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JAMA Aug 2023Neural tube defects are among the most common birth defects in the US.
IMPORTANCE
Neural tube defects are among the most common birth defects in the US.
OBJECTIVE
To review new evidence on the benefits and harms of folic acid supplementation for the prevention of neural tube defects to inform the US Preventive Services Task Force.
EVIDENCE REVIEW
Sources included PubMed, Cochrane Library, Embase, and trial registries from July 1, 2015, through July 2, 2021; references; and experts, with surveillance through February 10, 2023. Two investigators independently reviewed English-language randomized studies and nonrandomized cohort studies in very highly developed countries that focused on the use of folic acid supplementation for the prevention of neural tube defect-affected pregnancies; methodological quality was dually and independently assessed.
FINDINGS
Twelve observational studies (reported in 13 publications) were eligible for this limited update (N = 1 244 072). Of these, 3 studies (n = 990 372) reported on the effect of folic acid supplementation on neural tube defects. For harms, 9 studies were eligible: 1 randomized clinical trial (n = 431) reported on variations in twin delivery, 7 observational studies (n = 761 125) reported on the incidence of autism spectrum disorder, and 1 observational study (n = 429 004) reported on maternal cancer. Two cohort studies and 1 case-control study newly identified in this update reported on the association between folic acid supplementation and neural tube defects (n = 990 372). One cohort study reported a statistically significant reduced risk of neural tube defects associated with folic acid supplementation taken before pregnancy (adjusted relative risk [aRR], 0.54 [95% CI, 0.31-0.91]), during pregnancy (aRR, 0.62 [95% CI, 0.39-0.97]), and before and during pregnancy (aRR, 0.49 [95% CI, 0.29-0.83]), but this association occurred for only the later of 2 periods studied (2006-2013 and not 1999-2005). No other statistically significant benefits were reported overall. No study reported statistically significant harms (multiple gestation, autism, and maternal cancer) associated with pregnancy-related folic acid exposure.
CONCLUSIONS AND RELEVANCE
New evidence from observational studies provided additional evidence of the benefit of folic acid supplementation for preventing neural tube defects and no evidence of harms related to multiple gestation, autism, or maternal cancer. The new evidence was consistent with previously reviewed evidence on benefits and harms.
Topics: Female; Humans; Pregnancy; Autism Spectrum Disorder; Dietary Supplements; Folic Acid; Neural Tube Defects; Randomized Controlled Trials as Topic; Pregnancy Complications; Risk; Preconception Care; Prenatal Care
PubMed: 37526714
DOI: 10.1001/jama.2023.9864 -
Brain, Behavior, and Immunity Nov 2023The aetiology of autism spectrum disorder (ASD) is complex and, partly, accounted by genetic factors. Nonetheless, the genetic underpinnings of ASD are poorly defined.... (Review)
Review
The aetiology of autism spectrum disorder (ASD) is complex and, partly, accounted by genetic factors. Nonetheless, the genetic underpinnings of ASD are poorly defined. The presence of immune dysregulations in autistic individuals, and their families, supports a role of the immune system and its genetic regulators. Albeit immune responses belong either to the innate or adaptive arms, the overall immune system genetics is broad, and encompasses a multitude of functionally heterogenous pathways which may have different influences on ASD. Hence, to gain insights on the immunogenetic underpinnings of ASD, we conducted a systematic literature review of previous immune genetic and transcription studies in ASD. We defined a list of immune genes relevant to ASD and explored their neuro-immune function. Our review confirms the presence of immunogenetic variability in ASD, accounted by inherited variations of innate and adaptive immune system genes and genetic expression changes in the blood and post-mortem brain of autistic individuals. Besides their immune function, the identified genes control neurodevelopment processes (neuronal and synaptic plasticity) and are highly expressed in pre/peri-natal periods. Hence, our synthesis bolsters the hypothesis that perturbation in immune genes may contribute to ASD by derailing the typical trajectory of neurodevelopment. Our review also helped identifying some of the limitations of prior immunogenetic research in ASD. Thus, alongside clarifying the neurodevelopment role of immune genes, we outline key considerations for future work into the aetiology of ASD and possible novel intervention targets.
PubMed: 37717669
DOI: 10.1016/j.bbi.2023.09.010 -
Autism Research : Official Journal of... Dec 2023Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication and interaction, as well as rigid and unchanging interests... (Meta-Analysis)
Meta-Analysis Review
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication and interaction, as well as rigid and unchanging interests and behaviors. Several studies have reported that activated immune-inflammatory and nitro-oxidative pathways are accompanied by depletion of plasma tryptophan (TRP), increased competing amino acid (CAAs) levels, and activation of the TRP catabolite (TRYCAT) pathway. This study aims to systematically review and meta-analyze data on peripheral TRP, CAAs, TRYCAT pathway activity, and individual TRYCATs, including kynurenine (KYN) and kynurenic acid (KA) levels, in the blood and urine of ASD patients. After extensively searching PubMed, Google Scholar, and SciFinder, a total of 25 full-text papers were included in the analysis, with a total of 6653 participants (3557 people with ASD and 3096 healthy controls). Our results indicate that blood TRP and the TRP/CAAs ratio were not significantly different between ASD patients and controls (standardized mean difference, SMD = -0.227, 95% confidence interval, CI: -0.540; 0.085, and SMD = 0.158, 95% CI: -0.042; 0.359), respectively. The KYN/TRP ratio showed no significant difference between ASD and controls (SMD = 0.001, 95% CI: -0.169; 0.171). Blood KYN and KA levels were not significantly changed in ASD. Moreover, there were no significant differences in urine TRP, KYN, and KA levels between ASD and controls. We could not establish increases in neurotoxic TRYCATs in ASD. In conclusion, this study demonstrates no abnormalities in peripheral blood TRP metabolism, indoleamine 2,3-dioxygenase enzyme (IDO) activity, or TRYCAT production in ASD. Reduced TRP availability and elevated neurotoxic TRYCAT levels are not substantial contributors to ASD's pathophysiology.
Topics: Humans; Tryptophan; Kynurenine; Autism Spectrum Disorder; Kynurenic Acid
PubMed: 37909397
DOI: 10.1002/aur.3044 -
Nutrients Aug 2023Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, the prevalence of which has increased in children and adolescents over the years. Studies point to... (Review)
Review
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, the prevalence of which has increased in children and adolescents over the years. Studies point to deficiency of trace elements as one of the factors involved in the etiology of the disorder, with zinc being one of the main trace elements investigated in individuals with ASD. The aim of this review is to summarize scientific evidence about the relationship between zinc status and ASD in children and adolescents. This review has been registered in the International Prospective Register of Systematic Reviews (registration number CRD42020157907). The methodological guidelines adopted were in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were selected from an active investigation of the PubMed, Scopus, LILACS, and Google databases to search for observational studies. Fifty-two studies from twenty-two countries were included. The sample sizes ranged from 20 to 2635, and the participants ranged from 2 to 18 years old. Nine types of biological matrices were used, with hair, serum, and plasma being the most frequently used in the evaluation of zinc concentrations. Significant differences in zinc concentrations between the ASD and control groups were observed in 23 studies, of which 19 (36%) showed lower zinc concentrations in the ASD group. The classification of studies according to methodological quality resulted in high, moderate, and low quality in 10, 21, and 21 studies, respectively. In general, we did not observe a significant difference between zinc concentrations of children and adolescents with ASD compared to controls; however, studies point to an occurrence of lower concentrations of Zn in individuals with ASD. This review reveals that more prospective studies with greater methodological rigor should be conducted in order to further characterize this relation.
Topics: Humans; Adolescent; Child; Child, Preschool; Zinc; Trace Elements; Autism Spectrum Disorder; Prospective Studies; Databases, Factual
PubMed: 37630853
DOI: 10.3390/nu15163663 -
European Child & Adolescent Psychiatry Sep 2023Autism spectrum disorder (ASD) is a disabling neurodevelopmental condition with complex etiology. Emerging evidence has pointed to maternal atopy as a possible risk... (Review)
Review
Autism spectrum disorder (ASD) is a disabling neurodevelopmental condition with complex etiology. Emerging evidence has pointed to maternal atopy as a possible risk factor. It is hypothesized that maternal atopic disease during pregnancy can lead to increased levels of inflammatory cytokines in fetal circulation via placental transfer or increased production. These cytokines can then pass through the immature blood-brain barrier, causing aberrant neurodevelopment via mechanisms including premature microglial activation. The objective of this study is to systematically review observational studies that investigate whether a maternal history of atopic disease (asthma, allergy, or eczema/atopic dermatitis) is associated with a diagnosis of ASD in offspring. A search was conducted in Ovid MEDLINE, PsycINFO, and Embase databases for relevant articles up to November 2021; this was later updated in January 2022. Observational studies published in peer-reviewed journals were included. Data were synthesized and qualitatively analyzed according to the specific atopic condition. Quality assessment was done using the Newcastle-Ottawa Scale. Nine articles were identified, with all including asthma as an exposure, alongside four each for allergy and eczema. Findings were inconsistent regarding the association between a maternal diagnosis of either asthma, allergy, or eczema, and ASD in offspring, with variations in methodology contributing to the inconclusiveness. More consistent associations were demonstrated regarding maternal asthma that was treated or diagnosed during pregnancy. Evidence suggests that symptomatic maternal asthma during pregnancy could be associated with ASD in offspring, underscoring the importance of effective management of atopic conditions during pregnancy. Further research is needed, particularly longitudinal studies that use gold-standard assessment tools and correlate clinical outcomes with laboratory and treatment data.PROSPERO Registration Number and Date: CRD42018116656, 26.11.2018.
PubMed: 37661216
DOI: 10.1007/s00787-023-02285-7 -
Computers in Biology and Medicine Mar 2024Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social communication and repetitive and stereotyped behaviors. According... (Review)
Review
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social communication and repetitive and stereotyped behaviors. According to the World Health Organization, about 1 in 100 children worldwide has autism. With the global prevalence of ASD, timely and accurate diagnosis has been essential in enhancing the intervention effectiveness for ASD children. Traditional ASD diagnostic methods rely on clinical observations and behavioral assessment, with the disadvantages of time-consuming and lack of objective biological indicators. Therefore, automated diagnostic methods based on machine learning and deep learning technologies have emerged and become significant since they can achieve more objective, efficient, and accurate ASD diagnosis. Electroencephalography (EEG) is an electrophysiological monitoring method that records changes in brain spontaneous potential activity, which is of great significance for identifying ASD children. By analyzing EEG data, it is possible to detect abnormal synchronous neuronal activity of ASD children. This paper gives a comprehensive review of the EEG-based ASD identification using traditional machine learning methods and deep learning approaches, including their merits and potential pitfalls. Additionally, it highlights the challenges and the opportunities ahead in search of more effective and efficient methods to automatically diagnose autism based on EEG signals, which aims to facilitate automated ASD identification.
Topics: Child; Humans; Autism Spectrum Disorder; Brain; Electroencephalography; Prevalence; Machine Learning
PubMed: 38301514
DOI: 10.1016/j.compbiomed.2024.108075 -
Molecular Psychiatry Dec 2023To conduct a systematic review and meta-analysis assessing whether vision and/or eye disorders are associated with Autism Spectrum Disorder (ASD). (Meta-Analysis)
Meta-Analysis
AIM
To conduct a systematic review and meta-analysis assessing whether vision and/or eye disorders are associated with Autism Spectrum Disorder (ASD).
METHOD
Based on a pre-registered protocol (PROSPERO: CRD42022328485), we searched PubMed, Web of Knowledge/Science, Ovid Medline, Embase and APA PsycINFO up to 5 February 2022, with no language/type of document restrictions. We included observational studies 1) reporting at least one measure of vision in people of any age with a diagnosis of ASD based on DSM or ICD criteria, or ADOS; or 2) reporting the prevalence of ASD in people with and without vision disorders. Study quality was assessed with the Appraisal tool for Cross-Sectional Studies (AXIS). Random-effects meta-analyses were used for data synthesis.
RESULTS
We included 49 studies in the narrative synthesis and 46 studies in the meta-analyses (15,629,159 individuals distributed across multiple different measures). We found meta-analytic evidence of increased prevalence of strabismus (OR = 4.72 [95% CI: 4.60, 4.85]) in people with versus those without ASD (non-significant heterogeneity: Q = 1.0545, p = 0.7881). We also found evidence of increased accommodation deficits (Hedge's g = 0.68 [CI: 0.28, 1.08]) (non-significant heterogeneity: Q = 6.9331, p = 0.0741), reduced peripheral vision (-0.82 [CI: -1.32, -0.33]) (non-significant heterogeneity: Q = 4.8075, p = 0.4398), reduced stereoacuity (0.73 [CI: -1.14, -0.31]) (non-significant heterogeneity: Q = 0.8974, p = 0.3435), increased color discrimination difficulties (0.69 [CI: 0.27,1.10]) (non-significant heterogeneity: Q = 9.9928, p = 0.1890), reduced contrast sensitivity (0.45 [CI: -0.60, -0.30]) (non-significant heterogeneity: Q = 9.9928, p = 0.1890) and increased retinal thickness (=0.29 [CI: 0.07, 0.51]) (non-significant heterogeneity: Q = 0.8113, p = 0.9918) in ASD.
DISCUSSION
ASD is associated with some self-reported and objectively measured functional vision problems, and structural alterations of the eye, even though we observed several methodological limitations in the individual studies included in our meta-analyses. Further research should clarify the causal relationship, if any, between ASD and problems of vision during early life.
PROSPERO REGISTRATION
CRD42022328485.
Topics: Autism Spectrum Disorder; Humans; Vision Disorders; Strabismus; Prevalence; Child; Male; Cross-Sectional Studies; Female
PubMed: 37495888
DOI: 10.1038/s41380-023-02143-7 -
Neuroscience and Biobehavioral Reviews Nov 2023Individuals with autism spectrum disorder (ASD) exhibit atypical speech-in-noise (SiN) perception, but the scope of these impairments has not been clearly defined. We... (Review)
Review
Individuals with autism spectrum disorder (ASD) exhibit atypical speech-in-noise (SiN) perception, but the scope of these impairments has not been clearly defined. We conducted a systematic review of the behavioural research on SiN perception in ASD, using a comprehensive search strategy across databases (Embase, Pubmed, Web of Science, APA PsycArticles, LLBA, clinicaltrials.gov and PsyArXiv). We withheld 20 studies that generally revealed intact speech perception in stationary noise, while impairments in speech discrimination were found in temporally modulated noise, concurrent speech, and audiovisual speech perception. An association with auditory temporal processing deficits, exacerbated by suboptimal language skills, is shown. Speech-in-speech perception might be further impaired due to deficient top-down processing of speech. Further research is needed to address remaining challenges and gaps in our understanding of these impairments, including the developmental aspects of SiN processing in ASD, and the impact of gender and social attentional orienting on this ability. Our findings have important implications for improving communication in ASD, both in daily interactions and in clinical and educational settings.
Topics: Humans; Speech Perception; Autistic Disorder; Autism Spectrum Disorder; Speech; Auditory Perception
PubMed: 37797728
DOI: 10.1016/j.neubiorev.2023.105406 -
Molecular Genetics & Genomic Medicine Apr 2024RASopathies are associated with an increased risk of autism spectrum disorder (ASD). For neurofibromatosis type 1 (NF1) there is ample evidence for this increased risk,... (Review)
Review
BACKGROUND
RASopathies are associated with an increased risk of autism spectrum disorder (ASD). For neurofibromatosis type 1 (NF1) there is ample evidence for this increased risk, while for other RASopathies this association has been studied less. No specific ASD profile has been delineated so far for RASopathies or a specific RASopathy individually.
METHODS
We conducted a systematic review to investigate whether a specific RASopathy is associated with a specific ASD profile, or if RASopathies altogether have a distinct ASD profile compared to idiopathic ASD (iASD). We searched PubMed, Web of Science, and Open Grey for data about ASD features in RASopathies and potential modifiers.
RESULTS
We included 41 articles on ASD features in NF1, Noonan syndrome (NS), Costello syndrome (CS), and cardio-facio-cutaneous syndrome (CFC). Individuals with NF1, NS, CS, and CFC on average have higher ASD symptomatology than healthy controls and unaffected siblings, though less than people with iASD. There is insufficient evidence for a distinct ASD phenotype in RASopathies compared to iASD or when RASopathies are compared with each other. We identified several potentially modifying factors of ASD symptoms in RASopathies.
CONCLUSIONS
Our systematic review found no convincing evidence for a specific ASD profile in RASopathies compared to iASD, or in a specific RASopathy compared to other RASopathies. However, we identified important limitations in the research literature which may also account for this result. These limitations are discussed and recommendations for future research are formulated.
Topics: Humans; Autism Spectrum Disorder; Noonan Syndrome; Heart Defects, Congenital; Costello Syndrome; Failure to Thrive; Neurofibromatosis 1
PubMed: 38581124
DOI: 10.1002/mgg3.2428 -
Heliyon Jun 2024Autism spectrum disorder (ASD) is a behaviorally defined complex neurodevelopmental syndrome characterized by persistent social communication and interaction deficit.... (Review)
Review
Autism spectrum disorder (ASD) is a behaviorally defined complex neurodevelopmental syndrome characterized by persistent social communication and interaction deficit. Transcranial magnetic stimulation (TMS) is a promising and emerging tool for the intervention of ASD by reducing both core and associate symptoms. Several reviews have been published regarding TMS-based ASD treatment, however, a systematic review on study characteristics, specific stimulating parameters, localization techniques, stimulated targets, behavioral outcomes, and neuroimage biomarker changes is lagged behind since 2018. Here, we performed a systematic search on literatures published after 2018 in PubMed, Web of Science, and Science Direct. After screening, the final systematic review included 17 articles, composing seven randomized controlled trial studies and ten open-label studies. Two studies are double-blind, while the other studies have a moderate to high risk of bias attributing to inadequate subject- and evaluator-blinding to treatment allocation. Five studies utilize theta-burst stimulation mode, and the others apply repetitive TMS with low frequency (five studies), high frequency (six studies), and combined low and high frequency stimulation (one study). Most researchers prioritize the bilateral dorsolateral prefrontal lobe as stimulation target, while parietal lobule, inferior parietal lobule, and posterior superior temporal sulci have also emerged as new targets of attention. One third of the studies use neuronavigation based on anatomical magnetic resonance imaging to locate the stimulation target. After TMS intervention, discernible enhancements across a spectrum of scales are evident in stereotyped behavior, repetitive behavior, and verbal social domains. A comprehensive review of literature spanning the last five years demonstrates the potential of TMS treatment for ASD in ameliorating the clinical core symptoms.
PubMed: 38933955
DOI: 10.1016/j.heliyon.2024.e32251