1. A DEM, Eigsti IM. {{The art of common ground: emergence of a complex pragmatic language skill in adolescents with autism spectrum disorders}}. {J Child Lang}. 2015: 1-38.
ABSTRACT Deficits in pragmatic language are central to autism spectrum disorder (ASD). Here we investigate common ground, a pragmatic language skill in which speakers adjust the contents of their speech based on their interlocutor’s perceived knowledge, in adolescents with ASD and typical development (TD), using an experimental narrative paradigm. Consistent with prior research, TD participants produced shorter narrations when they shared knowledge with an interlocutor, an effect not observed at the group level in ASD. This effect was unrelated to general skills such as IQ or receptive vocabulary. In ASD, the effect was correlated with age and symptom severity: older and less severely affected participants did shorten their narratives. Several metrics (including explicit references to common ground, speech disfluencies, and communicative quality ratings) suggested that, although adolescents with ASD did not show implicit reductions in their narrative length, they were aware of common ground, and communicated differently in its presence.
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2. Berger NI, Ingersoll B. {{An Evaluation of Imitation Recognition Abilities in Typically Developing Children and Young Children with Autism Spectrum Disorder}}. {Autism Res}. 2015.
Previous work has indicated that both typically developing children and children with Autism Spectrum Disorder (ASD) display a range of imitation recognition behaviors in response to a contingent adult imitator. However, it is unknown how the two groups perform comparatively on this construct. In this study, imitation recognition behaviors for children with ASD and typically developing children were observed during periods of contingent imitation imbedded in a naturalistic imitation task. Results from this study indicate that children with ASD are impaired in their ability to recognize being imitated relative to typically developing peers as demonstrated both by behaviors representing basic social attention and more mature imitation recognition. Display of imitation recognition behaviors was independent of length of contingent imitation period in typically developing children, but rate of engagement in imitation recognition behaviors was positively correlated with length of contingent imitation period in children with ASD. Exploratory findings also suggest a link between the ability to demonstrate recognition of being imitated and ASD symptom severity, language, and object imitation for young children with ASD. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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3. Dababnah S, Parish SL. {{Feasibility of an empirically based program for parents of preschoolers with autism spectrum disorder}}. {Autism}. 2015.
This article reports on the feasibility of implementing an existing empirically based program, The Incredible Years, tailored to parents of young children with autism spectrum disorder. Parents raising preschool-aged children (aged 3-6 years) with autism spectrum disorder (N = 17) participated in a 15-week pilot trial of the intervention. Quantitative assessments of the program revealed fidelity was generally maintained, with the exception of program-specific videos. Qualitative data from individual post-intervention interviews reported parents benefited most from child emotion regulation strategies, play-based child behavior skills, parent stress management, social support, and visual resources. More work is needed to further refine the program to address parent self-care, partner relationships, and the diverse behavioral and communication challenges of children across the autism spectrum. Furthermore, parent access and retention could potentially be increased by providing in-home childcare vouchers and a range of times and locations in which to offer the program. The findings suggest The Incredible Years is a feasible intervention for parents seeking additional support for child- and family-related challenges and offers guidance to those communities currently using The Incredible Years or other related parenting programs with families of children with autism spectrum disorder.
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4. De Filippis B, Valenti D, de Bari L, De Rasmo D, Musto M, Fabbri A, Ricceri L, Fiorentini C, Laviola G, Anna Vacca R. {{Mitochondrial free radicals overproduction due to respiratory chain impairment in brain of a mouse model of Rett syndrome. Protective effect of CNF1}}. {Free Radic Biol Med}. 2015.
Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly caused by mutations in the X-linked MECP2 gene, associated with severe intellectual disability, movement disorders and autistic-like behaviours. Its pathogenesis remains mostly not understood, and no effective therapy is available. High circulating levels of oxidative stress markers in patients and the occurrence of oxidative brain damage in MeCP2-deficient mouse models suggest the involvement of oxidative stress in RTT pathogenesis. However, the molecular mechanism and the origin of oxidative stress have not been elucidated. Here we demonstrate that a redox imbalance arises from aberrant mitochondrial functionality in the brain of MeCP2-308 heterozygous female mice, the condition that more closely recapitulates that of RTT patients. The marked increase in the rate of hydrogen peroxide generation in the brain of RTT mice appears mainly produced by the dysfunctional complex II of the mitochondrial respiratory chain. In addition, both membrane potential generation and mitochondrial ATP synthesis are decreased in RTT mouse brains when succinate, the complex II respiratory substrate, is used as energy source. Respiratory chain impairment is brain area-specific, due to a decrease in either cAMP-dependent phosphorylation or protein levels of specific complex subunits. Further, we investigated whether the treatment of RTT mice with the bacterial protein CNF1, previously reported to ameliorate the neurobehavioural phenotype and brain bioenergetic markers in a RTT mouse model, exerts specific effects on brain mitochondrial function and consequently on hydrogen peroxide production. In RTT brains treated with CNF1, we observed the reactivation of respiratory chain complexes, the rescue of mitochondrial functionality and the prevention of brain hydrogen peroxide overproduction. Present results provide definitive evidence of mitochondrial reactive oxygen species overproduction in RTT mouse brain and highlight CNF1 efficacy in counteracting RTT-related mitochondrial defects.
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5. Doyle-Thomas KA, Lee W, Foster NE, Tryfon A, Ouimet T, Hyde KL, Evans AC, Lewis J, Zwaigenbaum L, Anagnostou E. {{Atypical functional brain connectivity during rest in autism spectrum disorders}}. {Ann Neurol}. 2015.
Connectivity atypicalities in autism spectrum disorders (ASD) have been extensively proposed. The default mode network (DMN) is critical in this study given the insight it provides for long-distance connectivity, and the importance of regions in this network for introspection and social emotion processing, areas affected in ASD. Still, study of this network is largely limited to adults; research earlier in development is lacking. Objective: To examine DMN connectivity in children/ adolescents with ASD. Methods: 115 children/ adolescents, ages 6-17 years [71 males with ASD and 44 group age-matched TD males] were included in these analyses. We examined group differences in (1) functional connectivity between the posterior cingulate cortex and regions across the brain, (2) connectivity within the DMN as a function of age and IQ, and (3) the association between DMN connectivity and empathic accuracy. Results: Individuals with ASD, relative to controls showed either stronger, and weaker connectivity between the PCC and DMN regions, depending on the region, but also showed stronger connectivity with non-DMN regions. A significant group-by-age interaction was observed in functional connectivity between the PCC and medial prefrontal cortex; connectivity increased with age in controls, but decreased in individuals with ASD. No effects of IQ were found. There was a significant group difference in the relation between DMN connectivity and empathic accuracy. Interpretation: Differences in functional connectivity may suggest the presence of neural atypicalities that impact the development of typical connectivity in ASD. In addition to affecting DMN dynamics, these atypicalities may also impact social-cognitive abilities. This article is protected by copyright. All rights reserved.
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6. Dutheil F, Chambres P, Hufnagel C, Auxiette C, Chausse P, Ghozi R, Paugam G, Boudet G, Khalfa N, Naughton G, Chamoux A, Mermillod M, Bertrand PR. {{‘Do Well B.’: Design Of WELL Being monitoring systems. A study protocol for the application in autism}}. {BMJ Open}. 2015; 5(2): e007716.
INTRODUCTION: Individuals with autism spectrum disorder (ASD) have difficulties in communication and social interaction resulting from atypical perceptual and cognitive information processing, leading to an accumulation of anxiety. Extreme overloading experienced internally may not be externally visible. Identifying stressful situations at an early stage may avoid socially problematic behaviour from occurring, such as self-injurious behaviour. Activation of the autonomous nervous system (ANS) is involved in the response to anxiety, which can be measured through heart rate variability and skin conductance with the use of portable devices, non-intrusively and pain-free. Thus, developing innovative analysis of signal perception and reaction is necessary, mainly for non-communicative individuals with autism. METHODS AND ANALYSIS: The protocol will take place in real life (home and social environments). We aim to associate modifications of the ANS with external events that will be recorded in a synchronous manner through a specific design (spy glasses with video/audio recording). Four phases will be carried out on ASD participants and aged-matched controls: (1) 24-hour baseline pre-experiment (physical activity, sleep), (2) 2 h in a real life situation, (3) 30 min in a quiet environment, interrupted by a few seconds of stressful sound, (4) an interview to record feelings about events triggering anxiety. ASD and control participants will be together for phases 2 and 3, revealing different physiological responses to the same situations, and thus identifying potentially problematic events. The novelty will be to apply time-series analyses (which led to several Nobel Prizes in quantitative finance) on ANS series (heart rate, heart rate variability, skin conductance) and wrist motion. ETHICS AND DISSEMINATION: Ethical approval has been obtained from Ethics Committee of Clermont-Ferrand (South-East I), France (2014-A00611-46). Trial findings will be disseminated via open-access peer-reviewed publications, conferences, clinical networks, public lectures and our websites. TRIAL REGISTRATION NUMBER: ClinicalTrials identifier NCT02275455.
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7. Garrido D, Carballo G, Franco V, Garcia-Retamero R. {{[Language comprehension disorders in non-verbal children with autism spectrum disorders and their implications in the family quality of life]}}. {Rev Neurol}. 2015; 60(5): 207-14.
INTRODUCTION. Language widely varies in children with autism spectrum disorders (ASD). Evidence, however, suggests that these children understand language worse than their peers with typical development, showing a delay in acquisition of receptive vocabulary. Research relating quality of life (QOL) and language is limited. AIMS. To increase our knowledge about structural aspects of language in children with ASD, and to determine the effects of deficits in understanding in children with ASD in their families’ QOL. SUBJECTS AND METHODS. We analyzed language comprehension in 26 non-verbal children with ASD (mean: 9.8 years) and 26 children with typical development (mean: 3.9 years) matched for age vocabulary, using standardized measures of receptive language. RESULTS. We found that levels of receptive vocabulary, auditory comprehension, and grammar comprehension in children with ASD are lower than typical levels for their age, and significantly differ from those in children with typical development. Parents of children with ASD also report severe communication problems in their children and lack of social support. Family QOL is influenced by language problems of children with ASD. CONCLUSIONS. There is a significant relationship between receptive language skills in children with ASD and perceptions of QOL in their families. These results can have important implications for designing clinical interventions.
8. Hiller RM, Young RL, Weber N. {{Sex differences in pre-diagnosis concerns for children later diagnosed with autism spectrum disorder}}. {Autism}. 2015.
In the absence of intellectual impairment, girls are diagnosed with autism spectrum disorder significantly less and later than boys. This study explored potential reasons for why autism spectrum disorder may be more difficult to identify in girls, based on carer concerns during the pre-diagnosis period. Carers of 92 boys and 60 girls diagnosed with autism spectrum disorder from school age completed an online survey addressing concerns regarding the child’s development during the pre-school years (pre-diagnosis). Significant sex differences were evident in key early concerns, as well as the strategies used to navigate pre-school social situations, and the types of restricted interests. Findings suggest, from carer perspective, that girls who went on to be diagnosed with autism spectrum disorder presented differently when compared to boys, providing insight into why the diagnosis of autism spectrum disorder may be more difficult to make with cognitively able girls.
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9. Kantojarvi K, Oikkonen J, Kotala I, Kallela J, Vanhala R, Onkamo P, Jarvela I. {{Association and Promoter Analysis of AVPR1A in Finnish Autism Families}}. {Autism Res}. 2015.
The arginine vasopressin receptor 1A gene (AVPR1A) is known to affect social communication and has been reported to associate with autism in several studies. Given that the microsatellite RS1 and a few SNPs in the promoter region of the AVPR1A have repeatedly associated with several traits, including autism it is rather surprising that the molecular explanation for these associations has remained unknown, although it has been reported that the allele length of the AVPR1A microsatellites might affect disease risk. Here we carried out an extended association analysis of three microsatellites and 12 tag single nucleotide polymorphisms (SNPs) in and around the AVPR1A gene in 205 Finnish families followed by promoter analysis. FBAT version v2.0.3 was used for family-based genetic association analyses of AVPR1A microsatellites and SNPs. The nearby microsatellite RS1 was found to harbor the best association. Interestingly, there are two potentially relevant transcription factor (TF) binding sites at RS1: for MEF2C and PBX, predicted with the Match algorithm in the TRANSFAC(R) database. Sequence variations changing the affinity of these TFs might partly explain the AVPR1A promoter region associations shown in autism. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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10. Kerns CM, Newschaffer CJ, Berkowitz SJ. {{Traumatic Childhood Events and Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2015.
Traumatic childhood events are associated with a wide range of negative physical, psychological and adaptive outcomes over the life course and are one of the few identifiable causes of psychiatric illness. Children with autism spectrum disorder (ASD) may be at increased risk for both encountering traumatic events and developing traumatic sequelae; however, this topic has been understudied. This review considers the rationale for examining traumatic events and related symptomology in individuals with ASD and summarizes the limited research on this topic. A conceptual framework for understanding the interplay of ASD, trauma and traumatic sequelae is proposed and recommendations for future research presented.
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11. Kosmicki JA, Sochat V, Duda M, Wall DP. {{Searching for a minimal set of behaviors for autism detection through feature selection-based machine learning}}. {Transl Psychiatry}. 2015; 5: e514.
Although the prevalence of autism spectrum disorder (ASD) has risen sharply in the last few years reaching 1 in 68, the average age of diagnosis in the United States remains close to 4-well past the developmental window when early intervention has the largest gains. This emphasizes the importance of developing accurate methods to detect risk faster than the current standards of care. In the present study, we used machine learning to evaluate one of the best and most widely used instruments for clinical assessment of ASD, the Autism Diagnostic Observation Schedule (ADOS) to test whether only a subset of behaviors can differentiate between children on and off the autism spectrum. ADOS relies on behavioral observation in a clinical setting and consists of four modules, with module 2 reserved for individuals with some vocabulary and module 3 for higher levels of cognitive functioning. We ran eight machine learning algorithms using stepwise backward feature selection on score sheets from modules 2 and 3 from 4540 individuals. We found that 9 of the 28 behaviors captured by items from module 2, and 12 of the 28 behaviors captured by module 3 are sufficient to detect ASD risk with 98.27% and 97.66% accuracy, respectively. A greater than 55% reduction in the number of behaviorals with negligible loss of accuracy across both modules suggests a role for computational and statistical methods to streamline ASD risk detection and screening. These results may help enable development of mobile and parent-directed methods for preliminary risk evaluation and/or clinical triage that reach a larger percentage of the population and help to lower the average age of detection and diagnosis.
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12. Porokhovnik LN, Passekov VP, Gorbachevskaya NL, Sorokin AB, Veiko NN, Lyapunova NA. {{Active ribosomal genes, translational homeostasis and oxidative stress in the pathogenesis of schizophrenia and autism}}. {Psychiatr Genet}. 2015; 25(2): 79-87.
BACKGROUND: Infantile autism and schizophrenia are severe multifactorial disorders with a pronounced genetic predisposition. Their pathogeneses are often associated with oxidative stress in the brain. Previously, we established that a cell’s resistance to oxidative stress depended on the copy number of transcriptionally active genes for rRNA (ribosomal genes) in the cell’s genome. The feature is measured cytogenetically in cultured lymphocytes derived from patients. It varies from 120 up to 190 copies per diploid genome, with an arithmetic mean of 150+/-4 (SE) copies in a healthy population (n=239), being considerably lower, according to our previous results, in a sample of patients with rheumatoid arthritis (n=49), another multifactorial disease with a proven significant role of oxidative stress in its pathogenesis: from 115 to 165 copies, with a mean of 140+/-4 (SE). Conversely, a sample of schizophrenic patients (n=42) previously showed a higher value of copy number of active rRNA genes compared with a healthy population: from 145 to 190 copies, with a mean of 170+/-4. This fact is of special interest in the context of the well-known, but still unexplained phenomenon of the reduced comorbidity rate of schizophrenia and rheumatoid arthritis. RESULTS: The copy number of active ribosomal genes was estimated in a sample of autistic children (n=51). In contrast with the schizophrenic patients studied previously, we found that the values were significantly lower than those in the healthy population: from 125 to 160 copies, with a mean of 142+/-5. In this work, we suggest a mathematical model of the oxidative stress dynamics on the basis of Lotka-Volterra’s approach to predator-prey interactions. In our model, the ‘prey’ represents reactive oxygen species, whereas the ‘predator’ simulates molecules of the antioxidant enzymes. The rate of biosynthesis of the latter is limited by the number of ribosomes available, which, in turn, is determined by the copy number of active rRNA genes. Analysis of the model showed the existence of a unique equilibrium point that makes biological sense. The reactive oxygen species level oscillatory approaches this equilibrium value, which inversely depends on the copy number of active rRNA genes. DISCUSSION: Our findings confirm the hypothesis of disturbance of the ‘translational homeostasis’ in the pathogeneses of autism and schizophrenia, and would help explain why oxidative stress markers are discovered in most autism studies, whereas similar reports related to schizophrenia are far less consistent.
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13. Samson AC, Hardan AY, Lee IA, Phillips JM, Gross JJ. {{Maladaptive Behavior in Autism Spectrum Disorder: The Role of Emotion Experience and Emotion Regulation}}. {J Autism Dev Disord}. 2015.
Maladaptive behavior is common in Autism Spectrum Disorder (ASD). However, the factors that give rise to maladaptive behavior in this context are not well understood. The present study examined the role of emotion experience and emotion regulation in maladaptive behavior in individuals with ASD and typically developing (TD) participants. Thirty-one individuals with ASD and 28 TD participants and their parents completed questionnaires assessing emotion experience, regulation, and maladaptive behavior. Compared to TD participants, individuals with ASD used cognitive reappraisal less frequently, which was associated with increased negative emotion experience, which in turn was related to greater levels of maladaptive behavior. By decreasing negative emotions, treatments targeting adaptive emotion regulation may therefore reduce maladaptive behaviors in individuals with ASD.
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14. Semrud-Clikeman M, Fine JG, Bledsoe J. {{Social functioning using direct and indirect measures with children with High Functioning Autism, nonverbal learning disability, and typically developing children}}. {Child Neuropsychol}. 2015: 1-18.
Social perception is an important underlying foundation for emotional development and overall adaptation. The majority of studies with children with High Functioning Autism (HFA) or nonverbal learning disabilities (NLD) evaluating social functioning have used measures of parent and/or teacher ratings. The present study utilized parent and teacher ratings of behavior as well as executive functioning in addition to direct measures of social perception. Three groups participated in this study (control [n = 38] HFA [n = 36], NLD [n = 31]). Results indicated that the HFA group experienced the most difficulty understanding emotional cues on the direct measure while both the HFA and NLD groups experienced difficulty with nonverbal cues. Significant difficulties were reported on the parent rating scale for sadness and social withdrawal for both clinical groups. Executive functioning was found to be particularly problematic for the clinical groups. The direct social perception measure was highly correlated with the measures of executive functioning and reflects the contribution that executive functions have on social functioning. These findings suggest that the clinical presentation on behavior rating scales may be very similar for children with HFA and NLD. Moreover, it appears that measures of executive functioning are sensitive to the clinical difficulties these groups experience. The findings also suggest there is a commonality in these disorders that warrants further investigation.
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15. Soltanifar A, Akbarzadeh F, Moharreri F, Ebrahimi A, Mokhber N, Minoocherhr A, Ali Naqvi SS. {{Comparison of parental stress among mothers and fathers of children with autistic spectrum disorder in Iran}}. {Iran J Nurs Midwifery Res}. 2015; 20(1): 93-8.
BACKGROUND: Most of the studies about parenting stress among parents of children with autistic spectrum disorder (ASD) have been conducted in western societies. The objective of this research, conducted in Iran, is to evaluate the parenting stress among fathers and mothers of children with ASD and find the correlation between severity of the disorder in children and the level of parental stress. MATERIALS AND METHODS: Participants included 42 couples having children aged between 2 and 12 diagnosed with ASD based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. The diagnosis was made by two child and adolescent psychiatrists. Demographic information of the participants was collected using a questionnaire. The severity of pervasive developmental disorder in children was determined based on Childhood Autism Rating Scale (CARS); stress of parents was measured using Parenting Stress Index (PSI). Collected information was analyzed by the SPSS (version 16) software. RESULTS: Evaluation of subscales in participants’ data showed a positive correlation coefficient between the PSI-parent domain and Childhood Autism Rating Scale-Parent form CARS-P rating (r = 0.339, P =0 0.028) and also between the total stress index and CARS-P rating (r = 0.333, P = 0.031) for fathers. It is thus suggested that fathers of children with more severe developmental disorders experience more stress. The results showed significant differences between fathers and mothers in the three PSI subscales including PSI-child domain score (P < 0.005), PSI-parent domain score (P < 0.005), and the total stress index (P < 0.005). Mothers had significantly more stress than fathers. CONCLUSIONS: These findings show that parents with ASD children have many emotional needs which should be considered in planning the effective treatment strategies for their children.
16. van Bon BW, Coe BP, Bernier R, Green C, Gerdts J, Witherspoon K, Kleefstra T, Willemsen MH, Kumar R, Bosco P, Fichera M, Li D, Amaral D, Cristofoli F, Peeters H, Haan E, Romano C, Mefford HC, Scheffer I, Gecz J, de Vries BB, Eichler EE. {{Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID}}. {Mol Psychiatry}. 2015.
Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) maps to the Down syndrome critical region; copy number increase of this gene is thought to have a major role in the neurocognitive deficits associated with Trisomy 21. Truncation of DYRK1A in patients with developmental delay (DD) and autism spectrum disorder (ASD) suggests a different pathology associated with loss-of-function mutations. To understand the phenotypic spectrum associated with DYRK1A mutations, we resequenced the gene in 7162 ASD/DD patients (2446 previously reported) and 2169 unaffected siblings and performed a detailed phenotypic assessment on nine patients. Comparison of our data and published cases with 8696 controls identified a significant enrichment of DYRK1A truncating mutations (P=0.00851) and an excess of de novo mutations (P=2.53 x 10-10) among ASD/intellectual disability (ID) patients. Phenotypic comparison of all novel (n=5) and recontacted (n=3) cases with previous case reports, including larger CNV and translocation events (n=7), identified a syndromal disorder among the 15 patients. It was characterized by ID, ASD, microcephaly, intrauterine growth retardation, febrile seizures in infancy, impaired speech, stereotypic behavior, hypertonia and a specific facial gestalt. We conclude that mutations in DYRK1A define a syndromic form of ASD and ID with neurodevelopmental defects consistent with murine and Drosophila knockout models.Molecular Psychiatry advance online publication, 24 February 2015; doi:10.1038/mp.2015.5.
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17. Weisman O, Agerbo E, Carter CS, Harris JC, Uldbjerg N, Henriksen TB, Thygesen M, Mortensen PB, Leckman JF, Dalsgaard S. {{Oxytocin-augmented labor and risk for autism in males}}. {Behav Brain Res}. 2015.
The use of synthetic oxytocin (OT) to induce and/or augment labor and delivery is on the rise. Maternal exposure to OT during birth may have adverse effects on the infant’s development, including increased risk for autism. Yet, studies that test this biologically plausible association and whether it is modified by sex are limited and show inconsistent findings. To this end, we conducted an epidemiological analysis, including all singleton live births in Denmark between 2000 and 2009 (N=557,040), with a follow-up through 2012. A total of 2110 children in this cohort were subsequently diagnosed with autistic disorder according to the ICD-10-DCR. Augmentation of labor with OT was modestly associated with an increased risk for autism in males (HR 1.13; 95% CI, 1.00-1.26; P=0.04), but not in females (0.99; 0.77-1.27; P=0.95). Among males exposed to OT augmentation, 560 were subsequently diagnosed with autistic disorder, and among those not exposed, 1177 met criteria for autism (incidence rate 103.2 and 81.4 per 100,000 person-years, respectively). Our findings suggest a modest association between OT-augmented labor and risk for autism in males. However, given the known benefits of using synthetic OT during labor and delivery caution is warranted when interpreting the findings. Future studies should also investigate dose-dependent effect of OT on infant’s development.
