Search Results (1,235)

The vector of modern obstetrics is aimed at finding ways to predict various placenta-associated complications, including those associated with neuronal dysfunction on in fetal growth restriction (FGR). The technology of fetal neuronal exosome (FNE) isolation from the maternal bloodstream opens up unique opportunities for detecting early signs of fetal brain damage. Using this method, FNEs were isolated from the blood of pregnant women with and without early-onset FGR, and the expression of a number of proteins in their composition was assessed (Western blotting). Significant changes in the level of proteins involved in neurogenesis (pro-BDNF (brain-derived neurotrophic factor), pro-NGF (nerve growth factor), TAG1/Contactin2) and presynaptic transmission (Synapsin 1, Synaptophysin) were revealed. The preliminary data on the expression of FNE proteins that perform post-translational modifications—sumoylation (SUMO 1, UBC9) and neddylation (NEDD8, UBC12)—were obtained. A relationship was established between altered protein expression and neonatal outcomes in newborns with growth restriction. Our study opens up new possibilities for non-invasive prenatal monitoring of fetal neurodevelopment disorders and possibilities of their correction in placenta-associated diseases. Full article

This study aims to describe neurological, visual, and auditory findings in children whose mothers had confirmed Zika virus (ZIKV) infection during pregnancy, with most of these children not presenting congenital microcephaly; Methods: an observational, longitudinal, and prospective study was conducted in Rio de Janeiro, Brazil, from March 2015 to January 2017, involving children with in utero exposure to Zika virus, following from birth up to 30 months of age. Results: Of the 2882 pregnant women admitted, 116 had a suspected ZIKV infection, of whom 33 had laboratory confirmation. Only one child presented with congenital microcephaly. Despite this, neurodevelopment delay was observed in 36.4% of children evaluated, radiological abnormalities in 29.1%, auditory abnormalities in 8.3%, and ophthalmological abnormalities in 10%. Conclusions: Newborns of mothers with confirmed ZIKV infection during pregnancy may present with varying degrees of visual, auditory, and neurological impairment, despite the presence of congenital microcephaly. Full article

Caffeine is commonly used to excess by the general public, and most pregnant women drink caffeine on a daily basis, which can become a habit. Maternal caffeine intake during pregnancy is associated with severe gestational outcomes. Due to its lipophilic nature, caffeine can cross the blood–brain barrier, placental barrier, and even amniotic fluid. It can be found in substantive amounts in breast milk and semen. There has been a reported drop in neonatal anthropometric measurements with increased caffeine consumption in some cohort studies. This narrative review using literature titles and abstracts from the electronic databases of PubMed, Embase, and Scopus investigates the data linking maternal caffeine use to unfavorable pregnancy outcomes. It also evaluates the validity of the recommendations made by health professionals on caffeine consumption by mothers from the available literature. The results of our comprehensive literature search of case–control studies, cohort studies, randomized control trials, and meta-analyses, imply that caffeine use during pregnancy is linked to miscarriage, stillbirth, low birth weight, and babies that are small for gestational age. It was also found that there may be effects on the neurodevelopment of the child and links to obesity and acute leukemia. These effects can even be seen at doses well below the daily advised limit of 200 mg. The genetic variations in caffeine metabolism and epigenetic changes may play a role in the differential response to caffeine doses. It is crucial that women obtain solid, evidence-based guidance regarding the possible risks associated with caffeine. Full article

Background/Objectives: Preterm infants are at a high risk of neurodevelopmental impairments due to immature brain development and the stressors of the neonatal intensive care unit (NICU) environment. To improve outcomes, incorporating a neuropromotion strategy by promoting nurturing encounters (NEs) is essential. Methods: In this 48-bed tertiary perinatal care center, an informal survey showed that staff lacked consistent knowledge about sensory neurodevelopment, while parents expressed a need for clearer guidance. This paper describes the development and implementation of the Sensory Developmental Care Map (SDCM) as part of a larger quality-improvement initiative. The SDCM is an educational tool designed to guide NICU staff and families in providing neuroprotective and neuropromotive care, based on the infant’s gestational age (GA). The SDCM was created by integrating evidence on sensory development across GAs and providing practical strategies to promote positive sensory input while protecting the developing brain. The map visually indicates when to protect or stimulate each sense, offering clear, developmentally appropriate guidance. Printed and digital versions of the map were made accessible to families and staff, with bedside copies and a poster displayed in the unit. Results: A post-implementation evaluation is ongoing, but preliminary feedback suggests that the SDCM improved the family understanding of sensory developmental care. The SDCM serves as a valuable resource for promoting appropriate sensory input for preterm infants and further enhancing developmentally supportive care within the NICU. Full article

The built physical and social environments are critical drivers of child neural and cognitive development. This study aimed to identify the factor structure and correlates of 29 environmental, education, and socioeconomic indicators of neighborhood resources as measured by the Child Opportunity Index 2.0 (COI 2.0) in a sample of youths aged 9–10 enrolled in the Adolescent Brain Cognitive Development (ABCD) Study. This study used the baseline data of the ABCD Study (n = 9767, ages 9–10). We used structural equation modeling to investigate the factor structure of neighborhood variables (e.g., indicators of neighborhood quality including access to early child education, health insurance, walkability). We externally validated these factors with measures of psychopathology, impulsivity, and behavioral activation and inhibition. Exploratory factor analyses identified four factors: Neighborhood Enrichment, Socioeconomic Attainment, Child Education, and Poverty Level. Socioeconomic Attainment and Child Education were associated with overall reduced impulsivity and the behavioral activation system, whereas increased Poverty Level was associated with increased externalizing symptoms, an increased behavioral activation system, and increased aspects of impulsivity. Distinct dimensions of neighborhood opportunity were differentially associated with aspects of psychopathology, impulsivity, and behavioral approach, suggesting that neighborhood opportunity may have a unique impact on neurodevelopment and cognition. This study can help to inform future public health efforts and policy about improving built and natural environmental structures that may aid in supporting emotional development and downstream behaviors. Full article

The early postnatal period is a critical neurodevelopmental stage characterized by rapid neural maturation and is adversely affected by early-life stressors. This study explored the behavioural, physiological, and epigenetic consequences of early-life stress in a population of homeless rescue kittens. This longitudinal study included 50 kittens rescued and placed into foster care by the Prince Edward Island Humane Society. They underwent behavioural testing at 8, 10, and 12 weeks of age. Hair cortisol concentration was measured at 8 weeks and served as a physiological marker of the previous 3 months’ cumulative stress response, which, for these kittens, included the late gestation period. A blood sample for relative telomere length measurement was taken at 10–12 weeks to estimate epigenetic changes as young kittens. Data were analyzed with respect to age and performance in all repeated measures tests, status as a stray or a surrender, and the presence of the dam in their foster homes. As expected, the performance of kittens in all tests changed over the 5 weeks of testing. Kittens separated from their mothers exhibited significantly higher hair cortisol concentrations (p = 0.02) and elongated relative telomere lengths (p = 0.04). No correlation was found between hair cortisol concentration and relative telomere lengths (p = 0.99). These results support the need for further study on the effects of epigenetics and early-life stress, both in kittens and across species. Full article

Background/Objectives: The experience of prenatal stress results in various physiological disorders due to an alteration of an offspring’s methylome and transcriptome. The objective of this study was to determine whether PNS affects DNA methylation (DNAm) and gene expression in the stress axis tissues of mature Brahman cows. Methods: Samples were collected from the paraventricular nucleus (PVN), anterior pituitary (PIT), and adrenal cortex (AC) of 5-year-old Brahman cows that were prenatally exposed to either transportation stress (PNS, n = 6) or were not transported (Control, n = 8). The isolated DNA and RNA samples were, respectively, used for methylation and RNA-Seq analyses. A gene ontology and KEGG pathway enrichment analysis of each data set within each sample tissue was conducted with the DAVID Functional Annotation Tool. Results: The DNAm analysis revealed 3, 64, and 99 hypomethylated and 2, 93, and 90 hypermethylated CpG sites (FDR < 0.15) within the PVN, PIT, and AC, respectively. The RNA-Seq analysis revealed 6, 25, and 5 differentially expressed genes (FDR < 0.15) in the PVN, PIT, and AC, respectively, that were up-regulated in the PNS group relative to the Control group, as well as 24 genes in the PIT that were down-regulated. Based on the enrichment analysis, several developmental and cellular processes, such as maintenance of the actin cytoskeleton, cell motility, signal transduction, neurodevelopment, and synaptic function, were potentially modulated. Conclusions: The methylome and transcriptome were altered in the stress axis tissues of mature cows that had been exposed to prenatal transportation stress. These findings are relevant to understanding how prenatal experiences may affect postnatal neurological functions. Full article

The Bland–Altman repeated-measures correlation (rmcorr) is widely used to estimate within-person correlations between two variables in repeated-measures data. However, it assumes the same slope for all subjects, which can be misleading when slopes vary. We propose an alternative method, the weighted mean within-person correlation (wmcorr), which calculates the average of all within-person correlations, weighted by the square root of the number of observations for each person. The wmcorr method was applied to real data examples and compared to the Bland–Altman rmcorr. Simulations (5000) were run to compare the mean significance levels (p-values) of rmcorr and wmcorr and to determine the relationship between estimated rmcorrs and wmcorrs. In most cases, rmcorr and wmcorr yielded similar results. However, in cases where subjects had at least moderately varying slopes, wmcorr provided a more visually intuitive estimate of the within-person correlation. Conflicting significance levels or opposite directions of rmcorr and wmcorr served as “warning signs” for potential data quality issues or the need for further data collection. The wmcorr method is proposed as an alternative to the Bland–Altman rmcorr for estimating within-person correlations in repeated-measures data. Researchers are encouraged to estimate both wmcorr and rmcorr, as discrepancies between the two can alert researchers to data patterns that warrant closer inspection before drawing conclusions about within-person relationships. Full article

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in various products, such as firefighting foams and non-stick cookware, due to their resistance to heat and degradation. However, these same properties make them persistent in the environment and human body, raising public health concerns. This study selected eleven PFAS commonly found in drinking water and exposed Caenorhabditis elegans to concentrations ranging from 0.1 to 200 µM to assess neurodevelopmental toxicity using a high-throughput, high-content screening (HTS) platform coupled with artificial intelligence for image analysis. Our findings showed that PFAS such as 6:2 FTS, HFPO-DA, PFBA, PFBS, PFHxA, and PFOS inhibited dopaminergic neuron activity, with fluorescence intensity reductions observed across concentrations from 0.1 to 100 µM. PFOS and PFBS also disrupted synaptic transmission, causing reduced motility and increased paralysis in aldicarb-induced assays, with the most pronounced effects at higher concentrations. These impairments in both neuron activity and synaptic function led to behavioral deficits. Notably, PFOS was one of the most toxic PFAS, affecting multiple neurodevelopmental endpoints. These results emphasize the developmental risks of PFAS exposure, highlighting the impact of both individual compounds and mixtures on neurodevelopment. This knowledge is essential for assessing PFAS-related health risks and informing mitigation strategies. Full article

Autism spectrum disorder (ASD) is an early-onset neurodevelopmental condition that now impacts 1 in 36 children in the United States and is characterized by deficits in social communication, repetitive behaviors, and restricted interests. Children with ASD also frequently experience co-morbidities including anxiety and ADHD, and up to 80% experience gastrointestinal (GI) symptoms such as constipation, diarrhea, and/or abdominal pain. Systemic immune activation and dysregulation, including increased pro-inflammatory cytokines, are frequently observed in ASD. Evidence has shown that the innate immune system may be impacted in ASD, as altered monocyte gene expression profiles and cytokine responses to pattern recognition ligands have been observed compared to typically developing (TD) children. In humans, circulating monocytes are often categorized into three subpopulations—classical, transitional (or “intermediate”), and nonclassical monocytes, which can vary in functions, including archetypal inflammatory and/or reparative functions, as well as their effector locations. The potential for monocytes to contribute to immune dysregulation in ASD and its comorbidities has so far not been extensively studied. This study aims to determine whether these monocyte subsets differ in frequency in children with ASD and if the presence of GI symptoms alters subset distribution, as has been seen for T cell subsets. Whole blood from ASD children with (ASD⁺GI⁺) and without gastrointestinal symptoms (ASD⁺GI⁻) and their TD counterparts was collected from children enrolled in the Childhood Autism Risk from Genetics and Environment (CHARGE) study. Peripheral blood mononuclear cells were isolated and stained for commonly used subset identifiers CD14 and CD16 as well as activation state markers CCR2, HLA-DR, PD-1, and PD-L1 for flow cytometry analysis. We identified changes in monocyte subpopulations and their expression of surface markers in children with ASD compared to TD children. These differences in ASD appear to be dependent on the presence or absence of GI symptoms. We found that the ASD⁺GI⁺ group have a different monocyte composition, evident in their classical, transitional, and nonclassical populations, compared to the ASD⁺GI⁻ and TD groups. Both the ASD⁺GI⁺ and ASD⁺GI⁻ groups exhibited greater frequencies of classical monocytes compared to the TD group. However, the ASD⁺GI⁺ group demonstrated lower frequencies of transitional and nonclassical monocytes than their ASD⁺GI⁻ and TD counterparts. CCR2⁺ classical monocyte frequencies were highest in the ASD⁺GI⁻ group. HLA-DR⁺ classical, transitional, and nonclassical monocytes were statistically comparable between groups, however, HLA-DR⁻ nonclassical monocyte frequencies were lower in both ASD groups compared to TD. The frequency of classical monocytes displaying exhaustion markers PD-1 and PD-L1 were increased in the ASD⁺GI⁺ group compared to ASD⁺GI⁻ and TD, suggesting potentially impaired ability for clearance of foreign pathogens or debris, typically associated with worsened inflammation. Taken together, the findings of differential proportions of the monocyte subpopulations and altered surface markers may explain some of the characteristics of immune dysregulation, such as in the gastrointestinal tract, observed in ASD. Full article

Background: The percentage of preterm infants requiring surgery before 44 weeks of postmenstrual age (PMA) varies between 19% and 36%. The potential impact of general anesthesia on the vulnerable developing brain of preterm infants remains unknown. Methods: A systematic review and meta-analysis on the impact of general anesthesia on brain integrity and neurodevelopmental outcomes in preterm infants undergoing surgery before 44 weeks PMA was conducted. Studies were identified via a PubMed, EMBASE (Ovid), and Cochrane CENTRAL search conducted from inception until 8 March 2023, following PRISMA guidelines. Brain abnormality was assessed using MRI-based brain volume and abnormality scores. Neurodevelopment was evaluated through Bayley Infant and Toddler Development (BSID) or Wechsler Preschool and Primary Scale of Intelligence (WPPSI) tests. Quality was assessed via the Cochrane ROBINS-I tool and GRADE. Results: Our systematic search identified 2883 records, leading to the inclusion of 12 observational studies. Very low-quality evidence suggests that preterm infants exposed to anesthesia were more likely to show postoperative brain abnormalities on MRI (OR 2.01, 95%CI 1.24–3.25, p = 0.005). They had lower neurodevelopmental scores on the BSID II and III (psychomotor developmental index: mean difference (MD) −10.98; 95%CI −12.04 to −9.91; p < 0.001 and cognitive composite score: (MD) −10.11; 95%CI −11.06 to −9.16; p < 0.001 at two years of age compared to preterm infants not exposed to anesthesia. Conclusion: Exposure to surgery and anesthesia before term age is associated with brain abnormalities and neurodevelopmental delay at two years, but conclusions are limited by low evidence quality, uncontrolled confounders, and the methodological biases of the included studies; thus further robust studies are required (PROSPERO:CRD42021255907). Full article

Background/Objectives: Postnatal growth faltering (PGF) is a risk factor for adverse neurodevelopment in very preterm neonates. The aim of this retrospective study was to determine which infants’ baseline characteristics, prenatal risk factors and neonatal morbidities are associated with two definitions of PGF: defined as loss of >2 weight z-scores (severe PGF) or as loss of >1 weight, length, and head circumference z-scores between birth and discharge (complex PGF); Methods: 146 premature newborns (<32 weeks of gestational age, <1500 g) were included in the study. Anonymized data including anthropometric measurements (weight, length, and head circumference), perinatal and neonatal data (demographics, maternal morbidities and previous pregnancies, and neonatal and perinatal morbidities) were extracted from the clinical electronic database. Changes in anthropometric age- and sex-specific z-scores using the Fenton 2013 preterm growth charts were calculated to diagnose severe PGF and complex PGF; Results: The incidence of severe PGF was 11% and complex PGF was 24%. Both PGF definitions were associated with bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity (ROP), longer respiratory support, and longer hospital stay. Severe PGF was associated with surgical necrotizing enterocolitis at 25% vs. 1.5%, p = 0.001. Complex PGF was associated with severe brain injury at 51% versus 27%, p = 0.007. Complex PGF was more common in newborns born most prematurely, while severe PGF was more common in newborns born small for gestational age (SGA); Conclusions: Both severe and complex PGF are associated with several important neonatal morbidities, which might explain why growth faltering is associated with suboptimal neurodevelopment. Appropriate early identification of faltered growth may influence medical and nutrition interventions which in turn could improve the outcome of very preterm newborns. Full article

Tetrabromobisphenol A bis (2-hydroxyethyl) ether (TBBPA-DHEE), a derivative of TBBPA, has been frequently detected in the environment. In this study, the median lethal concentration (LC₅₀) of TBBPA-DHEE at 96 h post-fertilization (hpf) was 1.573 mg/L. Based on the reported environmental concentrations, we investigated the effects of TBBPA-DHEE on the nervous system of zebrafish embryos following exposure to varying concentrations (0, 20, 100, and 500 μg/L) for 4 to 144 hpf. Our results indicated that exposure to 100 μg/L at 144 hpf led to behavioral abnormalities in zebrafish. Furthermore, exposure to TBBPA-DHEE inhibited the development of the central nervous system and motor neurons in zebrafish. Real-time polymerase chain reaction (PCR) analysis revealed that exposure to TBBPA-DHEE significantly downregulated the expression levels of neurodevelopmental genes (shha, syn2a, elavl3, gfap, and gap43). Additionally, TBBPA-DHEE increased oxidative stress in zebrafish. Transcriptomic analysis demonstrated that exposure to TBBPA-DHEE affected the signaling pathways involved in neurodevelopment. Overall, this study demonstrated that TBBPA-DHEE may disrupt the early development of the nervous system, leading to abnormal motor behavior in zebrafish larvae, and provided novel insights into the potential mechanisms of TBBPA-DHEE neurotoxicity. Full article

Background: Epilepsy is a neurological disorder defined by the occurrence of epileptic seizures, which can significantly affect children, often leading to learning and cognitive impairments. Microglia, the resident immune cells of the central nervous system, are essential in clearing damaged neurons through phagocytosis. Notably, GAB_BR-associated microglia have been implicated in regulating phagocytic activity. Since the phagocytic function of microglia is critical in the pathogenesis of epilepsy, this study aims to investigate the role of GAB_BR-associated microglia in the development of the immature brain following epileptic seizures. Methods: Epilepsy was induced in a mouse model by the intraperitoneal injection of KA. Changes in the expression of the GAB_BR-related gene, GAB_BR2, in hippocampal microglia were analyzed using single-nucleus RNA sequencing (snRNA-seq). Cognitive and emotional changes in the mice were assessed through behavioral analyses. The expression of GAB_BR2 was semi-quantitatively measured using Western blotting, quantitative reverse transcription PCR, and immunofluorescence. Additionally, the spatial relationship between GAB_BR2 and hippocampal neurons was evaluated using Imaris software. Results: The snRNA-seq analysis revealed that GAB_BR2 expression was elevated in activated microglia in the hippocampus during chronic epilepsy compared to the early phase of seizures. Behavioral assessments demonstrated heightened anxiety levels and learning and memory impairments in the chronic epilepsy group compared to the control group. GAB_BR2 expression was upregulated in chronic epilepsy. Three-dimensional reconstruction analyses revealed a significantly increased contact volume between GAB_BR-associated microglia and neurons in the chronic epilepsy group compared to the control group. Conclusions: GAB_BR-associated microglia significantly contribute to the progression of immature brain diseases by promoting neuronal phagocytic activity. Full article

Retinal neurodevelopment, vascularization, homeostasis, and stress response are influenced by factors such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tyrosine hydroxylase (TH), and erythropoietin (EPO). As retinopathy of prematurity (ROP) is a neurovascular retinal disease, this study analyzed the contributions of NGF (rs6330), BDNF (rs7934165), TH (rs10770141), and EPO (rs507392) genetic functional polymorphisms to the modulation of hematological and biochemical parameters of the first week of life and their association with ROP development. A multicenter cohort of 396 preterm infants (gestational age < 32 weeks or birth weight < 1500 g) was genotyped using MicroChip DNA and iPlex MassARRAY^® platform. Multivariate regression followed univariate assessment of ROP risk factors. NGF (GG) genotype was associated with a higher ROP risk (OR = 1.79), which increased further (OR = 2.38) when epistatic interactions with TH (allele C) and BDNF (allele G) were present. Significant circulating biomarker differences, including bilirubin, erythrocytes, monocytes, neutrophils, lymphocytes, and platelet markers, were found between ROP and non-ROP groups, with variations depending on the polymorphism. These findings suggest that NGF (rs6330) and its interactions with related genes contribute to ROP risk, providing valuable insights into the genetic and biological mechanisms underlying the disease and identifying potential predictive biomarkers. Full article