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This study aimed to review digital interventions in the treatment of autism spectrum disorder (ASD). A systematic review and meta-analysis was conducted. Nineteen studies were included. The interventions aimed to improve social skills (n = 11), developmental skills (n = 2) and 6 other different targets. Technology used were computer programs (n = 14), tablet apps (n = 3), a robot (n = 1) and an interactive DVD (n = 1). The meta-analysis resulted in an overall effect size (Cohen’s d) of 0.32 [0.12–0.51], indicating a small effect. Heterogeneity between studies was high (I 2  = 100%), limiting the generalization of results. Therefore, we recommend larger RCT studies, and guidelines for the development of trials evaluating digital interventions for ASD, for making comparison of future studies possible. Registration can be found online at Prospero: https://www.crd.york.ac.uk/prospero/ , registration no. CRD42020146542.

Oxidative stress has been proposed as being important in the pathophysiology of autism spectrum disorders (ASD), and heightened levels of oxidative stress has found in children with ASD. Our aim was to investigate, whether this change is temporary or persist into adulthood. We included 89 adult patients with ASD and sex and age matched controls. Plasma levels of antioxidants superoxide dismutase 1 (SOD1) and superoxide dismutase 2 (SOD2) and pro-oxidant xanthine oxidase (XO) were measured. Individuals with ASD had higher levels of SOD1, which furthermore correlated with autism severity as measured by autism quotient-score. We found no difference regarding SOD2 and XO between ASD group and controls. However, SOD1 and SOD2 were elevated in males compared to females.

Dysregulation of emotions, behaviour and attention is involved in several areas of childhood psychopathology, but knowledge about early developmental trajectories remains scarce. This study aims to explore continuity and associations of dysregulation in preschool age. Dysregulation was measured at age 2½ years and again at 5 years in a community-based birth cohort of 1099 children using the Child Behavior Checklist, preschool version (CBCL1½–5), answered by mothers. Based on the Dysregulation Profile (CBCL-DP) score, we defined four trajectory groups, using the 75th percentile from the Danish norm material as a cut-off. Associations between the four CBCL-DP trajectory groups and potential covariates, including child, parental and family factors, were analysed using univariate and multiple multinomial logistic regression. Nearly half (54%) of the children showed persistent low scores of CBCL-DP, 17% displayed continuing dysregulation problems, 13% had problems that increased from 2½ years to 5 years, whereas 16% of the children showed reduced problems across preschool age. Persistent dysregulation was associated with maternal postpartum depressive symptoms RRR = 2.20 (95% CI 1.29–3.75), low maternal educational level RRR = 1.69 (95% CI 1.08–2.66), and mothers’ smoking during pregnancy RRR = 2.87 (95% CI 1.09–7.55). Persistent problems of emotional, behavioural and attention regulation in children aged 2½ years to 5 years is influenced by maternal educational level and post-partum depression symptoms. The study draws clinical attention to early symptoms of dysregulation and to the importance of addressing the specific needs of mentally vulnerable parents in intervention planning.

Background Bisphenol A (BPA) is a non-persistent chemical with endocrine disrupting abilities used in a variety of consumer products. Fetal exposure to BPA is of concern due to the elevated sensitivity, which particularly relates to the developing brain. Several epidemiological studies have investigated the association between prenatal BPA exposure and neurodevelopment, but the results have been inconclusive. Objective To assess the association between in utero exposure to BPA and Attention Deficit/Hyperactivity Disorder (ADHD-) symptoms and symptoms of Autism Spectrum Disorder (ASD) in 2 and 5-year old Danish children. Method In the prospective Odense Child Cohort, BPA was measured in urine samples collected in gestational week 28 and adjusted for osmolality. ADHD and ASD symptoms were assessed with the use of the ADHD scale and ASD scale, respectively, derived from the Child Behaviour Checklist preschool version (CBCL/1½-5) at ages 2 and 5 years. Negative binomial and multiple logistic regression analyses were performed to investigate the association between maternal BPA exposure (continuous ln-transformed or divided into tertiles) and the relative differences in ADHD and ASD problem scores and the odds (OR) of an ADHD and autism score above the 75th percentile adjusting for maternal educational level, maternal age, pre-pregnancy BMI, parity and child age at evaluation in 658 mother-child pairs at 2 years of age for ASD-score, and 427 mother-child pairs at 5 years of age for ADHD and ASD-score. Results BPA was detected in 85.3% of maternal urine samples even though the exposure level was low (median 1.2 ng/mL). No associations between maternal BPA exposure and ASD at age 2 years or ADHD at age 5 years were found. Trends of elevated Odds Ratios (ORs) were seen among 5 year old children within the 3rd tertile of BPA exposure with an ASD-score above the 75th percentile (OR = 1.80, 95% CI 0.97,3.32), being stronger for girls (OR = 3.17, 95% CI 1.85,9.28). A dose-response relationship was observed between BPA exposure and ASD-score at 5 years of age (p-trend 0.06) in both boys and girls, but only significant in girls (p-trend 0.03). Conclusion Our findings suggest that prenatal BPA exposure even in low concentrations may increase the risk of ASD symptoms which may predict later social abilities. It is therefore important to follow-up these children at older ages, measure their own BPA exposure, and determine if the observed associations persist.

Autism spectrum disorder encompasses diverse patterns of social communication and repetitive, restricted behaviours. Various interventions have been developed to reduce the negative consequences of this disorder and improve levels of functioning, and recently interest in parent-mediated interventions has increased. Previous reviews and meta-analyses have investigated the effects of the parent-mediated interventions, however; a systematic review with meta-analysis of high quality has not been performed since 2013. This protocol for a systematic review with meta-analysis aims to describe the methods and purpose of synthesising current evidence regarding the effects (both positive and adverse) of parent-mediated interventions in both children with autism and their parents. Electronic searches will be conducted in Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), American Psychological Association PsycInfo (PsycInfo) and Science Citation Index Expanded (SCI-EXPANDED). Randomised clinical trials of parent-mediated interventions for children with autism and control groups of usual care, waiting list or no treatment will be included. Two reviewers will independently screen, select and collect data. Methodological quality of included studies will be evaluated using Cochrane methodology. The primary outcome will be autism symptom severity as measured by the Autism Diagnostic Observation Schedule. Secondary outcomes will be adaptive functioning, adverse effects, child language, child´s quality of life, parental quality of life and parental stress. Meta-analyses and Trial Sequential Analysis will be performed. This is the study protocol for a systematic review and meta-analysis of parent-mediated interventions versus usual care for children with ASD. Results of the review will inform clinicians and parents about the current evidence of the effects, both positive and negative, of parent-mediated interventions on younger children with autism and their parents, through improved methodology and inclusion of new studies. PROSPERO registration number: 385188.

Background Perfluoroalkyl substances (PFAS) are persistent chemicals used in everyday consumer products leading to ubiquitous human exposure. Findings of impaired neurodevelopment after prenatal exposure to PFAS are contradictory and few studies have assessed the impact of postnatal PFAS exposure. Language development is a good early marker of neurodevelopment but only few studies have investigated this outcome separately. We therefore investigated the association between prenatal and early postnatal PFAS exposure and delayed language development in 18 to 36-month-old Danish children. Methods The Odense Child Cohort is a large prospective cohort. From 2010 to 2012 all newly pregnant women residing in the Municipality of Odense, Denmark was invited to participate. Concentration of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) were assessed in maternal serum collected in the 1st trimester of pregnancy and in child serum at 18 months. Parents responded to the Danish adaption of the MacArthur-Bates Communicative Development Inventories (MB-CDI) when their child was between 18 and 36 months. Language scores were converted into sex and age specific percentile scores and dichotomized to represent language scores above or below the 15th percentile. We applied Multiple Imputation by Chained Equation and conducted logistic regressions investigating the association between prenatal and early postnatal PFAS exposure and language development adjusting for maternal age, pre-pregnancy BMI, education and respectively fish intake in pregnancy or childhood and duration of breastfeeding in early postnatal PFAS exposure models. Results We found no significant associations between neither prenatal nor early postnatal PFAS exposure and language development among 999 mother-child pairs. Conclusion In this low-exposed cohort the finding of no association between early postnatal PFAS exposure and language development should be interpreted with caution as we were unable to separate the potential adverse effect of PFAS exposure from the well documented positive effect of breastfeeding on neurodevelopment. We, therefore, recommend assessment of child serum PFAS at an older age as development of the brain proceeds through childhood and even a small impact of PFAS on neurodevelopment would be of public health concern at population level due to the ubiquitous human exposure.

IntroductionSubjects with schizophrenia have a 2–3 fold higher mortality rate than the general population and a reduced life expectancy of 10–20 years. Approximately one-third of this excess mortality has been attributed to obesity-related type 2 diabetes (T2D) and to cardiovascular disease. Glucagon-like peptide-1 (GLP-1) analogues increase satiety and delay gastric emptying, thereby reducing food intake and weight. GLP-1 analogues also exert beneficial effects on cardiovascular outcomes in high-risk patients with T2D.Our aim is to investigate whether 30 weeks add-on treatment with the GLP-1 analogue semaglutide can reduce HbA1c sufficiently to reverse pre-diabetes and the metabolic syndrome in overweight schizophrenic patients.Methods and analysisWe will perform a 30 week, two-armed, multicentre, superiority, double-blinded, randomised trial investigating the effect of weekly injections of semaglutide versus placebo in mental health facilities in Region of Southern Denmark and Region of Zealand, Denmark. In total, 154 adults with schizophrenia spectrum disease, aged 18–60 years treated with second generation antipsychotic treatment, HbA1c 39–47 mmol/mol and body mass index >27 kg/m2 will be randomised to injections of 1.0 mg semaglutide or placebo. The primary outcome is changes in HbA1c. Secondary outcomes encompass metabolic measures, psychotic symptoms and quality of life. Exploratory outcomes encompass insulin sensitivity, cardiovascular risk profile, medication adherence, general well-being and physical activity.Ethics and disseminationThis study will be carried out in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. This research has obtained approval from both the Danish Medicines Agency and The Regional Committees on Health Research Ethics for Southern Denmark.Trial registration numberNCT05193578 European Clinical Trials Database Number (EudraCT) 2020-004374-22, Regional Ethical Committee number S-20200182.

IntroductionNeurodevelopmental disorders, notably attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), present substantial challenges in mental health. Individuals referred for assessment in a psychiatric unit experience complex needs. This implies that their needs necessitate coordination across multiple sectors. Cross-sectoral collaboration models have emerged as essential strategies for addressing the complexities of these disorders. However, evidence of their existence, implementation and success remains limited. This protocol aims to outline a scoping review where we will explore existing collaboration models, evaluate their implementation and gain an understanding of how cross-sectoral collaboration models can be developed to ultimately benefit individuals referred for assessment of ADHD or ASD.Methods and analysisThis proposed scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. A comprehensive search will be conducted across PubMed, CINAHL, Embase, PsycINFO and Google Scholar, as well as grey literature sources, between 1 December 2024 and 1 January 2025. Inclusion criteria will encompass studies focusing on cross-sectoral collaboration for individuals referred for assessment of ADHD or ASD, published in English, Danish, Norwegian or Swedish. The search will use a three-block search string, with iterative refinement guided by familiarity with the evidence base. Data extraction will involve study characteristics and implementation details, using the Consolidated Framework for Implementation Research in combination with Proctor et al’s implementation outcomes framework. Results will be synthesised into descriptive tables, providing a comprehensive mapping of existing models and emphasising implementation feasibility.Ethics and disseminationEthical approval is not required for this protocol since it involves the review of existing literature without the involvement of human participants or personal data. Findings will be disseminated at national and international conferences and will be integrated into future efforts to develop cross-sectoral collaboration models in Denmark.

PurposeSevere mental illness (SMI) may interfere with parental caregiving practices and offspring development. Adhering to preventive well-child visits and maintaining good oral hygiene during early childhood requires parental involvement. Whether these activities are affected by parental SMI is unclear. The purpose of the present study was to determine whether children exposed to parental SMI are at increased risk of non-attendance to preventive well-child visits and vaccinations at age 0–5 years and of child dental caries experience at age 5 years. Furthermore, interactions between maternal psychiatric and sociodemographic variables in relation to an adverse child outcome were assessed.MethodsData were obtained from national Danish health registers. All children born in Denmark between January 1997 and December 2010 were followed from birth until their 6th birthday.Results679,339 children were included in the study (51% male). Of these, 49,059 children (7.8%) had at least one parent with a lifetime SMI diagnosis. Children of parents with SMI had elevated odds of missing well-child visits and vaccinations (OR 1.41; 95% CI 1.39–1.44, p < 0.0001), and of child dental caries (OR 1.58; 95% CI 1.55–1.62, p < 0.0001). In the presence of maternal SMI, low socioeconomic classification and single-mother status added more to the elevated risk than specific maternal diagnosis or timing of last psychiatric contact.ConclusionParents with SMI are less compliant with preventive child healthcare activities than parents without SMI. This indicates a need for practical support to these families in order to prevent inequality in health among their offspring.

Background Despite autism being a lifelong developmental condition affecting approximately 2% of children and young people worldwide, interventions aimed at improving core autism features are sparse. Paediatric Autism Communication Therapy (PACT) is among the first parent-mediated developmental interventions, provided in naturalistic settings, to show promising results in core feature improvement. Methods DAN-PACT is an investigator-initiated, independently funded, multicentre, parallel group superiority, randomised clinical trial, which aims to assess benefits and harms of PACT in 2.0–6.9-year-old children with a recent autism diagnosis, comparing PACT combined with management as usual to management as usual alone. Two hundred eighty autistic children from all regions of Denmark will be included. Primary outcome assessors, data managers, statisticians, and conclusion drawers will be blinded. The primary outcome is magnitude of autism features as measured by the ADOS-2 CSS. The sample size calculation is based on a minimal important difference of 0.66 points, corresponding to a 2–3-point difference in ADOS raw scores. Secondary outcomes are changes in child social communication skills measured with the BOSCC, child adaptive skills measured with the VABS-3, and parents’ assessment of their own and their child’s quality of life. Several exploratory outcomes will be assessed, including adverse events during the trial period. Trial staff will be trained to perform both PACT and enhanced management as usual, assessing manual fidelity of PACT and measuring a broad range of benefits and harms with repeated measures. Discussion DAN-PACT aims to minimise risks of bias, anchor the trial in a naturalistic clinical setting, and extend the scope of outcome measures used in previous PACT studies, achieved by blinding raters to all observational outcomes, including a large sample of young autistic children, and using an enhanced management as usual control sample. Trial limitations are the risk of missing data and the inability to blind parent participants to their group allocation and their rating of several secondary and exploratory outcomes. In addition, there is no consensus on the magnitude of the minimal important difference on ADOS-2 CSS or BOSCC, which are therefore estimated pragmatically. Trial registration ClinicalTrials.gov NCT05673096. Registered on December 22, 2022.