1. Bharat R, Uzaina, Yadav T, Niranjan S, Kurade P. mHealth Apps Delivering Early Intervention to Support Parents of Children With Autism Spectrum Disorder: A Scoping Review. Indian Pediatr;2023 (Feb 20)

CONTEXT: Early intervention, and parent-mediated intervention are effective in achieving early childhood development goals for children with autism spectrum disorder. There is a surge in mHealth technologies delivering such interventions. This review aims to explore the concept, context and methodology of implementation of such mHealth apps. EVIDENCE ACQUISITION: A search was conducted using NICE (National Institute of Clinical Excellence) healthcare database, including keyword ‘early intervention,’ ‘mHealth,’ ‘parent support,’ ‘apps,’ and ‘autism.’ The quantitative, qualitative, mixed-methods, case reports, grey literature, systematic reviews, clinical trials, and feasibility studies of children between 2 to 6 years with ASD were included from inception of database to December, 2021. Web/Internet-based or computer-dependent programs were excluded. The initial search yielded 3786 studies; 17 were finally included based on the inclusion and exclusion criteria. RESULTS: Studies on a total of 17 mhealth apps were reviewed. Nine apps, apart from TOBY (Therapy outcome by you), lacked a holistic approach and instead targeted a specific difficulty in autism. The provision of support to parents using apps was equally beneficial as in-person support, reduced costs, and improved outcomes in children. CONCLUSIONS: The review revealed limited evidence-based mHealth apps available currently in a community setting. This also underscores an opportunity for clinicians to re-direct parents towards evidence-based information and interventions.

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2. Bhat RS, Alonazi M, Al-Daihan S, El-Ansary A. Prenatal SSRI Exposure Increases the Risk of Autism in Rodents via Aggravated Oxidative Stress and Neurochemical Changes in the Brain. Metabolites;2023 (Feb 20);13(2)

The mechanisms underlying selective serotonin reuptake inhibitor (SSRI) use during pregnancy as a major autism risk factor are unclear. Here, brain neurochemical changes following fluoxetine exposure and in an autism model were compared to determine the effects on autism risk. The study was performed on neonatal male western albino rats which were divided into Groups one (control), two (propionic acid [PPA]-induced autism model), and three (prenatal SSRI-exposed newborn rats whose mothers were exposed to 5 mg/kg of fluoxetine over gestation days 10-20). SSRI (fluoxetine) induced significant neurochemical abnormalities in the rat brain by increasing lipid peroxide (MDA), Interferon-gamma (IFN-γ), and caspase-3 levels and by depleting Glutathione (GSH), Glutathione S-transferases (GST), Catalase, potassium (K+), and Creatine kinase (CK) levels, similarly to what has been discovered in the PPA model of autism when compared with control. Prenatal fluoxetine exposure plays a significant role in asset brain damage in newborns; further investigation of fluoxetine as an autism risk factor is thus warranted.

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3. Hirschmann S, Magnezi R, Bassan H, Tal O. Group versus individual occupational therapy for toddlers with autism as a means to improve access to public health-care services. Randomised controlled pilot study. Aust Occup Ther J;2023 (Feb 20)

INTRODUCTION: In recent years, the increasing prevalence of autism-spectrum disorder has resulted in an increased demand for therapies including occupational therapy. In this pilot trial, we aimed to compare the efficacy of group versus individual occupational therapy among toddlers with autism as a means to improve accessibility to care. METHODS: Toddlers (2-4 years) undergoing autism evaluation in our public child developmental centre were recruited and randomised to receive 12 weekly sessions of group or individual occupational therapy based on the same mode of intervention: Developmental, Individual-Differences and Relationship-based (DIR). Primary outcomes related to intervention implementation included waiting days, nonattendance, intervention period, number of sessions attended and therapist satisfaction. Secondary outcomes were the Adaptive Behaviour Assessment System questionnaire, the Paediatric Quality of Life Inventory and the Peabody Developmental Motor Scale (PDMS-2). RESULTS: Twenty toddlers with autism were included, 10 in each occupational therapy mode of intervention. Children waited fewer days before beginning group occupational therapy compared to individual therapy (52.4 ± 28.1 vs. 108.8 ± 48.0 days p < 0.01). Mean numbers of nonattendance was similar for both interventions (3.2 ± 2.82 vs. 2 ± 1.76, p > 0.05). Worker satisfaction scores were similar at the beginning and end of the study (6.1 ± 0.4 vs. 6.07 ± 0.49, p > 0.05). There were no significant differences between the percentage changes in individual and group therapy outcomes for adaptive score (6.0 ± 16.0 vs. 4.5 ± 17.9, p > 0.05), quality of life (1.3 ± 20.9 vs. 18.8 ± 24.5, p > 0.05) and fine motor skills (13.7 ± 36.1 vs. 15.1 ± 41.5, p > 0.05). CONCLUSIONS: In this pilot study, the group DIR-based occupational therapy for toddlers with autism improved access to services and allowed earlier interventions, with no clinical inferiority to individual therapy. Further research is required to examine group clinical therapy benefit.

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4. İsvan N, Bonardi A, Hiersteiner D. Effects of person-centred planning and practices on the health and well-being of adults with intellectual and developmental disabilities: a multilevel analysis of linked administrative and survey data. J Intellect Disabil Res;2023 (Feb 20)

BACKGROUND: A person-centred service planning and practice approach (PCP) is one that is driven by service users’ individual preferences, needs and priorities. The approach has been identified as a best practice and is codified in US policies that encourage and, in some contexts, require state systems of home and community-based services to adopt and demonstrate person-centred practice. However, there is insufficient research on PCP’s direct impact on outcomes for service users. This study aims to contribute to the evidence base in this area by investigating the association between service experiences and outcomes of adults with intellectual and developmental disabilities (IDD) receiving state-funded services. METHODS: The data for the study come from the 2018-2019 National Core Indicators® In-Person Survey that links survey responses with administrative records for a sample of 22 000 adults with IDD receiving services from 37 state developmental disabilities (DD) systems. Associations among service experiences and outcomes of survey participants are examined through multilevel regression techniques that include participant-level responses and state-level measures of PCP. The state-level measures are constructed by combining administrative records describing participants’ service plans with the priorities and goals they expressed in response to the survey. RESULTS: Case managers’ (CM) accessibility and attentiveness to individual preferences, as reported by survey participants, are significantly associated with self-reported outcomes such as perceived control over life decisions and sense of health and well-being. Controlling for participants’ experiences with their CMs, their reports of the person-centred content of their service plans have net positive associations with outcomes. After accounting for experiences with the service system as reported by participants, the state system’s person-centred orientation, measured by the extent to which service plans across the state reflect participants’ wishes for improving their social connections, remains a significant predictor of participants’ sense of control over their daily lives. CONCLUSIONS: This study contributes to the evidence base supporting PCP as a service model by identifying pathways that link person-centred service planning and delivery and person-centred orientation of state systems to positive outcomes reported by adults with IDD and by demonstrating the value of linking survey and administrative data. The key implication of the findings for policy and practice is that an overall person-centred orientation of state DD systems as well as PCP training for people who support planning for and delivery of direct supports will substantially improve the lives of adults with IDD.

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5. Knafl GJ. An analysis of birth defects and developmental disabilities for children of participants of the Air Force Health Study. Reprod Toxicol;2023 (Feb 20);117:108355.

Analyses were conducted of the occurrence of eight general categories of birth defects and developmental disabilities for children fathered by participants of the Air Force Heath Study (AFHS). Participants were male Air Force veterans of the Vietnam War. Children were categorized into conceived before and after the start of the participant’s Vietnam War service. Analyses accounted for correlation between outcomes for multiple children fathered by each of the participants. For each of the eight general categories of birth defects and developmental disabilities, the probability of its occurrence increased substantially for children conceived after compared to before the start of Vietnam War service. These results support the conclusion of an adverse effect on reproductive outcomes due to Vietnam War service. Data for children conceived after the start of Vietnam War service for participants with measured dioxin values were used to estimate dose-response curves for the effect of dioxin exposure on the occurrence of each of the eight general categories of birth defects and developmental disabilities. These curves were assumed to be constant up to a threshold and then monotonic after that threshold. For seven of the eight general categories of birth defects and developmental disabilities, the estimated dose-response curves increased nonlinearly after associated thresholds. These results support the conclusion that the adverse effect to conception after the start of Vietnam War service may be attributable to high enough exposures to dioxin, a toxic contaminant of Agent Orange used for herbicide spraying in the Vietnam War.

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6. Lipkin PH. Screening Success in the Age of Autism. JAMA Pediatr;2023 (Feb 20)

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7. Liu TL, Chen YL, Hsiao RC, Ni HC, Liang SH, Lin CF, Chan HL, Hsieh YH, Wang LJ, Lee MJ, Chou WJ, Yen CF. Adolescent-Caregiver Agreement Regarding the School Bullying and Cyberbullying Involvement Experiences of Adolescents with Autism Spectrum Disorder. Int J Environ Res Public Health;2023 (Feb 20);20(4)

School bullying and cyberbullying victimization and perpetration are prevalent in adolescents with autism spectrum disorder (AASD). However, the levels of adolescent-caregiver agreement regarding the bullying involvement of AASD and the factors associated with these levels remain to be evaluated. In the present study, we evaluated the levels of adolescent-caregiver agreement on the school bullying and cyberbullying involvement experiences of AASD and the factors associated with the levels of agreement. This study included 219 dyads of AASD and their caregivers. The school bullying and cyberbullying involvement experiences of the participating AASD were assessed using the School Bullying Experience Questionnaire and the Cyberbullying Experiences Questionnaire, respectively. Attention-deficit/hyperactivity disorder, oppositional defiant disorder (ODD), depressive and anxiety symptoms, and autistic social impairment were also assessed. AASD and their caregivers had poor to fair levels of agreement regarding the school bullying and cyberbullying victimization and perpetration experiences of AASD. Severe inattention, hyperactivity-impulsivity, ODD, depressive and anxiety symptoms, and autistic social impairment were associated with high levels of adolescent-caregiver agreement. When assessing the bullying involvement experiences of AASD, mental health professionals should obtain information from multiple sources. In addition, the factors influencing the levels of agreement should be considered.

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8. Mitchell ME, Cook LC, Shiers S, Tavares-Ferreira D, Akopian AN, Dussor G, Price TJ. Characterization of Fragile X Mental Retardation Protein expression in human nociceptors and their axonal projections to the spinal dorsal horn. J Comp Neurol;2023 (Feb 20)

Fragile X Mental Retardation Protein (FMRP) regulates activity-dependent RNA localization and local translation to modulate synaptic plasticity throughout the central nervous system. Mutations in the FMR1 gene that hinder or ablate FMRP function cause Fragile X Syndrome (FXS), a disorder associated with sensory processing dysfunction. FXS premutations are associated with increased FMRP expression and neurological impairments including sex dimorphic presentations of chronic pain. In mice, FMRP ablation causes dysregulated dorsal root ganglion (DRG) neuron excitability and synaptic vesicle exocytosis, spinal circuit activity, and decreased translation-dependent nociceptive sensitization. Activity-dependent, local translation is a key mechanism for enhancing primary nociceptor excitability that promotes pain in animals and humans. These works indicate that FMRP likely regulates nociception and pain at the level of the primary nociceptor or spinal cord. Therefore, we sought to better understand FMRP expression in the human DRG and spinal cord using immunostaining in organ donor tissues. We find that FMRP is highly expressed in DRG and spinal neuron subsets with substantia gelatinosa exhibiting the most abundant immunoreactivity in spinal synaptic fields. Here, it is expressed in nociceptor axons. FMRP puncta colocalized with Nav1.7 and TRPV1 receptor signals suggesting a pool of axoplasmic FMRP localizes to plasma membrane-associated loci in these branches. Interestingly, FMRP puncta exhibited notable colocalization with calcitonin gene-related peptide (CGRP) immunoreactivity selectively in female spinal cord. Our results support a regulatory role for FMRP in human nociceptor axons of the dorsal horn and implicate it in the sex dimorphic actions of CGRP signaling in nociceptive sensitization and chronic pain.

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9. Montgomery A, Masi A, Whitehouse A, Veenstra-VanderWeele J, Shuffrey L, Shen MD, Karlov L, Uljarevic M, Alvares G, Woolfenden S, Silove N, Eapen V. Identification of subgroups of children in the Australian Autism Biobank using latent class analysis. Child Adolesc Psychiatry Ment Health;2023 (Feb 20);17(1):27.

BACKGROUND: The identification of reproducible subtypes within autistic populations is a priority research area in the context of neurodevelopment, to pave the way for identification of biomarkers and targeted treatment recommendations. Few previous studies have considered medical comorbidity alongside behavioural, cognitive, and psychiatric data in subgrouping analyses. This study sought to determine whether differing behavioural, cognitive, medical, and psychiatric profiles could be used to distinguish subgroups of children on the autism spectrum in the Australian Autism Biobank (AAB). METHODS: Latent profile analysis was used to identify subgroups of children on the autism spectrum within the AAB (n = 1151), utilising data on social communication profiles and restricted, repetitive, and stereotyped behaviours (RRBs), in addition to their cognitive, medical, and psychiatric profiles. RESULTS: Our study identified four subgroups of children on the autism spectrum with differing profiles of autism traits and associated comorbidities. Two subgroups had more severe clinical and cognitive phenotype, suggesting higher support needs. For the ‘Higher Support Needs with Prominent Language and Cognitive Challenges’ subgroup, social communication, language and cognitive challenges were prominent, with prominent sensory seeking behaviours. The ‘Higher Support Needs with Prominent Medical and Psychiatric and Comorbidity’ subgroup had the highest mean scores of challenges relating to social communication and RRBs, with the highest probability of medical and psychiatric comorbidity, and cognitive scores similar to the overall group mean. Individuals within the ‘Moderate Support Needs with Emotional Challenges’ subgroup, had moderate mean scores of core traits of autism, and the highest probability of depression and/or suicidality. A fourth subgroup contained individuals with fewer challenges across domains (the ‘Fewer Support Needs Group’). LIMITATIONS: Data utilised to identify subgroups within this study was cross-sectional as longitudinal data was not available. CONCLUSIONS: Our findings support the holistic appraisal of support needs for children on the autism spectrum, with assessment of the impact of co-occurring medical and psychiatric conditions in addition to core autism traits, adaptive functioning, and cognitive functioning. Replication of our analysis in other cohorts of children on the autism spectrum is warranted, to assess whether the subgroup structure we identified is applicable in a broader context beyond our specific dataset.

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10. Niessen J, Lopez Marmol A, Ismail R, Schiele JT, Rau K, Wahl A, Sauer K, Heinzerling O, Breitkreutz J, Koziolek M. Application of biorelevant in vitro assays for the assessment and optimization of ASD-based formulations for pediatric patients. Eur J Pharm Biopharm;2023 (Feb 20)

Amorphous solid dispersions (ASD) have been a successful formulation strategy to overcome the poor aqueous solubility of many novel drugs, but the development of pediatric formulations presents a special challenge due to variable gastrointestinal conditions in children. It was the aim of this work to design and apply a staged biopharmaceutical test protocol for the in vitro assessment of ASD-based pediatric formulations. Ritonavir was used as a model drug with poor aqueous solubility. Based on the commercial ASD powder formulation, a mini-tablet and a conventional tablet formulation were prepared. Drug release from the three formulations was studied in different biorelevant in vitro assays (i.e. MicroDiss, two-stage, transfer model, tiny-TIM) to consider different aspects of human GI physiology. Data from the two-stage and transfer model tests indicated that by controlled disintegration and dissolution excessive primary precipitation can be prevented. However, this advantage of the mini-tablet and tablet formulation did not translate into better performance in tiny-TIM. Here, the in vitro bioaccessibility was comparable for all three formulations. In the future, the staged biopharmaceutical action plan established herein will support the development of ASD-based pediatric formulations by improving the mechanistic understanding so that formulations are developed for which drug release is robust against variable physiological conditions.

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11. Pignataro A, Krashia P, De Introna M, Nobili A, Sabetta A, Stabile F, La Barbera L, D’Addario SL, Ventura R, Cecconi F, D’Amelio M, Ammassari-Teule M. Chemogenetic rectification of the inhibitory tone onto hippocampal neurons reverts autistic-like traits and normalizes local expression of estrogen receptors in the Ambra1+/- mouse model of female autism. Transl Psychiatry;2023 (Feb 20);13(1):63.

Female, but not male, mice with haploinsufficiency for the proautophagic Ambra1 gene show an autistic-like phenotype associated with hippocampal circuits dysfunctions which include loss of parvalbuminergic interneurons (PV-IN), decrease in the inhibition/excitation ratio, and abundance of immature dendritic spines on CA1 pyramidal neurons. Given the paucity of data relating to female autism, we exploit the Ambra1(+/-) female model to investigate whether rectifying the inhibitory input onto hippocampal principal neurons (PN) rescues their ASD-like phenotype at both the systems and circuits level. Moreover, being the autistic phenotype exclusively observed in the female mice, we control the effect of the mutation and treatment on hippocampal expression of estrogen receptors (ER). Here we show that excitatory DREADDs injected in PV_Cre Ambra1(+/-) females augment the inhibitory input onto CA1 principal neurons (PN), rescue their social and attentional impairments, and normalize dendritic spine abnormalities and ER expression in the hippocampus. By providing the first evidence that hippocampal excitability jointly controls autistic-like traits and ER in a model of female autism, our findings identify an autophagy deficiency-related mechanism of hippocampal neural and hormonal dysregulation which opens novel perspectives for treatments specifically designed for autistic females.

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12. Randazzo M, Prato A, Messina M, Meli C, Casabona A, Rizzo R, Barone R. Neuroactive Amino Acid Profile in Autism Spectrum Disorder: Results from a Clinical Sample. Children (Basel);2023 (Feb 20);10(2)

Biological bases of autism spectrum disorder (ASD) include both genetic and epigenetic causes. Patients with ASD show anomalies in the profile of certain plasma amino acids, including neuroactive amino acids. Monitoring plasma amino acids may be relevant for patient care and interventions. We evaluated the plasma amino acid profile in samples extracted from dry blood spots by electrospray ionization-tandem mass spectrometry. Fourteen amino acids and eleven amino acid ratios were examined in patients with ASD and intellectual disability (ID), and neurotypical control subjects (TD). The amino acid profile in the ASD group showed reduced levels of ornithine (p = 0.008), phenylalanine (p = 0.042) and tyrosine (p = 0.013). The statistically significant amino acid ratios were Leu+Val/Phe+Tyr (p = 0.002), Tyr/Leu (p = 0.007) and Val/Phe (p = 0.028), such differences remaining significant only in the comparison between ASD and TD. Finally, a positive correlation emerged between the score of the restricted and repetitive behavior on ADOS-2 and the citrulline levels in the ASD group (p = 0.0047). To conclude, patients with ASD may show a distinguishable metabolic profile useful for studying their metabolic pathways in order to develop screening tests and targeted therapies.

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13. Sturrock A, Foy K, Freed J, Adams C, Leadbitter K. The impact of subtle language and communication difficulties on the daily lives of autistic children without intellectual disability: Parent perspectives. Int J Lang Commun Disord;2023 (Feb 20)

BACKGROUND: Autistic children without intellectual disability will likely experience higher level language and communication difficulties. These may appear subtle, in that they are not immediately evident to those who do not know the child well and may not manifest in all environments. Because of this, the impact of such difficulties may be underestimated. This phenomenon has similarly attracted little research attention, meaning the extent to which subtle language and communication difficulties contribute to the needs of autistic individuals without intellectual disability may be underspecified in clinical services. AIMS: To offer a detailed exploration of how relatively subtle language and communication difficulties impact on autistic children without intellectual disability and what strategies parents recognize can mediate those negative effects. METHODS & PROCEDURES: Twelve parents of autistic children from the target group (aged 8-14 years, attending mainstream school) were interviewed about how subtle language and communication difficulties impact their autistic child. Rich accounts were derived then analysed using thematic analysis. Eight of the children discussed had previously been interviewed independently in a parallel study. Comparisons are discussed in this paper. OUTCOMES & RESULTS: Parents reported heterogeneous but pervasive higher level language and communication difficulties which universally impacted key areas of the children’s function: peer relationships, developing independence and performance in education. Communication difficulties were also universally associated with negative emotional responses, social withdrawal and/or negative self-perceptions. While parents identified a range of ad hoc strategies and naturally occurring opportunities that improved outcomes, there was little mention of the means to address primary language and communication difficulties. The current study showed a number of parallels with child accounts, demonstrating the benefits of collecting data from both sources in clinical and research investigations. However, parents were more concerned about longer term implications of language and communication difficulties and highlighted their impact on the child developing functional independence. CONCLUSIONS & IMPLICATIONS: Subtle language and communication difficulties, typically identified in this higher ability autistic group, can impact significantly on key areas of childhood function. Support strategies seem to be parent generated and inconsistently applied across individuals, without the benefit of coherent specialist services. Dedicated provision and resources targeting areas of functional need may be beneficial to the group. In addition, the commonly reported association between subtle language and communication difficulties and emotional well-being indicates the need for greater exploration using empirical methods, and joined-up clinical working between speech and language therapy and mental health services. WHAT THIS PAPER ADDS: What is already known on the subject There is now a wide understanding of how language and communication difficulties can impact the individual. However, where those difficulties are relatively subtle, for example, in children without intellectual disability and where difficulties are not immediately evident, less is known. Research has often speculated on how identified differences in higher level structural language and pragmatic difficulties might impact on the function of autistic children. However, to date dedicated exploration of this phenomenon is limited. The current author group explored first-hand accounts of children. Corroborative evidence from parents of the same children would add further weight to understanding this phenomenon. What this paper adds to the existing knowledge This study provides a detailed exploration of parents’ perspective relating to the impact of language and communication difficulties on autistic children without intellectual disability. It provides corroborative detail that support child accounts of the same phenomenon, indicating the impact on peer relationships, school outcomes and emotional well-being. Parents also report functional concerns around the child’s ability to develop independence and this paper demonstrates how parents and children might deviate in their accounts, with parents reporting increased concerns around the longer term implications of early language and communication difficulties. What are the potential or actual clinical implications of this work? Relatively subtle language and communication difficulties can have a significant impact on the lives of autistic children without intellectual disability. Greater service provision for this group is therefore indicated. Interventions could focus on areas of functional concern where language is implicated, for example, peer relationships, developing independence and school success. Additionally, the relationship between language and emotional well-being points to further integration between speech and language therapy and mental health services. Differences found between parental and child reports highlight the need to collect data from both parties during clinical investigations. Parental strategies may offer benefits for the wider population.

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14. Thongkorn S, Kanlayaprasit S, Kasitipradit K, Lertpeerapan P, Panjabud P, Hu VW, Jindatip D, Sarachana T. Investigation of autism-related transcription factors underlying sex differences in the effects of bisphenol A on transcriptome profiles and synaptogenesis in the offspring hippocampus. Biol Sex Differ;2023 (Feb 20);14(1):8.

BACKGROUND: Bisphenol A (BPA) has been linked to susceptibility to autism spectrum disorder (ASD). Our recent studies have shown that prenatal BPA exposure disrupted ASD-related gene expression in the hippocampus, neurological functions, and behaviors associated with ASD in a sex-specific pattern. However, the molecular mechanisms underlying the effects of BPA are still unclear. METHODS: Transcriptome data mining and molecular docking analyses were performed to identify ASD-related transcription factors (TFs) and their target genes underlying the sex-specific effects of prenatal BPA exposure. Gene ontology analysis was conducted to predict biological functions associated with these genes. The expression levels of ASD-related TFs and targets in the hippocampus of rat pups prenatally exposed to BPA were measured using qRT-PCR analysis. The role of the androgen receptor (AR) in BPA-mediated regulation of ASD candidate genes was investigated using a human neuronal cell line stably transfected with AR-expression or control plasmid. Synaptogenesis, which is a function associated with genes transcriptionally regulated by ASD-related TFs, was assessed using primary hippocampal neurons isolated from male and female rat pups prenatally exposed to BPA. RESULTS: We found that there was a sex difference in ASD-related TFs underlying the effects of prenatal BPA exposure on the transcriptome profiles of the offspring hippocampus. In addition to the known BPA targets AR and ESR1, BPA could directly interact with novel targets (i.e., KDM5B, SMAD4, and TCF7L2). The targets of these TFs were also associated with ASD. Prenatal BPA exposure disrupted the expression of ASD-related TFs and targets in the offspring hippocampus in a sex-dependent manner. Moreover, AR was involved in the BPA-mediated dysregulation of AUTS2, KMT2C, and SMARCC2. Prenatal BPA exposure altered synaptogenesis by increasing synaptic protein levels in males but not in females, but the number of excitatory synapses was increased in female primary neurons only. CONCLUSIONS: Our findings suggest that AR and other ASD-related TFs are involved in sex differences in the effects of prenatal BPA exposure on transcriptome profiles and synaptogenesis in the offspring hippocampus. These TFs may play an essential role in an increased ASD susceptibility associated with endocrine-disrupting chemicals, particularly BPA, and the male bias of ASD.

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15. Wieckowski AT, Williams LN, Rando J, Lyall K, Robins DL. Sensitivity and Specificity of the Modified Checklist for Autism in Toddlers (Original and Revised): A Systematic Review and Meta-analysis. JAMA Pediatr;2023 (Feb 20)

IMPORTANCE: The Modified Checklist for Autism in Toddlers (M-CHAT) and the M-CHAT, Revised With Follow-up (M-CHAT-R/F)-henceforth referred to as M-CHAT(-R/F)-are the most commonly used toddler screeners for autism spectrum disorder (ASD). Their use often differs from that in the original validation studies, resulting in a range of estimates of sensitivity and specificity. Also, given the variability in reports of the clinical utility of the M-CHAT(-R/F), researchers and practitioners lack guidance to inform autism screening protocols. OBJECTIVE: To synthesize variability in sensitivity and specificity of M-CHAT(-R/F) across multiple factors, including procedures for identifying missed cases, likelihood level, screening age, and single compared with repeated screenings. DATA SOURCES: A literature search was conducted with PubMed, Web of Science, and Scopus to identify studies published between January 1, 2001, and August 31, 2022. STUDY SELECTION: Articles were included if the studies used the M-CHAT(-R/F) (ie, original or revised version) to identify new ASD cases, were published in English-language peer-reviewed journals, included at least 10 ASD cases, reported procedures for false-negative case identification, screened children by 48 months, and included information (or had information provided by authors when contacted) needed to conduct the meta-analysis. DATA EXTRACTION AND SYNTHESIS: The systematic review and meta-analysis was conducted within the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The Quality Assessment of Diagnostic Accuracy Studies-2 tool evaluated bias in sample selection. Data extraction and quality assessment were performed by 2 authors independently. The overall diagnostic accuracy of the M-CHAT(-R/F) was assessed with the hierarchic summary receiver operating characteristic (HSROC) model. MAIN OUTCOMES AND MEASURES: Sensitivity, specificity, diagnostic odds ratios, and HSROC curves of M-CHAT(-R/F). RESULTS: The review included 50 studies with 51 samples. The pooled sensitivity of M-CHAT(-R/F) was 0.83 (95% CI, 0.77-0.88), and the pooled specificity was 0.94 (95% CI, 0.89-0.97). Heterogeneity analyses revealed greater diagnostic accuracy for low- vs high-likelihood samples, a concurrent vs prospective case confirmation strategy, a large vs small sample size, use of M-CHAT(-R/F) Follow-up, and non-English vs English only. CONCLUSIONS AND RELEVANCE: Overall, results of this study suggest the utility of the M-CHAT(-R/F) as an ASD screener. The wide variability in psychometric properties of M-CHAT(-R/F) highlights differences in screener use that should be considered in research and practice.

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16. Wu SH, Li X, Qin DD, Zhang LH, Cheng TL, Chen ZF, Nie BB, Ren XF, Wu J, Wang WC, Hu YZ, Gu YL, Lv LB, Yin Y, Hu XT, Qiu ZL. Corrigendum to « Induction of core symptoms of autism spectrum disorders by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys » [Sci. Bull. 66(9) (2021) 937-946. Sci Bull (Beijing);2023 (Feb 20)

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