Measuring autism-associated traits in the general population: Factor structure and measurement invariance across sex and diagnosis status of the Social Communication Questionnaire.

LAY ABSTRACT: Using questionnaires in research relies on the expectation that they measure the same things across different groups of individuals. If this is not true, then interpretations of results can be misleading when researchers compare responses across different groups of individuals or use in it a group that differs from that in which the questionnaire was developed. For the questionnaire we investigated, the Social Communication Questionnaire (SCQ), we found that parents of boys and girls responded to questionnaire items in largely the same way but that the SCQ measured traits and behaviors slightly differently depending on whether the children had autism. Based on these results, we concluded that researchers using this questionnaire should carefully consider these differences when deciding how to interpret findings. SCQ scores as a reflection of "autism-associated traits" in samples that are mostly or entirely made up of individuals without an autism diagnosis may be misleading and we encourage a more precise interpretation of scores as a broader indication of social-communicative and behavioral traits.

The association of cognitive abilities with language disorder in 8-year-old children: A population-based clinical sample.

BACKGROUND: Despite accumulated evidence that language development depends on basic cognitive processes, the balance in contributions of verbal and non-verbal cognitive skills to language abilities is still underexplored. Little is known about which cognitive measures best predict the degree of severity in children with language disorder (LD). AIMS: To examine the association between verbal and non-verbal cognitive abilities with language abilities in typically developing and language impaired 8-year-old children, as well as which cognitive abilities are most effective in distinguishing LD severity levels. METHODS & PROCEDURES: Children (N = 509) from the Language-8 Study, which oversampled probable cases of children with LD from a population-based cohort in Norway, were assessed at 8 years. Language skills were assessed using the Norwegian Clinical Evaluation of Language Fundamentals-4 (CELF-4). Children's verbal and non-verbal cognitive abilities were assessed via standardized cognitive measures. An exploratory factor analysis (EFA) was first conducted to uncover the underlying factor structure of the cognitive variables. Using a hierarchical multiple regression analysis, we then examined to what extent the non-verbal cognition factor explained language abilities above and beyond verbal cognition factors. Lastly, multinomial logistic regression was used to examine which cognitive measures best predicted the degree of severity in the children with LD. OUTCOMES & RESULTS: The EFA resulted in three factors (Verbal Cognition, Processing Speed and Memory, and Non-Verbal Cognition). The hierarchical multiple regression analysis revealed that all three cognitive factors contributed significantly to individual variation in language abilities. Non-Verbal Cognition explained 5.4% variance in language abilities above and beyond that accounted for by Verbal Cognition and Processing Speed and Memory. Results from the multinomial logistic regression analysis indicated that cognitive subtests, including Familiar Sequences, WASI Vocabulary and WASI Similarities, not only distinguished LD from typically developing children, but were also efficient in distinguishing severity of LD symptoms. CONCLUSIONS & IMPLICATIONS: This study confirms concurrent links between language and non-verbal cognitive skills above and beyond the contribution of verbal cognitive skills. The results provide further evidence that children with LD experience both language and cognitive problems in mid-childhood. Our findings suggest implications for LD intervention and diagnosis. The findings support the importance of measuring both verbal and non-verbal cognitive skills when making an LD diagnosis, and point to the potential of targeting underlying cognitive skills as one strategy to support language abilities. WHAT THIS PAPER ADDS: What is already known on the subject Language development is dependent on basic cognitive processes. These include both verbal and non-verbal cognitive abilities. Children with LD often experience both language and cognitive problems. There is evidence that performance on cognitive tests may be associated with the degree of severity of LD. What this paper adds to existing knowledge The current results from a large population-based cohort establish that a number of verbal and non-verbal cognitive abilities are tightly linked to variation in language abilities and the degree of severity of LD. Our study confirms concurrent links between language and non-verbal cognitive abilities above and beyond the contribution of verbal cognitive abilities. We also identify specific verbal and non-verbal cognitive tests that distinguish between typical children and children with LD, as well as LD severity. What are the potential or actual clinical implications of this work? Our findings support the importance of measuring both verbal and non-verbal cognitive skills when making an LD diagnosis. Our findings also point to the potential of targeting underlying cognitive skills as one strategy to support language abilities. We suggest that future intervention studies focus on the impact of non-verbal cognitive skills on language development in children with LD.

Adherence to a healthy and potentially sustainable Nordic diet is associated with child development in The Norwegian Mother, Father and Child Cohort Study (MoBa).

BACKGROUND: The rapid neurodevelopment that occurs during the first years of life hinges on adequate nutrition throughout fetal life and early childhood. Therefore, adhering to a dietary pattern based on healthy foods during pregnancy and the first years of life may be beneficial for future development. The aim of this paper was to investigate the relationship between adherence to a healthy and potentially sustainable Nordic diet during pregnancy and in early childhood and child development. METHODS: This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa) and uses data from the Medical Birth Registry of Norway (MBRN). In 83,800 mother-child pairs, maternal pregnancy diet and child diet at 6 months, 18 months and 3 years were scored according to adherence to the New Nordic Diet (NND). NND scores were calculated both as a total score and categorized into low, medium, or high adherence. Child communication and motor development skills were reported by parents at 6 months, 18 months, 3 and 5 years, using short forms of the Ages and Stages Questionnaire and the Child Development Inventory. Associations of NND adherence with child development were estimated with linear and logistic regression in crude and adjusted models. RESULTS: When examining the NND and child developmental scores as percentages of the total scores, we found positive associations between the NND scores (both maternal pregnancy diet and child diet) and higher scoring on child development (adjusted [Formula: see text] s [95% confidence intervals] ranging from 0.007 [0.004, 0.009] to 0.045 [0.040, 0.050]). We further found that low and medium adherence to NND were associated with higher odds of later emerging developmental skills compared to high NND adherence at nearly all measured timepoints (odds ratios [95% CI] ranging from significant values 1.15 [1.03-1.29] to 1.79 [1.55, 2.06] in adjusted analyses). CONCLUSIONS: Our findings support that adherence to a healthy and potentially sustainable diet early in life is important for child development every step of the way from pregnancy until age 5 years.

Pathways From Preschool Language Difficulties to School-Age Internalizing Problems.

PURPOSE: Early language difficulties are associated with later internalizing problems across different ages and for different aspects of language. The mechanisms behind this association are, however, less understood. In the current study, we investigated longitudinal associations between language difficulties at 5 years and internalizing problems at 6 years. We also examined emotion regulation, empathy, assertiveness, and social engagement at 6 years as possible pathways for this association. METHOD: A subsample from the Norwegian Mother, Father and Child Cohort Study (MoBa) was used (N = 928). Structural equation models were developed to test the longitudinal associations and indirect pathways between language and internalizing problems. RESULTS: The results showed high stability for internalizing problems from 5 to 6 years (ß = .59, p < .001). Furthermore, semantic language difficulties predicted change in internalizing problems (ß = .12, p < .001). Finally, the path between semantic language and internalizing problems was partially mediated by social engagement and emotion regulation, with the indirect pathways accounting for 55% of the initial association. For girls, there was a significantly stronger correlation (p < .05) between semantic language difficulties and internalizing problems at baseline (r = .30, p < .001) than for boys (r = .16, p < .001). Otherwise, there were no sex differences. CONCLUSIONS: Indirect pathways from language difficulties to internalizing problems were identified through social engagement and emotion regulation. The results may guide targets for intervention in groups of children with language difficulties at risk for developing internalizing problems.

What are we optimizing for in autism screening? Examination of algorithmic changes in the M-CHAT.

The present study objectives were to examine the performance of the new M-CHAT-R algorithm to the original M-CHAT algorithm. The main purpose was to examine if the algorithmic changes increase identification of children later diagnosed with ASD, and to examine if there is a trade-off when changing algorithms. We included 54,463 screened cases from the Norwegian Mother and Child Cohort Study. Children were screened using the 23 items of the M-CHAT at 18 months. Further, the performance of the M-CHAT-R algorithm was compared to the M-CHAT algorithm on the 23-items. In total, 337 individuals were later diagnosed with ASD. Using M-CHAT-R algorithm decreased the number of correctly identified ASD children by 12 compared to M-CHAT, with no children with ASD screening negative on the M-CHAT criteria subsequently screening positive utilizing the M-CHAT-R algorithm. A nonparametric McNemar's test determined a statistically significant difference in identifying ASD utilizing the M-CHAT-R algorithm. The present study examined the application of 20-item MCHAT-R scoring criterion to the 23-item MCHAT. We found that this resulted in decreased sensitivity and increased specificity for identifying children with ASD, which is a trade-off that needs further investigation in terms of cost-effectiveness. However, further research is needed to optimize screening for ASD in the early developmental period to increase identification of false negatives.

Age of walking and intellectual ability in autism spectrum disorder and other neurodevelopmental disorders: a population-based study.

BACKGROUND: Delayed walking is common in intellectual disability (ID) but may be less common when ID occurs with autism spectrum disorder (ASD). Previous studies examining this were limited by reliance on clinical samples and exclusion of children with severe motor deficits. OBJECTIVE: To examine in a population-based sample if age of walking is differentially related to intellectual ability in children with ASD versus other neurodevelopmental disorders (NDD). METHODS: Participants were from the nested Autism Birth Cohort Study of the Norwegian Mother, Father and Child Cohort Study (MoBa). Cox proportional hazards regression assessed if diagnosis (ASD n = 212 vs. NDD n = 354), continuous nonverbal IQ, and their interaction, were associated with continuous age of walking. RESULTS: The relationship between nonverbal IQ and age of walking was stronger for NDD than for ASD (Group × nonverbal IQ interaction, χ2  = 13.93, p = .0002). This interaction was characterized by a 21% decrease in the likelihood of walking onset at any given time during the observation period per 10-point decrease in nonverbal IQ (hazard ratio = 0.79, 95% CI: 0.78-0.85) in the NDD group compared to 8% (hazard ratio = 0.92, 95% CI: 0.86-0.98) in the ASD group. CONCLUSIONS: The finding that age of walking is less strongly related to low intellectual ability in children with ASD than in children without other NDDs supports the hypothesis that ID in ASD may result from heterogeneous developmental pathways. Late walking may be a useful stratification variable in etiological research focused on ASD and other NDDs.

Functional Outcomes of Children Identified Early in the Developmental Period as at Risk for ASD Utilizing the The Norwegian Mother, Father and Child Cohort Study (MoBa).

Early identification of autism spectrum disorder (ASD) is regarded as crucial for swift access to early intervention and, subsequently, better outcomes later in life. However, current instruments miss large proportions of children who later go on to be diagnosed with ASD, raising a question of what these instruments measure. The present study utilized data from the Norwegian Mother, Father, and Child Cohort Study and the Autism Birth Cohort study to explore the subsequent developmental and diagnostic characteristics of children raising developmental concern on the six-critical discriminative item criterion of the M-CHAT (DFA6) at 18 months of age (N = 834). The DFA6 identified 28.8% of children diagnosed with ASD (N = 163), but 4.4% with language disorder (N = 188) and 81.3% with intellectual disability (N = 32) without ASD. Scoring in the «at-risk¼ range was associated with lower IQ, impaired functional language, and greater severity of autism symptoms whether children had ASD or not.

Preschool Speech Intelligibility and 8-Year Literacy: A Moderated Mediation Analysis.

Purpose The aims of this study were (a) to examine the relationship between speech intelligibility at the age of 5 years and literacy skills at the age of 8 years, (b) to explore the possible mediating or moderating role of broader language skills at 5 years in the relationship of interest, and (c) to assess whether the potential risk factors (child gender; maternal education levels; and family history of speech, language, reading, and writing difficulties) influence the relationship between speech intelligibility and literacy in terms of moderated mediation effects. Method We used mother-reported questionnaire data on 16,184 children participating in the population-based, prospective Norwegian Mother, Father and Child Cohort Study as well as conducted linear regression analyses using the PROCESS macro in SPSS. In addition, logistic regression was conducted to make predictions about risk. Results The association between speech intelligibility at 5 years and literacy skills at 8 years was statistically significant (ß = .168, p < .001). Children with speech problems at 5 years had a risk ratio of 2.38 (95% CI [2.10, 2.70]) and an odds ratio of 2.74 (95% CI [2.35, 3.19]), as compared to children without such problems. Broader language skills at 5 years partially mediated the relationship between speech intelligibility at 5 years and literacy at 8 years, and the effect of language skills appeared to be moderated by child gender, a family history of language difficulties, a family history of reading difficulties, and maternal education. Conclusions Severity of speech problems indexed by parent-reported speech intelligibility in preschool predicted school-age literacy problems. Broader language skills are a crucial mediating mechanism through which these problems are linked, and the mediated relationship is amplified by female gender, low maternal education, family history of language difficulties, and family history of reading difficulties. The findings call for increased use of a multiple-risk model when planning early interventions in children with unclear speech.

Predicting Literacy Skills at 8 Years From Preschool Language Trajectories: A Population-Based Cohort Study.

Purpose This article explored the predictive values of three main language delay (LD) trajectories (i.e., persistent, late onset, and transient) across 3-5 years on poor literacy at 8 years. Additionally, the effect of gender was assessed, using both gender-neutral and gender-specific thresholds. Method The data comprised mother-reported questionnaire data for 8,371 children in the Norwegian Mother, Father, and Child Cohort Study. Analyses were conducted using binary logistic regression in SPSS to make predictions about risk. Results LD reported at preschool age was associated with excess risk of poor literacy at 8 years with odds ratios ranging from 3.19 to 9.75 dependent on trajectory, persistent LD being the strongest predictor. The odds ratio of transient LD was similar to that of late-onset LD. Gender was not found to play an important role in the association between oral language and literacy, as the gender difference disappeared when gender-specific deficit criterion was used. Conclusion Our study supports the longitudinal association between preschool oral language and school-aged literacy skills and highlights the importance of different LD trajectories across preschool ages in predicting later literacy. Furthermore, practitioners are recommended to consider gender-specific cutoffs in relation to language and literacy measures.

Piloting the Use of a Short Observation List for ASD-Symptoms in Day-Care: Challenges and Further Possibilities.

Early symptoms of autism spectrum disorder (ASD) develop through the second year of life, making a stable ASD diagnosis possible around 24 months of age. However, in general, children with ASD are diagnosed later. In this study we explored the use of a short observation list to detect symptoms associated with ASD in children 12-24 months of age attending typical day-care centers. The results indicate that a short observation list used by day-care teachers does not reveal sufficient properties to be independently used in young children in day-care centers. Further studies should explore multiple and repeated measures for early detection of symptoms associated with ASD in typical day-care centers.

Diagnosing autism spectrum disorder among children in Norway. / Diagnostisering av autismespekterforstyrrelser hos barn i Norge.

BACKGROUND: The percentage share of children who are diagnosed with autism spectrum disorder has increased considerably since the 1990s in Norway as well as in other countries. It has previously been demonstrated that there is considerable variation between counties with respect to diagnostic practice. MATERIAL AND METHOD: We calculated the percentage of children with autism spectrum disorder by using patient data obtained from the Norwegian Patient Registry and population data obtained from the National Registry. The calculations were made for the country as a whole as well as by county. The diagnostic assessments and documentation were mapped by linking the Norwegian Patient Registry with the Norwegian Mother, Father and Child Cohort study. We also reviewed patient records obtained from the specialist health service and considered whether diagnostic practice satisfied the research criteria for autism spectrum disorder. RESULTS: By the age of eight, 1.1 % of boys and 0.3 % of girls had been diagnosed with autism spectrum disorder. The overall percentages varied from 0.3 to 1.0 between counties. From 2008 to 2016, these percentages increased in all age groups. Our review of patient records included 503 children. In 95 % of cases the patient records provided a high standard of documentation that the diagnostic research criteria had been satisfied. The assessments were largely conducted in accordance with the guidelines drawn up by the various health trusts. INTERPRETATION: Autism diagnoses are generally well documented within the Norwegian specialist health service and meet the diagnostic criteria. In the counties that demonstrate a low prevalence of autism, it appears the health service fails to recognise autism in many children, particularly girls, or the diagnosis is determined late.

Sensitivity and specificity of early screening for autism.

BACKGROUND: Early identification and diagnosis is beneficial for children with autism spectrum disorder (ASD). Universal early screening is recommended by many experts, but disputed because evidence is limited, and sensitivity and specificity in general populations are largely unknown. AIMS: To estimate the sensitivity and specificity of early population-based screening for ASDs. METHOD: The study was based on the Norwegian Mother and Child Cohort Study. The 36-month cohort questionnaire included the Social Communication Questionnaire (SCQ), a 40-item screening instrument for ASD. RESULTS: A total of 58 520 mothers (58%) responded to the questionnaire. By the end of follow-up on 31 December 2015, 385 (0.7%) individuals with ASD had been identified among the responders' children. The distributions of SCQ scores in those with ASD and other children had large degrees of overlap. With the cut-off of 15 recommended in the SCQ manual, screening sensitivity was 20% (95% CI 16-24) for ASD overall. For children with ASD who had not developed phrase speech at 36 months, sensitivity was 46% (95% CI 35-57%), whereas it was 13% (95% CI 9-17) for children with ASD with phrase speech. Screening specificity was 99% (95% CI 99-99). With the currently recommended cut-off of 11, sensitivity increased to 42% for ASD overall (95% CI 37-47), 69% (95% CI 58-79) for ASD without phrase speech and 34% (95% CI 29-40) for ASD with phrase speech. Specificity was then reduced to 89% (95% CI 89-90). CONCLUSIONS: Early ASD screening with a parent checklist had low sensitivity. It identified mainly individuals with ASD with significant developmental delay and captured very few children with ASD with cognitive skills in the normal range. Increasing sensitivity was not possible without severely compromising specificity. DECLARATION OF INTEREST: C.L. receives royalty for the Social Communication Questionnaire, which she has co-authored.

Clinical Features of Children With Autism Who Passed 18-Month Screening.

OBJECTIVES: We compared sex-stratified developmental and temperamental profiles at 18 months in children screening negative for autism spectrum disorder (ASD) on the Modified Checklist for Autism in Toddlers (M-CHAT) but later receiving diagnoses of ASD (false-negative group) versus those without later ASD diagnoses (true-negative group). METHODS: We included 68 197 screen-negative cases from the Norwegian Mother and Child Cohort Study (49.1% girls). Children were screened by using the 6 critical items of the M-CHAT at 18 months. Groups were compared on domains of the Ages and Stages Questionnaire and the Emotionality Activity Sociability Temperament Survey. RESULTS: Despite passing M-CHAT screening at 18 months, children in the false-negative group exhibited delays in social, communication, and motor skills compared with the true-negative group. Differences were more pronounced in girls. However, with regard to shyness, boys in the false-negative group were rated as more shy than their true-negative counterparts, but girls in the false-negative group were rated as less shy than their counterparts in the true-negative group. CONCLUSIONS: This is the first study to reveal that children who pass M-CHAT screening at 18 months and are later diagnosed with ASD exhibit delays in core social and communication areas as well as fine motor skills at 18 months. Differences appeared to be more pronounced in girls. With these findings, we underscore the need to enhance the understanding of early markers of ASD in boys and girls, as well as factors affecting parental report on early delays and abnormalities, to improve the sensitivity of screening instruments.

Early prenatal exposure to pandemic influenza A (H1N1) infection and child psychomotor development at 6 months - A population-based cohort study.

BACKGROUND: Studies investigating gestational influenza and child neurodevelopment are still scarce, particularly concerning timing of infection in pregnancy. This is the first study to investigate associations between gestational influenza and infant psychomotor development and temperament at 6 months. METHODS: Data from The Norwegian Influenza Pregnancy Cohort, established during the 2009 swine flu pandemic, were utilized. Information on influenza infection, vaccination, maternal health and child health and development is available from questionnaires, national registry data and maternal blood samples drawn at delivery. Maternal influenza A H1N1 pdm09 infection was serologically confirmed. 609 children with complete data were identified. Children of exposed and non-exposed mothers were compared using generalized linear models. RESULTS: Children exposed to influenza during gestational weeks (gw) 0-8 had adjusted general development scores indicating slightly delayed development compared to non-exposed children (0.28 standard deviations (SD) 95% confidence interval (CI): -0. 01; 0.58; p = 0.06). The temperamental scores of children exposed during gw 0-8 were slightly higher (0.31 SD; 95% CI: -0. 03; 0.64; p = 0.07) than non-exposed children indicating a more difficult temperament. In comparison, the developmental scores for children exposed in gw 9-40 were -0.31 SD (95% CI: -0. 65; 0.04; p = 0.09) better than non-exposed children, while the temperamental scores were 0.17 (95% CI: -0. 23; 0.56; p = 0.36) for the same period. CONCLUSION: Modest associations were found between maternal influenza A (H1N1) pdm infection during gestational weeks 0-8 and psychomotor development at 6 months.

Maternal cell phone use in early pregnancy and child's language, communication and motor skills at 3 and 5 years: the Norwegian mother and child cohort study (MoBa).

BACKGROUND: Cell phone use during pregnancy is a public health concern. We investigated the association between maternal cell phone use in pregnancy and child's language, communication and motor skills at 3 and 5 years. METHODS: This prospective study includes 45,389 mother-child pairs, participants of the MoBa, recruited at mid-pregnancy from 1999 to 2008. Maternal frequency of cell phone use in early pregnancy and child language, communication and motor skills at 3 and 5 years, were assessed by questionnaires. Logistic regression was used to estimate the associations. RESULTS: No cell phone use in early pregnancy was reported by 9.8% of women, while 39%, 46.9% and 4.3% of the women were categorized as low, medium and high cell phone users. Children of cell phone user mothers had 17% (OR = 0.83, 95% CI: 0.77, 0.89) lower adjusted risk of having low sentence complexity at 3 years, compared to children of non-users. The risk was 13%, 22% and 29% lower by low, medium and high maternal cell phone use. Additionally, children of cell phone users had lower risk of low motor skills score at 3 years, compared to children of non-users, but this association was not found at 5 years. We found no association between maternal cell phone use and low communication skills. CONCLUSIONS: We reported a decreased risk of low language and motor skills at three years in relation to prenatal cell phone use, which might be explained by enhanced maternal-child interaction among cell phone users. No evidence of adverse neurodevelopmental effects of prenatal cell phone use was reported.

The influence of parental concern on the utility of autism diagnostic instruments.

The parental report-based Autism Diagnostic Interview-Revised (ADI-R) and the clinician observation-based Autism Diagnostic Observation Schedule (ADOS) have been validated primarily in U.S. clinics specialized in autism spectrum disorder (ASD), in which most children are referred by their parents because of ASD concern. This study assessed diagnostic agreement of the ADOS-2 and ADI-R toddler algorithms in a more broadly based sample of 679 toddlers (age 35-47 months) from the Norwegian Mother and Child Cohort. We also examined whether parental concern about ASD influenced instrument performance, comparing toddlers identified based on parental ASD concern (n = 48) and parent-reported signs of developmental problems (screening) without a specific concern about ASD (n = 400). The ADOS cutoffs showed consistently well-balanced sensitivity and specificity. The ADI-R cutoffs demonstrated good specificity, but reduced sensitivity, missing 43% of toddlers whose parents were not specifically concerned about ASD. The ADI-R and ADOS dimensional scores agreed well with clinical diagnoses (area under the curve ≥ 0.85), contributing additively to their prediction. On the ADI-R, different cutoffs were needed according to presence or absence of parental ASD concern, in order to achieve comparable balance of sensitivity and specificity. These results highlight the importance of taking parental concern about ASD into account when interpreting scores from parental report-based instruments such as the ADI-R. While the ADOS cutoffs performed consistently well, the additive contributions of ADI-R and ADOS scores to the prediction of ASD diagnosis underscore the value of combining instruments based on parent accounts and clinician observation in evaluation of ASD. Autism Res 2017, 10: 1672-1686. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Correction for Mahic et al., "Maternal Immunoreactivity to Herpes Simplex Virus 2 and Risk of Autism Spectrum Disorder in Male Offspring".

[This corrects the article DOI: 10.1128/mSphere.00016-17.].

Maternal Immunoreactivity to Herpes Simplex Virus 2 and Risk of Autism Spectrum Disorder in Male Offspring.

Maternal infections during pregnancy are associated with risk of neurodevelopmental disorders, including autism spectrum disorders (ASDs). Proposed pathogenetic mechanisms include fetal infection, placental inflammation, and maternal cytokines or antibodies that cross the placenta. The Autism Birth Cohort comprises mothers, fathers, and offspring recruited in Norway in 1999 to 2008. Through questionnaire screening, referrals, and linkages to a national patient registry, 442 mothers of children with ASD were identified, and 464 frequency-matched controls were selected. Immunoglobulin G (IgG) antibodies to Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), and HSV-2 in plasma collected at midpregnancy and after delivery were measured by multiplexed immunoassays. High levels of HSV-2 IgG antibodies in maternal midpregnancy plasma were associated with increased risk of ASD in male offspring (an increase in HSV-2 IgG levels from 240 to 640 arbitrary units/ml was associated with an odds ratio of 2.07; 95% confidence interval, 1.06 to 4.06; P = 0.03) when adjusted for parity and child's birth year. No association was found between ASD and the presence of IgG antibodies to Toxoplasma gondii, rubella virus, CMV, or HSV-1. Additional studies are needed to test for replicability of risk and specificity of the sex effect and to examine risk associated with other infections. IMPORTANCE The cause (or causes) of most cases of autism spectrum disorder is unknown. Evidence from epidemiological studies and work in animal models of neurodevelopmental disorders suggest that both genetic and environmental factors may be implicated. The latter include gestational infection and immune activation. In our cohort, high levels of antibodies to herpes simplex virus 2 at midpregnancy were associated with an elevated risk of autism spectrum disorder in male offspring. These findings provide support for the hypothesis that gestational infection may contribute to the pathogenesis of autism spectrum disorder and have the potential to drive new efforts to monitor women more closely for cryptic gestational infection and to implement suppressive therapy during pregnancy.

Attitudes of the autism community to early autism research.

Investigation into the earliest signs of autism in infants has become a significant sub-field of autism research. This work invokes specific ethical concerns such as use of 'at-risk' language, communicating study findings to parents and the future perspective of enrolled infants when they reach adulthood. This study aimed to ground this research field in an understanding of the perspectives of members of the autism community. Following focus groups to identify topics, an online survey was distributed to autistic adults, parents of children with autism and practitioners in health and education settings across 11 European countries. Survey respondents (n = 2317) were positively disposed towards early autism research, and there was significant overlap in their priorities for the field and preferred language to describe infant research participants. However, there were also differences including overall less favourable endorsement of early autism research by autistic adults relative to other groups and a dislike of the phrase 'at-risk' to describe infant participants, in all groups except healthcare practitioners. The findings overall indicate that the autism community in Europe is supportive of early autism research. Researchers should endeavour to maintain this by continuing to take community perspectives into account.