Risk Factors For Autism Spectrum Disorder Research Articles

Prenatal & Perinatal Risk Factors of Autism Spectrum Disorder

Background: Autism spectrum disorder (ASD) is lifelong neurodevelopmental disorder characterized by impairments in social function, communication, and certain behaviors. The etiology of ASD is unclear & it is believed to be multi-factorial, among those several prenatal & perinatal factors are found to be significant. So, the necessity of this study is to detect the presence of known risk factors of ASD which in turn may help in the early diagnosis and intervention for better long-term outcomes. Objective: To find out prenatal and perinatal risk factors of ASD. Method: A case control study was conducted with 112 cases of ASD and 201 controls of 2-6 years of age. The study was carried out in Center for Neurodevelopment and Autism in Children (CNAC), in the department of Paediatrics, Bangabandhu Sheikh Mujib Medical University and Autism Welfare Foundation (AWF). ASD was diagnosed by DSM-IV TR criteria. Mothers were interviewed and data were collected by semistructured questionnaires. Results: Total 5 risk factors were identified as the risk factors of ASD. They were: advanced paternal age (OR=2.84) and maternal age (OR=1.87); male baby (OR=2.01); environmental stress during pregnancy (OR=1.61) and preterm delivery (OR=1.80). Conclusions: It is concluded that advanced paternal age, maternal age, male baby, environmental stress during pregnancy and preterm delivery are associated with increased risk of ASD. BANGLADESH J CHILD HEALTH 2022; VOL 46 (3) : 115-121

Investigation of Liver X Receptor Gene Variants and Oxysterol Dysregulation in Autism Spectrum Disorder.

The NR1H2 gene produces the Liver X Receptor Beta (LXRB) protein, which is crucial for brain cholesterol metabolism and neuronal development. However, its involvement in autism spectrum disorder (ASD) remains largely unexplored, aside from animal studies. This study is the first to explore the potential link between autism and rs2695121/rs17373080 single nucleotide polymorphisms (SNPs) in the regulatory regions of NR1H2, known for their association with neuropsychiatric functions. Additionally, we assessed levels of oxysterols (24-Hydroxycholesterol, 25-Hydroxycholesterol, 27-Hydroxycholesterol), crucial ligands of LXR, and lipid profiles. Our cohort comprised 107 children with ASD and 103 healthy children aged 2-18 years. Clinical assessment tools included the Childhood Autism Rating Scale, Autistic Behavior Checklist, and Repetitive Behavior Scale-Revised. Genotyping for SNPs was conducted using PCR-RFLP. Lipid profiles were analyzed with Beckman Coulter kits, while oxysterol levels were determined through liquid chromatography-tandem mass spectrometry. Significantly higher total cholesterol (p = 0.003), LDL (p = 0.008), and triglyceride (p < 0.001) levels were observed in the ASD group. 27-Hydroxycholesterol levels were markedly lower in the ASD group (p ≤ 0.001). ROC analysis indicated the potential of 27-Hydroxycholesterol to discriminate ASD diagnosis. The SNP genotype and allele frequencies were similar in both groups (p > 0.05). Our findings suggest that disturbances in oxysterol metabolism, previously linked to neurodegeneration, may constitute a risk factor for ASD and contribute to its heterogeneous phenotype.

Environmental Risk Factors in Autism Spectrum Disorder: A Narrative Review.

Existing evidence indicates that environmental factors might contribute up to 50% of the variance in autism spectrum disorder (ASD) risk. This structured narrative review offers a comprehensive synthesis of current knowledge on environmental risk factors in ASD, including evaluation of conflicting evidence, exploration of underlying mechanisms, and suggestions for future research directions. Analysis of diverse epidemiological investigations indicates that certain environmental factors, including advanced parental age, preterm birth, delivery complications, and exposure to toxic metals, drugs, air pollutants, and endocrine-disrupting chemicals, are linked to an increased ASD risk through various mechanisms such as oxidative stress, inflammation, hypoxia, and its consequences, changes in neurotransmitters, disruption of signaling pathways and some others. On the other hand, pregnancy-related factors such as maternal diabetes, maternal obesity, and caesarian section show a weaker association with ASD risk. At the same time, other environmental factors, such as vaccination, maternal smoking, or alcohol consumption, are not linked to the risk of ASD. Regarding nutritional elements data are inconclusive. These findings highlight the significance of environmental factors in ASD etiology and emphasize that more focused research is needed to target the risk factors of ASD. Environmental interventions targeting modifiable risk factors might offer promising avenues for ASD prevention and treatment.

The role of the CNTNAP2 gene in the development of autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which genetic and environmental factors interact in its development. Research suggests that the contactin associated protein 2 (CNTNAP2) gene may play a role in ASD pathophysiology, yet more studies involving human participants and animal models of autism are needed. One such model may be the use of prenatal valproic acid (VPA) model to induce autism-like behaviors in offspring rats. The aim of this study was twofold: (1) to examine the association of the CNTNAP2 gene rs2710102 variant with ASD in children; and (2) to examine the effect of prenatal exposure to VPA on Cntnap2 gene expression in the rat brain. The study included 167 children of European ancestry—81 diagnosed with ASD (20 girls, 61 boys; age 4.9 ± 1.4 years) and 86 controls (44 girls, 42 boys; 5.1 ± 1.2 years). In vivo experiments were conducted in 80 rats (40 with the VPA model of autism), with Cntnap2 gene expression analysis in the amygdala, hippocampus, prefrontal cortex, and cerebellum. Results demonstrated that the frequency of the CNTNAP2 gene rs2710102 GG genotype was significantly higher in children with ASD when compared with controls (33.3 vs 19.8%; OR=2.03, 95%CI [1.004, 4.102], p = 0.035), although, potentially due to bias in cohort selection, in the ASD children this polymorphism did not meet Hardy-Weinberg expectations (χ2 =5.40, p = 0.02). In addition, Cntnap2 gene expression was significantly lower (p < 0.01) in the amygdala and hippocampus of VPA rats when compared with controls, regardless of sex. These results support previous research and provide evidence for the CNTNAP2 gene as a risk factor for ASD.

The Association Between Children's Autism Spectrum Disorders and Central Nervous System Infections: Using a Nationwide Claims Database.

Several studies have reported an association of autism spectrum disorder (ASD) with central nervous system (CNS) infections and intrauterine infections; however, the results remain unclear. This study aimed to examine this issue using an extensive national database. Utilizing JMDC medical claims database, we conducted a retrospective cohort study of children with at least three years of follow-up from birth, ensuring the mother's information was available. The focus was on the relationship between ASD incidence and exposures like viral meningitis/encephalitis, bacterial meningitis, and intrauterine infections. Cox proportional hazards was used to calculate hazard ratios (HRs) with covariates such as presence of maternal history of mental illness, preterm, low birth weight, respiratory and cardiac disorder, epilepsy, and cranial malformations. Sensitivity analysis was performed on sibling and multiple birth cohorts to adjust for genetic factors. Out of 276,195 mother-child pairs, bacterial meningitis was observed in 1326 (0.5%), viral meningitis/encephalitis in 6066 (2.2%), intrauterine infection in 3722 (1.3%), and ASD in 14,229 (5.2%) children. The adjusted HRs (95% confidence interval, p value) for ASD were 1.40 (1.25-1.57, p < 0.001), 1.14 (1.02-1.26, p = 0.013), and 1.06 (0.87-1.30, p = 0.539) for viral meningitis/encephalitis, intrauterine infection, and bacterial meningitis, respectively. After sensitivity analysis, the HRs for viral meningitis/encephalitis and ASD remained significantly high. Viral meningitis/encephalitis may be an independent risk factor for ASD. Awareness of this risk among healthcare professionals can lead to early intervention and potentially improved outcomes for affected children.

Neonatal Risk Factors for ASD and ADHD and Therapeutic Regimens for their Management in Children and AdolescentSD and ADHD?

Background: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both neurodevelopmental disorders that affect children early in life. Both conditions have a complicated origin. Objectives: This study aims to evaluate the neonatal complications linked with ASD and ADHD and to outline the utilization of psychotropic medications in the management of children and adolescents with ASD. Methods: This study was conducted from January to April 2022 at the National Center for Autism/Medical City Complex in Baghdad. It involved 120 children with neurodevelopmental disorders and 120 control participants. A questionnaire was used to collect the data, which was then analyzed using SPSS 25. Results: Five perinatal factors have significant associations with child behavioral disorders, as indicated by a P-value of less than 0.05. These factors are Low birth weight (LBW), newborn complications, preterm birth, being the last child, and children delivered via a cesarean section. Additionally, the types of behavioral disorders have significant associations with the use of psychotropic medications. Around 50% of children with both ASD and ADHD, as well as children with ADHD alone, have used psychotropic medications. By comparison, only about 27% of children with ASD have used these medications. Conclusions: Neonatal risk factors may be linked to neurodevelopmental disorders. Medications are used to manage ASD and ADHD in children and youth.

Dietary nutrients that potentially mitigate autism spectrum disorder and dietary recommendations for children and pregnant women

AbstractThe increasing incidence of autism spectrum disorder (ASD) worldwide poses serious social and family problems. Various risk factors for ASD are gradually being recognized, and there are also various options for the treatment of ASD. It is worth noting that dietary interventions have been shown to have a positive effect in terms of mitigating and preventing some psychiatric disorders, such as epilepsy, Parkinson's disease, and ASD, and they are gradually receiving attention as a safe adjuvant treatment. In this review, based on the current understanding of the pathogenic factors and intervention strategies for ASD, different dietary patterns that can be selected for children with ASD are discussed in depth. Moreover, a review was conducted on the use of dietary factors, such as natural products from food sources, prebiotics, and probiotics, as effective supplements to existing dietary patterns. As increasing evidence shows that maternal risk factors, such as obesity, diabetes, and hypertension, are associated with an increased risk of ASD in offspring, dietary suggestions are also made for pregnant woman with ASD‐related risk factors to counteract the impact of these risk factors. With compensation from food‐derived natural products, prebiotics, and probiotics, suitable dietary patterns can further enhance the effectiveness of dietary interventions for ASD. In addition, dietary recommendations for pregnant woman may reduce the potential impact of obesity, diabetes, and hypertension and may help to prevent the occurrence of ASD to the maximum extent possible.

عوامل الخطر قبل الولادة وأثناء الولادة و بعد الولادة المرتبطة باضطراب طيف التوحد في فلسطين: دراسة الحالات و الشواهد

Background: Autism spectrum disorder (ASD) is a multifactorial neurodevelopment disorder. Several prenatal, perinatal, and postnatal factors are suggested as risk factors for ASD. This study aimed to correlate prenatal, perinatal, and postnatal factors in a limited number of cases in Palestine. Methods: A case-control study involved 120 children (60 typically diagnosed with ASD and 60 healthy matched with the ASD group). The parents of the children in both groups were asked to fill out the questionnaire. Results: The study showed a higher male-to-female ratio in the ASD group. A family history of ASD was reported in 38.3% of the ASD group and 11.7% in the healthy group. Three prenatal risk factors, including maternal passive smoking, preserving follow-up prenatal visits, and experiencing psychological stress by mothers, were significantly associated with ASD. Most of the postnatal factors were significantly associated with increased ASD risk. The studied perinatal factors were not significantly associated with ASD. The parental factors, such as paternal age greater than 30 years and lower levels of education, displayed significant risk factors associated with ASD. Conclusion: This study found significant associations between several prenatal, postnatal, and parental factors and ASD in a sample of Palestinian children. المقدمة: اضطراب طيف التوحد هو اضطراب نمائي عصبي متعدد العوامل. تم تحديد العديد من العوامل قبل الولادة و أثناء الولادة و بعد الولادة كعوامل قد تكون مرتبطة بالاصابة باضطراب طيف التوحد. هدفت هذه الدراسة لفحص ارتباط عدة عوامل قبل الولادة و أثناء الولادة و بعد الولادة في عدد محدود من حالات التوحد في فلسطين. المنهجية: تمت الدراسة من خلال جمع معلومات من عينة ضمت 120 طفل (60 تم تشخيصهم بطيف التوحد و 60 طفل سليم و متطابقين مع مجموعة التوحد). تمت الاجابة على الاستبيان من قبل أولياء الأمور في المجموعتين. النتائج: أظهرت الدراسة أن نسبة الذكور الى الاناث في مجموعة طيف التوحد كانت أعلى. تم تحديد نسبة وجود تاريخ عائلي في 38.3% من مجموعة طيف التوحد و 11.7% من مجموعة الاطفال السليمين. تم تحديد ثلاثة عوامل خطورة قبل الولادة مرتبطة بشكل وثيق مع اضطراب طيف التوحد و تشمل التدخين السلبي للأم، متابعة زيارات الرعاية قبل الولادة، و التعرص للاجهاد النفسي من قبل الأمهات. معظم عوامل الخطر بعد الولادة كانت مرتبطة بشكل وثيق بزيادة خطر الاصابة بطيف التوحد. عوامل الخطر أثناء الولادة التي تمت دراستها لم ترتبط بشكل وثيق باضطراب طيف التوحد. العوامل المتعلقة بالوالدين مثل عمر الأب أكثر من 30 عام و مستويات التعليم المتدنية أظهرت ارتباطا وثيقا بالإصابة بطيف التوحد. الاستنتاج: وجدت الدراسة ارتباطات وثيقة بين عدة عوامل قبل الولادة و أثناء الولادة و بعد الولادة مع طيف التوحد في عينة من الأطفال الفلسطينيين.

Causal effects of gut microbiota on autism spectrum disorder: A two-sample mendelian randomization study.

There is increasing evidence that alterations in gut microbiota (GM) composition are associated with autism spectrum disorder (ASD), but no reliable causal relationship has been established. Therefore, a 2-sample Mendelian randomization (MR) study was conducted to reveal a potential causal relationship between GM and ASD. Instrumental variables for 211 GM taxa were obtained from genome-wide association studies (GWAS) and Mendelian randomization studies to estimate their impact on ASD risk in the iPSYCH-PGC GWAS dataset (18,382 ASD cases and 27,969 controls). Inverse variance weighted (IVW) is the primary method for causality analysis, and several sensitivity analyses validate MR results. Among 211 GM taxa, IVW results confirmed that Tenericutes (P value = .0369), Mollicutes (P value = .0369), Negativicutes (P value = .0374), Bifidobacteriales (P value = .0389), Selenomonadales (P value = .0374), Bifidobacteriaceae (P value = .0389), Family XIII (P value = .0149), Prevotella7 (P value = .0215), Ruminococcaceae NK4A214 group (P value = .0205) were potential protective factors for ASD. Eisenbergiella (P value = .0159) was a possible risk factor for ASD. No evidence of heterogeneous, pleiotropic, or outlier single-nucleotide polymorphism was detected. Additionally, further sensitivity analysis verified the robustness of the above results. We confirm a potential causal relationship between certain gut microbes and ASD, providing new insights into how gut microbes mediate ASD. The association between them needs to be further explored and will provide new ideas for the prevention and treatment of ASD.

Particulate matter 2.5 causally increased genetic risk of autism spectrum disorder

BackgroundGrowing evidence suggested that particulate matter (PM) exhibit an increased risk of autism spectrum disorder (ASD). However, the causal association between PM and ASD risk remains unclear.MethodsWe performed two-sample Mendelian randomization (MR) analyses, using instrumental variables (IVs) sourced from the largest genome-wide association studies (GWAS) databases. We employed three MR methods: inverse-variance weighted (IVW), weighted median (WM), and MR-Egger, with IVW method serving as our primary MR method. Sensitivity analyses were performed to ensure the stability of these findings.ResultsThe MR results suggested that PM2.5 increased the genetic risk of ASD (β = 2.41, OR = 11.13, 95% CI: 2.54–48.76, P < 0.01), and similar result was found for PM2.5 absorbance (β = 1.54, OR = 4.67, 95% CI: 1.21–18.01, P = 0.03). However, no such association was found in PM10 (β = 0.27, OR = 1.30, 95% CI: 0.72–2.36, P = 0.38). After adjusting for the false discovery rate (FDR) correction, our MR results remain consistent. Sensitivity analyses did not find significant heterogeneity or horizontal pleiotropy.ConclusionsOur findings indicate that PM2.5 is a potential risk factor for ASD. Effective strategies to mitigate air pollutants might lead to a reduced incidence of ASD.

Exploring the influences of education, intelligence and income on mental disorders

BackgroundPrevious studies have shown that educational attainment (EA), intelligence and income are key factors associated with mental disorders. However, the direct effects of each factor on major mental disorders are...

Korean Clinical Guideline for Autism Spectrum Disorder - Clinical Features, Course, Epidemiology, and Cause.

Autism spectrum disorder (ASD) is a heterogeneous developmental disorder characterized by impairments in two core areas: 1) social communication and interaction and 2) restricted and repetitive patterns of behaviors and interests. In general, ASD is known to be a lifelong disorder. Follow-up studies from childhood to adulthood have reported that the severity of the key symptoms ASD decreases over time. However, chronic health problems including mental health occur in many patients with ASD. The prevalence of ASD has increased from around 0.04% in the 1970s to 2.8% at present. The average age of diagnosis in developed countries is 38-120 months of age. Recent evidence suggests that biological factors which include genetic, congenital, immunological, neuroanatomical, biochemical, and environmental ones are important in causing autism. Until now, early signs and various risk factors of ASD have been suggested.

Clinical and demographic characteristics of autistic children in Al-Hilla city

Abstract Background: An increase in the number of cases of autism spectrum disorder (ASD) has been reported around the world in the recent years, identifying the major risk factors and main associations helps increase our knowledge and planning for future studies. Objective: To identify the major risk factors for ASD and associated medical and psychiatric comorbidities in Al-Hilla city. Materials and Methods: This is a record review study done in five centers for behavioral therapy of autistic children in Al-Hilla city from January 15, 2023, to May 15, 2023, on 204 children with ASD, their ages ranged from 2 to 12 years old, full history and clinical examination was done for all children. Results: Out of 204 children studied, 70.58% were males and 29.4% were females with a male-to-female ratio of 2.4:1. Their ages ranged from 2 to 12 years old, and 62.7% presented between 4 and 6 years of age. About 62.7% presented with speech delay, 17.6% had a family history of similar problems, 19.6% had sleep disturbance, 41.2% had gastrointestinal problems, 13.7% had epilepsy, and 50.9% had hyperactivity. Conclusion: We found a higher male-to-female ratio, delayed presentation to medical attention, most children present with speech delay and most patients had associated medical and psychiatric problems.

Inborn errors of immunity present with neuropsychiatric symptoms overlapping with autistic behavioral symptoms

Autism spectrum disorder (ASD) is a behaviorally defined syndrome affected by multiple genetic and environmental factors. A wide variety of risk factors for ASD have been identified and many of these affect immune functions. This may not be surprising, since the immune system and the nervous system share common signaling mechanisms and affect each other as a part of the neuroimmune network. The ever-expanding scope of inborn errors of immunity (IEIs) has revealed multiple pathogenic gene variants that manifest overlapping clinical features of common neuropsychiatric diseases, including ASD. These IEIs often cause dysregulated immune activation and resultant chronic inflammation affecting multiple organs. Some IEIs also cause changes in morphogenesis and plasticity of the central nervous system. Such patients often present with a puzzling array of clinical features and some of them may be diagnosed with ASD or other neuropsychiatric conditions. The progress of our understanding of disease mechanisms for IEIs at the molecular levels has led to gene-specific treatment measures in some diseases. In addition, some ASD patients are found to have laboratory findings of neuroinflammation that resemble those seen in IEI patients. This may pave the way for applying specific treatment measures used for IEI patients in such ASD patients. This review focuses on describing IEIs that have overlapping features of ASD. Emphasis is also on IEIs that can be treated by targeting identified disease mechanisms. Such information may be helpful for clinicians who are considering genetic/metabolic workup in ASD patients.

Prenatal caffeine exposure induces autism-like behaviors in offspring under a high-fat diet via the gut microbiota-IL-17A-brain axis

Prenatal caffeine exposure (PCE) is a significant contributor to intrauterine growth retardation (IUGR) in offspring, which has been linked to an increased susceptibility to autism spectrum disorder (ASD) later in life. Additionally, a high-fat diet (HFD) has been shown to exacerbate ASD-like behaviors, but the underlying mechanisms remain unclear. In this study, we first noted in the rat model of IUGR induced by PCE that male PCE offspring exhibited typical ASD-like behaviors post-birth, in contrast to their female counterparts. The female PCE offspring demonstrated only reduced abilities in free exploration and spatial memory. Importantly, both male and female PCE offspring displayed ASD-like behaviors when exposed to HFD. We further observed that PCE + HFD offspring exhibited damaged intestinal mucus barriers and disturbed gut microbiota, resulting in an increased abundance of Escherichia coli (E. coli). The induced differentiation of colonic Th17 cells by E. coli led to an increased secretion of IL-17A, which entered the hippocampus through peripheral circulation and caused synaptic damage in hippocampal neurons, ultimately resulting in ASD development. Our strain transplantation experiment suggested that E. coli-mediated increase of IL-17A may be the core mechanism of ASD with a fetal origin. In conclusion, PCE and HFD are potential risk factors for ASD, and E. coli-mediated IL-17A may play a crucial role in fetal-originated ASD through the gut-brain axis.

Study of Machine Learning Models to Detect Autism Spectrum Disorder

ASD is a spectrum disorder, some people with ASD may have mild symptoms and can live independently, while others may need more support and assistance in their daily lives. Some of the risk factors for ASD include having an older parent, being born prematurely, having a sibling with ASD, or being exposed to certain infections or toxins during pregnancy some of the common types of treatments include behavioural therapy, occupational therapy, physical therapy, and passionate about their interests. Such as the Modified Checklist for Autism in Toddlers, observational tools, such as the Autism Diagnostic Observation Schedule, and developmental assessments, such as the Mullen Scales of Early Learning. This study refers to some Machine Learning (ML) based applications that are able to detect Autism among individuals. This comprehensive review explores the innovative integration of machine learning (ML) models in the detection and diagnosis of Autism Spectrum Disorder (ASD). It begins by highlighting the complexities and diagnostic challenges of ASD, noting the limitations of traditional assessment methods. The review then delves into the realm of artificial intelligence (AI), discussing how AI, particularly ML and deep learning techniques, are revolutionizing the approach to ASD detection. It covers various ML models, including supervised, unsupervised, and reinforcement learning, and their application using behavioural, genetic, and neuroimaging data. A significant focus is given to the use of Logistic Regression and Hybrid Autism Screening Models in predicting ASD. The review also examines the efficacy and performance of supervised and deep learning models in ASD detection, evaluating their accuracy and precision. By providing a detailed analysis of the current state of AI in healthcare, specifically for ASD, this review underscores the potential of ML models in offering more accurate, accessible, and efficient diagnosis methods for ASD

Maternal immune activation during pregnancy is associated with more difficulties in socio-adaptive behaviors in autism spectrum disorder

Autism spectrum disorder (ASD) are neurodevelopmental conditions characterised by deficits in social communication and interaction and repetitive behaviours. Maternal immune activation (MIA) during the mid-pregnancy is a known risk factor for ASD. Although reported in 15% of affected individuals, little is known about the specificity of their clinical profiles. Adaptive skills represent a holistic approach to a person's competencies and reflect specifically in ASD, their strengths and difficulties. In this study, we hypothesised that ASD individual with a history of MIA (MIA+) could be more severely socio-adaptively impaired than those without MIA during pregnancy (MIA-). To answer this question, we considered two independent cohorts of individuals with ASD (PARIS study and FACE ASD) screened for pregnancy history, and used supervised and unsupervised machine learning algorithms. We included 295 mother–child dyads with 14% of them with MIA+. We found that ASD-MIA+ individuals displayed more severe maladaptive behaviors, specifically in their socialization abilities. MIA+ directly influenced individual's socio-adaptive skills, independent of other covariates, including ASD severity. Interestingly, MIA+ affect persistently the socio-adaptive behavioral trajectories of individuals with ASD. The current study has a retrospective design with possible recall bias regarding the MIA event and, even if pooled from two cohorts, has a relatively small population. In addition, we were limited by the number of covariables available potentially impacted socio-adaptive behaviors. Larger prospective study with additional dimensions related to ASD is needed to confirm our results. Specific pathophysiological pathways may explain these clinical peculiarities of ASD- MIA+ individuals, and may open the way to new perspectives in deciphering the phenotypic complexity of ASD and for the development of specific immunomodulatory strategies.

B - 10 The Effect of Gestational Age on Development of Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder.

Studies show individuals with comorbid neurodevelopmental disorders of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have poorer emotional, behavioral, and cognitive outcomes. While preterm birth (< 37weeks) is an identified risk factor for ASD and ADHD, it is important to consider gestational age (ga) as it relates to the development of comorbid ASD/ADHD (ASD/ADHD). The current study aims to understand the relationship between level of prematurity (LoP) and neurodevelopmental disorders. Participants included 10,711 children/adolescents (52.5% male) from the Environmental Influences on Child Health Outcomes (ECHO) Program. LoP was categorized as Extremely Preterm (36weeks). Chi-square analysis was conducted to examine the relationship between LoP and neurodevelopmental disorder diagnoses as indicated in medical records. Logistic regression was also conducted to analyze the relationship between ga (weeks) and neurodevelopmental disorder diagnosis. 1521 individuals were diagnosed with ASD (n = 537), ADHD (n = 778), or ASD/ADHD (n = 206); ga ranged from 22 to 43weeks. Results indicated the relationship between LoP and diagnoses was significant, ꭓ2(9, 10,771) = 148.31, p < 0.001. Extremely Preterm individuals were more likely than Full-term individuals to have ASD, ADHD, or ASD/ADHD. It was found that the odds of having a neurodevelopmental disorder decreased by 5.8% per 1-week ga increase (95% CI[-0.069, -0.048]). Results indicate gestational age is associated with greater risk of neurodevelopmental disorders, including comorbid ASD/ADHD. Improved understanding of the association between level of prematurity and comorbid ASD/ADHD diagnoses may help inform early intervention services enhancing children's outcomes throughout the lifespan.

23 Association between Autism Spectrum Disorder and Parental Immigration among a Cohort of Preschool Children in Manitoba

Abstract Background Recent data indicate that rates of autism spectrum disorder (ASD) are increasing and therefore, studies exploring risk factors for ASD that can further support early diagnosis and intervention are needed. A link between immigration and autism has been made by several international studies, but despite high rates of immigration, a Canadian study examining this association has not been conducted. Objectives To determine the proportion of children diagnosed with ASD at Manitoba’s primary autism referral site (the only publicly funded site for ASD evaluation of children &amp;lt;6 years of age) that were born to immigrant parents, and compare it with the known proportion of immigrants in Manitoba. Also, to compare demographic and clinical characteristics of children whose parents are immigrants with those whose parents were born in Canada. Design/Methods We conducted a retrospective chart review of &amp;gt;2000 electronic records that identified all children &amp;lt;6 years diagnosed with ASD at the referral site between May 2016 and September 2021. Data on parental immigration, demographics, diagnostic evaluation, and medical history was collected. Descriptive statistics were used to compare the relative proportion of children with ASD from immigrant parents with the proportion of immigrants in Manitoba based on 2016 census data. Results A total of 1865 children were diagnosed with ASD during the study period. The mean age at referral and diagnosis was 2.81 (SD 1.26) years and 3.88 (SD 2.90) years respectively; 78% were male and 13.5% were born preterm. The proportion of children with ASD from immigrant parents (36%) was greater than the expected proportion (18.3%) of immigrants based on Manitoba census data (p &amp;lt; 0.001). The most common countries of origin of immigration were the Philippines (30.7%), India (11.6%), Nigeria (8.6%), and Ethiopia (6.4%). Overall, children of immigrants were younger at referral (2.71 years, SD = 0.98 versus 2.91 years, SD = 1.43; p &amp;lt;0.001), less likely to have a family history of ASD (17.1% versus 35.6%; p = &amp;lt;0.001) and less likely to have comorbidities (46.8% versus 53.9%; p &amp;lt;0.001) including global developmental delay (18% versus 27.6%; p &amp;lt;0.001). Conclusion At Manitoba’s primary autism referral site, there was a greater proportion of children diagnosed with ASD born to immigrant parents than expected when compared to the Manitoba population. Overall, children of immigrants were younger, less likely to have comorbidities, developmental delay, and a family history of ASD. Future prospective studies are required to better understand the complex relationship between immigration and ASD diagnosis.

Bidirectional genetic overlap between autism spectrum disorder and cognitive traits

Autism spectrum disorder (ASD) is a highly heritable condition with a large variation in cognitive function. Here we investigated the shared genetic architecture between cognitive traits (intelligence (INT) and educational attainment (EDU)), and risk loci jointly associated with ASD and the cognitive traits. We analyzed data from genome-wide association studies (GWAS) of INT (n = 269,867), EDU (n = 766,345) and ASD (cases n = 18,381, controls n = 27,969). We used the bivariate causal mixture model (MiXeR) to estimate the total number of shared genetic variants, local analysis of co-variant annotation (LAVA) to estimate local genetic correlations, conditional false discovery rate (cond/conjFDR) to identify specific overlapping loci. The MiXeR analyses showed that 12.7k genetic variants are associated with ASD, of which 12.0k variants are shared with EDU, and 11.1k are shared with INT with both positive and negative relationships within overlapping variants. The majority (59–68%) of estimated shared loci have concordant effect directions, with a positive, albeit modest, genetic correlation between ASD and EDU (rg = 0.21, p = 2e−13) and INT (rg = 0.22, p = 4e−12). We discovered 43 loci jointly associated with ASD and cognitive traits (conjFDR<0.05), of which 27 were novel for ASD. Functional analysis revealed significant differential expression of candidate genes in the cerebellum and frontal cortex. To conclude, we quantified the genetic architecture shared between ASD and cognitive traits, demonstrated mixed effect directions, and identified the associated genetic loci and molecular pathways. The findings suggest that common genetic risk factors for ASD can underlie both better and worse cognitive functioning across the ASD spectrum, with different underlying biology.