Association of Growth During Infancy With Neurodevelopment and Obesity in Children Born Very Preterm: The Environmental influences on Child Health Outcomes Cohort.

OBJECTIVE: To evaluate associations between change in weight z-score after neonatal intensive care unit (NICU) discharge and neurodevelopmental outcomes and obesity at 12-48 months of age among individuals born very preterm. STUDY DESIGN: This secondary analysis used data from infants born very preterm participating in the Environmental influences on Child Health Outcomes cohort (n=1400). Growth during infancy was calculated as change in weight z-score between NICU discharge and follow-up at a mean of 27 months of age. Very low weight gain was defined as a change in weight z-score <-1.67; very high weight gain was a change in weight z-score >1.67. Neurodevelopmental outcomes included the Bayley Scales of Infant and Toddler Development, Child Behavior Checklist 1.5-5 years, and Modified Checklist for Autism in Toddlers. Multivariable linear regression was used to estimate associations between increase in weight z-score and neurodevelopmental outcomes. RESULTS: Very low weight gain between NICU discharge and follow-up (experienced by 6.4% of participants) was associated with lower scores on cognitive (adjusted mean difference: -4.26; 95% confidence interval: -8.55, -0.04) and language (adjusted mean difference: -4.80; 95% confidence interval: -9.70, -0.11) assessments. Very high weight gain (experienced by 13.6% of participants) was associated with an increased obesity risk (adjusted relative risk: 6.20; 95% confidence interval: 3.99, 9.66) but not with neurodevelopmental outcomes. CONCLUSIONS: Very high weight gain in the first 12-48 months after NICU discharge was associated with a higher risk of obesity at follow-up; very low weight gain was associated with lower scores on cognitive and language assessments.

Postural control before and after transitional locomotor tasks in children on the autism spectrum: A case-control study.

BACKGROUND: Instrumented measurements of postural control provide a more accurate insight into the motor development of children with autism. This study aimed to identify postural control deficits in autistic children during quiet standing before and after transient locomotor task. It was hypothesized that the parameters that characterize the trajectory of center of foot pressure (COP) displacement would be higher in autistic children compared to typically developing children. METHODS: Sixteen autistic children aged 6-10 but without a comorbidity diagnosis, were enrolled in the study group. The control group comprised 16 typically developing peers. The assessment of the transitional task comprised four different conditions: unperturbed and perturbed transition, stepping up, and stepping down tasks. Analysis of the COP signal was carried out for three distinct phases, i.e., phase 1 - quiet standing before step initiation, phase 2 - transit, and phase 3 - quiet standing until measurement completion. FINDINGS: The two-way ANOVA with a 2 × 4 factorial design (group × testing condition) revealed a group effect on all posturographic variables in the antero-posterior and medio-lateral directions of phase 1 and in the antero-posterior direction of phase 3. The Bonferroni post-hoc test showed the means of all those variables were significantly higher for the autistic than for typically developing children. Group allocation also had an effect on the time of transit and step length, which turned out to be significantly longer in autistic children compared to healthy peers. INTERPRETATION: Autistic children show increased postural sway before and after transitional locomotor tasks compared to typically developing children. The trial was prospectively registered in the Australian and New Zealand Clinical Trials Registry (no. ACTRN12621001113842; date registered: 23.08.2021).

The challenges for early intervention and its effects on the prognosis of autism spectrum disorder: a systematic review.

Autism spectrum disorder (ASD) is expressed with neurobehavioral symptoms of different degrees of intensity. It is estimated that, for every three cases detected, there are two cases that reach adulthood without treatment. Objective: To establish what challenges are still present in the implementation of early intervention (EI) and its effects on the prognosis of ASD. Methods: A systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (Prisma) methodology was carried out in the PubMed and ScienceDirect databases in January 2023. The search keywords were "autism spectrum disorder", "early intervention" and "prognosis". Results: Sixteen studies were included, two randomized and 14 non-randomized. Knowledge about the signs of ASD, diagnostic and therapeutic methods, age at the start of treatment, and socioeconomic factors were the main challenges encountered in the implementation of the EI. Conclusion: EI is capable of modifying the prognosis of ASD and challenges in its implementation persist, especially in developing regions with low socioeconomic status.

O transtorno do espectro autista (TEA) expressa-se com sintomas neurocomportamentais de diferentes graus de intensidade. Estima-se que, para cada três casos detectados, existam dois casos que atingem a idade adulta sem tratamento. Objetivo: Estabelecer quais são os desafios ainda presentes na implementação efetiva da intervenção precoce (IP) e quais são os seus efeitos no prognóstico do TEA. Métodos: Revisão sistemática com a metodologia Preferred Reporting Items for Systematic Reviews and Meta-Analyses (Prisma) foi realizada nos bancos de dados PubMed e ScienceDirect em janeiro de 2023. As palavras-chave da pesquisa foram "autism spectrum disorder", "early intervention" e "prognosis". Resultados: Dezesseis estudos foram incluídos, sendo dois randomizados e 14 não randomizados. O conhecimento sobre os sinais do TEA, os métodos diagnósticos e terapêuticos, a idade de início de tratamento e os fatores socioeconômicos foram os principais desafios encontrados na implementação da IP. Conclusão: A IP é capaz de modificar o prognóstico do TEA e os desafios em sua implementação ainda afetam, principalmente, regiões em desenvolvimento e de baixo status socioeconômico.

Policies for Individuals With Autism: Gaps, Research, and Recommendations.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social, behavioral, and learning challenges. Individuals with autism and their families often struggle to get an appropriate diagnosis and continuation of specialty services, including general healthcare, mental health and transition services, special education, employment, and social and emotional support. This paper presents information about the current policies and support mechanisms that exist to help these individuals and their families. This paper identifies the gaps and recommends areas of improvement based on evidence-based research and current data. ASD is a lifelong disability without a cure, but by constructing robust policies and providing enhanced support, the quality of lives of those with ASD and their families can be improved.

"Giving Me the Self-Confidence to Tackle It": Mothers' Experiences Participating In The Engaged Eaters Program, A Caregiver-Mediated Feeding Intervention.

The purpose of this study was to understand caregivers' experience of participating in a caregiver-mediated in-home feeding intervention, the Engaged Eaters Program, for their young autistic child. This qualitative study utilized a thematic approach to analyze post-intervention semi-structured interviews with thirteen mothers of autistic children between the ages of 2 to 7 years after they participated in the intervention. Interview questions focused on the child and family experience, what worked well, what could be improved, and how the intervention integrated into family routines. Four major themes were identified: In-Home Intervention, Parent Skill and Knowledge, Increased Social Participation, and Parent Responsibilities and Challenges. Sub-themes provided descriptions of learning practical tools to support their child, increasing self-efficacy, and impacts on family life. Mothers described an increase in tangible skills that were easily practiced in the home environment that improved their confidence and self-efficacy in feeding their children. They also described how participation did require more work and time commitment for them beyond their regular responsibilities. The caregiver experience is essential to understand for intervention effectiveness while simultaneously addressing child, caregiver, and family needs. By focusing on the mothers' experiences, individualized needs, and self-efficacy, we were able to better understand how integrating an intervention into the family context and daily routines may be beneficial for the whole family.

Role of autonomic, nociceptive, and limbic brainstem nuclei in core autism features.

Although multiple theories have speculated about the brainstem reticular formation's involvement in autistic behaviors, the in vivo imaging of brainstem nuclei needed to test these theories has proven technologically challenging. Using methods to improve brainstem imaging in children, this study set out to elucidate the role of the autonomic, nociceptive, and limbic brainstem nuclei in the autism features of 145 children (74 autistic children, 6.0-10.9 years). Participants completed an assessment of core autism features and diffusion- and T1-weighted imaging optimized to improve brainstem images. After data reduction via principal component analysis, correlational analyses examined associations among autism features and the microstructural properties of brainstem clusters. Independent replication was performed in 43 adolescents (24 autistic, 13.0-17.9 years). We found specific nuclei, most robustly the parvicellular reticular formation-alpha (PCRtA) and to a lesser degree the lateral parabrachial nucleus (LPB) and ventral tegmental parabrachial pigmented complex (VTA-PBP), to be associated with autism features. The PCRtA and some of the LPB associations were independently found in the replication sample, but the VTA-PBP associations were not. Consistent with theoretical perspectives, the findings suggest that individual differences in pontine reticular formation nuclei contribute to the prominence of autistic features. Specifically, the PCRtA, a nucleus involved in mastication, digestion, and cardio-respiration in animal models, was associated with social communication in children, while the LPB, a pain-network nucleus, was associated with repetitive behaviors. These findings highlight the contributions of key autonomic brainstem nuclei to the expression of core autism features.

Emerging drugs for the treatment of irritability associated with autism spectrum disorder.

INTRODUCTION: Autism spectrum disorder (ASD) is an early-onset disorder with a prevalence of 1% among children and reported disability-adjusted life years of 4.31 million. Irritability is a challenging behavior associated with ASD, for which medication development has lagged. More specifically, pharmacotherapy effectiveness may be limited against high adverse effects (considering side effect profiles and patient medication sensitivity); thus, the possible benefits of pharmacological interventions must be balanced against potential adverse events in each patient. AREAS COVERED: After reviewing the neuropathophysiology of ASD-associated irritability, the benefits and tolerability of emerging medications in its treatment based on randomized controlled trials were detailed in light of mechanisms and targets of action. EXPERT OPINION: Succeeding risperidone and aripiprazole, monotherapy with memantine may be beneficial. In addition, N-acetylcysteine, galantamine, sulforaphane, celecoxib, palmitoylethanolamide, pentoxifylline, simvastatin, minocycline, amantadine, pregnenolone, prednisolone, riluzole, propentofylline, pioglitazone, and topiramate, all adjunct to risperidone, and clonidine and methylphenidate outperformed placebo. These effects were through glutamatergic, γ-aminobutyric acidergic, inflammatory, oxidative, cholinergic, dopaminergic, and serotonergic systems. All medications were reported to be safe and tolerable. Considering sample size, follow-up, and effect size, further studies are necessary. Along with drug development, repositioning and combining existing drugs supported by the mechanism of action is recommended.

5Minutes4Myself: Development of a Wellness Program for Caregivers of Children with Autism.

Background. Many caregivers of autistic children experience increased stress, and diminished health often due to the caregiving demands. Purpose. The project aim was to design a feasible and sustainable wellness program tailored to these caregivers' lives. Methods. In this collaborative research-informed project, participants (N = 28) were mostly female, white, and well-educated. In focus groups, we delineated lifestyle issues, then designed, delivered and assessed an initial program with one cohort; and repeated this process with a second group. Findings. Focus group data were transcribed then coded qualitatively to inform following steps. Data analysis identified lifestyle issues key to program design, desired program elements, and after program delivery, affirmed elements and recommended changes. The team used meta-inferences to guide program revisions after each cohort. Implications. Caregivers viewed resulting 5Minutes4Myself program as filling a significant service gap; its hybrid design used in-person coaching and a habit-building app with mindfulness content to support lifestyle change.

Automated diagnosis of autism with artificial intelligence: State of the art.

Autism spectrum disorder (ASD) represents a panel of conditions that begin during the developmental period and result in impairments of personal, social, academic, or occupational functioning. Early diagnosis is directly related to a better prognosis. Unfortunately, the diagnosis of ASD requires a long and exhausting subjective process. We aimed to review the state of the art for automated autism diagnosis and recognition in this research. In February 2022, we searched multiple databases and sources of gray literature for eligible studies. We used an adapted version of the QUADAS-2 tool to assess the risk of bias in the studies. A brief report of the methods and results of each study is presented. Data were synthesized for each modality separately using the Split Component Synthesis (SCS) method. We assessed heterogeneity using the I 2 statistics and evaluated publication bias using trim and fill tests combined with ln DOR. Confidence in cumulative evidence was assessed using the GRADE approach for diagnostic studies. We included 344 studies from 186,020 participants (51,129 are estimated to be unique) for nine different modalities in this review, from which 232 reported sufficient data for meta-analysis. The area under the curve was in the range of 0.71-0.90 for all the modalities. The studies on EEG data provided the best accuracy, with the area under the curve ranging between 0.85 and 0.93. We found that the literature is rife with bias and methodological/reporting flaws. Recommendations are provided for future research to provide better studies and fill in the current knowledge gaps.

Quantitative assessment of tip-toe behavior in individuals with autism spectrum disorder and intellectual disability: A cross-sectional study.

The term "toe walking" describes walking on the toes with a lack of heel strike upon initiation of the stance phase of gait. In individuals with autism spectrum disorder (ASD), this phenomenon, or "tip-toe behavior" (TTB), can be present in a substantial proportion of subjects even during standing. In this study, we investigated TTB in 50 persons with ASD (age range 4-26 years). We evaluated TTB through an observational/report-based assessment protocol. Subsequently, we employed a new structured video-based coding protocol based on standardized video recordings, focusing on static and dynamic conditions. Finally, the findings of the two protocols were compared. Twenty-four subjects with TTB were identified and classified according to three functional groups: TTB1, present only during running (6 subjects); TTB2, present during walking and running (11 subjects); and TTB3, present during standing, walking, and running (7 subjects). Moreover, we found that TTB3 subjects exhibited a significantly higher quantity of TTB compared with subjects in the TTB1 and TTB2 groups during both standing and walking tests. Additionally, a high quantity of TTB in the static test was found to be related to a high quantity of TTB in the dynamic test. Variables such as age, autism severity, intellectual disability, and gender were not significantly associated with the mean percent of TTB both in static and dynamic tests in multivariate analysis. This structured video-based coding approach appears feasible and useful for assessing TTB in individuals with ASD and it has the potential to provide insights into TTB trajectories and aid in designing possible interventions.

The challenges for early intervention and its effects on the prognosis of autism spectrum disorder: a systematic review / Os desafios para a intervenção precoce e seus efeitos no prognóstico do transtorno do espectro autista: uma revisão sistemática

ABSTRACT. Autism spectrum disorder (ASD) is expressed with neurobehavioral symptoms of different degrees of intensity. It is estimated that, for every three cases detected, there are two cases that reach adulthood without treatment. Objective: To establish what challenges are still present in the implementation of early intervention (EI) and its effects on the prognosis of ASD. Methods: A systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (Prisma) methodology was carried out in the PubMed and ScienceDirect databases in January 2023. The search keywords were "autism spectrum disorder", "early intervention" and "prognosis". Results: Sixteen studies were included, two randomized and 14 non-randomized. Knowledge about the signs of ASD, diagnostic and therapeutic methods, age at the start of treatment, and socioeconomic factors were the main challenges encountered in the implementation of the EI. Conclusion: EI is capable of modifying the prognosis of ASD and challenges in its implementation persist, especially in developing regions with low socioeconomic status.

RESUMO. O transtorno do espectro autista (TEA) expressa-se com sintomas neurocomportamentais de diferentes graus de intensidade. Estima-se que, para cada três casos detectados, existam dois casos que atingem a idade adulta sem tratamento. Objetivo: Estabelecer quais são os desafios ainda presentes na implementação efetiva da intervenção precoce (IP) e quais são os seus efeitos no prognóstico do TEA. Métodos: Revisão sistemática com a metodologia Preferred Reporting Items for Systematic Reviews and Meta-Analyses (Prisma) foi realizada nos bancos de dados PubMed e ScienceDirect em janeiro de 2023. As palavras-chave da pesquisa foram "autism spectrum disorder", "early intervention" e "prognosis". Resultados: Dezesseis estudos foram incluídos, sendo dois randomizados e 14 não randomizados. O conhecimento sobre os sinais do TEA, os métodos diagnósticos e terapêuticos, a idade de início de tratamento e os fatores socioeconômicos foram os principais desafios encontrados na implementação da IP. Conclusão: A IP é capaz de modificar o prognóstico do TEA e os desafios em sua implementação ainda afetam, principalmente, regiões em desenvolvimento e de baixo status socioeconômico.

Transtorno do espectro do autismo e o uso materno e paterno de medicamentos, tabaco, álcool e drogas ilícitas / Maternal and paternal licit and illicit drug use, smoking and drinking and autism spectrum disorder

Resumo O presente estudo objetivou investigar a associação entre o TEA e o uso materno e paterno de medicamentos, tabaco, álcool e drogas ilícitas. Trata-se de um estudo caso-controle realizado com crianças e adolescentes diagnosticados com TEA e indivíduos neurotípicos. Os dados foram colhidos por meio de entrevista com as mães ou responsáveis. Foram analisadas as variáveis sexo e idade das crianças/adolescentes; idade dos pais; uso de medicamentos antes e durante a gestação; classes de medicamentos usados na gestação; tabagismo materno e paterno; etilismo materno e paterno; uso de drogas ilícitas pelos pais. Para a análise das informações, utilizou-se o modelo de regressão logística, além da razão de chances (OR) bruta e ajustada. Os resultados mostraram que, após os ajustes, foi encontrada associação entre o uso materno na gestação de antitérmicos/analgésicos (OR = 2,26; IC95% 1,29-3,95; p < 0,040) com o TEA. Já o uso de tabaco, álcool e drogas ilícitas materno e paterno, antes e durante a gestação, não apontou relação com o TEA. Os dados encontrados sugerem que existe influência de fatores ambientais no desenvolvimento do TEA.

Abstract The aim of this study was to investigate the association between maternal and paternal licit and illicit drug use, smoking and drinking and autism spectrum disorder (ASD). We conducted a case-control study with children and adolescents diagnosed with ASD and neurotypical individuals. The data were collected using a semi-structured questionnaire administered during interviews with the children's mothers or guardians. The following variables were analyzed: child sex and age; maternal and parental age; use of medicines before and during pregnancy; classes of medicines used during pregnancy; maternal and paternal smoking; maternal and paternal drinking; maternal and paternal illicit drug use. The data were analyzed using logistic regression and crude and adjusted odds ratios (OR). After adjustment, the results showed an association between maternal use of antipyretics/pain killers during pregnancy (OR = 2.26; 95%CI 1.29-3.95; p < 0.040) and ASD. No association was found between maternal and paternal smoking, drinking and illicit drug use before and during pregnancy and ASD. The findings suggest that the development of ASD is influenced by environmental factors.

Uso do método de Pontos para a Reestruturação de Objetivos Fonéticos e Oro-Musculares (PROMPT) no Transtorno do Espectro Autista: um estudo de caso / Use of the Prompts for Reestructuring Oral Muscular Phonetic Targets (PROMPT) in Autism Spectrum Disorder: a case study

RESUMO O Transtorno do Espectro Autista (TEA) é classificado pelo Manual de Diagnóstico e Estatístico de Transtornos Mentais (DSM-5) como um Transtorno do Neurodesenvolvimento, sendo caracterizado, principalmente, por alterações na comunicação social e pela presença de um repertório restrito de atividades e interesses. Na literatura, há muitos estudos sobre autismo, fala e linguagem, mas poucos correlacionando fala e autismo. Este estudo teve como finalidade realizar um estudo de caso que abordou autismo, fala e PROMPT (Pontos para a Reestruturação de Objetivos Fonéticos e Oro-Musculares) e mensurou a melhora da fala no participante com autismo, utilizando o método. Foram definidas palavras-alvo para toda a intervenção, conforme o Sistema de Observação e Análise (SOA) e Hierarquia Motora de Fala (HMF), que fazem parte da avaliação de PROMPT. Após a avaliação, o participante foi atendido por 16 sessões, uma vez semanalmente. Após análise dos dados, observou-se melhora em todos os aspectos que foram delineados de acordo com a avaliação no pré-tratamento, como controle fonatório, controle mandibular, controle lábio-facial e controle lingual, como também no movimento sequenciado, apesar deste não ser o objetivo traçado na avaliação. Também foi possível mensurar melhora no número de vocábulos adequados, número de fonemas adequados, porcentagens de consoantes corretas - revisado (PCC-R) e inteligibilidade.

ABSTRACT Autism Spectrum Disorder (ASD) is classified by Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a neurodevelopmental disorder, whose characteristics are mainly deficits in social communication and a restricted range of interests. There are several studies about autism, speech, and language in the literature, but few correlate speech and autism. This study aims to carry out a case study that will address autism, speech, and PROMPT (Restructuring Oral Muscular Phonetic Targets) and also to describe the speech improvement in the participant with autism using the method. The target words were defined for the entire intervention according to the System Analysis Observation (SAO) and Motor Speech Hierarchy (MSH), which are parts of the PROMPT evaluation. After the evaluation, the participant was attended for 16 sessions, once weekly, with the objective of improving their speech. After analyzing the data, it was possible to observe improvement in all aspects outlined according to the pre-treatment evaluation of the method such as phonatory control, mandibular control, lip-facial control and lingual control as well as in the sequenced movement although this was not the aim outlined in the evaluation. It was also possible to measure the improvement of an adequate number of words, an adequate number of phonemes, percentages of correct consonants - revised (PCC-R), and intelligibility.

Parental perspectives on oral health-related quality of life in children and adolescents with autism spectrum disorder: A systematic review.

BACKGROUND: Children with autism spectrum disorder (ASD) face unique challenges related to oral health, which can negatively impact their day-to-day lives, significantly compromising their overall quality of life. Primary caregivers of children with ASD have a critical role in delivering and seeking oral health care. Hence, it is vital to study their perspective towards their children's oral health and its impact on their quality of life. AIM: To explore the parental perception of oral health-related quality of life in children with autism. METHODS: A systematic electronic and manual search was conducted in Medline (via PubMed), Embase, Google Scholar, Scopus, and LILACS of articles published from January 2003 to May 2023 using appropriate MeSH terms, keywords, and other terms. A four-phase study selection process was followed according to PRISMA guidelines, and data extraction and synthesis were performed using an extraction form. The selected studies were critically appraised using the QATSDD and Crombie's assessment tool. The inter-reviewer agreement was assessed using the kappa with a linear weighting coefficient. RESULTS: Out of the 885 results, 15 studies were included in the review after the two selection phases, and the study characteristics were summarized in tabular form. Study quality varied considerably, and out of a total possible QATSDD score of 42, scores for the individual studies ranged from 14 to 40. The risk of bias for the seven criteria was found to be low. CONCLUSION: The parental perception of the OHRQoL in children with ASD is poor, and the most significant perceived impact is on the child's functional and social well-being aspects. Parental-Caregiver Perception Questionnaire was the most commonly used. The most frequent symptoms include bad breath, food lodgment, mouth breathing and night grinding. The familial impact and influence on the OHRQoL of siblings were also studied.

The Acquisition of Relative Clauses in Autism: The Role of Executive Functions and Language.

PURPOSE: Relative clauses present a well-known processing asymmetry between object-extracted and subject-extracted dependencies across both typical and atypical populations. The present study aimed at exploring the comprehension of object and subject relative clauses as conceptualized by the Relativized Minimality framework in autistic children and in a group of age- and IQ-matched typically-developing children. The study also explored the way performance in relative clauses would be affected by the children's language and executive function skills. METHOD: Relative clause comprehension was tested through a sentence-picture matching task and language was tested with a receptive vocabulary task. Executive functions were assessed through backward digit recall and a Flanker test. RESULTS: Object relative clauses were harder to parse for both groups than subject relatives, while number mismatch between the moved object Noun Phrase and the intervening subject Noun Phrase in object relatives boosted both groups' performances. Typically-developing children's performance in object relatives was predicted by both language and executive functions, while autistic children failed to use language and did not systematically draw on their executive functions in object relative clause comprehension. CONCLUSION: The findings suggest that relative clause processing in autism follows a normal developmental trajectory, and that difficulty with parsing object relative clauses stems from reduced language and executive functions rather than deficits in the children's morphosyntactic skills.

Relationship between caregiver adverse childhood events and age of autism spectrum diagnosis.

BACKGROUND: The age at which children are diagnosed with autism spectrum disorder (ASD) has not significantly decreased in the past 20 years. Adverse childhood events (ACEs) experienced by caregivers of autistic children may predict delays in caregivers attending ASD diagnostic evaluations, negatively impacting the age at which the child is diagnosed with ASD. The purpose of this study was to further explore the caregiver delay response by analyzing recurring events common in caregivers of children at risk for ASD. METHODS: We used a quantitative research design with convenience sampling to categorize caregivers of children referred for an ASD diagnostic evaluation into three groups based on their ACEs score and medical history. FINDINGS: A higher percentage of caregivers with four or more ACEs compared to the national average was noted. Parental separation or divorce, verbal aggression, emotional abuse, and parental alcohol or substance abuse occurred most frequently, and the latter predicted a prolonged time in attending the diagnostic evaluation. DISCUSSION: ACEs experienced by caregivers of children with ASD may delay the age of ASD diagnosis. Further investigation into the effect of ACEs on caregivers' mental health status and executive functioning is warranted to develop best practice for assisting caregivers in ASD recognition, diagnosis, and care management. APPLICATION TO PRACTICE: Clinicians should consider caregiver ACEs score when referring a child for a diagnostic developmental evaluation. Resources to address caregiver mental health needs should be provided at the onset of the referral process to increase the likelihood of caregiver adherence.

Antidepressants in pregnancy: applying causal epidemiological methods to understand service-use outcomes in women and long-term neurodevelopmental outcomes in exposed children.

Background: Antidepressants are commonly prescribed during pregnancy, despite a lack of evidence from randomised trials on the benefits or risks. Some studies have reported associations of antidepressants during pregnancy with adverse offspring neurodevelopment, but whether or not such associations are causal is unclear. Objectives: To study the associations of antidepressants for depression in pregnancy with outcomes using multiple methods to strengthen causal inference. Design: This was an observational cohort design using multiple methods to strengthen causal inference, including multivariable regression, propensity score matching, instrumental variable analysis, negative control exposures, comparison across indications and exposure discordant pregnancies analysis. Setting: This took place in UK general practice. Participants: Participants were pregnant women with depression. Interventions: The interventions were initiation of antidepressants in pregnancy compared with no initiation, and continuation of antidepressants in pregnancy compared with discontinuation. Main outcome measures: The maternal outcome measures were the use of primary care and secondary mental health services during pregnancy, and during four 6-month follow-up periods up to 24 months after pregnancy, and antidepressant prescription status 24 months following pregnancy. The child outcome measures were diagnosis of autism, diagnosis of attention deficit hyperactivity disorder and intellectual disability. Data sources: UK Clinical Practice Research Datalink. Results: Data on 80,103 pregnancies were used to study maternal primary care outcomes and were linked to 34,274 children with at least 4-year follow-up for neurodevelopmental outcomes. Women who initiated or continued antidepressants during pregnancy were more likely to have contact with primary and secondary health-care services during and after pregnancy and more likely to be prescribed an antidepressant 2 years following the end of pregnancy than women who did not initiate or continue antidepressants during pregnancy (odds ratioinitiation 2.16, 95% confidence interval 1.95 to 2.39; odds ratiocontinuation 2.40, 95% confidence interval 2.27 to 2.53). There was little evidence for any substantial association with autism (odds ratiomultivariableregression 1.10, 95% confidence interval 0.90 to 1.35; odds ratiopropensityscore 1.06, 95% confidence interval 0.84 to 1.32), attention deficit hyperactivity disorder (odds ratiomultivariableregression 1.02, 95% confidence interval 0.80 to 1.29; odds ratiopropensityscore 0.97, 95% confidence interval 0.75 to 1.25) or intellectual disability (odds ratiomultivariableregression 0.81, 95% confidence interval 0.55 to 1.19; odds ratiopropensityscore 0.89, 95% confidence interval 0.61 to 1.31) in children of women who continued antidepressants compared with those who discontinued antidepressants. There was inconsistent evidence of an association between initiation of antidepressants in pregnancy and diagnosis of autism in offspring (odds ratiomultivariableregression 1.23, 95% confidence interval 0.85 to 1.78; odds ratiopropensityscore 1.64, 95% confidence interval 1.01 to 2.66) but not attention deficit hyperactivity disorder or intellectual disability; however, but results were imprecise owing to smaller numbers. Limitations: Several causal-inference analyses lacked precision owing to limited numbers. In addition, adherence to the prescribed treatment was not measured. Conclusions: Women prescribed antidepressants during pregnancy had greater service use during and after pregnancy than those not prescribed antidepressants. The evidence against any substantial association with autism, attention deficit hyperactivity disorder or intellectual disability in the children of women who continued compared with those who discontinued antidepressants in pregnancy is reassuring. Potential association of initiation of antidepressants during pregnancy with offspring autism needs further investigation. Future work: Further research on larger samples could increase the robustness and precision of these findings. These methods applied could be a template for future pharmaco-epidemiological investigation of other pregnancy-related prescribing safety concerns. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/80/19) and will be published in full in Health Technology Assessment; Vol. 27, No. 15. See the NIHR Journals Library website for further project information.

About one in seven women experience depression during pregnancy. Left untreated, this may harm them and their unborn babies. However, the decision to take antidepressants during pregnancy is difficult because women often worry about the risks to their unborn baby. Research findings have been inconsistent, so women often do not have clear information to enable them to make informed decisions. We studied women's and children's outcomes after starting (compared with not starting) or continuing (compared with stopping) antidepressants in pregnancy. We used a large UK primary care database and several novel methods of analysis. We tracked 80,103 pregnancies of women with depression for up to 2 years after pregnancy. We also tracked 34,274 children from these pregnancies for at least 4 years to check for developmental outcomes. Women prescribed antidepressants were more likely than women not prescribed antidepressants to use general practice and mental health services during and after pregnancy, and to be prescribed antidepressants 2 years after pregnancy. This suggests that antidepressants were being prescribed to women with greater clinical need. Women who continued antidepressants in pregnancy had no higher likelihood than those who discontinued antidepressants of autism, attention deficit hyperactivity disorder or intellectual disability in their children. This should reassure women making the decision to continue taking their medications in pregnancy. Women who started antidepressants in pregnancy may possibly have had a slightly higher likelihood of autism in their children than those who did not start them. These findings were not seen in all analyses and were based on smaller numbers; therefore, they should be viewed with caution. Importantly, over 98 in every 100 children of women who initiated or continued antidepressants in pregnancy did not receive an autism diagnosis. The findings may help women and clinicians make informed decisions on treatment with antidepressants in pregnancy.

Audiogenic Seizures and Social Deficits: No Aggravation Found in Krushinsky-Molodkina Rats.

Epilepsy or epileptic syndromes affect more than 70 million people, often comorbid with autism spectrum disorders (ASD). Seizures are concerned as a factor for social regression in ASD. A stepwise experimental approach to this problem requires an animal model to provoke seizures and monitor subsequent behavior. We used rats of the Krushinsky-Molodkina (KM) strain as a validated inbred genetic model for human temporal lobe epilepsy, with recently described social deficiency and hypolocomotion. Generalized tonic-clonic seizures in KM rats are sound-triggered, thus being controlled events in drug-naïve animals. We studied whether seizure experience would aggravate contact deficits in these animals. Locomotor and contact parameters were registered in "the elevated plus maze", "socially enriched open field", and "social novelty/social preference tests" before and after sound-provoked seizures. The triple seizure provocations minimally affected the contact behavior. The lack of social drive in KM rats was not accompanied by a submissive phenotype, as tested in "the tube dominance test", but featured with a poor contact repertoire. Here, we confirmed our previous findings on social deficits in KM rats. The contact deficiency was dissociated from hypolocomotion and anxiety and did not correlate with seizure experience. It was established that experience of rare, generalized tonic-clonic convulsions did not lead to an impending regress in contact motivation, as seen in an animal model of genetic epilepsy and comorbid social deficiency. One of the oldest animal models for epilepsy has a translational potential to study mechanisms of social behavioral deficits in future neurophysiological and pharmacological research.

Comparative strengths and challenges on face-to-face and computer-based attention tasks in autistic and neurotypical toddlers.

The objectives were to compare patterns of visual attention in toddlers diagnosed with autism spectrum disorder (ASD) as compared to their sex- and age-matched neurotypical (NT) peers. Participants included 23 toddlers with ASD and 19 NT toddlers (mean age: 25.52 versus 25.21 months, respectively) assessed using computerized tasks to measure sustained attention, disengaging attention, and cognitive control, as well as an in-person task to assess joint attention. Toddlers in the ASD group showed increased looking durations on the sustained attention task, as well as reduced frequencies of responding to and initiating joint attention compared to NT peers, but showed no differences on tasks of disengaging attention and cognitive control. The results suggest that toddlers with ASD have attentional strengths that may provide a foundation for building attention, communicative, and ultimately, academic skills.

The association between polygenic risk scores for mental disorders and social cognition: A scoping review.

People with mental disorders, such as psychosis or autism spectrum disorder (ASD), often present impairments in social cognition (SC), which may cause significant difficulties in real-world functioning. SC deficits are seen also in unaffected relatives, indicating a genetic substratum. The present review evaluated the evidence on the association between SC and the polygenic risk score (PRS), a single metric of the molecular genetic risk to develop a specific disorder. In July 2022, we conducted systematic searches in Scopus and PubMed following the PRISMA-ScR guidelines. We selected original articles written in English reporting results on the association between PRSs for any mental disorder and domains of SC either in people with mental disorders or controls. The search yielded 244 papers, of which 13 were selected for inclusion. Studies tested mainly PRSs for schizophrenia, ASD, and attention-deficit hyperactivity disorder. Emotion recognition was the most investigated domain of SC. Overall, evidence revealed that currently available PRSs for mental disorders do not explain variation in SC performances. To enhance the understanding of mechanisms underlying SC in mental disorders, future research should focus on the development of transdiagnostic PRSs, study their interaction with environmental risk factors, and standardize outcome measurement.