Incidence Of Autism Spectrum Disorders Research Articles

Prevalence and Cumulative Incidence of Autism Spectrum Disorders and the Patterns of Co-Occurring Neurodevelopmental Disorders in a Total Population Sample of 5-Years-Old Children

Background: Whether there is a true increase in Autism Spectrum Disorder (ASD) frequency or not remains unclear. Additionally, the rates of co-existing neurodevelopmental disorders (NDD) in a total population sample hasn't been fully examined before. Methods: All 5-year-old children in the catchment area in Japan underwent the screening annually from the year 2013 - 2016. Screen-positive children were invited to a comprehensive assessment, including child and parent interview, behavioral observation, and cognitive and motor function testing. All cases were reviewed by a multidisciplinary team. ASD prevalence and cumulative incidence were computed. Outcomes: Caregivers of 3,954 children returned the screening, among which 559 children underwent the assessment with 87 children receiving an ASD diagnosis. Adjusted ASD prevalence was 3.22% (95% Confidence Interval (CI): 2.66 - 3.76). The male to female ratio of the crude prevalence was 2.2:1. The cumulative incidence of ASD up to 5 years of age for the total study years was 1.31 (95% CI: 1.00 - 1.62). A generalized linear model revealed no significant linear trends in 5-year cumulative incidence over the study years. Only 11.5% of children had ASD alone; the remaining 88.5% were found to have at least one co-existing NDD. Interpretation: Our findings demonstrate the stability of the 5-year cumulative incidence of ASD, implying no true rise in ASD incident cases over the 4-year study period in the study catchment area. High rates of co-existing NDDs reflect the importance of investigating broad developmental challenges in ASD children. Funding: Grants-in-Aid for Scientific Research and Hirosaki Institute of Neuroscience. Declaration of Interest: The authors have no financial relationships relevant to this article to disclose. Ethical Approval: This study was approved by the Committee of Medical Ethics of Hirosaki University Graduate School of Medicine. Moreover, the information security policies of the city and committee were followed to protect the personal data of the participants.

CHANGABLE ENVIRONMENTAL RISK FACTORS IN AUTISM: VITAMIN D AND FOLIC ACID

Autism Spectrum Disorder (ASD) is a severe neuro-developmental disorder which generally starts during infancy as well as mostly in the first 3 years of life. ASD is characterized by social, behavioral, and communication symptoms. Genetics and certain environmental factors may play a role in the pathogenesis of autism, although the etiology of the disease is unknown. Maternal nutrition is important for development of the fetal brain. The mother’s nutritional condition before and during pregnancy may affect the risk of ASD incidence. Vitamin D deficiency is taken into consideration as a possible risk factor for development of ASD. Compared to healthy peers, children with ASD were indicated to have lower levels of vitamin D. However, it is not clear yet if this condition was influenced by the fact that whether patients with ASD are born with lower levels of vitamin D or they are exposed to sunlight lesser. Also f olic acid supplementation during pregnancy and blood folate levels in children with autism are environmental factors contributing to autism incidence through dietary intake. The aim of this study is to explain the relationship between vitamin D, folic acid and ASD.

Autism Spectrum Disorder: Incidence and Time Trends Over Two Decades in a Population-Based Birth Cohort.

We retrospectively identified autism spectrum disorder (ASD) incident cases among 31,220 individuals in a population-based birth cohort based on signs and symptoms uniformly abstracted from medical and educational records. Inclusive and narrow research definitions of ASD (ASD-RI and ASD-RN, respectively) were explored, along with clinical diagnoses of ASD (ASD-C) obtained from the records. The incidence of ASD-RI, ASD-RN, and ASD-C increased significantly from 1985 to 1998, then ASD-RI and ASD-RN plateaued while the rate of ASD-C continued to increase during 1998-2004. The rising incidence of research-defined ASD may reflect improved recognition and documentation of ASD signs and symptoms. Although the frequency of threshold ASD symptoms stabilized, the rate of ASD-C continued to increase, narrowing the gap between clinical ascertainment and symptom documentation.

Metformin Administration During Early Postnatal Life Rescues Autistic-Like Behaviors in the BTBR T+ Itpr3tf/J Mouse Model of Autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disability characterized by impaired social interactions, stereotypical repetitive behavior and restricted interests. Although the global incidence of ASD has increased over time, the etiology of ASD is poorly understood, and there is no effective pharmacological intervention for treating ASD. Recent studies have suggested that metformin has the potential to treat ASD. Thus, in this study, we assessed the therapeutic effects of early metformin treatment in a BTBR T+ Itpr3tf/J (BTBR) mouse model of ASD. We observed that early metformin administration significantly reversed social approach deficits, attenuated repetitive grooming and reduced marble burying in BTBR mice. Metformin did not change the general locomotor activity or anxiety-like behavior in both BTBR and C57BL/6J (B6) mice. Our findings suggest that early metformin treatment may have beneficial effects on ameliorating behavioral deficits in ASD.

Traumatic Brain Injury in Early Childhood and Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

Early childhood (< 3 years of age) is a critical period for neurodevelopment. This study investigated the correlation between early childhood traumatic brain injury (TBI) and subsequent risk of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental delay (DD) by analyzing a national-scale cohort. Data from the National Health Insurance Research Database, which comprises health care information from > 99% of the Taiwanese population, were analyzed. Children with TBI in their early childhood were enrolled from 1998-2008, and the incidence of subsequent ADHD, ASD, or DD (according to ICD-9 criteria) was assessed and compared with controls without TBI. Patients' age, number of TBI events, and TBI severity were investigated for the risk of ADHD, ASD, or DD. A total of 7,801 and 31,204 children were enrolled in the TBI and control cohorts, respectively. The TBI cohort exhibited a higher incidence of subsequent ADHD, ASD, or DD than the controls (all P < .001). Diagnoses of ADHD, ASD, or DD in the TBI cohort were made at a younger age compared with the controls. Cox regression demonstrated the highest hazard ratios (HRs) of ADHD, ASD, or DD with repeated TBI events, severe TBI, and TBI events before 1 year of age, with the exception that the HR of ASD did not significantly increase after repeated TBI (P = .335). In addition, cumulative HRs (> 10 years) of ADHD, ASD, or DD were increased after TBI (all P < .001). Data from this study suggest that the incidence of ADHD, ASD, and DD significantly increased after TBI events in early childhood (< 3 years of age). The risk factors include severe TBI, repeated TBI events, and TBI at a younger age. The long-term follow-up demonstrated an increased cumulative risk of ADHD, ASD, and DD after TBI.

Diagnosis incidence of autism spectrum disorders is underestimated in Australian children, and there are inequalities in access to diagnosis and treatment services: a data linkage study of health service usage

IntroductionThe prevalence and diagnosis incidence of autism spectrum disorders (ASD) are difficult to determine. Estimates of ASD burden in Australia are produced from sample surveys of disability, and government records of welfare disability payments. While disability does affect many people with ASD, ASD itself is not a disability.&#x0D; Objectives and ApproachFor our retrospective population-based cohort study of breast cancer survivors diagnosed from 2007 to 2010 in British Columbia (BC), 2007-2011 in Manitoba (MB), 2007-2010 in Ontario (ON), and 2007-2012 in Nova Scotia (NS), we linked provincial cancer registries, clinical and health administrative databases, and followed cases alive at 30 months post-diagnosis to five years from diagnosis. For each province, we calculated percent adherence, overuse, and underuse of recommended follow-up care, including surveillance for recurrent and new cancer, surveillance for late effects, and general preventive care. We also examined variation among provinces and over time.&#x0D; ResultsSurvivor numbers were 23,700 (ON), 9493 (BC), 2688 (MB), and 2735 (NS). Annual oncologist visit guideline compliance varied provincially (e.g. Year 2 ON=32.7%, BC=15.0%). For most provinces and follow-up years, the majority of survivors had fewer oncologist visits than recommended. However, survivors had additional annual breast cancer-related visits to a primary care provider. Surveillance breast imaging guideline compliance was high (e.g. Year 2, ON=81.1%, MB=72.0%, NS=52.8%, BC =49.7%), with rates declining in ON and MB (to approximately 64%), but increasing in NS and BC (to approximately 58%) by Year 5. Overuse of breast imaging was identified in NS (9.1%-20.7% overuse in follow-up years 2-5). As per the guideline, 72.9%-79.7% (Years 2-5) of BC survivors had no imaging for metastastic disease, highest among all provinces.&#x0D; Conclusion/ImplicationsThe diagnosis incidence of ASD in Australian children is higher than previously estimated. The prevalence of ASD is therefore also underestimated. Multidisciplinary ASD assessment and treatment services are underutilised, likely due to out-of-pocket co-payments reducing affordability. These findings have significant implications for government health service planning for ASD.

Maternal Type 1 Diabetes and Risk of Autism in Offspring

Children exposed in utero to maternal type 2 diabetes (T2D) or gestational diabetes (GDM) diagnosed by 26 weeks gestation are at increased risk of autism spectrum disorders (ASD). Here we assessed the association between ASD and in utero exposure to maternal type 1 diabetes (T1D). Data were from 419,425 singleton children born at 28-44 weeks’ gestation from 1995-2012 at Kaiser Permanente Southern California (KPSC) hospitals. Children were tracked from birth until the first of the following: date of clinical diagnosis of ASD, last date of continuous KPSC membership, death due to any cause, or December 31, 2016. Relative risks of ASD were estimated by hazard ratio (HR) using Cox regression models adjusted for birth year, maternal age, parity, education, household income, race/ethnicity, history of comorbidity, and sex of the child. A total of 621 children were exposed to T1D, 9,453 to T2D, 11,922 to GDM diagnosed by 26 weeks gestation, and 24,5to GDM diagnosed after 26 weeks gestation. During a median of 6.3 (interquartile range of 3.4-11.2) years after birth, 5,624 children were diagnosed with ASD (19 exposed to T1D, 221 to T2D, 250 to GDM by 26 weeks, 360 to GDM after 26 weeks, and 4,774 not exposed to maternal diabetes). Unadjusted annual ASD incidence rates per 1000 children were 4.7 (T1D), 3.7 (T2D), 3.1 GDM by 26 weeks, 2.2 (GDM after 26 weeks) and 1.9 (unexposed). Relative to no diabetes exposure, the adjusted HRs for exposure to maternal diabetes were 2.5 (95% CI, 1.4-4.4) for T1D, 1.5 (95% CI, 1.3-1.7) for T2D, 1.4 (95% CI, 1.2-1.6) for GDM by 26 weeks, and 1.0 (95% CI, 0.9-1.1) for GDM after 26 weeks gestation respectively. Thus, exposures to T1D, T2D and GDM diagnosed by 26 weeks gestation were all associated with an increased risk of autism spectrum disorders in offspring. Exposure to T1D imparted the highest risk, followed by exposure to T2D and GDM diagnosed by 26 weeks. Rising rates of maternal diabetes may be one factor contributing to rising rates of ASD. Disclosure A. Xiang: None. X. Wang: None. M.P. Martinez: None. K.A. Page: None. T.A. Buchanan: None.

Brief Report: Gender and Age of Diagnosis Time Trends in Children with Autism Using Australian Medicare Data.

Recent evidence suggests the male predominance in Autism Spectrum Disorder (ASD) may be decreasing. Secondary analyses of Australian Medicare data (paediatrician/child psychiatrist items for diagnosing ASD before age 13) were used (N = 73,463 unique children from 1-July-2008 to 30-June-2016). Cumulative incidence of ASD in 4-year-olds in 2015/2016 was 1.10% [95% CI 1.06-1.14], males 1.66% [95% CI 1.60-1.72] and females 0.51% [95% CI 0.47-0.55]. New diagnoses significantly increased in older (5-12years) males and females but not younger (0-4years) children, from 2010/2011 to 2015/2016. The M:F ratio decreased in older children (4.1-3.0), but not significantly in younger children (4.2-3.5). Identification of older males and females is contributing to the increased in ASD in Australia and proportionally more older females are being diagnosed.

No effect of prenatal vitamin D deficiency on autism-relevant behaviours in multiple inbred strains of mice

Autism Spectrum Disorders (ASD) is a group of neurodevelopmental disorders commonly characterised by verbal and non-verbal communication deficits, impaired social interaction and repetitive, stereotypic behaviours. The aetiology of ASD is most likely a combination of genetic and environmental factors. Epidemiological evidence suggests that prenatal vitamin D deficiency is associated with an increased incidence of ASD. The overall aim of this study was to investigate prenatal vitamin D deficiency on ASD-related behavioural phenotypes in multiple inbred strains of mice. We included two commonly used inbred mouse strains (C57BL/6J and BALB/c) as well as inbred BTBR mice, which show ASD-related behaviours, such as excessive self-grooming, hyperlocomotion, social interaction deficits and altered communication. We also studied the effect of prenatal vitamin D deficiency in a fourth strain; an F1 cross of C57BL/6J x BTBR mice, which have a partial BTBR phenotype. To implement prenatal vitamin D deficiency, female mice were placed on vitamin D deplete diets for ten weeks, including mating and gestation, until littering, when all dams were switched to the control diet. Behavioural symptoms related to ASD were measured, including isolation-induced ultrasonic vocalisations to measure communication, the three-chambered social interaction task to observe social interaction, the open field test to examine hyperlocomotion, assessment of grooming and rearing behaviour and finally the active place avoidance task to observe spatial learning and memory in response to a mild foot shock. Prenatal vitamin D deficiency had a negative impact on preference for social novelty in C57BL/6J mice, despite similar vocalisation phenotypes, and prenatal vitamin D-deficient F1 mice were found to be hypolocomotive in the open field test yet performed better on the active place avoidance task. Despite clear differences between strains, there were no other consistent significant main effects of maternal diet on the behaviour of the offspring. Vitamin D deficiency has been implicated as a risk factor for ASD and these data show that there is greater variation between different inbred strains in ASD-related behaviour, suggesting that prenatal vitamin D deficiency is not sufficient to recapitulate an ASD phenotype in multiple inbred strains of mice.

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Insights from outside BJOG

Vitamin D Receptor Gene Polymorphisms Associated with Childhood Autism.

Background: Autism spectrum disorder (ASD) is a group of heterogeneous, behaviorally defined disorders whereby currently no biological markers are common to all affected individuals. A deregulated immune response may be contributing to the etiology of ASD. The active metabolite of vitamin D3 has an immunoregulatory role mediated by binding to the vitamin D receptor (VDR) in monocyte, macrophages, and lymphocytes. The effects of vitamin D and interaction with the VDR may be influenced by polymorphism in the VDR gene. Methods: Genetic association of four different VDR polymorphisms (Apa-I, Bsm-I, Taq-I, Fok-I) associated with susceptibility to the development of autism in children was investigated. Results: We uniquely found an association between the presence of the T allele at position Taq-I and presence of the a allele at position Apa-I of the VDR gene with decreased ASD incidence. There was also an association between female gender and the presence of the T allele. We found no statistical significant correlation between VDR single nucleotide polymorphisms (SNPs) and vitamin D3 concentration in serum of ASD children. Conclusion: Genetic polymorphism in two SNP in VDR may be correlated with development of ASD symptoms by influencing functionality of vitamin D3 metabolism, while vitamin D3 levels were not significantly different between ASD and non-ASD children.

Dendritic spine anomalies and PTEN alterations in a mouse model of VPA-induced autism spectrum disorder

Mounting evidence suggests that the etiology of autism spectrum disorders (ASDs) is profoundly influenced by exposure to environmental factors, although the precise molecular and cellular links remain ill-defined. In this study, we examined how exposure to valproic acid (VPA) during pregnancy is associated with an increased incidence of ASD. A mouse model was established by injecting VPA at embryonic day 13, and its behavioral phenotypes including impaired social interaction, increased repetitive behaviors and decreased nociception were observed at postnatal days 21–42. VPA-treated mice showed dysregulation of synaptic structure in cortical neurons, including a reduced proportion of filopodium-type and stubby spines and increased proportions of thin and mushroom-type spines, along with a decreased spine head size. We also found that VPA-treatment led to decreased expression of phosphate and tensin homolog (PTEN) and increased levels of p-AKT protein in the hippocampus and cortex. Our data suggest that there is a correlation between VPA exposure and dysregulation of PTEN with ASD-like behavioral and neuroanatomical changes, and this may be a potential mechanism of VPA-induced ASD.

Gestational Exposure to Air Pollution Alters Cortical Volume, Microglial Morphology, and Microglia-Neuron Interactions in a Sex-Specific Manner.

Microglia are the resident immune cells of the brain, important for normal neural development in addition to host defense in response to inflammatory stimuli. Air pollution is one of the most pervasive and harmful environmental toxicants in the modern world, and several large scale epidemiological studies have recently linked prenatal air pollution exposure with an increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD). Diesel exhaust particles (DEP) are a primary toxic component of air pollution, and markedly activate microglia in vitro and in vivo in adult rodents. We have demonstrated that prenatal exposure to DEP in mice, i.e., to the pregnant dams throughout gestation, results in a persistent vulnerability to behavioral deficits in adult offspring, especially in males, which is intriguing given the greater incidence of ASD in males to females (∼4:1). Moreover, there is a striking upregulation of toll-like receptor (TLR) 4 gene expression within the brains of the same mice, and this expression is primarily in microglia. Here we explored the impact of gestational exposure to DEP or vehicle on microglial morphology in the developing brains of male and female mice. DEP exposure increased inflammatory cytokine protein and altered the morphology of microglia, consistent with activation or a delay in maturation, only within the embryonic brains of male mice; and these effects were dependent on TLR4. DEP exposure also increased cortical volume at embryonic day (E)18, which switched to decreased volume by post-natal day (P)30 in males, suggesting an impact on the developing neural stem cell niche. Consistent with this hypothesis, we found increased microglial-neuronal interactions in male offspring that received DEP compared to all other groups. Taken together, these data suggest a mechanism by which prenatal exposure to environmental toxins may affect microglial development and long-term function, and thereby contribute to the risk of neurodevelopmental disorders.

Role of environmental and genetic factors in autism spectrum disorder

The aim of this study was to find out the environmental as well as genetic factors responsible for increasing the number of autism spectrum disorder (ASD) patients in Bangladesh. A questionnaire was developed based on 12 environmental factors and genetic aspects. Sixty six patients of ASD and 66 non-ASD control were selected randomly. Among the environmental factors, the age of the mother, premature birth, air pollution, age of the father, hypoxia during childbirth and oral contraceptive came out as significant (p&lt;0.05) factors for ASD incidence compared to the control. Association of multiple factors on an individual was found to be crucial to enhance the risk and exposure to five and six factors was statistically significant (p&lt;0.05) for ASD development. Prospective parents should try to keep the number of risk factors as low as possible before 1-2 months of pregnancy, during pregnancy and 1-2 years after the child birth (for child only).

The connectomes of males and females with autism spectrum disorder have significantly different white matter connectivity densities

Autism spectrum disorder (ASD) encompasses a set of neurodevelopmental conditions whose striking sex-related disparity (with an estimated male-to-female ratio of 4:1) remains unknown. Here we use magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) to identify the brain structure correlates of the sex-by-ASD diagnosis interaction in a carefully selected cohort of 110 ASD patients (55 females) and 83 typically-developing (TD) subjects (40 females). The interaction was found to be predicated primarily upon white matter connectivity density innervating, bilaterally, the lateral aspect of the temporal lobe, the temporo-parieto-occipital junction and the medial parietal lobe. By contrast, regional gray matter (GM) thickness and volume are not found to modulate this interaction significantly. When interpreted in the context of previous studies, our findings add considerable weight to three long-standing hypotheses according to which the sex disparity of ASD incidence is (A) due to WM connectivity rather than to GM differences, (B) modulated to a large extent by temporoparietal connectivity, and (C) accompanied by brain function differences driven by these effects. Our results contribute substantially to the task of unraveling the biological mechanisms giving rise to the sex disparity in ASD incidence, whose clinical implications are significant.

Sex-specific gene–environment interactions underlying ASD-like behaviors

The male bias in the incidence of autism spectrum disorders (ASDs) is one of the most notable characteristics of this group of neurodevelopmental disorders. The etiology of this sex bias is far from known, but pivotal for understanding the etiology of ASDs in general. Here we investigate whether a "three-hit" (genetic load × environmental factor × sex) theory of autism may help explain the male predominance. We found that LPS-induced maternal immune activation caused male-specific deficits in certain social responses in the contactin-associated protein-like 2 (Cntnap2) mouse model for ASD. The three "hits" had cumulative effects on ultrasonic vocalizations at postnatal day 3. Hits synergistically affected social recognition in adulthood: only mice exposed to all three hits showed deficits in this aspect of social behavior. In brains of the same mice we found a significant three-way interaction on corticotropin-releasing hormone receptor-1 (Crhr1) gene expression, in the left hippocampus specifically, which co-occurred with epigenetic alterations in histone H3 N-terminal lysine 4 trimethylation (H3K4me3) over the Crhr1 promoter. Although it is highly likely that multiple (synergistic) interactions may be at work, change in the expression of genes in the hypothalamic-pituitary-adrenal/stress system (e.g., Crhr1) is one of them. The data provide proof-of-principle that genetic and environmental factors interact to cause sex-specific effects that may help explain the male bias in ASD incidence.

Autism Spectrum Disorders and Communication Disorders: Influences of Advanced Parental Age and Use of Assisted Reproductive Technology

Research suggests that two prenatal factors, advanced parental age and use of assisted reproductive technology (ART), may independently increase the likelihood for the development of autism spectrum disorder (ASD) and other neurodevelopmental disorders. Our study evaluated the effect of advanced maternal and paternal ages (i.e., ages 35 and over) at the time of conception with and without the use of ART on the incidence of ASD and communication disorders (CD). We hypothesized that advanced parental age would be the strongest independent risk factor for the incidence of ASD and/or CD in offspring compared to younger parental age and use of ART. Information on 122 children was obtained through confidential survey. Parental ages at time of conception, diagnoses, use of ART, and infertility were considered. Results indicated that the risk of having a child with a CD increased significantly with either advanced maternal or paternal age. The risk of having a child diagnosed with ASD and/or CD was significantly higher for couples of advanced age, and the risk was significantly decreased for younger couples. Mothers of advanced age used ART at a significantly higher rate; however, this risk of having a child diagnosed with ASD and/or CD was not increased. Identification of risk factors (particularly combinations of risk factors) is essential for early detection of ASD and CD. The findings of our study, combined with other epidemiological data, may help to guide the development of prenatal screening tools and procedures. Implications are discussed.

Autistic feature and 2D:4D finger ratio relations children and adolescents with congenital adrenal hyperplasia

Objective: Because congenital adrenal hyperplasia (CAH) and autism spectrum disorders (ASD) is rarely seen, it is difficult to assess whether the increased incidence of ASD in girls with CAH. ASD behaviors and 2D: 4D finger ratio changes in patients with androgen overproduction have been reported. The aim of this study is determining the 2D:4D finger ratios and ASD features in girls with CAH and normal control group. Methods: The study group will consist of thirty female children and adolescents between the ages of 3 and 15 who are diagnosed with classic CAH who were followed at the Pediatric Endocrinology Department of Duzce University Medical Faculty Hospital. For the control group, 30 healthy children and adolescents equalized with CAH patients in terms of age and gender will be taken. Al patients and controls examined for psychiatric disorders. by clinicians Patients and control groups filled Autism Behavior Checklist and semistructured sociodemographic form that evaluated the gender, age, pregnancy and birth complications, history of mothers’ cigarette and alcohol use. 2D:4D ratios were measured in both of control and CAH groups. Findings: KAH group right and left hand 2D:4D ratios were statistically lower compared to controls and also lower 2D:4D ratios had association with high ABC scores. When compared with control group, CAH group ABC scores were significantly higher. In KAH group there was a positive correlation between 2D:4D ratios and ABC scores. Conclusion: In light of present study findings, suggest that high androgen may have effect on low 2D:4D ratios and high ASD symptoms. Further researches with a large sample are needed in this field.

Paternal and maternal age at pregnancy and autism spectrum disorders in offspring

Background The prevalence of autism spectrum disorders(ASDs) has increased 10 times over the past half century,while paternal and maternal age at pregnancy has alsoincreased. Studies looking for an association between paternalor maternal age at pregnancy and ASDs in offspring have notbeen conclusive.Objective To assess for possible associations between paternaland maternal age at pregnancy and ASDs in offspring.Methods This case-control study had 50 case and 100control subjects, each case was matched for age and genderto two controls. Case subjects were obtained by consecutivesampling of patients aged 18 months to 7 years who visited theDevelopmental Behavioral &amp; Community Pediatrics OutpatientClinic and private growth and development centers from Januaryto April 2013, while control group were children of the sameage range and same gender who visited pediatric outpatientclinic at Sanglah Hospital mostly due to acute respiratory tractinfection, without ASDs as assessed by the DSM-IV-TR criteria.We interviewed parents to collect the following data: maternaland paternal age at pregnancy, child’s birth weight, historyof asphyxia, hospital admission during the neonatal period,pathological labor, maternal smoking during pregnancy, paternalsmoking, and gestational age. Data analysis was performed withChi-square and Fisher’s exact tests.Results Multivariable analysis showed that higher paternal ageat pregnancy was associated with ASDs in offspring (OR 6.3;95%CI 2.0 to 19.3; P 0.001). However, there was no significantassociation between maternal age during pregnancy and theincidence of ASDs. Asphyxia and paternal smoking were alsoassociated with higher incidence of ASDs in the offspring (OR10.3; 95%CI 1.9 to 56.5; P 0.007 and OR 3.2; 95%CI 1.5 to 6.9;P 0.003, respectively).Conclusion􀀃􀀳􀁄􀁗􀁈􀁕􀁑􀁄􀁏􀀃􀁄􀁊􀁈􀀃􀂕􀀗􀀓􀀃􀁜􀁈􀁄􀁕􀁖􀀃􀁌􀁑􀁆􀁕􀁈􀁄􀁖􀁈􀁇􀀃􀁗􀁋􀁈􀀃􀁕􀁌􀁖􀁎􀀃􀁒􀁉􀀃􀀤􀀶'􀁖􀀃in offspring by 6.3 times. In addition, paternal smoking increased the risk of ASDs in offspring by 3.2 times and asphyxia increasedthe risk of ASDs in offspring by 10.3 times.

Risk of epilepsy and autism in full and half siblings-A population-based cohort study.

Epilepsy and autism spectrum disorder (ASD) often occur together in the same individual. However, it remains unknown whether siblings of children with ASD have an increased risk of epilepsy and vice versa. This study determines the risk of ASD and epilepsy among younger siblings of children with ASD and epilepsy. The study included all children born in Denmark between January 1, 1980 and 31 December 2006 who participated in follow-up until December 31, 2012 (1,663,302 children). We used Cox regression to calculate the adjusted hazard ratio (aHR) and the Kaplan-Meier method to calculate the cumulative incidence. The overall aHR of epilepsy in younger siblings increased by 70% (aHR 1.70, 95% confidence interval [CI] 1.34-2.16%) if the older sibling had ASD compared with siblings where the older sibling did not have ASD. The cumulative incidence of epilepsy at 20 years of age was 2.54% (95% CI 1.97-3.26%) if the older sibling had ASD, whereas the cumulative incidence of epilepsy at 20 years of age was 1.63% (95% CI 1.60-1.66%) if the older sibling did not have ASD. The overall aHR of ASD in younger siblings increased by 54% if the older sibling had epilepsy (aHR 1.54, 95% CI 1.32-1.80) compared with siblings where the older sibling did not have epilepsy. The cumulative incidence of ASD at 20 years of age was 2.06% (95% CI 1.84-2.32%) if the older sibling had epilepsy, whereas the cumulative incidence of ASD at 20 years of age was 1.27% (95% CI 1.25-1.29%) if the older sibling did not have epilepsy. The cross-disorder sibling risk of epilepsy and ASD was increased for the two disorders, which suggests that genes or environmental factors shared by family members may play a causal role in the co-occurrence of ASD and epilepsy.