Search Results (636)

Objective: This study investigated the association between paternal preconception paternal body mass index (BMI) categories and physical/neurodevelopmental outcomes in Chinese small-for-gestational-age (SGA) children. Methods: A prospective cohort study enrolled 412 singleton SGA infants born at Peking University People’s Hospital in 2020–2022. Fathers were stratified into underweight, normal-weight, overweight, and obese groups. Follow-up assessments at 24–36 months evaluated growth parameters weight, height, BMI Z-scores and neurodevelopment using the Ages and Stages Questionnaire-3 (ASQ-3) and ASQ: Social–Emotional (ASQ:SE). Multivariable regression was adjusted for paternal covariates. Results: In SGA offspring, paternal underweight correlated with lower birth weights vs. normal/obese paternal BMI and the highest severe SGA rates. Prospective monitoring identified elevated BMI Z-scores (ΔZ = +0.40) and 8.7-fold heightened obesity risk in the paternal obesity group versus normal-weight counterparts. Neurodevelopmental evaluations demonstrated gross motor impairments in both underweight (ΔZ = −0.22) and obese paternal subgroups (ΔZ = −0.25) compared with the normal-weight group, with the obesity cohort additionally exhibiting problem-solving deficiencies (ΔZ = −0.19). The paternal obesity group manifested three-fold greater likelihood of social–emotional delays than the normal-weight group. The underweight and obese paternal groups showed 3.46-fold and 2.73-fold higher probabilities of gross motor deficits, respectively, while obesity was linked to 3.27-fold elevated problem-solving impairment risk-all comparisons versus normal paternal BMI. Overweight status showed no significant links to growth or neurodevelopmental outcomes. Normal-weight fathers had lower risks of obesity and neurodevelopmental issues. Conclusions: This study revealed U-shaped paternal BMI–neurodevelopment links in SGA offspring. Paternal obesity raised offspring obesity/neurodevelopmental risks, while underweight linked to severe SGA and motor deficits, highlighting paternal weight optimization’s modifiable role. Full article

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in childhood and adolescence, characterized by symptoms of inattention, hyperactivity, and impulsivity. These symptoms often interfere with academic, social, and family functioning. In recent years, the use of digital tools and video games has garnered attention as an innovative and engaging approach for neurocognitive rehabilitation. The primary objective of this randomized controlled study was to investigate the comparative effects of two cognitive intervention approaches—one based on new technologies and one using traditional methods—on attention, inhibitory control, and processing speed in children and adolescents diagnosed with ADHD. Thirty-three participants aged 6–17 years were randomly assigned to either an experimental group (n = 17), which received Nintendo Switch-based therapy, or a control group (n = 16), which received traditional board game therapy. Both interventions lasted 8 weeks and included 16 sessions. Outcomes were assessed using the WISC-V, STROOP, and CARAS-R tests. Results showed significant within-group improvements in both groups. The control group exhibited gains in sustained attention and inhibitory control (CARAS-R and STROOP tests, p < 0.05), while the experimental group improved significantly in processing speed, as measured by the WISC-V (p = 0.001). However, no significant differences were found between groups. These findings suggest that both interventions may be effective for enhancing different cognitive processes in children with ADHD. Importantly, the use of familiar digital technologies like the Nintendo Switch may promote greater motivation and adherence to treatment. Further research with larger samples and long-term follow-up is warranted to validate and extend these preliminary findings, as the current sample size was not powered to detect medium or small effects. Full article

Introduction: Globally, approximately 53 million children under the age of five live with some form of developmental disability. Exposure to heavy metals has been identified in the literature as a contributing factor in the etiology of neurodevelopmental disorders, however it usually is understudied. Even at low concentrations, these toxicants pose a risk to neurodevelopment, when affecting children early as in the prenatal period. This study aims to systematically review the literature on the associations between exposure to toxic heavy metals and neurodevelopmental outcomes in children. Method: The review was registered at the International Prospective Register of Systematic Review-PROSPERO, under number CRD420250653229 and searches were conducted in the PubMed, Scopus, Web of Science, EMBASE, Lilacs and PsycInfo databases. Results: A total of 68 articles were included, comprising 48 longitudinal studies and 20 cross-sectional studies, published between 2006 and 2025, with a combined sample of 215,195 individuals from 23 countries. Lead was the most consistently investigated metal, appearing in 75% of the studies, followed by mercury, cadmium, and arsenic. Most findings referred to prenatal exposure. Cognitive and motor outcomes were predominantly affected by exposure to Pb and Hg, while behavioral outcomes showed negative associations mainly with Pb and As. Conclusions: The majority of the studies analyzed indicated adverse effects resulting from exposure to heavy metals during pregnancy, especially in the early months, highlighting the vulnerability of the developing brain. Full article

Background: Monocarboxylate-transporter-8-(MCT8) deficiency, or Allan–Herndon–Dudley syndrome (AHDS), is a rare X-linked disorder caused by pathogenic variants in the SLC16A2 gene, leading to impaired transport of thyroid hormones, primarily T3 and T4, across cell membranes. The resulting central hypothyroidism and peripheral hyperthyroidism cause neurodevelopmental impairment and thyrotoxicosis. Despite the availability of therapy options, e.g., with triiodothyroacetic acid (TRIAC), diagnosis is often delayed, partly due to normal TSH levels or incomplete genetic panels. MCT8 deficiency is not yet included in newborn-screening programs worldwide. Case Description: We present a case of an infant genetically diagnosed with MCT8 deficiency at 5 months of age after presenting with muscular hypotonia, lack of head control, and developmental delay. Thyroid function testing revealed a normal TSH, low free T4, and significantly elevated free T3 and free T3/T4 ratio. Treatment with TRIAC (Emcitate^®) was initiated promptly, with close drug monitoring. Despite persistent motor deficits and dystonia, some developmental progress was observed, as well as reduction in hyperthyroidism. Discussion/Conclusions: This case underscores the importance of early free T3 and fT3/fT4 ratio testing in infants with unexplained developmental delay. Broader inclusion of SLC16A2 in genetic panels and consideration of newborn screening could improve early diagnosis and outcomes in this rare but treatable condition. Full article

This review highlights the emerging functional implications of nonsense-mediated mRNA decay (NMD) in human diseases, with a focus on its therapeutic potential for cardiovascular disease. NMD, conserved from yeast to humans, is involved in apoptosis, autophagy, cellular differentiation, and gene expression regulation. NMD is a highly conserved surveillance mechanism that degrades mRNAs containing premature termination codons (PTCs) located upstream of the final exon-exon junction. NMD serves to prevent the translation of aberrant mRNA and prevents the formation of defective protein products that could result in diseases. Key players in this pathway include up-frameshift proteins (UPFs), nonsense-mediated mRNA decay associated with p13K-related kinases (SMGs), and eukaryotic release factors (eRFs), among others. Dysregulation of NMD has been linked to numerous pathological conditions such as dilated cardiomyopathy, cancer, viral infections, and various neurodevelopmental and genetic disorders. This review will examine the regulatory mechanisms by which NMD regulation or dysregulation may contribute to disease mitigation or progression and its potential for cardiovascular disease therapy. We will further explore how modulating NMD could prevent the outcomes of mutations underlying genetically induced cardiovascular conditions and its applications in personalized medicine due to its role in gene regulation. While recent advances have provided valuable insights into NMD machinery and its therapeutic potential, further studies are needed to clarify the precise roles of key NMD components in cardiovascular disease prevention and treatment. Full article

Neurodevelopmental disorders are one of the most prevalent conditions today, and among the limitations in activity and restrictions in the participation of children and their families, we find intervention in activities of daily living; therefore, research focused on outcome measurement is one of the most active lines, and after COVID-19, telerehabilitation has garnered special interest. Background/Objectives: The study objective was to evaluate the effectiveness of a mobile health (mHealth) application in improving the performance of activities of daily living in children with neurodevelopmental disorders. Methods: The study employed a quasi-experimental design with a control group, using a fully remote mHealth-based intervention. The instruments used were a sociodemographic ad hoc, Pediatric Evaluation of Disability Inventory Computer, Family Outcomes Survey, Family Confidence Scale, and System Usability Scale. The final sample consisted of 13 participants. Results: The mHealth intervention showed significant improvements in occupational performance in the experimental group, especially in the global score and in the Responsibility dimension of the PEDI-CAT. No relevant differences were observed in the CON-FAN and FOS scales between groups, although the latter showed improvements over time. The usability of the app was rated positively (SUS = 69.75). Conclusions: The developed application presents good usability for families of children with neurodevelopmental disorders, but to obtain better outcome measures, the intervention should combine face-to-face sessions and the use of mHealth, as well as employing the family-centered model. Full article

Background and Objectives: Patent ductus arteriosus (PDA) is one of the most common cardiovascular conditions affecting preterm infants, with incidence rates reaching 60% in neonates born before 28 weeks gestation. Traditional clinical assessment alone often proves inadequate for accurate diagnosis, potentially leading to both overtreatment and undertreatment. Targeted neonatal echocardiography (TnECHO) has emerged as a powerful bedside tool that enables neonatologists to perform focused cardiac evaluations, providing real-time assessment of ductal significance and systemic hemodynamics. This systematic review aimed to comprehensively evaluate the clinical utility of TnECHO in the management of PDA in preterm infants, with specific focus on its diagnostic accuracy, impact on treatment decisions, and influence on clinical outcomes. Materials and Methods: Following PRISMA guidelines, we conducted a systematic search of PubMed, Web of Science, and Scopus from inception (earliest available date of each database) through February 2025. The search strategy combined terms for “Targeted Neonatal Echocardiography” and “Patent Ductus Arteriosus.” We included observational studies and randomized controlled trials (RCTs) evaluating TnECHO in PDA management, while excluding reviews and case reports. Data extraction focused on study design, population characteristics, TnECHO protocols, and clinical outcomes. Results: From 173 initial records, 11 studies met inclusion criteria. Eight studies were rated as high-quality (NOS score ≥ 7). TnECHO implementation was associated with a 49% reduction in PDA ligation rates and decreased need for multiple treatment courses. Studies demonstrated improved diagnostic precision in assessing shunt significance and myocardial function, leading to more tailored therapeutic approaches. The establishment of dedicated TnECHO services enhanced interdisciplinary collaboration between neonatologists and cardiologists. However, limitations included operator dependence, variable institutional protocols, and occasional missed minor cardiac anomalies. Conclusions: TnECHO represents a transformative approach to PDA management in preterm infants, enabling physiology-guided decision-making that reduces unnecessary interventions while maintaining patient safety. Current evidence supports its role in improving diagnostic accuracy and optimizing treatment timing. Future research should prioritize multicenter RCTs to establish standardized protocols and evaluate long-term neurodevelopmental outcomes. The integration of TnECHO into routine neonatal practice requires investment in training programs and quality assurance measures to maximize its clinical potential. Full article

Background/objectives: Optimal infant nutrition, particularly exclusive breastfeeding for the first 6 months, is crucial for both immediate and long-term health. The early years of life are essential for brain development due of the rapid maturation of social, emotional, cognitive and motor capacities. While benefits of breastfeeding are well established, its long-term impact on neurodevelopment remains underexplored. This study investigates the relationship between breastfeeding duration and neurodevelopment outcomes at 5 years of age. Methods: This prospective cohort study followed 92 term-born infants in Varna, Bulgaria (2017–2024). Parents provided informed consent and completed questionnaires regarding demographic characteristics, feeding practices and atopic diseases. At 5 years of age, children were assessed using the Neurodevelopmental Test for Five-Year-Olds. Results: Feeding practices differed significantly across groups (p < 0.001), with exclusive breastfeeding more prevalent among children breastfed for longer. At 5 years, significant differences were observed in language development (p = 0.037) and behavioral outcomes (p = 0.001). A linear regression model for behavioral outcomes (F = 2.29, p = 0.011, R² = 0.297) showed that breastfeeding for 6–12 months was associated with more favorable behavior (Estimate = −5.88, p = 0.026), compared to less than 6 months. In contrast, paternal secondary education (Estimate = 3.58, p = 0.048) compared to higher education and mixed ethnicity (Estimate = 12.55, p = 0.023) compared with Bulgarian ethnicity were associated with poorer behavioral outcomes (Estimate = 3.58, p = 0.048). Conclusions: Breastfeeding for 6 to 12 months may be associated with improved behavioral development, and to a lesser extent, language outcomes at age five. However, these domain-specific associations were not consistently supported across all statistical methods and should be interpreted with caution. Neurodevelopment is influenced by a complex interplay of nutritional, social and environmental factors. Longitudinal studies are needed to clarify the long-term effects of breastfeeding duration on neurodevelopment. Full article

Background: Cerebral palsy (CP) is a lifelong neurodevelopmental disorder characterised by motor impairment and commonly associated with comorbidities such as cognitive, communicative, and behavioural difficulties. While the physical and functional aspects of CP have been extensively studied, the mental health needs of this population remain largely underexplored, particularly concerning suicidal ideation and self-injurious behaviours. The purpose of this review is to synthesise the existing literature on suicidality in individuals with CP, explore theoretical and clinical risk factors, and identify key gaps in the current evidence base. Methods: A narrative literature review was conducted focusing on studies addressing suicidal ideation, self-harm, or related psychiatric outcomes in individuals with CP. Additional literature on risks and protective factors was included to support theoretical inferences and clinical interpretations. Results: Only a limited number of studies addressed suicidality directly in CP populations. However, several reports document elevated rates of depression, anxiety, and emotional distress, particularly among adults and individuals with higher levels of functioning. Communication barriers, chronic pain, social exclusion, and lack of accessible mental health services emerged as critical risk factors. Protective elements included strong family support, inclusive environments, and access to augmentative communication. Conclusions: Suicidality in individuals with CP is a neglected yet potentially serious concern. Evidence suggests underdiagnosis due to factors such as communication barriers and diagnostic overshadowing. Future research should prioritise disability-informed methodologies and validated tools for suicidal ideation, while clinicians should incorporate routine, adapted mental health screening in CP care to ensure early detection and person-centred management. Full article

Objectives: The increasing use of fetal MRI has increased the diagnosis of posterior fossa malformations, yet the long-term neurodevelopmental outcomes of affected fetuses remain unclear. This study aims to examine the long-term neurodevelopmental outcomes of fetuses with structural posterior fossa malformation diagnosed on fetal MRI. Methods: A historical cohort study was conducted at a single tertiary referral center, including fetuses diagnosed with structural posterior fossa malformations and apparently healthy fetuses who underwent fetal brain MRI between 2011 and 2019. Maternal, pregnancy, and newborn characteristics were compared between groups, alongside long-term neurodevelopmental outcomes using the Vineland Adaptive Behavior Scales II (VABS-II) questionnaire. This included an extensive assessment of malformation types, additional structural, genetic, or neurodevelopmental anomalies, and outcomes. Results: A total of 126 fetuses met the inclusion criteria, of which 70 were apparently healthy fetuses, and 56 had structural posterior fossa malformations. Among the latter, 18 pregnancies were terminated, 4 resulted in neonatal death, and 11 were lost to follow-up. No significant differences were found in the overall neurodevelopmental outcomes between fetuses with structural posterior fossa malformation (93.4 ± 19.0) and apparently healthy fetuses (99.8 ± 13.8). Motor skills scores were lower among fetuses with structural posterior fossa malformations (87.7 ± 16.5 vs. 99.3 ± 17.2, p = 0.01) but remained within the normal range. Conclusion: Fetuses with structural posterior fossa malformations may exhibit normal long-term neurodevelopmental outcomes if no additional anomalies are detected during thorough prenatal screening that includes proper sonographic, biochemical and genetic screening, as well as fetal MRI. Further research with larger cohorts and longer-term assessments is recommended to validate these findings and support clinical decision-making. Full article

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, largely due to its profound intratumoral heterogeneity and immunosuppressive microenvironment. Various classifications of GBM subtypes were created based on transcriptional and methylation profiles. This effort, followed by the development of new technology such as single-nuclei sequencing (snRNAseq) and spatial transcriptomics, led to a better understanding of the glioma cells’ plasticity and their ability to transition between diverse cellular states. GBM cells can mimic neurodevelopmental programs to resemble oligodendrocyte or neural progenitor behavior and hitchhike the local neuronal network to support their growth. The tumor microenvironment, especially under hypoxic conditions, drives the tumor cell clonal selection, which then reshapes the immune cells’ functions. These adaptations contribute to immune evasion by progressively disabling T cell and myeloid cell functions, ultimately establishing a highly immunosuppressive tumor milieu. This complex and metabolically constrained environment poses a major barrier to effective antitumor immunity and limits the success of conventional therapies. Understanding the dynamic interactions between glioma cells and their microenvironment is essential for the development of more effective immunotherapies and rational combination strategies aimed at overcoming resistance and improving patient outcomes. Full article

Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a wide array of neurotropic viruses, including influenza viruses, herpesviruses (HSV-1 and 2, CMV, VZV, EBV, HHV-6 and 8), hepatitis B and C viruses, HIV, HERVs, HTLV, Zika virus, BoDV, coronaviruses (including SARS-CoV-2), and others. These pathogens can contribute to schizophrenia through mechanisms such as direct microinvasion, persistent central nervous system infection, immune-mediated neuroinflammation, molecular mimicry, and the disturbance of the blood–brain barrier. Prenatal exposure to viral infections can trigger maternal immune activation, resulting in cytokine-mediated alterations in the neurological development of the foetus that persist into adulthood. Genetic studies highlight the role of immune-related loci, including major histocompatibility complex polymorphisms, in modulating susceptibility to infection and neurodevelopmental outcomes. Clinical data also support the “mild encephalitis” hypothesis, suggesting that a subset of schizophrenia cases involve low-grade chronic neuroinflammation. Although antipsychotics have some immunomodulatory effects, adjunctive anti-inflammatory therapies show promise, particularly in treatment-resistant cases. Despite compelling associations, pathogen-specific links remain inconsistent, emphasising the need for longitudinal studies and integrative approaches such as viromics to unravel causal relationships. This review supports a “multi-hit” model in which viral infections interfere with hereditary and immunological susceptibilities, enhancing schizophrenia risk. Elucidating these virus–immune–brain interactions may facilitate the discovery of biomarkers, targeted prevention, and novel therapeutic strategies for schizophrenia. Full article

Per- and polyfluoroalkyl substances (PFASs) have gained significant attention due to their widespread distribution in the environment and potential adverse health effects. While ingestion, especially through contaminated drinking water, is considered the primary route of human exposure, recent research suggests that other pathways, such as inhalation and dermal absorption, also play a significant role. This review provides a concise overview of the toxicological impacts of both legacy and emerging PFASs, such as GenX and perfluorobutane sulfonic acid (PFBS), with a particular focus on their effects on the liver, kidneys, and immune and nervous systems, based on findings from recent in vivo, in vitro, and epidemiological studies. Despite the transition to PFAS alternatives, much of the existing toxicity data focus on a few legacy compounds, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), which have been linked to adverse immune outcomes, particularly in children. However, evidence for carcinogenic risk remains limited to populations with extremely high exposure levels, and data on neurodevelopmental effects remain underexplored. While epidemiological and experimental animal studies supported these findings, significant knowledge gaps persist, especially regarding emerging PFASs. Therefore, this review examines the visceral, neural, and immunotoxicity data for emerging PFASs and mixtures from recent studies. Given the known risks from well-studied PFASs, a precautionary principle should be adopted to mitigate human health risks posed by this large and diverse group of chemicals. Full article

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are neurodevelopmental disorders with lifelong functional implications. Their potential role as emerging risk factors for cardiovascular diseases (CVDs) is increasingly acknowledged. The aim of this study was to conduct a comprehensive evaluation and meta-analysis of Mendelian Randomization (MR) studies exploring the causal effects of ADHD and ASD on various cardiovascular outcomes and vice versa. Three databases were searched, study quality was evaluated using a STROBE-MR checklist, and relevant data were extracted. In total, 14 studies revealed genetic associations between ADHD or ASD susceptibility and selected CVDs and vice versa. Notably, genetic markers for ADHD were linked to an increased risk of coronary artery disease, heart failure, and various types of stroke. Genetic predisposition to ASD raised the likelihood of atrial fibrillation and heart failure. Atrial fibrillation showed a causal relationship with elevated ADHD risk. Interestingly, hypertension was not associated with ADHD or ASD at the genetic level. Further efforts are needed to fully elucidate the basis of causal links from a mechanistic perspective. Overall, the results highlight the need for cardiovascular risk assessment and management in the clinical care of individuals with ADHD and ASD. Full article

Pyridoxine-dependent epilepsy (PDE) represents a group of rare developmental and epileptic encephalopathies. The most common PDE is caused by biallelic pathogenic variants in ALDH7A1 (PDE-ALDH7A1; OMIM #266100), which encodes α-aminoadipate semialdehyde (α-AASA) dehydrogenase, a key enzyme in lysine catabolism. Affected individuals present with seizures unresponsive to conventional anticonvulsant medications but responsive to high-dose of pyridoxine (vitamin B6). Adjunctive lysine restriction and arginine supplementation have also shown potential in improving neurodevelopmental outcomes. Given the significant benefit of early intervention, PDE-ALDH7A1 is a strong candidate for newborn screening (NBS). However, traditional biomarkers are biochemically unstable at room temperature (α-AASA and piperideine-6-carboxylate) or lack sufficient specificity (pipecolate), limiting their utility for biomarker-based NBS. The recent identification of two novel and stable biomarkers, 2S,6S-/2S,6R-oxopropylpiperidine-2-carboxylate (2-OPP) and 6-oxo-pipecolate (oxo-PIP), offers renewed potential for biochemical NBS. We evaluated the feasibility of incorporating 2-OPP, oxo-PIP, and pipecolate into routine butylated FIA-MS/MS workflows used for biochemical NBS. A total of 9402 dried blood spots (DBS), including nine confirmed PDE-ALDH7A1 patients and 9393 anonymized controls were analyzed using a single multiplex assay. 2-OPP emerged as the most sensitive biomarker, identifying all PDE-ALDH7A1 patients with 100% sensitivity and a positive predictive value (PPV) of 18.4% using a threshold above the 99.5th percentile. Combining elevated 2-OPP (above the 99.5th percentile) with either pipecolate or oxo-PIP (above the 85.0th percentile) as secondary marker detected within the same multiplex FIA-MS/MS assay further improved the PPVs to 60% and 45%, respectively, while maintaining compatibility with butanol-derivatized method. Notably, increasing the 2-OPP threshold above the 99.89th percentile, in combination with either pipecolate or oxo-PIP above the 85.0th percentile resulted in both 100% sensitivity and 100% PPV. This study supports the strong potential of 2-OPP-based neonatal screening for PDE-ALDH7A1 within existing NBS infrastructures. The ability to multiplex 2-OPP, pipecolate and oxo-PIP within a single assay offers a robust, practical, high-throughput and cost-effective approach. These results support the inclusion of PDE-ALDH7A1 in existing biochemical NBS panels. Further prospective studies in larger cohorts are needed to refine cutoffs and confirm clinical performance. Full article