Exposure to Environmental Pesticides and the Risk of Autism Spectrum Disorders: A Population-Based Case-Control Study.

Background and Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by challenges in communication, social interactions, and repetitive behaviors. Although the factors that influence the development of this condition are unknown, certain chemical compounds such as pesticides have been proposed as possible contributors. Due to the lack of an established causal link between pesticide exposure and ASD, this study aimed to evaluate this potential association. Materials and Methods: A case-control study was carried out to ascertain the prevalence and risk associated with ASD in relation to pesticide exposure over a 21-year study period (2000-2021). Results: We included 2821 individuals diagnosed with ASD residing in areas of both high and low pesticide exposure in southern Spain. There was a rise in the ASD prevalence rate in regions with elevated pesticide use when compared to regions with low use [odds ratio (OR): 1.34, 95% confidence interval (CI), (1.24-1.44)]. Notably, men had the highest likelihood, with an OR: 1.42, 95% CI, (1.30-1.55). Furthermore, after performing multiple binary logistic regression adjusted for age, sex, and geographical area, males exhibited a higher likelihood compared to females [OR: 2.41, 95% CI, (2.21-2.62)]. Conclusions: Overall, this research suggests a connection between heightened environmental pesticide exposure due to increased agricultural use and autism.

Evaluating screening for autism spectrum disorder using cluster randomization.

We evaluated the rate of autism spectrum disorder (ASD) in a group invited to a screening program compared to the rates in two groups who received usual care. The population eligible for screening was all children in Iceland registered for their 30-month well-child visits at primary healthcare centers (PHCs) from March 1, 2016, to October 31, 2017 (N = 7173). The PHCs in the capital area of Reykjavik were the units of cluster randomization. Nine PHCs were selected for intervention (invited group), while eight PHCs received usual care (control group 1). PHCs outside the capital area were without randomization (control group 2). An interdisciplinary team, including a pediatrician contributing with physical and neurological examination, a psychologist evaluating autism symptoms using a diagnostic instrument, and a social worker interviewing the parents, reached a consensus on the clinical diagnosis of ASD according to the ICD-10 diagnostic system. Children in the population were followed up for at least two years and 119 cases were identified. The overall cumulative incidence of ASD was 1.66 (95% confidence interval (CI): 1.37, 1.99). In the invited group the incidence rate was 2.13 (95% CI: 1.60, 2.78); in control group 1, the rate was 1.83 (95% CI: 1.31, 2.50); and in control group 2, the rate was 1.02 (95% CI: 0.66, 1.50). Although the rate of ASD was higher in the invited group than in the control groups, the wide confidence intervals prevented us from concluding definitively that the screening detected ASD more readily than usual care.

Early childhood exposure to environmental phenols and parabens, phthalates, organophosphate pesticides, and trace elements in association with attention deficit hyperactivity disorder (ADHD) symptoms in the CHARGE study.

BACKGROUND: A growing body of literature investigated childhood exposure to environmental chemicals in association with attention-deficit/hyperactivity disorder (ADHD) symptoms, but limited studies considered urinary mixtures of multiple chemical classes. This study examined associations of concurrent exposure to non-persistent chemicals with ADHD symptoms in children diagnosed with autism spectrum disorder (ASD), developmental delay (DD), and typical development (TD). METHODS: A total of 549 children aged 2-5 years from the Childhood Autism Risks from Genetics and Environment (CHARGE) case-control study were administered the Aberrant Behavior Checklist (ABC). This study focused on the ADHD/noncompliance subscale and its two subdomains (hyperactivity/impulsivity, inattention). Sixty-two chemicals from four classes (phenols/parabens, phthalates, organophosphate pesticides, trace elements) were quantified in child urine samples, and 43 chemicals detected in > 70% samples were used to investigate their associations with ADHD symptoms. Negative binomial regression was used for single-chemical analysis, and weighted quantile sum regression with repeated holdout validation was applied for mixture analysis for each chemical class and all chemicals. The mixture analyses were further stratified by diagnostic group. RESULTS: A phthalate metabolite mixture was associated with higher ADHD/noncompliance scores (median count ratio [CR] = 1.10; 2.5th, 97.5th percentile: 1.00, 1.21), especially hyperactivity/impulsivity (median CR = 1.09; 2.5th, 97.5th percentile: 1.00, 1.25). The possible contributors to these mixture effects were di-2-ethylhexyl phthalate (DEHP) metabolites and mono-2-heptyl phthalate (MHPP). These associations were likely driven by children with ASD as these were observed among children with ASD, but not among TD or those with DD. Additionally, among children with ASD, a mixture of all chemicals was associated with ADHD/noncompliance and hyperactivity/impulsivity, and possible contributors were 3,4-dihydroxy benzoic acid, DEHP metabolites, MHPP, mono-n-butyl phthalate, and cadmium. CONCLUSIONS: Early childhood exposure to a phthalate mixture was associated with ADHD symptoms, particularly among children with ASD. While the diverse diagnostic profiles limited generalizability, our findings suggest a potential link between phthalate exposure and the comorbidity of ASD and ADHD.

Maternal and paternal licit and illicit drug use, smoking and drinking and autism spectrum disorder. / Transtorno do espectro do autismo e o uso materno e paterno de medicamentos, tabaco, álcool e drogas ilícitas.

The aim of this study was to investigate the association between maternal and paternal licit and illicit drug use, smoking and drinking and autism spectrum disorder (ASD). We conducted a case-control study with children and adolescents diagnosed with ASD and neurotypical individuals. The data were collected using a semi-structured questionnaire administered during interviews with the children's mothers or guardians. The following variables were analyzed: child sex and age; maternal and parental age; use of medicines before and during pregnancy; classes of medicines used during pregnancy; maternal and paternal smoking; maternal and paternal drinking; maternal and paternal illicit drug use. The data were analyzed using logistic regression and crude and adjusted odds ratios (OR). After adjustment, the results showed an association between maternal use of antipyretics/pain killers during pregnancy (OR = 2.26; 95%CI 1.29-3.95; p < 0.040) and ASD. No association was found between maternal and paternal smoking, drinking and illicit drug use before and during pregnancy and ASD. The findings suggest that the development of ASD is influenced by environmental factors.

O presente estudo objetivou investigar a associação entre o TEA e o uso materno e paterno de medicamentos, tabaco, álcool e drogas ilícitas. Trata-se de um estudo caso-controle realizado com crianças e adolescentes diagnosticados com TEA e indivíduos neurotípicos. Os dados foram colhidos por meio de entrevista com as mães ou responsáveis. Foram analisadas as variáveis sexo e idade das crianças/adolescentes; idade dos pais; uso de medicamentos antes e durante a gestação; classes de medicamentos usados na gestação; tabagismo materno e paterno; etilismo materno e paterno; uso de drogas ilícitas pelos pais. Para a análise das informações, utilizou-se o modelo de regressão logística, além da razão de chances (OR) bruta e ajustada. Os resultados mostraram que, após os ajustes, foi encontrada associação entre o uso materno na gestação de antitérmicos/analgésicos (OR = 2,26; IC95% 1,29-3,95; p < 0,040) com o TEA. Já o uso de tabaco, álcool e drogas ilícitas materno e paterno, antes e durante a gestação, não apontou relação com o TEA. Os dados encontrados sugerem que existe influência de fatores ambientais no desenvolvimento do TEA.

[Catatonia in youth with developmental disabilities: challenges in recognition and management]. / Katatonie bij jongeren met een ontwikkelingsstoornis: uitdagingen in herkenning en aanpak.

Catatonia in children and adolescents is not rare and, as in adults, has a favorable outcome, provided it is recognized and treated promptly. Nevertheless, in clinical practice we encounter several obstacles in terms of diagnosis and treatment in this population of patients. We describe a 14-year-old boy with an intellectually disability and autism spectrum disorder (ASD) in which clinicians did not diagnose catatonia until 1 year after the development of symptoms. Moreover, hesitations surrounding the correct treatment led to its delayed initiation. With this case report we aim to contribute to reduced reluctance and increased alertness in the treatment of catatonia in adolescents with developmental disorders.

Sex, hormones and cerebrovascular function: from development to disorder.

Proper cerebrovascular development and neurogliovascular unit assembly are essential for brain growth and function throughout life, ensuring the continuous supply of nutrients and oxygen. This involves crucial events during pre- and postnatal stages through key pathways, including vascular endothelial growth factor (VEGF) and Wnt signaling. These pathways are pivotal for brain vascular growth, expansion, and blood-brain barrier (BBB) maturation. Interestingly, during fetal and neonatal life, cerebrovascular formation coincides with the early peak activity of the hypothalamic-pituitary-gonadal axis, supporting the idea of sex hormonal influence on cerebrovascular development and barriergenesis.Sex hormonal dysregulation in early development has been implicated in neurodevelopmental disorders with highly sexually dimorphic features, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Both disorders show higher prevalence in men, with varying symptoms between sexes, with boys exhibiting more externalizing behaviors, such as aggressivity or hyperactivity, and girls displaying higher internalizing behaviors, including anxiety, depression, or attention disorders. Indeed, ASD and ADHD are linked to high prenatal testosterone exposure and reduced aromatase expression, potentially explaining sex differences in prevalence and symptomatology. In line with this, high estrogen levels seem to attenuate ADHD symptoms. At the cerebrovascular level, sex- and region-specific variations of cerebral blood flow perfusion have been reported in both conditions, indicating an impact of gonadal hormones on the brain vascular system, disrupting its ability to respond to neuronal demands.This review aims to provide an overview of the existing knowledge concerning the impact of sex hormones on cerebrovascular formation and maturation, as well as the onset of neurodevelopmental disorders. Here, we explore the concept of gonadal hormone interactions with brain vascular and BBB development to function, with a particular focus on the modulation of VEGF and Wnt signaling. We outline how these pathways may be involved in the underpinnings of ASD and ADHD. Outstanding questions and potential avenues for future research are highlighted, as uncovering sex-specific physiological and pathological aspects of brain vascular development might lead to innovative therapeutic approaches in the context of ASD, ADHD and beyond.

[Study on primary screening technique for children with autism spectrum disorder].

To explore screening tools for children with autism spectrum disorder (ASD), which are convenient for primary hospitals, it can provide basic data for formulating ASD prevention policies. This was a cross-sectional study by cluster sampling. Huyi District and Xincheng District were extracted for investigation in Xi'an City. From July 2021 to September 2022, all children aged from 3 months to 36 months who live in the two districts were subjected to primary screening. The child care physician used the routine screening tool "warning signs checklist for screening psychological, behavioral and developmental problems of children" and cartoon pictures of "early high-risk warning signs of autism", the children who were positive in the initial screening were referred to the district level maternal and child health hospital for re-screening, and those who were positive in the re-screening were referred to Xi 'an Children's Hospital for diagnosis. The results showed that a total of 17 905 children aged from 3 months to 36 months were initially screened in the two districts, including 10 588 children aged from 18 months to 36 months, 50 children who were positive in the initial screening and 50 children who were re-screened. 23 children (18 boys and 5 girls) were diagnosed with ASD. The prevalence rate of ASD in children was 2.17‰ (95% confidence interval:1.29‰-3.06‰). 42 children were positive for "warning signs checklist" at the preliminary screening, and 19 were confirmed as ASD. 27 children were positive for "cartoon pictures" in the preliminary screening, and 23 were confirmed with ASD. The "cartoon pictures" in the preliminary screening and diagnosis of consistent rate was higher than the "warning signs checklist", two kinds of screening methods comparison were statistically significant difference in the odds of consistent (χ2=11.01, P=0.001). In conclusion, relying on the three-level network of maternal and child health care, it is conducive to the whole process management of screening and diagnosis of children with ASD, and to guide the formulation of prevention policies. The cartoon pictures of "early high-risk warning signs of autism" can assist the identification of children with ASD based on the "warning signs checklist", which is simple, effective and suitable for promotion in the community health care.

Pre- and Perinatal Risk Factors for Youth with Autism Spectrum Disorder Versus Youth with Other Mental Health Disorders.

Research has linked pre- and perinatal complications (PPCs) with increased risk for autism spectrum disorder (ASD). However, PPCs are also known risk factors for other mental health disorders. This study explored which PPCs are specific risk factors for ASD, as opposed to other forms of psychopathology, among a large sample of clinically-referred youth. Archival data were used from 1177 youth who were evaluated at a hospital-based autism clinic. Results from logistic regressions indicated that use of tobacco, alcohol, or drugs, or experiencing amniocentesis predicted inclusion in the non-ASD group, while physical difficulties with delivery predicted inclusion in the ASD group. Possible explanations and implications for these findings are discussed.

Early identification of autism spectrum disorder in children with CHD attending a Cardiac Developmental Outcomes Program.

OBJECTIVE: To determine the prevalence and timing of autism spectrum disorder diagnosis in a cohort of congenital heart disease (CHD) patients receiving neurodevelopmental follow-up and identify associated risk factors. METHOD: Retrospective single-centre observational study of 361 children undergoing surgery for CHD during the first 6 months of life. Data abstracted included age at autism spectrum disorder diagnosis, child and maternal demographics, and medical history. RESULTS: Autism spectrum disorder was present in 9.1% of children with CHD, with a median age at diagnosis of 34 months and 87.9% male. Prematurity, history of post-operative extracorporeal membrane oxygenation, and seizures were higher among those with autism (p = 0.013, p = 0.023, p = 0.001, respectively). Infants with autism spectrum disorder were older at the time of surgery (54 days vs 13.5 days, p = 0.002), and infants with surgery at ≥ 30 days of age had an increased risk of autism spectrum disorder (OR 2.31; 95% CI =1.12, 4.77, p = 0.023). On multivariate logistic regression analysis, being male (OR 4.85, p = 0.005), surgery ≥ 30 days (OR 2.46, p = 0.025), extracorporeal membrane oxygenation (OR 4.91, p = 0.024), and seizures (OR 4.32, p = 0.003) remained associated with increased odds for autism spectrum disorder. Maternal age, race, ethnicity, and surgical complexity were not associated. CONCLUSIONS: Children with CHD in our cohort had more than three times the risk of autism spectrum disorder and were diagnosed at a much earlier age compared to the general population. Several factors (male, surgery at ≥ 30 days, post-operative extracorporeal membrane oxygenation, and seizures) were associated with increased odds of autism. These findings support the importance of offering neurodevelopmental follow-up after cardiac surgery in infancy.

Impacto de la pandemia por COVID-19 en la conducta alimentaria de niñas, niños y adolescentes con trastorno del espectro autista / Impact of the COVID-19 pandemic on the eating behaviors of children and adolescents with autism spectrum disorder

Introducción. Los niños con trastorno del espectro autista (TEA) presentan dificultades de adaptación a situaciones estresantes, como la pandemia por COVID-19. Objetivo. Evaluar el impacto del primer año de pandemia en las dificultades alimentarias de niños con TEA. Población y métodos. Se invitó a participar a cuidadores de niños con TEA no sindromático (edad: 2-18 años) de una unidad de neurodesarrollo. Los participantes respondieron en línea un cuestionario y la escala de evaluación de problemas de conducta alimentaria (BPFAS por su sigla en inglés) antes y durante el primer año de pandemia. Se calculó un puntaje de prioridad (producto entre promedio de frecuencia y problema) para cada ítem del BPFAS. Resultados. El 56,6 % (86/152) de los cuidadores contestó la encuesta (madre 74,4 %), mediana de edad 6,3 años (p25-p75: 4,7-8,2); el 80,2 % de los niños eran de sexo masculino; el 58,1 % mantuvo terapia durante la pandemia y el 61,6 % presentaba problemas de comportamiento previo a esta. Durante el primer año de pandemia, los niños presentaron mayor intensidad en dificultades conductuales (34,9 %) y de alimentación (61,6 %); sin embargo, el 31,4 % refirió mejoría en la alimentación. No existieron diferencias significativas entre puntajes BPFAS antes y durante la pandemia. Los ítems con mayor puntaje de prioridad fueron "se levanta de la mesa durante la hora de comer", "no probar alimentos nuevos", "no come verduras", "no come frutas". Conclusiones. Hubo alta frecuencia de dificultades en las conductas alimentarias durante el primer año de pandemia. No se presentaron diferencias en las características de estas conductas antes y durante la pandemia.

Introduction. Children with autism spectrum disorder (ASD) have difficulties adapting to stressful situations, such as the COVID-19 pandemic. Objective. To assess the impact of the first year of the pandemic on feeding difficulties in children with ASD. Population and methods. The caregivers of children and adolescents with non-syndromic ASD (age: 2­18 years) from a neurodevelopment unit were invited to participate. Participants completed a questionnaire and the Behavioral Pediatrics Feeding Assessment Scale (BPFAS) online before and during the first year of the pandemic. A priority score (product between the average frequency and the problem) for each BPFAS item was estimated. Results. Among the caregivers, 56.6% (86/152) completed the survey (mother: 74.4%); children's median age was 6.3 years (p25­p75: 4.7­8.2); 80.2% of children were males; 58.1% continued with their therapy during the pandemic; and 61.6% had behavioral problems before the pandemic. During the first year of the pandemic, children had greater behavioral problems (34.9%) and feeding difficulties (61.6%); however, 31.4% of caregivers referred improvements in feeding. There were no significant differences in the BPFAS scores before and during the pandemic. The following items obtained the highest priority scores: gets up from table during meal, does not try new food, does not eat vegetables, does not eat fruits. Conclusions. A high frequency of feeding difficulties was noted during the first year of the pandemic. No differences were observed in feeding characteristics before and during the pandemic.

Prevalence and nature of prior developmental and medical concerns in toddlers who screen positive for autism in primary care.

LAY ABSTRACT: The American Academy of Pediatrics recommends that all children be screened for autism at their 18- and 24-month well-child visit. For children who screen positive for autism, it is unknown whether this usually represents the first time a developmental concern has been raised or if other developmental concerns typically precede a positive autism screen. Such knowledge could help guide providers in how to appropriately convey feedback regarding autism screening. This study found that, for close to 80% of children with a positive autism screen, caregivers or providers had a prior autism, language, motor, or other developmental concern documented in the electronic health record. Many also had other prior concerns frequently linked to autism, such as sleep and gastrointestinal problems, and received physical or speech therapy. On average, prior to screening children who received a positive Modified-Checklist for Autism in Toddlers had two documented concerns by at 1 year of age and three concerns by 2 years of age. These findings imply that screening for autism as a part of routine pediatric care likely takes place in the context of larger conversations regarding existing developmental concerns, allowing for a less stigmatizing discussion of autism. Framing the presence of prior concerns in the setting of a positive screen in this context may create a reaffirming space for existing caregiver concerns and a lessened emotional burden on caregivers.

[Association between maternal gestational diabetes mellitus and the risk of autism spectrum disorder in offspring]. / æ¯äº²å¦Šå¨ ç³–å°¿ç— ä¸Žå­ä»£å­¤ç‹¬ç—‡è°±ç³»éšœç¢å‘ç”Ÿé£Žé™©çš„å ³è”åˆ†æž.

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.

Neurodevelopmental impairments in children with septo-optic dysplasia spectrum conditions: a systematic review.

BACKGROUND: Septo-optic dysplasia (SOD) is a rare condition diagnosed in children with two or more of the following: hypopituitarism, midline brain abnormalities, and optic nerve hypoplasia. Children with SOD experience varied visual impairment and endocrine dysfunction. Autistic-like behaviours have been reported; however, their nature and prevalence remain to be fully understood. The present systematic review aimed to explore the type and prevalence of neurodevelopmental impairments in children with SOD spectrum conditions. METHODS: The search was conducted in PubMed, EMBASE, and PsycInfo. Hand-searching reference lists of included studies was conducted. All peer-reviewed, observational studies assessing behavioural and cognitive impairments or autism spectrum disorder (ASD) symptoms in children (< 18 years) with SOD, optic nerve hypoplasia, and SOD-plus were included. Studies were excluded if they did not report standardised measures of neurodevelopmental impairments or ASD outcomes. RESULTS: From 2132 screened articles, 20 articles reporting data from a total of 479 children were included in prevalence estimates. Of 14 studies assessing cognitive-developmental outcomes, 175 of 336 (52%) children presented with intellectual disability or developmental delay. A diagnosis of ASD or clinical level of symptoms was observed in 65 of 187 (35%) children across five studies. Only five studies assessed for dysfunction across behavioural, emotional, or social domains and reported impairments in 88 of 184 (48%) of children assessed. LIMITATIONS: Importantly, high heterogeneity among the samples in relation to their neuroanatomical, endocrine, and optic nerve involvement meant that it was not possible to statistically assess the relative contribution of these confounding factors to the specific neurodevelopmental phenotype. This was further limited by the variation in study designs and behavioural assessments used across the included studies, which may have increased the risk of information bias. CONCLUSIONS: This systematic review suggests that the prevalence of neurodevelopmental impairments in children within the SOD spectrum may be high. Clinicians should therefore consider including formal assessments of ASD symptoms and neurodevelopmental impairments alongside routine care. There is, additionally, a need for further research to define and validate a standardised battery of tools that accurately identify neurodevelopmental impairments in SOD spectrum conditions, and for research to identify the likely causal mechanisms.

Factor analysis of the autism spectrum screening questionnaire in a population-based child sample.

PURPOSE: The aim of this study was to investigate several possible factor structures of the Autism Spectrum Screening Questionnaire (ASSQ). MATERIALS AND METHODS: We used the 27-item screening tool for school-aged children in a general population of 8-year-old children (n = 3,538) and compared the occurring solutions to previously published factor models. RESULTS: A one-factor solution and a four-factor solution were identified in Exploratory Factor Analysis (EFA) and confirmed with Confirmatory Factor Analysis (CFA), while two-, three-, five- and six-factor solutions were rejected. In CFA, our four-factor solution showed the best goodness-of-fit indexes when compared with factor models previously presented by Posserud et al. and Ehlers et al. CONCLUSIONS: The results indicate a strong underlying connection between all ASSQ items which is elicited by the one-factor solution. Although as a screening tool, ASSQ is functioning with the unifactorial solution, the four factors can help to identify certain clusters of autism spectrum traits.

Neurodevelopmental Outcomes of a Cohort of Children with Tuberous Sclerosis Complex with Epileptic Spasms.

The neurodevelopmental outcomes in children with tuberous sclerosis complex (TSC) with epileptic spasms remain underdiagnosed and might be responsible for significant morbidity and mortality burdens, even after spasms abate. The study was a cross-sectional study over 18 months at a tertiary care pediatric hospital, involving 30 children with TSC who had epileptic spasms. They were assessed with Diagnostic and Statistical Manual of Mental Disorders-5 criteria for autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and intellectual disability (ID), and childhood psychopathology measurement schedule (CPMS) for behavioral disorders. The median age at onset of epileptic spasms was 6.5 (1-12) months, and the age at enrolment was 5 (1-15) years. Of 30 children, 2 (6.7%) had only ADHD, 15 (50%) had only ID/GDD (global developmental delay), 4 (13.3%) had ASD and ID/GDD, 3 (10%) had ADHD and ID/GDD, and 6 (20%) had none. The median intelligence quotient/development quotient (IQ/DQ) score was 60.5 (20-105). CPMS assessment revealed significant behavioral abnormalities in almost half the children. Eight (26.7%) patients were completely seizure-free for at least 2 years, 8 (26.7%) had generalized tonic-clonic seizures, 11 (36.6%) had focal epilepsy, and 3 (10%) had evolved into Lennox-Gastaut syndrome. A high proportion of neurodevelopment disorders, including ASD, ADHD, ID/GDD, and behavioral disorders were seen in this pilot study with a small cohort of children with TSC with epileptic spasms.

Iron Deficiency in Attention-Deficit Hyperactivity Disorder, Autism Spectrum Disorder, Internalizing and Externalizing Disorders, and Movement Disorders.

This article reviews the role of iron in brain development and function, with a focus on the association between iron deficiency (ID) and neuropsychiatric conditions. First, we describe how ID is defined and diagnosed. Second, the role of iron in brain development and function is summarized. Third, we review current findings implicating ID in a number of neuropsychiatric conditions in children and adolescents, including attention deficit hyperactivity disorder and other disruptive behavior disorders, depressive and anxiety disorders, autism spectrum disorder, movement disorders, and other situations relevant to mental health providers. Last, we discuss the impact of psychotropic medication on iron homeostasis.

Examining the relationship between autism spectrum disorder and neural tube defects.

Folate and vitamin B12 deficiencies have been strongly associated with neural tube defects, preliminary research suggests folate and B12 deficiency may also be associated with autism spectrum disorder (ASD). We examined the association between neural tube defects and ASD as a further avenue to examine the hypothesis that ASD is related to maternal folate and B12 deficiency during pregnancy. A retrospective case-control study was performed using the Military Health System Data Repository. Cases and matched controls were followed from birth until at least 6 months after their first autism diagnosis. International Classification of Diseases, 9th Revision, codes were used to identify neural tube defects in the health records. A total of 8760 cases between the ages of 2 and 18 years were identified. The prevalence of any neural tube defect was 0.11% in children without ASD and 0.64% in children with ASD. Children with autism were over 6 times as likely to have a neural tube defect. The increased odds of neural tube defect in children diagnosed with ASD, found through our methodology, supports prior studies. Although additional studies are needed to elucidate the relationship between ASD and maternal folate and vitamin B12 deficiency during pregnancy this study supports their use during pregnancy.

Co-occurring conditions in children with Down syndrome and autism: a retrospective study.

BACKGROUND: Down syndrome (DS) is one of the most common genetic causes of intellectual disability, and it is associated with an increased incidence of numerous co-occurring conditions. Autism spectrum disorder (ASD) is common in persons with DS, with rates reported as high as 39%. However, little is known regarding co-occurring conditions in children with both DS and ASD. METHODS: A single-center retrospective review of prospective longitudinally collected clinical data was performed. Any patient with a confirmed diagnosis of DS evaluated at a large, specialized Down Syndrome Program in a tertiary pediatric medical center between March 2018 and March 2022 was included. A standardized survey which included demographic and clinical questions was administered during each clinical evaluation. RESULTS: In total, 562 individuals with DS were included. The median age was 10 years (IQR: 6.18-13.92). Of this group, 72 (13%) had a co-occurring diagnosis of ASD (DS+ASD). Individuals with DS+ASD were more likely to be male (OR 2.23, CI 1.29-3.84) and had higher odds of a current or prior diagnosis of constipation (OR 2.19, CI 1.31-3.65), gastroesophageal reflux (OR 1.91, CI 1.14-3.21), behavioral feeding difficulties (OR 2.71, CI 1.02-7.19), infantile spasms (OR 6.03, CI 1.79-20.34) and scoliosis (OR 2.73, CI 1.16-6.40). There were lower odds of congenital heart disease in the DS+ASD group (OR 0.56, CI 0.34-0.93). There was no observed difference in prematurity or Neonatal Intensive Care Unit complications between groups. Individuals with DS+ASD had similar odds of having a history of congenital heart defect requiring surgery to those with DS only. Furthermore, there was no difference in rates of autoimmune thyroiditis or celiac disease. There was also no difference in rates of diagnosed co-occurring neurodevelopmental or mental health conditions in this cohort, including anxiety disorders and attention-deficit/hyperactivity disorder. CONCLUSIONS: This study identifies a variety of medical conditions which are more frequent in children with DS+ASD than DS alone, providing important information for the clinical management of these patients. Future research should investigate the role of some of these medical conditions in the development of ASD phenotypes, and whether there may be distinct genetic and metabolic contributions towards these conditions.

Risk of Major Psychiatric Disorders Among Children and Adolescents Surviving Malignancies: A Nationwide Longitudinal Study.

PURPOSE: Evidence suggests an increased long-term risk of major psychiatric disorders (MPDs) in childhood and adolescent cancer survivors (CACSs). However, definitive conclusions regarding such associations and whether such associations vary for different types of cancers remain unclear. METHODS: Using a nationwide data set from 2001 to 2011, we enrolled CACSs and likewise randomly selected individuals without cancer from the general population (1:10 ratio) who were matched to the CACSs with regard to demographic data. We investigated eight organ system-related cancers. The primary outcomes were the risks of seven MPD diagnoses: autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and post-traumatic stress disorder. RESULTS: CACSs (n = 5,121; mean age = 9.08 years) showed increased risks of six MPD diagnoses than controls (n = 51,210), with results as follows (in descending order): ASD (hazard ratio [HR], 10.42; associated 95% CI, 4.58 to 23.69), ADHD (HR, 6.59; 95% CI, 4.91 to 8.86), BD (HR, 2.93; 95% CI, 1.26 to 6.80), MDD (HR, 1.88; 95% CI, 1.26 to 2.79), OCD (HR, 3.37; 95% CI, 1.33 to 8.52), and post-traumatic stress disorder (HR, 6.10; 95% CI, 1.46 to 25.54). CACSs also showed earlier ages at diagnoses of ADHD, schizophrenia, MDD, and OCD than controls. The risks of MPD diagnoses vary according to specific cancer types/categories. Brain cancer and lymphatic/hematopoietic tissue cancer were associated with the greatest number of MPD diagnoses (ie, each was associated with six diagnoses). In addition, ASD and ADHD were associated with most organ system-related cancers (ie, each was associated with five categories). CONCLUSION: We found that CACSs were at higher risks of MPD diagnoses than controls. Follow-up care should include psychosocial interventions focusing on early signs of mental health problems and early interventions in this high-risk group.

Tympanostomy Tube Placement in Children with Autism Spectrum Disorder.

OBJECTIVE: The frequency of tympanostomy tube (TT) placement among United States children with autism spectrum disorder (ASD) is not known. We explored the rate of TT placement in children with ASD in the United States and compared this to children without ASD. We further examined demographic and behavioral factors that might vary between the two groups. METHODS: We utilized data from the National Health Interview Survey (NHIS) administered in 2014. This survey samples a representative population of patients across the United States and includes children under 18 years of age. The 2014 version of the NHIS survey was chosen as it identifies both autism and TT placement among sampled patients. Descriptive statistics and univariable and multivariable logistic regression analyses were performed. RESULTS: In total, 11,730 children (239 [2.0%] with ASD) were included. Overall, 34 (14.2%) children with ASD underwent TT placement versus 987 (8.6%) in children without ASD (p = 0.002) ASD diagnosis was associated with increased odds of TT placement (1.52 OR, 95% CI 1.04-2.22). Male sex, white race, and non-Hispanic ethnicity were also associated with increased odds of TT placement. Age at the time of TT surgery was not different between those with versus without ASD. CONCLUSION: Children with ASD have an increased rate of TT placement compared to children without ASD. The reason(s) for this increased rate might include the following: higher rates of infection in ASD, over-diagnosis of ear infection or hearing disability in a difficult-to-examine population, and/or a predilection toward aggressive treatment in this at-risk group. LEVEL OF EVIDENCE: 3-National database study Laryngoscope, 133:2407-2412, 2023.