Sleep and internalizing problems in primary school children with attention-deficit hyperactivity disorder.

BACKGROUND: Internalizing and externalizing problems have received great attention, and children with ADHD exhibit high rates of comorbid internalizing and externalizing disorders. This study aimed to explore the relationship between sleep and internalizing problems in children with attention-deficit hyperactivity disorder (ADHD) and the probable mediating role of externalizing problems. METHODS: A total of 203 primary school children diagnosed with ADHD for the first time were recruited for this study. Children with ADHD were evaluated by Children's Sleep Habits Questionnaire (CSHQ), Strengths and Difficulties Questionnaire (SDQ). Internalizing problems were represented by emotional symptoms and peer problems of SDQ, and externalizing problems were represented by conduct problems and hyperactivity-inattention problems of SDQ. Multi-step linear regression analysis was used to investigate the mediating effect of externalizing problems on the relationship between sleep and internalizing problems. RESULTS: Sleep in children with ADHD was associated with emotional problems in internalizing problems, and conduct problems in externalizing problems mediated the association between sleep and emotional problems. CONCLUSION: For children with ADHD, when it is difficult to identify internalizing problems, especially emotional problems, we can take sleep and externalizing problems as clues to improve our clinical ability to recognize and deal with emotional problems. IMPACT: 1. We first explored the possible mediating role of conduct problems between sleep and emotional problems in primary school children with ADHD. 2. When it is difficult to identify internalizing problems, especially emotional problems, we can take sleep and externalizing problems as clues to improve our clinical ability to recognize emotional problems for children with ADHD. 3. For children with ADHD with potential internalizing problems, especially emotional problems, interventions for their sleep and externalizing problems may be the possible methods to deal with.

Efficacy of differential reinforcement of other behaviors therapy for tic disorder: a meta-analysis.

INTRODUCTION: Recently, studies on behavioral tic suppression techniques have gained popularity as opposed to pharmacological alternatives that often have potentially dangerous side effects. Differential Reinforcement of Other Behaviors therapy (DRO) is one such behavioral technique whose efficacy in tic suppression has been experimentally demonstrated albeit in studies with very few patients, and lacking statistical power. Here, we conducted a meta-analysis of these studies to improve their overall power and explore whether DRO intervention is really effective for tic suppression. MATERIALS AND METHODS: PubMed, Embase, PsycINFO, and Cochrane Library were searched from inception to August 30, 2023. Only original interventional studies that examined the efficacy of DRO for tic suppression were included. RESULTS: A total of 8 no control interventional studies involving 79 children with tic disorders were recruited. Most of the children had moderate tic severity. The pooled mean Yale Global Tic Severity Scale (YGTSS) score was 24.64 (95% CI: 21.99 - 30.12, p = < 0.00001, I2 = 87%). In terms of efficacy of the DRO technique for tic suppression, the results showed that DRO was effective in reducing tic frequency among the children. The pooled standardized mean difference (SMD) was -10.25 (95% CI: -14.71 - -5.79, p = < 0.00001) with I2 = 94%. CONCLUSION: In conclusion, this study revealed that DRO is potentially an effective tic suppression technique for temporarily managing tic disorder. It also showed that DRO could be employed for both moderate and severe tic disorders. However, the technique bears crucial limitations that limit its implementation outside of experimental settings. More studies are needed to address these limitations and improve its applicability in the real world.

Altered intra- and inter-network brain functional connectivity associated with prolonged screen time in pre-school children with autism spectrum disorder.

Prolonged screen time (ST) has adverse effects on autistic characteristics and language development. However, the mechanisms underlying the effects of prolonged ST on the neurodevelopment of children with autism spectrum disorder (ASD) remain unclear. Neuroimaging technology may help to further explain the role of prolonged ST in individuals with ASD. This study included 164 cases, all cases were divided into low-dose ST exposure (LDE group 108 cases) and high-dose ST exposure (HDE group 56 cases) based on the average ST of all subjects. Spatial independent component analysis (ICA) was used to identify resting state networks (RSNs) and investigate intra- and inter-network alterations in ASD children with prolonged ST. We found that the total Childhood Autism Rating Scale (CARS) scores in the HDE group were significantly higher than those in the LDE group (36.2 ± 3.1 vs. 34.6 ± 3.9, p = 0.008). In addition, the developmental quotient (DQ) of hearing and language in the HDE group were significantly lower than those in the LDE group (31.5 ± 13.1 vs. 42.5 ± 18.5, p < 0.001). A total of 13 independent components (ICs) were identified. Between-group comparison revealed that the HDE group exhibited decreased functional connectivity (FC) in the left precuneus (PCUN) of the default mode network (DMN), the right middle temporal gyrus (MTG) of the executive control network (ECN), and the right median cingulate and paracingulate gyri (MCG) of the attention network (ATN), compared with the LDE group. Additionally, there was an increase in FC in the right orbital part of the middle frontal gyrus (ORBmid) of the salience network (SAN), compared with the LDE group. The inter-network analysis revealed increased FC between the visual network (VN) and basal ganglia (BG) and decreased FC between the sensorimotor network (SMN) and DMN, SMN and ATN, SMN and auditory network (AUN), and DMN and SAN in the HDE group, compared with the LDE group. There was a significant negative correlation between altered FC values in MTG and total CARS scores in subjects (r = - 0.18, p = 0.018).  Conclusion: ASD children with prolonged ST often exhibit lower DQ of language development and more severe autistic characteristics. The alteration of intra- and inter-network FC may be a key neuroimaging feature of the effect of prolonged ST on neurodevelopment in ASD children.  Clinical trial registration: ChiCTR2100051141. What is Known: • Prolonged ST has adverse effects on autistic characteristics and language development. • Neuroimaging technology may help to further explain the role of prolonged ST in ASD. What is New: • This is the first study to explore the impact of ST on intra- and inter-network FC in children with ASD. • ASD children with prolonged ST have atypical changes in intra- and inter-brain network FC.

A study of the effects of screen exposure on the neuropsychological development in children with autism spectrum disorders based on ScreenQ.

PURPOSE: To investigate the relationship between multi-dimensional aspects of screen exposure and autistic symptoms, as well as neuropsychological development in children with ASD. METHODS: We compared the ScreenQ and Griffiths Development Scales-Chinese Language Edition (GDS-C) of 636 ASD children (40.79 ± 11.45 months) and 43 typically developing (TD) children (42.44 ± 9.61 months). Then, we analyzed the correlations between ScreenQ and Childhood Autism Rating Scale (CARS), and GDS-C. We further used linear regression model to analyze the risk factors associated with high CARS total scores and low development quotients (DQs) in children with ASD. RESULTS: The CARS of children with ASD was positively correlated with the ScreenQ total scores and "access, frequency, co-viewing" items of ScreenQ. The personal social skills DQ was negatively correlated with the "access, frequency, content, co-viewing and total scores" of ScreenQ. The hearing-speech DQ was negatively correlated with the "frequency, content, co-viewing and total scores" of ScreenQ. The eye-hand coordination DQ was negatively correlated with the "frequency and total scores" of ScreenQ. The performance DQ was negatively correlated with the "frequency" item of ScreenQ. CONCLUSION: ScreenQ can be used in the study of screen exposure in children with ASD. The higher the ScreenQ scores, the more severe the autistic symptoms tend to be, and the more delayed the development of children with ASD in the domains of personal-social, hearing-speech and eye-hand coordination. In addition, "frequency" has the greatest impact on the domains of personal social skills, hearing-speech, eye-hand coordination and performance of children with ASD.

Comparison of the efficacy of parent-mediated NDBIs on developmental skills in children with ASD and fidelity in parents: a systematic review and network meta-analysis.

BACKGROUND: Recently, studies on behavioral interventions for autism have gained popularity. Naturalistic Developmental Behavior Interventions (NDBIs) are among the most effective, evidence-based, and widely used behavior interventions for autism. However, no research has been conducted on which of the several NDBI methods is most effective for parents and children with autism spectrum disorders. Therefore, we conducted a network meta-analysis to compare the specific effects of each type of parental-mediated NDBI on children's developmental skills and parent fidelity. METHODS: PubMed, Embase, Cochrane Library, Medline, Web of Science, China National Knowledge Infrastructure (CNKI), CINAHL, and Wanfang databases were searched from inception to August 30, 2023. A total of 32 randomized controlled trial studies that examined the efficacy of different NDBIs were included. RESULTS: Parents of children with ASD who received Pivotal Response Treatment (PRT) reported significant improvements in their children's social skills (SUCRA, 74.1%), language skills (SUCRA, 88.3%), and parenting fidelity (SUCRA, 99.5%). Moreover, parents who received Early Start Denver Model (ESDM) reported significant improvements in their children's language (SMD = 0.41, 95% CI: 0.04, 0.79) and motor skills (SMD = 0.44, 95% CI: 0.09, 0.79). In terms of the efficacy of improving parent fidelity, the results showed that the Improving Parents as Communication Teachers (ImPACT) intervention significantly improved parent fidelity when compared with the treatment-as-usual group (TAU) (SMD = 0.90, 95% CI: 0.39, 1.42) and the parental education intervention (PEI) (SMD = 1.10, 95% CI:0.28, 1.91).There was a difference in parent fidelity among parents who received PRT(SMD = 3.53, 95% CI: 2.26, 4.79) or ESDM(SMD = 1.42, 95% CI: 0.76, 2.09) training compared with PEI. CONCLUSION: In conclusion, this study revealed that parents can achieve high fidelity with the ImPACT intervention, and it can serve as an early first step for children newly diagnosed with ASD. It also showed that parent-mediated ESDM is effective in improving language and motor skills for children with ASD and can be used as part of the second stage of parent training. Parent-mediated PRT can also be used as a third stage of parent training with sufficient training intensity to further improve language, social, and motor skills.

Vitamin D3 improves iminodipropionitrile-induced tic-like behavior in rats through regulation of GDNF/c-Ret signaling activity.

Children with chronic tic disorders (CTD), including Tourette syndrome (TS), have significantly reduced serum 25-hydroxyvitamin D [25(OH)D]. While vitamin D3 supplementation (VDS) may reduce tic symptoms in these children, its mechanism is unclear. The study aim was to investigate the effects and mechanisms of vitamin D deficiency (VDD) and VDS on TS model behavior. Forty 5-week-old male Sprague-Dawley rats were randomly divided into (n = 10 each): control, TS model, TS model with VDD (TS + VDD), or TS model with VDS (TS + VDS; two intramuscular injections of 20,000 IU/200 g) groups. The VDD model was diet-induced (0 IU vitamin D/kg); the TS model was iminodipropionitrile (IDPN)-induced. All groups were tested for behavior, serum and striatal 25(OH)D and dopamine (DA), mRNA expressions of vitamin D receptor (VDR), glial cell line-derived neurotrophic factor (GDNF), protooncogene tyrosine-protein kinase receptor Ret (c-Ret), and DA D1 (DRD1) and D2 (DRD2) receptor genes in the striatum. TS + VDD had higher behavior activity scores throughout, and higher total behavior score at day 21 compared with TS model. In contrast, day 21 TS + VDS stereotyped behavior scores and total scores were lower than TS model. The serum 25(OH)D in TS + VDD was < 20 ng/mL, and lower than control. Striatal DA of TS was lower than control. Compared with TS model, striatal DA of TS + VDD was lower, while in TS + VDS it was higher than TS model. Furthermore, mRNA expression of VDR, GDNF, and c-Ret genes decreased in TS model, and GDNF expression decreased more in TS + VDD, while TS + VDS had higher GDNF and c-Ret expressions. VDD aggravates, and VDS ameliorates tic-like behavior in an IDPN-induced model. VDS may upregulate GDNF/c-Ret signaling activity through VDR, reversing the striatal DA decrease and alleviating tic-like behavior.

Circulating retinol and 25(OH)D contents and their association with symptoms in children with chronic tic disorders.

The present study measured serum levels of vitamin A (VA) and vitamin D (VD) in children with chronic tic disorders (CTD) and investigated their potential association with CTD and comorbidity of attention deficit hyperactivity disorder (ADHD) and the association of their co-insufficiencies or deficiencies with CTD symptoms. A total of 176 children (131 boys and 45 girls, median age of 9 years) with CTD were recruited as the CTD group. During the same period, 154 healthy children were selected as the healthy control (HC) cohort. Circulating retinol and 25-hydroxyvitamin D (25[OH]D) levels were measured for all participants using high-performance liquid chromatography (HPLC) and tandem mass spectrometry. The Yale Global Tic Severity Scale (YGTSS) was employed for the assessment of tic status and CTD impairment. The Swanson, Nolan, and Pelham Rating Scale (SNAP-IV) and the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) were used to evaluate comorbidity symptoms. CTD pediatric participants exhibited markedly diminished circulating retinol and 25(OH)D levels compared to HCs. Moreover, VA and VD deficiencies and their co-insufficiencies/deficiencies were more prevalent in CTD participants than HCs. Circulating 25(OH)D levels were inversely proportional to the YGTSS motor tic scores. YGTSS scores in CTD children with only VA or VD insufficiency or deficiency or with VA and VD co-insufficiency/deficiency did not differ from those in CTD children with normal VA and VD. CTD children with comorbid ADHD displayed reduced circulating retinol and 25(OH)D concentrations and elevated prevalence of VD deficiency compared to CTD participants without comorbid ADHD. Lower serum retinol content was intricately linked to the presence of elevated CTD and comorbid ADHD. VA and VD deficiencies and their co-insufficiencies/deficiencies were markedly enhanced in CTD pediatric participants compared to HCs. Lower VA concentration was linked to the presence of enhanced CTD and comorbid ADHD. Therefore, children with CTD, especially with comorbid ADHD, may be at a higher risk of VA or VD deficiency, which may prompt the clinicians to consider whether blood tests for VA and VD in CTD children would be helpful for clinical care.

Novel de novo ZNF148 truncating variant causing autism spectrum disorder, attention deficit hyperactivity disorder, and intellectual disability.

ZNF148 gene is a Krüppel-type transcription factor that has transcriptional regulatory function. Heterozygous variant in ZNF148 gene causes an intellectual disability syndrome characterized by global developmental delay, absence, or hypoplasia of corpus callosum, wide intracerebral ventricles, and dysmorphic facial features, while its associations with ASD and ADHD have not been reported. We report a new patient with intellectual disability, autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). The patient had a novel heterozygous truncating variant c.1818dupC (p.Lys607Glnfs*11) in the ZNF148 gene. This variation produces a ZNF148 truncated protein with a deletion of the C-terminal activation domain and may destabilize the protein by affecting the transcriptional activation function. Brain MRI shows normal brain development. Here, we identify a novel ZNF148 heterozygous truncating variant in a patient with distinct phenotypes of ASD and ADHD, which expands the genotype-phenotype spectrum of ZNF148, and indicates ZNF148 is also a potential target gene for ASD.

Both epilepsy and anti-seizure medications affect bone metabolism in children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.

The relationship between screen time before bedtime and behaviors of preschoolers with autism spectrum disorder and the mediating effects of sleep.

BACKGROUND: There are overlapping effects of screen time and sleep on children's behavior. The purpose of this study was to explore the relationship of screen time with behavior problems in children with autism spectrum disorder (ASD) and the probable mediating effects of sleep, in order to provide evidence for the need for clinical identification and intervention. METHODS: A sample of 358 preschoolers with ASD were included. We investigated the children's basic characteristics of sex and age, ASD symptoms (ABC, CARS, and ADOS-2), neurodevelopment (GDS-C), sleep habits (CSHQ), and behavior (CBCL). Pearson correlation tests were used to determine the direct correlations among children's screen time, CBCL, and CSHQ. Linear regression analysis was used to explore whether screen time predicted total score of CBCL. Multi-step linear regression analysis was used to investigate the mediating effect of sleep on the relationship between screen time and total score of CBCL. RESULTS: Screen time before bedtime was correlated with CBCL and CSHQ, which indicated that screen time before bedtime was correlated with sleep and behavior in children with ASD. Screen time before bedtime was a predictor of CBCL total score (indicating children's behavior), and CSHQ total score (indicating children's sleep habits) played a partial mediating role between screen time before bedtime and children's behavior. CONCLUSION: Clinicians should support and educate parents of children with ASD, which should focus on managing screen time, especially screen time before bedtime.

Association of feeding patterns in infancy with later autism symptoms and neurodevelopment: a national multicentre survey.

BACKGROUND: We aimed to compare differences in infant feeding patterns (breastfeeding and complementary food supplementation) between children with the autism spectrum disorder (ASD) and typically developing (TD) children through a multicentre study. The relationship between these patterns and later core symptoms and neurodevelopment in children with ASD was also investigated. METHODS: We analysed breastfeeding and complementary feeding patterns in 1389 children with ASD and 1190 TD children. The Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) was used to assess neurodevelopmental levels. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), Childhood Autism Rating Scale (CARS), and ASD Warning Behavior Subscale of the CNBS-R2016 were used to assess ASD symptoms. RESULTS: Children with ASD had a shorter breastfeeding duration in infancy (8 (3-12) months vs. 10 (6-14) months, P < 0.001), later introduction of complementary foods (P < 0.001), and poorer acceptance of complementary foods (P < 0.001) than TD children. Total ABC and CARS scores were lower in the group of children with ASD who had been breastfed for 12 months or more than in the group who had been breastfed for less than 6 months. Children with ASD who were given complementary food after 6 months had lower general quotient (GQ), adaptive ability, fine motor and language scores than those who were given complementary food within 4-6 months. Children with ASD with poor acceptance of complementary foods had higher ABC and SRS scores and lower gross motor scores than those who had good acceptance. CONCLUSIONS: Children with ASD have a shorter duration of breastfeeding, a later introduction of complementary foods, and poorer acceptance of complementary foods than TD children. These feeding patterns may be related to the symptoms and growth of children with ASD. The research suggests that continued breastfeeding for longer than 12 months may be beneficial in reducing ASD symptoms and that infants who have difficulty introducing complementary foods should be followed up for neurodevelopment. TRIAL REGISTRATION: The ethics committee of the Children's Hospital of Chongqing Medical University approved the study. Approval Number: (2018) IRB (STUDY) NO. 121, and registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000031194, registered on 23/03/2020).

The association of vitamin A, zinc and copper levels with clinical symptoms in children with autism spectrum disorders in Jilin Province, China.

BACKGROUND: This study evaluated vitamin A (VA), copper (Cu), and zinc (Zn) levels in the population with autism spectrum disorder (ASD) in Jilin Province, China. Furthermore, we examined their links to core symptoms and neurodevelopment, as well as gastrointestinal (GI) comorbidities and sleep disorders. METHODS: This study included 181 children with autism and 205 typically developing (TD) children. The participants had not taken vitamin/mineral supplements in the prior three months. High-performance liquid chromatography was used to measure serum VA levels. By using inductively coupled plasma-mass spectrometry, Zn and Cu concentrations in plasma were determined. Importantly, the Childhood Autism Rating Scale, the Social Responsiveness Scale, and the Autism Behavior Checklist were used to measure core ASD symptoms. However, the Griffith Mental Development Scales-Chinese were used to measure neurodevelopment. GI comorbidities and sleep abnormalities were assessed with the 6 Item-Gastrointestinal Severity Index and Children's Sleep Habits Questionnaire, respectively. Children with ASD with GI issues were grouped according to severity (low GI severity and high GI severity groups). RESULTS: (i) The difference in VA, Zn, Cu levels and the Zn/Cu ratio between ASD and TD children is small. But children with ASD had lower VA levels and Zn/Cu ratio, higher Cu levels than TD children. Cu levels in children with ASD were associated with the severity of core symptoms. (ii) Children with ASD were much more likely than their TD counterparts to suffer from GI comorbidities or sleep problems. Furthermore, it was observed that high GI severity was associated with lower levels of VA, whereas low GI severity was associated with higher levels of VA. (iii) The children with ASD who had both lower VA and lower Zn/Cu ratio had more severe scores on the Autism Behavior Checklist, but not on other measures. CONCLUSION: Children with ASD had lower VA and Zn/Cu ratio, and higher Cu levels. Cu levels in children with ASD were weakly correlated with one subscale on social or self-help. ASD children with lower VA levels may face more serious GI comorbidities. Children with ASD combined VA-Zn/Cu lower had more severe core symptoms. TRIAL REGISTRATION: Registration number: ChiCTR-OPC-17013502. Date of registration: 2017-11-23.

Neurodevelopmental domain characteristics and their association with core symptoms in preschoolers with autism spectrum disorder in China: a nationwide multicenter study.

BACKGROUND: Autism spectrum disorder (ASD) is a group of clinically heterogenic neurodevelopmental disorders, with intellectual disability being one of its common comorbidities. No large-sample, multicenter study has focused on the neurodevelopmental aspect of preschoolers with ASD. This study investigated the neurodevelopmental characteristics of preschoolers with ASD in China and explored the association between them and the core symptoms. METHODS: We enrolled 1019 ASD preschoolers aged 2-7 years old from 13 cities around China between May 2018 and December 2019, and used the revised Children Neuropsychological and Behavior Scale (CNBS-R2016) to assess their neurodevelopment. Their autistic core behaviors were evaluated based on their Social Responsiveness Scale (SRS), Autism Behavior Checklist (ABC), Child Autism Rating Scale (CARS), and communication warning behavior (CWB) scores in the CNBS-R2016. RESULTS: Based on general developmental quotient (GQ) < 70, 68.4% of the preschoolers with ASD had a developmental delay (DD), rated mild in 32.7% of them. The highest DD rate (> 70%) was found in language and personal-social skills, followed by fine motor skills (68.9%). Gross motor skills had the lowest DD rate (34.0%). We found that fine motor, language, and personal-social developmental quotients (DQs) were significantly lower than gross motor skills in no DD (GQ > 70), mild DD (GQ 55-69), and moderate and below DD groups (GQ ≤ 54). Furthermore, the DQs for language and personal-social skills were significantly lower than for gross and fine motor skills in both DD groups. The ABC, SRS, CARS, and CWB scores in the no DD group were the lowest, moderate in the mild DD group, and highest in the moderate and below DD group. Besides, negative correlations were found between the DQs of the four domains and the ABC, SRS, CARS, and CWB scores, of which the language and personal-social skills DQs had the strongest correlations. CONCLUSIONS: Preschoolers with ASD had unbalanced neurodevelopment domain patterns and their neurodevelopmental levels were negatively correlated with the autism core symptoms. Hence, pediatricians should actively evaluate the neurodevelopment of children with ASD and conduct long-term follow-up during their early childhood to promote early diagnosis and develop personalized intervention plans. TRIAL REGISTRATION: ChiCTR2000031194 , registered on 03/23/2020.

Non-parental caregivers, low maternal education, gastrointestinal problems and high blood lead level: predictors related to the severity of autism spectrum disorder in Northeast China.

BACKGROUND: The prevalence of autism spectrum disorder (ASD) has increased rapidly in recent years. Environmental factors may play an important role in the pathogenesis of ASD. These factors may include socioeconomic factors, nutritional factors, heavy metal exposure, air pollution, etc. Our aim is to analyze possible environmental factors associated with the severity of ASD. METHODS: All participating children were divided into two groups (mild and moderate/severe) according to the severity of their symptoms, as determined by their Childhood Autism Rating Scale (CARS) scores. The socioeconomic, demographic factors and the nutritional factors that may affect the severity of ASD were included in the logistic regression to analyze whether they were predictors that affected the severity of ASD. RESULTS: Logistic regression showed that caregivers(P = 0.042), maternal education (P = 0.030), gastrointestinal problems (P = 0.041) and a high serum concentration of lead (P = 0.003) were statistically significantly associated with ASD severity. CONCLUSION: Many environmental factors affect the severity of ASD. We concluded that non-parental caregivers, low maternal education, gastrointestinal problems and high blood lead level maybe predictors that affected the severity of ASD in northeast China.

Early life exposure to triclosan from antimicrobial daily necessities may increase the potential risk of autism spectrum disorder: A multicenter study in China.

BACKGROUND: Autism spectrum disorders (ASD) are a group of complex neurodevelopmental disorders with unclear etiologies. Our recent work indicated that maternal exposure to triclosan (TCS) significantly increased the autistic-like behavior in rats, possibly through disrupting neuronal retinoic acid signaling. Although environmental endocrine disruptors (EEDs) have been associated with autism in humans, the relationship between TCS, one of the EEDs found in antibacterial daily necessities, and autism has received little attention. OBJECTIVE: The aims of this multicenter study were to evaluate TCS concentrations in typically developing (TD) children and ASD children, and to determine the relationship between TCS levels and the core symptoms of ASD children. METHODS: A total of 1345 children with ASD and 1183 TD children were enrolled from 13 cities in China. Ages ranged between 2 and 7 years. A questionnaire was used to investigate the maternal use of antibacterial daily necessities (UADN) during pregnancy. The core symptoms of ASD were evaluated using the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Social Response Scale (SRS), and the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). The TCS concentration was measured using LC-MS/MS. RESULTS: Maternal UADN during pregnancy may be an unrecognized potential environmental risk factor for ASD (OR=1.267, P = 0.023). Maternal UADN during pregnancy strongly correlated with TCS levels in the offspring (Adjusted ß = 0.277, P < 0.001). TCS concentration was higher in ASD children (P = 0.005), and positively correlated with ABC (Sensory subscales: P = 0.03; Social self-help subscales: P = 0.011) and SRS scale scores (Social awareness subscales: P = 0.045; Social communication subscales: P = 0.001; Autism behavior mannerisms subscales: P = 0.006; SRS total score: P = 0.003) in ASD children. This association was more pronounced in boys than in girls. CONCLUSION: To our knowledge, this is the first case-control study to examine the correlation between TCS and ASD. Our results suggest that maternal UADN during pregnancy may be a potential risk of ASD in offspring. Further detection of TCS levels showed that maternal UADN during pregnancy may be associated with excessive TCS exposure. In addition, the level of TCS in children with ASD is higher than TD children. The higher levels of TCS in children with ASD may be significantly associated with more pronounced core symptoms, and this association was more significant in male children with ASD.

Sleep problems in children with autism spectrum disorder: a multicenter survey.

BACKGROUND: High prevalence of sleep problems have been reported in children with Autism Spectrum Disorder (ASD). This study aims to investigate the sleep conditions of ASD children in China, and explore the relationship between the common sleep problems and core symptoms and developmental levels. METHODS: Using a cross-sectional design, we included 2 to 7-year-old children from 13 cities in China: 1310 with ASD and 1158 with typically-developing (TD) children. The neurodevelopmental level was evaluated with the revised Children Neuropsychological and Behavior Scale (CNBS-R2016). ASD were diagnosed with DSM-5 and Child Autism Rating Scale (CARS). the Social Responsiveness Scale (SRS), the Autism Behavior Checklist (ABC) and the communication warning behavior sub-scale in CNBS-R2016 valued autism behaviors. The children' s sleep habits questionnaire (CSHQ) assessed sleep conditions. RESULTS: The prevalence of sleep disorders in ASD children was significantly higher than that in TD (67.4% vs. 51%, p < 0.01), and among them the four dimensions with the highest prevalence of sleep problems were bedtime resistance (25.6%), sleep anxiety (22.7%), sleep onset delay (17.9%) and daytime sleepiness (14.7%). ASD children with sleep onset delay or sleep anxiety had higher ABC, SRS scores and higher scores on communication warning behavior with sleep anxiety, with daytime sleepiness had higher ABC, SRS and CARS scores, and with bedtime resistance had higher SRS total scores. Differences in the neurodevelopmental level were not significant. CONCLUSION: Children with ASD have a higher prevalence of sleep problems. Bedtime resistance, anxiety, sleep onset delay and daytime sleepiness may be related to the core symptoms, but not be related to the developmental level in ASD children. In the clinic, sleep assessment should be included in the routine of ASD visits, and during the intervention, sleep hygiene education is as important as the treatment of biological factors. TRIAL REGISTRATION: The study was approved by the ethics committee of the Children's Hospital of Chongqing Medical University, Approval Number: (2018) IRB (STUDY) NO. 121, and registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000031194 ).

[Association between serum trace elements and core symptoms in children with autism spectrum disorder: a national multicenter survey].

OBJECTIVE: To study the association of serum levels of trace elements with core symptoms in children with autism spectrum disorder (ASD). METHODS: From September 2018 to September 2019, an investigation was performed for 1 020 children with ASD and 1 038 healthy children matched for age and sex in the outpatient service of grade A tertiary hospitals and special education institutions in 13 cities of China. Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood Autism Rating Scale (CARS) were used to assess the core symptoms of the children with ASD. The inductively coupled plasma mass spectrometry was used to measure serum levels of trace elements magnesium, iron, copper, and zinc. RESULTS: The children with ASD had significantly lower serum levels of magnesium, copper, and zinc than the healthy children (P < 0.05). The children with severe ASD had significantly lower serum levels of magnesium and zinc than those with mild-to-moderate ASD (P < 0.05). The results of partial correlation analysis showed that serum magnesium level was negatively correlated with the total score of ABC and the score of communication (r=-0.318 and -0.282 respectively; P 0.001), and serum zinc level was negatively correlated with the total score of ABC and the scores of communication and somatic movement (r=-0.221, -0.270, and -0.207 respectively; P < 0.001). CONCLUSIONS: The serum levels of magnesium and zinc may be associated with core symptoms in children with ASD, which requires further studies. The nutritional status of trace elements should be monitored for children with ASD in clinical practice.

A prospective observational study on critically ill children with diaphragmatic dysfunction: clinical outcomes and risk factors.

BACKGROUND: Diaphragmatic dysfunction (DD) has a great negative impact on clinical outcomes, and it is a well-recognized complication in adult patients with critical illness. However, DD is largely unexplored in the critically ill pediatric population. The aim of this study was to identify risk factors associated with DD, and to investigate the effects of DD on clinical outcomes among critically ill children. METHODS: Diaphragmatic function was assessed by diaphragm ultrasound. According to the result of diaphragmatic ultrasound, all enrolled subjects were categorized into the DD group (n = 24) and the non-DD group (n = 46). Collection of sample characteristics in both groups include age, sex, height, weight, primary diagnosis, complications, laboratory findings, medications, ventilatory time and clinical outcomes. RESULTS: The incidence of DD in this PICU was 34.3%. The level of CRP at discharge (P = 0.003) in the DD group was higher than the non-DD group, and duration of elevated C-reactive protein (CRP) (P < 0.001), sedative days (P = 0.008) and ventilatory treatment time (P < 0.001) in the DD group was significantly longer than the non-DD group. Ventilatory treatment time and duration of elevated CRP were independently risk factors associated with DD. Patients in the DD group had longer PICU length of stay, higher rate of weaning or extubation failure and higher mortality. CONCLUSION: DD is associated with poorer clinical outcomes in critically ill childern, which include a longer PICU length of stay, higher rate of weaning or extubation failure and a higher mortality. The ventilatory treatment time and duration of elevated CRP are main risk factors of DD in critically ill children. TRIAL REGISTRATION: Current Controlled Trials ChiCTR1800020196 , Registered 01 Dec 2018.

[Intelligence structure and clinical features of school-age children with attention deficit hyperactivity disorder and specific learning disorder].

OBJECTIVE: To study the intelligence structure and clinical features of children with attention deficit hyperactivity disorder (ADHD) and specific learning disorder (SLD). METHODS: A retrospective analysis was performed on 88 school-age children with ADHD. According to the presence or absence of SLD, they were divided into two groups: simple ADHD group with 45 children and ADHD+SLD group with 43 children. Intelligence structure and clinical features were compared between the two groups. RESULTS: Compared with the simple ADHD group, the ADHD+SLD group had significantly lower verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), and full intelligence quotient (FIQ) (P<0.05), significantly lower scores of VIQ factors (including information, similarities, arithmetic, and recitation) (P<0.05), and significantly lower scores of PIQ factors (including picture completion, picture arrangement, block design, and object assembly) (P<0.05). The development of SLD was negatively correlated with FIQ, VIQ, and PIQ. It was also negatively correlated with the scores of intelligence structure factors (including information, similarities, arithmetic, recitation, picture completion, picture arrangement, block design, and object assembly) (P<0.05). CONCLUSIONS: Children with ADHD and SLD have poorer FIQ, VIQ, and PIQ than those with ADHD alone, which mainly manifests as the weak abilities of most intelligence structure factors. It is necessary to pay attention to the management and intervention of SLD in school-age children with ADHD.

[Effect of parental training based on Early Start Denver Model combined with intensive training on children with autism spectrum disorder and its impact on parenting stress].

OBJECTIVE: To explore the effect of parental training based on the Early Start Denver Model (ESDM) combined with intensive training on the treatment outcome of children with autism spectrum disorder (ASD) and its impact on parenting stress. METHODS: Seventy children aged 2-5 years who were diagnosed with ASD were enrolled in the study. They were divided into an ESDM group and a parental training group by the random number table method (n=35 each). The ESDM group received intensive training based on ESDM. In addition to intensive ESDM-based training, parents of the children in the parental training group received ESDM skills training. Both groups were assessed by Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Autism Treatment Evaluation Checklist (ATEC) and Parenting Stress Index-Short Form (PSI-SF) before and after the intervention of 3 months. RESULTS: After 3 months of intervention, the total scores of ABC, CARS and ATEC were both significantly decreased in the two groups (P<0.05). There was no significant difference in the total scores of ABC, CARS and ATEC between the two groups before and after intervention (P>0.05). The change between ABC, CARS and ATEC total scores in the two groups had no significant difference (P>0.05). After 3 months of intervention, the total scores of PSI-SF were both significantly decreased in the two groups (P<0.05). The difficult child sub-scale scores in PSI-SF were significantly decreased in the ESDM group (P<0.05). While three sub-scale scores of parent distress, parent-child dysfunctional interaction and difficult child in PSI-SF were significantly decreased in the parental training group (P<0.05). Before and after intervention of 3 months, no significant difference was found in PSI-SF total scores between the two groups. Compared with the ESDM group, the change between PSI-SF total scores and two sub-scales of PSI-SF (parent distress and difficult child) were significantly bigger in the parental training group (P<0.05). CONCLUSIONS: Both the combination of intensive training and parent training based on ESDM and ESDM intensive training alone can improve the core symptoms of children with ASD aged 2-5 years and relieve the parenting stress, however, the former is more effective in relieving parenting stress.