A 1-Day Training Course to Disseminate the BREF Psychoeducational Program to Caregivers and Promote Network Establishment between Psychiatry Departments and Family Associations.

OBJECTIVE: Although international guidelines state that psychoeducation to caregivers should be provided systematically, it remains insufficiently available in psychiatry. This study reports the development and evaluation of an original training course aimed to provide participants with the knowledge and skills to implement "BREF," a psychoeducational program for caregivers. METHODS: The BREF program training course, a free, 1-day course incorporating peer role-play was developed. In addition to psychiatrists, nurses, and psychologists, caregivers were involved as preceptors. Participants were mental health professionals and volunteer caregivers. Participants to the first 28 sessions of the course (n=467) completed a post-course questionnaire (n=341) and a cross-sectional questionnaire (n=56). Quantitative data on satisfaction, learning, and behavior changes following the course were collected equating to levels 1, 2, and 3 of Kirkpatrick's model. RESULTS: After the course, high levels of satisfaction and commitment were observed with 100% of responders recommending the course and 81% intending to implement the BREF program. Confidence mean score to implement BREF was 7.9/10 (±1.4) with no significant effect of course session. At cross-sectional evaluation, 73% of responders reported improvements in skills related to providing psychoeducation to caregivers, 64% stated that the BREF program was implemented/under implementation, and 66% stated that their department had connected with a family association. CONCLUSIONS: Training course sessions alone can increase psychoeducational programs for caregivers and network establishment. The BREF program training course demonstrates a high level of participant satisfaction and is a promising method to disseminate psychoeducation to caregivers, thus addressing a major shortage in mental health organization.

Perceptions of parents of the impact of autism spectrum disorder on their quality of life and correlates: comparison between mothers and fathers.

PURPOSE: To compare mothers and fathers perceptions of the impact of autism spectrum disorder on their Quality of Life (QoL), we used the Parental-Developmental Disorders-Quality of Life scale (Par-DD-QoL). METHOD: The perception of QoL of mothers and fathers was compared for 130 pairs of parents of children with ASD and the associated variables were investigated. RESULTS: Mothers perceived a significantly greater impact of ASD on their QoL than fathers. Parents perceived a higher impact of ASD on global QoL when their child's adaptive skills were low and when the level of aberrant behaviors was high. More precisely, the perception of QoL by the mothers was negatively associated with their child's internalized disorders, whereas the perception of QoL by the fathers was negatively associated with their child's externalized disorders. Neither the mothers' nor the fathers' perception of the impact on QoL was associated with their children's age or the severity of their autistic symptoms. Some parental factors, such as being members of a family association, having benefited from training in ASD and having experienced a disruption in professional activity were associated with a greater impact on their QoL. CONCLUSION: Our finding that the perceived impact of ASD on QoL differed between mothers and fathers argues for individualized psychosocial support. Moreover, the strong correlation between the child's clinical characteristics and the perception by parents of a higher impact of ASD on QoL should be seen as red flag concerning the needs of the parents in terms of social and educational support. TRIAL REGISTRATION NUMBER: NCT02625116 (October 2015).

Neural correlates of interoceptive accuracy: Beyond cardioception.

Interoceptive accuracy (IAc), the precision with which one assesses the signals arising from one's own body, is receiving increasing attention in the literature. IAc has mainly been approached as an individual trait and has been investigated through the cardiac modality using mostly non-ecological methods. Such studies consensually designate the anterior insular cortex as the main brain correlate of IAc. However, there is a lack of brain imaging studies investigating IAc in a broader and more ecological way. Here, we used a novel ecological task in which participants monitored their general bodily reactions to external events and investigated brain regions subtending intraindividual (i.e. trial-by-trial) variations of IAc. At each trial, participants had to rate the intensity of their bodily reactions to an emotional picture. We recorded participants' skin conductance response (SCR) to the picture as an indicator of actual physiological response intensity. We fitted a functional magnetic resonance imaging (fMRI) model using, as regressors, the SCR value, the rating and the product of the two (as a proxy of participants' IAc) obtained trial per trial. We observed that activity in the dorsomedial prefrontal cortex (dmPFC) increased when individuals' IAc decreased. This result reveals general mechanism of error processing in intraindividual variations of IAc, which are unspecific to interoception. Our result has a practical impact in the clinical domain. Namely, it supports the predictive coding framework whereby IAc deficits may reflect impairments in processing a mismatch between actual interoceptive signals and predictions.

Is there a dysbiosis in individuals with a neurodevelopmental disorder compared to controls over the course of development? A systematic review.

Many scientific papers reported that an unbalanced gut microbiota could lead to or worsen neurodevelopmental disorders (NDD). A dysbiosis may then be observed in the course of development and mark a dysfunction within what is called the gut-brain axis. The aim of this systematic review is to investigate potential evidence of dysbiosis in children and young adults with NDD compared to controls. Using the PRISMA guidelines we systematically reviewed studies that compared the gut microbiota in NDD participants (with an age inferior to thirty) to the gut microbiota of controls, regardless of the data analysis methods used. The MEDLINE, Scopus and PsycINFO databases were searched up to September 2018. 31 studies with a total sample size of 3002 ASD (Autism Spectrum Disorder) and 84 ADHD (Attention Deficit Hyperactivity Disorder) participants were included in this systematic review. Independent data extraction and quality assessment were conducted. The quality of the studies was rated from low to high. Population characterization and experimental methods were highly heterogeneous in terms of the data available, selection of criteria, and dysbiosis measurement. A dysbiosis was reported in 28 studies in terms of either diversity, bacterial composition or metabolome dysfunction. Due to heterogeneity, a quantitative synthesis was not applicable. In this paper, we discuss the different biases to understand the complexity of microbiota and neurodevelopmental disorders to provide leads for future cohort studies looking to answer the questions raised by the trillions of microorganisms that inhabit key body niches.

Detection of Morphological Abnormalities in Schizophrenia: An Important Step to Identify Associated Genetic Disorders or Etiologic Subtypes.

Current research suggests that alterations in neurodevelopmental processes, involving gene X environment interactions during key stages of brain development (prenatal period and adolescence), are a major risk for schizophrenia. First, epidemiological studies supporting a genetic contribution to schizophrenia are presented in this article, including family, twin, and adoption studies. Then, an extensive literature review on genetic disorders associated with schizophrenia is reviewed. These epidemiological findings and clinical observations led researchers to conduct studies on genetic associations in schizophrenia, and more specifically on genomics (CNV: copy-number variant, and SNP: single nucleotide polymorphism). The main structural (CNV) and sequence (SNP) variants found in individuals with schizophrenia are reported here. Evidence of genetic contributions to schizophrenia and current knowledge on genetic syndromes associated with this psychiatric disorder highlight the importance of a clinical genetic examination to detect minor physical anomalies in individuals with ultra-high risk of schizophrenia. Several dysmorphic features have been described in schizophrenia, especially in early onset schizophrenia, and can be viewed as neurodevelopmental markers of vulnerability. Early detection of individuals with neurodevelopmental abnormalities is a fundamental issue to develop prevention and diagnostic strategies, therapeutic intervention and follow-up, and to ascertain better the underlying mechanisms involved in the pathophysiology of schizophrenia.

Oxytocin Fails to Recruit Serotonergic Neurotransmission in the Autistic Brain.

Oxytocin (OT), a neuropeptide involved in affiliation has been shown to enhance social skills in patients with autism spectrum disorders (ASD). Nevertheless, OT improvements seem ephemeral. Animal research has demonstrated OT action on serotonin (5-HT), an interaction that we also found in the healthy human brain. Whether such synaptic interplay also occurs in ASD patients is unknown. To address this issue, we mapped the effects of intranasal OT on 5-HT in 18 patients with ASD and 24 healthy controls (HC) in a double blind, placebo controlled, within subject PET-scan experiment. Each participant underwent two scans: baseline and spray (OT or placebo). Using the radiotracer [18 F]MPPF, marking the 5-HT 1A receptor (5-HT1AR), we measured MPPF-Binding Potential (BP) as an index of OT-induced serotonin functional modulation. At baseline ASD patients did not differ from controls for 5-HT1AR concentration and distribution. However, while OT significantly increased MPPF BP in several brain regions of HC, no changes were observed in the ASD group. Serotonin serum concentration analysis corroborated these results. Our findings suggest a disturbed OT-serotonin interaction in autism. This may limit the potential benefits of OT in these patients and open the ways to investigate combined OT-serotonin treatments.

Using ESDM 12 hours per week in children with autism spectrum disorder: feasibility and results of an observational study.

BACKGROUND: Early intervention for Autism Spectrum Disorder (ASD) in France is heterogeneous and poorly evaluated to date. Early Start Denver Model (ESDM) is a developmental and behavioral model of intervention for toddlers with ASD which has already shown very interesting outcomes on the development of children with ASD in various studies with different settings. However, it is not possible with the current research to agree on the best setting. Thus, we implemented an ESDM program according to our context where children are often pre-schooling early from 30 months old. This therapy was applied by a multidisciplinary team working in close collaboration with parents and other partners. SUBJECTS AND METHODS: A prospective observational study including 19 toddlers with ASD was conducted. We evaluated improvement on the cognitive level of toddlers with ASD receiving therapist-delivered ESDM intervention for 12 hours per week. RESULTS: Significant improvements in verbal and nonverbal cognitive skills at the Mullen Scale of Early Learning were obtained after 10 months of intervention in our sample. The largest improvement was in receptive language development quotient with a mean improvement of 19.6 points. We also observed promising outcomes in daily adaptive behavior, with a slight improvement in communication at the Vineland Adaptive Behavioral Scale. These outcomes, when compared to the conclusions of previous studies, are leading us to the need for a therapy duration beyond 10 months. CONCLUSIONS: Our outcomes were very encouraging even with low cognitive and nonverbal children. These outcomes may be confirmed in a multicenter randomized controlled trial that is ongoing.

News in early intervention in autism.

BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental trouble which prevents the child from socio-communicative interaction, and learning from his environment. Non-medical early intervention attempts to improve prognosis. We will review the main current hypothesis, intervention models and scientific supports about early intervention. METHODS: We conducted a search of the literature published on Medline between 2010 and 2015 related to intervention models provided to children with ASD aged less than 3 years. Data were extracted from systematic reviews and recent randomized controlled trials with moderate to high GRADE quality of evidence. RESULTS: Early intervention refers to brain plasticity theory. With the epidemiological studies of infant "at risk" there is an attempt to intervene earlier before full syndrome is present. Interventions tend to follow more on a developmental hierarchy of socio-communicative skills and to focus on the dyadic relation between the child and the caregivers to improve the core autistic symptoms. Over the last 6 years, there's been news and fine-tuned ways about early intervention, and more and more systematic evaluation. CONCLUSION: However, there are only few interventions which were evaluated in trial with a strong GRADE recommendation and all of them have methodological concerns. It is important to be cautious in recommendations for mental health politic, even if it is important to improve access to services for all children and their families, hence finance and design rigorous project in research.

The Child "after": between maternal Depression and Transmission of the traumatism.

Born a little time after the death of his sister, our patient, Antoine, 13 years old, was suffering from severe obsessional compulsive disorders, which needed care in the hospital and adapted treatment. We tried to know if what we were led to observe by this adolescent could be explained by works and thoughts around the notion of substitute child. Building our thought on various theoretical approaches, including neurosciences, we tried to think the psychopathological signs of this patient by two ways. One is about the birth and the growth in the presence of depressed parents, and this since the pregnancy. The other one is about the necessity to deal with the traumatic story of the family, met by the parents, who are still facing it, that leads to the question of the transmission of the traumatism from the mother to the baby. Using the notion of maternal primary care, we proposed the term 'the child after', which appeared to us more able to represent the dynamic and the place really given to these children. This term could mean the question of an undone grief, a traumatism without temporality, and a relation between the mother and the child which seems to be uncertain because of the investment of the child as an impossible reparation of an unscarred loss.

NMDA antagonist agents for the treatment of symptoms in autism spectrum disorder: a systematic review and meta-analysis.

Aims: This systematic review and meta-analysis aimed to assess the efficacy of NMDA antagonists in ASD (Autism Spectrum Disorder) on the core (communication and social interaction, repetitive behavior) and associated symptoms (irritability) of ASD, as well as their safety. Methods: PubMed, CENTRAL, CINHAL, EMBASE, and PsycINFO databases were searched until November 2023. Two authors independently selected the studies and extracted data. Randomized controlled trials assessing the efficacy of NMDA receptor antagonists in participants with ASD aged <18 years were included. The quality of the studies was assessed using the Risk of Bias-2 tool. A random-effect meta-analysis model was used to calculate standardized mean differences (SMD) or odds ratios (OR) using meta package in R. Results: This systematic review included ten studies (588 participants). Most studies did not report scales assessing core symptoms of ASD. Meta-analysis of efficacy on ASD core symptoms included three studies (248 participants). NMDA antagonists were not superior to placebo [SMD = 0.29; CI 95% (-1,94; 1.35); I2 = 0%]. NMDA antagonists was not superior to placebo concerning response (four studies, 189 participants) [OR = 2.4; CI 95% (0.69; 8.38); I2 = 35%]. Meta-analysis of efficacy on irritability included three studies (186 participants); NMDA antagonists were not superior to placebo [MD irritability = -1.94; CI 95% (-4.66; 0.77); I2 = 0%]. Compared with placebo, significantly more participants in the NMDA antagonist group reported at least one adverse event (five studies, 310 participants) [OR = 2.04; CI 95% (1.17; 3.57); I2 = 0%]. Conclusion: Current evidence does not support the effectiveness of NMDA antagonists in the treatment of ASD symptoms or irritability. Further research is needed due to the limited and low quality data available. Systematic Review Registration: PROSPERO CRD42018110399.

Parent and professional perspectives on implementing the Pediatric Autism Communication Therapy: A mixed-methods analysis.

LAY ABSTRACT: Factors influencing the implementation of parent-mediated intervention are insufficiently studied. This study examines for the first-time factors of implementation into clinical practice across the world of Pediatric Autism Communication Therapy, an internationally disseminated, evidence-based, parent-mediated therapy. From both the parents' and the professionals' perspectives, parents attitudes (e.g. self-reflection abilities and videotaping management) and life-circumstances (e.g. stressed families condition and time) were central factors. In this type of therapy, the target is a child's development; still, this improvement is dependent on the parent's behavior when interacting with their child. What's more, Pediatric Autism Communication Therapy method (video reflection, empowerment of parent, play-based) was enabler according to most of the parents. And more, most professionals report factors linked to the Implementation Process that is planning, execution, reflection and assessment in implementation of a new therapy. Indeed, the professionals underlined barriers related to the population seen in practice, flexibility of schedule, support from colleagues and manager. All these factors could be improved and addressed with a formal implementation plan including factors related to the parents of each country.

Clinical predictors of psychotropic medication prescription in children with ASD of the ELENA cohort.

Psychotropic drugs are often used to treat behavior problems in ASD with some evidence supporting efficacity (e.g.: risperidone and irritability) but also significant side effects at the short and longer-term. It is then essential to know better the factors associated with the prescription of these medications and potentially implement early behavioral and psychosocial intervention or cognitive remediation before to use medication. We designed a case-control study based on the population of the ELENA cohort to assess the factors associated with early psychotropic drugs use in children with ASD. Externalized behavior symptoms (measured by the Child Behavior Checklist) is the leading risk factor during the first years of follow-up (aOR = 2.8; CI [1.04; 7.67]; p = 0.04). Age, gender, autism severity, adaptive behaviors, or internalized behaviors were not associated with psychotropic medication prescription. Low IQ and parents who had received training tended to increase the risk of psychotropic medication prescription during follow-up but were not statistically significant. These findings underscore the need for early identification of symptoms of externalizing behaviour, early appropriate information for parents about treatment with and without medication, early analysis of externalising behaviour and targeted treatments.

Parental experience of parent-mediated intervention for children with ASD: A systematic review and qualitative evidence synthesis.

LAY ABSTRACT: The effectiveness of parent-mediated interventions in the field of autism spectrum disorder is well documented but information on the experience of parents involved in parent-mediated interventions is limited.This study is the first synthesis of evidence concerning the experience of parents involved in parent-mediated interventions. It synthesizes the voice of 345 parents across the world into four general themes: barriers to implementation and logistical issues, feeling overwhelmed and stressed (a need for support), facilitators of implementation, and empowerment in the parent and improvement in the child.The findings of our study provide evidence that parent-mediated interventions should be adapted to the needs of each family. Specific care and support should be offered to parents in addition to parent-mediated interventions. Our study, however, highlights which outcomes are important to parents and should be considered in future studies.

Dyadic coping and coparenting among couples after their child's recent autism diagnosis.

LAY ABSTRACT: We investigated how couples support each other after their child's autism diagnosis and whether this affects the way they work together to raise their child. We recruited 70 couples raising a child on the autism spectrum. Both partners were asked to complete the same questionnaires measuring how they perceived the experience of having a child on the autism spectrum, how they used their relationship to support each other during stressful situations, how competent they felt completing their parenting tasks, and the coparenting relationship to explore how they worked together as a team when parenting their child. Parents participated in the study 1-36 months after their child's autism diagnosis. We used statistical techniques that allowed us to see the impact mothers and fathers had on each other. Overall, parents who felt more competent and supported by their partner worked better as a team to raise their child on the spectrum. Fathers invested in the coparenting relationship more when mothers felt more supported by fathers. Mothers invested in the coparenting relationship more when fathers felt more competent parenting their child. Further research is needed to better understand how we can support couples as their child gets older.

Factors associated with age of diagnosis in children with autism spectrum disorders: Report from a French cohort.

LAY ABSTRACT: Autism spectrum disorder is an early onset neurodevelopmental disorder and diagnosis can be made as early as 18 months of age. Early diagnosis of autism spectrum disorder is critical as it leads to early intervention. Age of autism spectrum disorder diagnosis has been linked to the child profile as autism spectrum disorder is characterized by strong heterogeneity, but is also influenced by socio-economic factors. There is paucity of data on age of diagnosis of autism spectrum disorder in France. We therefore examined the age of autism spectrum disorder diagnosis in 554 children and adolescents enrolled in the ELENA cohort study with respect to the influences of child profile, family antecedents, and socio-economic factors. The mean age of diagnosis was 4.9 years (±2.8 years). Early diagnosis, before 3 years of age, was related to the co-occurrence of intellectual disability, higher autism spectrum disorder symptom severity, and lower communicative abilities. Children in low socio-economic status families tended to have an earlier diagnosis, but these children also had greater degree of intellectual impairment compared to children in high socio-economic status families. The age of autism spectrum disorder diagnosis was not associated with the presence of an older sibling with autism spectrum disorder. The observed current trend of an inverse relationship between socio-economic status and age of diagnosis of autism spectrum disorder suggests equitable access to autism spectrum disorder services in France where health coverage is universal and free. Better screening of more subtle/less severe forms of autism spectrum disorder is needed, as well as further assessment of the link between the co-occurrence of autism spectrum disorder and intellectual impairment in children in lower socio-economic status families.

Diagnostic Process for Autism Spectrum Disorder: A Meta-Analysis of Worldwide Clinical Practice Guidelines for the Initial Somatic Assessment.

(1) Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is highly associated with various somatic conditions that can be masked by the core symptoms of ASD and thus complicate the diagnosis. Identifying co-occurring somatic disorders is critical for providing effective healthcare and social services for ASD populations and influences their long-term outcomes. A systematic assessment of co-occurring somatic conditions is essential during this ASD diagnostic process. Therefore, this study aimed to identify the organization and content of the initial somatic assessment (ISA). (2) Methods: We conducted a systematic review of the clinical practice guidelines (CPG) for the ASD diagnostic process published between January 2005 and December 2019 in English and French and performed an appraisal following the Appraisal of Guidelines Research and Evaluation, second edition (AGREE-II). (3) Results: We selected 14 CPGs that were heterogeneous in quality, with methodological scores between 32.3 and 91.9. Clinical examinations are the first step in the ISA, and the participation of pediatric, neuropediatric, and genetic specialists was highly recommended by the majority of the CPGs. The recommendations included hearing screening tests (10/14), visual examinations (8/14), and systematic genetic investigations (4/14). The CPGs also described additional investigations that should be conducted based on numerous warning signs. (4) Conclusions: Screening for consensual international warning signs is necessary to perform a comprehensive and systematic ISA during the ASD diagnostic process. A "referral form" could be used to guide clinicians and improve the coordination process. This tool may reinforce epidemiological data on co-occurring somatic disorders in patients with ASD.

Predictors of cognitive, behavioural and academic difficulties in NF1.

The impact of the Neurofibromatosis type 1 (NF1) on cognition have been subject to much clinical investigation, but environmental modifiers of disease expression have not yet been systematically investigated. The aim of this paper is to determine the role of demographic and environmental factors such as age, sex, socioeconomic status, parental NF1 status and neurological complications on the cognitive, behavioural and academic outcomes in NF1. Participants included 206 children aged 4-18 years seen within the Manchester clinical research NF1 service. Multiple linear regression models were used to study the effect of the hypothesized predictor variables on cognitive, behavioural and academic outcomes. Relative to population norms, 80% of the NF1 sample demonstrated significantly lower scores in at least one cognitive, behavioural or academic domains. Family history of NF1 and lower SES were independently associated with poorer cognitive, behavioural and academic outcomes. Neurological problems such as epilepsy and hydrocephalus were associated with lower IQ and academic skills. Cognitive and behavioural phenotypes emerge commonly via a complex interplay between genes and environmental factors, and this is true also of a monogenic condition such as NF1. Early interventions and remedial education may be targeted to risk groups such those with familial NF1, families with lower SES and those with associated neurological comorbidities.

Association of Attention-Deficit/Hyperactivity Disorder in Childhood and Adolescence With the Risk of Subsequent Psychotic Disorder: A Systematic Review and Meta-analysis.

Importance: Growing evidence supports an association between attention-deficit/hyperactivity disorder (ADHD) in childhood and subsequent psychotic disorders. Both disorders share physiopathological features such as attention deficits, dopaminergic imbalance, and genetic susceptibility. However, the results of epidemiologic studies have been conflicting. Objective: To provide a quantitative synthesis of studies exploring the association between ADHD and the risk of subsequent psychotic disorder. Data Sources: A systematic literature search of the MEDLINE, Scopus, PsycInfo, and Web of Science databases was performed from inception until the final analysis on July 7, 2020. No restriction of language was applied. Study Selection: Cohort and case-control studies examining the relative risk of developing a psychotic disorder in people diagnosed with ADHD at younger than 18 years compared with control individuals without ADHD. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed in reporting results. Two independent reviewers extracted the data and assessed the risk of bias of individual studies using the Newcastle-Ottawa Scale. Preferably adjusted odds ratios (aORs) or hazard ratios from the identified studies were extracted, and ORs were computed when they were not adjusted. A random-effects model was used to calculate the pooled relative effect using the meta package in R. Main Outcomes and Measures: An association between ADHD (exposure) and psychotic disorder (outcomes); both diagnoses were based on international classification. Results: A total of 15 studies were included in the review. Twelve studies were pooled in the meta-analysis, representing 1.85 million participants. A diagnosis of ADHD in childhood was associated with a significant increase in the risk of subsequent psychotic disorder, with a pooled relative effect of 4.74 (95% CI, 4.11-5.46; I2 = 43% [95% CI, 0%-70%]). No significant between-group differences were found for subgroup analyses according to psychotic disorder (odds ratio [OR], 5.04; 95% CI, 4.36-5.83) or schizophrenia (OR, 4.59; 95% CI, 3.83-5.50) outcomes, cohort (OR, 4.64; 95% CI, 4.04-5.34) or case-control (OR, 6.81; 95% CI, 4.21-11.03) study design, and adjusted (OR, 4.72; 95% CI, 4.11-5.46) or unadjusted (OR, 3.81; 95% CI, 1.39-10.49) estimates. Meta-regressions were not significant when sex and bias score were used as covariates. No evidence of publication bias was found. Conclusions and Relevance: These findings suggest that childhood ADHD is associated with an increased risk of a subsequent psychotic disorder. Further studies are required to determine the mechanisms linking these common conditions and whether early intervention for ADHD might reduce the risk of subsequent psychotic disorder.

Association between prenatal and perinatal factors and the severity of clinical presentation of children with ASD: Report from the ELENA COHORT.

Many studies have suggested that prenatal and perinatal factors increase the risk for autism spectrum disorder (ASD). However, few reports have addressed the question of their influence on the severity of the clinical presentation of children with ASD. Our objective was to determine the prenatal and perinatal factors that are associated with the severity of autistic symptoms and intellectual and adaptive functioning deficits. Data were collected from a subset of 169 children with a confirmed diagnosis of ASD, recruited from the ELENA cohort. A risk of premature delivery was associated, with an increased risk for severe autistic symptoms and placental pathologies and birth complications were associated with an increased risk of communication adaptive deficits, in multivariate analysis. Our results highlight the importance of systematic screening for these pre/perinatal factors, especially in mothers at risk of having a child with ASD.

Efficacy of parent-mediated communication-focused treatment in toddlers with autism (PACT) delivered via videoconferencing: a randomised controlled trial study protocol.

INTRODUCTION: Intervention in the preschool period is currently recommended for autism spectrum disorder. Therapies delivered by parents are particularly suitable for young children. Preschool Autism Communication Trial (PACT) is a parent-mediated therapy that has shown a significant and sustained impact on autism symptom reduction. However, access to such evidence-based therapies for families is limited due to autism centres located in large urban areas. Using videoconferencing to deliver PACT training to parents may improve accessibility for families living in underserved areas. METHODS AND ANALYSIS: This single-blind randomised controlled trial, involving six sites in France, will investigate the efficacy of a telehealth, videoconferencing-based, parent-mediated PACT therapy on autism symptoms, over a 12-month period. It will compare PACT plus treatment as usual (TAU) against TAU only in a cohort of 238 toddlers (119 per group) aged 18-36 months at inclusion and living with their families more than 40 min away from the specialist centres for autism. Primary outcome will include change of overall autism score on the Autism Diagnostic Observation Scale (ADOS) at 12 months. Secondary outcomes will measure change in child skills, child functioning, impact on parents (stress, health, priorities) and implementation characteristics. Repeated measures analyses will be used to test the effect of PACT intervention on the overall ADOS module 1 score over the 12-month study period. Linear mixed models will be used with time, treatment allocation and the interaction between treatment and time as fixed effects and individual variation as random effect. ETHICS AND DISSEMINATION: This protocol (V.5, date: 25 October 2019) is approved by the French National Review Board (reference no 2018-A02516-49). The results will be disseminated via peer-reviewed journals TRIAL REGISTRATION NUMBER: NCT04244721.