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Mismanagement of hazardous waste (HW) causes severe threats to ecosystems and human health. We conducted a systematic literature review and evaluated the evidence regarding the association between residential exposure to HW and childhood neurobehavioral effects. We consulted international agencies websites and conducted a search on MEDLINE and EMBASE databases by applying a “Population-Exposure-Comparator-Outcome” question. The evidence evaluation, based on the quality of the studies and their concordance, was graded in sufficient/limited/inadequate. Documents from international agencies were not found. Of the seventy-five studies screened, nine met the eligibility criteria. Studies agree on the association between residential exposure to HW sites and negative neurodevelopmental effects. The evidence of the association was attributed limited to cognitive and behavioral outcomes, and inadequate to Autism Spectrum Disorder. The evidence was evaluated sufficient for HW sites releasing lead and cognitive disorders. Residential exposure to unsafe HW sites may contribute to childhood neurobehavioral alterations. It is urgent to implement environmental remediation of contaminated sites and counteracting illegal and unsafe HW management practices. [ABSTRACT FROM AUTHOR]

The main goal of the current work was to assess the age sensitivity of a novel battery of cool and hot Executive Function (EF) tasks developed for the middle childhood period: the Executive Brain Battery (EBB). To this end, we carried out a first study in which the EBB was administered to six age groups ranging from 6 to 11. Additionally, in a second study, we compared children at the end of middle childhood (age 11 years) and adult performance in the EBB. Results showed that tasks included in the EBB were suitable for all age groups, with more age-related changes being found in cool than hot EF tasks. Moreover, at the end of middle childhood, children reach an adult-like performance in most of these cool and hot tasks. The present findings extend previous research suggesting that cool and hot EFs exhibit different patterns of age-related growth in middle childhood. Additionally, the EEB could become a useful tool for research on EFs during middle childhood that could be adapted for a wide range of populations. [ABSTRACT FROM AUTHOR]

Early life adversity (ELA) is a heterogeneous group of negative childhood experiences that can lead to abnormal brain development and more severe psychiatric, neurological, and medical conditions in adulthood. According to the immune hypothesis, ELA leads to an abnormal immune response characterized by high levels of inflammatory cytokines. This abnormal immune response contributes to more severe negative health outcomes and a refractory response to treatment in individuals with a history of ELA. Here, we examine this hypothesis in the context of recent rodent studies that focus on the impact of ELA on microglia, the resident immune cells in the brain. We review recent progress in our ability to mechanistically link molecular alterations in microglial function during a critical period of development with changes in synaptic connectivity, cognition, and stress reactivity later in life. We also examine recent research showing that ELA induces long-term alterations in microglial inflammatory response to "secondary hits" such as traumatic brain injury, substance use, and exposure to additional stress in adulthood. We conclude with a discussion on future directions and unresolved questions regarding the signals that modify microglial function and the clinical significance of rodent studies for humans. [ABSTRACT FROM AUTHOR]

The assessment for ADHD is particularly challenging in the presence of known or suspected coexisting conditions or presentations, such as other neurodevelopmental conditions, mental health conditions or intellectual disability, but accurate identification of aetiology is vital to ensure appropriate and effective support or intervention is offered. This paper focuses on the assessment for ADHD in the context of possible or known developmental trauma, two presentations with significant overlap and co-occurrence. Using theoretical knowledge and clinical experience we attempt to offer a framework to guide assessment. An overview of each of these presentations is given; similarities and differences in key domains for each presentation are defined; and features in a child's presentation that may have been attributed to possible ADHD but may in fact be related to developmental trauma are identified. Guidance regarding the approach to assessment of ADHD for a child who may also present with developmental trauma, is woven through the paper. [ABSTRACT FROM AUTHOR]

Selenoproteins regulate pathways controlling neurodevelopment, e.g., redox signaling and thyroid hormone metabolism. However, studies investigating maternal selenium in relation to child neurodevelopmental disorders are scarce. 719 mother-child pairs from the prospective population-based Odense Child Cohort study in Denmark were included. Three selenium biomarkers, i.e. concentrations of serum selenium, selenoprotein P (SELENOP), and activity of glutathione peroxidase 3 (GPX3), along with serum copper, zinc and iron were measured in early third trimester (at 28.9+/-0.8 weeks of pregnancy). ADHD and ASD traits in children were assessed systematically using the established Child Behaviour Checklist at 5 years of age, based on a Danish reference cohort with cut-off at 90th percentile. Multivariable regression models adjusted for biologically relevant confounders were applied. 155 of 719 (21.6 %) children had ASD traits and 59 of 719 (8.2 %) children had traits of ADHD at 5 years of age. In crude and adjusted models, all three selenium biomarkers associated inversely with ADHD traits. For ADHD, fully adjusted OR for 10 μg/L increment in selenium was 0.76 (95 % CI 0.60, 0.94), for one mg/L increment in SELENOP was 0.73 (0.56, 0.95), and for 10 U/L increment in GPx3 was 0.93 (0.87,1.00). Maternal total selenium was inversely associated with child ASD traits, OR per 10 μg/L increment was 0.85 (0.74, 0,98). SELENOP and GPx3 were not associated with ASD traits. The associations were specific to selenium, as other trace elements such as copper, zinc, or iron were not associated with the outcomes. The results provide coherent evidence for selenium deficiency as a risk factor for ADHD and ASD traits in an environment with borderline supply, the causality of which should be elucidated in a randomized controlled trial. [Display omitted] • Analysis of maternal Se status and child ADHD- & ASD traits in 719 pregnancies. • Low maternal Se, SELENOP and GPx3 associated with ADHD traits in children. • Low maternal Se associated with ASD traits in children. • The associations were dose-dependent and robust after adjusting for confounders. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) impacts the developing brain. Here, a technique was applied to define, in 3D, developmental changes in the brains of ZIKV-infected mice. Postnatal day 1 mice were uninfected or ZIKV-infected, then analysed by iodine staining and micro-CT scanning (diffusible iodine contrast-enhanced micro-CT; diceCT) at 3-, 6-, and 10-days post-infection (dpi). Multiple brain regions were visualised using diceCT: the olfactory bulb, cerebrum, hippocampus, midbrain, interbrain, and cerebellum, along with the lens and retina of the eye. Brain regions were computationally segmented and quantitated, with increased brain volumes and developmental time in uninfected mice. Conversely, in ZIKV-infected mice, no quantitative differences were seen at 3 or 6 dpi when there were no clinical signs, but qualitatively, diverse visual defects were identified at 6–10 dpi. By 10 dpi, ZIKV-infected mice had significantly lower body weight and reduced volume of brain regions compared to 10 dpi-uninfected or 6 dpi ZIKV-infected mice. Nissl and immunofluorescent Iba1 staining on post-diceCT tissue were successful, but RNA extraction was not. Thus, diceCT shows utility for detecting both 3D qualitative and quantitative changes in the developing brain of ZIKV-infected mice, with the benefit, post-diceCT, of retaining the ability to apply traditional histology and immunofluorescent analysis to tissue. [ABSTRACT FROM AUTHOR]

Aim: Understanding the physiological role of ATP6V1A, a component of the cytosolic V1 domain of the proton pump vacuolar ATPase, in regulating neuronal development and function. Methods: Modeling loss of function of Atp6v1a in primary murine hippocampal neurons and studying neuronal morphology and function by immunoimaging, electrophysiological recordings and electron microscopy. Results: Atp6v1a depletion affects neurite elongation, stabilization, and function of excitatory synapses and prevents synaptic rearrangement upon induction of plasticity. These phenotypes are due to an overall decreased expression of the V1 subunits, that leads to impairment of lysosomal pH‐regulation and autophagy progression with accumulation of aberrant lysosomes at neuronal soma and of enlarged vacuoles at synaptic boutons. Conclusions: These data suggest a physiological role of ATP6V1A in the surveillance of synaptic integrity and plasticity and highlight the pathophysiological significance of ATP6V1A loss in the alteration of synaptic function that is associated with neurodevelopmental and neurodegenerative diseases. The data further support the pivotal involvement of lysosomal function and autophagy flux in maintaining proper synaptic connectivity and adaptive neuronal properties. [ABSTRACT FROM AUTHOR]

Prescriptions for antiseizure medications (ASMs) have been rapidly growing over the last several decades due, in part, to an expanding list of clinical indications for which they are now prescribed. This trend has raised concern for potential adverse neurodevelopmental outcomes in ASM-exposed pregnancies. Recent large scale population studies have suggested that the use of topiramate (TOPAMAX, Janssen-Cilag), when prescribed for seizure control, migraines, and/or weight management, is associated with an increased risk for autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD) in exposed offspring. Here, we critically review epidemiologic evidence demonstrating the neurobehavioral teratogenicity of topiramate and speculate on the neuromolecular mechanisms by which prenatal exposure may perturb neurocognitive development. Specifically, we explore the potential role of topiramate's pharmacological interactions with ligand- and voltage-gated ion channels, especially GABAergic signaling, its effects on DNA methylation and histone acetylation, whether topiramate induces oxidative stress, and its association with fetal growth restriction as possible mechanisms contributing to neurodevelopmental toxicity. Resolving this biology will be necessary to reduce the risk of adverse pregnancy outcomes caused by topiramate or other ASMs. [ABSTRACT FROM AUTHOR]

Cells configure their metabolism in a synchronized and timely manner to meet their energy demands throughout development and adulthood. Transitions of developmental stages are coupled to metabolic shifts, such that glycolysis is highly active during cell proliferation, whereas oxidative phosphorylation prevails in postmitotic states. In the cerebellum, metabolic transitions are remarkable given its protracted developmental timelines. Such distinctive feature, along with its high neuronal density and metabolic demands, make the cerebellum highly vulnerable to metabolic insults. Despite the expansion of metabolomic approaches to uncover biological mechanisms, little is known about the role of metabolism on cerebellar development and maintenance. To illuminate the intricate connections between metabolism, physiology, and cerebellar disorders, we examined here the impact of metabolism on cerebellar growth, maturation, and adulthood through the lens of inborn errors of metabolism. [ABSTRACT FROM AUTHOR]

Introduction: Prenatal exposure to supraphysiological glucocorticoid (GC) levels may lead to long‐lasting developmental changes in numerous biological systems. Our prior study identified an association between prenatal GC prophylaxis and reduced cognitive performance, electrocortical changes, and altered autonomic nervous system (ANS) activity in children aged 8–9 years. This follow‐up study aimed to examine whether these findings persisted into adolescence. Material and Methods: Prospective observational follow‐up study involving twenty‐one 14‐ to 15‐year‐old adolescents born to mothers who received betamethasone for induction of fetal lung maturation in threatened preterm birth, but who were born with a normal weight appropriate for their gestational age (median 37+4 gestational weeks). Thirty‐five children not exposed to betamethasone served as the reference group (median 37+6 gestational weeks). The primary endpoint was cognitive performance, measured by intelligence quotient (IQ). Key secondary endpoints included symptoms of attention‐deficit/hyperactivity disorder (ADHD) and metabolic markers. Additionally, we determined electrocortical (electroencephalogram), hypothalamus–pituitary–adrenal axis (HPAA), and ANS activity in response to a standardized stress paradigm. Results: No statistically significant group difference was observed in global IQ (adjusted mean: betamethasone 103.9 vs references 105.9, mean difference −2.0, 95% confidence interval [CI]: −7.12 to 3.12, p = 0.44). Similarly, ADHD symptoms, metabolic markers, the overall and stress‐induced activity of the HPAA and the ANS did not differ significantly between groups. However, the betamethasone group exhibited reduced electrocortical activity in the frontal brain region (spectral edge frequency–adjusted means: 16.0 Hz vs 17.8 Hz, mean difference −1.83 Hz, 95% CI: −3.21 to −0.45, p = 0.01). Conclusions: In 14‐ to 15‐year‐old adolescents, prenatal GC exposure was not associated with differences in IQ scores or ANS activity compared to unexposed controls. However, decelerated electrocortical activity in the frontal region potentially reflects disturbances in the maturation of cortical and/or subcortical brain structures. The clinical significance of these changes remains unknown. Given the small sample size, selective participation/loss of follow‐up and potential residual confounding, these findings should be interpreted cautiously. Further research is required to replicate these results in larger cohorts before drawing firm clinical conclusions. [ABSTRACT FROM AUTHOR]

Clinical studies demonstrate that the risk of developing neurological disorders is increased by overconsumption of the commonly used drugs, alcohol, nicotine and cannabis. These drug-induced neurological disorders, which include substance use disorder (SUD) and its co-occurring emotional conditions such as anxiety and depression, are observed not only in adults but also with drug use during adolescence and after prenatal exposure to these drugs, and they are accompanied by long-lasting disturbances in brain development. This report provides overviews of clinical and preclinical studies, which confirm these adverse effects in adolescents and the offspring prenatally exposed to the drugs and include a more in-depth description of specific neuronal systems, their neurocircuitry and molecular mechanisms, affected by drug exposure and of specific techniques used to determine if these effects in the brain are causally related to the behavioral disturbances. With analysis of further studies, this review then addresses four specific questions that are important for fully understanding the impact that drug use in young individuals can have on future pregnancies and their offspring. Evidence demonstrates that the adverse effects on their brain and behavior can occur: (1) at low doses with short periods of drug exposure during pregnancy; (2) after pre-conception drug use by both females and males; (3) in subsequent generations following the initial drug exposure; and (4) in a sex-dependent manner, with drug use producing a greater risk in females than males of developing SUDs with emotional conditions and female offspring after prenatal drug exposure responding more adversely than male offspring. With the recent rise in drug use by adolescents and pregnant women that has occurred in association with the legalization of cannabis and increased availability of vaping tools, these conclusions from the clinical and preclinical literature are particularly alarming and underscore the urgent need to educate young women and men about the possible harmful effects of early drug use and to seek novel therapeutic strategies that might help to limit drug use in young individuals. [ABSTRACT FROM AUTHOR]

Neurotrophins and their receptors are distinctly expressed during brain development and play crucial roles in the formation, survival, and function of neurons in the nervous system. Among these molecules, brain-derived neurotrophic factor (BDNF) has garnered significant attention due to its involvement in regulating GABAergic system development and function. In this review, we summarize and compare the expression patterns and roles of neurotrophins and their receptors in both the developing and adult brains of rodents, macaques, and humans. Then, we focus on the implications of BDNF in the development and function of GABAergic neurons from the cortex and the striatum, as both the presence of BDNF single nucleotide polymorphisms and disruptions in BDNF levels alter the excitatory/inhibitory balance in the brain. This imbalance has different implications in the pathogenesis of neurodevelopmental diseases like autism spectrum disorder (ASD), Rett syndrome (RTT), and schizophrenia (SCZ). Altogether, evidence shows that neurotrophins, especially BDNF, are essential for the development, maintenance, and function of the brain, and disruptions in their expression or signaling are common mechanisms in the pathophysiology of brain diseases. [ABSTRACT FROM AUTHOR]

Consumption of sucrose‐sweetened drinks (SSDs) during pregnancy and breastfeeding can lead to various health and metabolism issues, but the potential impact on neurodevelopment and long‐term effects remains unclear. This study aims to examine how maternal consumption of SSDs during gestation and lactation influences anxiety and depression‐related behavior in adult offspring. Adult female CD‐1 mice were randomly assigned to a control group (CG) or a sucrose group (SG) 2 weeks before gestation. The SG had 2 h of access to an SSD (15% w/w, 0.6 kcal/ml) for 2 weeks before mating, during pregnancy, and throughout lactation, totaling 8 weeks. Adult offspring were then evaluated for depressive‐related behaviors and anxiety‐related behaviors. Our findings reveal that perigestational consumption of SSDs does not lead to offspring presenting behaviors related to depression, but it does increase swimming behavior. However, maternal consumption of SSDs could impact the fighting response due to a diminished motivational component. In contrast, perigestational consumption of SSDs has apparent effects on anxiety‐related behavior. Furthermore, female offspring appeared to be particularly vulnerable, exhibiting a higher anxiety index compared with controls. These findings indicate that females could be more vulnerable to the effects of maternal consumption of SSDs, being more susceptible to the presence of anxiety‐related behaviors. [ABSTRACT FROM AUTHOR]

The antidepressant venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, is commonly prescribed to treat major depressive disorder and is found at high concentrations in the aquatic environment. Concerns have been raised related to the health of aquatic organisms in response to this nontargeted pharmaceutical exposure. For instance, we previously demonstrated that exposure to venlafaxine perturbs neurodevelopment, leading to behavioural alterations in zebrafish (Danio rerio). We also observed disruption in serotonin expression in the pineal and raphe, regions critical in regulating circadian rhythms, leading us to hypothesize that zygotic exposure to venlafaxine disrupts the circadian locomotor rhythm in larval zebrafish. To test this, we microinjected zebrafish embryos with venlafaxine (1 or 10 ng) and recorded the locomotor activity in 5‐day‐old larvae over a 24‐h period. Venlafaxine deposition reduced larval locomotor activity during the light phase, but not during the dark phase of the diurnal cycle. The melatonin levels were higher in the dark compared to during the light photoperiod and this was not affected by embryonic venlafaxine deposition. Venlafaxine exposure also did not affect the transcript abundance of clock genes, including clock1a, bmal2, cry1a and per2, which showed a clear day/night rhythmicity. A notable finding was that exposure to luzindole, a melatonin receptor antagonist, decreased the locomotor activity in the control group in light, whereas the activity was higher in larvae raised from the venlafaxine‐deposited embryos. Overall, zygotic exposure to venlafaxine disrupts the locomotor activity of larval zebrafish fish during the day, demonstrating the capacity of antidepressants to disrupt the circadian rhythms in behaviour. Our results suggest that disruption in melatonin signalling may be playing a role in the venlafaxine impact on circadian behaviour, but further investigation is required to elucidate the possible mechanisms in larval zebrafish. [ABSTRACT FROM AUTHOR]

Ambient air pollution is ubiquitous and poses a significant public health concern as a harmful neurotoxicant. During childhood and adolescence, ongoing developmental processes may render the brain especially vulnerable to air pollution. Primary targets for air pollution neurotoxicity include neurons and glial cells, which have heterogeneous functions that are essential to neurodevelopment. A growing body of human neuroimaging research shows that exposure to air pollution is linked to changes in brain structure and function in youth. Given dynamic changes in brain maturation, direction and magnitude of air pollution effects tend to be dependent on timing and brain region. Exposure to outdoor air pollution has been linked to adverse health effects, including potential widespread impacts on the CNS. Ongoing brain development may render children and adolescents especially vulnerable to neurotoxic effects of air pollution. While mechanisms remain unclear, promising advances in human neuroimaging can help elucidate both sensitive periods and neurobiological consequences of exposure to air pollution. Herein we review the potential influences of air pollution exposure on neurodevelopment, drawing from animal toxicology and human neuroimaging studies. Due to ongoing cellular and system-level changes during childhood and adolescence, the developing brain may be more sensitive to pollutants' neurotoxic effects, as a function of both timing and duration, with relevance to cognition and mental health. Building on these foundations, the emerging field of environmental neuroscience is poised to further decipher which air toxicants are most harmful and to whom. [ABSTRACT FROM AUTHOR]

Recent studies report conflicting results regarding the relationship between labour epidural analgesia (LEA) in mothers and neurodevelopmental disorders in their offspring. We evaluated behavioural and neuropsychological test scores in children of mothers who used LEA. Children enrolled in the Raine Study from Western Australia and delivered vaginally from a singleton pregnancy between 1989 and 1992 were evaluated. Children exposed to LEA were compared with unexposed children. The primary outcome was the parent-reported Child Behaviour Checklist (CBCL) reporting total, internalising, and externalising behavioural problem scores at age 10 yr. Score differences, an increased risk of clinical deficit, and a dose-response based on the duration of LEA exposure were assessed. Secondary outcomes included language, motor function, cognition, and autistic traits. Of 2180 children, 850 (39.0%) were exposed to LEA. After adjustment for covariates, exposed children had minimally increased CBCL total scores (+1.41 points; 95% confidence interval [CI] 0.09 to 2.73; P =0.037), but not internalising (+1.13 points; 95% CI –0.08 to 2.34; P =0.066) or externalising (+1.08 points; 95% CI –0.08 to 2.24; P =0.068) subscale subscores. Increased risk of clinical deficit was not observed for any CBCL score. For secondary outcomes, score differences were inconsistently observed in motor function and cognition. Increased exposure duration was not associated with worse scores in any outcomes. Although LEA exposure was associated with slightly higher total behavioural scores, there was no difference in subscores, increased risk of clinical deficits, or dose–response relationship. These results argue against LEA exposure being associated with consistent, clinically significant neurodevelopmental deficits in children. [ABSTRACT FROM AUTHOR]

Cross-sectional studies in adults have demonstrated associations between early life adversity (ELA) and reduced hippocampal volume, but the timing of these effects is not clear. The present study sought to examine whether ELA predicts changes in hippocampal volume over time in a large sample of early adolescents. The Adolescent Brain Cognitive Development Study provides a large dataset of tabulated neuroimaging, youth-reported adverse experiences, and parent-reported financial adversity from a sample of children around the United States. Linear mixed effects modeling was used to determine the relationship between ELA and hippocampal volume change within youth (n = 7036) from ages 9–10 to 11–12 years. Results of the models indicated that the number of early adverse events predicted bilateral hippocampal volume change (β = −0.02, t = −2.02, p <.05). Higher adversity was associated with lower hippocampal volume at Baseline (t = 5.55, p <.01) and at Year 2 (t = 6.14, p <.001). These findings suggest that ELA may affect hippocampal development during early adolescence. Prevention and early intervention are needed to alter the course of this trajectory. Future work should examine associations between ELA, hippocampal development, and educational and socioemotional outcomes. [ABSTRACT FROM AUTHOR]

• Levetiracetam (LEV) is a 1st line anti-seizure medication (ASM) in the UK. • There is no high-quality evidence comparing PwID to those without ID prescribed LEV. • Concerns exist regarding LEV's behavioural & psychological side-effects in PwID. • This is the largest study of PwID trialled on LEV & compared to non-ID controls. • Findings largely support prescribing of LEV for PwID as a first line ASM. People with Intellectual Disabilities (PwID) are twenty times more likely than general population to have epilepsy. Guidance for prescribing antiseizure medication (ASM) to PwID is driven by trials excluding them. Levetiracetam (LEV) is a first-line ASM in the UK. Concerns exist regarding LEV's behavioural and psychological adverse effects, particularly in PwID. There is no high-quality evidence comparing effectiveness and adverse effects in PwID to those without, prescribed LEV. Pooled casenote data for patients prescribed LEV (2000–2020) at 18 UK NHS Trusts were analysed. Demographics, starting and maximum dose, adverse effects, dropouts and seizure frequency between ID (mild vs. moderate-profound (M/P)) and general population for a 12-month period were compared. Descriptive analysis, Mann-Whitney, Fisher's exact and logistic regression methods were employed. 173 PwID (mild 53 M/P 120) were compared to 200 without ID. Mean start and maximum dose were similar across all groups. PwID (Mild & M/P) were less likely to withdraw from treatment (P = 0.036). No difference was found between ID and non-ID or between ID groups (Mild vs M/P) in LEV's efficacy i.e. >50 % seizure reduction. Significant association emerged between ID severity and psychiatric adverse effects (P = 0.035). More irritability (14.2 %) and aggression (10.8 %) were reported in M/P PwID. PwID and epilepsy have high rates of premature mortality, comorbidities, treatment resistance and polypharmacy but remain poorly researched for ASM use. This is the largest studied cohort of PwID trialled on LEV compared to general population controls. Findings support prescribing of LEV for PwID as a first-line ASM. [ABSTRACT FROM AUTHOR]

Fms-like tyrosine kinase 1 (FLT1) has been shown to regulate processes such as angiogenesis, neurogenesis, and cognitive impairment. However, the role of FLT1 in prenatal stress (PS) is unclear. The purpose of this study was to investigate the role of FLT1 in PS mothers and their offspring. Wire mesh restrainers were used to construct PS rat model. The levels of FLT1, IL-1β, IL-6, and ROS in clinical samples and rat samples were detected by qRT-PCR, ELisa kit, and DCFH-DA fluorescence kit. Morris water maze assay and forced swimming assay were used to test the cognitive function of offspring young rats. The apoptosis level of hippocampal neurons and the expression of NMDARs were detected by MTT assay, TUNEL assay, and Western blot. The results showed that FLT1 was upregulated in PS mothers and positively correlated with PS degree. The level of FLT1 was elevated in PS model rats. Knockdown of FLT1 reduced maternal ROS and MDA levels and increased SOD levels in PS rats. Knockdown of FLT1 also reduced the secretion of IL-1β, IL-6, and cortisol in PS rats. Inhibition of FTL1 alleviated cognitive impairment in PS offspring pups. Inhibition of FTL1 reduced hippocampal neuronal apoptosis and increased the expression of NMDARs in PS progeny. In conclusions, we demonstrated that knockdown of FLT1 inhibits maternal oxidative stress, inflammation, and cortisol secretion in PS rats. In addition, knockdown of FLT1 also alleviated cognitive dysfunction and neurodevelopmental abnormalities in PS offspring pups. [ABSTRACT FROM AUTHOR]

Background: Very few adequately powered studies exploring early thresholds for intervention in the management of post-hemorrhagic ventricular dilatation (PHVD) in preterm infants have identified consistent neurodevelopmental advantages at 12–30 months. We aimed to conduct a meta-analysis on the efficacy and safety of early versus conservative thresholds for intervention, primarily aimed at normalizing cerebrospinal fluid (CSF) pressure, in the management of PHVD in preterm infants. Methods: Multiple databases were searched for eligible papers, and prospective randomized trials involving preterm infants were selected. The results are expressed as relative risks (RRs) with 95% confidence intervals (CIs). The main outcome was survival without moderate-to-severe neurodevelopmental impairment at 12–30 months. Results: Ten articles representing seven randomized trials comparing early versus conservative thresholds for interventions were included. Five trials (n = 545 infants) reported no difference in the main outcome between early and conservative groups [RR 0.99 (0.71, 1.37)]. Sensitivity analysis excluding data from a medication trial did not alter the main outcome [RR 1.15 (0.95, 1.39)]. Infants in the early threshold group received significantly more interventions [RR 1.48 (1.05, 2.09)]. Deaths before discharge/during the initial study period [RR 1.04 (0.70, 1.54)] or a composite of death or shunt insertion [RR 1.04 (0.86, 1.27)] were comparable between the two groups. Conclusions: Early intervention for PHVD, before a clinical or ultrasound threshold is met, leads to additional clinical procedures but does not improve survival without moderate–severe neurodevelopmental impairment at 12–30 months. Caution should be exercised in interpreting these results due to significant variation between the studies. 7UFkxJAhmB87qqN8qZfYzb Supplementary file 3 (MP4 131172 kb) [ABSTRACT FROM AUTHOR]

This study examined the association between prenatal cannabis exposure and autism spectrum disorder (ASD) diagnoses and traits. A total sample of 11,570 children (ages 1–18; 53% male; 25% Hispanic; 60% White) from 34 cohorts of the National Institutes of Health‐funded environmental influences on child health outcomes consortium were included in analyses. Results from generalized linear mixed models replicated previous studies showing that associations between prenatal cannabis exposure and ASD traits in children are not significant when controlling for relevant covariates, particularly tobacco exposure. Child biological sex did not moderate the association between prenatal cannabis exposure and ASD. In a large sample and measuring ASD traits continuously, there was no evidence that prenatal cannabis exposure increases the risk for ASD. This work helps to clarify previous mixed findings by addressing concerns about statistical power and ASD measurement. Lay Summary: This study examined the relationship between prenatal cannabis exposure and autism traits. We found that there was no association between maternal cannabis use during pregnancy and child autism traits once potential confounds were controlled. Although there was no evidence that prenatal cannabis exposure increases the risk for autism traits, prenatal cannabis exposure may still be associated with other facets of child development and behavior that were outside of the scope of this study. [ABSTRACT FROM AUTHOR]

Iron supplementation is commonly recommended for the prevention and treatment of maternal iron deficiency (ID) or iron deficiency anemia (IDA). However, the impacts of prophylactic of therapeutic prenatal iron supplementation on child neurodevelopment in upper middle-income (UMI) and high-income countries (HICs), where broad nutritional deficiencies are less common, are unclear. To investigate this, we conducted a systematic review, searching four databases (Medline, CINAHL, EMBASE, Cochrane Library) through 1 May 2023. Randomized controlled trials (RCTs) assessing oral or intravenous iron supplementation in pregnant women reporting on child neurodevelopment (primary outcome: age-standardized cognitive scores) were eligible. We included three RCTs (five publications) from two HICs (Spain and Australia) (N = 935 children; N = 1397 mothers). Due to clinical heterogeneity of the RCTs, meta-analyses were not appropriate; findings were narratively synthesized. In non-anemic pregnant women, prenatal iron for prevention of IDA resulted in little to no difference in cognition at 40 days post-partum (1 RCT, 503 infants; very low certainty evidence). Similarly, the effect on the intelligence quotient at four years was very uncertain (2 RCTs, 509 children, very low certainty evidence). No RCTs for treatment of ID assessed offspring cognition. The effects on secondary outcomes related to language and motor development, or other measures of cognitive function, were unclear, except for one prevention-focused RCT (302 children), which reported possible harm for children's behavioral and emotional functioning at four years. There is no evidence from UMI countries and insufficient evidence from HICs to support or refute benefits or harms of prophylactic or therapeutic prenatal iron supplementation on child neurodevelopment. [ABSTRACT FROM AUTHOR]

Introduction: Primitive reflexes (PR) induce involuntary automatic movements in response to specific stimuli. This study aimed to determine the prevalence of active PR in young high-level football players. Methodology: Sixty-nine national-level football players from a French academy were tested (17.0 ± 1.4 years; 69.6 ± 8.0 kg; 178.9 ± 6.9 cm) to evaluate the persistence of PR, following the methodology of the Institute for Neuro-Physiological Psychology (INPP) and the classification by a global score (GS). Based on the sum of seven tests, each was rated between 0 = null and 4 = max. The GS is classified into five categories from no activity to maximal (0-1=no activity, 2-7 = low, 8-13 =medium, 14-21 = high, and 22-28 =maximal). Result: Around two-thirds (68.1%) of players presented active PR at different activity levels. Among them, a small proportion (7.2%) had medium GS, while 60.9% had a low GS. The GS was not dependent on field position or the age of the players (p > 0.05). However, playing football in an age category higher than their own was associated with significantly more active primitive reflexes (PR) compared to being in their age category (p < 0.01). The results showed that 72.7% of "upgraded" football players had low GS and 18.2% had medium GS, compared to 55.3% and 2.1% in the non-upgraded group. Discussion: The findings of the current study demonstrate that PR could still be active in a healthy population of high-level football players. Practicing a single sport for years and upgrading players could create a negative environment that can ultimately lead to the activation of otherwise integrated PR. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitors (SSRIs), including citalopram, are widely used antidepressants during pregnancy. However, the effects of prenatal exposure to citalopram on neurodevelopment remain poorly understood. We aimed to investigate the impact of citalopram exposure on early neuronal differentiation of human embryonic stem cells using a multi-omics approach. Citalopram induced time- and dose-dependent effects on gene expression and DNA methylation of genes involved in neurodevelopmental processes or linked to depression, such as BDNF, GDF11, CCL2, STC1, DDIT4 and GAD2. Single-cell RNA-sequencing analysis revealed distinct clusters of stem cells, neuronal progenitors and neuroblasts, where exposure to citalopram subtly influenced progenitor subtypes. Pseudotemporal analysis showed enhanced neuronal differentiation. Our findings suggest that citalopram exposure during early neuronal differentiation influences gene expression patterns associated with neurodevelopment and depression, providing insights into its potential neurodevelopmental impact and highlighting the importance of further research to understand the long-term consequences of prenatal SSRI exposure. [ABSTRACT FROM AUTHOR]

Research Highlights When exposed to rhythmic patterns with temporal regularity, adults exhibit an inherent ability to extract and anticipate an underlying sequence of regularly spaced beats, which is internally constructed, as beats are experienced even when no events occur at beat positions (e.g., in the case of rests). Perception of rhythm and synchronization to periodicity is indispensable for development of cognitive functions, social interaction, and adaptive behavior. We evaluated neural oscillatory activity in premature newborns (n = 19, mean age, 32 ± 2.59 weeks gestational age) during exposure to an auditory rhythmic sequence, aiming to identify early traces of periodicity encoding and rhythm processing through entrainment of neural oscillations at this stage of neurodevelopment. The rhythmic sequence elicited a systematic modulation of alpha power, synchronized to expected beat locations coinciding with both tones and rests, and independent of whether the beat was preceded by tone or rest. In addition, the periodic alpha‐band fluctuations reached maximal power slightly before the corresponding beat onset times. Together, our results show neural encoding of periodicity in the premature brain involving neural oscillations in the alpha range that are much faster than the beat tempo, through alignment of alpha power to the beat tempo, consistent with observations in adults on predictive processing of temporal regularities in auditory rhythms. In response to the presented rhythmic pattern, systematic modulations of alpha power showed that the premature brain extracted the temporal regularity of the underlying beat. In contrast to evoked potentials, which are greatly reduced when there is no sounds event, the modulation of alpha power occurred for beats coinciding with both tones and rests in a predictive way. The findings provide the first evidence for the neural coding of periodicity in auditory rhythm perception before the age of term. In response to the presented rhythmic pattern, systematic modulations of alpha power showed that the premature brain extracted the temporal regularity of the underlying beat.In contrast to evoked potentials, which are greatly reduced when there is no sounds event, the modulation of alpha power occurred for beats coinciding with both tones and rests in a predictive way.The findings provide the first evidence for the neural coding of periodicity in auditory rhythm perception before the age of term. [ABSTRACT FROM AUTHOR]

Objective A ventricle-to-brain index (VBI) >0.35 is associated with low scores on the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) in preterm infants with birth weight <1,250 g. However, VBI obtained at the third ventricle has only moderate interobserver reliability. The objective of this study was to test (1) reliability of VBI measured at the foramen of Monro on the latest ultrasonogram (US) before discharge using the intraclass correlation coefficient (ICC) and (2) the relationship between VBI and BSID-III scores at ≥18 months corrected age. Study Design The present study is a single-center retrospective cohort study. Results The study included 270 preterm infants born at 23 0/7 to 28 6/7 weeks of gestational age. The ICC of VBI between independent measurements by two study radiologists on the first 50 patients was 0.934. Factors associated with the value of VBI included severe intraventricular hemorrhage, bronchopulmonary dysplasia, and systemic steroid administration for BPD but not postmenstrual age. In multivariate analysis, VBI was negatively and independently associated with cognitive (p = 0.002), language (p = 0.004), and motor (p < 0.001) BSID-III scores. The association between VBI and BSID-III scores was observed even in infants in whom the latest US was obtained before term equivalent age. The association between VBI and BSID-III scores was also observed after excluding those with severe intraventricular hemorrhage. Conclusion In this very preterm cohort the measurement of VBI had excellent reliability. Moreover, VBI measurements were negatively associated with motor, language, and cognitive BSID-III scores. Key Points Mean values of VBI are stable with postmenstrual age. Values at the foramen of Monro are reliable and reproducible. VBI is negatively associated with Bayley scores. The association is observed even before term age. [ABSTRACT FROM AUTHOR]

ObjectivesMethodsResultsDiscussionTo synthesize evidence from animal models of neurodevelopmental disorders (NDD) using maternal choline supplementation, to characterize current knowledge on the mechanisms of choline’s protective effects against NDD, and to identify gaps in knowledge for future study.A literature review was conducted in PubMed to identify studies using prenatal choline supplementation interventions in rodent models of neurodevelopmental disorders. 24 studies were identified, and behavioral and biological findings were extracted from each. Studies examining both genetic and environmental risk factors were included.Maternal choline supplementation during gestation is protective against both genetic and environmental NDD risk factors. Maternal choline supplementation improves both cognitive and affective outcomes throughout the lifespan in NDD models. Prenatal choline improved these outcomes through its participation in processes like neurogenesis, epigenetic regulation, and anti-inflammatory signaling.Maternal choline supplementation improves behavioral and neurobiological outcomes in animal models of NDD, paralleling findings in humans. Animal models provide a unique opportunity to study the mechanisms by which gestational choline improves neurodevelopmental outcomes. This is especially important since nearly 90% of pregnant people in the United States are deficient in choline intake. However, much is still unknown about the mechanisms through which choline and its derivatives act. Further research into this topic, especially mechanistic studies in animal models, is critical to modernize maternal choline intake guidelines and to develop interventions to increase maternal choline intake in vulnerable populations. [ABSTRACT FROM AUTHOR]

Background: Research indicates that preterm infants requiring prolonged mechanical ventilation often exhibit suboptimal neurodevelopment at follow-up, coupled with altered brain development as detected by magnetic resonance imaging (MRI) at term-equivalent age (TEA). However, specific regions of brain dysmaturation and the subsequent neurodevelopmental phenotype following early-life adverse respiratory exposures remain unclear. Additionally, it is uncertain whether brain dysmaturation mediates neurodevelopmental outcomes after respiratory adversity. This study aims to investigate the relationship between early-life adverse respiratory exposures, brain dysmaturation at TEA, and the developmental phenotype observed during follow-up in extremely preterm infants. Methods: 89 infants born < 29 weeks' gestation from 2019 to 2021 received MRI examinations at TEA for structural and lobe brain volumes, which were adjusted with sex-and-postmenstrual-age expected volumes for volume residuals. Assisted ventilation patterns in the first 8 postnatal weeks were analyzed using kmlShape analyses. Patterns for motor, cognition, and language development were evaluated from corrected age 6 to 12 months using Bayley Scales of Infant Development, third edition. Mediation effects of brain volumes between early-life respiratory exposures and neurodevelopmental phenotypes were adjusted for sex, gestational age, maternal education, and severe brain injury. Results: Two distinct respiratory trajectories with varying severity were identified: improving (n = 35, 39%) and delayed improvement (n = 54, 61%). Compared with the improving group, the delayed improvement group exhibited selectively reduced brain volume residuals in the parietal lobe (mean − 4.9 cm3, 95% confidence interval − 9.4 to − 0.3) at TEA and lower motor composite scores (− 8.7, − 14.2 to − 3.1) at corrected age 12 months. The association between delayed respiratory improvement and inferior motor performance (total effect − 8.7, − 14.8 to − 3.3) was partially mediated through reduced parietal lobe volume (natural indirect effect − 1.8, − 4.9 to − 0.01), suggesting a mediating effect of 20%. Conclusions: Early-life adverse respiratory exposure is specifically linked to the parietal lobe dysmaturation and neurodevelopmental phenotype of motor delay at follow-up. Dysmaturation of the parietal lobe serves as a mediator in the connection between respiratory adversity and compromised motor development. Optimizing respiratory critical care may emerge as a potential avenue to mitigate the consequences of altered brain growth and motor developmental delay in this extremely preterm population. [ABSTRACT FROM AUTHOR]

Cohen Syndrome (CS) is a rare autosomal recessive disorder caused by biallelic mutations in the VPS13B gene. It is characterized by multiple clinical features, including acquired microcephaly, developmental delay, intellectual disability, neutropenia, and retinal degeneration. VPS13B is part of the bridge-like lipid transport (BLTP) protein family, which in mammals also includes VPS13A, -C, and -D. The proteins of this family are peripheral membrane proteins with different sub-cellular localization, but all share similar structural features and have been proposed to act as lipid transport proteins at organellar membrane contact sites. VPS13B is localized at the Golgi apparatus and is essential for the maintenance of organelle architecture. Here we present a review of the experimental data on the function of the protein at the cellular level, discussing the potential link with disease phenotype and review the studies on animal models recapitulating features of the human disease. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that impairs communication, socialization, and behavior. The association of ASD with folic acid has been investigated due to the importance of this vitamin for neurological health. This study is an update of the publication ‘Folic acid and autism: What do we know?’ and aims to systematically review studies examining the relationship between folic acid and ASD. The search resulted in 2,389 studies on folic acid and ASD, which were selected by two reviewers based on their titles and abstracts. Studies meeting the inclusion criteria were fully read. The 52 included studies involved 10,429 individuals diagnosed with ASD and assessed the intake of vitamin B6, folic acid, and vitamin B12; serum levels of these vitamins, homocysteine, and methionine; therapeutic interventions using folic acid; and the association between maternal exposure to this vitamin and the risk of ASD. The evidence of insufficient folic acid intake in most individuals with ASD remains consistent in this update. No association was found between maternal exposure to folic acid and the risk of ASD in their children. Despite observed improvements in communication, socialization, and behavior in individuals with ASD following folic acid interventions, it is crucial to consider the individuality and complexity of ASD. Given the relevance of the topic, there remains a need for more high-quality research and clinical trials characterized by rigorous methodological designs. [ABSTRACT FROM AUTHOR]

Background: Screen exposure among children continues to increase worldwide. It has negative effects on children of developmental age, including obesity, poor attention, sleep disorders, vision problems, language delays, and deficits in communication skills. It has been reported that parental depression is associated with both increased screen time for children and poor function and skills in children. However, other studies have reported no association between screen time and parental depression. Research methodology: A cross-sectional study was conducted using a convenience sample of 340 parents of 4- to 6-year-old children in the Qassim Region of Saudi Arabia. Data were collected from the primary health care vaccination clinic by contacting parents of children aged 4 to 6 years to fill out the Social Communication Questionnaire (SCQ) for the child and the Patient Health Questionnaire-9 (PHQ9) for the parents. Research results: We conducted a regression analysis to assess the influence of screen time exposure on social communication skills (SCQ score). The results of this study indicated that there was no significant effect observed (B = 0.283, P > 0.05), indicating that a positive correlation between screen time usage and SCQ score may not apply to the entire population. Conversely, we discovered a crucial link between screen time exposure and parental depression (PHQ), as it displayed noteworthy impact values (B = 1.136, P < 0.05), indicating an affirmative correlation between them. In addition, our results also indicated apparent positive associations between parental depression and SCQ scores (B = 0.229, P < 0.05). Conclusion: Our findings revealed that there was a significant association between parental depression and both screen time exposure and SCQ score, while there was no correlation between screen time exposure and SCQ score. [ABSTRACT FROM AUTHOR]

DDX3X syndrome is a neurodevelopmental disorder accounting for up to 3% of cases of intellectual disability (ID) and affecting primarily females. Individuals diagnosed with DDX3X syndrome can also present with behavioral challenges, motor delays and movement disorders, epilepsy, and congenital malformations. DDX3X syndrome is caused by mutations in the X‐linked gene DDX3X, which encodes a DEAD‐box RNA helicase with critical roles in RNA metabolism, including mRNA translation. Emerging discoveries from animal models are unveiling a fundamental role of DDX3X in neuronal differentiation and development, especially in the neocortex. Here, we review the current knowledge of genetic and neurobiological mechanisms underlying DDX3X syndrome and their relationship with clinical phenotypes. [ABSTRACT FROM AUTHOR]

To investigate prospectively the impact of physical activity during pregnancy on infant neurodevelopment, considering relevant confounding factors, physical activity intensity and the trimester of pregnancy in which it is performed. Prospective follow-up study of 791 pregnant women from the first trimester of pregnancy to 40 days postpartum. Three intensity levels of physical activity were assessed in each trimester of pregnancy by the International Physical Activity Questionnaire (IPAQ). Infant neuro development was assessed at 40 days postpartum by the third edition of the Bayley Scales for Infant Development-Third Edition (BSID-III). Analysis adjusted by sociodemographics, anxiety symptoms, lifestyle habits, quality of diet, body mass index, postpartum depressive symptoms and mother-infant attachment. ANCOVA analysis have shown that 40 days old infants of mothers in the moderate and high PA groups in the third trimester obtained 3.2 and 3.8 points higher scores respectively in the language total scale; and 4.1 and 5.1 points higher scores respectively in the motor total scale than infants of mothers in the low PAgroup. Moderate to high intensity physical activity during pregnancy has a positive impact on infant neurodevelopment. More specific recommendations must be incorporated in international guidelines and into maternal education sessions to improve infants' neurodevelopment. [ABSTRACT FROM AUTHOR]

Background. The majority of deaths in patients with schizophrenia and other severe mental illnesses (SMIs) are caused by natural causes, such as cardiovascular diseases (CVDs). The increased risk of CVD and other somatic diseases in SMIs cannot be fully explained by the contribution of traditional risk factors, behavioral risk factors, patients' lifestyle peculiarities, and the influence of antipsychotics. The present review has the following main objectives: (1) to aggregate evidence that neurodevelopmental disorders are the basis of SMIs; (2) to provide a review of studies that have addressed the shared genetic architecture of SMI and cardiovascular disease; and (3) to propose and substantiate the consideration of somatic diseases as independent endophenotypes of SMIs, which will make it possible to place the research of somatic diseases in SMIs within the framework of the concepts of the "neurodevelopmental continuum and gradient" and "endophenotype". Methods. A comprehensive literature search was performed on 1 July 2024. The search was performed using PubMed and Google Scholar databases up to June 2024. Results. The current literature reveals considerable overlap between the genetic susceptibility loci for SMIs and CVDs. We propose that somatic diseases observed in SMIs that have a shared genetic architecture with SMIs can be considered distinct physical health-related endophenotypes. Conclusions. In this narrative review, the results of recent studies of CVDs in SMIs are summarized. Reframing schizophrenia as a multisystem disease should contribute to the activation of new research on somatic diseases in SMIs. [ABSTRACT FROM AUTHOR]

Activation of the maternal immune system during gestation has been associated with an increased risk for neurodevelopmental disorders in the offspring, particularly schizophrenia and autism spectrum disorder. Microglia, the tissue-resident macrophages of the central nervous system, are implicated as potential mediators of this increased risk. Early in development, microglia start populating the embryonic central nervous system and in addition to their traditional role as immune responders under homeostatic conditions, microglia are also intricately involved in various early neurodevelopmental processes. The timing of immune activation may interfere with microglia functioning during early neurodevelopment, potentially leading to long-term consequences in postnatal life. In this review we will discuss the involvement of microglia in brain development during the prenatal and early postnatal stages of life, while also examining the effects of maternal immune activation on microglia and neurodevelopmental processes. Additionally, we discuss recent single cell RNA-sequencing studies focusing on microglia during prenatal development, and hypothesize how early life microglial priming, potentially through epigenetic reprogramming, may be related to neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Aberrant condensation and localization of the RNA-binding protein (RBP) fused in sarcoma (FUS) occur in variants of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Changes in RBP function are commonly associated with changes in axonal cytoskeletal organization and branching in neurodevelopmental disorders. Here, we asked whether branching defects also occur in vivo in a model of FUS-associated disease. We use two reported Xenopus models of ALS/FTD (of either sex), the ALS-associated mutant FUS(P525L) and a mimic of hypomethylated FUS, FUS(16R). Both mutants strongly reduced axonal complexity in vivo. We also observed an axon looping defect for FUS(P525L) in the target area, which presumably arises due to errors in stop cue signaling. To assess whether the loss of axon complexity also had a cue-independent component, we assessed axonal cytoskeletal integrity in vitro. Using a novel combination of fluorescence and atomic force microscopy, we found that mutant FUS reduced actin density in the growth cone, altering its mechanical properties. Therefore, FUS mutants may induce defects during early axonal development. [ABSTRACT FROM AUTHOR]

Background: A large body of work has reported a link between prenatal exposure to infection and increased psychiatric risk in offspring. However, studies to date have focused primarily on exposure to severe prenatal infections and/or individual psychiatric diagnoses in clinical samples, typically measured at single time points, and without accounting for important genetic and environmental confounders. In this study, we investigated whether exposure to common infections during pregnancy is prospectively associated with repeatedly assessed child psychiatric symptoms in a large population‐based study. Methods: Our study was embedded in a prospective pregnancy cohort (Generation R; n = 3,598 mother–child dyads). We constructed a comprehensive prenatal infection score comprising common infections for each trimester of pregnancy. Child total, internalizing, and externalizing problems were assessed repeatedly using the parent‐rated Child Behavioral Checklist (average age: 1.5, 3, 6, 10, and 14 years). Linear mixed‐effects models were run adjusting for a range of confounders, including child polygenic scores for psychopathology, maternal chronic illness, birth complications, and infections during childhood. We also investigated trimester‐specific effects and child sex as a potential moderator. Results: Prenatal exposure to infections was associated with higher child total, internalizing, and externalizing problems, showing temporally persistent effects, even after adjusting for important genetic and environmental confounders. We found no evidence that prenatal infections were associated with changes in child psychiatric symptoms over time. Moreover, in our trimester‐specific analysis, we did not find evidence of significant timing effects of prenatal infection on child psychiatric symptoms. No interactions with child sex were identified. Conclusions: Our research adds to evidence that common prenatal infections may be a risk factor for psychiatric symptoms in children. We also extend previous findings by showing that these associations are present early on, and that rather than changing over time, they persist into adolescence. However, unmeasured confounding may still explain in part these associations. In the future, employing more advanced causal inference designs will be crucial to establishing the degree to which these effects are causal. [ABSTRACT FROM AUTHOR]

The development of the human central nervous system initiates in the early embryonic period until long after delivery. It has been shown that several neurological and neuropsychiatric diseases originate from prenatal incidents. Mathematical models offer a direct way to understand neurodevelopmental processes better. Mathematical modelling of neurodevelopment during the embryonic period is challenging in terms of how to 'Approach', how to initiate modelling and how to propose the appropriate equations that fit the underlying dynamics of neurodevelopment during the embryonic period while including the variety of elements that are built-in naturally during the process of neurodevelopment. It is imperative to answer where and how to start modelling; in other words, what is the appropriate 'Approach'? Therefore, one objective of this study was to tackle the mathematical issue broadly from different aspects and approaches. The approaches were divided into three embryonic categories: cell division, neural tube growth and neural plate growth. We concluded that the neural plate growth approach provides a suitable platform for simulation of brain formation/neurodevelopment compared to cell division and neural tube growth. We devised a novel equation and designed algorithms that include geometrical and topological algorithms that could fit most of the necessary elements of the neurodevelopmental process during the embryonic period. Hence, the proposed equations and defined mathematical structure would be a platform to generate an artificial neural network that autonomously grows and develops. [ABSTRACT FROM AUTHOR]

AIM: Congenital Zika Virus Syndrome (CZS) presents notable hurdles to neurodevelopment, with language development emerging as a crucial aspect. This study investigates sleep patterns and language skills in children with CZS, aiming to explore the potential synchronization of sleep development with their neurodevelopment. METHOD: We studied cross-sectionally 135 children with CZS aged 0 to 48 months, investigating sleep using the BISQ Questionnaire. Language development was assessed using the Early Language Milestone Scale, while motor development and cognitive and social ability were assessed using the Bayley Scales of Infant and Young Child Development 3rd edition. We also studied longitudinally a cohort of 16 children (initially aged 0 to 12 months) whom we followed for four years, assessing at one-year intervals. RESULTS: Sleep disturbances and language deficits were highly frequent in this population. In the 0–12 months group, a late bedtime and frequent nighttime awakenings were associated with poorer auditory expressive skills. At 13–24 months, nighttime awakenings were associated with poorer auditory expressive skills, while among 25–36-month-olds decreased auditory receptive skills were associated with longer sleep onset latency and reduced nighttime sleep duration. CONCLUSION: The brain alterations caused by Zika virus infection affect both sleep disturbances and delays in language development. It is possible that sleep disturbance may be a mediating factor in the pathway between CZS and delayed language development, as the three analyzed language skills showed a correlation with sleep parameters. [ABSTRACT FROM AUTHOR]

Background: Screen-time is the amount of time a person spends in front of an electronic/digital device such as television, a smartphone, a tablet or a computer. Objective: To study the impact of screen timeon children’s mental and physical health. Materials and Methods: This cross-sectional study was carried out in the Pediatric Outpatient Department to examine screen habits in 280 children between the ages of 1 and 5 years. Results: The study population had a mean age of 40.9 months, with females making up 63.57% of the participants and males accounting for 36.4%. A majority of the study participants belonged to the lower middle-class category, comprising 44.6% of the sample. Older children (48 - 60 months) exhibited higher levels of electronic media exposure compared to younger age groups (12-24 months) (p< 0.001). Minimal high media exposure time was observed in males compared to females (p=0.048). Conclusion: The most commonly used electronic media devices in the population were smartphones (95.7%) and televisions (98.5%). On average, families had 3.37 ± 0.79 electronic media devices. Higher electronic media exposure was noted in the upper and upper-middle socioeconomic groups compared to other socioeconomic categories (p<0.001). [ABSTRACT FROM AUTHOR]

Fetal cerebral ventriculomegaly is one of the most common fetal neurological disorders identified prenatally by neuroimaging. The challenges in the evolving landscape of conditions like fetal cerebral ventriculomegaly involve accurate diagnosis and how best to provide prenatal counseling regarding prognosis as well as postnatal management and care of the infant. The purpose of this narrative review is to discuss the literature on fetal ventriculomegaly, including postnatal management and neurodevelopmental outcome, and to provide practice recommendations for pediatric neurologists. [ABSTRACT FROM AUTHOR]

Skin-to-skin care (SSC) is an important part of parent and infant care during the neonatal period and into infancy. SSC should be initiated immediately after birth and practiced as a standard of care in all settings, as well as in the home. There is strong evidence that SSC has a positive effect on breastfeeding and human milk feeding in both term and preterm infants, as well as on mortality, cardiopulmonary stability, and thermoregulation. SSC reduces pain and infant stress, enhances parent–infant bonding, has neurodevelopmental benefits, and has positive effects on parental mental health. The safety and feasibility of providing SSC has been established in term and preterm infants, and SSC is recommended as best practice for all infants. The benefits of SSC outweigh the risks in most situations, and despite challenges, care providers should implement procedures and accommodations to ensure that SSC occurs as a safe and positive experience for the parent, family, infant, and health care team. This statement includes all families as defined and determined by themselves, and recognizes that health communication, language, and terminology must be individualized to meet specific family needs by the health care team. [ABSTRACT FROM AUTHOR]

[Display omitted] • Prenatal exposure to infections may influence child brain development. • Changes in frontal and temporal lobe regions were regions of interest. • Caution in interpretation is warranted given the small effect sizes. Maternal infection during pregnancy has been identified as a prenatal risk factor for the later development of psychopathology in exposed offspring. Neuroimaging data collected during childhood has suggested a link between prenatal exposure to maternal infection and child brain structure and function, potentially offering a neurobiological explanation for the emergence of psychopathology. Additionally, preclinical studies utilizing repeated measures of neuroimaging data suggest that effects of prenatal maternal infection on the offspring's brain may normalize over time (i.e., catch-up growth). However, it remains unclear whether exposure to prenatal maternal infection in humans is related to long-term differential neurodevelopmental trajectories. Hence, this study aimed to investigate the association between prenatal exposure to infections on child brain development over time using repeated measures MRI data. We leveraged data from a population-based cohort, Generation R, in which we examined prospectively assessed self-reported infections at each trimester of pregnancy (N = 2,155). We further used three neuroimaging assessments (at mean ages 8, 10 and 14) to obtain cortical and subcortical measures of the offspring's brain morphology with MRI. Hereafter, we applied linear mixed-effects models, adjusting for several confounding factors, to estimate the association of prenatal maternal infection with child brain development over time. We found that prenatal exposure to infection in the third trimester was associated with a slower decrease in volumes of the pars orbitalis, rostral anterior cingulate and superior frontal gyrus, and a faster increase in the middle temporal gyrus. In the temporal pole we observed a divergent pattern, specifically showing an increase in volume in offspring exposed to more infections compared to a decrease in volume in offspring exposed to fewer infections. We further observed associations in other frontal and temporal lobe structures after exposure to infections in any trimester, though these did not survive multiple testing correction. Our results suggest that prenatal exposure to infections in the third trimester may be associated with slower age-related growth in the regions: pars orbitalis, rostral anterior cingulate and superior frontal gyrus, and faster age-related growth in the middle temporal gyrus across childhood, suggesting a potential sensitive period. Our results might be interpreted as an extension of longitudinal findings from preclinical studies, indicating that children exposed to prenatal infections could exhibit catch-up growth. However, given the lack of differences in brain volume between various infection groups at baseline, there may instead be either a longitudinal deviation or a subtle temporal deviation. Subsequent well-powered studies that extend into the period of full brain development (∼25 years) are needed to confirm whether the observed phenomenon is indeed catch-up growth, a longitudinal deviation, or a subtle temporal deviation. [ABSTRACT FROM AUTHOR]

Air pollution (AP) exposures have been associated with autism (ASD), schizophrenia (SCZ), and attention deficit hyperactivity disorder (ADHD), male-biased neurodevelopmental disorders that are linked to alterations in brain fronto-striatal neurotransmitter systems. The current study sought to assess how developmental exposures of mice to inhaled ambient ultrafine particle (UFP) air pollution, considered its most reactive component, alters fronto-striatal functional correlations. Mice were exposed via inhalation to concentrated ambient UFPs from postnatal days (PND) 4–7 and 10–13. Frontal cortex, striatum, and serum were collected at PND14 and PND50 to evaluate both acute and persistent effects. UFP-induced changes, more extensive and persistent in males, included elimination of frontal cortical kynurenine correlations with striatal neurotransmitter function, persistent immunosuppression of approximately 50%, and striatal neurotransmitter turnover correlations with serum corticosterone. More limited effects in females did not show persistence. Collectively, these findings depict an apparently physiologically-integrated UFP-induced persistent male-biased vulnerability to brain fronto-striatal system dysfunction that could contribute to behavioral deficits associated with neurodevelopmental disorders. Further studies are needed to ascertain the interactive physiological mechanisms of male fronto-striatal vulnerability and their relation to behavioral impairments, mechanisms of apparent female compensation, and specific contaminants of AP that underlie this vulnerability. [ABSTRACT FROM AUTHOR]

Purpose: To assess the psychometric properties of available developmental assessments for infants, aged 0–24 months. Methods: A scoping review was conducted using the PRISMA Extension for Scoping Reviews as a guideline. The following four databases: Medline, CINAHL, Embase, and Web of Science were used to retrieve articles. Assessments were analyzed for psychometric properties of reliability and validity. Results: Fifteen developmental assessments were identified and evaluated based on their psychometric properties from 20 number of articles. Results: Three assessments including Bayley Scales of Infant and Toddler Development 3rd Edition (BSID-III), Caregiver Reported Early Development Instruments (CREDI), and Ages and Stages Questionnaire 3rd Edition (ASQ-3), were identified to have the most supporting evidence. Conclusion: This study provided clinicians with an updated list of all-encompassing infant developmental assessments. Certain assessments require additional evidence regarding their psychometric properties to substantiate their clinical utility. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to assess the utility of the Ages and Stages Questionnaire–3rd Edition (ASQ‐3) and the Vineland Adaptive Behavior Scales–2nd Edition (VABS‐II) as neurodevelopmental screening tools for infants exposed to antiseizure medications in utero, and to examine their suitability for use in large‐population signal generation initiatives. Methods: Participants were women with epilepsy who were recruited from 21 hospitals in England and Northern Ireland during pregnancy between 2014 and 2016. Offspring were assessed at 24 months old using the Bayley Scales of Infant Development–3rd Edition (BSID‐III), the VABS‐II, and the ASQ‐3 (n = 223). The sensitivity and specificity of the ASQ‐3 and VABS‐II to identify developmental delay at 24 months were examined, using the BSID‐III to define cases. Results: The ASQ‐3 identified 65 children (29.1%) as at risk of developmental delay at 24 months using standard referral criteria. Using a categorical approach and standard referral criteria to identify delay in the ASQ‐3 and BSID‐III at 24 months, the ASQ‐3 showed excellent sensitivity (90.9%) and moderate specificity (74.1%). Utilizing different cut‐points resulted in improved properties and may be preferred in certain contexts. The VABS‐II exhibited the strongest psychometric properties when borderline impairment (>1 SD below the mean) was compared to BSID‐III referral data (sensitivity = 100.0%, specificity = 96.6%). Significance: Both the ASQ‐3 and VABS‐II have good psychometric properties in a sample of children exposed to antiseizure medications when the purpose is the identification of at‐risk groups. These findings identify the ASQ‐3 as a measure that could be used effectively as part of a tiered surveillance system for teratogenic exposure by identifying a subset of individuals for more detailed investigations. Although the VABS‐II has excellent psychometric properties, it is more labor‐intensive for both the research team and participants and is available in fewer languages than the ASQ‐3. [ABSTRACT FROM AUTHOR]

We describe the language ability of children at age 9.5 years who were born to women with an opioid use disorder and examine the associations between prenatal opioid exposure, sex, social adversity, caregiver psychological factors, and child language. Data were drawn from the regional prospective longitudinal Canterbury Methadone in Pregnancy study. At the 9.5-year wave, 80 children who were born to mothers in Methadone Maintenance Treatment and their caregivers, and 98 non-exposed comparison children were assessed using a comprehensive standardized measure of language. Information related to social adversity and caregiver psychological factors was obtained from comprehensive caregiver interviews. At age 9.5 years, opioid-exposed children had lower language scores than the non-exposed children, however their group average was within the normal range on the CELF-4 norms. A series of multivariate hierarchical regression models predicting low language at 9.5 years showed sex and opioid-exposure status predicted low language in the first step. The addition of social adversity factors significantly improved the model. The further addition of caregiver psychological factors did not improve prediction. Only sex was a significant predictor throughout. In this sample, children prenatally exposed to opioids were at higher risk of low language outcomes. However, the child being male and social adversity were important influencing factors. This suggests early language support services are indicated for opioid-exposed children, particularly boys and those in socially adverse circumstances. [ABSTRACT FROM AUTHOR]

FBRSL1, together with FBRS and AUTS2 (Activator of Transcription and Developmental Regulator; OMIM 607270), constitutes a tripartite AUTS2 gene family. AUTS2 and FBRSL1 are evolutionarily more closely related to each other than to FBRS (Fibrosin 1; OMIM 608601). Despite its paralogous relation to AUTS2, FBRSL1's precise role remains unclear, though it likely shares functions in neurogenesis and transcriptional regulation. Herein, we report the clinical presentation with therapeutic approaches and the molecular etiology of a patient harboring a de novo truncating variant (c.371dupC) in FBRSL1, leading to a premature stop codon (p.Cys125Leufs*7). Our study extends previous knowledge by highlighting potential interactions and implications of this variant, alongside maternal and paternal duplications, for the patient's phenotype. Using sequence conservation data and in silico analysis of the truncated protein, we generated a predicted domain structure. Furthermore, our in silico analysis was extended by taking into account SNP array results. The extension of in silico analysis was performed due to the possibility that the coexistence of FBRSL1 truncating variant contemporary with maternal and paternal duplication could be a modifier of proband's phenotype and/or influence the novel syndrome clinical characteristics. FBRSL1 protein may be involved in neurodevelopment due to its homology with AUTS2, together with distinctive neuronal expression profiles, and thus should be considered as a potential modulation of clinical characteristics in a novel syndrome. Finally, considering that FBRSL1 is apparently involved in neurogenesis and in transcriptional regulatory networks that orchestrate gene expression, together with the observation that different genetic syndromes are associated with distinct genomic DNA methylation patterns, the specific episignature has been explored. [ABSTRACT FROM AUTHOR]

Establishing a functional nervous system is a complex process requiring tightly controlled gene expression programs to achieve the correct differentiation of distinct neuronal subtypes. The molecular programs required for neurons to acquire neuron-type-specific, and core pan-neuronal features mostly rely on sequence-specific transcription factors (TFs), which recognize and bind to cis-regulatory motifs present in the promoters of target genes. Recently, we investigated the role and mode of action of the NF-Y complex, a ubiquitously expressed transcriptional master regulator, in the Caenorhabditis elegans nervous system. We found that NFYA-1 is a pervasive regulator of neuron-specific and pan-neuronal gene batteries that are essential for neuronal development and function. Furthermore, we concluded that NFYA-1 acts cell autonomously by either directly binding to conserved motifs in target gene promoter regions or indirectly by regulating other transcriptional regulators to fine-tune gene expression. However, further studies are required to fully define the impact of the NF-Y complex on nervous system regulatory networks and how NF-Y coordinates with other TFs in this regard. [ABSTRACT FROM AUTHOR]

Background: Radio-Tartaglia syndrome or RATARS is an unfamiliar disease caused by a heterozygous mutation of the SPEN gen in the 1p36 chromosome. Clinically, it is represented by global developmental delay and intellectual disability; however, it can also be associated with other relevant comorbidities that embark on the cardiovascular, gastrointestinal, musculoskeletal, integumentary as well as endocrinological systems. Case Report: A 3-year-old pediatric male patient from Venezuela is referred to genetic counseling due to neurodevelopmental delay, microcephaly and dysmorphisms. The initial diagnostic impression consisted of Williams syndrome. Further studies revealed mild supravalvular stenosis, but no important changes in brain imaging or laboratory analysis. The patient’s diagnosis was later replaced with RATARS after a complete exome sequencing revealed heterozygous SPEN pathogenic genes. Conclusion: The diagnostic process of RATARS must become a pillar of further investigation given its uncertainty when clinically diagnosed hence the necessity of a clear confirmation through exome sequencing. This case report highlights the importance of genetic testing in patients with neurodevelopmental delay due to a possible but uncommon correlation with rare diseases such as RATARS. [ABSTRACT FROM AUTHOR]