Family History Of Autism Spectrum Disorder Research Articles

عوامل الخطر قبل الولادة وأثناء الولادة و بعد الولادة المرتبطة باضطراب طيف التوحد في فلسطين: دراسة الحالات و الشواهد

Background: Autism spectrum disorder (ASD) is a multifactorial neurodevelopment disorder. Several prenatal, perinatal, and postnatal factors are suggested as risk factors for ASD. This study aimed to correlate prenatal, perinatal, and postnatal factors in a limited number of cases in Palestine. Methods: A case-control study involved 120 children (60 typically diagnosed with ASD and 60 healthy matched with the ASD group). The parents of the children in both groups were asked to fill out the questionnaire. Results: The study showed a higher male-to-female ratio in the ASD group. A family history of ASD was reported in 38.3% of the ASD group and 11.7% in the healthy group. Three prenatal risk factors, including maternal passive smoking, preserving follow-up prenatal visits, and experiencing psychological stress by mothers, were significantly associated with ASD. Most of the postnatal factors were significantly associated with increased ASD risk. The studied perinatal factors were not significantly associated with ASD. The parental factors, such as paternal age greater than 30 years and lower levels of education, displayed significant risk factors associated with ASD. Conclusion: This study found significant associations between several prenatal, postnatal, and parental factors and ASD in a sample of Palestinian children. المقدمة: اضطراب طيف التوحد هو اضطراب نمائي عصبي متعدد العوامل. تم تحديد العديد من العوامل قبل الولادة و أثناء الولادة و بعد الولادة كعوامل قد تكون مرتبطة بالاصابة باضطراب طيف التوحد. هدفت هذه الدراسة لفحص ارتباط عدة عوامل قبل الولادة و أثناء الولادة و بعد الولادة في عدد محدود من حالات التوحد في فلسطين. المنهجية: تمت الدراسة من خلال جمع معلومات من عينة ضمت 120 طفل (60 تم تشخيصهم بطيف التوحد و 60 طفل سليم و متطابقين مع مجموعة التوحد). تمت الاجابة على الاستبيان من قبل أولياء الأمور في المجموعتين. النتائج: أظهرت الدراسة أن نسبة الذكور الى الاناث في مجموعة طيف التوحد كانت أعلى. تم تحديد نسبة وجود تاريخ عائلي في 38.3% من مجموعة طيف التوحد و 11.7% من مجموعة الاطفال السليمين. تم تحديد ثلاثة عوامل خطورة قبل الولادة مرتبطة بشكل وثيق مع اضطراب طيف التوحد و تشمل التدخين السلبي للأم، متابعة زيارات الرعاية قبل الولادة، و التعرص للاجهاد النفسي من قبل الأمهات. معظم عوامل الخطر بعد الولادة كانت مرتبطة بشكل وثيق بزيادة خطر الاصابة بطيف التوحد. عوامل الخطر أثناء الولادة التي تمت دراستها لم ترتبط بشكل وثيق باضطراب طيف التوحد. العوامل المتعلقة بالوالدين مثل عمر الأب أكثر من 30 عام و مستويات التعليم المتدنية أظهرت ارتباطا وثيقا بالإصابة بطيف التوحد. الاستنتاج: وجدت الدراسة ارتباطات وثيقة بين عدة عوامل قبل الولادة و أثناء الولادة و بعد الولادة مع طيف التوحد في عينة من الأطفال الفلسطينيين.

The Combination of Mind and Brain Alteration in A Resource-Limited Country: Autism Spectrum Disorders and Epilepsy in A Child Psychiatry Unit in Dakar

Purpose of the study: Autism spectrum disorders (ASD) and epilepsy can coexist in the same person, constituting poor bilateral prognosis factors. This study describes the sociodemographic elements of patients with ASD and studies the clinico-paraclinical aspects of their epilepsy and its evolution in 2003. Patients and Methods: Cross-sectional and descriptive study in Child psychiatry at CHNU Fann, with analysis of the files of all patients followed between January 2004 and September 2018 for ASD with/without epilepsy. We used a standardized survey with several items. Results: Forty -five patients with ASD collected, with an epileptic frequency of 37.8%. The main history was fetal suffering (24.4%) and parental inbreeding (22.2%). Most of the symptoms of ASD were seen before 3 years old (66.6%) and epilepsy started before 5 years (94%). Seizures were generalized (58.8%), mainly tonic-clonic (80%) or focal (35.3%), with a frequency of 2 seizures / day at 1 seizure / week. The EEG showed abnormalities in frontal areas in 60%, and Centro-parietal in 26.6%. Brain imaging and evoked auditory potential were normal respectively in 93.9%, and 87.2%. Management was multimodal for ASD (neuropsychological, psychomotor, speech therapy) and medicated for epilepsy, mainly by monotherapy (82.4%) with Valproate (58.8%), Phenobarbital (17.6). Forty percent of patients were out of school and 55.6% in primary school. Twenty-five patients were self-reliant to moderately independent, mainly the epileptics (60%). The 2023 evaluation of this cohort concerns 60% of patients with epilepsy in complete remission and behavioral and language stability under continuous management. Conclusion: We find a statistic difference by age between epilepsy and ASD with a genetic predisposition related to parental inbreeding and a family history of ASD and epilepsy and to a lesser extent the existence of acute fetal suffering. The contribution of EEG was significant with a predilection of frontal abnormalities whose epileptic treatment appears to improve the impact in children's behavioral disorders.

Restricted and repetitive behaviors and association with cognition and adaptive functioning in children with autism spectrum disorder in Singapore.

One of the core features of autism spectrum disorder (ASD) is restricted, repetitive patterns of behavior, interests and activities (RRBs). RRBs are known to adversely affect cognition and adaptive functioning. We explored the relationship of RRBs with cognition and adaptive functioning in children with ASD in an Asian setting. This cross-sectional study was conducted at a tertiary developmental pediatrics center in Singapore from September 2019 to October 2021. Parent-child dyads (parents and their children ≤7 years old diagnosed with ASD) were recruited. Parents completed the Repetitive Behavior Questionnaire-2 (RBQ-2), which reports total score and two subscales - Motor/Sensory Behaviors (RBQ-2 MS) and Rigidity/Routines/Preoccupation with Restricted Interests (RBQ-2 RRPRI). Standardized assessments included Mullen Scales of Early Learning (MSEL) and Vineland Adaptive Behavior Scales (VABS-II). Data analysis utilized descriptive statistics and Pearson's correlation. Parents of 113 children [75.2% male, mean (SD) age 5.0 (1.2) years] participated. Median (IQR) RBQ-2 score was 29.0 (11.0). Significant negative correlations (adjusted for age, gender and family history of ASD) were observed for total RBQ-2 scores with MSEL ELC scores (r = -0.248, n = 101, p = 0.014) and VABS-II ABC scores (r = -0.281, n = 88, p = 0.009). Specifically, these correlations of fair strength were seen only with the RBQ-2 MS subscale for both ELC (r = -0.321, n = 101, p = 0.001) and ABC (r = -0.3478, n = 88, p = 0.001). In children with ASD, severity of RRBs correlated with adverse cognition and adaptive functioning measures in our study, consistent with Western literature. While our study does not show causality, it adds to literature serving as a foundation for further research for both clinicians and researchers to target RRBs in improving outcomes with children in ASD.

23 Association between Autism Spectrum Disorder and Parental Immigration among a Cohort of Preschool Children in Manitoba

Abstract Background Recent data indicate that rates of autism spectrum disorder (ASD) are increasing and therefore, studies exploring risk factors for ASD that can further support early diagnosis and intervention are needed. A link between immigration and autism has been made by several international studies, but despite high rates of immigration, a Canadian study examining this association has not been conducted. Objectives To determine the proportion of children diagnosed with ASD at Manitoba’s primary autism referral site (the only publicly funded site for ASD evaluation of children <6 years of age) that were born to immigrant parents, and compare it with the known proportion of immigrants in Manitoba. Also, to compare demographic and clinical characteristics of children whose parents are immigrants with those whose parents were born in Canada. Design/Methods We conducted a retrospective chart review of >2000 electronic records that identified all children <6 years diagnosed with ASD at the referral site between May 2016 and September 2021. Data on parental immigration, demographics, diagnostic evaluation, and medical history was collected. Descriptive statistics were used to compare the relative proportion of children with ASD from immigrant parents with the proportion of immigrants in Manitoba based on 2016 census data. Results A total of 1865 children were diagnosed with ASD during the study period. The mean age at referral and diagnosis was 2.81 (SD 1.26) years and 3.88 (SD 2.90) years respectively; 78% were male and 13.5% were born preterm. The proportion of children with ASD from immigrant parents (36%) was greater than the expected proportion (18.3%) of immigrants based on Manitoba census data (p < 0.001). The most common countries of origin of immigration were the Philippines (30.7%), India (11.6%), Nigeria (8.6%), and Ethiopia (6.4%). Overall, children of immigrants were younger at referral (2.71 years, SD = 0.98 versus 2.91 years, SD = 1.43; p <0.001), less likely to have a family history of ASD (17.1% versus 35.6%; p = <0.001) and less likely to have comorbidities (46.8% versus 53.9%; p <0.001) including global developmental delay (18% versus 27.6%; p <0.001). Conclusion At Manitoba’s primary autism referral site, there was a greater proportion of children diagnosed with ASD born to immigrant parents than expected when compared to the Manitoba population. Overall, children of immigrants were younger, less likely to have comorbidities, developmental delay, and a family history of ASD. Future prospective studies are required to better understand the complex relationship between immigration and ASD diagnosis.

Early-life differences in the gut microbiota composition and functionality of infants at elevated likelihood of developing autism spectrum disorder

Evidence from cross-sectional human studies, and preliminary microbial-based intervention studies, have implicated the microbiota-gut-brain axis in the neurobiology of autism spectrum disorder (ASD). Using a prospective longitudinal study design, we investigated the developmental profile of the fecal microbiota and metabolome in infants with (n = 16) and without (n = 19) a family history of ASD across the first 36 months of life. In addition, the general developmental levels of infants were evaluated using the Mullen Scales of Early Learning (MSEL) test at 5 and 36 months of age, and with ADOS-2 at 36 months of age. At 5 months of age, infants at elevated-likelihood of ASD (EL) harbored less Bifidobacterium and more Clostridium and Klebsiella species compared to the low-likelihood infants (LL). Untargeted metabolic profiling highlighted that LL infants excreted a greater amount of fecal γ-aminobutyric acid (GABA) at 5 months, which progressively declined with age. Similar age-dependent patterns were not observed in the EL group, with GABA being consistently low across all timepoints. Integrated microbiome-metabolome analysis showed a positive correlation between GABA and Bifidobacterium species and negative associations with Clostridium species. In vitro experiments supported these observations demonstrating that bifidobacteria can produce GABA while clostridia can consume it. At the behavioral level, there were no significant differences between the EL and LL groups at 5 months. However, at 36 months of age, the EL group had significantly lower MSEL and ADOS-2 scores compared to the LL group. Taken together, the present results reveal early life alterations in gut microbiota composition and functionality in infants at elevated-likelihood of ASD. These changes occur before any behavioral impairments can be detected, supporting a possible role for the gut microbiota in emerging behavioral variability later in life.

Behavioural reactions to an emotion evoking task in infants at increased likelihood for autism spectrum disorder

Infants at increased likelihood for autism spectrum disorder (ASD) exhibit more negative affect and avoidance behaviour than typically developing infants, and children with ASD express fear differently than typically developing peers. We examined behavioural reactions to emotion-evoking stimuli in infants at increased familial likelihood for ASD. Participants included 55 increased likelihood (IL) infants (i.e., siblings of children diagnosed with ASD) and 27 typical likelihood (TL) infants (i.e., no family history of ASD). At 18 months, we showed infants two masks that commonly elicit fearful responses in older children and examined potential behavioural differences in approach, avoidance, ‘freezing’, crying, gaze aversion, and smiling. At 24 months, infants were assessed with the Toddler Module of the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2). Results of video-based coding showed that (1) IL infants exhibited more intense avoidance behaviour than TL infants in response to masks, and (2) intensity of avoidance and duration of freezing were positively correlated with ADOS-2 symptom severity scores. Findings suggest that differences in response to emotion-eliciting stimuli may predict later ASD symptoms. Such behavioural differences may inform early detection and intervention in ASD.

Epigenetic changes in sperm are associated with paternal and child quantitative autistic traits in an autism-enriched cohort.

There is a need to consider paternal contributions to autism spectrum disorder (ASD) more strongly. Autism etiology is complex, and heritability is not explained by genetics alone. Understanding paternal gametic epigenetic contributions to autism could help fill this knowledge gap. In the present study, we explored whether paternal autistic traits, and the sperm epigenome, were associated with autistic traits in children at 36 months enrolled in the Early Autism Risk Longitudinal Investigation (EARLI) cohort. EARLI is a pregnancy cohort that recruited and enrolled pregnant women in the first half of pregnancy who already had a child with ASD. After maternal enrollment, EARLI fathers were approached and asked to provide a semen specimen. Participants were included in the present study if they had genotyping, sperm methylation data, and Social Responsiveness Scale (SRS) score data available. Using the CHARM array, we performed genome-scale methylation analyses on DNA from semen samples contributed by EARLI fathers. The SRS-a 65-item questionnaire measuring social communication deficits on a quantitative scale-was used to evaluate autistic traits in EARLI fathers (n = 45) and children (n = 31). We identified 94 significant child SRS-associated differentially methylated regions (DMRs), and 14 significant paternal SRS-associated DMRs (fwer p < 0.05). Many child SRS-associated DMRs were annotated to genes implicated in ASD and neurodevelopment. Six DMRs overlapped across the two outcomes (fwer p < 0.1), and, 16 DMRs overlapped with previous child autistic trait findings at 12 months of age (fwer p < 0.05). Child SRS-associated DMRs contained CpG sites independently found to be differentially methylated in postmortem brains of individuals with and without autism. These findings suggest paternal germline methylation is associated with autistic traits in 3-year-old offspring. These prospective results for autism-associated traits, in a cohort with a family history of ASD, highlight the potential importance of sperm epigenetic mechanisms in autism.

Infant sleep predicts trajectories of social attention and later autism traits.

Children with neurodevelopmental disorders including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) often experience sleep disturbances, but little is known about when these sleep differences emerge and how they relate to later development. We used a prospective longitudinal design in infants with a family history of ASD and/or ADHD to examine infant sleep and its relation to trajectories of attention and later neurodevelopmental disorders. We formed factors of Day and Night Sleep from parent-reported measures (including day/night sleep duration, number of naps in the day, frequency of night awakenings and sleep onset problems). We examined sleep in 164 infants at 5-, 10- and 14-months with/without a first-degree relative with ASD and/or ADHD who underwent a consensus clinical assessment for ASD at age 3. By 14-months, infants with a first-degree relative with ASD (but not ADHD) showed lower Night Sleep scores than infants with no family history of ASD; lower Night Sleep scores in infancy were also associated with a later ASD diagnosis, decreased cognitive ability, increased ASD symptomatology at 3-years, and developing social attention (e.g., looking to faces). We found no such effects with Day Sleep. Sleep disturbances may be apparent at night from 14-months in infants with a family history of ASD and also those with later ASD, but were not associated with a family history of ADHD. Infant sleep disturbances were also linked to later dimensional variation in cognitive and social skills across the cohort. Night Sleep and Social Attention were interrelated over the first 2 years of life, suggesting that this may be one mechanism through which sleep quality influences neurodevelopment. Interventions targeted towards supporting families with their infant's sleep problems may be useful in this population.

Associations between attentional biases to fearful faces and social-emotional development in infants with and without an older sibling with autism

During the first year of life, infants become increasingly attuned to facial emotion, with heightened sensitivity to faces conveying threat observed by age seven months as illustrated through attentional biases (e.g., slower shifting away from fearful faces). Individual differences in these cognitive attentional biases have been discussed in relation to broader social-emotional functioning, and the current study examines these associations in infants with an older sibling with autism spectrum disorder (ASD), a group with an elevated likelihood of a subsequent ASD diagnosis (ELA; n = 33), and a group of infants with no family history of ASD who are at low likelihood of ASD (LLA; n = 24). All infants completed a task measuring disengagement of attention from faces at 12 months (fearful, happy, neutral), and caregivers completed the Infant-Toddler Social and Emotional Assessment at 12, 18, and/or 24 months. For the full sample, greater fear bias in attention disengagement at 12 months related to more internalizing behaviors at 18 months, and this was driven by the LLA infants. When examining groups separately, findings revealed that LLA with a greater fear bias had more difficult behaviors at 12, 18, and 24 months; in contrast, ELA showed the opposite pattern, and this was most pronounced for ELA who later received an ASD diagnosis. These preliminary group-level findings suggest that heightened sensitivity to fearful faces might serve an adaptive function in children who later receive an ASD diagnosis, but in infants with no family history of ASD, increased biases might reflect a marker of social-emotional difficulties.

Prenatal maternal stress and the severity of autism spectrum disorder: A cross-sectional study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder linked to several genetic and environmental factors including antenatal stress. Hence, we aimed to examine whether a mother's stress during pregnancy is associated with the severity of autism spectrum disorder in children. The study was conducted with 459 mothers of children with autism (aged 2-14 years) who were attending rehabilitation and educational centers in the two major cities of Makkah and Jeddah in Saudi Arabia. Environmental factors, consanguinity, and ASD family history were assessed using a validated questionnaire. The Prenatal Life Events Scale questionnaire was used to assess whether the mothers were exposed to stress during pregnancy. Two models of ordinal regression analysis were conducted including gender, child age maternal age, parental age, maternal education, parental education, income nicotine exposure, mother taking medication during pregnancy, family history of ASD, gestation, consanguinity, exposure of prenatal life events (in model 1), and severity of prenatal life events (in model 2). Family history of ASD showed a statistically significant association with the severity of ASD in both regression models (p = .015, odds ratio [OR]: 4.261 in Model 1, and p = .014, OR: 4.901 in model 2). In model 2, the moderate severity prenatal life events showed higher statistically significant adjusted odds ratio for ASD severity compared to no stress (p = .031; OR: 3.82). Within the limitations of this study, prenatal stressors showed some potential contribution to ASD severity. Family history of ASD was the only factor that showed a persistent association with ASD severity. A study that assesses the effect of COVID-19 stress on ASD prevalence and severity is recommended.

Behavioral and physiological differences during an emotion-evoking task in children at increased likelihood for autism spectrum disorder.

Literature examining emotional regulation in infants with autism spectrum disorder (ASD) has focused on parent report. We examined behavioral and physiological responses during an emotion-evoking task designed to elicit emotional states in infants. Infants at an increased likelihood for ASD (IL; have an older sibling with ASD; 96 not classified; 29 classified with ASD at age two) and low likelihood (LL; no family history of ASD; n = 61) completed the task at 6, 12, and 18 months. The main findings were (1) the IL-ASD group displayed higher levels of negative affect during toy removal and negative tasks compared to the IL non-ASD and LL groups, respectively, (2) the IL-ASD group spent more time looking at the baseline task compared to the other two groups, and (3) the IL-ASD group showed a greater increase in heart rate from baseline during the toy removal and negative tasks compared to the LL group. These results suggest that IL children who are classified as ASD at 24 months show differences in affect, gaze, and heart rate during an emotion-evoking task, with potential implications for understanding mechanisms related to emerging ASD.

Inter-trial theta phase consistency during face processing in infants is associated with later emerging autism.

A growing body of research suggests that consistency in cortical activity may be a promising neurophysiological marker of autism spectrum disorder (ASD). In the current study we examined inter-trial coherence, a measure of phase consistency across trials, in the theta range (t-ITC: 3-6Hz), as theta has been implicated in the processing of social and emotional stimuli in infants and adults. The sample included infants who had an older sibling with a confirmed ASD diagnosis and typically developing (TD) infants with no family history of ASD. The data were collected as part of the British Autism Study of Infant Siblings (BASIS) study. Infants between 6 and 10months of age (Mage = 7.34, SDage = 1.21) performed a visual face processing task that included faces and scrambled, "face noise", stimuli. Follow-up assessments in higher likelihood infants were completed at 24 and again at 36months to determine diagnostic outcomes. Analysis focused on posterior t-ITC during early (0-200ms) and late (200-500ms) visual processing stages commonly investigated in infant studies. t-ITC over posterior scalp regions during late stage face processing was significantly higher in TD and higher likelihood infants without ASD (HRA-), indicating reduced consistency in theta-band responses in higher likelihood infants who eventually receive a diagnosis of ASD (HRA+). These findings indicate that the temporal dynamics of theta during face processing relate to ASD outcomes. Reduced consistency of oscillatory dynamics at basic levels of infant sensory processing could have downstream effects on learning and social communication. LAY SUMMARY: We examined the consistency in brain responses to faces in infants at lower or higher familial likelihood for autism. Our results show that the consistency of EEG responses was lower during face processing in higher likelihood infants who eventually received a diagnosis of autism. These findings highlight that reduced consistency in brain activity during face processing in the first year of life is related to emerging autism.

Fragile X premutation carrier screening in Pakistani preconception women in primary care consultation

PurposeWomen of reproductive age who carry fragile X premutation (PM) alleles have 56 to 200 CGG repeats in the 5′-untranslated region of FMR1 gene are at increased risk for producing children with intellectual disabilities (ID) or autism spectrum disorders (ASD) due to expansion of PM alleles to full mutation alleles (> 200 repeats) during maternal transmission.MethodsIn present study fragile X PM carrier screening was performed in total 808 women who were consulting primary health care centers for preconception care in Khyber Pakhtunkhwa region of Pakistan between April, 2018 and December, 2020. Polymerase chain reaction (PCR) was performed for detection of PM carrier women and the CGG repeats number was confirmed by Southern blotting and capillary electrophoresis.ResultsThe prevalence rate for PM carriers among preconception women was found to be 0.7% that was contributed by 0.5% women in risk group (RG1) with family history of ID and 0.2% in risk group 2 (RG2) with family history of ASD. PM carrier women had at least one affected child or sibling. In addition, the preconception women with FMR1 PM alleles were found to be at increased risk for primary ovary insufficiency (RG1: P = 0.0265, RG2: P = 0.0389), postpartum depression (RG1: P = 0.0240, RG2: P = 0.0501) and neuropsychiatric disorders (RG1: P = 0.0389, RG2: P = 0.0432).ConclusionsCurrent study provides first evidence of fragile X PM carrier screening in Pakistani preconception women in primary care consultation. Findings of current study may help to improve preconception care and to reduce burden of fragile X associated disorders in our population.

Effectiveness and Adverse Effects of Risperidone in Children with Autism Spectrum Disorder in a Naturalistic Clinical Setting at a University Hospital in Oman.

Objective This study aimed at examining the effectiveness of treating children with autism spectrum disorder (ASD) who present with irritability, aggression, and disruptive behavior at the Sultan Qaboos University Hospital (SQUH) in Muscat, Oman, with risperidone, and to note any sex-based differences among this cohort. Method This was a retrospective study conducted at the Department of Behavioral Medicine at SQUH over two years from January 2017 to December 2018. This study included all children aged 3 to 18 years attending the Child and Adolescent Mental Health Service (CAMHS) outpatient clinic with a diagnosis of ASD, based on the DSM-5 criteria, and comorbid disruptive behavior, who had been prescribed risperidone. Result This study identified 95 ASD patients (72 males). Male patients' BMI score after 12 months of risperidone treatment showed an increase by 0.62 (1.57 SD; P=0.001); however, there was no significant change among female patients. Somnolence was noted in 69.6% of female patients as compared to 34.7% of males (P=0.003). Among those with a family history of ASD, 5 out of 17 patients had treatment success (29.4%), whereas 70 out of 78 patients (90.0%) who did not have a similar history had successful treatment. Conclusion In conclusion, low-dose risperidone monotherapy is effective and well tolerated among some children with ASD who present with disruptive behavior in a naturalistic clinical setting. However, we found that some of the side effects, such as weight gain and somnolence, were concerning.

Early trajectories of motor skills in infant siblings of children with autism spectrum disorder.

Delays in motor development are not considered a core feature of autism spectrum disorder (ASD). Yet, recent studies of infant siblings of children with ASD suggest that early delays in motor skills may be associated with later delays in developmental areas considered to be core features of an ASD diagnosis. While these studies demonstrate the longitudinal association between core features and motor delays observed at single time points, there is considerable interest in studying the trajectories of motor development over the first 3 years of life. To accomplish this, we investigated early trajectories of motor development in a cohort of 499 infant siblings of children with ASD and 176 children with no family history of ASD. Data for the current study were drawn from the prospective, multi-site, Canadian Infant Sibling Study. We evaluated trajectories of fine and gross motor development over the first 3 years using group-based trajectory modeling. Our results show that membership for both fine and gross motor trajectory groups was related to expressive language skills, receptive language skills, ASD symptom severity scores, and diagnostic classification at age 3. These results provide evidence that the trajectory of a child's early motor development may have important prognostic implications in ASD.

Affect and gaze responses during an Emotion-Evoking Task in infants at an increased likelihood for autism spectrum disorder

BackgroundThe majority of research examining emotional difficulties in autism spectrum disorder (ASD) prior to age 2 relies on parent report.MethodsWe examined behavioral responses (affect and gaze) during emotionally salient tasks designed to elicit mildly positive and negative emotional states in infants. At 12 and 18 months, infants at an increased likelihood for an ASD diagnosis (IL; have an older sibling with ASD; n = 60) and low likelihood (LL; no family history of ASD; n = 21) completed the Emotion-Evoking (EE) Task and parents completed the Infant Behavior Questionnaire-Revised (IBQ-R). All children received an Autism Diagnostic Observation Scale—second Edition assessment for ASD symptomatology at 24 months.ResultsThe main findings were (1) the IL group displayed higher rates of negative affect and spent less time looking at the task objects compared to the LL group, and (2) affect and gaze scores at 12 and 18 months, but not scores on the IBQ-R, predicted ASD symptoms at 24 months.LimitationsThe data were drawn from an IL sample and may not be generalizable to the general ASD population, and the children were not followed to determine a diagnosis of ASD.ConclusionThese results suggest that behavioral responses can provide important information that complements parent reports of emotional regulation in IL infants as early as 12 months of age.

Autism spectrum disorder screening in children aged 16-30 months using the Modified Checklist for Autism in Toddlers-Revised (M-CHAT-R)

Background Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a global prevalence of 7.6 in 1,000 children. The Modified Checklist for Autism in Toddlers - Revised (M-CHAT-R) is one of many screening tools for ASD. It is fast, easy to use, and has been translated and validated in the Indonesian language.&#x0D; Objective To determine the prevalence of ASD in Indonesia and its risk factors.&#x0D; Methods A cross-sectional study was conducted from March to October 2020. In the first protocol (March to July 2020), 219 children aged 16-30 months from 20 hospital walk-in clinics in five districts of Jakarta were included. Subjects’ parents filled out the M-CHAT-R questionnaire during their visit. A series of questions were asked to provide information about probable risk factors associated with ASD: gender, family history of ASD, preterm birth, low birth weight (LBW), and history of seizures. The second protocol (August to October 2020) was completed by parents via an online form, where 746 children aged 16-30 months were enrolled. Therefore, a total of 965 subjects were eligible for statistical analysis.&#x0D; Results Of 965 subjects, 56.58% were males. Subjects’ mean of age was 22.59 (SD 4.15) months. M-CHAT-R screening showed that 34 (3.52%) subjects were at high risk of developing ASD. Only male gender was significantly associated with ASD.&#x0D; Conclusion We screened for ASD in healthy 16-30-month-old Indonesian children. The rate of high-risk M-CHAT-R score was 3.52%. Male gender was a significant risk factor for high-risk M-CHAT-R results.

Facial asymmetry in parents of children on the autism spectrum.

Greater facial asymmetry has been consistently found in children with autism spectrum disorder (ASD) relative to children without ASD. There is substantial evidence that both facial structure and the recurrence of ASD diagnosis are highly heritable within a nuclear family. Furthermore, sub-clinical levels of autistic-like behavioural characteristics have also been reported in first-degree relatives of individuals with ASD, commonly known as the 'broad autism phenotype'. Therefore, the aim of the current study was to examine whether a broad autism phenotype expresses as facial asymmetry among 192 biological parents of autistic individuals (134 mothers) compared to those of 163 age-matched adults without a family history of ASD (113 females). Using dense surface-modelling techniques on three dimensional facial images, we found evidence for greater facial asymmetry in parents of autistic individuals compared to age-matched adults in the comparison group (p= 0.046, d= 0.21 [0.002, 0.42]). Considering previous findings and the current results, we conclude that facial asymmetry expressed in the facial morphology of autistic children may be related to heritability factors. LAY ABSTRACT: In a previous study, we showed that autistic children presented with greater facial asymmetry than non-autistic children. In the current study, we examined the amount of facial asymmetry shown on three-dimensional facial images of 192 parents of autistic children compared to a control group consisting of 163 similarly aged adults with no known history of autism. Although parents did show greater levels of facial asymmetry than those in the control group, this effect is statistically small. We concluded that the facial asymmetry previously found in autistic children may be related to genetic factors.

Measuring social-communication difficulties in school-age siblings of children with autism spectrum disorder: Standardized versus naturalistic assessment.

Younger siblings of children with autism spectrum disorder (ASD; high-risk siblings) are at elevated risk for developing the broader autism phenotype (BAP), which consists of subclinical features of ASD. We examined conversational skills in a naturalistic context and standardized assessments of pragmatic language and communication skills in high-risk and low-risk school-age children with BAP (n=22) and ASD (n=18) outcomes, as well as comparison children without ASD or BAP (n=135). Children with BAP characteristics exhibited lower conversational skills than comparison children, but did not differ on any of three standardized measures. Only the conversational ratings significantly predicted membership in the BAP versus Comparison group. This suggests that naturalistic tasks are crucial when assessing social-communication difficulties in children with a family history of ASD. LAY SUMMARY: The broader autism phenotype (BAP) consists of subclinical features of autism spectrum disorder (ASD) and is more common among family members of those with ASD. School-age children with BAP characteristics exhibited lower conversational skills than comparison children, but did not differ on standardized language measures tapping similar abilities. This suggests that naturalistic tasks may be more sensitive to the social-communication difficulties seen in some children with a family history of ASD than the standardized language tests used in most evaluations.

Prediction of Autism Risk From Family Medical History Data Using Machine Learning: A National Cohort Study From Denmark

BackgroundA family history of specific disorders (e.g., autism, depression, epilepsy) has been linked to risk for autism spectrum disorder (ASD). This study examines whether family history data could be used for ASD risk prediction. MethodsWe followed all Danish live births, from 1980 to 2012, of Denmark-born parents for an ASD diagnosis through April 10, 2017 (N = 1,697,231 births; 26,840 ASD cases). Linking each birth to three-generation family members, we identified 438 morbidity indicators, comprising 73 disorders reported prospectively for each family member. We tested various models using a machine learning approach. From the best-performing model, we calculated a family history risk score and estimated odds ratios and 95% confidence intervals for the risk of ASD. ResultsThe best-performing model comprised 41 indicators: eight mental conditions (e.g., ASD, attention-deficit/hyperactivity disorder, neurotic/stress disorders) and nine nonmental conditions (e.g., obesity, hypertension, asthma) across six family member types; model performance was similar in training and test subsamples. The highest risk score group had 17.0% ASD prevalence and a 15.3-fold (95% confidence interval, 14.0–17.1) increased ASD risk compared with the lowest score group, which had 0.6% ASD prevalence. In contrast, individuals with a full sibling with ASD had 9.5% ASD prevalence and a 6.1-fold (95% confidence interval, 5.9–6.4) higher risk than individuals without an affected sibling. ConclusionsFamily history of multiple mental and nonmental conditions can identify more individuals at highest risk for ASD than only considering the immediate family history of ASD. A comprehensive family history may be critical for a clinically relevant ASD risk prediction framework in the future.