Atopic Dermatitis: Disease Background and Risk Factors.

Multiple risk factors have been associated with the development of atopic dermatitis (AD). Recent advances in understanding the role of genetics in this disease have been made, with discovery of the filaggrin (FLG) gene as the most notable so far. In addition to FLG gene mutations as a risk factor for AD, a positive family history of atopic or allergic disease in either parent has been shown to confer a greater risk of developing AD. Atopic dermatitis usually presents early in life and is thought to represent the initial step in the "atopic march," which is characterized by the development of other atopic diseases later in life such as asthma, allergic rhinitis, and/or rhinoconjunctivitis, food allergies, and hay fever. Other comorbid diseases that have been associated with AD include increase risk of viral and bacterial skin infections, neuropsychiatric diseases such as attention-deficit hyperactivity disorders (ADHD), and autistic spectrum disorder (ASD). Patients with AD have also been found to have worse sleep quality overall compared to patients without AD. In this chapter, we will discuss the risk factors associated with development of atopic dermatitis as well as the most commonly reported comorbidities in patients with this disease.

[Tooth decay and autism spectrum disorders in children: is there a connection?] / Karies zubov i rasstroistva autisticheskogo spektra u detei: est' li svyaz'?

OBJECTIVE: The study of caries lesions of children 7 and 12 years old with different degrees of severity of autism and concomitant intellectual disabilities, in comparison with a control group of neurotypical patients of similar age. MATERIALS AND METHODS: The main study group included children with ASD ages 7 and 12 (n=214), and the comparison group included neurotypical children of the same age (n=140). To assess the incidence of dental caries, indicators of the prevalence and intensity of the process were used. RESULTS: The prevalence of dental caries in children with ASD is lower than in the comparison group or comparable. The average caries prevalence was found in the 7- and 12-year-old groups in children with mild autism without concomitant intellectual deficits (80.89±3.40 and 76.65±4.24, respectively). In children with severe and extremely severe autism, regardless of the presence of intellectual disability, the prevalence of dental caries was high in both age groups, which is comparable with the same indicator and age of neurotypical children. Moreover, both age groups of neurotypical children were also comparable in caries prevalence (89.67±1.65 and 90.32±1.20 respectively). Caries intensity did not seem to be related to years of autistic disorder (significantly lower in the group of 12-year-old children with ASD, compared to 7-year-olds). Caries intensity in children with ASD increased with increasing severity of autism and concomitant intellectual disability. CONCLUSION: Further comprehensive studies in terms of included variables are needed to identify contributing factors (impact of family socioeconomic opportunities, increased parental care, etc.).

Trajectory of depressive symptoms over adolescence in autistic and neurotypical youth.

BACKGROUND: Adolescence coincides with a dramatic rise in the onset of psychiatric conditions including depression. Depression symptoms may be particularly prevalent and impairing for youth with autism spectrum disorder (ASD). While prior research suggests adolescence is associated with worsening depression symptoms for typically developing (TD) and autistic youth, it is unclear if they follow a similar course. METHOD: The study examined the trajectory of depressive symptoms in autistic and neurotypical youth over a 4-year longitudinal study using linear and logistic mixed effects models. In youth with clinically relevant depressive scores (t-score > 65), moderating factors (i.e., diagnosis, age, puberty, sex) were explored. During Year 1, the sample included 244 youth 10-to-13 years: 140 in the ASD group (36 females) and 104 in the TD group (46 females). RESULTS: Autistic youth had elevated depression scores compared to TD peers (p < 0.001) and females were higher than males in both groups (p = 0.001). There was significant diagnosis by age (p < 0.001) and diagnosis by pubertal stage (p < 0.05) interactions. In the ASD group, elevated depressive scores presented in early adolescence and decreased during middle adolescence and puberty, whereas the TD group showed the opposite trend with an increase in depression symptoms with advancing development. LIMITATIONS: Limitations include an unequal sex distribution (fewer females), non-representative autistic sample (e.g., cognition and race/ethnicity), and potential confound of the COVID-19 pandemic. CONCLUSIONS: Autistic youth present with higher rates of depressive symptoms early in development; yet, approaching middle adolescence and puberty, the symptom trajectory in the autistic youth declines coinciding with an increase in the TD youth. While group trajectories are divergent, they lead to similar levels of depression in late adolescence with higher symptoms in females. Findings suggest a period of quiescence in depressive symptomology influenced by biopsychosocial factors impacting affective profiles.

Parenting attitude towards children with autism spectrum disorders: the Japan environment and children's study.

OBJECTIVE: The primary objective of this study was to investigate the parenting attitudes towards children with autism spectrum disorders in early childhood in Japan. DESIGN: This study was a cohort study. The participants were enrolled from January 2011 to March 2014. We obtained the prevalence of autism spectrum disorders at 3 years of age, parenting attitudes and other factors from questionnaires. We divided the participants into two groups, an autism spectrum disorders group and a non-autism spectrum disorders group, and compared the parenting attitudes. SETTING: This study used data from a Japanese birth cohort study: the Japan Environment and Children's Study, conducted across 15 regional centres in Japan. PARTICIPANTS: The full dataset of the Japan Environment and Children's Study comprised 104 059 records. We excluded 17 889 records because the answer for the autism spectrum disorders in the questionnaire was blank. As a result, we analysed the remaining 82 411 mother-child pairs. MAIN OUTCOME MEASURES: The primary outcome variable was parenting attitudes at 3.5 years of age, which was assessed using a questionnaire. We asked respondents 16 questions related to parenting attitudes, and they answered based on their behaviours. The independent variable was the prevalence of autism spectrum disorders at 3 years of age. RESULTS: Of the 82 411 participants, the children with autism spectrum disorders at 3 years of age were 372 (0.45%). In most questions about parenting attitudes, the autism spectrum disorders group had unfavourable responses. The difference was particularly noticeable when the parents taught their children social discipline. Unfavourable parenting attitudes were 16.6% in the autism spectrum disorders group and 0.8% in the non-autism spectrum disorders group in the question item with the largest difference between the two groups, a significant difference. CONCLUSIONS: Parents of children with autism spectrum disorders tended to have unfavourable attitudes, suggesting the importance of parental training.

Beyond imagination: Sorting out and treating psychosis in the context of autism spectrum disorder.

In the last decades, growing caseness for Autism Spectrum Disorder (ASD) has been observed, owing to the diagnostic accretion of low-impairment forms, over and above other possible causes. Unrecognized ASD is likely to be mislabeled as a psychotic disorder (PD), as people in the spectrum may show 'pseudopsychotic' symptoms, resembling both negative and positive symptoms. On the other hand, PDs are likely to be overlooked when they arise in people with ASD, due to the 'diagnostic overshadowing' of new-onset conditions by lifelong core autistic symptoms. The three available metanalyses on the occurrence of psychosis in adults with ASD convergently reported a rate of PDs that is at least ten times higher than in the general population. Therefore, the lack of literature addressing risk factors, outcomes, and treatment options for psychosis in the context of ASD is utterly concerning. The present review aims to summarize up-to-date knowledge of PDs with comorbid ASD in terms of clinical features, course, and treatment.

Autism in patients with eosinophilic gastrointestinal disease: A systematic review with meta-analysis.

PURPOSE: Neurodevelopmental disorders, such as autism spectrum disorder (ASD), have been increasingly associated with eosinophilic gastrointestinal disorders (EGID). However, the relationship between these diseases remains unclear. We performed a systematic review with meta-analysis to address this issue. METHODS: The search was performed according to the PRISMA guidelines using descriptors for ASD and EGIDs from the MEDLINE, Embase, PsycInfo, LILACS, and Web of Science databases. Observational studies with the prevalence of ASD in any EGID were included. The study protocol was registered on the PROSPERO platform under the number CRD42023455177. RESULTS: The total dataset comprised 766,082 participants. The result of the single-arm meta-analysis showed an overall prevalence of ASD in the population with EGID of 21.59% (95% CI: 10.73-38.67). There was an association between EGID and ASD (OR: 3.44; 95% CI: 1.25-2.21), also significant when restricted only to EoE (OR: 3.70; 95% CI: 2.71-5.70). DISCUSSION: Recent studies have implicated the influence of an inadequate epithelial barrier integrity in the pathogenesis of several diseases. The role of this mechanism can be extended to situations beyond allergic reactions, including other conditions with underlying immunological mechanisms. Several diseases are potentially related to the systemic effect of bacterial translocation in tissues with defective epithelial barriers. CONCLUSION: Our meta-analysis provides evidence that supports the consideration of EGID in patients with ASD and ASD in patients with EGID. Despite its limitations, the results should also be validated by future studies, preferably using multicenter prospective designs in populations with low referral bias.

Attention-deficit Hyperactivity Disorder and Autism Spectrum Disorder: Towards Better Diagnosis and Management.

Background: Attention-deficit hyperactivity disorder (ADHA) is one of the most common comorbid disorders of autism spectrum disorder (ASD) that can accompany autism, triggered by it, or be a consequence of it. Objective: This review explored the prevalence of the comorbidity of both disorders, neurobiological background, symptoms, latest assessment methods, and therapeutic approaches. Results and Discussion: It concluded that effective assessment, diagnosis and management of ADHD in ASD children and adults is essential for this group of patients to thrive and live a good quality of life. Further research is recommended to explore the most effective intervention for such important members of our society. Conclusion: More studies are needed to understand the mechanisms underlying these comorbidities, and to prevent the misdiagnosis and mismanagement of these disorders. Also, to develop up to date personalized therapeutic plans for such children.

Identification and support of autistic individuals within the UK Criminal Justice System: a practical approach based upon professional consensus with input from lived experience.

BACKGROUND: Autism spectrum disorder (hereafter referred to as autism) is characterised by difficulties with (i) social communication, social interaction, and (ii) restricted and repetitive interests and behaviours. Estimates of autism prevalence within the criminal justice system (CJS) vary considerably, but there is evidence to suggest that the condition can be missed or misidentified within this population. Autism has implications for an individual's journey through the CJS, from police questioning and engagement in court proceedings through to risk assessment, formulation, therapeutic approaches, engagement with support services, and long-term social and legal outcomes. METHODS: This consensus based on professional opinion with input from lived experience aims to provide general principles for consideration by United Kingdom (UK) CJS personnel when working with autistic individuals, focusing on autistic offenders and those suspected of offences. Principles may be transferable to countries beyond the UK. Multidisciplinary professionals and two service users were approached for their input to address the effective identification and support strategies for autistic individuals within the CJS. RESULTS: The authors provide a consensus statement including recommendations on the general principles of effective identification, and support strategies for autistic individuals across different levels of the CJS. CONCLUSION: Greater attention needs to be given to this population as they navigate the CJS.

Association of cerebral palsy with autism spectrum disorder and attention-deficit/hyperactivity disorder in children: a large-scale nationwide population-based study.

OBJECTIVE: To examine the association of cerebral palsy with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), providing evidence for interdisciplinary medical service for children with cerebral palsy. DESIGN: A large-scale nationwide population-based study. SETTING: The National Health Interview Survey (NHIS). PATIENTS: 177 899 children aged 3-17 years among NHIS participants from 1997 to 2003 and 2008 to 2018. RESULTS: Among the 177 899 children included in this analysis, 602 (0.33%) had cerebral palsy, 1997 (1.16%) had ASD, and 13 697 (7.91%) had ADHD. Compared with children without cerebral palsy, children with cerebral palsy had a higher prevalence of ASD (6.09% vs 1.15%; p<0.001) and ADHD (15.91% vs 7.89%; p<0.001). After adjustment for age, sex, race/ethnicity, family highest education level, family income level and geographical region, the OR among children with cerebral palsy, compared with children without cerebral palsy, was 5.07 (95% CI 3.25 to 7.91) for ASD (p<0.001) and 1.95 (95% CI 1.43 to 2.66) for ADHD (p<0.001). Furthermore, the association of cerebral palsy with ASD and ADHD remained significant in all subgroups stratified by age, sex and race. CONCLUSION: In a large, nationally representative sample of US children, this study shows that children with cerebral palsy are at an increased risk of ASD and ADHD.

Clinical, socio-demographic, and parental correlates of early autism traits in a community cohort of toddlers.

Identifying factors linked to autism traits in the general population may improve our understanding of the mechanisms underlying divergent neurodevelopment. In this study we assess whether factors increasing the likelihood of childhood autism are related to early autistic trait emergence, or if other exposures are more important. We used data from 536 toddlers from London (UK), collected at birth (gestational age at birth, sex, maternal body mass index, age, parental education, parental language, parental history of neurodevelopmental conditions) and at 18 months (parents cohabiting, measures of socio-economic deprivation, measures of maternal parenting style, and a measure of maternal depression). Autism traits were assessed using the Quantitative Checklist for Autism in Toddlers (Q-CHAT) at 18 months. A multivariable model explained 20% of Q-CHAT variance, with four individually significant variables (two measures of parenting style and two measures of socio-economic deprivation). In order to address variable collinearity we used principal component analysis, finding that a component which was positively correlated with Q-CHAT was also correlated to measures of parenting style and socio-economic deprivation. Our results show that parenting style and socio-economic deprivation correlate with the emergence of autism traits at age 18 months as measured with the Q-CHAT in a community sample.

Additive interaction between birth asphyxia and febrile seizures on autism spectrum disorder: a population-based study.

BACKGROUND: Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder that can significantly impact an individual's ability to socially integrate and adapt. It's crucial to identify key factors associated with ASD. Recent studies link both birth asphyxia (BA) and febrile seizures (FS) separately to higher ASD prevalence. However, investigations into the interplay of BA and FS and its relationship with ASD are yet to be conducted. The present study mainly focuses on exploring the interactive effect between BA and FS in the context of ASD. METHODS: Utilizing a multi-stage stratified cluster sampling, we initially recruited 84,934 Shanghai children aged 3-12 years old from June 2014 to June 2015, ultimately including 74,251 post-exclusion criteria. A logistic regression model was conducted to estimate the interaction effect after controlling for pertinent covariates. The attributable proportion (AP), the relative excess risk due to interaction (RERI), the synergy index (SI), and multiplicative-scale interaction were computed to determine the interaction effect. RESULTS: Among a total of 74,251 children, 192 (0.26%) were diagnosed with ASD. The adjusted odds ratio for ASD in children with BA alone was 3.82 (95% confidence interval [CI] 2.42-6.02), for FS alone 3.06 (95%CI 1.48-6.31), and for comorbid BA and FS 21.18 (95%CI 9.10-49.30), versus children without BA or FS. The additive interaction between BA and FS showed statistical significance (P < 0.001), whereas the multiplicative interaction was statistically insignificant (P > 0.05). LIMITATIONS: This study can only demonstrate the relationship between the interaction of BA and FS with ASD but cannot prove causation. Animal brain experimentation is necessary to unravel its neural mechanisms. A larger sample size, ongoing monitoring, and detailed FS classification are needed for confirming BA-FS interaction in ASD. CONCLUSION: In this extensive cross-sectional study, both BA and FS were significantly linked to ASD. The coexistence of these factors was associated with an additive increase in ASD prevalence, surpassing the cumulative risk of each individual factor.

Preeclampsia Onset, Days to Delivery, and Autism Spectrum Disorders in Offspring: Clinical Birth Cohort Study.

BACKGROUND: Maternal preeclampsia is associated with a risk of autism spectrum disorders (ASD) in offspring. However, it is unknown whether the increased ASD risk associated with preeclampsia is due to preeclampsia onset or clinical management of preeclampsia after onset, as clinical expectant management of preeclampsia allows pregnant women with this complication to remain pregnant for potentially weeks depending on the onset and severity. Identifying the risk associated with preeclampsia onset and exposure provides evidence to support the care of high-risk pregnancies and reduce adverse effects on offspring. OBJECTIVE: This study aimed to fill the knowledge gap by assessing the ASD risk in children associated with the gestational age of preeclampsia onset and the number of days from preeclampsia onset to delivery. METHODS: This retrospective population-based clinical cohort study included 364,588 mother-child pairs of singleton births between 2001 and 2014 in a large integrated health care system in Southern California. Maternal social demographic and pregnancy health data, as well as ASD diagnosis in children by the age of 5 years, were extracted from electronic medical records. Cox regression models were used to assess hazard ratios (HRs) of ASD risk in children associated with gestational age of the first occurrence of preeclampsia and the number of days from first occurrence to delivery. RESULTS: Preeclampsia occurred in 16,205 (4.4%) out of 364,588 pregnancies; among the 16,205 pregnancies, 2727 (16.8%) first occurred at <34 weeks gestation, 4466 (27.6%) first occurred between 34 and 37 weeks, and 9012 (55.6%) first occurred at ≥37 weeks. Median days from preeclampsia onset to delivery were 4 (IQR 2,16) days, 1 (IQR 1,3) day, and 1 (IQR 0,1) day for those first occurring at <34, 34-37, and ≥37 weeks, respectively. Early preeclampsia onset was associated with greater ASD risk (P=.003); HRs were 1.62 (95% CI 1.33-1.98), 1.43 (95% CI 1.20-1.69), and 1.23 (95% CI 1.08-1.41), respectively, for onset at <34, 34-37, and ≥37 weeks, relative to the unexposed group. Within the preeclampsia group, the number of days from preeclampsia onset to delivery was not associated with ASD risk in children; the HR was 0.995 (95% CI 0.986-1.004) after adjusting for gestational age of preeclampsia onset. CONCLUSIONS: Preeclampsia during pregnancy was associated with ASD risk in children, and the risk was greater with earlier onset. However, the number of days from first preeclampsia onset to delivery was not associated with ASD risk in children. Our study suggests that ASD risk in children associated with preeclampsia is not increased by expectant management of preeclampsia in standard clinical practice. Our results emphasize the need to identify effective approaches to preventing the onset of preeclampsia, especially during early pregnancy. Further research is needed to confirm if this finding applies across different populations and clinical settings.

Genetically identified mediators associated with increased risk of stroke and cardiovascular disease in individuals with autism spectrum disorder.

Growing evidence suggested that individuals with autism spectrum disorder (ASD) associated with stroke and cardiovascular disease (CVD). However, the causal association between ASD and the risk of stroke and CVD remains unclear. To validate this, we performed two-sample Mendelian randomization (MR) and two-step mediation MR analyses, using relevant genetic variants sourced from the largest genome-wide association studies (GWASs). Two-sample MR evidence indicated causal relationships between ASD and any stroke (OR = 1.1184, 95% CI: 1.0302-1.2142, P < 0.01), ischemic stroke (IS) (OR = 1.1157, 95% CI: 1.0237-1.2160, P = 0.01), large-artery atherosclerotic stroke (LAS) (OR = 1.2902, 95% CI: 1.0395-1.6013, P = 0.02), atrial fibrillation (AF) (OR = 1.0820, 95% CI: 1.0019-1.1684, P = 0.04), and heart failure (HF) (OR = 1.1018, 95% CI: 1.0007-1.2132, P = 0.05). Additionally, two-step mediation MR suggested that type 2 diabetes mellitus (T2DM) partially mediated this effect (OR = 1.14, 95%CI: 1.02-1.28, P = 0.03). The mediated proportion were 10.96% (95% CI: 0.58%-12.10%) for any stroke, 11.77% (95% CI: 10.58%-12.97%) for IS, 10.62% (95% CI: 8.04%-13.20%) for LAS, and 7.57% (95% CI: 6.79%-8.36%) for HF. However, no mediated effect was observed between ASD and AF risk. These findings have implications for the development of prevention strategies and interventions for stroke and CVD in patients with ASD.

Are Symptoms of Obstructive Sleep Apnea During Pregnancy Associated With Autism Spectrum Disorder in Children: A Case-Control Study.

BACKGROUND: Obstructive sleep apnea complicates 10% to 32% or greater of pregnancies, however, reports on long-term effects on the children of pregnancies affected by obstructive sleep apnea are limited. OBJECTIVE: We sought to test the hypothesis that the children of pregnant people with symptoms of obstructive sleep apnea during pregnancy have an increased incidence of autism spectrum disorder. METHODS: This was a case-control study comparing the pregnancies of people whose children were later diagnosed with autism spectrum disorder without a known associated genetic condition to those whose children were diagnosed with autism spectrum disorder with a known associated genetic condition. RESULTS: Of the 51 total parents who were eligible and consented to participate, 4 had a child with autism associated with a known genetic condition, and 47 had a child with autism with no known genetic condition. The prevalence of any snoring (50.0% and 36.2%, respectively) and daytime tiredness (75.0% and 89.4%, respectively) were similar between both groups. CONCLUSIONS: In this study, the prevalence of any snoring and falling asleep while driving during pregnancy was higher in the sampled population than typically reported in pregnant people. While the sample size for this study was small, our preliminary results suggest that parents of children with autism have a high prevalence of sleep-related concerns during their pregnancies, which indicates the need for further investigation - especially for obstructive sleep apnea. Future studies exploring the neurodevelopmental outcomes of children of a cohort of pregnant people with known presence or absence of obstructive sleep apnea during pregnancy is warranted.

Predicting autism spectrum disorder using maternal risk factors: A multi-center machine learning study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a complex environmental etiology involving maternal risk factors, which have been combined with machine learning to predict ASD. However, limited studies have considered the factors throughout preconception, perinatal, and postnatal periods, and even fewer have been conducted in multi-center. In this study, five predictive models were developed using 57 maternal risk factors from a cohort across ten cities (ASD:1232, typically developing[TD]: 1090). The extreme gradient boosting model performed best, achieving an accuracy of 66.2 % on the external cohort from three cities (ASD:266, TD:353). The most important risk factors were identified as unstable emotions and lack of multivitamin supplementation using Shapley values. ASD risk scores were calculated based on predicted probabilities from the optimal model and divided into low, medium, and high-risk groups. The logistic analysis indicated that the high-risk group had a significantly increased risk of ASD compared to the low-risk group. Our study demonstrated the potential of machine learning models in predicting the risk for ASD based on maternal factors. The developed model provided insights into the maternal emotion and nutrition factors associated with ASD and highlighted the potential clinical applicability of the developed model in identifying high-risk populations.

Exploring the association between early-life air pollution exposure and autism spectrum disorders in children: A systematic review and meta-analysis.

The objective of this meta-analysis is to investigate the association between air pollution and the vulnerability of children to autism spectrum disorders (ASD). A thorough examination and analysis of data obtained from a compilation of 14 studies was undertaken, with a particular emphasis on investigating the effects of nitrogen dioxide (NO2), oxide of nitrogen (NOx), ozone (O3), and particulate matter (PM10 and PM2.5) on individuals diagnosed with ASD. The findings demonstrate a moderate association between exposure to nitrogen dioxide (NO2) and ASD, as indicated by a combined odds ratio (OR) of 1.13 and a 95% confidence interval (CI) spanning from 0.77 to 1.549. O3 shows a combined odds ratio (OR) of 0.82, along with a 95% confidence interval (CI) ranging from 0.49 to 1.14. NOx shows a moderate level of heterogeneity (I² = 75.9%, p = 0.002), suggesting that the impact of NOx on the risk of ASD. There is a statistically significant relationship between exposure to O3 and ASD, although the strength of this relationship is diminished. The findings demonstrated a noteworthy correlation between exposure to PM10 and PM2.5 and the occurrence of ASD. The study found a significant correlation, in relation to PM2.5, with a combined odds ratio (OR) of 1.22 and a 95% confidence interval (CI) ranging from 1.11 to 1.34. The findings have significant implications for the formulation of programs aimed at reducing exposure to harmful chemicals, especially among vulnerable groups such as children.