Maternal obesity in pregnancy and lactation is linked to metabolic disturbances and neurodevelopmental problems in offspring, increasing the risk of psychiatric disorders in adulthood. We proposed that maternal N-acetyl cysteine (NAC) supplementation during lactation, a critical period for neurodevelopment, potentially protects offspring from developing cognitive impairment in adulthood. Fifteen young female ICR mice were randomly allocated to different experimental groups: high-fat diet (HFD; 60.3% fat before mating, during pregnancy and lactation), HFD-NAC of 300 mg/kg/day during lactation, CD (high-fat diet before mating, during pregnancy, and regular chow control diet of 8.2% fat during lactation), CD-NAC of 300 mg/kg/day during lactation and control group consuming regular chow diet. The serum inflammatory markers of the offspring were evaluated post-weaning, while metabolic markers, microglial density, and cognitive performance were assessed in adulthood using the novel Object Recognition and Morris Water Maze tests. Our results demonstrate maternal obesity during gestation and lactation increased body weight, hepatic steatosis, and microglial cell density in the dentate gyrus (DG) and cortex. Furthermore, these offspring exhibited reduced spatial learning abilities in adulthood, regardless of sex. However, maternal NAC administration during lactation and maternal diet intervention significantly reduced brain microglial density and improved both male and female offspring metabolic profiles. More importantly, NAC supplementation during lactation, regardless of maternal diet, enhanced male offspring's learning ability in adulthood. Our findings indicate that administering NAC to obese mothers during the critical lactation period may offer protection against metabolic disturbances and cognitive deficits in adult offspring previously exposed to maternal obesity.

Existing literature suggests an association between prenatal exposure to fine particulate air pollution (PM2.5) and cerebral palsy (CP). However, the impact of individual PM2.5 components (SO42-, NH4+, NO3-, SS, BC, dust, OM) on CP risk remains unknown.

To examine the associations between prenatal exposure to PM2.5 components, and risk of CP among term births in Ontario, Canada.

This was a retrospective cohort study that examined term births (gestational age ≥37 completed weeks) from April 2002 to December 2020. PM2.5 total mass and composition measures were assigned to maternal residence at birth using satellite-based estimates and ground-level monitoring data. Cohort data were compiled using health administrative databases. Single-pollutant distributed lag cox proportional hazard models, with and without additional adjustment for PM2.5 residuals, were used to investigate the associations between gestational exposures to PM2.5 total mass and its components.

2,193,427 mother-infant pairs were identified, of which 3907 were diagnosed with CP during the follow-up period. Increased risk of CP was found for SO42- exposure during early pregnancy in both residual-adjusted (HR: 1.052, 95 % CI: 1.009-1.097, per IQR = 0.94 μg/m3), and non-adjusted models (HR: 1.050, 95 % CI: 1.007-1.095, per IQR = 0.94 μg/m3). The concentration-response relationship between the sensitive window found for SO42- and CP risk (weeks 4-9 of gestation) showcased a supralinear pattern.

Prenatal exposure to SO42- may be associated with increased CP risk during the early pregnancy period. Associations between prenatal PM2.5 total mass and composition exposure and CP risk should be further investigated.

Autism Spectrum Disorder (ASD) is a range of neurodevelopmental conditions characterized by impaired social interaction, learning, and restricted or repetitive behaviors. The underlying causes of ASD are still debated, but researchers have found many physiological traits like gut problems and impaired immune system to help understand the etiology of ASD. Cerebrospinal fluid (CSF) plays a critical role in maintaining the homeostasis of the neuronal environment and has, therefore, been analyzed in multiple conditions impacting the central nervous system. The study of CSF is crucial to understanding neurological disorders as its composition changes with the disorders, and these changes may indicate various disorder-related physiological mechanisms. For this systematic review, we searched PubMed, Scopus, and Web of Science for studies published between 1977 and 2025 and selected 49 studies after manual screening. We took stock of the evidence supporting the hypothesis that ASD alters the properties and composition of CSF. We systematically report on the different attributes of CSF in the ASD population that could be potential biomarkers and assist in understanding the origins and progression of ASD. We found that in CSF, immune markers, proteins, extra-axial CSF, folate, oxytocin, and vasopressin showed changes in ASD compared to the neurotypicals. We observed gaps in the literature due to variations in age and sample size and noted biases related to sex (i.e., samples are predominantly including male participants) and age (i.e., a handful of studies were conducted on adults). Our review highlights the need for more research on CSF in ASD to improve our understanding of this disorder and identify CSF biomarkers.

The current study aimed at investigating the efficacies of probiotics in alleviating the symptoms of irritability/emotional lability in individuals with a neurodevelopmental condition.

Randomized placebo-controlled trials were identified through searching major electronic databases from inception to December, 2023. The outcome of interests included improvements in the symptoms of irritability/emotional lability. Outcomes were quantitatively expressed as effect size (ES) based on standardized mean difference (SMD) with 95 % confidence interval (CI).

Seven studies with 1479 participants were included in this meta-analysis. The primary results revealed a significant improvement in the symptoms of irritability/emotional lability in individuals with neurodevelopmental conditions receiving probiotics compared with the placebos (SMD= -0.17, p = 0.03). Subgroup analyses demonstrated an association between a significant improvement in the symptoms of irritability/emotional lability and the use probiotics relative to placebos only in studies using multiple-strain probiotics (SMD=-0.19, p = 0.04, three studies with 452 participant) but not in those adopting single-strain regimens.

Our study supported the use of probiotics for alleviating the symptoms of irritability/emotional lability in individuals with neurodevelopmental conditions, mainly in those receiving multiple-strain probiotics as supplements. Nevertheless, the limited number of studies targeting irritability as their primary outcomes, and most did not investigate other confounding factors such as dietary habits or consumption of other nutritional supplements may impair the robustness of evidence. Our results, which were derived from a limited number of available trials, warrant further large-scale clinical investigations for verification.

Infections can impair cognitive development, but their role on adverse childhood educational outcomes is unknown. We examined the associations of infectious morbidity and inflammatory biomarkers with grade repetition and school absenteeism.

We followed 2762 Colombian children aged 5-12 years for a school year. We quantified inflammatory biomarkers at enrolment and prospectively recorded incidence of gastrointestinal and respiratory infections, doctor visits and absent days from school using pictorial diaries. We estimated adjusted relative risks (ARR) with 95% confidence intervals (CI) for grade repetition and absenteeism by infectious morbidity burden and inflammatory biomarker categories, and percentages of the associations mediated through absenteeism.

Morbidity was associated with increased risk of grade repetition. ARR (95% CI) of grade repetition comparing high versus no incidence of gastrointestinal, respiratory and ear infections were, respectively, 2.17 (1.00, 4.72), 2.31 (1.28, 4.16) and 2.57 (1.13, 5.86). Infections also predicted school absenteeism, which mediated 35%, 31% and 38% of the corresponding morbidity-grade repetition associations. Elevated white blood cells (WBC), especially granulocytes, were related to increased grade repetition and school absenteeism risks.

Childhood infections and elevated WBC are associated with grade repetition and school absenteeism. Absenteeism does not fully explain the morbidity-grade repetition associations.

Borneol is widely used in the world, but in China, as a component of traditional Chinese medicine (TCM), it has a long history. According to the difference of composition and structure, borneol can be divided into natural borneol (NB) and synthetic borneol (SB). To explore the effect of borneol toxicity on environmental health, especially on aquatic animals, 6-hour post fertilization (hpf) zebrafish embryos were exposed to 10, 30, 50, or 70 mg/L NB or SB for 96 h. Various concentrations of borneol were applied to zebrafish embryos for 96 h, and the lethal curve was obtained. The exposure of borneol caused the heart rate to slow down and yolk sac edema. After exposure to borneol, the number of macrophages and neutrophils and the development of thymus were inhibited in zebrafish larvae. The gene expression level of cxcl-c1c, il-8 and il-1β were up-regulated after borneol exposure. While the expression level of chemokines ccl1 were decreased. After exposure to NB, the gene expression level of IFN-γ showed a trend of increasing first, then decreasing and then increasing, but it always showed an upward trend in the SB exposure group. After exposure to NB, the gene expression level of rag1 decreased, but in the SB exposure group, it increased first and then decreased. Through H&E staining, we also evaluated the pathologic changes of the spleen in adult zebrafish treated with borneol and found that the spleen was injured in borneol treated group. Finally, the locomotor behavior of zebrafish larvae was decreased after NB and SB exposure. NB and SB exposure affected the expression level of neurodevelopmental-related genes (epfa4, gap43, gfap, synapsinlla) and the specific expression of related genes (krox-20, pax2) in the brain region. Therefore, our research results show that borneol has immune and neurotoxic effects on zebrafish larvae, and the toxicity of SB was higher than that of NB, which is helpful to evaluate the safety of this drug more comprehensively.

This study analyzes the impact of PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) on health-related quality of life (HRQoL) and the psychological functioning of children and adolescents aged 2 to 1 years.

A cross-sectional descriptive study was conducted with 62 participants (31 males and 31 females) diagnosed with PFAPA. The Strengths and Difficulties Questionnaire (SDQ) and the Family Impact Module scale of Pediatric Quality of Life Inventory (PedsQL) were used to assess psychological functioning and HRQoL, respectively.

Participants exhibited predominantly low HRQoL, particularly in physical health and emotional functioning. School functioning was also affected. However, social functioning and family relationships showed more favorable scores. A positive correlation was observed between age and emotional symptoms. Family concern was the most significantly impacted aspect.

PFAPA syndrome has a significant impact on the HRQoL of affected children and adolescents, particularly in physical and emotional aspects. A holistic approach is necessary for disease management, considering not only physical symptoms but also psychosocial and academic factors, as well as the impact on the family.

We sought to investigate whether maternal inflammatory cytokines during pregnancy are associated with histologic inflammatory or vascular lesions in the placenta and/or correlated with gene expression patterns in the placenta.

We leveraged data from a large randomized controlled trial (RCT) at a single site. Maternal serum was collected in the second and third trimesters, and a composite inflammatory score was created using five measured biomarkers (CRP, IL-6, IL-1ra, IL-10, and TNF-α). Placentas were collected at delivery for histological analysis and four major patterns of placental injury were characterized. Fresh small chorionic villous biopsies were collected for placental genome-wide mRNA profiling. Transcripts showing >2-fold differential expression over the 4-SD range of circulating inflammatory biomarkers were reported, adjusting for potential confounders.

The primary analysis included 601 participants. A one standard deviation increase in the third-trimester inflammatory composite was associated with increased odds of chronic inflammation in the placenta (OR: 1.23, 95% CI 1.01, 1.51;). This was driven primarily by elevations in IL-10 (OR: 1.37; 99% CI: 1.06, 1.77). Higher maternal IL-10 in circulation was associated with bioinformatic indications of reduced pro-inflammatory gene regulation pathways in the placenta (AP1 decreased 25%, p = 0.003; NF-kB decreased 53%, p = 0.003) and indications of increased STAT family signaling pathways which mediate signaling through the IL-10 receptor (increased 73%, p = 0.002).

Our results indicate that elevated maternal circulating IL-10 during pregnancy is associated with chronic inflammatory lesions in the placenta at delivery. Additionally, higher levels of circulating IL-10 are associated with upregulated STAT signaling pathways in placental tissues.

The present study employed Mendelian randomization to scrutinize the causal connections that may exist between 91 distinct inflammatory markers and six neuropsychiatric disorders, namely Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD), anxiety disorders (ANX), depressive disorders (DEP), and unexplained encephalopathy (UE).

The methodology utilized involved the standard inverse variance weighting method within a two-sample, two-way Mendelian randomization framework and integrated statistics from genome-wide association studies. To ascertain the robustness of the identified causal associations, sensitivity analyses were performed with the aid of the MR-Egger method and the weighted median test.

The results revealed that 14 distinct systemic inflammatory modulators are potentially causally linked to the risk of developing various neuropsychiatric disorders. Specifically, five were associated with AD, eight with ANX, six with DEP, and one with UE. However, the causal associations involving systemic inflammatory markers with PD and MS require further investigation, particularly with the identification of additional significant genetic variants. Furthermore, the concentration levels of 33 systemic inflammatory factors could be modulated by the occurrence of neuropsychiatric conditions, indicated by this study. These include five affected by AD, eight by PD, six by MS, 12 by ANX, five by DEP, and five by UE.

Accumulating evidence implicates immune dysregulation and chronic inflammation in neurodevelopmental disorders (NDDs), often manifesting as abnormal alterations in peripheral blood immune cell levels. The mononuclear phagocyte system, including monocytes and microglia, has been increasingly recognized for its involvement in the pathogenesis of NDDs. However, due to inconsistent findings in the literature, whether monocytes can serve as a reliable biomarker for NDDs remains controversial. To address this issue, we conducted a systematic review and meta-analysis of studies examining monocyte counts in NDD individuals. A comprehensive search was conducted across PubMed, Web of Science, and Scopus databases. Variables extracted for analysis encompassed the author's name, year of study, sample size, patient's age, type of disease, mean, standard deviation of monocytes and sex ratio. A total of 2503 articles were found by searching the three databases. After removed duplicates and screening titles, abstracts, and full texts, 17 articles met the inclusion criteria, and 20 independent studies were included in the meta-analysis. The results indicated significantly increased monocyte counts in 5 type NDDs compared to Typical Development (TD) groups (g = 0.36, 95%CI [0.23, 0.49]). Subgroup analyses revealed no significant differences in monocyte counts across different NDD types, gender, or age. These findings suggest that aberrant alterations in monocyte counts are common in NDD cases, indicating their potential as biomarkers for these conditions. Future research should further investigate the role of monocyte in understanding the mechanisms, early detection, and clinical diagnosis of NDDs.

There is a current, absence of reliable, blood-sparing, diagnostic tools to measure and trend real-time changes in the levels of inflammation and its effects on the immune cells in the infant.

We deployed the BiophysicaL Immune Profiling for Infants (BLIPI) system in the neonatal intensive care unit to describe immune cell biophysical profiles using 50 microliters of blood per sample from term and preterm infants.

A total of 19 infants (8 term, 11 preterm) were recruited and 24 blood samples were collected in their first month. Based on the profiles of immune cells' size and deformation, there was a clear distinction between term and preterm infants, with 48/50 markers significantly different. A preterm infant with late-onset bacterial sepsis had notable size and deformability differences compared to the rest of the preterm cohort. There was a significant correlation between immune cell biophysical profiles and clinical markers such as C-reactive protein, white blood cell counts, and immature-to-total neutrophil (I:T) ratios, with Pearson correlation coefficients for linear regression models of 0.98, 0.97 and 0.94 respectively.

This study highlights the potential for the biophysical immune cell profiling system to provide an overview of the infant's current immune activation and response.

We present a novel, minimally invasive diagnostic system that leverages the physical properties of immune cells to provide a rapid and direct assessment of the immune status, requiring 20 times less blood volume than standard tests. This study demonstrates the potential of a compact, deployable system that is capable of performing biophysical profiling to assess immune cell activation in term and preterm infants, by revealing distinct differences in cell size and deformation between groups. The system's sensitive, quantitative measures were correlated with routine clinical biomarkers, highlighting its ability to provide a rapid, minimally invasive, real-time monitoring of neonatal immune status.

Background and Objectives: Kawasaki disease (KD) is a childhood systematic vasculitis. Emerging evidence suggests a link between KD and long-term neurological implications. This study examines the association between KD and subsequent neuropsychiatric and neurodevelopmental disorders using national health data from South Korea. Materials and Methods: Using the National Health Information Database, we identified KD patients diagnosed between 2002 and 2021 and selected those born between 2008 and 2015. Propensity score matching with a 1:4 ratio was applied to create a control group. The incidence of neuropsychiatric and neurodevelopmental disorders from 2017 to 2021 was analyzed using Cox proportional hazard models, adjusting for age, sex, and urbanicity. Results: This study included 41,806 KD subjects and 163,829 matched controls. KD was associated with an increased risk of certain neuropsychiatric disorders: anxiety disorder (HR: 1.124, 1.047-1.207), sleep-related disorder (HR: 1.257, 1.094-1.444), movement disorder (HR: 1.227, 1.030-1.461), and any neuropsychiatric disorder (HR: 1.102, 1.053-1.153). For neurodevelopmental disorders, KD patients showed a lower incidence of intellectual disability (HR: 0.747, 0.641-0.871) but an increased risk of tic disorder (HR: 1.148, 1.020-1.292). Male gender and urban residency were associated with higher incidence rates for certain conditions. Conclusions: This study demonstrates that KD patients show increased risks for anxiety, sleep-related disorder, movement disorder, and tic disorder, a reduced incidence of intellectual disability, and a higher risk of tic disorder. These findings highlight the need for long-term neurological monitoring in KD patients and provide insights into its potential neurodevelopmental impact.

The COVID-19 pandemic presents significant future health challenges. Its impact on pregnant women and their newborn is a particular area of concern. This study aims to examine the potential role of maternal immune activation (MIA), due to SARS-CoV-2 infection, on early neurodevelopment.

We analysed 107 mother-infant dyads from the COGESTCOV-19 study in Cantabria, Spain, which included 59 SARS-CoV-2 exposed (cases) and 48 unexposed (controls) mothers, recruited between December 2020 and February 2022. Cytokine levels (IL-6 and IL-10) were obtained from maternal blood and cord blood. Neurodevelopment was assessed using the Neonatal Behavioral Assessment Scale (NBAS) at six weeks of age. Trimester of infection was considered in the main analyses.

Results showed no significant overall delays in early neurodevelopment due to maternal SARS-CoV-2 infection. Control infants performed better in some NBAS items. However, cases infants showed trimester-specific differences. First-trimester exposure was related to motor and reflex delays, second-trimester to poorer performances in motor tasks and autonomic stability, and third-trimester to weaker state organization, regulation, and reflexes. Some correlations between cytokine levels and NBAS performance showed moderate associations.

These findings highlight the need for ongoing neurodevelopmental monitoring of infants born during the COVID-19 pandemic. The study enhances our understanding of MIA's impact on early development, emphasizing the importance of addressing homeostatic mechanisms in mothers and newborns.

There is limited research on the association between maternal depression and autism spectrum disorder, and existing studies face significant limitations, including inadequate control for confounders, reliance on self-reported data, small sample sizes and lack of investigation into mediating factors. This study addresses these gaps by examining the direct relationship and the potential mediating effects of preterm birth, low birth weight and low Apgar scores.

We analysed linked administrative health data involving 223,068 mother-offspring pairs in New South Wales, Australia. Maternal perinatal depressive disorders and offspring autism spectrum disorder were assessed using the International Classification of Diseases, Tenth Revision, Australian Modification (ICD-10 AM). A generalised linear model was employed to examine the association. The mediation effects of preterm birth, low birth weight and low Apgar scores were assessed through mediation analysis.

After adjusting for a range of potential confounders, offspring of mothers with antenatal, postnatal and overall perinatal depressive disorders had a 61% (risk ratio = 1.61, 95% confidence interval = [1.12, 2.32]), 85% (risk ratio = 1.85, 95% confidence interval = [1.20, 2.86]) and 80% (risk ratio = 1.80, 95% confidence interval = [1.33, 2.43]) higher risk of autism spectrum disorder, respectively. Only about 1.29% and 1.31% of the effect of maternal antenatal depressive disorders on offspring autism spectrum disorder was mediated by preterm birth and low Apgar scores, respectively. Low birth weight had no significant mediating effect on the association.

Maternal perinatal depressive disorders are associated with an increased risk of autism spectrum disorder in offspring. Preterm birth and low Apgar scores were weak mediators of this association. Early intervention strategies that aim to enhance maternal mental health and mitigate the risk of exposed offspring are needed.

Prenatal alcohol exposure (PAE) affects around 40,000 newborns every year and poses a significant health risk. Although much is already known about the neurotoxic mechanisms of PAE, new findings continue to emerge. Studies with mouse models show that PAE leads to overexpression of proinflammatory cytokines and chemokines in the brain, which disrupts important neurodevelopmental processes such as cell migration, survival and proliferation of neurons. The chemokine CXCL16 is overexpressed in the brain following various impairments, including PAE. This study shows that CXCL16 expression varies by developmental stage and sex, consistent with known sexual dimorphism in immune responses. In females, CXCL16 expression may be influenced by estrogen-related mechanisms, possibly related to the alcohol-mediated rebound effect described here. In contrast, the male hippocampus shows greater resilience to PAE-induced CXCL16 changes. Furthermore, the presence of CXCL16 in neuronal nuclei suggests a role in gene regulation, similar to other chemokines such as CCL5 and CXCL4. These findings shed light on the role of chemokines in hippocampal neuroplasticity and may pave the way for better treatment of fetal alcohol spectrum disorder (FASD).

Suicide is a significant public health problem, with increased rates in low- and middle-income countries such as Mexico; therefore, suicide prevention is important. Suicide is a complex and multifactorial phenomenon in which biological and social factors are involved. Several studies on the biological mechanisms of suicide have analyzed the proteome of the dorsolateral prefrontal cortex (DLPFC) in people who have died by suicide. The aim of this work was to analyze the protein expression profile in the DLPFC of individuals who died by suicide in comparison to age-matched controls in order to gain information on the molecular basis in the brain of these individuals and the selection of potential biomarkers for the identification of individuals at risk of suicide. In addition, this information was analyzed using machine learning (ML) algorithms to propose a model for predicting suicide.

Brain tissue (Brodmann area 9) was sampled from male cases (n=9) and age-matched controls (n=7). We analyzed the proteomic differences between the groups using two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Bioinformatics tools were used to clarify the biological relevance of the differentially expressed proteins. In addition, this information was analyzed using machine learning (ML) algorithms to propose a model for predicting suicide.

Twelve differentially expressed proteins were also identified (t 14 ≤ 0.5). Using Western blotting, we validated the decrease in expression of peroxiredoxin 2 and alpha-internexin in the suicide cases. ML models were trained using densitometry data from the 2D gel images of each selected protein and the models could differentiate between both groups (control and suicide cases).

Our exploratory pathway analysis highlighted oxidative stress responses and neurodevelopmental pathways as key processes perturbed in the DLPFC of suicides. Regarding ML models, KNeighborsClassifier was the best predicting conditions. Here we show that these proteins of the DLPFC may help to identify brain processes associated with suicide and they could be validated as potential biomarkers of this outcome.

Vertebrate development is regulated by several complex well-characterized morphogen signaling pathways, transcription factors, and structural proteins, but less is known about the enzymatic pathways that regulate early development. We have identified that factors from the inflammation-mediating cyclooxygenase (COX) signaling pathway are expressed at early stages of development in avian embryos. Using Gallus gallus (chicken) as a research model, we characterized the spatiotemporal expression of a subset of genes and proteins in the COX pathway during early neural development stages. Specifically, here we show expression patterns of COX-1, COX-2, and microsomal prostaglandin E synthase-2 (mPGES-2) as well as the genes encoding these enzymes (PTGS1, PTGS2, and PTGES-2). Unique expression patterns of individual players within the COX pathway suggest that they may play non-canonical/non-traditional roles in the embryo compared to their roles in the adult. Future work should examine the function of the COX pathway in tissue specification and morphogenesis and determine if these expression patterns are conserved across species.

Neurodevelopmental disorders (NDDs) are increasingly linked to genetic mutations that disrupt key neuronal processes. The KCNB2 gene encodes a crucial component of voltage-gated potassium channels, essential for regulating neuronal excitability and synaptic transmission. Mutations in KCNB2 typically alter potassium channel inactivation, leading to various NDDs, including autism spectrum disorders (ASD), intellectual disabilities (ID), and epilepsy. This narrative review synthesizes findings from genetic, molecular, and clinical studies on the KCNB2 gene and its role in NDDs. Relevant literature was identified through database searches in PubMed, Embase, PsycINFO, Scopus, and Web of Science, focusing on studies that examine KCNB2's molecular mechanisms, pathogenic mutations, and clinical implications in NDDs. In addition to its role in excitability, KCNB2's impact on cognitive processes, such as memory and attention, is considered, highlighting the need for further research. Potential interventions, including pharmacological modulation and gene therapy, are also discussed. Future research should focus on characterizing KCNB2 variants, expanding genetic screening, and advancing targeted therapies to improve outcomes for individuals affected by KCNB2-related disorders.

The vagus nerve (VN) is the primary parasympathetic nerve, providing two-way communication between the body and brain through a network of afferent and efferent fibers. Evidence suggests that altered VN signaling is linked to changes in the neuroimmune system, including microglia. Dysfunction of microglia, the resident innate immune cells of the brain, is associated with various neurodevelopmental disorders, including schizophrenia, attention deficit hyperactive disorder (ADHD), autism spectrum disorder (ASD), and epilepsy. While the mechanistic understanding linking the VN, microglia, and neurodevelopmental disorders remains incomplete, vagus nerve stimulation (VNS) may provide a better understanding of the VN's mechanisms and act as a possible treatment modality. In this review we examine the VN's important role in modulating the immune system through the inflammatory reflex, which involves the cholinergic anti-inflammatory pathway, which releases acetylcholine. Within the central nervous system (CNS), the direct release of acetylcholine can also be triggered by VNS. Homeostatic balance in the CNS is notably maintained by microglia. Microglia facilitate neurogenesis, oligodendrogenesis, and astrogenesis, and promote neuronal survival via trophic factor release. These cells also monitor the CNS microenvironment through a complex sensome, including groups of receptors and proteins enabling microglia to modify neuroimmune health and CNS neurochemistry. Given the limitations of pharmacological interventions for the treatment of neurodevelopmental disorders, this review seeks to explore the application of VNS as an intervention for neurodevelopmental conditions. Accordingly, we review the established mechanisms of VNS action, e.g., modulation of microglia and various neurotransmitter pathways, as well as emerging preclinical and clinical evidence supporting VNS's impact on symptoms associated with neurodevelopmental disorders, such as those related to CNS inflammation induced by infections. We also discuss the potential of adapting non-invasive VNS for the prevention and treatment of these conditions. Overall, this review is intended to increase the understanding of VN's potential for alleviating microglial dysfunction involved in schizophrenia, ADHD, ASD, and epilepsy. Additionally, we aim to reveal new concepts in the field of CNS inflammation and microglia, which could serve to understand the mechanisms of VNS in the development of new therapies for neurodevelopmental disorders.

This study investigates the impact of maternal glycemic levels during early and late pregnancy on offspring neurodevelopment in China.

Fasting plasma glucose (FPG) and triglyceride (TG) levels were measured in maternal blood during pregnancy, and the TyG index was calculated to assess insulin resistance. Hyperglycemia was defined as FPG > 5.1 mmol/L. Neurodevelopmental outcomes in offspring aged 6-36 months were evaluated using the China Developmental Scale for Children, focusing on developmental delay (DD) and developmental quotient (DQ). Mothers were categorized into four glycemic groups: healthy glycemia group (HGG), early pregnancy hyperglycemia group (EHG), late pregnancy hyperglycemia group (LHG), and full-term hyperglycemia group (FHG). Linear and logistic regression models were applied.

Among 1888 mother-child pairs, hyperglycemia and FPG were associated with an increased risk of overall DD (aOR = 1.68; 95% CI 1.07-2.64) and lower DQ (aBeta = -1.53; 95% CI -2.70 to -0.36). Elevated FPG was linked to DD in fine motor and social behaviors. Compared to HGG, LHG and FHG significantly increased the risk of overall DD (aOR = 2.18; 95% CI 1.26-3.77; aOR = 2.64; 95% CI 1.38-5.05), whereas EHG did not. Male offspring were particularly vulnerable to early pregnancy hyperglycemia (aBeta = -2.80; 95% CI -4.36 to -1.34; aOR = 2.05; 95% CI 1.10-3.80).

Maternal glycemic levels during pregnancy influence offspring neurodevelopment, with persistent hyperglycemia significantly increasing DD risk. Early pregnancy hyperglycemia particularly affects male offspring, underscoring the need for glycemic management during pregnancy.

Epilepsy is one of the most common neurological disorders. Calcium dysregulation and neuroinflammation are essential and common mechanisms in epileptogenesis. Sarco/endoplasmic reticulum (ER) Ca2+-ATPase 2b (SERCA2b), a crucial calcium regulatory pump, plays pathological roles in various calcium dysregulation-related diseases. However, the link between SERCA2b and neuroinflammation in epilepsy remains undetermined. This study aimed to establish the relationship between SERCA2b, oxidative stress, and neuroinflammation in epilepsy to elucidate the underlying molecular mechanism in epileptogenesis. Neuroinflammation and oxidative stress were induced in N2a cells using lipopolysaccharide (LPS) and hydrogen peroxide (H2O2). However, experimental temporal lobe epilepsy (TLE) was induced in mice using pilocarpine. Further, effects of oxidative stress and neuroinflammation on SERCA2b and ER stress markers were assessed at protein and mRNA levels. Calcium imaging was employed to determine intracellular calcium levels. SERCA2b expression significantly decreased after LPS, H2O2, and pilocarpine exposure at both mRNA and protein levels, mediated by upregulating neuroinflammation. This downregulation of SERCA2b was associated with increased production of reactive oxygen species and elevated intracellular calcium levels, leading to elevated ER stress markers. Our findings highlight a link between oxidative stress, neuroinflammation and SERCA2b in TLE. The results suggest that targeting SERCA2b could restore calcium homeostasis and ER stress processes, potentially providing a therapeutic option for TLE. This study underscores the importance of SERCA2b in the pathophysiology of epilepsy and its potential as a therapeutic target.

The balance of omega-6/omega-3 (n-6/n-3) is crucial for proper brain function as they have opposite physiological roles.

To analyze the association between maternal serum ratios of n-6/n-3 in the first and third trimesters of pregnancy and the neurodevelopment of their children in the early days after birth in the population of Northern Spain's Mediterranean region.

Longitudinal study in which 336 mother-child pairs participated. Mother serum concentrations of long-chain polyunsaturated fatty acids (LCPUFAs), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) were determined. Sociodemographic, clinical, lifestyle habits, and obstetrical variables were collected. The Bayley Scales of Infant and Toddler Development (BSID-III) was used to assess infant neurodevelopment. Multiple linear regression models adjusting for confounding factors were performed.

In the third trimester, a higher maternal n-6/n-3 ratio was negatively associated with infant motor development (β = -0.124, p = 0.023). Similarly, higher ARA/DHA ratios were negatively associated with total motor (β = -2.005, p = 0.002) and fine motor development (β = -0.389, p = 0.001). No significant associations were observed in the first trimester nor for the ARA/EPA ratio in the third trimester.

Our findings indicate that an elevated n-6/n-3 ratio and ARA/DHA ratio in the third trimester of pregnancy are associated with poorer motor development outcomes in infants. These results highlight the importance of optimizing maternal fatty acid balance during pregnancy to support fetal neurodevelopment, suggesting a need for further research to verify these associations and elucidate underlying mechanisms.

Despite the prevalence and significant concern of COVID-19 in maternal and offspring health, little is known about the impact of COVID-19 during pregnancy on newborn immunity and neurodevelopment. This study aimed to examine 1) the relationship between maternal COVID-19 during pregnancy and newborn immune profiles and investigate the 2) associations between specific newborn immune profiles and the risk of subsequent diagnosis of a neurodevelopmental disorder (NDD) among children with prenatal exposure to COVID-19. Newborn dried bloodspots (NBS) from 545 children born at Kaiser Permanente Northern California between January 2020 and September 2021 (460 [223 males, 237 females] to COVID-19-infected [COVID+] mothers; 85 [45 males, 40 females] to COVID-19-uninfected [COVID-] mothers) were used to profile newborn immune molecules via a 42-plex cytokine/chemokine assay. Among the 460 children born to COVID+ mothers, 73 (47 males, 27 females) were later diagnosed with an NDD. In the first set of analyses examining the association between maternal COVID-19 infection during pregnancy and newborn immune profile, the results adjusted for covariates but uncorrected for multiple comparisons showed that newborns of COVID+ mothers had significantly higher levels of IL-22 (estimate [est.] = 0.16, 95 % Cl 0.01, 0.3, p = 0.04) and GM-CSF (est. = 0.27, 95 % Cl 0.09, 0.46, p = 0.004) compared to newborns of COVID- mothers. These differences were no longer statistically significant after multiple comparison adjustments. In the second analysis exploring the association between newborn profile and later diagnosis of NDD among newborns born to COVID+ mothers, the results adjusted for covariates revealed an association between higher neonatal levels of IL-22 (hazard ratio [HR] = 0.49, 95 % Cl 0.33, 0.75, p = 0.001) and lower risk of a later diagnosis of an NDD, which remained significant after multiple comparison adjustments (p = 0.04). Other neonatal cytokines/chemokines/growth factors such as sCD40L (HR = 0.7, 95 % Cl 0.57, 0.9, p = 0.009), IP-10 (HR = 0.46, 95 % Cl 0.25, 0.83, p = 0.009), MIG (HR = 0.52, 95 % Cl 0.3, 0.9, p = 0.02), FLT-3L (HR = 0.45, 95 % Cl 0.24, 0.83, p = 0.01), PDGF AB/BB (HR = 0.56, 95 % Cl 0.36, 0.99, p = 0.046), VEGF (HR = 0.57, 95 % Cl 0.34, 0.98, p = 0.04), and IL-4 (HR = 0.48, 95 % Cl 0.26, 0.93, p = 0.03) were no longer statistically significant after multiple comparison adjustments. Despite the imbalance between the number of COVID-19 exposed and unexposed newborns in this study cohort, our novel findings enhance our understanding of the potential impact of maternal COVID-19 infection during pregnancy on the developing neonatal immune system. Our findings highlight the role of immune molecules, beyond those considered to be pro-inflammatory, that may be crucial in maternal and newborn immunity against COVID-19 infection during pregnancy. Furthermore, our results suggest that reduced levels of neonatal immune molecules in newborns of COVID + mothers may be linked to an increased risk of a subsequent diagnosis of an NDD.

Toxoplasmosis presents notable hazards in the context of pregnancy, impacting the health of the mother and the neurodevelopment of the fetus via immune reactions and possible vertical transmission. The maternal immune response from chronic Toxoplasma gondii (T. gondii) infection may negatively influence fetal neurodevelopment. This research evaluated the association between the seroprevalence of chronic T. gondii and cytomegalovirus infection in pregnant women and the neuropsychological development of their children at 12 months of age. A follow-up study evaluated women during the gestational period and their respective infants. The pregnant women were tested for the presence of antibodies to infectious agents: T. gondii, cytomegalovirus (CMV), syphilis, human immunodeficiency virus (HIV), hepatitis B and C. Detailed information about the newborns was extracted from medical records. At 12 ± 3 months of age, the infant's neurodevelopment was assessed using the Bayley-III Scales of Infant and Toddler Development by a trained specialist under the supervision of a neuropsychologist. A statistically significant association was found between maternal IgG anti-T. gondii levels and lower scores on the Bayley-III cognition scale, with a non-standardized β-coefficient of -0.078 (95 %-CI: -0.144 to -0.013), accounting for 35.1 % of the variation in this outcome. These results suggest that chronic maternal T. gondii infection, even without vertical transmission, may be associated with subtle changes in the child's cognitive development. Therefore, monitoring and early intervention are essential to identify and address possible delays in childhood neurodevelopment related to chronic maternal toxoplasmosis.

Ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) is a chromatin modifier responsible for regulating the demethylation of histone H3 lysine 27 trimethylation (H3K27me3), which is crucial for human neurodevelopment. To date, the impact of UTX on neurodevelopment remains elusive. Therefore, this study aimed to investigate the potential molecular mechanisms underlying the effects of UTX on neurodevelopment through untargeted metabolomics based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We found that UTX knockout in neurones leads to cell death and apoptosis in the hippocampus and cortex, as well as induces impaired learning and memory functions in mice. Moreover, UTX deletion contributed to significant metabolic perturbations in brain tissues. A total of 223 differential metabolites were identified between wild-type (WT) and UTX cKO mice. Pathway analysis indicated that the metabolic pathways mainly affected by UTX deletion were alanine, aspartate, and glutamate metabolism, resulting in significant alterations in L-alanine, L-aspartate, D-aspartate, N-acetylaspartylglutamate, L-glutamate, and argininosuccinic acid. These data emphasised that UTX may exert a key effect in neurodevelopment and that the underlying mechanism may be related to the regulation of the alanine, aspartate, and glutamate metabolism pathways, especially the characteristic metabolites involved in this pathway.

We aimed at investigating the efficacies of probiotics in alleviating the core and associated symptoms of autism spectrum disorder (ASD).

Randomized placebo-controlled trials were identified from major electronic databases from inception to Nov 2023. The outcomes of interests including improvements in the total and associated symptoms of ASD were quantitatively expressed as effect size (ES) based on standardized mean difference (SMD) with 95% confidence interval (CI).

Ten studies with 522 participants (mean age = 8.11) were included in this meta-analysis. The primary results revealed significant improvement in total symptoms in the probiotics group compared with the controls (SMD = - 0.19, p = 0.03, ten studies, n = 522) but not the core symptoms (i.e., repetitive restricted behaviors, As affiliations 3 and 5 are same, we have deleted the duplicate affiliations and renumbered accordingly. Please check and confirm.problems with social behaviors/communication). Subgroup analyses demonstrated improvement in total symptoms in probiotics users relative to their controls only in studies using multiple-strain probiotics (SMD = - 0.26, p = 0.03, five studies, n = 288) but not studies using single-strain regimens. Secondary results showed improvement in adaptation (SMD = 0.37, p = 0.03, three studies, n = 139) and an improvement trend in anxiety symptoms in the probiotics group compared with controls (SMD = - 0.29, 95% CI - 0.60 to 0.02, p = 0.07, three studies, n = 163) but failed to demonstrate greater improvement in the former regarding symptoms of irritability/aggression, hyperactivity/impulsivity, inattention, and parental stress.

Our study supported probiotics use against the overall behavioral symptoms of ASD, mainly in individuals receiving multiple-strain probiotics as supplements. However, our results showed that probiotics use was only associated with improvement in adaptation and perhaps anxiety, but not core symptoms, highlighting the impact of adaptation on quality of life rather than just the core symptoms. Nevertheless, the limited number of included trials warrants further large-scale clinical investigations.

Childhood infection might be associated with adverse child development and neurocognitive outcomes, but the results have been inconsistent.

Two population-based record-linkage cohorts of all singleton children born at term in New South Wales, Australia, from 2001 to 2014, were set up and followed up to 2019 for developmental outcome (N=276 454) and school performance (N=644 291). The primary outcome was developmentally high risk (DHR) at age 4-6 years and numeracy and reading below the national minimum standard at age 7-9 years. Cox regression was used to assess the association of childhood infection ascertained from hospital records with each outcome adjusting for maternal, birth and child characteristics, and sensitivity analyses were conducted assessing E-values and sibling analysis for discordant exposure.

A higher proportion of children with an infection-related hospitalisation were DHR (10.9% vs 8.7%) and had numeracy (3.7% vs 2.7%) and reading results (4.3% vs 3.1%) below the national minimum standard, compared with those without infection-related hospitalisation. In the multivariable analysis, children with infection-related hospitalisation were more likely to be DHR (adjusted HR 1.12, 95% CI 1.08 to 1.15) and have numeracy (adjusted HR 1.22, 95% CI 1.18 to 1.26) and reading results (adjusted HR 1.16, 95% CI 1.12 to 1.20) below the national minimum standard. However, these results may be impacted by unmeasured confounding, based on E-values of 1.48-1.74, and minimal association with education outcome was found in the sibling analysis.

Infection-related hospitalisation was modestly associated with adverse child development and school performance, but the association may be explained by shared familial factors, particularly in those with most socioeconomic disadvantages.

Exome sequencing (ES) has emerged as an essential tool in the evaluation of neurodevelopmental disorders (NDD) of unknown etiology. Genome sequencing (GS) offers advantages over ES due to improved detection of structural, copy number, repeat number and non-coding variants. However, GS is less commonly utilized due to higher cost and more intense analysis. Here, we present nine cases of pediatric NDD that were molecularly diagnosed with GS between 2017 and 2022, following non-diagnostic ES. All individuals presented with global developmental delay or regression. Other features present in our cohort included epilepsy, white matter abnormalities, brain malformation and dysmorphic features. Two cases were diagnosed on GS due to newly described gene-disease relationship or variant reclassification (MAPK8IP3, CHD3). Additional features missed on ES that were later detected on GS were: intermediate-size deletions in three cases who underwent ES that were not validated for CNV detection, pathogenic variants within the non-protein coding genes SNORD118 and RNU7-1, pathogenic variant within the promoter region of GJB1, and a coding pathogenic variant within BCAP31 which was not sufficiently covered on ES. GS following non-diagnostic ES led to the identification of pathogenic variants in this cohort of nine cases, four of which would not have been identified by reanalysis alone.

Severe neonatal inflammatory conditions in very preterm infants (VPT: <32 weeks gestational age, GA) are linked to adverse neurodevelopmental outcomes. Differences in white matter (WM) microstructure of the corpus callosum (CC) have been observed at age 6 in VPT children with a history of severe neonatal inflammation. The goal of this study was to determine whether these CC differences can be detected at term-equivalent age using diffusion MRI (dMRI), and whether neonatal inflammation is associated with altered WM in additional tracts implicated in the encephalopathy of prematurity.

We conducted a retrospective study of VPT infants (n = 152) born at 22-32 weeks GA, classified based on the presence (I+, n = 80) or absence (I-, n = 72) of severe neonatal inflammatory conditions (bronchopulmonary dysplasia, necrotizing enterocolitis, or culture-positive sepsis). Analysis of covariance (ANCOVA) assessed group differences in near-term dMRI mean fractional anisotropy (FA) and mean diffusivity (MD) across seven segments of the CC and the anterior thalamic radiation, arcuate fasciculus, cingulum, corticospinal tract, inferior longitudinal fasciculus, superior cerebellar peduncle, and uncinate fasciculus. Due to imbalance of GA in the full sample, secondary ANCOVA analyses were performed in a GA-matched subset (n = 42) to further isolate the effect of inflammation.

FA was significantly lower in the I+ group compared to the I- group in the anterior frontal, posterior parietal, temporal, and occipital segments of the CC, and in the cingulum, inferior longitudinal fasciculus, and superior cerebellar peduncle. This general pattern persisted in the GA-matched subset, with significant differences in the anterior frontal and temporal CC segments.

VPT infants with severe neonatal inflammation had lower FA in multiple white matter tracts, suggesting that inflammation-related alterations in WM development begin in the neonatal period. The observed differences detected using dMRI at term-equivalent age corroborate prior findings and may provide a window of opportunity for early identification of VPT infants at increased risk of poor neurodevelopmental outcomes.

The interaction between the gut-microbiota-derived metabolites and brain has long been recognized in both health and disease. The liver, as the primary metabolic organ for nutrients in animals or humans, plays an indispensable role in signal transduction. Therefore, in recent years, Researcher have proposed the Gut-Liver-Brain Axis (GLBA) as a supplement to the Gut-Brain Axis. The GLBA plays a crucial role in numerous physiological and pathological mechanisms through a complex interplay of signaling pathways. However, gaps remain in our knowledge regarding the developmental and functional influences of the GLBA communication pathway. The gut microbial metabolites serve as communication agents between these three distant organs, functioning prominently within the GLBA. In this review, we provide a comprehensive overview of the current understanding of the GLBA, focusing on signaling molecules role in animal and human health and disease. In this review paper elucidate its mechanisms of communication, explore its implications for immune, and energy metabolism in animal and human, and highlight future research directions. Understanding the intricate communication pathways of the GLBA holds promise for creating innovative treatment approaches for a wide range of immune and metabolic conditions.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted interests and repetitive behavior. To date, no single cause has been demonstrated but both genetic and environmental factors are believed to be involved in abnormal brain development. In recent years, immunological and mitochondrial dysfunctions acquired particular interest in the study of the molecular mechanisms underlying the pathophysiology of ASD. For this reason, our study focused on evaluating the mitochondrial component and activation of the NLRP3 inflammasome, a critical player of the innate immune system. The assembly of NLRP3 with ASC mediates activation of Caspase-1, which in turn, by proteolytic cleavage, activates Gasdermin D and the proinflammatory cytokines IL-1β/IL-18 with their subsequent secretion. Using primary fibroblasts of autistic and control patients we studied basal and stimulated conditions. Specifically, LPS and ATP were used to activate the NLRP3 inflammasome and MCC950 for its inhibition. In addition, FCCP was used as a mitochondrial stressor and MitoTEMPO as a scavenger of mitochondrial ROS. Our results showed a hyperactivation of NLRP3 inflammasome in ASDs, as evidenced by the co-localization of the two main components, NLRP3 and ASC, by the higher levels of ASC specks, oligomers and dimers and by the increased amounts of active Caspase-1 and IL-1β. In addition, increased mitochondrial superoxide anion and reduced mitochondrial membrane potential were detected in ASD cells. These data are in accordance with the abnormal mitochondrial morphology evidenced by transmission electron microscopy analysis. Interestingly, NLRP3 inflammasome inhibition with MCC950 improved mitochondrial parameters, while the use of MitoTEMPO, in addition to decrease mitochondrial ROS production, was able to prevent NLRP3 inflammasome activation suggesting for the first time an abnormal bidirectional crosstalk between mitochondria and NLRP3 inflammasome in ASD.

DNA methylation levels at specific sites can be used to proxy C-reactive protein (CRP) levels, providing a potentially more stable and accurate indicator of sustained inflammation and associated health risk. However, its use has been primarily limited to adults or preterm infants, and little is known about determinants for - or offspring outcomes of - elevated levels of this epigenetic proxy in cord blood. The aim of this study was to comprehensively map prenatal predictors and long-term neurobehavioral outcomes of neonatal inflammation, as assessed with an epigenetic proxy of inflammation in cord blood, in the general pediatric population.

Our study was embedded in the prospective population-based Generation R Study (n = 2,394). We created a methylation profile score of CRP (MPS-CRP) in cord blood as a marker of neonatal inflammation and validated it against serum CRP levels in mothers during pregnancy, as well as offspring at birth and in childhood. We then examined (i) which factors (previously associated with sustained inflammation) explain variability in MPS-CRP at birth, including a wide range of prenatal lifestyle and clinical conditions, pro-inflammatory exposures, as well as child genetic liability to elevated CRP levels; and (ii) whether MPS-CRP at birth associates with child neurobehavioral outcomes, including global structural MRI and DTI measures (child mean age 10 and 14 years) as well as psychiatric symptoms over time (Child Behavioral Checklist, at mean age 1.5, 3, 6, 10 and 14 years).

MPS-CRP at birth was validated with serum CRP in cord blood (cut-off > 1 mg/L) (AUC = 0.72). Prenatal lifestyle pro-inflammatory factors explained a small part (i.e., < 5%) of the variance in the MPS-CRP at birth. No other prenatal predictor or the polygenic score of CRP in the child explained significant variance in the MPS-CRP at birth. The MPS-CRP at birth prospectively associated with a reduction in global fractional anisotropy over time on mainly a nominal threshold (β = -0.014, SE = 0.007, p = 0.032), as well as showing nominal associations with structural differences (amygdala [(β = 0.016, SE = 0.006, p = 0.010], cerebellum [(β = -0.007, SE = 0.003, p = 0.036]). However, no associations with child psychiatric symptoms were observed.

Prenatal exposure to lifestyle-related pro-inflammatory factors was the only prenatal predictor that accounted for some of the individual variability in MPS-CRP levels at birth. Further, while the MPS-CRP prospectively associated with white matter alterations over time, no associations were observed at the behavioral level. Thus, the relevance and potential utility of using epigenetic data as a marker of neonatal inflammation in the general population remain unclear. In the future, the use of epigenetic proxies for a wider range of immune markers may lend further insights into the relationship between neonatal inflammation and adverse neurodevelopment within the general pediatric population.

Chronic systemic inflammation is linked to cognitive decline pathogenesis. This study investigates the association between systemic inflammation markers and cognitive decline progression in a clinical cohort.

This prospective observational cohort study enrolled 295 participants. Cognitive decline progression was defined by an increase in clinical dementia rating (CDR) scores. The study examines the correlation between systemic inflammation markers, including systemic Inflammation Response Index (SIRI), systemic Immune-Inflammation Index (SII), prognostic Inflammatory and Nutritional Index (PIV), and cognitive impairment progression.

The presence of the APOE 4 allele and diabetes mellitus was associated with elevated PIV levels (P < 0.05). Additionally, AD patients had the highest SII levels, indicating increased inflammation compared to individuals with MCI and SCD (P < 0.05). After a mean follow-up of 17 months, 117 patients (51.31%) experienced cognitive decline progression. AD diagnosis, CDR, and SII were significant predictors of cognitive decline progression (All P < 0.05).

This study highlights the clinical significance of elevated systemic inflammation markers in identifying individuals at risk of cognitive decline. Addressing inflammation may offer a promising approach to improving cognitive health and mitigating age-related cognitive decline.

A collection of chronic central motor, postural, and activity restriction symptoms are referred to as cerebral palsy (CP). Previous research suggests that a number of perinatal variables, including hypoxia, may be linked to CP. And the pathophysiological process that causes brain injury in growing fetuses is mostly caused by amniotic fluid infection and intra-amniotic inflammation. Still, there is still much to learn about the molecular mechanism of CP. The goal of this study was to identify the molecular mechanism of Liuwei Dihuang pill (LWDHP) in the treatment of CP using network pharmacology and bioinformatics. The Chinese medicine database provided the LWDHP components and targets, the CP illness gene data set was gathered from a disease, and the expression profile of children with CP was chosen from anther database. Using the Kyoto Encyclopedia of Genes and Genomes and gene ontology databases, a network of interactions between proteins was created, and functional enrichment analysis was carried out. Analysis of traditional Chinese medicine found that the key active ingredients of LWDHP are quercetin, Stigmasterol and kaempferol. Through enrichment analysis, it was found that the hub genes for LWDHP treatment of CP are CXCL8, MMP9, EGF, PTGS2, SPP1, BCL2L1, MMP1, and AR. K EGG analysis found that LWDHP treatment of CP mainly regulates PI3K-Akt signaling pathway, IL-17 signaling pathway, Jak-STAT signaling pathway, NF-kappa B signaling pathway, etc. To summarize, LWDHP regulates immunological and inflammatory variables through a variety of components, targets, and signaling pathways, which plays a significant role in the development and management of CP.

Schizophrenia (SZ) is a complex mental illness characterized by disturbances in thinking, emotionality, and behavior, significantly impacting the quality of life for individuals affected and those around them. The etiology of SZ involves intricate interactions between genetic and environmental factors, although the precise mechanisms remain incompletely understood. Genetic predisposition, neurotransmitter dysregulation (particularly involving dopamine and serotonin), and structural brain abnormalities, including impaired prefrontal cortex function, have been implicated in SZ development. However, increasing evidence reveals the role of environmental factors, such as nutrition, during critical periods like pregnancy and lactation. Epidemiological studies suggest that early malnutrition significantly increases the risk of SZ symptoms manifesting in late adolescence, a crucial period coinciding with peak myelination and brain maturation. Prenatal undernutrition may disrupt myelin formation, rendering individuals more susceptible to SZ pathology. This review explores the potential relationship between prenatal undernutrition, myelin alterations, and susceptibility to SZ. By delineating the etiopathogenesis, examining genetic and environmental factors associated with SZ, and reviewing the relationship between SZ and myelination disorders, alongside the impact of malnutrition on myelination, we aim to examine how malnutrition might be linked to SZ by altering myelination processes, which contribute to increasing the understanding of SZ etiology and help identify targets for intervention and management.

Exposure to maternal inflammation is associated with an increased risk of neurocognitive and developmental disorders in offspring. Early diagnosis and intervention improves childhood motor and cognitive functioning. Neonatal cerebral MRI and remote app-based generalised movement assessments (GMAs) are both predictive of adverse neurocognitive outcomes but have only been used in infants at significantly increased risk for these outcomes, rather than following in utero exposure to maternal inflammatory disorders.

Pregnant women with inflammatory bowel disease were assessed clinically and biochemically in each trimester of pregnancy in this single centre prospective study. Neonatal cerebral MRIs were performed at 6-12 weeks post-corrected term. Two GMA videos were filmed using the 'BabyMoves' app from 12 to 16 weeks of age. MRIs and GMAs were assessed by a blinded highly qualified practitioner using validated scoring systems.

40/53 of invited maternal-infant dyads were recruited. C-reactive protein was elevated antenatally in less than 13%. 5/37 neonatal MRIs had incidental or obstetric trauma related gross anatomical abnormalities, with none abnormal on validated gross abnormality scoring. 3/35 GMAs were abnormal, with one GMA abnormality being clinically significant. Of those with abnormal GMAs, 2/3 were in exposed to severely active IBD in-utero.

Neonatal cerebral MRI and GMA for neurocognitive screening is feasible in the setting of maternal inflammatory bowel disease, where the risk of cerebral palsy is poorly defined and thus burdensome screening interventions are less appealing to parents. Larger studies are required to stratify adverse neurocognitive outcome risk in infants born to women with maternal inflammatory disorders, but these data are reassuring for women with IBD in remission antenatally.

Maternal nutrition is essential in fetal development; thus, disordered eating may influence this process and contribute to the development of offspring psychiatric disorders.

To investigate the association of maternal eating disorders and prepregnancy body mass index (BMI) with offspring psychiatric diagnoses.

This population-based cohort study used Finnish national registers to assess all live births from January 1, 2004, through December 31, 2014, with follow-up until December 31, 2021. The data analyses were conducted from September 1, 2023, to September 30, 2024.

Maternal eating disorder and prepregnancy BMI.

Primary outcomes were 9 neurodevelopmental and psychiatric offspring diagnoses. Cox proportional hazards modeling adjusted for potential risk factors in the development of the outcome disorders was applied in 2 models. Secondary analyses were stratified for adverse birth outcomes (prematurity, small size for gestational age, and low Apgar score) or comorbid offspring eating disorders. Categories of BMI (calculated as weight in kilograms divided by height in meters squared) included underweight (BMI <18.5), normal weight (18.5-24.9), overweight (25.0-29.9), obesity (30.0-34.9), and severe obesity (≥35.0).

The mean (SD) age of 392 098 included mothers was 30.15 (5.38) years, 42 590 mothers (10.86%) were born outside of Finland, 6273 mothers (1.60%) had a history of an eating disorder, 23 114 mothers (5.89%) had prepregnancy underweight, and 208 335 (53.13%) mothers had overweight or obesity. Among 649 956 included offspring, 332 359 (51.14%) were male, and 106 777 (16.43%) had received a neurodevelopmental or psychiatric diagnosis. Maternal eating disorders, prepregnancy underweight, and overweight or obesity were associated with most of the studied mental diagnoses in offspring, even after adjusting for potential covariates. The largest effect sizes were observed for maternal eating disorders not otherwise specified in association with offspring sleep disorders (hazard ratio [HR], 3.34 [95% CI, 2.39-4.67]) and social functioning and tic disorders (HR, 2.79 [95% CI, 2.21-3.52]), while for maternal severe prepregnancy obesity, offspring intellectual disabilities (HR, 2.04 [95% CI, 1.83-2.28]) had the largest effect size. Adverse birth outcomes further increased the risk of offspring having other feeding disturbances of childhood and infancy (eg, HR, 4.53 [95% CI, 2.97-6.89] for maternal eating disorders) and attention-deficit/hyperactivity disorder and conduct disorder (eg, HR, 2.27 [95% CI, 1.74-2.96] for maternal anorexia nervosa).

In this population-based cohort study including 392 098 mothers and 649 956 offspring, offspring from mothers with an eating disorder history or prepregnancy BMI outside normal weight were at higher risk of psychiatric disorders. The results differed somewhat between the 2 exposures with regard to which offspring diagnoses had associations, and effect sizes were typically larger for maternal eating disorders vs BMI. These findings suggest a need to consider these 2 exposures clinically to help prevent offspring mental illness.