Association between ultrasonography foetal anomalies and autism spectrum disorder.

Multiple pieces of evidence support the prenatal predisposition of autism spectrum disorder (ASD). Nevertheless, robust data about abnormalities in foetuses later developing into children diagnosed with ASD are lacking. Prenatal ultrasound is an excellent tool to study abnormal foetal development as it is frequently used to monitor foetal growth and identify foetal anomalies throughout pregnancy. We conducted a retrospective case-sibling-control study of children diagnosed with ASD (cases); their own typically developing, closest-in-age siblings (TDS); and typically developing children from the general population (TDP), matched by year of birth, sex and ethnicity to investigate the association between ultrasonography foetal anomalies and ASD. The case group was drawn from all children diagnosed with ASD enrolled at the National Autism Research Center of Israel. Foetal ultrasound data from the foetal anatomy survey were obtained from prenatal ultrasound clinics of Clalit Health Services in southern Israel. The study comprised 659 children: 229 ASD, 201 TDS and 229 TDP. Ultrasonography foetal anomalies were found in 29.3% of ASD cases versus only 15.9% and 9.6% in the TDS and TDP groups [adjusted odds ratio (aOR) = 2.23, 95% confidence interval (CI) = 1.32-3.78, and aOR = 3.50, 95%CI = 2.07-5.91, respectively]. Multiple co-occurring ultrasonography foetal anomalies were significantly more prevalent among ASD cases. Ultrasonography foetal anomalies in the urinary system, heart, and head and brain were the most significantly associated with ASD diagnosis (aORUrinary = 2.08, 95%CI = 0.96-4.50 and aORUrinary = 2.90, 95%CI = 1.41-5.95; aORHeart = 3.72, 95%CI = 1.50-9.24 and aORHeart = 8.67, 95%CI = 2.62-28.63; and aORHead&Brain = 1.96, 95%CI = 0.72-5.30 and aORHead&Brain = 4.67, 95%CI = 1.34-16.24; versus TDS and TDP, respectively). ASD females had significantly more ultrasonography foetal anomalies than ASD males (43.1% versus 25.3%, P = 0.013) and a higher prevalence of multiple co-occurring ultrasonography foetal anomalies (15.7% versus 4.5%, P = 0.011). No sex differences were seen among TDS and TDP controls. ASD foetuses were characterized by a narrower head and a relatively wider ocular-distance versus TDP foetuses (ORBPD = 0.81, 95%CI = 0.70-0.94, and aOROcular distance = 1.29, 95%CI = 1.06-1.57). Ultrasonography foetal anomalies were associated with more severe ASD symptoms. Our findings shed important light on the multiorgan foetal anomalies associated with ASD.

Breastfeeding patterns in infants are associated with a later diagnosis of autism Spectrum disorder.

Breastfeeding is associated with medical and developmental benefits. This study aimed to assess associations between nutritional patterns in the first year of life and the likelihood of autism spectrum disorder (ASD). 270 children diagnosed with ASD (cases) and 500 neurotypical children (controls) matched to cases by sex, ethnicity, and birth date (± 3 months) were included in this retrospective case-control study. Both groups were ascertained from children born between 2014 and 2017 whose development/nutrition were monitored at mother-child health clinics in southern Israel. Conditional logistic regression was used to determine the independent association of nutritional patterns with ASD while adjusting for socio-demographic and clinical characteristics. Both exclusive and partial breastfeeding modes were associated with decreased odds of ASD diagnosis (aOR = 0.221, 95%CI = 0.136-0.360; aOR = 0.494, 95%CI = 0.328-0.743, respectively). A breastfeeding duration of >12 months was associated with lower ASD odds (aOR = 0.418, 95%CI = 0.204-0.855), while the introduction of solids after 6 months of age was associated with higher ASD odds than the introduction of solids at 6 months (aOR = 2.455, 95%CI = 1.116-4.201). These findings suggest that a longer period of exclusive breastfeeding is associated with a subsequent reduced likelihood of ASD diagnosis, thus reiterating the importance of proper post-natal nutrition for infant neurodevelopment.

Idiosyncratic pupil regulation in autistic children.

Recent neuroimaging and eye tracking studies have suggested that children with autism spectrum disorder (ASD) may exhibit more variable and idiosyncratic brain responses and eye movements than typically developing (TD) children. Here we extended this research for the first time to pupillometry recordings. We successfully completed pupillometry recordings with 103 children (66 with ASD), 4.5-years-old on average, who viewed three 90 second movies, twice. We extracted their pupillary time-course for each movie, capturing their stimulus evoked pupillary responses. We then computed the correlation between the time-course of each child and those of all others in their group. This yielded an average inter-subject correlation value per child, representing how similar their pupillary responses were to all others in their group. ASD participants exhibited significantly weaker inter-subject correlations than TD participants, reliably across all three movies. Differences across groups were largest in responses to a naturalistic movie containing footage of a social interaction between two TD children. This measure enabled classification of ASD and TD children with a sensitivity of 0.82 and specificity of 0.73 when trained and tested on independent datasets. Using the largest ASD pupillometry dataset to date, we demonstrate the utility of a new technique for measuring the idiosyncrasy of pupil regulation, which can be completed even by young children with co-occurring intellectual disability. These findings reveal that a considerable subgroup of ASD children have significantly more unstable, idiosyncratic pupil regulation than TD children, indicative of more variable, weakly regulated, underlying neural activity.

Sleep disturbances are associated with greater healthcare utilization in children with autism spectrum disorder.

BACKGROUND: Sleep disturbances are frequently reported in children with autism spectrum disorder (ASD) and are associated with the severity of co-occurring symptoms. This study's aim was to examine the extent of healthcare utilization and clinical outcomes associated with sleep disturbances in children with ASD. STUDY DESIGN: A retrospective, cross-sectional study of 541 children with ASD from the Azrieli National Center for Autism and Neurodevelopment Research (ANCAN) whose parents completed the Children's Sleep Habits Questionnaire (CSHQ). Children with a total CSHQ score ≥ 48 were defined as having sleep disturbances. Sociodemographic characteristics, ASD diagnostic measures, chronic co-occurring conditions, medication usage, hospitalizations, visits to the emergency room (ER), and visits to specialists were compared in ASD children with and without sleep disturbances. Multivariate logistic regression models were then used to assess the independent association of sleep disturbances with clinical characteristics and healthcare utilization. RESULTS: Of the 541 children with ASD, 257 (47.5%) had sleep disturbances. Children with sleep disturbances exhibited higher rates of multiple (≥ 3) co-occurring conditions (19.1% vs. 12.7%; p = 0.0414) and prescribed medications (45.5% vs. 32.7%; p = 0.0031) than other children. Finally, ASD children with sleep disturbances were 1.72 and 2.71 times more likely to visit the ER and be hospitalized than their counterparts (aOR = 1.72; 99%CI = 1.01-2.95; and aOR = 2.71; 99%CI = 1.10-6.67, respectively). CONCLUSIONS: Our findings suggest that sleep disturbances are associated with greater healthcare utilization among children with ASD. Further studies could examine whether treating sleep disturbances in children with ASD yields additional clinical benefits beyond improvements in sleep.

Association between rare, genetic variants linked to autism and ultrasonography fetal anomalies in children with autism spectrum disorder.

BACKGROUND: Recent evidence suggests that certain fetal anomalies detected upon prenatal ultrasound screenings are associated with autism spectrum disorder (ASD). In this cross-sectional study, we aimed to identify genetic variants associated with fetal ultrasound anomalies (UFAs) in children with ASD. METHODS: The study included all children with ASD who are registered in the database of the Azrieli National Center of Autism and Neurodevelopment and for whom both prenatal ultrasound and whole exome sequencing (WES) data were available. We applied our in-house integrative bioinformatics pipeline, AutScore, to these WES data to prioritize rare, gene-disrupting variants (GDVs) probably contributing to ASD susceptibily. Univariate statistics and multivariable regression were used to assess the associations between UFAs and GDVs identified in these children. RESULTS: The study sample comprised 126 children, of whom 43 (34.1%) had at least one UFA detected in the prenatal ultrasound scan. A total of 87 candidate ASD genetic variants were detected in 60 children, with 24 (40%) children carrying multiple variants. Children with UFAs were more likely to have loss-of-function (LoF) mutations (aOR = 2.55, 95%CI: 1.13-5.80). This association was particularly noticeable when children with structural anomalies or children with UFAs in their head and brain scans were compared to children without UFAs (any mutation: aOR = 8.28, 95%CI: 2.29-30.01; LoF: aOR = 5.72, 95%CI: 2.08-15.71 and any mutation: aOR = 6.39, 95%CI: 1.34-30.47; LoF: aOR = 4.50, 95%CI: 1.32-15.35, respectively). GDVs associated with UFAs were enriched in genes highly expressed across all tissues (aOR = 2.76, 95%CI: 1.14-6.68). There was a weak, but significant, correlation between the number of mutations and the number of abnormalities detected in the same children (r = 0.21, P = 0.016). CONCLUSIONS: The results provide valuable insights into the potential genetic basis of prenatal organogenesis abnormalities associated with ASD and shed light on the complex interplay between genetic factors and fetal development.

Idiosyncratic pupil regulation in autistic children.

Recent neuroimaging and eye-tracking studies have suggested that children with autism exhibit more variable and idiosyncratic brain responses and eye movements than typically developing (TD) children. Here, we extended this research to pupillometry recordings. We successfully acquired pupillometry recordings from 111 children (74 with autism), 4.5-years-old on average, who viewed three 90 s movies, twice. We extracted their pupillary time-course for each movie, capturing their stimulus evoked pupillary responses. We then computed the correlation between the time-course of each child and those of all others in their group as well as between each autistic child and all children in the TD group. This yielded an average inter-subject correlation value per child, representing how similar their pupillary responses were to all others in their group or the comparison group. Children with autism exhibited significantly weaker inter-subject correlations than TD children in all comparisons. These differences were independent of previously reported differences in gaze inter-subject correlations and were largest in responses to a naturalistic movie containing footage of a social interaction between two TD children. The results demonstrate the utility of measuring the idiosyncrasy of pupil regulation, which can be performed with passive viewing of movies even by young children with co-occurring intellectual disability. These findings reveal that a considerable number of children with autism have significantly less stable, idiosyncratic pupil regulation than TD children, indicative of more variable, weakly regulated, underlying neural activity.

The Importance of Language Delays as an Early Indicator of Subsequent ASD Diagnosis in Public Healthcare Settings.

Previous studies have reported that ASD children with more severe symptoms are diagnosed earlier. However, previous studies in community settings have mostly relied on retrospective parental reports without the use of quantitative standardized test scores. Here, we evaluated the association of language, cognitive, and ASD severity standardized scores with the age of diagnosis in 1-6-year-old children diagnosed in a public healthcare setting. The results revealed that language scores were the strongest variable associated with the age of diagnosis, explaining ~ 30% of the variability across children. Indeed, all children diagnosed before 30-months of age exhibited moderate-to-severe language delays. These results further substantiate the prominence of language delay as a highly visible symptom associated with earlier ASD diagnosis in community clinical settings.

Sleep disturbances are associated with irritability in ASD children with sensory sensitivities.

BACKGROUND: Parent reports suggest that 44-84% of children with ASD exhibit sleep disturbances that are of clinical concern. Previous studies have reported that, in children with ASD, the severity of sleep disturbances is associated with the severity of either sensory problems or aberrant behaviors, but none have performed combined analyses with measures of both sensory and aberrant behaviors symptom domains from the same children. METHODS: We examined parent reports of 237 children with ASD, 1.4-8.7 years old, using the child sleep habits questionnaire (CSHQ), sensory profile (SP), and aberrant behaviors checklist (ABC). RESULTS: The analyses revealed that sleep disturbances were most strongly associated with SP sensory sensitivity and ABC irritability scores. Together these scores explained 35% of the variance in total CSHQ scores. Moreover, sensory sensitivity scores moderated the association between irritability and sleep disturbances, indicating that sleep disturbances were significantly associated with irritability only in children with moderate to severe sensory sensitivities. CONCLUSION: We suggest that the three symptom domains may interact and exacerbate each other such that successful intervention in one symptom domain may have positive impact on the others. Further intervention studies testing this hypothesis are highly warranted.

Adherence to treatment and parents' perspective about effectiveness of melatonin in children with autism spectrum disorder and sleep disturbances.

OBJECTIVE: Melatonin is considered an effective pharmacological treatment for the sleep disturbances that are reported in > 50% of children with autism spectrum disorder (ASD). However, real-life data about the long-term course and effectiveness of melatonin treatment in children with ASD is lacking. METHODS: In this retrospective cohort study, we assessed the adherence to melatonin treatment and parents' perspective of its effect on sleep quality and daytime behavior in children with ASD via a parental phone survey of children in the Azrieli National Center for Autism and Neurodevelopment Research (ANCAN) database. Cox regression analysis was used to assess the effect of key demographic and clinical characteristics on treatment adherence. RESULTS: Melatonin was recommended for ~ 8% of children in the ANCAN database. These children were characterized by more severe symptoms of autism. The median adherence time for melatonin treatment exceeded 88 months, with the most common reason for discontinuation being a lack of effectiveness (14%). Mild side-effects were reported in 14% of children, and 86%, 54%, and 45% experienced improvements in sleep onset, sleep duration and night awakenings, respectively. Notably, melatonin also improved the daytime behaviors of > 28% of the children. Adherence to treatment was independently associated with improvements in night awakenings and educational functioning (aHR = 0.142, 95%CI = 0.036-0.565; and aHR = 0.195, 95%CI = 0.047-0.806, respectively). CONCLUSIONS: Based on parents' report, melatonin is a safe and effective treatment that improves both sleep difficulties and daily behavior of children with ASD.

Comparison of three bioinformatics tools in the detection of ASD candidate variants from whole exome sequencing data.

Autism spectrum disorder (ASD) is a heterogenous multifactorial neurodevelopmental condition with a significant genetic susceptibility component. Thus, identifying genetic variations associated with ASD is a complex task. Whole-exome sequencing (WES) is an effective approach for detecting extremely rare protein-coding single-nucleotide variants (SNVs) and short insertions/deletions (INDELs). However, interpreting these variants' functional and clinical consequences requires integrating multifaceted genomic information. We compared the concordance and effectiveness of three bioinformatics tools in detecting ASD candidate variants (SNVs and short INDELs) from WES data of 220 ASD family trios registered in the National Autism Database of Israel. We studied only rare (< 1% population frequency) proband-specific variants. According to the American College of Medical Genetics (ACMG) guidelines, the pathogenicity of variants was evaluated by the InterVar and TAPES tools. In addition, likely gene-disrupting (LGD) variants were detected based on an in-house bioinformatics tool, Psi-Variant, that integrates results from seven in-silico prediction tools. Overall, 372 variants in 311 genes distributed in 168 probands were detected by these tools. The overlap between the tools was 64.1, 22.9, and 23.1% for InterVar-TAPES, InterVar-Psi-Variant, and TAPES-Psi-Variant, respectively. The intersection between InterVar and Psi-Variant (I âˆ© P) was the most effective approach in detecting variants in known ASD genes (PPV = 0.274; OR = 7.09, 95% CI = 3.92-12.22), while the union of InterVar and Psi Variant (I U P) achieved the highest diagnostic yield (20.5%).Our results suggest that integrating different variant interpretation approaches in detecting ASD candidate variants from WES data is superior to each approach alone. The inclusion of additional criteria could further improve the detection of ASD candidate variants.

Children with autism exhibit similar longitudinal changes in core symptoms when placed in special or mainstream education settings.

LAY ABSTRACT: Today, children with autism spectrum disorder (ASD) are placed in mainstream or special education settings somewhat arbitrarily with no clear clinical recommendations. Here, we compared changes in core ASD symptoms, as measured by the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) clinical assessment, across ASD preschool children placed in special or mainstream education. Longitudinal changes in ADOS-2 scores did not differ significantly across settings over a 1- to 2-year period. While some children improved in core ASD symptoms, others deteriorated in both settings. This highlights the need to identify specific criteria for establishing meaningful placement recommendations.

Association Between Early Developmental Milestones and Autism Spectrum Disorder.

Early diagnosis and treatment of autism spectrum disorder (ASD) has been shown to lead to better prognosis. Here, we examined the association of commonly measured early developmental milestones (DMs) with later diagnosis of ASD. We conducted a case-control study of 280 children with ASD (cases) and 560 typically developed children (controls) matched to cases by date of birth, sex, and ethnicity in a control/case ratio of 2:1. Both cases and controls were ascertained from all children whose development was monitored at mother-child health clinics (MCHCs) in southern Israel. DM failure rates during the first 18 months of life in three developmental categories (motor, social, and verbal) were compared between cases and controls. Conditional logistic regression models were used to assess the independent association of specific DMs with the risk of ASD, while adjusting for demographic and birth characteristics.Significant case-control differences in DM failure rates were observed as early as 3 months of age (p < 0.001), and these differences increased with age. Specifically, cases were 2.4 times more likely to fail ≥ 1 DM at 3 months (aOR = 2.39; 95%CI = 1.41-4.06), and 15.3 times more likely to fail ≥ 3 DMs at 18 months (aOR = 15.32; 95%CI = 7.75-30.28). The most notable DM-ASD association was observed for social DM failure at 9-12 months (aOR = 4.59; 95%CI = 2.59-8.13). Importantly, the sex or ethnicity of the participants did not affect these DM-ASD associations. Our findings highlight the potential role of DMs as early signs of ASD that could facilitate earlier referral and diagnosis of ASD.

Early diagnosis of autism in the community is associated with marked improvement in social symptoms within 1-2 years.

LAY ABSTRACT: It is widely believed that early diagnosis and treatment of autism spectrum disorder is essential for better outcome. This is demonstrated by the American Academy of Pediatrics recommendation to screen all 1.5-2.5-year-old toddlers for autism spectrum disorder. However, multiple longitudinal studies of children diagnosed with autism spectrum disorder at 1.5-6 years of age and treated in community settings have not reported any associations between earlier diagnosis and improved outcome in core autism spectrum disorder symptoms. In this study, we measured changes in core autism spectrum disorder symptoms over a 1-2-year period in 131 children diagnosed with autism spectrum disorder at 1.2-5 years of age, and treated in the community. The results revealed that children who were diagnosed before 2.5 years of age were three times more likely to exhibit considerable improvements in social autism spectrum disorder symptoms in comparison to children diagnosed at later ages. These results highlight the importance of early diagnosis and treatment of autism spectrum disorder even in community settings with heterogeneous services. In addition, these results motivate further prioritization of universal screening for autism spectrum disorder before 2.5 years of age.

Sleep Disturbances and Sensory Sensitivities Co-Vary in a Longitudinal Manner in Pre-School Children with Autism Spectrum Disorders.

Previous research has demonstrated that sleep disturbances are positively correlated with sensory sensitivities in children with ASD. Most of these studies, however, were based on cross-sectional analyses, where the relationship across symptom domains was examined at a single time-point. Here, we examined the development of 103 pre-school children with ASD over a 1-3-year period. The results revealed that spontaneous longitudinal changes in sleep disturbances were specifically correlated with changes in sensory sensitivities and not with changes in other sensory processing domains nor with changes in core ASD symptoms. These finding demonstrate a consistent longitudinal relationship between sleep disturbances and sensory sensitivities, which suggests that these symptoms may be generated by common or interacting underlying physiological mechanisms.

Association Between Antenatal Antimicrobial Therapy and Autism Spectrum Disorder-A Nested Case-Control Study.

Background: Multiple prenatal factors have been associated with autism spectrum disorder (ASD) risk. However, current data about the association between antimicrobial use during pregnancy and ASD is limited. Methods: A nested matched case-control study of children with ASD (cases), and children without ASD or other psychiatric or genetic disorders (controls). We compared the use of antimicrobial therapy during the 3 months before conception or during pregnancy between mothers of cases and controls and used multivariate conditional logistic regression models to assess the independent association between maternal use of antimicrobials during pregnancy and the risk of ASD in their offspring. Results: More than half of the mothers in the study (54.1%) used antimicrobial drugs during the 3 months before conception or during pregnancy. Rates of antimicrobial use were lower for mothers of children with ASD compared to mothers of controls (49.0 vs. 55.1%, respectively; p = 0.02), especially during the third trimester of pregnancy (18.8 vs. 22.9%, respectively; p = 0.03), and for the use of penicillins (15.7 vs. 19.7%, respectively; p = 0.06). These case-control differences suggest that antimicrobial administration during pregnancy was associated with a reduced risk of ASD in the offspring (aOR = 0.75, 95% CI = 0.61-0.92). Interestingly, this association was seen only among Jewish but not for the Bedouin mothers (aOR = 0.62, 95% CI = 0.48-0.79 and aOR = 1.21, 95% CI = 0.82-1.79). Conclusions: The reduced risk of ASD associated with prenatal antimicrobials use only in the Jewish population suggest the involvement of other ethnic differences in healthcare services utilization in this association.

Factors Affecting Family Compliance with Genetic Testing of Children Diagnosed with Autism Spectrum Disorder.

There is broad consensus about the importance of post-diagnostic genetic testing for children with ASD. However, the extent of compliance with these tests and the factors affecting compliance have rarely been examined. We surveyed a sample of 114 families with a child with ASD in Israel, where such genetic testing is funded by the government. We found that only one-third of these families completed post-diagnosis genetic testing for their child. The main factor influencing compliance was the doctor's recommendation (OR 11.6; 95% CI 3.2-42.4; p < 0.001). Furthermore, > 50% of the non-compliant families reported that genetic testing was irrelevant to them. Our findings highlight the importance of providing clear recommendations and explanations regarding the benefits and relevance of post-diagnosis genetic testing for children with ASD.

Basic oculomotor function is similar in young children with ASD and typically developing controls.

A variety of eye tracking studies have demonstrated that young children with ASD gaze at images and movies of social interactions differently than typically developing children. These findings have supported the hypothesis that gaze behavior differences are generated by a weaker preference for social stimuli in ASD children. The hypothesis assumes that gaze differences are not caused by abnormalities in oculomotor function including saccade frequency and kinematics. Previous studies of oculomotor function have mostly been performed with school-age children, adolescents, and adults using visual search, anti-saccade, and gap saccade tasks that are less suitable for young pre-school children. Here, we examined oculomotor function in 144 children (90 with ASD and 54 controls), 1-10-years-old, as they watched two animated movies interleaved with the presentation of multiple salient stimuli that elicited saccades-to-targets. The results revealed that the number of fixations, fixation duration, number of saccades, saccade duration, saccade accuracy, and saccade latency did not differ significantly across groups. Minor initial differences in saccade peak velocity were not supported by analysis with a linear mixed model. These findings suggest that most children with ASD exhibit similar oculomotor function to that of controls, when performing saccades-to-targets or freely viewing child-friendly movies. This suggests that previously reported gaze abnormalities in children with ASD are not due to underlying oculomotor deficiencies. LAY SUMMARY: This study demonstrates that children with ASD perform similar eye movements to those of controls when freely observing movies or making eye movements to targets. Similar results were apparent across groups in the number of eye movements, their accuracy, duration, and other measures that assess eye movement control. These findings are important for interpreting previously reported differences in gaze behavior of children with ASD, which are likely due to atypical social preferences rather than impaired control of eye movements.

Ethnic Disparities in the Diagnosis of Autism in Southern Israel.

The prevalence of autism spectrum disorder (ASD) is continuously rising worldwide, with remarkable differences in ASD rates being reported across ethnic and socioeconomic groups. We conducted a prospective cohort study to identify the reasons for differences in ASD rates between the Bedouin and Jewish populations in southern Israel. Screening, referral, and diagnosis of toddlers aged 16-36 months were compared between Bedouin and Jewish populations. ASD screening was conducted at 35 randomly selected mother and child health centers (MCHCs) by trained nurses using the Modified Checklist for Autism in Toddlers with follow-up (M-CHAT/F) instrument. Toddlers screened positive at the MCHCs were monitored throughout the referral and diagnosis process at a single medical center until a diagnosis was determined by a physician specialist using DSM-5 criteria. The study cohort comprised 3,343 toddlers (996 Jewish and 2,347 Bedouin). Bedouin toddlers, compared to Jewish toddlers, were less likely to screen positive with M-CHAT/F (3.0% vs. 3.9%; P = 0.165), were significantly less likely to begin the hospital diagnosis process (HR = 0.38, 95% CI: 0.14-1.08; P = 0.068), and had a higher rates of loss-to-follow-up during the hospital diagnosis process (42.9% vs. 15.6%, respectively; P = 0.001). The results suggest that ethnic-specific barriers in the diagnosis process of ASD contribute to under-diagnosis of ASD in the Bedouin population. Facilitating the diagnosis process for Bedouin families will help to identify more children with ASD at earlier ages and consequently close the ethnic gap in ASD rates. LAY SUMMARY: We followed Bedouin and Jewish toddlers aged 16-36 months from southern Israel through their autism spectrum disorder (ASD) screening referral and diagnosis to identify the reasons for the differences in ASD prevalence between these ethnic groups. Jewish and Bedouin toddlers were equally identified in the ASD screening. However, Bedouin toddlers were less likely to complete the diagnosis process due to higher rates of loss-to-follow-up and slower diagnosis process. Facilitating ASD diagnosis for the Bedouin population will help identifying more toddlers with ASD.

Association Between Abnormal Fetal Head Growth and Autism Spectrum Disorder.

OBJECTIVE: Despite evidence for the prenatal onset of abnormal head growth in children with autism spectrum disorder (ASD), studies on fetal ultrasound data in ASD are limited and controversial. METHOD: We conducted a longitudinal matched case-sibling-control study on prenatal ultrasound biometric measures of children with ASD, and 2 control groups: (1) their own typically developed sibling (TDS) and (2) typically developed population (TDP). The cohort comprised 528 children (72.7% male), 174 with ASD, 178 TDS, and 176 TDP. RESULTS: During the second trimester, ASD and TDS fetuses had significantly smaller biparietal diameter (BPD) than TDP fetuses (adjusted odds ratio for the z score of BPD [aORzBPD] = 0.685, 95% CI = 0.527-0.890, and aORzBPD = 0.587, 95% CI = 0.459-0.751, respectively). However, these differences became statistically indistinguishable in the third trimester. Interestingly, head biometric measures varied by sex, with male fetuses having larger heads than female fetuses within and across groups. A linear mixed-effect model assessing the effects of sex and group assignment on fetal longitudinal head growth indicated faster BPD growth in TDS versus both ASD and TDP in male fetuses (ß = 0.084 and ß = 0.100 respectively; p < .001) but not in female fetuses, suggesting an ASD-sex interaction in head growth during gestation. Finally, fetal head growth showed conflicting correlations with ASD severity in male and female children across different gestation periods, thus further supporting the sex effect on the association between fetal head growth and ASD. CONCLUSION: Our findings suggest that abnormal fetal head growth is a familial trait of ASD, which is modulated by sex and is associated with the severity of the disorder. Thus, it could serve as an early biomarker for ASD.