypes (52.0 ± 16.8). The renal phenotype was associated with earlier delivery (34.6 weeks), lower birth weight (2196 g), higher NICU admission (10.7%), and lower Apgar scores. The sFlt-1/PlGF ratio demonstrated moderate discrimination for the renal phenotype (AUC = 0.69). Conclusions: Angiogenic imbalance varies across multisystem phenotypes of preeclampsia and is associated with meaningful perinatal differences. The sFlt-1/PlGF ratio may contribute to phenotype-based risk stratification, supporting a move toward precision obstetrics. Prospective studies are needed to validate phenotype-oriented classification models. Full article

COASY-related disorders (CRDs) are a spectrum of autosomal recessive conditions caused by the dysfunction of CoA synthase, an enzyme responsible for the final steps of CoA synthesis. Clinical manifestations of CRDs are highly variable, ranging from perinatal lethal pontocerebellar hypoplasia to childhood-onset neurodegenerative brain iron accumulation, which is often recognized after clinical regression. Recent reports have described a few individuals with CRD who screened positive for carnitine palmitoyltransferase-I deficiency by newborn screening (NBS). However, heterogeneous clinical presentations, conflicting biochemical/molecular sequencing of CPT1A, and a lack of metabolic characterization have led to lengthy, costly diagnostic journeys. To address some of these aspects, this investigation retrospectively evaluated NBS acylcarnitine patterns in five CRD cases using Collaborative Laboratory Integrated Reports (CLIR). A total of 25 metabolites/ratios were identified to deviate significantly from reference ranges and were primarily composed of elevated free carnitine and reduced long-chain acylcarnitine levels. While low acylcarnitine concentrations are often not reported due to a lack of lower reference cutoffs, ratios involving these metabolites relative to short-chain acylcarnitines could aid in identifying CRD cases via NBS. When comparing this pattern to CPT-Ia cases, we confirmed a nearly identical acylcarnitine pattern between these, and thus support the need to consider CRD in cases with NBS results suggestive of CPT-Ia. This study is the first case series to characterize NBS patterns in patients with CRD and highlights the unique opportunity for early detection, particularly in cases that are neonatally asymptomatic and have unremarkable confirmatory biochemical results. Full article

Biological E’s BEVAC^® is a recombinant DNA hepatitis B vaccine that has been used in India for more than a decade in routine early-life immunization and has recently been prequalified by the World Health Organization (WHO). This multicentre, single-blind, parallel-group, randomized phase IV trial, conducted at seven study sites in India, compared the immunogenicity and safety of BEVAC^® with a licensed comparator vaccine (GeneVac-B^®, Serum Institute of India Pvt. Ltd, Pune, India.) in healthy term neonates and infants. Participants received three 0.5 mL doses administered intramuscularly at birth (within 24 h), 6 weeks of age, and 14 weeks of age. The primary endpoint was seroprotection (anti-HBs IgG ≥10 mIU/mL) at 28 days after the third dose (Day 126), compared using a non-inferiority margin of −10%. Secondary endpoints included safety and tolerability outcomes through Day 126. A total of 468 neonates were randomized (234 per group), of whom 44% were female. At Day 126, seroprotection rates were 98.2% (95% CI: 95.39, 99.50) with BEVAC^® and 99.1% (95% CI: 96.78, 99.89) with the comparator; the between-group difference was −0.9% (95% CI: −3.09, 1.24), meeting the prespecified non-inferiority criterion. Solicited adverse events within 7 days after any dose occurred in 29.1% (95% CI: 23.3, 35.3) of BEVAC^® recipients and 35.0% (95% CI: 28.9, 41.5) of comparator recipients, most commonly pyrexia, injection-site pain, and swelling; all were mild-to-moderate. No serious adverse events were reported. BEVAC^® demonstrated non-inferior immunogenicity to the licensed comparator and a comparable safety profile. Full article

Background/Objectives: Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy caused by dysregulation of the alternative complement pathway, often related to genetic mutations or autoantibodies. The introduction of complement C5 inhibitors, such as eculizumab and ravulizumab, has significantly improved renal and overall outcomes. However, complement inhibition impairs host defense against encapsulated bacteria, markedly increasing the risk of invasive infections, particularly Neisseria meningitidis. Vaccination against meningococcal groups ACWY and B, along with temporary antibiotic prophylaxis, is therefore recommended before initiating anti-C5 therapy. Methods: We report the clinical course of a 13-year-old boy with aHUS secondary to anti–complement factor H (CFH) autoantibodies and CFHR3–CFHR1 homozygous deletion, treated with C5 inhibitors. Results: Despite complete meningococcal vaccination and a previous course of antibiotic prophylaxis, the patient developed meningitis during ongoing complement inhibitor therapy. Conclusions: This case highlights that breakthrough invasive infections may occur despite adherence to recommended preventive strategies. It underscores the need for sustained clinical vigilance, timely vaccine boosters, and careful reassessment of the risk–benefit balance of continued complement inhibition therapy. Full article

Cerebral palsy (CP) is a non-progressive neurological condition associated with neuroinflammation, motor impairments, and gastrointestinal dysfunction mediated by the gut–brain axis. Preserving the intestinal epithelial barrier integrity may represent a therapeutic strategy, and quercetin is a bioactive compound with potential intestinal protective effects. This study investigated the effects of neonatal quercetin treatment on morphometric parameters, oxidative stress markers, and epithelial barrier gene expression in an experimental CP model. Wistar rats were distributed into four groups according to health status and treatment with a vehicle (V) or quercetin (Q, 10 mg/kg, intraperitoneally): healthy control (CV and CQ) and CP (CPV and CPQ) (n = 10/group). Intestinal morphology, oxidative stress markers, and gene expression (occludin, zonulin, and mucin 2) were evaluated. CP animals showed segment-specific alterations, with structural impairment predominantly in the ileum and increased oxidative damage in the jejunum. Quercetin attenuated oxidative stress markers and modulated antioxidant enzyme activity in CP, increased jejunal tight-junction gene expression in both healthy and CP groups, and enhanced MUC2 expression only in healthy animals, without fully reversing CP-induced morphological changes. In conclusion, neonatal quercetin modulates oxidative stress and epithelial barrier-related gene expression, supporting its potential as an adjuvant strategy for intestinal barrier protection in experimental CP. Full article

Background and Objectives: Thrombocytopenia complicates 6.6–11.6% of pregnancies. While gestational thrombocytopenia (GT) is usually benign, etiologies such as immune thrombocytopenia (ITP), preeclampsia, and HELLP syndrome require individualized management. This study aimed to characterize the etiological spectrum, maternal peripartum hematologic outcomes, blood product utilization, and mode of delivery in a tertiary-center cohort of thrombocytopenic pregnancies and to assess whether platelet count should influence delivery mode decisions. Materials and Methods: This retrospective cohort study included 137 thrombocytopenic pregnant women at a tertiary center (2010–2019), categorized by etiology and severity. Peripartum hemoglobin, hematocrit, and platelet counts were compared between delivery groups. Blood product utilization was recorded and analyzed using t-test, ANOVA, chi-square, Fisher’s exact, and Fisher–Freeman–Halton tests; binary logistic regression was used for multivariable analysis. Results: GT (43.1%) and ITP (32.1%) were the most prevalent diagnoses; cesarean delivery rate was 52.6%. Postpartum Hb was higher in the vaginal delivery group (10.24 ± 1.28 vs. 9.80 ± 1.26 g/dL; p = 0.003), while platelet counts were paradoxically lower (p = 0.039). Platelet transfusion rates did not differ significantly between delivery modes (23.1% vs. 27.8%; p = 0.621). Severe thrombocytopenia required platelet transfusion in 92.6% of cases versus 11.6% (moderate) and 0% (mild) (p < 0.001). RBC transfusion was highest in gestational hypertensive disease (41.2%) versus GT (5.1%) and ITP (2.3%) (p < 0.001). General anesthesia was used in 75% of cesarean cases. Conclusions: Delivery mode in thrombocytopenic pregnancies should be guided by obstetric indications, not platelet count alone. Although postpartum platelet counts declined more steeply after vaginal delivery, this did not increase transfusion requirements. Gestational hypertensive disorders carried the greatest hemorrhagic burden, highlighting the need for etiology-specific multidisciplinary planning. The high general anesthesia rate warrants prospective institutional audit of anesthetic decision-making protocols to determine adherence to current neuraxial anesthesia thresholds. This study is limited to maternal peripartum hematologic outcomes; neonatal outcomes were not captured and should be addressed in future prospective research. Full article

Background: The care and management of a pregnant woman suffering from end-stage brain cancer is surrounded by medical, legal, and ethical controversies. When this brain pathology leads to brain death (BD), continuation of life-sustaining treatments has been considered futile and unethical. An exception could be the case of pregnancy, in order to deliver a healthy neonate. Aim: The presentation of a pregnant woman with a terminal stage brain astrocytoma, admitted in the intensive care unit (ICU) to support the pregnancy, until optimal fetal viability, after she had neurological deterioration and confirmed BD, and a brief literature review of previously relevant published cases. Case Presentation: A 36-year-old woman with a medical history of brain astrocytoma in the last 2 years was admitted in ICU for the first time due to status epilepticus, six months after she stopped anticonvulsant therapy. Her epilepsy was controlled, and a pregnancy of 14 weeks was confirmed. Two weeks later, she deteriorated. After a multidisciplinary approach, it was decided to mechanically ventilate the patient and support the pregnancy. Brain death was determined after a couple of days. Results: A cesarean section was performed 11 weeks after BD diagnosis (at 27 weeks of gestational age) resulting in the delivery of a live, premature infant, weighing 549 gr. Conclusions: Maternal corporeal support can maximize the chances for survival in the neonate by prolonging the pregnancy of a brain-dead woman. Full article

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is among the most common inherited enzymatic disorders worldwide and is an important risk factor for neonatal hyperbilirubinemia. Regional data from Western Saudi Arabia based on universal newborn screening remain limited. Objectives: To determine the prevalence of G6PD deficiency among newborns delivered at a tertiary center in Jeddah, Saudi Arabia, and to evaluate its association with clinically relevant outcomes, including early-onset jaundice (<24 h), need for phototherapy, admission for hyperbilirubinemia management, and readmission after discharge. Methods: We conducted a retrospective cohort study at King Abdulaziz Medical City, Western Region, Jeddah, Saudi Arabia, between January 2020 and May 2025. Cord blood samples from live-born infants were screened using a qualitative fluorescent spot test. Demographic variables (sex, gestational age, birth weight) and jaundice-related outcomes were extracted from the electronic medical record. Categorical variables were compared using chi-square testing, with p < 0.05 considered statistically significant. Results: Among 14,964 screened newborns, 489 were identified as G6PD deficient, yielding a prevalence of 3.3%. Prevalence was higher in males than in females (5.6% vs. 0.9%). Among the G6PD-deficient infants, early-onset jaundice occurred in 17.2%, phototherapy was required in 36.0%, and 16.5% were admitted for hyperbilirubinemia management. Readmission for worsening jaundice requiring phototherapy occurred in 11.0%, and no exchange transfusions were required. Compared with term infants, late preterm infants had higher rates of early-onset jaundice (11/49, 22.4% vs. 73/440, 16.6%) and phototherapy use (22/49, 45.0% vs. 154/440, 35.0%) (p < 0.01). Conclusions: G6PD deficiency was identified in a substantial proportion of newborns in this large screened cohort and was associated with clinically significant jaundice-related outcomes, particularly among late preterm infants. These findings underscore the importance of universal screening and structured postnatal follow-up to reduce the risk of severe hyperbilirubinemia and its complications. Early identification of G6PD-deficient infants should be accompanied by careful bilirubin monitoring, clear discharge planning, and timely post-discharge follow-up, especially for those born late preterm. Full article

Background/Objectives: Myelodysplastic syndromes (MDS) are associated with a significant risk of progression to acute myeloid leukemia (AML), affecting approximately 30% of patients. In high-risk MDS, leukemic transformation may occur within a short time frame, highlighting the need for early and reliable biomarkers of disease progression. Increasing evidence suggests that immune dysregulation and cytotoxic T-cell dysfunction contribute to disease evolution. This study aimed to evaluate PD-1 and CD57 expressions on CD8⁺ T cells and to investigate the CD8⁺PD-1⁺/CD4⁺PD-1⁺ ratio (PERLS) as a potential immunological marker predictive of leukemic transformation. Methods: Thirty-one patients with MDS were prospectively followed over a 12-month period. At baseline, patients underwent routine clinical and laboratory evaluation, including multiparameter flow cytometric assessment of bone marrow blasts. An extended immunophenotypic analysis of bone marrow samples was performed at study entry to assess PD-1 and CD57 expression on CD8⁺ T cells. Cytogenetic and molecular analyses were conducted when clinical findings suggested disease progression. Patients who developed signs of progression were re-evaluated approximately one month later, during the progression phase, to assess dynamic immunological changes. Results: Of the thirty-one patients included, eighteen progressed to AML, whereas thirteen remained clinically stable. Patients who progressed demonstrated a significant increase in PD-1 and CD57 expression on CD8⁺ T cells compared with stable patients. Moreover, a markedly higher CD8⁺PD-1⁺/CD4⁺PD-1⁺ (PERLS) ratio was observed in patients who subsequently developed AML, particularly during the progression phase. Conclusions: Dynamic immunophenotypic monitoring reveals that increased PD-1 on CD8⁺ T cells and an elevated PERLS ratio are associated with imminent leukemic transformation in MDS. These findings support the incorporation of immune-based biomarkers, particularly the CD8⁺PD-1⁺/CD4⁺PD-1⁺ ratio, into routine risk assessment to enable earlier identification of disease progression and timely therapeutic intervention. Full article

Myocardial ischemia–reperfusion injury (MIRI) significantly limits the clinical benefits of reperfusion therapy, underscoring a pressing need for effective interventions. This study examines the cardioprotective effects and underlying mechanisms of the natural amide alkaloid N-p-trans-Coumaroyltyramine (p-CT). Using hypoxia/reoxygenation (H/R) models in neonatal rat cardiomyocytes and in vivo rat MIRI models, we assessed p-CT pretreatment on cell viability, cardiac function, serum injury markers (lactate dehydrogenase, creatine kinase-MB, cardiac troponin T, and myoglobin), myocardial histopathology, ultrastructural alterations, and infarct size. The systematic screening and validation of potential targets were conducted via label-free quantitative proteomics, molecular docking, and Western blot. The results demonstrated that p-CT pretreatment dose-dependently mitigated H/R-induced cellular injury, improved cardiac function in MIRI rats, reduced serum markers of myocardial damage, alleviated pathological and ultrastructural injury in myocardial tissue, and significantly diminished infarct size. Proteomic analysis revealed 19 differentially expressed proteins specifically reversed by p-CT, with Titin-cap (Tcap) exhibiting the most pronounced downregulation in the MIRI model—a change effectively restored by p-CT pretreatment. Molecular docking indicated strong binding affinity between p-CT and Tcap protein. In summary, p-CT represents a promising cardioprotective agent, likely exerting its effects by targeting Tcap protein and upregulating its expression, thereby helping preserve cardiomyocyte structural and functional integrity. Full article