ASD Risk Research Articles

Increased risk of clinically relevant neurodevelopmental disorders in survivors of congenital diaphragmatic hernia: a population-based study.

Neurodevelopmental disorders (ND) have been recognized as the most common and potentially most disabling outcome of congenital diaphragmatic hernia (CDH). Our aim was to evaluate the incidence of ND in patients with a history of CDH referred for ND assessment on the basis of clinically relevant symptoms rather than through a screening process. The study was a nationwide, population-based prospective nested case-control study within a cohort of newborn children who survived the newborn period in Sweden during the observational period from 1st January 1982 until 31st December 2015. In the study period, 641 non-syndromic CDH survivors were identified, and 3080 control cases were selected. Significantly higher incidence of clinically relevant any ND (11.5% vs 5.6%,p < 0.001), ASD (3.9% vs 2.1%,p:0.011), and intellectual disorder (6.6% vs 0.7%,p < 0.001) were observed in CDH compared to controls. When compared with controls, those with CDH were found to have a 2.179 times higher risk to develop any ND (p < 0.001), 1.867 times higher risk for ASD (p = 0.008), and 10.63 times higher for intellectual disorder (p < 0.001). CDH survivors have a higher risk of clinically relevant ND than the general population, independent of the effect of screening.

ZMYND11 Functions in Bimodal Regulation of Latent Genes and Brain-like Splicing to Safeguard Corticogenesis.

Despite the litany of pathogenic variants linked to neurodevelopmental disorders (NDD) including autism (ASD) and intellectual disability 1,2 , our understanding of the underlying mechanisms caused by risk genes remain unclear. Here, we leveraged a human pluripotent stem cell model to uncover the neurodevelopmental consequences of mutations in ZMYND11 , a newly implicated risk gene 3,4 . ZMYND11, known for its tumor suppressor function, encodes a histone-reader that recognizes sites of transcriptional elongation and acts as a co-repressor 5,6 . Our findings reveal that ZMYND11-deficient cortical neural stem cells showed upregulation of latent developmental pathways, impairing progenitor and neuron production. In addition to its role on histones, ZMYND11 controls a brain-specific isoform switch involving the splicing regulator RBFOX2. Extending our findings to other chromatin-related ASD risk factors revealed similar developmental pathway activation and splicing dysregulation, partially rescuable through ZMYND11's regulatory functions.

Neurodevelopmental disorders in children born to mothers involved in maternal motor vehicle crashes.

To evaluate the association between maternal MVCs during pregnancy and neurodevelopmental disorders (NDDs, including intellectual disability, ADHD, ASD, and infantile cerebral palsy) in children. This population-based cohort of live births in Taiwan was analyzed, comparing children born to mothers involved in MVCs during pregnancy with those without such exposure. Children were linked to the insurance database to identify the possible diagnosis of NDDs. The Cox proportional hazards regression model was used to estimate the relative hazards. A total of 19,277 children with maternal MVCs and 76,015 children without exposure were included. Children exposed to maternal MVCs during the first two trimesters or whose mothers sustained mild to severe injuries showed a higher risk of intellectual disability. Severe maternal injuries also increased the risk of infantile cerebral palsy (aHR = 3.86; 1.27-11.78). MVCs in the third trimester, or mild maternal injuries, were associated with a higher risk of ASD (third trimester: aHR = 1.40; 1.04-1.87; mild injuries: aHR = 1.38; 1.09-1.74). Children exposed to maternal MVCs with severe injuries had a higher risk of intellectual disability and cerebral palsy. Third-trimester exposure may increase the risk of ASD. However, these findings should be interpreted cautiously as genetic factors may contribute to the observed association. There is some evidence linking maternal MVCs during pregnancy to the development of neurodevelopmental disorders in children. Children of mothers with severely injured were more likely to suffer from infantile cerebral palsy and intellectual disability. The risk of autism spectrum disorder is higher in children whose mothers are involved in MVCs during the late stage of pregnancy, and there is also an increased risk of intellectual disability during the first two trimesters.

Association of Parental Prenatal Mental Health on Offspring Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis.

Parental prenatal mood and anxiety disorders (PMAD) are linked to child neurodevelopmental disorders (NDDs), but evaluations of the magnitude and mechanisms of this association are limited. This study estimates the strength of the association and whether it is impacted by genetic and environmental factors. A systematic search of PubMed, CENTRAL, PsycINFO, OVID, and Google Scholar was performed for articles published from January 1988 to January 2024. Of 2,170 articles screened, 64 met the inclusion criteria. Meta-analyses were conducted on 20 studies, and 44 were included in the narrative synthesis. We conducted random-effects meta-analyses, along with tests for heterogeneity (I2) and publication bias (Egger's test). The review followed PRISMA and MOOSE guidelines. Maternal PMADs were associated with a significantly increased risk of ADHD (OR 1.91, 95% CI 1.45-2.52) and ASD (OR 1.57, 95% CI 1.37-1.81) in children. Paternal PMADs were also associated with the risk of NDDs, with combined odds for ASD and ADHD (OR 1.24, 95% CI 1.15-1.34). Several studies suggested that the link between parental PMADs and offspring NDDs might be impacted by both genetic and environmental factors, including the impact of ongoing parental depression on child behavior. Parental PMADs are significantly associated with an increased risk of NDDs in children. These associations may be influenced by both genetic predispositions and environmental factors. Understanding these pathways is important for informing interventions aimed at mitigating mental health risks in families and supporting child development.

Widespread Associations between Behavioral Metrics and Brain Microstructure in ASD.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behaviors. A diagnosis of ASD is provided by a clinician following cognitive and behavioral evaluations, but there is currently no biomarker associating these metrics with neurological changes. Our lab has previously found that g-ratio, the proportion of axon width to myelin diameter, and axonal conduction velocity, which is associated with the capacity of an axon to carry information, are both decreased in ASD individuals. By associating these differences with performance on cognitive and behavioral tests, we can evaluate which tests most reveal changes in the brain. Analyzing 273 participants (148 with ASD) ages 8-to-17 (49% female) through an NIH-sponsored Autism Centers of Excellence (ACE) network (Grant#: MH100028), we observe widespread associations between behavioral and cognitive evaluations of autism and between behavioral and microstructural metrics. Analyzing data from all participants, conduction velocity but not g-ratio was significantly associated with many behavioral metrics. However, this pattern was reversed when looking solely at ASD participants. This reversal may suggest that the mechanism underlying differences between autistic and non-autistic individuals may be distinct from the mechanism underlying ASD behavioral severity. Two additional machine learning cluster analyses applied to neuroimaging data reinforce the association between neuroimaging and behavioral metrics and suggest that age-related maturation of brain metrics may drive changes in ASD behavior. By associating neuroimaging metrics with ASD, it may be possible to measure and identify individuals at high risk of ASD before behavioral tests can detect them.

Molecular and cellular dynamics of the developing human neocortex at single-cell resolution.

The development of the human neocortex is a highly dynamic process and involves complex cellular trajectories controlled by cell-type-specific gene regulation1. Here, we collected paired single-nucleus chromatin accessibility and transcriptome data from 38 human neocortical samples encompassing both the prefrontal cortex and primary visual cortex. These samples span five main developmental stages, ranging from the first trimester to adolescence. In parallel, we performed spatial transcriptomic analysis on a subset of the samples to illustrate spatial organization and intercellular communication. This atlas enables us to catalog cell type-, age-, and area-specific gene regulatory networks underlying neural differentiation. Moreover, combining single-cell profiling, progenitor purification, and lineage-tracing experiments, we have untangled the complex lineage relationships among progenitor subtypes during the transition from neurogenesis to gliogenesis in the human neocortex. We identified a tripotential intermediate progenitor subtype, termed Tri-IPC, responsible for the local production of GABAergic neurons, oligodendrocyte precursor cells, and astrocytes. Remarkably, most glioblastoma cells resemble Tri-IPCs at the transcriptomic level, suggesting that cancer cells hijack developmental processes to enhance growth and heterogeneity. Furthermore, by integrating our atlas data with large-scale GWAS data, we created a disease-risk map highlighting enriched ASD risk in second-trimester intratelencephalic projection neurons. Our study sheds light on the gene regulatory landscape and cellular dynamics of the developing human neocortex.

Exploring Prenatal Factors Linked to Autism Spectrum Disorder

Autism spectrum disorder is caused by a variety of determinants. This study focuses on how the mother’s exposure to pesticides, ozone pollution, and infections, as well as the mother’s pre-existing disorders, including diabetes and preeclampsia, result in the development of autism spectrum disorder in the child. It also examines the role that maternal immune activation and autoantibodies have on the risk of ASD in the mother’s offspring. In addition, it analyzes specific circumstances during childbirth, which include maternal hemorrhage and the use of forceps, and addresses their potential impacts on the risk of autism in the child. Lastly, this study describes the association between incorrect brain development and ASD. Along with compiling the several different maternal circumstances during pregnancy that could cause autism, this study also mentions the link between early brain overgrowth and ASD. Essentially, it clears up any confusion about specific conjectures regarding possible maternal factors that contribute to autism spectrum disorder by presenting the data in a clear and organized manner.

Exposure to heavy metals in utero and autism spectrum disorder at age 3: a meta-analysis of two longitudinal cohorts of siblings of children with autism

BackgroundAutism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder. Risk is attributed to genetic and prenatal environmental factors, though the environmental agents are incompletely characterized.MethodsIn Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk in Babies Learning Early Signs (MARBLES), two pregnancy cohorts of siblings of children with ASD, urinary metals concentrations during two pregnancy time periods (< 28 weeks and ≥ 28 weeks of gestation) were measured using inductively coupled plasma mass spectrometry. At age three, clinicians assessed ASD with DSM-5 criteria. In an exposure-wide association framework, using multivariable log binomial regression, we examined each metal for association with ASD status, adjusting for gestational age at urine sampling, child sex, age at pregnancy, race/ethnicity and education. We meta-analyzed across the two cohorts.ResultsIn EARLI (n = 170) 17% of children were diagnosed with ASD, and 44% were classified as having non-neurotypical development (Non-TD). In MARBLES (n = 231), 21% were diagnosed with ASD, and 14% classified as Non-TD. During the first and second trimester period (< 28 weeks), having cadmium concentration over the level of detection was associated with 1.69 (1.08, 2.64) times higher risk of ASD, and 1.29 (0.95, 1.75)times higher risk of Non-TD.A doubling of first and second trimester cesium concentration was marginally associated with 1.89 (0.94, 3.80) times higher risk of ASD, and a doubling of third trimester cesium with 1.69 (0.97, 2.95) times higher risk of ASD.ConclusionExposure in utero to elevated levels of cadmium and cesium, as measured in urine collected during pregnancy, was associated with increased risk of developing ASD.

Transcriptome analysis identifies an ASD-Like phenotype in oligodendrocytes and microglia from C58/J amygdala that is dependent on sex and sociability

BackgroundAutism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with higher incidence in males and is characterized by atypical verbal/nonverbal communication, restricted interests that can be accompanied by repetitive behavior, and disturbances in social behavior. This study investigated brain mechanisms that contribute to sociability deficits and sex differences in an ASD animal model.MethodsSociability was measured in C58/J and C57BL/6J mice using the 3-chamber social choice test. Bulk RNA-Seq and snRNA-Seq identified transcriptional changes in C58/J and C57BL/6J amygdala within which DMRseq was used to measure differentially methylated regions in amygdala.ResultsC58/J mice displayed divergent social strata in the 3-chamber test. Transcriptional and pathway signatures revealed immune-related biological processes differ between C58/J and C57BL/6J amygdala. Hypermethylated and hypomethylated genes were identified in C58/J versus C57BL/6J amygdala. snRNA-Seq data in C58/J amygdala identified differential transcriptional signatures within oligodendrocytes and microglia characterized by increased ASD risk gene expression and predicted impaired myelination that was dependent on sex and sociability. RNA velocity, gene regulatory network, and cell communication analysis showed diminished oligodendrocyte/microglia differentiation. Findings were verified using Bulk RNA-Seq and demonstrated oxytocin’s beneficial effects on myelin gene expression.LimitationsOur findings are significant. However, limitations can be noted. The cellular mechanisms linking reduced oligodendrocyte differentiation and reduced myelination to an ASD phenotype in C58/J mice need further investigation. Additional snRNA-Seq and spatial studies would determine if effects in oligodendrocytes/microglia are unique to amygdala or if this occurs in other brain regions. Oxytocin’s effects need further examination to understand its’ potential as an ASD therapeutic.ConclusionsOur work demonstrates the C58/J mouse model’s utility in evaluating the influence of sex and sociability on the transcriptome in concomitant brain regions involved in ASD. Our single-nucleus transcriptome analysis elucidates potential pathological roles of oligodendrocytes and microglia in ASD. This investigation provides details regarding regulatory features disrupted in these cell types, including transcriptional gene dysregulation, aberrant cell differentiation, altered gene regulatory networks, and changes to key pathways that promote microglia/oligodendrocyte differentiation. Our studies provide insight into interactions between genetic risk and epigenetic processes associated with divergent affiliative behavior and lack of positive sociability.

Systematic Review and Meta-Analysis of the Effect of Osteoporosis on Reoperation Rates and Complications after Surgical Management of Lumbar Degenerative Disease.

There is considerable heterogeneity in findings and a lack of consensus regarding the interplay between osteoporosis and outcomes in patients with lumbar degenerative spine disease. Therefore, the purpose of this systematic review and meta-analysis was to gather and analyze existing data on the effect of osteoporosis on radiographic, surgical, and clinical outcomes following surgery for lumbar degenerative spinal disease. A systematic review was performed to determine the effect of osteoporosis on the incidence of adverse outcomes after surgical intervention for lumbar degenerative spinal diseases. The approach focused on the radiographic outcomes, reoperation rates, and other medical and surgical complications. Subsequently, a meta-analysis was performed on the eligible studies. The results of the meta-analysis suggested that osteoporotic patients experienced increased rates of adjacent segment disease (ASD; p=0.015) and cage subsidence (p=0.001) while demonstrating lower reoperation rates than non-osteoporotic patients (7.4% vs. 13.1%; p=0.038). The systematic review also indicated that the length of stay, overall costs, rates of screw loosening, and rates of wound and other medical complications may increase in patients with a lower bone mineral density. Fusion rates, as well as patient-reported and clinical outcomes, did not differ significantly between osteoporotic and non-osteoporotic patients. Osteoporosis was associated with an increased risk of ASD, cage migration, and possibly postoperative screw loosening, as well as longer hospital stays, incurring higher costs and an increased likelihood of postoperative complications. However, a link was not established between osteoporosis and poor clinical outcomes.

Exposure to maternal cannabis use disorder and risk of autism spectrum disorder in offspring: A data linkage cohort study

This study aimed to investigate the association between pre-pregnancy, prenatal and perinatal exposures to cannabis use disorder (CUD) and the risk of autism spectrum disoder (ASD) in offspring. Data were drawn from the New South Wales (NSW) Perinatal Data Collection (PDC), population-based, linked administrative health data encompassing all-live birth cohort from January 2003 to December 2005. This study involved 222 534 mother-offspring pairs. . The exposure variable (CUD) and the outcome of interest (ASD) were identified using the 10th international disease classification criteria, Australian Modified (ICD-10-AM). We found a three-fold increased risk of ASD in the offspring of mothers with maternal CUD compared to non-exposed offspring. In our sensitivity analyses, male offspring have a higher risk of ASD associated with maternal CUD than their female counterparts. In conclusion, exposure to maternal CUD is linked to a higher risk of ASD in offspring, with a stronger risk in male offspring. Further research is needed to understand these gender-specific effects and the relationship between maternal CUD and ASD risk in children.

Hyperglycemia as a gestational factor associated with Autism Spectrum Disorder: a review of the literature

Introduction: Autism Spectrum Disorder is a neurodevelopmental disorder characterized by deficits in social interaction, communication, and repetitive behaviors. The etiology, which has been the subject of studies, is influenced by a range of factors, including genetic, environmental, and gestational aspects. Methods: This article aims to review the literature, exploring the gestational causes associated with ASD, concentrating on intrauterine hyperglycemia. Results: The analysis reveals a scarcity of empirical studies, highlighting the need for additional research, especially in the Brazilian context. Conclusion: The results show that hyperglycemia during pregnancy can increase the risk of ASD, highlighting the importance of further research in this area.

Identification of a molecular network regulated by multiple ASD high risk genes.

Genetic sequencing has identified high-confidence ASD risk genes with loss-of-function mutations. How the haploinsufficiency of distinct ASD risk genes causes ASD remains to be elucidated. In this study, we examined the role of four top-ranking ASD risk genes, ADNP, KDM6B, CHD2, and MED13, in gene expression regulation. ChIP-seq analysis reveals that gene targets with the binding of these ASD risk genes at promoters are enriched in RNA processing and DNA repair. Many of these targets are found in ASD gene database (SFARI), and are involved in transcription regulation and chromatin remodeling. Common gene targets of these ASD risk genes include a network of high confidence ASD genes associated with gene expression regulation, such as CTNNB1 and SMARCA4. We further directly examined the transcriptional impact of the deficiency of these ASD risk genes. Our mRNA profiling with qPCR assays in cells with the knockdown of Adnp, Kdm6b, Chd2 or Med13 has revealed an intricate pattern of their cross-regulation, as well as their influence on the expression of other ASD genes. In addition, some synaptic genes, such as Snap25 and Nrxn1, are strongly regulated by deficiency of the four ASD risk genes, which could be through the direct binding at promoters or indirectly through the targets like Ctnnb1 or Smarca4. The identification of convergent and divergent gene targets that are regulated by multiple ASD risk genes will help to understand the molecular mechanisms underlying common and unique phenotypes associated with haploinsufficiency of ASD-associated genes.

Causal effects of PM2.5 exposure on neuropsychiatric disorders and the mediation via gut microbiota: A Mendelian randomization study

BackgroundGrowing evidence has revealed the impacts of exposure to fine particulate matter (PM2.5) and dysbiosis of gut microbiota on neuropsychiatric disorders, but the causal inference remains controversial due to residual confounders in observational studies. MethodsThis study aimed to examine the causal effects of exposure to PM2.5 on 4 major neuropsychiatric disorders (number of cases = 18,381 for autism spectrum disorder [ASD], 38,691 for attention deficit hyperactivity disorder [ADHD], 67,390 for schizophrenia, and 21,982 cases for Alzheimer’s disease [AD]), and the mediation pathway through gut microbiota. Two-sample Mendelian randomization (MR) analyses were performed, in which genetic instruments were identified from genome-wide association studies (GWASs). The included GWASs were available from (1) MRC Integrative Epidemiology Unit (MRC-IEU) for PM2.5, PMcoarse, PM10, and NOX; (2) the Psychiatric Genomics Consortium (PGC) for ASD, ADHD, and schizophrenia; (3) MRC-IEU for AD; and (4) MiBioGen for gut microbiota. Multivariable MR analyses were conducted to adjust for exposure to NOX, PMcoarse, and PM10. We also examined the mediation effects of gut microbiota in the associations between PM2.5 exposure levels and neuropsychiatric disorders, using two-step MR analyses. ResultsEach 1 standard deviation (1.06 ug/m3) increment in PM2.5 concentrations was associated with elevated risk of ASD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.00–2.02), ADHD (1.51, 1.15–1.98), schizophrenia (1.47, 1.15–1.87), and AD (1.57, 1.16–2.12). For all the 4 neurodevelopmental disorders, the results were robust under various sensitivity analyses, while the MR-Egger method yielded non-significant outcomes. The associations remained significant for all the 4 neuropsychiatric disorders after adjusting for PMcoarse, while non-significant after adjusting for NOX and PM10. The effects of PM2.5 exposure on ADHD and schizophrenia were partially mediated by Lachnospiraceae and Barnesiella, with the proportions ranging from 8.31% to 15.77%. ConclusionsThis study suggested that exposure to PM2.5 would increase the risk of neuropsychiatric disorders, partially by influencing the profile of gut microbiota. Comprehensive regulations on air pollutants are needed to help prevent neuropsychiatric disorders.

Surveillance and monitoring program of child neurodevelopment in population born during social confinement due to covid contigence: monteria-colombia experience

IntroductionThe American Academy of Pediatrics reports an incidence of 1 in every 54 children (Council on Children with Disabilities, 2021). The unique circumstances surrounding children born in 2020, who have experienced the COVID-19 pandemic since birth, present a distinct set of challenges for their neurodevelopmental well-being. The pandemic has led to reduced opportunities for learning and social interaction, masking mandates, decreased social support for research, and the potential misattribution of Autism Spectrum Disorders ASD symptoms to the effects of social isolation.ObjectivesThis study aims to develop such a program for children born during the COVID-19 pandemic (2020-2022).MethodsAll children born in March 2020 were included in the study. The initial assessment involved administering the ASQ-3 to evaluate their development across the specified domains. Diagnostic Evaluation: Among the population, 6% (4 children) displayed concerning signs on the ASQ-3, warranting further diagnostic evaluation by specialized health professionals for possible ASD.ResultsEarly Intervention and School Monitoring: Of the remaining 72% (46 children), who did not require diagnostic evaluation, intervention guidelines were provided, both within the school environment and at home. These children were reevaluated after a three-month period. Follow-up in the School Environment: Those children who underwent reevaluation were categorized into three groups: Nine children fell into the “gray” category on the ASQ-3 and were subsequently referred for diagnostic evaluation. Thirty-seven children progressed to the “white” category on the ASQ-3 after receiving intervention guidelines in both school and home settings. The findings of this research underscore the potential impact of the COVID-19 pandemic on the neurodevelopment of children born in 2020. 6% of the evaluated population were referred for diagnostic evaluation due to signs of ASD, suggesting a potential association between the pandemic and an increased risk of ASD within this cohort.72% of children who received intervention guidelines demonstrated significant improvements in their neurodevelopment, highlighting the critical role of early intervention and school-based monitoringConclusionsImplementing support strategies within educational settings was linked to positive developments in neurodevelopmental outcomes. Consequently, school-based neurodevelopmental monitoring, complemented by cohesive curricular guidelines, emerges as a beneficial approach for enhancing child development outcomes. The ASQ-3, as a structured instrument, proves invaluable in facilitating neurodevelopmental surveillance within educational settings, particularly in contexts with high demand and limited access to specialized care.Disclosure of InterestNone Declared

Risk factors for isolated atrial septal defect secundum morbidity

Atrial septal defect secundum is a common type of congenital heart defect and even more common among children born premature. The aim of this study was to assess premature birth as a potential associated risk factors for cardiac morbidity in children with isolated ASD II. In this retrospective national registry-based case–control study all children born in Sweden between 2010 and 2015 with an isolated ASD II diagnosis were included. Association between premature birth and cardiac morbidity in children with isolated ASD II was assessed by different outcomes-models using conditional logistic regression and adjustments were made for confounding factors. Overall, 11% of children with an isolated ASD II received treatment for heart failure. Down syndrome was the only independent risk factors for associated with cardiac morbidity in children with ASD II (OR = 2.25 (95%CI 1.25–4.07). Preterm birth in children was not associated with an increased risk of ASD II cardiac morbidity.

Associations between ADHD and risk of six psychiatric disorders: a Mendelian randomization study

BackgroundObservational studies and diagnostic criteria have indicated that Attention Deficit Hyperactivity Disorder (ADHD) frequently comorbid with various psychiatric disorders. Therefore, we conducted a Mendelian randomization (MR) study to explore this potential genetic association between ADHD and six psychiatric disorders.MethodsUsing a two-sample Mendelian randomization (MR) design, this study systematically screened genetic instrumental variables (IVs) based on the genome-wide association studies (GWAS) of ADHD and six psychiatric disorders, with the inverse variance weighted (IVW) method as the primary approach.ResultsThe study revealed a positive and causal association between ADHD and the risk of ASD, with an odds ratio (OR) of 2.328 (95%CI: 1.241–4.368) in the IVW MR analysis. Additionally, ADHD showed a positive causal effect on an increased risk of schizophrenia, with an OR of 1.867 (95%CI: 1.260–2.767) in the IVW MR analysis. However, no causal effect of Tic disorder, Mental retardation, Mood disorders and Anxiety disorder with ADHD was found in the analysis mentioned above.ConclusionOur MR analysis provides robust evidence of the causal role of ADHD in increasing the risk of ASD and schizophrenia. However, ADHD is not associated with the risk of Tic Disorder, Mental Retardation, Mood Disorders and Anxiety Disorder. This suggests the need for increased attention to the co-occurrence of ADHD-ASD or ADHD-schizophrenia and the implementation of timely intervention and treatment.

Does prenatal exposure to antidepressants cause autism? - literature review

Autism spectrum disorder is an increasingly diagnosed disorder among children, yet its pathogenesis is still unknown. Possible causes are sought in genetic mutations, cellular processes occurring in the nervous system during development and external factors affecting the fetus during the prenatal period. In recent years, there have been an increasing number of reports linking the occurrence of the spectrum to antidepressant medications, especially from the SSRI group, taken by pregnant women for depressive disorders, which occur in up to a dozen percent of women in this group. The involvement of serotonin in the development of the nervous system during the fetal period is taken as the reason for this phenomenon. To date, no clear consensus has been reached on this issue, and many distractors in the research are highlighted, such as the effect of maternal depression on fetal development, among others. There is no doubt that further research is needed to better assess the risk of ASD associated with SSRI use and dosage during pregnancy

Neurodevelopmental outcomes after prenatal exposure to lamotrigine monotherapy in women with epilepsy: a systematic review and meta-analysis

BackgroundLamotrigine has become one of the most commonly prescribed antiseizure medications (ASM) in epileptic women during pregnancy and therefore requires regular updates regarding its safety. The aim of this study was to estimate the association between in utero exposure to lamotrigine monotherapy and the occurrence of neurodevelopmental outcomes.MethodsAll comparative studies assessing the occurrence of neurodevelopmental outcomes after epilepsy-indicated lamotrigine monotherapy exposure during pregnancy were searched. First, references were identified through a snowballing approach, then, through electronic databases (Medline and Embase) from 2015 to June 2022. One investigator evaluated study eligibility and extracted data and a second independent investigator reviewed the meta-analysis (MA). A systematic review and random-effects model approach were performed using a collaborative WEB-based meta-analysis platform (metaPreg.org) with a registered protocol (osf.io/u4gva).ResultsOverall, 18 studies were included. For outcomes reported by at least 4 studies, the pooled odds ratios and 95% confidence interval obtained with the number of exposed (N1) and unexposed children (N0) included were: neurodevelopmental disorders as a whole 0.84 [0.66;1.06] (N1 = 5,271; N0 = 22,230); language disorders or delay 1.16 [0.67;2.00] (N1 = 313; N0 = 506); diagnosis or risk of ASD 0.97 [0.61;1.53] (N1 = at least 5,262; N0 = 33,313); diagnosis or risk of ADHD 1.14 [0.75;1.72] (N1 = at least 113; N0 = 11,530) and psychomotor developmental disorders or delay 2.68 [1.29–5.56] (N1 = 163; N0 = 220). The MA of cognitive outcomes included less than 4 studies and retrieved a significant association for infants exposed to lamotrigine younger than 3 years old but not in the older age groups.ConclusionPrenatal exposure to lamotrigine monotherapy is not found to be statistically associated with neurodevelopmental disorders as a whole, language disorders or delay, diagnosis or risk of ASD and diagnosis or risk of ADHD. However, the MA found an increased risk of psychomotor developmental disorders or delay and cognitive developmental delay in less than 3 years old children. Nevertheless, these findings were based exclusively on observational studies presenting biases and on a limited number of included children. More studies should assess neurodevelopmental outcomes in children prenatally exposed to lamotrigine.

Исследование эффективности применения Денверской модели ранней помощи детям с аутизмом и с риском РАС. Систематический обзор

&lt;p style="text-align: justify;"&gt;Autism spectrum disorders are a high-frequency group of developmental disorders with a wide variety in the manifestation of key symptoms. The results of numerous studies point to the extremely important role of early initiation of corrective and developmental measures in the further trajectory of the development of a child with autism. To date, the Denver Early Intervention Model, which has been implemented in the practice of providing help to children with ASD for about 25 years, is the most well-known in early intervention services. During this time, a large number of studies have been conducted and evidence of efficacy has been obtained, but the data of scientific studies are very contradictory. The purpose of this work was to review the available scientific literature reflecting the results of research on the application of the Denver model in working with children of early and early preschool age with ASD and the risk of ASD. The effects of the model are considered separately for different types of studies, from case studies to meta-analyses of data, due to differences in results. In general, the presented results of studies on the effectiveness of the Denver model indicate positive results in terms of reducing the severity of autism symptoms, developing social skills and intelligence. At the same time, there is a reduced effect on the generalization of data in meta-analyses, which may be due to the wide variety of diagnostic methods used, which examine one area of development, but reflect different aspects of it.&lt;/p&gt;