Changes in mothers' and fathers' stress level, mental health and coping strategies during the 3 years following ASD diagnosis.

BACKGROUND: ASD in a child affects parental mental health, with elevated levels of stress, anxiety and depression reported in parents. METHOD: In this study, we examined mothers' and fathers' stress, anxiety and depression, as well as their coping strategies in a sample of 103 children and adolescents enrolled in the ELENA cohort study in France at diagnosis and three years after diagnosis. RESULTS: Results showed that mothers had higher levels of stress and anxiety / depression than fathers and used more social support coping strategies at diagnosis, which might be explained by increased levels of parental involvement. Mothers' stress level significantly decreased during the three years following ASD diagnosis but no such decrease was observed in fathers' stress level. A significant decrease in anxiety and depression was observed for both parents, suggesting that parental distress is particularly elevated during the critical diagnosis period. Results finally yielded a significant decrease in emotion-focused coping strategy in mothers over the three-year period, an ineffective strategy that takes places at the time of diagnosis but then decreases during the period following ASD diagnosis, in relation to the acceptance process. CONCLUSIONS: Implications in terms of addressing the unmet mental health needs of parents and their coping strategies are discussed.

Predictors of an earlier diagnosis of Autism Spectrum Disorder in children and adolescents: a systematic review (1987-2017).

Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder in which the first signs generally emerge at approximately 12 months of age but its diagnosis is feasible only from the age of 18 months. According to the literature, the average age of diagnosis ranges from 2.7 to 7.2 years, which raises the question of factors associated with early diagnosis as a condition for early intervention. In this systematic review, we aim to identify clinical, social, and environmental factors associated with the age at which the diagnosis of ASD is confirmed in children. A literature search was performed in the Pubmed, Web of Sciences, PsycInfo, and Cochrane databases. Among the 530 publications identified, 50 were selected according to the inclusion criteria. This review focuses on studies conducted in 21 countries using data collected over a period from 1987 to 2017. These studies were published before December 31st, 2019. The results suggest that the diagnosis of ASD occurs earlier if there is a delay in social communication or the presence of intellectual disability. There is a low level of evidence concerning associations between the age at diagnosis and sex, race, parental education, or socioeconomic status and accessibility to health care. Further studies using large and well-characterized data sets are needed to simultaneously explore clinical and socio-environmental factors involved in early diagnosis.

Screen time and associated risks in children and adolescents with autism spectrum disorders during a discrete COVID-19 lockdown period.

Background: The COVID-19 pandemic may affect the screen time of children and adolescents with Autism Spectrum Disorders (ASD). This study aimed to examine the screen time of children and adolescents with ASD during a discrete lockdown period in France and identify risk factors for excessive screen time. Methods: The study sample consisted of 249 ASD subjects, 3-17 years of age, enrolled in the ELENA cohort. Information about the screen time was collected using the COVID-19 questionnaire specially created for this study. The clinical, socio-demographic and familial characteristics were collected from the last ELENA follow-up visit. Results: More than one third of subjects exceeded recommended levels of screen time and almost half of parents reported that their child spent more time using screen since COVID-19 pandemic beginning. Excessive screen time was significantly related to age with higher screen time in adolescents. Risk factors for excessive screen time were high withdrawn behaviors and low socioeconomic status for children, and older age and male gender for adolescents. Conclusion: These results imply to adapt the recommendations already formulated in general population concerning the good use of screens in youth with ASD. Specific recommendations and suitable guidance are needed to help children and adolescents with ASD and their parents implement the more optimal use of screen time activities for educational, therapeutic and social goals. Trial registration number: NCT02625116.

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.

Anxiety and depression in parents of children with autism spectrum disorder during the first COVID-19 lockdown: Report from the ELENA cohort.

BACKGROUND: The Covid-19 pandemic had a strong impact on mental health in the general population. This study conducted during the first lockdown in France considered parents of children with Autism Spectrum Disorder (ASD) prospectively followed in the ELENA Cohort. OBJECTIVES: We aimed to (1) compare the Anxiety and Depression (AaD) levels during the lockdown between mothers and fathers, (2) compare the parent's AaD between the lockdown and the last ELENA follow-up visit, and (3) identify risk factors for parental AaD during lockdown among socio-demographic and children's clinical characteristics. METHODS: The Hospital Anxiety and Depression Scale (HADS) was used to assess AaD in 134 parent's pairs. Parents also completed the Questionnaire about their living conditions during COVID-19, their child's interventions and perceived changes about their child's behaviors and sleep. Child's ASD severity, intellectual and socio-adaptive skills and parent's socio-demographic characteristics were collected from ELENA follow-up. RESULTS: The parents' AaD levels were lower during the lockdown compared to the last ELENA visit that coincided in 96% with the child's ASD diagnosis. The AaD levels were more pronounced in mothers and significantly associated with the child's challenging behaviors, parents' teleworking and perceived knowledge about COVID-19. The perception of an insufficient knowledge was the only risk factor for mothers' AaD. CONCLUSION: Our findings highlighted the pertinence for an assessment of the mental health of main caregivers of children with ASD, consideration of their gender characteristics, and the importance of providing relevant information during pandemic. Future studies examining the pandemic long-term effects are needed. TRIAL REGISTRATION NUMBER: NCT02625116.

Association between residential proximity to agricultural crops and adaptive behaviors in children with autism spectrum disorder from the French ELENA cohort.

Influences of pesticide exposures on the clinical expression of children with ASD not known. The aim of this study was to analyze the associations between early residential proximity to agricultural crops, proxy of exposure to pesticides, and adaptive behaviors in children with ASD. Children with ASD were recruited within the Etude Longitudinale de l'Enfant avec Autisme (ELENA) French cohort. Adaptive behaviors were assessed with the second edition of the Vineland Adaptive Behavior Scales (VABS-II). Baseline subscores in communication, daily living skills and socialization were considered. Residential exposure to agricultural crops was estimated by crops acreage within a 1000m radius around homes. We ran multiple linear regression models to investigate the associations between exposures to agricultural crops during the pregnancy (n = 183), the first two years of life (n = 193) and adaptive behaviors in children with ASD. The mean (SD) age of children at the inclusion in the ELENA cohort was 6.1 (3.5) years, 39% of them presented an intellectual disability (ID). The mean communication score was 73.0 (15.8). On average, the crop acreage covered 29(27)% of the acreage formed by the 1000m radius around homes. Each increase of 20% in the crop acreage was associated with a significant decrease in communication score of the VABS-II in children without ID for the pregnancy (ß = -2.21, 95%CI: 4.16 to -0.27) and the first two years of life (ß = -1.90, 95%CI: 3.68 to -0.11) periods. No association was found in children with ID. This study opens perspectives for future works to better understand ASD phenotypes.

Impact of containment and mitigation measures on children and youth with ASD during the COVID-19 pandemic: Report from the ELENA cohort.

BACKGROUND: Containment, involving separation and restriction of movement of people due to the COVID-19 pandemic, and mitigation, also referred to as lockdown, involving closure of schools, universities and public venues, has had a profound impact on people's lives globally. The study focuses on the effects of containment and mitigation measures, on the behavior of children and youth (CaY) with Autism Spectrum Disorders (ASD). The study primary aim was to examine the impact of these urgent measures on the behaviors, communication, sleep, and nutritional status of the CaY. A secondary aim was to explore risk and protective factors on behavior change including sociodemographic variables, living conditions, ASD symptom severity and continuity of interventions. METHODS: The study sample consisted of 239 ASD subjects, 2-21 years of age, enrolled in the ELENA cohort in France at Stage 3 confinement and mitigation measures announced on March 16, 2020. A parent informant completed the COVID-19 questionnaire. RESULTS: Of the domains examined, challenging behaviors, communicative skills and sleep had the greatest impact; in terms of risk and protective factors, subject age, ASD severity, single parenthood, daily living skills, and intervention continuity were most likely to impact behaviors; living conditions were not linked to behavior change. CONCLUSIONS: The findings highlight the topography of behavioral change in CaY with ASD following institution of containment and mitigation measures during the COVID-19 pandemic and help identify risk and protective factors to help better address needs and tailor interventions in the future.

Comorbidity Burden in Adults With Autism Spectrum Disorders and Intellectual Disabilities-A Report From the EFAAR (Frailty Assessment in Ageing Adults With Autism Spectrum and Intellectual Disabilities) Study.

Background: Autism spectrum disorder (ASD) is an early-onset and lifelong neurodevelopmental condition frequently associated with intellectual disability (ID). Although emerging studies suggest that ASD is associated with premature ageing and various medical comorbidities, as described for ID, data are scarce. Objectives: To determine the comorbidity burden and its association with distinct clinical presentation in terms of ASD severity, adaptive skills, level of autonomy, and drug exposure in a well-phenotyped sample of individuals with ASD-ID-the EFAAR (Frailty Assessment in Ageing Adults with Autism Spectrum and Intellectual Disabilities) cohort. Methods: A total of 63 adults with ASD-ID, with a mean age of 42.9 ± 15.1 years, were recruited from 2015 to 2017 from nine specialized institutions. They underwent detailed clinical examinations, including screening for comorbidities, ASD severity [Childhood Autism Rating Scale (CARS)], adaptive functioning [Vineland Adaptive Behavior Scale II (VABS-II)], autonomy [activities of daily living (ADLs)], and drug use [polypharmacy and the Drug Burden Index (DBI)]. The comorbidity burden was evaluated using the Cumulative Illness Rating Scale (CIRS-G) and its sub-scores [the severity index (CIRS-SI) and severe comorbidity (CIRS-SC)]. Results: We found a large range of comorbidities, including gastrointestinal disorders and mental and neurological diseases. Overall, 25% of our ASD-ID sample had chronic kidney disease with the associated increased cardiovascular risk factors. The comorbidity burden was high (mean CIRS-G total score of 10.6 ± 4.8), comparable with that observed among patients older than those in our population hospitalized in geriatric departments. Furthermore, the comorbidity burden positively correlated with age, decreased autonomy, and polypharmacy. Conclusion: The severity of the comorbidity burden associated with premature ageing in adults with ASD and ID highlight their crucial need of personalized medical care.

Investigating the natural history and prognostic factors of ASD in children: the multicEntric Longitudinal study of childrEN with ASD - the ELENA study protocol.

INTRODUCTION: There is global concern about the increasing prevalence of autism spectrum disorders (ASDs), which are early-onset and long-lasting disorders. Although ASDs are considered to comprise a unique syndrome, their clinical presentation and outcome vary widely. Large-scale and long-term cohort studies of well-phenotyped samples are needed to better understand the course of ASDs and their determinants. The primary objective of the multicEntric Longitudinal study of childrEN with ASD (ELENA) study is to understand the natural history of ASD in children and identify the risk and prognostic factors that affect their health and development. METHODS AND ANALYSIS: This is a multicentric, longitudinal, prospective, observational cohort in which 1000 children with ASD diagnosed between 2 and 16 years of age will be recruited by 2020 and followed over 6 years. The baseline follow-up starts with the clinical examination to establish the ASD diagnosis. A battery of clinical tools consisting of the Autism Diagnostic Observation Schedule, the revised version of the Autism Diagnostic Interview, measures of intellectual functioning, as well as large-scale behavioural and developmental measurements will allow us to study the heterogeneity of the clinical presentation of ASD subtypes. Subsequent follow-up at 18 months and at 3, 4.5 and 6 years after the baseline examination will allow us to explore the developmental trajectories and variables associated with the severity of ASD. In addition to the children's clinical and developmental examinations, parents are invited to complete self-reported questionnaires concerning perinatal and early postnatal history, congenital anomalies, genetic factors, lifestyle factors, medical and psychiatric comorbidities, and the socioeconomic environment. As of 1 November 2018, a total of 766 participants have been included. ETHICS AND DISSEMINATION: Ethical approval was obtained through the Marseille Mediterranean Ethics Committee (ID RCB: 2014-A01423-44), France. We aim to disseminate the findings through national and international conferences, international peer-reviewed journals, and social media. TRIAL REGISTRATION NUMBER: NCT02625116; Pre-results.

Novel interpretation of molecular diagnosis of congenital toxoplasmosis according to gestational age at the time of maternal infection.

From a prospective cohort of 344 women who seroconverted for toxoplasmosis during pregnancy, 344 amniotic fluid, 264 placenta, and 216 cord blood samples were tested for diagnosis of congenital toxoplasmosis using the same PCR assay. The sensitivity and negative predictive value of the PCR assay using amniotic fluid were 86.3% and 97.2%, respectively, and both specificity and positive predictive value were 100%. Using placenta and cord blood, sensitivities were 79.5% and 21.2%, and specificities were 92% and 100%, respectively. In addition, the calculation of pretest and posttest probabilities and the use of logistic regression allowed us to obtain curves that give a dynamic interpretation of the risk of congenital toxoplasmosis according to gestational age at maternal infection, as represented by the three sample types (amniotic fluid, placenta, and cord blood). Two examples are cited here: for a maternal infection at 25 weeks of amenorrhea, a negative result of prenatal diagnosis allowed estimation of the probability of congenital toxoplasmosis at 5% instead of an a priori (pretest) risk estimate of 33%. For an infection at 10 weeks of amenorrhea associated with a pretest congenital toxoplasmosis risk of 7%, a positive PCR result using placenta at birth yields a risk increase to 43%, while a negative result damps down the risk to 0.02%. Thus, with a molecular diagnosis performing at a high level, and in spite of the persistence of false negatives, posttest risk curves using both negative and positive results prove highly informative, allowing a better assessment of the actual risk of congenital toxoplasmosis and finally an improved decision guide to treatment.

Specific activity of class II histone deacetylases in human breast cancer cells.

Although numerous studies have underlined the role of histone deacetylases (HDAC) in breast physiology and tumorigenesis, little is known on the particular contribution of the various classes of HDACs in these processes. Using estrogen receptor-alpha (ERalpha)-positive MCF-7 breast cancer cells, the effects of MC1575 and MC1568, two novel class II-specific HDAC inhibitors, were analyzed on cell proliferation, apoptosis, and estrogen signaling. The specificity of these HDAC inhibitors was validated by measuring histone and alpha-tubulin acetylation and by the specific in vitro inhibition of recombinant HDAC4 using histone and nonhistone substrates, contrasting with the lack of inhibition of class I HDACs. In addition, MC1575 did not inhibit class I HDAC gene expression, thus confirming the specific targeting of class II enzymes. Similar to trichostatin A (TSA), MC1575 displayed a dose-dependent antiproliferative effect and induced cell cycle arrest although this blockade occurred at a different level than TSA. Moreover, and in contrast to TSA, MC1575 had no effect on MCF-7 cells apoptosis. Interestingly, MC1575 was able to increase p21(waf1/CIP1) mRNA levels but did not regulate the expression of other genes such as cyclin D1, p27, p14(ARF), Bcl2, Baxalpha, Trail-R1, and Trail-R2. Finally, MC1575 strongly induced ERbeta gene expression but did not decrease ERalpha expression, nor did it switch hydroxytamoxifen to an agonist activity. Altogether, these data suggest that the class II HDAC subfamily may exert specific roles in breast cancer progression and estrogen dependence.