1. The value of diffusion tensor imaging for differentiating autism spectrum disorder with language delay from developmental language disorder among toddlers : Erratum. Medicine (Baltimore) ;2020 (Dec 18) ;99(51):e23796.

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2. Ahn H, Seo GH, Oh A, Lee Y, Keum C, Heo SH, Kim T, Choi J, Kim GH, Ko TS, Yum MS, Lee BH, Choi IH. Diagnosis of Schaaf-Yang syndrome in Korean children with developmental delay and hypotonia. Medicine (Baltimore) ;2020 (Dec 18) ;99(51):e23864.

Schaaf-Yang syndrome (SYS) is a recently identified disorder caused by a loss-of-function mutation in a maternally imprinted gene, MAGEL2, at 15q11.2q13. Due to its extreme rarity and wide range of clinical severity, clinical suspicion is difficult for a physician. In the current study, its frequency among the Korean pediatric patients with developmental delay (DD) or intellectual disability (ID) was assessed. As the first report of Korean patients with SYS, our study aims to increase the awareness of this condition among the physicians taking care of the pediatric patients with DD/ID and hypotonia.The patients diagnosed with SYS by whole-exome sequencing (WES) among the 460 Korean pediatric patients with DD/ID were included, and their clinical and molecular features were reviewed.Four patients (0.9%) were diagnosed with SYS. Profound DD (4 patients), multiple anomalies including joint contractures and facial dysmorphism (4 patients), generalized hypotonia (3 patients), and severe respiratory difficulty requiring mechanical ventilation (3 patients) were noted in most cases, similar to those in previous reports. Sleep apnea (2 patients), autistic features (2 patients), a high grade of gastroesophageal reflux (1 patient), and seizures (1 patient) were found as well. A total of 3 different truncating MAGEL2 mutations were identified. A previously-reported mutation, to be the most common one, c.1996dupC, was found in 2 patients. The other 2 mutations, c.2217delC and c.3449_3450delTT were novel mutations. As MAGEL2 is maternally imprinted, 2 patients had inherited the MAGEL2 mutation from their respective healthy fathers.SYS is an extremely rare cause of DD/ID. However, hypotonia, joint contractures, profound DD/ID and facial dysmorphism are the suggestive clinical features for SYS. As a maternally imprinted disorder, it should be reminded that SYS may be inherited in form of a mutation from a healthy father.

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3. Allenmark F, Shi Z, Pistorius RL, Theisinger LA, Koutsouleris N, Falkai P, Müller HJ, Falter-Wagner CM. Acquisition and Use of ‘Priors’ in Autism : Typical in Deciding Where to Look, Atypical in Deciding What Is There. J Autism Dev Disord ;2020 (Dec 29)

Individuals with Autism Spectrum Disorder (ASD) are thought to under-rely on prior knowledge in perceptual decision-making. This study examined whether this applies to decisions of attention allocation, of relevance for ‘predictive-coding’ accounts of ASD. In a visual search task, a salient but task-irrelevant distractor appeared with higher probability in one display half. Individuals with ASD learned to avoid ‘attentional capture’ by distractors in the probable region as effectively as control participants-indicating typical priors for deploying attention. However, capture by a ‘surprising’ distractor at an unlikely location led to greatly slowed identification of a subsequent target at that location-indicating that individuals with ASD attempt to control surprise (unexpected attentional capture) by over-regulating parameters in post-selective decision-making.

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4. Bottema-Beutel K, Kim SY. A Systematic Literature Review of Autism Research on Caregiver Talk. Autism Res ;2020 (Dec 29)

Describing how caregivers’ talk to their autistic children, and how their talk may influence social and language outcomes, has important implications for developmental theory and intervention research. In this systematic literature review, we examine 294 caregiver talk variables extracted from 65 studies, provide a narrative overview of research findings, and link measurement approaches to various theories of language development. The majority of variables included only talk directed to children (90%), and specified the speech act being performed (57%). More than one-third of variables measured talk that was responsive to children’s attention, activities, or communication (38%), and slightly less than a third measured variables that elicited children’s communication or engagement. Semantic aspects of talk were specified in 41% of variables, structural features were measured in 20% of variables, and suprasegmental features were measured in only 1% of variables. Talk quantity (without reference to other aspects of talk) was measured in 8% of variables. We found strong support that talk related to children’s attention is implicated in autistic children’s language development, but this construct has been measured inconsistently in terms of semantic, structural, and functional features. There is also evidence for bi-directional relationships between caregiver’s talk and autistic children’s development on a variety of semantic and structural variables. LAY SUMMARY : In our review, we found many differences in how researchers measured caregiver’s talk, but also some promising leads. Researchers should continue examining caregiver talk related to children’s focus of attention to clarify how this type of language contributes to autistic children’s development. We also found interesting research on how children influence caregiver’s talk, and encourage researchers to continue to study how this occurs.

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5. Cárdenas-de-la-Parra A, Lewis JD, Fonov VS, Botteron KN, McKinstry RC, Gerig G, Pruett JR, Jr., Dager SR, Elison JT, Styner MA, Evans AC, Piven J, Collins DL. A voxel-wise assessment of growth differences in infants developing autism spectrum disorder. Neuroimage Clin ;2020 (Dec 29) ;29:102551.

Autism Spectrum Disorder (ASD) is a phenotypically and etiologically heterogeneous developmental disorder typically diagnosed around 4 years of age. The development of biomarkers to help in earlier, presymptomatic diagnosis could facilitate earlier identification and therefore earlier intervention and may lead to better outcomes, as well as providing information to help better understand the underlying mechanisms of ASD. In this study, magnetic resonance imaging (MRI) scans of infants at high familial risk, from the Infant Brain Imaging Study (IBIS), at 6, 12 and 24 months of age were included in a morphological analysis, fitting a mixed-effects model to Tensor Based Morphometry (TBM) results to obtain voxel-wise growth trajectories. Subjects were grouped by familial risk and clinical diagnosis at 2 years of age. Several regions, including the posterior cingulate gyrus, the cingulum, the fusiform gyrus, and the precentral gyrus, showed a significant effect for the interaction of group and age associated with ASD, either as an increased or a decreased growth rate of the cerebrum. In general, our results showed increased growth rate within white matter with decreased growth rate found mostly in grey matter. Overall, the regions showing increased growth rate were larger and more numerous than those with decreased growth rate. These results detail, at the voxel level, differences in brain growth trajectories in ASD during the first years of life, previously reported in terms of overall brain volume and surface area.

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6. Carmona-Serrano N, López-Belmonte J, López-Núñez JA, Moreno-Guerrero AJ. Trends in Autism Research in the Field of Education in Web of Science : A Bibliometric Study. Brain Sci ;2020 (Dec 21) ;10(12)

Autism spectrum disorder (ASD) is conceived as a neurodevelopmental disorder. The scientific literature welcomes studies that reflect the possible singularities that people with ASD may present both in their daily lives and at an educational level. The main objective of this study is to analyze the scientific production on the term autism in Web of Science, focused on the educational field, in order to identify the research trends in this field of study. The intention is to offer researchers who study autism in the educational field some clear research directions. A bibliometric-type methodology was developed using the scientific mapping technique. For this purpose, a performance analysis and a co-word analysis were carried out. Work was conducted with an analysis unit of 5512 documents. The results show that the volume of production has been irregular from the beginning to the present. The collection of documents on the subject began to be relevant, in terms of the volume of production, from 2007, and this has persisted to the present. It is concluded that there are two lines of research. The first is the line focused on mothers of children with ASD and the second is the line of research focused on young people with ASD. In addition, since 2012, new lines of research have been generated, focused on the diagnosis and inclusion of these students in educational centers.

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7. Downs J, Lotan M, Elefant C, Leonard H, Wong K, Buckley N, Stahlhut M. Implementing telehealth support to increase physical activity in girls and women with Rett syndrome-ActivRett : protocol for a waitlist randomised controlled trial. BMJ Open ;2020 (Dec 29) ;10(12):e042446.

INTRODUCTION : Individuals with Rett syndrome (RTT) experience impaired gross motor skills, limiting their capacity to engage in physical activities and participation in activities. There is limited evidence of the effectiveness of supported physical activity interventions. This study aims to evaluate the effects of a telehealth-delivered physical activity programme on physical activity, sedentary behaviour and quality of life in RTT. METHODS AND ANALYSIS : This is a multicentre study, conducted in Australia, Denmark and Israel. It is a randomised waitlist-controlled trial comparing an intervention to support physical activity with usual care. Participants are children and adults with RTT, recruited from the Australian Rett Syndrome Database, the Danish Center for Rett Syndrome and the Rett Syndrome Association of Israel. The intervention duration is 12 weeks, including fortnightly telephone contact to plan, monitor and develop individual activity programmes. Outcomes are measured at baseline, at 13 weeks and then at 25 weeks. The primary outcomes are sedentary behaviour assessed with an activPAL accelerometer and the number of daily steps measured with a StepWatch Activity Monitor. Secondary outcomes include sleep, behaviour and quality of life. Caregiver experiences will be assessed immediately after the intervention using a satisfaction questionnaire. Group differences for each outcome will be evaluated with analysis of covariance, adjusting for baseline values on an intention-to-treat basis. ETHICS AND DISSEMINATION : Ethics approval has been obtained in Western Australia from the Child and Adolescent Health Services (RGS3371), in Denmark from the Capital Region Ethics Committee (H-19040514) and in Israel from the Ariel University Institutional Review Board (AU-HEA-ML-20190331). Manuscripts on the development of the intervention from pilot work and the results of the intervention will be submitted to peer-reviewed journals. Results will be presented at conferences and consumer forums. We will develop an online resource documenting the physical activity programme and available supporting evidence. TRIAL REGISTRATION NUMBER : NCT04167059 ; Pre-results.

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8. Hall Pistorio K, Kearney KB, Eshman S, Thomas K, Carey G. Using a Literacy Based Behavioral Intervention to Teach College Students with Intellectual and Developmental Disabilities to Request a Classroom Accommodation. Behav Modif ;2020 (Dec 29):145445520982978.

Many individuals with an intellectual and developmental disabilities (IDD) are attending postsecondary education programs, yet they are not always proficient in using self-advocacy skills, such as requesting an academic accommodation. Access to these accommodations is vital for success in the postsecondary settings. Literacy based behavioral interventions (LBBIs) use a combination of print, visuals, and rehearsal and are an effective tool for teaching a range of skills including job skills to this population, but have not been investigated with a self-advocacy skill. In this study, a pre-service teacher was taught to deliver an LBBI to postsecondary students with IDD so they would learn to request and use a free online tool to record class lectures. Results showed that students were able to master the skill with the pre-service teacher delivered LBBI and maintain the skill after removal of the LBBI.

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9. Harris JC. Developmental Neuropsychiatry dyslexia, animal models, prenatal and perinatal risk for autism, neuroimaging, and syndrome updates. Curr Opin Psychiatry ;2020 (Dec 29) ;Publish Ahead of Print

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10. Hessl D, Libero L, Schneider A, Kerns C, Winder-Patel B, Heath B, Lee J, Coleman C, Sharma N, Solomon M, Nordahl CW, Amaral DG. Fear Potentiated Startle in Children With Autism Spectrum Disorder : Association With Anxiety Symptoms and Amygdala Volume. Autism Res ;2020 (Dec 29)

Atypical responses to fearful stimuli and the presence of various forms of anxiety are commonly seen in children with autism spectrum disorder (ASD). The fear potentiated startle paradigm (FPS), which has been studied both in relation to anxiety and as a probe for amygdala function, was carried out in 97 children aged 9-14 years including 48 (12 female) with ASD and 49 (14 female) with typical development (TD). In addition, exploratory analyses were conducted examining the association between FPS and amygdala volume as assessed with magnetic resonance imaging in a subset of the children with ASD with or without an anxiety disorder with available MRI data. While the startle latency was increased in the children with ASD, there was no group difference in FPS. FPS was not significantly associated with traditional Diagnostic and Statistical Manual (DSM) or « autism distinct » forms of anxiety. Within the autism group, FPS was negatively correlated with amygdala volume. Multiple regression analyses revealed that the association between FPS and anxiety severity was significantly moderated by the size of the amygdala, such that the association between FPS and anxiety was significantly more positive in children with larger amygdalas than smaller amygdalas. These findings highlight the heterogeneity of emotional reactivity associated with ASD and the difficulties in establishing biologically meaningful probes of altered brain function. LAY SUMMARY : Many children with autism spectrum disorder (ASD) have additional problems such as anxiety that can greatly impact their lives. How these co-occurring symptoms develop is not well understood. We studied the amygdala, a region of the brain critical for processing fear and a laboratory method called fear potentiated startle for measuring fear conditioning, in children with ASD (with and without an anxiety disorder) and typically developing children. Results showed that the connection between fear conditioning and anxiety is dependent on the size of the amygdala in children with ASD.

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11. Jones G, Jassi A. Modified Cognitive Behavior Therapy for Severe, Treatment Resistant Obsessive-Compulsive Disorder in an Adolescent With Autism Spectrum Disorder : The Importance of Parental Involvement. J Cogn Psychother ;2020 (Nov 1) ;34(4):319-335.

The prevalence of obsessive-compulsive disorder (OCD) is higher among young people with autism spectrum disorders (ASD). Case studies and randomized controlled trials show that modified cognitive behavioral therapy (CBT) can be effective for young people with OCD and co-morbid ASD. This case study describes modified CBT for an adolescent with severe, treatment-resistant OCD and co-morbid ASD, and highlights the importance of family accommodation and parental mental health in pediatric OCD. Modifications to the standard evidence-based CBT for OCD protocol included extended psychoeducation, visual session material, mini exposure and response prevention hierarchies and parallel parent sessions to address familial accommodation and parental mental health. Progress was measured at seven times points throughout treatment using clinician administered, youth and parent self-report measures. Outcome data indicated significant improvements in OCD symptoms, general functioning, and maternal mental health as well as significant reductions in family accommodation. Gains were maintained over a 12-month follow-up period. This case study illustrates that modified CBT can be effective in youth with OCD and ASD and discusses the importance of familial accommodation and parental mental health.

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12. Khalulyan A, Byrd K, Tarbox J, Little A, Moll H. The role of eye contact in young children’s judgments of others’ visibility : A comparison of preschoolers with and without autism spectrum disorder. J Commun Disord ;2020 (Dec 29) ;89:106075.

Typically-developing (TD) children under age 5 often deny that they can see a person whose eyes are covered (e.g., Moll & Khalulyan, 2017). This has been interpreted as a manifestation of their preference for reciprocal interactions. We investigated how 3- to 4-year-old children with autism spectrum disorder (ASD, n = 12) respond in this situation. Because a lack of interpersonal connectedness and reciprocal communication are core features of this disorder, we predicted that young children with ASD will not make mutual regard a condition for seeing another person and therefore acknowledge being able to see her. Against this prediction, children with ASD gave the same negative answers as a group of TD (n = 36) age-mates. Various interpretations are discussed, including the possibility that some children with ASD are capable of relating to others as second persons.

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13. Kirchner RM, Walton KM. Symptoms of Autism Spectrum Disorder in Children With Down Syndrome and Williams Syndrome. Am J Intellect Dev Disabil ;2021 (Jan 1) ;126(1):58-74.

Research suggests that people with a Williams syndrome (WS) or Down syndrome (DS) diagnosis display an increased prevalence of autism spectrum disorder (ASD) when compared to the general population. This study aimed to examine characteristics of ASD in a group of children with DS or WS. Results suggest that children with DS and WS exhibit higher levels of autism symptoms than the general population, particularly in the area of unusual behaviors, and that these elevations are not solely due to deficits in adaptive behavior. There are many possible explanations for these elevations, such as issues with measurement, etiological overlap, or similar behavioral phenotypes. More research is needed to further our understanding of the overlap of ASD symptoms in these populations.

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14. Lin IC, Tseng LY, Lee YT. Post-traumatic Stress Disorder in an Adolescent with Asperger Syndrome. Psychiatr Danub ;2020 (Autumn) ;32(3-4):436-437.

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15. Nadeem A, Ahmad SF, Al-Harbi NO, Attia SM, Bakheet SA, Alsanea S, Ali N, Albekairi TH, Alsaleh NB. Aggravation of autism-like behavior in BTBR T+tf/J mice by environmental pollutant, di-(2-ethylhexyl) phthalate : Role of nuclear factor erythroid 2-related factor 2 and oxidative enzymes in innate immune cells and cerebellum. Int Immunopharmacol ;2021 (Feb) ;91:107323.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder which manifests itself in early childhood and is distinguished by recurring behavioral patterns, and dysfunction in social/communication skills. Ubiquitous environmental pollutant, di-2-ethylhexyl phthalate (DEHP) is one of the most frequently used plasticizers in various industrial products, e.g. vinyl flooring, plastic toys, and medical appliances. DEHP gets easily released into the environment and leads to human exposure through various routes. DEHP has been described to be linked with oxidative stress in various organs in animal/human studies. Increased concentration of DEHP has also been detected in ASD children which indicates an association between phthalates exposure and ASD. However, effect of DEHP on autism-like behavior has not been investigated previously. Therefore, this study probed the effect of DEHP on autism-like behavior (marble burying, self-grooming and sociability) and innate immune cells (dendritic cells/neutrophils)/cerebellar oxidant-antioxidant balance (NFkB, iNOS, NADPH oxidase, nitrotyrosine, lipid peroxides, Nrf2, SOD, GPx) in BTBR and C57 mice. Our data show that DEHP treatment causes worsening of autism-like behavior in BTBR mice which is associated with enhancement of oxidative stress in innate immune cells and cerebellum with concomitant lack of antioxidant protection. DEHP also causes oxidative stress in C57 mice in both innate immune cells and cerebellar compartment, however there is Nrf2-mediated induction of enzymatic antioxidants which protects them from upregulated oxidative stress. This proposes the notion that ubiquitous environmental pollutants such as DEHP may be involved in the pathogenesis/progression of ASD through dysregulation of antioxidant-antioxidant balance in innate immune cells and cerebellum.

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16. Pizzamiglio L, Focchi E, Cambria CM, Ponzoni L, Ferrara S, Bifari F, Desiato G, Landsberger N, Murru L, Passafaro M, Sala M, Matteoli M, Menna E, Antonucci F. The DNA repair protein ATM as target in autism spectrum disorder. JCI Insight ;2020 (Dec 29)

Impairment of GABAergic system has been reported in epilepsy, autism, ADHD and schizophrenia. We recently demonstrated that Ataxia Telangiectasia Mutated (ATM) shapes directly the development of GABAergic system. Here, we show for the first time how the abnormal expression of ATM impacts the pathological condition of autism. We exploit two different animal models of autism, the Mecp2y/- mouse model of Rett syndrome, and mice prenatally exposed to valproic acid, and found increased ATM levels. Accordingly, the treatment with the specific ATM kinase inhibitor KU55933 (KU) normalises molecular, functional and behavioural defects in these mouse models such as the i) delayed GABAergic development, ii) hippocampal hyper-excitability, iii) low cognitive performances, iv) social impairments. Mechanistically, we demonstrate that KU administration to wild type hippocampal neurons leads to i) higher Egr4 activity on Kcc2b promoter, ii) increased expression of Mecp2, iii) potentiated GABA-transmission. These results provide evidences and molecular substrates for the pharmacological development of ATM inhibition in autism spectrum disorders.

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17. Vanzo RJ, Prasad A, Staunch L, Hensel CH, Serrano MA, Wassman ER, Kaplun A, Grandin T, Boles RG. The Temple Grandin Genome : Comprehensive Analysis in a Scientist with High-Functioning Autism. J Pers Med ;2020 (Dec 29) ;11(1)

Autism spectrum disorder (ASD) is a heterogeneous condition with a complex genetic etiology. The objective of this study is to identify the complex genetic factors that underlie the ASD phenotype and other clinical features of Professor Temple Grandin, an animal scientist and woman with high-functioning ASD. Identifying the underlying genetic cause for ASD can impact medical management, personalize services and treatment, and uncover other medical risks that are associated with the genetic diagnosis. Prof. Grandin underwent chromosomal microarray analysis, whole exome sequencing, and whole genome sequencing, as well as a comprehensive clinical and family history intake. The raw data were analyzed in order to identify possible genotype-phenotype correlations. Genetic testing identified variants in three genes (SHANK2, ALX1, and RELN) that are candidate risk factors for ASD. We identified variants in MEFV and WNT10A, reported to be disease-associated in previous studies, which are likely to contribute to some of her additional clinical features. Moreover, candidate variants in genes encoding metabolic enzymes and transporters were identified, some of which suggest potential therapies. This case report describes the genomic findings in Prof. Grandin and it serves as an example to discuss state-of-the-art clinical diagnostics for individuals with ASD, as well as the medical, logistical, and economic hurdles that are involved in clinical genetic testing for an individual on the autism spectrum.

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18. Venker CE, Mathée J, Neumann D, Edwards J, Saffran J, Ellis Weismer S. Competing Perceptual Salience in a Visual Word Recognition Task Differentially Affects Children With and Without Autism Spectrum Disorder. Autism Res ;2020 (Dec 28)

Differences in visual attention have long been recognized as a central characteristic of autism spectrum disorder (ASD). Regardless of social content, children with ASD show a strong preference for perceptual salience-how interesting (i.e., striking) certain stimuli are, based on their visual properties (e.g., color, geometric patterning). However, we do not know the extent to which attentional allocation preferences for perceptual salience persist when they compete with top-down, linguistic information. This study examined the impact of competing perceptual salience on visual word recognition in 17 children with ASD (mean age 31 months) and 17 children with typical development (mean age 20 months) matched on receptive language skills. A word recognition task presented two images on a screen, one of which was named (e.g., Find the bowl !). On Neutral trials, both images had high salience (i.e., were colorful and had geometric patterning). On Competing trials, the distracter image had high salience but the target image had low salience, creating competition between bottom-up (i.e., salience-driven) and top-down (i.e., language-driven) processes. Though both groups of children showed word recognition in an absolute sense, competing perceptual salience significantly decreased attention to the target only in the children with ASD. These findings indicate that perceptual properties of objects can disrupt attention to relevant information in children with ASD, which has implications for supporting their language development. Findings also demonstrate that perceptual salience affects attentional allocation preferences in children with ASD, even in the absence of social stimuli. LAY SUMMARY : This study found that visually striking objects distract young children with autism spectrum disorder (ASD) from looking at relevant (but less striking) objects named by an adult. Language-matched, younger children with typical development were not significantly affected by this visual distraction. Though visual distraction could have cascading negative effects on language development in children with ASD, learning opportunities that build on children’s focus of attention are likely to support positive outcomes.

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19. Wang X, Ding R, Song Y, Wang J, Zhang C, Han S, Han J, Zhang R. Transcutaneous Electrical Acupoint Stimulation in Early Life Changes Synaptic Plasticity and Improves Symptoms in a Valproic Acid-Induced Rat Model of Autism. Neural Plast ;2020 ;2020:8832694.

Autism spectrum disorder (ASD) is a developmental disorder characterized by social behavior deficit in childhood without satisfactory medical intervention. Transcutaneous electrical acupoint stimulation (TEAS) is a noninvasive technique derived from acupuncture and has been shown to have similar therapeutic effects in many diseases. Valproic acid- (VPA-) induced ASD is a known model of ASD in rats. The therapeutic efficacy of TEAS was evaluated in the VPA model of ASD in the present study. The offspring of a VPA-treated rat received TEAS in the early life stage followed by a series of examinations conducted in their adolescence. The results show that following TEAS treatment in early life, the social and cognitive ability in adolescence of the offspring of a VPA rat were significantly improved. In addition, the abnormal pain threshold was significantly corrected. Additional studies demonstrated that the dendritic spine density of the primary sensory cortex was decreased with Golgi staining. Results of the transcriptomic study showed that expression of some transcription factors such as the neurotrophic factor were downregulated in the hypothalamus of the VPA model of ASD. The reduced gene expression was reversed following TEAS. These results suggest that TEAS in the early life stage may mitigate disorders of social and recognition ability and normalize the pain threshold of the ASD rat model. The mechanism involved may be related to improvement of synaptic plasticity.

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20. Wang Z, Ding R, Wang J. The Association between Vitamin D Status and Autism Spectrum Disorder (ASD) : A Systematic Review and Meta-Analysis. Nutrients ;2020 (Dec 29) ;13(1)

The association between vitamin D status and autism spectrum disorder (ASD) is well-investigated but remains to be elucidated. We quantitatively combined relevant studies to estimate whether vitamin D status was related to ASD in this work. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to include eligible studies. A random-effects model was applied to pool overall estimates of vitamin D concentration or odds ratio (OR) for ASD. In total, 34 publications involving 20,580 participants were identified in this present study. Meta-analysis of 24 case-control studies demonstrated that children and adolescents with ASD had significantly lower vitamin D concentration than that of the control group (mean difference (MD) : -7.46 ng/mL, 95% confidence interval (CI) : -10.26 ; -4.66 ng/mL, p < 0.0001, I(2) = 98%). Quantitative integration of 10 case-control studies reporting OR revealed that lower vitamin D was associated with higher risk of ASD (OR : 5.23, 95% CI : 3.13 ; 8.73, p < 0.0001, I(2) = 78.2%). Analysis of 15 case-control studies barring data from previous meta-analysis reached a similar result with that of the meta-analysis of 24 case-control studies (MD : -6.2, 95% CI : -9.62 ; -2.78, p = 0.0004, I(2) = 96.8%), which confirmed the association. Furthermore, meta-analysis of maternal and neonatal vitamin D showed a trend of decreased early-life vitamin D concentration in the ASD group (MD : -3.15, 95% CI : -6.57 ; 0.26, p = 0.07, I(2) = 99%). Meta-analysis of prospective studies suggested that children with reduced maternal or neonatal vitamin D had 54% higher likelihood of developing ASD (OR : 1.54, 95% CI : 1.12 ; 2.10, p = 0.0071, I(2) = 81.2%). These analyses indicated that vitamin D status was related to the risk of ASD. The detection and appropriate intervention of vitamin D deficiency in ASD patients and pregnant and lactating women have clinical and public significance.

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