Correlation of Co-Morbidities with Symptom Severity of Children with Autism Spectrum Disorder: A Cross-Sectional Survey.

This study aims to identify potential correlations of the severity of symptoms of children with autism spectrum disorder (ASD) with serum nutritional levels, body composition indicators, diet partiality, and sleep disturbances. The cohort of this cross-sectional study included 120 children with ASD and 110 typically developing (TD) children to assess symptoms of ASD, and to measure serum levels of vitamins and minerals and the body composition values. Diet partiality and sleep disturbances were assessed by administering questionnaires. The serum levels of folic acid, copper, and vitamin B were lower in children with ASD than in TD children, while magnesium and homocysteine were higher (p < 0.05). Children with ASD had greater chest circumference, abdominal skinfold thickness, and body mass index (BMI) than TD children (p < 0.05), and higher prevalences of diet partiality and sleep disturbances (p < 0.001). Lower vitamin A levels and higher vitamin D levels were related to social impairment in children with ASD. Moreover, there were significantly positive correlations of BMI, chest circumference, diet partiality, and sleep disturbances with severity of ASD symptoms (p < 0.05). Collectively, rational nutritional supplementation, dietary management, and behavioral interventions are essential for children with ASD.

E-Health Family Interventions for Parents of Children With Autism Aged 0-6 Years: A Scoping Review.

OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with onset in infancy. Early intervention is critical to improve the prognosis for these children. E-health interventions have tremendous potential. This review aimed to determine the status and effectiveness of family interventions for parents of children aged 0-6 years with ASD in the context of e-health. METHODS: The review methodology was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. PubMed, Web of Science, and China National Knowledge Infrastructure were searched from inception to June 2022. The searches were limited to children with ASD of the age range between 0 and 6 years. We collated the available information and used descriptive statistics to analyze the synthesized data. RESULTS: Our initial search identified 3,672 articles, of which 30 studies met the inclusion criteria. The 30 articles selected were released between 2012 and 2022. All articles are in English. Most articles reviewed were from high-income countries (27/30, 90.0%), especially from the United States (16/30, 53.3%). Four major themes emerged from the 30 studies that matched the inclusion criteria, as follows: 1) type of e-health interventions, 2) duration of interventions, 3) clinical aspects of e-health interventions, and 4) evidence for intervention effectiveness, looking into the positive, negative, and mixed findings of previous studies. CONCLUSION: These findings suggest that a wide variety of e-health interventions may actually help support both children with ASD aged 0-6 years and their parents.

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OBJECTIVES: To explore the association between maternal gestational diabetes mellitus (GDM) exposure and the development of autism spectrum disorder (ASD) in offspring. METHODS: A case-control study was conducted, recruiting 221 children with ASD and 400 healthy children as controls. Questionnaires and interviews were used to collect information on general characteristics of the children, socio-economic characteristics of the family, maternal pregnancy history, and maternal disease exposure during pregnancy. Multivariate logistic regression analysis was used to investigate the association between maternal GDM exposure and the development of ASD in offspring. The potential interaction between offspring gender and maternal GDM exposure on the development of ASD in offspring was explored. RESULTS: The proportion of maternal GDM was significantly higher in the ASD group compared to the control group (16.3% vs 9.4%, P=0.014). After adjusting for variables such as gender, gestational age, mode of delivery, parity, and maternal education level, maternal GDM exposure was a risk factor for ASD in offspring (OR=2.18, 95%CI: 1.04-4.54, P=0.038). On the basis of adjusting the above variables, after further adjusting the variables including prenatal intake of multivitamins, folic acid intake in the first three months of pregnancy, and assisted reproduction the result trend did not change, but no statistical significance was observed (OR=1.94, 95%CI: 0.74-5.11, P=0.183). There was an interaction between maternal GDM exposure and offspring gender on the development of ASD in offspring (P<0.001). Gender stratified analysis showed that only in male offspring of mothers with GDM, the risk of ASD was significantly increased (OR=3.67, 95%CI: 1.16-11.65, P=0.027). CONCLUSIONS: Maternal GDM exposure might increase the risk of ASD in offspring. There is an interaction between GDM exposure and offspring gender in the development of ASD in offspring.

Untargeted metabolomics reveals hepatic metabolic disorder in the BTBR mouse model of autism and the significant role of liver in autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, and the etiology is unknown. Metabolic dysfunction is present in patients with ASD. In the current study, untargeted metabolomics was employed to screen the differential metabolites in the liver of BTBR mouse model of autism, and MetaboAnalyst 4.0 was used for metabolic pathway analysis. Mice were killed, and liver samples were collected for untargeted metabolomics analysis and examination of histopathology. Finally, 12 differential metabolites were identified. The intensities of phenylethylamine, 4-Guanidinobutanoic acid, leukotrieneD4, and SM(d18:1/24:1(15Z)) were significantly upregulated (p < .01), and the intensities of estradiol, CMP-N-glycoloylneuraminate, retinoyl ß-glucuronide,4-phosphopantothenoylcysteine, aldophosphamide, taurochenodesoxycholic acid, taurocholic acid, and dephospho-CoA were significantly downregulated (p < .01) in the BTBR group compared with C57 control group, indicating that differences between BTBR and C57 groups were observed in metabolic patterns. Disturbed pathways of the BTBR mice involved lipid metabolism, retinol metabolism, and amino acid and energy metabolism, revealing that bile acid-mediated activation of LXRα might contribute to metabolic dysfunction of lipid and leukotriene D4 produced by the activation of 5-LOX led to hepatic inflammation. Pathological changes in the liver tissue, such as hepatocyte vacuolization, and small amounts of inflammatory and cell necrosis, further supported metabolomic results. Moreover, Spearman's rank correlation revealed that there is a strong relationship between metabolites across liver and cortex, suggesting liver may exert action by connecting peripheral and neural systems. These findings were likely to be of pathological importance or a cause/consequence of autism, and may provide insight into key metabolic dysfunction to target potential therapeutic strategies relating to ASD.

Factors associated with reporting good maternal health-related knowledge among rural mothers of Yemen.

Increasing women's knowledge about maternal health is an important step towards empowering them and making them aware of their rights and health status, allowing them to seek appropriate health care. In Yemen, the ongoing conflict has hampered the delivery of health information to women in public health facilities. This study examined rural women's knowledge of, and attitude towards, maternal and child health in Yemen and identified the factors associated with good maternal health knowledge. The study was conducted between August and November 2018. A sample of 400 women aged 15-49 years who had delivered in the 6 months prior to the survey were systematically selected from selected public health facilities in Abyan and Lahj. Women were interviewed using a structured questionnaire to gather data on their demographic and economic characteristics, obstetric history and responses to health knowledge and attitude questions. Women's knowledge level was assessed as poor or good using the mean score as a cut-off. Chi-squared test and multiple logistic regression analysis were used to identify statistically significant factors associated with good maternal health knowledge. The percentage of women who had good knowledge was 44.8% (95% CI: 39.8-49.8). Women's attitude towards maternal health was negative in the areas of early ANC attendance, managing dietary regime and weight during pregnancy, facility delivery, PNC visits, cord care and mother and child health management. Women with primary education, whose husbands had received no formal education, who had their first ANC visit from the second trimester of pregnancy and who had fewer than four ANC visits were more likely to have poor health knowledge. Conversely, those with higher household income and only one child were more likely to have good maternal health knowledge. Overall, women's knowledge on maternal and child health care in rural areas of Yemen was low. Strategies are needed to increase rural women's knowledge on maternal and child health in this conflict-affected setting.

Untargeted Metabolomic Analysis Reveals the Metabolic Disturbances and Exacerbation of Oxidative Stress in the Cerebral Cortex of a BTBR Mouse Model of Autism.

The etiology and pathology of autism spectrum disorders (ASDs) are still poorly understood, which largely limit the treatment and diagnosis of ASDs. Emerging evidence supports that abnormal metabolites in the cerebral cortex of a BTBR mouse model of autism are involved in the pathogenesis of autism. However, systematic study on global metabolites in the cerebral cortex of BTBR mice has not been conducted. The current study aims to characterize metabolic changes in the cerebral cortex of BTBR mice by using an untargeted metabolomic approach based on UPLC-Q-TOF/MS. C57BL/6 J mice were used as a control group. A total of 14 differential metabolites were identified. Compared with the control group, the intensities of PI(16:0/22:5(4Z,7Z,10Z,13Z,16Z)), PC(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/18:1(9Z)), PA(16:0/18:1(11Z)), 17-beta-estradiol-3-glucuronide, and N6,N6,N6-trimethyl-L-lysine decreased significantly (p < 0.01) and the intensities of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline, LysoPC(20:4(5Z,8Z,11Z,14Z)/0:0), adenosine monophosphate, adenosine-5'-phosphosulfate, LacCer(d18:1/12:0),3-dehydro-L-gulonate, N-(1-deoxy-1-fructosyl)tryptophan, homovanillic acid, and LPA(0:0/18:1(9Z)) increased significantly (p < 0.01) in the BTBR group. These changes in metabolites were closely related to perturbations in lipid metabolism, energy metabolism, purine metabolism, sulfur metabolism, amino acid metabolism, and carnitine biosynthesis. Notably, exacerbation of the oxidative stress response caused by differential prooxidant metabolites led to alteration of antioxidative systems in the cerebral cortex and resulted in mitochondrial dysfunction, further leading to abnormal energy metabolism as an etiological mechanism of autism. A central role of abnormal metabolites in neurological functions associated with behavioral outcomes and disturbance of sulfur metabolism and carnitine biosynthesis were found in the cerebral cortex of BTBR mice, which helped increase our understanding for exploring the pathological mechanism of autism.

Mental health issues in parents of children with autism spectrum disorder: A multi-time-point study related to COVID-19 pandemic.

Given the unpredictability and challenges brought about by the 2019 novel coronavirus (COVID-19) pandemic, this study aimed to investigate the impact trend of the prolonged pandemic on the mental health of parents of children with autism spectrum disorder (ASD). The 8112 participants included parents of children with ASD and parents of typically developing (TD) children at two sites (Heilongjiang and Fujian province, China). The parents completed a set of self-report questionnaires covering demographic characteristics, influences related to COVID-19, COVID-19 concerns and perceived behaviors, as well as the Connor-Davidson resilience scale (CD-RISC), self-rating anxiety scale (SAS), and self-rating depression scale (SDS) by means of an online survey platform. Data were collected by three cross-sectional surveys carried out in April 2020 (Time 1), October 2020 (Time 2), and October 2021 (Time 3). The results of quantitative and qualitative comparisons showed that: (i) parents of children with ASD had lower levels of resilience, and more symptoms of anxiety and depression than parents of TD children at each time point (all P < 0.05); and (ii) there were significant time-cumulative changes in resilience, anxiety, and depression among all participants (all P < 0.05). The logistic regression analyzes after adjusting for demographic characteristics revealed that the following factors were significantly associated with poor resilience and a higher rate of anxiety and depression in parents of children with ASD: time-point, the effect of COVID-19 on children's emotions and parents' emotions, changes in relationships, changes in physical exercise, changes in daily diet during the COVID-19 pandemic, and COVID-19-related psychological distress. In conclusions, the parents did not report improvements in resilience, anxiety, or depression symptoms from Time 1 to Time 2 or 3, indicating that cumulative mental health issues increased when, surprisingly, the COVID-19 restrictions were eased. The psychological harm resulting from the COVID-19 pandemic is far-reaching, especially among parents of children with ASD.

Prevalence of epilepsy in autism spectrum disorders: A systematic review and meta-analysis.

LAY ABSTRACT: Autistic individuals experience higher co-occurring medical conditions than the general population, and yet the estimates of autistic individuals with epilepsy are not updated. Co-occurrence of epilepsy in autistic individuals often aggravated cognitive impairment and increased the risk of poor long-term prognosis. Thus, an updated systematic review and meta-analysis was conducted to study the relevant articles published from inception to 2020, evaluate the prevalence of epilepsy in autistic individuals, and further explore the putative factors influencing the prevalence. A total of 66 studies from 53 articles were included in this study. The results showed that epilepsy is more common in autistic individuals than in the general population. The prevalence of epilepsy in autistic individuals in the clinical sample-based studies was higher than that in the population-based based cross-sectional or cohort studies. The prevalence of epilepsy in autistic adults was higher than that in autistic children. A significantly increased prevalence of epilepsy was detected in the autistic adolescent group (11-17 years old), and a higher trend of prevalence of epilepsy was observed in the autistic pre-school group (⩽ 6 -years-old) than that of the autistic school-aged group (7-10 years-old). The prevalence of epilepsy increased with age, female rate, and low intellectual function rate of autistic individuals. However, the human development index of countries was negatively associated with the pooled prevalence, which could be attributed to the different levels of awareness, diagnostic technologies, and autism-service support worldwide. About 1/10 autistic individuals also had epilepsy, which was common in the clinical setting, adolescents, adults, females, or patients with intellectual disability and less common in the country with high human development index. Thus, these findings provided critical and innovative views on the prevalence of epilepsy in autistic individuals and contributed to the targeted clinical management and preventive measures.

The association between gene polymorphisms in voltage-gated potassium channels Kv2.1 and Kv4.2 and susceptibility to autism spectrum disorder.

Background: Autism spectrum disorder (ASD) is a heritable form of neurodevelopmental disorder that arises through synaptic dysfunction. Given the involvement of voltage-gated potassium (Kv) channels in the regulation of synaptic plasticity, we aimed to explore the relationship between the genetic variants in the KCNB1 and KCND2 genes (encoding Kv2.1 and Kv4.2, respectively) and the risk of developing ASD. Methods: A total of 243 patients with ASD and 243 healthy controls were included in the present study. Sixty single nucleotide polymorphisms (SNPs) (35 in KCNB1 and 25 in KCND2) were genotyped using the Sequenom Mass Array. Results: There were no significant differences in the distribution of allele frequencies and genotype frequencies in KCNB1 between cases and controls. However, the differences were significant in the allelic distribution of KCND2 rs1990429 (p Bonferroni < 0.005) and rs7793864 (p Bonferroni < 0.005) between the two groups. KCND2 rs7800545 (p FDR = 0.045) in the dominant model and rs1990429 (p FDR < 0.001) and rs7793864 (p FDR < 0.001) in the over-dominant model were associated with ASD risk. The G/A genotype of rs1990429 in the over-dominant model and the G/A-G/G genotype of rs7800545 in the dominant model were correlated with lower severity in the Autism Diagnostic Interview-Revised (ADI-R) restricted repetitive behavior (RRB) domain. Conclusion: Our results provide evidence that KCND2 gene polymorphism is strongly associated with ASD susceptibility and the severity of RRB.

Prenatal Folic Acid Supplements and Offspring's Autism Spectrum Disorder: A Meta-analysis and Meta-regression.

We systematically reviewed the evidence on the association between maternal folic acid supplementation and the risk of offspring's autism spectrum disorders (ASD). A total of 10 studies with 23 sub-studies (9795 ASD cases) were included. Folic acid supplementation during early pregnancy was associated with a lower risk of offspring's ASD [OR 0.57, 95% CI 0.41-0.78]. The consumption of a daily amount of at least 400 µg folic acid from dietary sources and supplements, was associated with a reduced risk of offspring ASD [OR 0.55, 95% CI 0.36-0.83]. Critical effective maternal folic acid supplementation strategies, such as intake timing and intake dosage, may aid the reduction in the risk of offspring ASD. This meta-analysis provided new insights for the prevention of offspring's ASD.