Diagnosis Of Autistic Disorder Research Articles

Early Signs

Early Signs

Comments of the current study on the etiology of autism spectrum disorders

Autism spectrum disorder (ASD) was proposed in the Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM-5), released May 2013. The new diagnosis encompasses previous diagnoses of autistic disorder, Asperger’s syndrome, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified (PDD-NOS). So ASD is a group of developmental disabilities that can cause significant social, communication and behavioral challenges. To estimate a prevalence is 0.1%–1%. The importance of lifelong influence and social burden has attracted extensive attention and focus of research. Searching for the cause of ASD is the hotspot of medical study in China and all of the world recently.

Demographic correlates of children and adolescents with Autistic disorder

Introduction: Comparison of the demographic characteristics of patients provides useful information to their identification. This study aimed to determine the demographic characteristics of children and adolescents with autistic disorder (AD). Methods: In this cross-sectional case-control study, 115 children and adolescents with AD were selected from Autism Society Rehabilitation Center in Tabriz, Iran, and 112 normal children and adolescents from the public schools, in 2014. The participants in both groups were matched regarding age and gender. Diagnosis of AD was performed using diagnostic and statistical manual of mental disorders-4th edition (DSM-IV) criteria and clinical diagnostic interviews by two child and adolescent psychiatrists. The demographic information of children and adolescents and their parents were collected from the medical records of children and interviews with their mothers. Results: Most of the children with autism had second or higher birth order and had families with more than three members. Mothers of children with autism had significantly lower levels of education and were mostly housewives. Fathers of autistic children mostly had high school diploma and fewer had university education, and most of them were employed. However, there was no statistically significant difference between the AD group and the control group regarding the average height and weight of children and the residence (urban or rural) and age of parents at childbirth.Conclusion: The demographic characteristics of the two groups of children and adolescents with AD and normal controls were different from each other regarding family size, birth order, parent occupation, and parent education variables.

A pilot double-blind placebo-controlled trial of pioglitazone as adjunctive treatment to risperidone: Effects on aberrant behavior in children with autism

To assess the safety and efficacy of pioglitazone added to risperidone in the treatment of irritability in autistic disorder (AD), we conducted this study. In a 10-week, randomized, double-blind, parallel-group, placebo-controlled clinical trial, 44 outpatients of both genders aged 4–12 years with a diagnosis of AD and a score of ≥12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale were included. Mean change of ABC-C irritability subscale score as primary outcome, change in other ABC-C subscale scores and partial and complete responses were compared between two groups. Twenty patients completed the trial in each group. Level of reduction and effect of time×treatment interaction in the treatment group were significant for irritability (P=0.03), lethargy/social withdrawal (P=0.04) and hyperactivity/non-compliance (P=0.03) but not for stereotypic behavior and inappropriate speech subscales compared with the placebo group. Vomiting and headache were the most frequent reported side-effects. Results of this preliminary study indicate positive effects of pioglitazone compared with placebo in improving the behavioral symptoms of AD.

An ontology for Autism Spectrum Disorder (ASD) to infer ASD phenotypes from Autism Diagnostic Interview-Revised data

ObjectiveOur goal is to create an ontology that will allow data integration and reasoning with subject data to classify subjects, and based on this classification, to infer new knowledge on Autism Spectrum Disorder (ASD) and related neurodevelopmental disorders (NDD). We take a first step toward this goal by extending an existing autism ontology to allow automatic inference of ASD phenotypes and Diagnostic & Statistical Manual of Mental Disorders (DSM) criteria based on subjects’ Autism Diagnostic Interview-Revised (ADI-R) assessment data. Materials and methodsKnowledge regarding diagnostic instruments, ASD phenotypes and risk factors was added to augment an existing autism ontology via Ontology Web Language class definitions and semantic web rules. We developed a custom Protégé plugin for enumerating combinatorial OWL axioms to support the many-to-many relations of ADI-R items to diagnostic categories in the DSM. We utilized a reasoner to infer whether 2642 subjects, whose data was obtained from the Simons Foundation Autism Research Initiative, meet DSM-IV-TR (DSM-IV) and DSM-5 diagnostic criteria based on their ADI-R data. ResultsWe extended the ontology by adding 443 classes and 632 rules that represent phenotypes, along with their synonyms, environmental risk factors, and frequency of comorbidities. Applying the rules on the data set showed that the method produced accurate results: the true positive and true negative rates for inferring autistic disorder diagnosis according to DSM-IV criteria were 1 and 0.065, respectively; the true positive rate for inferring ASD based on DSM-5 criteria was 0.94. DiscussionThe ontology allows automatic inference of subjects’ disease phenotypes and diagnosis with high accuracy. ConclusionThe ontology may benefit future studies by serving as a knowledge base for ASD. In addition, by adding knowledge of related NDDs, commonalities and differences in manifestations and risk factors could be automatically inferred, contributing to the understanding of ASD pathophysiology.

Risk of autistic disorder after exposure to general anaesthesia and surgery: a nationwide, retrospective matched cohort study.

Deficits of learning, memory and cognition have been observed in newborn animals exposed to general anaesthetics. However, conclusions from clinical studies conducted in humans to investigate the relationship between anaesthesia and neurodevelopmental disorders have been inconsistent. Autistic disorder is typically recognised earlier than other neurobehavioural disorders. Although certain genes apparently contribute to autistic disorder susceptibility, other factors such as perinatal insults and exposure to neurotoxic agents may play a crucial role in gene-environmental interaction. This study was designed to investigate the association of exposure to general anaesthesia/surgery with autistic disorder. We hypothesised that exposure to general anaesthesia and surgery before 2 years of age is associated with an increased risk of developing autistic disorder. A retrospective matched-cohort study. A medical university. Data from the National Health Insurance Research Database of Taiwan from 2001 to 2010 were analysed. The birth cohort included 114,435 children, among whom 5197 were exposed to general anaesthesia and surgery before the age of 2 years. The 1 : 4 matched controls comprised 20,788 children. The primary endpoint was the diagnosis of autistic disorder after the first exposure to general anaesthesia and surgery. No differences were found in the incidence of autistic disorder between the exposed group (0.96%) and the unexposed controls (0.89%) (P = 0.62). Cox proportional regression showed that the hazard ratio of exposure to general anaesthesia and surgery was 0.93 [95% confidence interval (95% CI) 0.57 to 1.53] after adjusting for potential confounders. Age at first exposure did not influence the risk of autistic disorder. No relationship was found between the total number of exposures and the risk of autistic disorder. Exposure to general anaesthesia and surgery before the age of 2 years age at first exposure and number of exposures were not associated with the development of autistic disorder.

Assessment of severity of autism using the Indian scale for assessment of autism.

Background:The Indian Scale for Assessment of Autism (ISAA) was developed to assess the severity of autism among Indian cases.Aims:The present study evaluated the ISAA in relation to the Childhood Autism Rating Scale (CARS) and the Developmental Disability- Children Global Assessment Scale (DD-CGAS).Materials and Methods:Indian children with ICD 10 diagnoses of Autistic disorder (AD, n = 50), Intellectual Disability (ID, n = 50), Attention Deficit Hyperactivity Disorder (ADHD, n = 26), other psychiatric disorders (PD-N=25) and control children without psychiatric disorders (n = 65) were evaluated using the ISAA, DD-CGAS and the CARS (total n = 216).Statistical Analyses:In addition to descriptive statistics and correlation, analysis of variance (ANOVA) was used to assess whether the ISAA scores were significantly different across diagnostic groups.Results:Total ISAA scores were significantly higher among children diagnosed with autistic disorder compared to four other diagnostic groups. Total ISAA scores were significantly correlated with CARS scores and DD-CGAS scores. Groups sub-divided on the basis of recommended ISAA cutoff points of severity showed significant differences in CARS scores.Conclusion:The ISAA can thus be used to assess severity of AD among Indian children.

Quality of life in mothers of preschoolers with high-functioning pervasive developmental disorders.

Parents of children with pervasive developmental disorders (PDD) are likely to experience serious distress. The aims of this study were to (i) assess distress among mothers of preschoolers with high-functioning PDD (HFPDD); and (ii) examine its relation to the child's behavioral characteristics. Participants were 30 mothers of preschoolers with HFPDD, and 30 mothers of a matched control group. Short Form 36 Health Survey Questionnaire (version 2), and the Strengths and Difficulties Questionnaire were used for assessment. The children's autistic traits were assessed using the total number of items for the DSM-IV-TR autistic disorder diagnosis. Mothers in the HFPDD group were more distressed mentally than physically. Neither physical nor mental distress in the group was related to the child's autistic traits, while their mental distress was significantly related to the child's behavior problems. Mothers in the HFPDD group were at increased risk of impaired mental wellbeing. Maternal mental distress in the group was significantly related to general behavior problems, but not to autistic traits in the child.

N-acetylcysteine as an adjunctive therapy to risperidone for treatment of irritability in autism: a randomized, double-blind, placebo-controlled clinical trial of efficacy and safety.

According to the proposed interference of N-acetylcysteine (NAC) with pathophysiologic processes of autistic disorders (ADs), we aimed to assess the effectiveness and safety of NAC as an adjunct to risperidone in the treatment of ADs in a randomized, double-blind, clinical trial. The participants were referred outpatients between 4 and 12 years of age with the diagnosis of ADs and a score of more than 12 on Aberrant Behavior Checklist-Community (ABC-C) Irritability subscale score. The participants were randomized into 2 groups. One group received risperidone plus NAC, and the other group received risperidone plus placebo. The dose of risperidone was titrated between 1 and 2.0 mg/d, and the dose of NAC was 600 to 900 mg/d. The main outcome was mean decrease in the ABC-C irritability subscale score from baseline at 5 and 10 weeks. Changes in other subscales were considered as secondary outcome measures. Forty patients completed the 10-week trial. Baseline characteristics including age, sex and body weight, as well as baseline scores in 5 subscales did not demonstrate statistically significant difference between the 2 groups. Repeated-measures analysis showed significant effect for time × treatment interaction in irritability (P = 0.01) and hyperactivity/noncompliance (P = 0.02) subscales. By week 10, the NAC group showed significantly more reduction in irritability (P = 0.02) and hyperactivity/noncompliance (P = 0.01) subscales scores. N-acetylcysteine can be considered as an adjuvant therapy for ADs with beneficial therapeutic outcomes.

Recent update of autism spectrum disorders.

In patients with a language developmental delay, it is necessary to make a differential diagnosis for autism spectrum disorders (ASDs), specific language impairment, and mental retardation. It is important that pediatricians recognize the signs and symptoms of ASDs, as many patients with language developmental delays are ultimately diagnosed with ASDs. Pediatricians play an important role in the early recognition of ASDs, because they are usually the first point of contact for children with ASDs. A revision of the diagnostic criteria of ASDs was proposed in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) that was released in May 2013. The autism spectrum describes a range of conditions classified as neurodevelopmental disorders in the fifth edition of the DSM. The new diagnostic criteria encompasses previous elements from the diagnosis of autistic disorder, Asperger disorder, childhood disintegrative disorder, and pervasive developmental disorder-not otherwise specified. An additional change to the DSM includes synthesizing the section on social and communication deficits into one domain. In ASD patients, the appropriate behavioral therapies and rehabilitation treatments significantly affect the prognosis. Therefore, this makes early diagnosis and treatment very important. In conclusion, pediatricians need to be able to recognize the signs and symptoms of ASDs and be attentive to them in order to make an early diagnosis and provide treatment.

DSM-5 changes and the prevalence of parent-reported autism spectrum symptoms in Fragile X syndrome.

We used survey methodology to assess parent-reported autism symptomology in 758 individuals (639 males; 119 females) with fragile X syndrome (FXS). Caregivers reported whether their child with FXS had been diagnosed with an autism spectrum disorder (ASD) and endorsed symptoms based on a list of observable behaviors related to ASD diagnoses. Symptom counts were categorized based on DSM-IV-TR and DSM-5 criteria. Based on behavioral symptoms endorsed by caregivers, 38.7% of males and 24.7% of females met criteria for DSM-IV-TR diagnosis of autistic disorder. Significantly fewer males (27.8%) and females (11.3%) met criteria for ASD based on DSM-5 criteria. Although 86.4% of males and 61.7% of females met criteria for the restricted and repetitive behavior domain for DSM-5, only 29.4% of males and 13.0% of females met criteria for the social communication and interaction (SCI) domain. Relaxing the social communication criteria by one symptom count led to a threefold increase in those meeting criteria for ASD, suggesting the importance of subthreshold SCI symptoms for individuals with FXS in ASD diagnoses. Findings suggest important differences in the way ASD may be conceptualized in FXS based on the new DSM-5 criteria.

Low rates of depressed mood and depression diagnoses in a clinic review of children and adolescents with autistic disorder.

The purpose of this study was to investigate the prevalence of depression diagnoses and related clinical data in an outpatient sample of youth with autistic disorder. Records of 123 psychiatrically referred children and adolescents with a Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of autistic disorder were examined. Mood disorder diagnoses and chief complaints along with family mood disorder history were the primary variables analyzed. Four subjects (3%) presented with depressed mood. Irritability complaints were frequent (n=78, 63%). Six subjects (5%) received a mood disorder diagnosis; all with mood disorder, not otherwise specified. No subjects received a depressive disorder diagnosis. Family history of mood disorders was common. Findings raise questions about the appropriate characterization and potential misdiagnoses of depression in youth with autistic disorder.

English

The aim of this study was to investigate a previously overlooked, universally introduced environmental factor, fetal and retroviral contaminants in childhood vaccines, absent prior to change points (CPs) in autistic disorder (AD) prevalence with subsequent dose-effect evidence and known pathologic mechanisms of action.  Worldwide population based cohort study was used for the design of this study. The United States, Western Australia, United Kingdom and Denmark settings were used. All live born infants who later developed autistic disorder delivered after 1 January 1970, whose redacted vaccination and autistic disorder diagnosis information is publicly available in databases maintained by the US Federal Government, Western Australia, UK, and Denmark. The live births, grouped by father’s age, were from the US and Australia. The children vaccinated with MMRII, Varicella and Hepatitis A vaccines varied from 19 to 35 months of age at the time of vaccination. Autistic disorder birth year change points were identified as 1980.9, 1988.4 and 1996 for the US, 1987 for UK, 1990.4 for Western Australia, and 1987.5 for Denmark. Change points in these countries corresponded to introduction of or increased doses of human fetal cell line-manufactured vaccines, while no relationship was found between paternal age or Diagnostic and Statistical Manual (DSM) revisions and autistic disorder diagnosis. Further, linear regression revealed that Varicella and Hepatitis A immunization coverage was significantly correlated to autistic disorder cases. R software was used to calculate change points. Autistic disorder change points years are coincident with introduction of vaccines manufactured using human fetal cell lines, containing fetal and retroviral contaminants, into childhood vaccine regimens. This pattern was repeated in the US, UK, Western Australia and Denmark. Thus, rising autistic disorder prevalence is directly related to vaccines manufactured utilizing human fetal cells. Increased paternal age and DSM revisions were not related to rising autistic disorder prevalence.   Key words: Autism disorder, change point, vaccine, paternal age.

Autism spectrum disorders and race, ethnicity, and nativity: a population-based study.

Our understanding of the influence of maternal race/ethnicity and nativity and childhood autistic disorder (AD) in African Americans/blacks, Asians, and Hispanics in the United States is limited. Phenotypic differences in the presentation of childhood AD in minority groups may indicate etiologic heterogeneity or different thresholds for diagnosis. We investigated whether the risk of developing AD and AD phenotypes differed according to maternal race/ethnicity and nativity. Children born in Los Angeles County with a primary AD diagnosis at ages 3 to 5 years during 1998-2009 were identified and linked to 1995-2006 California birth certificates (7540 children with AD from a cohort of 1,626,354 births). We identified a subgroup of children with AD and a secondary diagnosis of mental retardation and investigated heterogeneity in language and behavior. We found increased risks of being diagnosed with AD overall and specifically with comorbid mental retardation in children of foreign-born mothers who were black, Central/South American, Filipino, and Vietnamese, as well as among US-born Hispanic and African American/black mothers, compared with US-born whites. Children of US African American/black and foreign-born black, foreign-born Central/South American, and US-born Hispanic mothers were at higher risk of exhibiting an AD phenotype with both severe emotional outbursts and impaired expressive language than children of US-born whites. Maternal race/ethnicity and nativity are associated with offspring's AD diagnosis and severity. Future studies need to examine factors related to nativity and migration that may play a role in the etiology as well as identification and diagnosis of AD in children.

Drug-refractory aggression, self-injurious behavior, and severe tantrums in autism spectrum disorders: A chart review study

Aggression, self-injurious behavior, and severe tantrums are impairing symptoms frequently experienced by individuals with autism spectrum disorders. Despite US Food and Drug Administration approval of two atypical antipsychotics targeting these symptoms in youth with autistic disorder, they remain frequently drug refractory. We define drug-refractory aggression, self-injurious behavior, and severe tantrums in people with autism spectrum disorders as behavioral symptoms requiring medication adjustment despite previous trials of risperidone and aripiprazole or previous trials of three psychotropic drugs targeting the symptom cluster, one of which was risperidone or aripiprazole. We reviewed the medical records of individuals of all ages referred to our clinic for autism spectrum disorder diagnostic evaluation, as well as pharmacotherapy follow-up notes for all people meeting autism spectrum disorder criteria, for drug-refractory symptoms. Among 250 consecutively referred individuals, 135 met autism spectrum disorder and enrollment criteria, and 53 of these individuals met drug-refractory symptom criteria. Factors associated with drug-refractory symptoms included age 12 years or older (p < 0.0001), diagnosis of autistic disorder (p = 0.0139), and presence of intellectual disability (p = 0.0273). This pilot report underscores the significance of drug-refractory aggression, self-injurious behavior, and severe tantrums; suggests the need for future study clarifying factors related to symptom development; and identifies the need for focused treatment study of this impairing symptom domain.

Autism Detection in Early Childhood (ADEC): Reliability and validity data for a level 2 screening tool for autistic disorder.

The Autism Detection in Early Childhood (ADEC; Young, 2007) was developed as a Level 2 clinician-administered autistic disorder (AD) screening tool that was time-efficient, suitable for children under 3 years, easy to administer, and suitable for persons with minimal training and experience with AD. A best estimate clinical Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR; American Psychiatric Association, 2000) diagnosis of AD was made for 70 children using all available information and assessment results, except for the ADEC data. A screening study compared these children on the ADEC with 57 children with other developmental disorders and 64 typically developing children. Results indicated high internal consistency (α = .91). Interrater reliability and test-retest reliability of the ADEC were also adequate. ADEC scores reliably discriminated different diagnostic groups after controlling for nonverbal IQ and Vineland Adaptive Behavior Composite scores. Construct validity (using exploratory factor analysis) and concurrent validity using performance on the Autism Diagnostic Observation Schedule (Lord et al., 2000), the Autism Diagnostic Interview-Revised (Le Couteur, Lord, & Rutter, 2003), and DSM-IV-TR criteria were also demonstrated. Signal detection analysis identified the optimal ADEC cutoff score, with the ADEC identifying all children who had an AD (N = 70, sensitivity = 1.0) but overincluding children with other disabilities (N = 13, specificity ranging from .74 to .90). Together, the reliability and validity data indicate that the ADEC has potential to be established as a suitable and efficient screening tool for infants with AD.

Association between regression and self injury among children with autism

Self injurious behaviors (SIBs) are challenging clinical problems in individuals with autism spectrum disorders (ASDs). This study is one of the first and largest to utilize inpatient data to examine the associations between autism, developmental regression, and SIBs. Medical records of 125 neurobehavioral hospitalized patients with diagnoses of ASDs and SIBs between 4 and 17 years of age were reviewed. Data were collected from medical records on the type and frequency of SIBs and a history of language, social, or behavioral regression during development. The children with a history of any type of developmental regression (social, behavioral, or language) were more likely to have a diagnosis of autistic disorder than other ASD diagnoses. There were no significant differences in the occurrence of self injurious or other problem behaviors (such as aggression or disruption) between children with and without regression. Regression may influence the diagnostic considerations in ASDs but does not seem to influence the clinical phenotype with regard to behavioral issues. Additional data analyses explored the frequencies and subtypes of SIBs and other medical diagnoses in ASDs, with intellectual disability and disruptive behavior disorder found most commonly.

Komorbide psychiatrische Störungen und Differenzialdiagnostik bei nicht-intelligenzgeminderten Erwachsenen mit Autismus-Spektrum-Störung

Autism spectrum conditions (ASC) without intellectual disability are often diagnosed late in life. Little is known about co-occurring psychiatric disorders and differential diagnosis of ASC in adulthood, particularly with regard to personality disorders. What kind of comorbid psychiatric disorders occur in ASC? Which are the most prevalent differential diagnoses in a sample of patients who seek autism specific clinical diagnostics? 118 adults who were referred with a presumed diagnosis of autistic disorder, were diagnosed with autism specific instruments and the prevalence of further psychiatric disorders was investigated. 59 (50%) fulfilled the criteria of ASC. 36% of the individuals with ASC fulfilled also criteria for a DSM-IV axis-I psychiatric disorder. Affective disorders (24%) and social phobia (14%) were the most prevalent comorbid disorders. The most frequent differential diagnoses were depression, social phobia, paranoid, avoidant and narcissistic personality disorder.

Epidemiology of autistic disorder in Bahrain: prevalence and obstetric and familial characteristics

European and North American studies show that the prevalence of autistic disorder is inccreasing. This study was performed to identify the prevalence of autistic disorder in Bahrain, and determine some of the demographic and family characteristics. Using a case-control design, 100 children who received a diagnosis of autistic disorder according to DSM-IV-TR during the period 2000-2010 were selected. An equal numberofcontrols who had received a diagnosis of nocturnal enuresis and no psychopathology were selected, matched for sex and age group. The prevalence of autistic disorder was estimated as 4.3 per 10,000 population, with a male:female sex ratio of 4:1. Significantly more cases than controls were delivered by caesarean section and had mothers who suffered prenatal complications. The prevalence estimate in Bahrain is comparable to previous reports using similar methods. Obstetric complications and caesarean section delivery may be associated with autistic disorder.

Autism and Mental Retardation Among Offspring Born After In Vitro Fertilization

Between 1978 and 2010, approximately 5 million infants were born after in vitro fertilization (IVF) treatments. Yet limited information on neurodevelopment after IVF exists, especially after the first year of life. To examine the association between use of any IVF and different IVF procedures and the risk of autistic disorder and mental retardation in the offspring. A population-based, prospective cohort study using Swedish national health registers. Offspring born between 1982 and 2007 were followed up for a clinical diagnosis of autistic disorder or mental retardation until December 31, 2009. The exposure of interest was IVF, categorized according to whether intracytoplasmic sperm injection (ICSI) for male infertility was used and whether embryos were fresh or frozen. For ICSI, whether sperm were ejaculated or surgically extracted was also considered. Relative risks (RRs) for autistic disorder and mental retardation and rates per 100,000 person-years, comparing spontaneously conceived offspring with those born after an IVF procedure and comparing 5 IVF procedures used in Sweden vs IVF without ICSI with fresh embryo transfer, the most common treatment. We also analyzed the subgroup restricted to singletons. Of the more than 2.5 million infants born, 30,959 (1.2%) were conceived by IVF and were followed up for a mean 10 (SD, 6) years. Overall, 103 of 6959 children (1.5%) with autistic disorder and 180 of 15,830 (1.1%) with mental retardation were conceived by IVF. The RR for autistic disorder after any procedure compared with spontaneous conception was 1.14 (95% CI, 0.94-1.39; 19.0 vs 15.6 per 100,000 person-years). The RR for mental retardation was 1.18 (95% CI, 1.01-1.36; 46.3 vs 39.8 per 100,000 person-years). For both outcomes, there was no statistically significant association when restricting analysis to singletons. Compared with IVF without ICSI with fresh embryo transfer, there were statistically significantly increased risks of autistic disorder following ICSI using surgically extracted sperm and fresh embryos (RR, 4.60 [95% CI, 2.14-9.88]; 135.7 vs 29.3 per 100,000 person-years); for mental retardation following ICSI using surgically extracted sperm and fresh embryos (RR, 2.35 [95% CI, 1.01-5.45]; 144.1 vs 60.8 per 100,000 person-years); and following ICSI using ejaculated sperm and fresh embryos (RR, 1.47 [95% CI, 1.03-2.09]; 90.6 vs 60.8 per 100,000 person-years). When restricting the analysis to singletons, the risks of autistic disorder associated with ICSI using surgically extracted sperm were not statistically significant, but the risks associated with ICSI using frozen embryos were significant for mental retardation (with frozen embryos, RR, 2.36 [95% CI, 1.04-5.36], 118.4 vs 50.6 per 100,000 person-years]; with fresh embryos, RR, 1.60 [95% CI, 1.00-2.57], 80.0 vs 50.6 per 100,000 person-years). Compared with spontaneous conception, IVF treatment overall was not associated with autistic disorder but was associated with a small but statistically significantly increased risk of mental retardation. For specific procedures, IVF with ICSI for paternal infertility was associated with a small increase in the RR for autistic disorder and mental retardation compared with IVF without ICSI. The prevalence of these disorders was low, and the increase in absolute risk associated with IVF was small.