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.

Pediatric psychiatric emergency rooms during COVID-19: a multi-center study.

BACKGROUND: The COVID-19 (SARS-CoV-2) pandemic has been a major stressor for the mental health and well-being of children and adolescents. Surveys and reports from hotlines indicate a significant rise in mental health problems. As the psychiatric emergency room (ER) is a first-line free-of-charge facility for psychiatric emergencies, we expected to see a significant increase in visits, specifically of new patients suffering from anxiety, depression, or stress-related disorders. METHODS: Data from two psychiatric hospital ERs and one general hospital were included. All visits of children and adolescents from the computerized files between March and December of 2019 were analyzed anonymously and compared to the same months in 2020, using multilevel linear modeling. RESULTS: There was a significant decline in the total number of visits (p = .017), specifically among those diagnosed as suffering from stress-related, anxiety, and mood disorder groups (p = .017), and an incline in the proportion of visits of severe mental disorders (p = .029). DISCUSSION: The limited use of child and adolescent psychiatric emergency facilities during the pandemic highlights the importance of tele-psychiatry as part of emergency services. It also suggests the importance of the timeline of the emergence of clinically relevant new psychiatric diagnoses related to the pandemic. Future studies are needed to establish the long-term effects of the pandemic and the expeditious use of tele-psychiatry.

Improving the parent-child relationship and child adjustment through parental reflective functioning group intervention.

Parental reflective functioning (PRF) is a core element in the parent-child relationship. This study set out to investigate changes in PRF following the DUET program, a 12-week group intervention program. We proposed that the DUET intervention would enhance maternal reflective capacities, resulting in better mother-child emotional availability, better child self-regulation, and decreased child behavioral problems. Seventy mothers completed the DUET group intervention. Of these mothers, nine mothers were first allocated to the waiting-list group and thereafter were included in an intervention group. PRF was measured using observation (mind-mindedness) and an interview (PDI). Following the intervention, a significant improvement was evident in PRF, in parental beliefs about feeling, and in parental sense of efficacy. In addition, the mother-child interaction was more positive, child behavioral problems decreased, and child self-regulation increased. This improvement remained stable over a period of 6 months. Clinical and future directions of this study are discussed.

Mother-Infant Sleep and Maternal Emotional Distress in Solo-Mother and Two-Parent Families.

OBJECTIVE: This study examined for the first time mother-infant sleep and emotional distress in solo mother families compared with two-parent families and explored whether the links between mother-infant sleep and maternal emotional distress differ as a function of family structure. METHODS: Thirty-nine solo-mother families and 39 two-parent families, with an infant within the age range of 6-18 months participated in the study. Actigraphy and sleep diaries were used to assess maternal and infant sleep at home. Mothers completed questionnaires to assess maternal depressive and anxiety symptoms, social support, sleeping arrangements, breastfeeding, and demographics. RESULTS: Solo mothers were older and more likely to breastfeed and share a bed with their infants than married mothers. There were no significant differences between the groups in mother-infant sleep and maternal emotional distress, while controlling for maternal age, breastfeeding, and sleeping arrangements. Family structure had a moderating effect on the associations between maternal emotional distress and mother-infant sleep. Only in solo-mother families, higher maternal emotional distress was associated with lower maternal and infant sleep quality. CONCLUSIONS: Our findings suggest that, although there are no significant differences in maternal and infant sleep between solo-mother families and two-parent families, the strength of the associations between maternal emotional distress and both infant and maternal sleep quality are stronger in solo-mother families, compared with two-parent families. Hopefully, understanding which aspects of parenting may contribute to the development of sleep problems in solo-mother families could be helpful in tailoring interventions to this growing population.

RSRC1 mutation affects intellect and behaviour through aberrant splicing and transcription, downregulating IGFBP3.

RSRC1, whose polymorphism is associated with altered brain function in schizophrenia, is a member of the serine and arginine rich-related protein family. Through homozygosity mapping and whole exome sequencing we show that RSRC1 mutation causes an autosomal recessive syndrome of intellectual disability, aberrant behaviour, hypotonia and mild facial dysmorphism with normal brain MRI. Further, we show that RSRC1 is ubiquitously expressed, and that the RSRC1 mutation triggers nonsense-mediated mRNA decay of the RSRC1 transcript in patients' fibroblasts. Short hairpin RNA (shRNA)-mediated lentiviral silencing and overexpression of RSRC1 in SH-SY5Y cells demonstrated that RSRC1 has a role in alternative splicing and transcription regulation. Transcriptome profiling of RSRC1-silenced cells unravelled specific differentially expressed genes previously associated with intellectual disability, hypotonia and schizophrenia, relevant to the disease phenotype. Protein-protein interaction network modelling suggested possible intermediate interactions by which RSRC1 affects gene-specific differential expression. Patient-derived induced pluripotent stem cells, differentiated into neural progenitor cells, showed expression dynamics similar to the RSRC1-silenced SH-SY5Y model. Notably, patient neural progenitor cells had 9.6-fold downregulated expression of IGFBP3, whose brain expression is affected by MECP2, aberrant in Rett syndrome. Interestingly, Igfbp3-null mice have behavioural impairment, abnormal synaptic function and monoaminergic neurotransmission, likely correlating with the disease phenotype.

Autism Prevalence and Severity in Bedouin-Arab and Jewish Communities in Southern Israel.

The vast majority of autism spectrum disorder (ASD) research focuses on Caucasian populations in western world countries. While it is assumed that autism rates are similar across ethnic groups regardless of genetic background and environmental exposures, few studies have specifically examined how autism prevalence and severity may differ between majority and minority populations with distinct characteristics. Therefore, we evaluated ethnic differences in ASD prevalence and severity of Bedouin-Arab and Jewish children in the south of Israel. We compared demographic and clinical characteristics of 104 children from a Bedouin-Arab minority with 214 Jewish children who were referred to the main ASD clinic in Southern Israel with suspected communication disorders. Data were obtained from medical records. Jewish children's referral rates were almost 6 times more than that of Bedouin-Arab referral rates (21:1000 and 3.6:1000, respectively). The percentage of high functioning children with ASD was much higher in Jewish than in Bedouin-Arab children (29.6 and 2.6%, respectively). Bedouin-Arab children showed more severe autistic manifestations. Moreover, Bedouin-Arab children were more likely than Jewish children to have additional diagnosis of intellectual disability (14.5 and 6.9%, respectively). Autism prevalence and severity differs markedly between the Bedouin-Arab and Jewish populations in the south of Israel. Most striking is the almost complete absence of children with high-functioning autism in the Bedouin community. A better understanding of the causes for autism prevalence and severity differences across ethnic groups is crucial for revealing the impact of multiple genetic and environmental factors that may affect autism development in each group.

[DSM-5 AND AUTISM: DIAGNOSTIC CHANGES AND CLINICAL IMPLICATIONS IN EARLY CHILDHOOD].

Autistic spectrum disorders (ASDs) are characterized by significant disability in interpersonal communication, social interactions and patterns of unusual behavior. In recent decades the worldwide prevalence of ASDs is rising almost exponentially, without a clear known etiological explanation. Until recently, ASDs were defined by the American Manual of Psychiatric Diagnoses: The DSM-IV-TR, under one conceptual umbrella of "Pervasive Developmental Disorders" (PDD). Under this category, there were five separate diagnoses. The DSM-5 eliminated the separate,diagnoses and created one continuum (Autism Spectrum Disorder = ASD). By this definition, the symptomatic manifestation was reduced and the criteria for diagnosis are fixed for the entire spectrum. The differences between individuals are expressed in the levels of severity rated. Studies evaluating the transition from PDD to ASD, found an increase in the specificity of the diagnosis and its potential ability to distinguish between clinical and non-clinical populations. Alongside the increase in consistency and stability, there is a decrease in sensitivity, and about a quarter of the children who were previously diagnosed with PDD are not diagnosed as such, due to a failure to meet all the necessary symptoms. These changes especially affect the clinical diagnosis of young children as their symptomatic manifestation is not yet clear and distinct enough due to their age and maturation processes. This article discusses the clinical implications of these findings and demonstrates it from a case report.

Mealtime dynamics in child feeding disorder: the role of child temperament, parental sense of competence, and paternal involvement.

OBJECTIVE: We examined how child temperament, parental sense of competence, and paternal involvement predicted observed mealtime dynamics. METHOD: 97 families of children with feeding disorder (FD), sleep problems (SP), and typically developing (TD) children participated in the study. Data were collected during home visits, where mother-child and father-child mealtime dynamics were videotaped and parents completed questionnaires. RESULTS: More mother-child and father-child conflict and control was observed during mealtimes in the FD than SP and TD groups. Among the FD group, maternal sense of competence was negatively correlated with mother-child conflict and control, and child temperament was linked to father-child conflict and control, but only for families in which fathers were highly involved. These correlations were not significant among the SP and TD groups. CONCLUSION: Different patterns of results were seen for mothers and fathers and among the FD and control groups. Clinical implications for the treatment of FD are discussed.

The Caregiving Environment and Developmental Outcomes of Preterm Infants: Diathesis Stress or Differential Susceptibility Effects?

The interactions between premature birth and the caregiving environment on infants' cognitive and social functioning were examined. Participants were 150 infants (83 preterm, 67 full-term) and their parents. When infants were 6 months old, parents reported on their levels of emotional distress, and triadic family interactions were filmed and coded. At 12 months of age, the infants' cognitive and social functioning was assessed. Prematurity moderated the effects of maternal (but not paternal) emotional distress and triadic interactions on infants' cognitive and social outcomes. Whereas for cognitive functioning the interactions were consistent with a diathesis-stress approach, for social functioning the interactions were consistent with a differential susceptibility approach. The differential effects of the caregiving environment between groups and outcomes are discussed.

Infant sleep development from 3 to 6 months postpartum: links with maternal sleep and paternal involvement.

The aims of this longitudinal study were to examine (a) development of infant sleep and maternal sleep from 3 to 6 months postpartum; (b) concomitant and prospective links between maternal sleep and infant sleep; and (c) triadic links between paternal involvement in infant caregiving and maternal and infant sleep. The study included 57 families that were recruited during pregnancy. Maternal and infant sleep was assessed using actigraphy and sleep diaries for 5 nights. Both fathers and mothers completed a questionnaire assessing the involvement of fathers relative to mothers in infant caregiving. The results demonstrated moderate improvement in infant and maternal sleep percent between 3 and 6 months. Maternal sleep percent at 3 months significantly predicted infant sleep percent at 6 months. Greater paternal involvement in infant daytime and nighttime caregiving at 3 months significantly predicted more consolidated maternal and infant sleep at 6 months. These findings suggest that maternal sleep is an important predictor of infant sleep and that increased involvement of fathers in infant caregiving responsibilities may contribute to improvements in both maternal and infant sleep during the first 6 months postpartum.

The role of the father in child sleep disturbance: child, parent, and parent-child relationship.

The majority of studies on child sleep problems focus primarily on mothers, neglecting paternal influences. Guided by the transactional framework, we explored how child temperament, paternal and maternal stress, and the parent-child interactions differ between families having children with sleep disturbances and a selected comparison group. The role of paternal involvement in child caregiving as a moderator of these differences was assessed. The sample consisted of 51 children (1-3 years old) and their mothers and fathers. Data were collected during home visits, when mothers and fathers completed questionnaires and were interviewed. In addition, mother-child and father-child interactions were videotaped. Results indicate that compared to the comparison group, fathers rated children with sleep disturbances as fussier, both their mothers and fathers experienced higher levels of stress, and reported using more bedtime interactions that interfere with child's sleep-wake self-regulation. In addition, their fathers were less sensitive during father-child interaction and less involved in child caregiving. Finally, paternal involvement moderated the group differences seen in maternal stress, suggesting that high paternal involvement acted as a buffer to protect parents of children with sleep disturbances from experiencing parental stress. The important role of fathers in families having children with sleep disturbances is discussed.

Oculomotor randomness is higher in autistic children and increases with the severity of symptoms.

A variety of studies have suggested that at least some children with autism spectrum disorder (ASD) view the world differently. Differences in gaze patterns as measured by eye tracking have been demonstrated during visual exploration of images and natural viewing of movies with social content. Here we analyzed the temporal randomness of saccades and blinks during natural viewing of movies, inspired by a recent measure of "randomness" applied to micro-movements of the hand and head in ASD (Torres et al., 2013; Torres & Denisova, 2016). We analyzed a large eye-tracking dataset of 189 ASD and 41 typically developing (TD) children (1-11 years old) who watched three movie clips with social content, each repeated twice. We found that oculomotor measures of randomness, obtained from gamma parameters of inter-saccade intervals (ISI) and blink duration distributions, were significantly higher in the ASD group compared with the TD group and were correlated with the ADOS comparison score, reflecting increased "randomness" in more severe cases. Moreover, these measures of randomness decreased with age, as well as with higher cognitive scores in both groups and were consistent across repeated viewing of each movie clip. Highly "random" eye movements in ASD children could be associated with high "neural variability" or noise, poor sensory-motor control, or weak engagement with the movies. These findings could contribute to the future development of oculomotor biomarkers as part of an integrative diagnostic tool for ASD.

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.

Large increase in ASD prevalence in Israel between 2017 and 2021.

Accurate estimation of annual changes in autism spectrum disorders (ASD) prevalence is critical for planning the expansion of diagnostic, education, and intervention services at an adequate rate. Previous studies from Israel have reported that ASD prevalence among 8-year-old children has increased from estimates of 0.3% in 2008 to 0.65% in 2015 and 1.3% in 2018. Here, we analyzed data acquired from the National Insurance Institute of Israeli (NII), a governmental organization that approves and monitors all ASD children who receive welfare services in Israel, and Clalit Health Services (CHS), the largest Health Maintenance Organization in Israel that provides health services to ~52% of the population. Data from both sources included annual data files from 2017 to 2021 containing the number of ASD cases per year of birth for 1-17-year-old children. This allowed us to estimate annual ASD prevalence among 3.5 million children born between 2000 and 2020 in Israel. Both data sources revealed a nearly two-fold increase in ASD prevalence among 1-17-year-old children from 2017 to 2021. Estimated prevalence rates differed across age groups with 2-3-year-old (day-care) children increasing from 0.27% to 1.19% (>4 fold change), 4-6-year-old (pre-school) children increasing from 0.8% to 1.83%, and 8-year-old children increasing from 0.82% to 1.56% in NII data. These results demonstrate that autism prevalence continues to increase in Israel with a shift towards diagnosis at earlier ages. These findings highlight the challenge facing health and education service providers in meeting the needs of a rapidly growing autism population.

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.

Posttraumatic stress disorder among preschoolers exposed to ongoing missile attacks in the Gaza war.

BACKGROUND: The prevalence and manifestation of posttraumatic stress symptoms in young children may differ from that observed in adults. This study examined sociodemographic, familial, and psychosomatic correlates of posttraumatic stress disorder (PTSD) among preschool children and their mothers who had been exposed to ongoing missile attacks in the Gaza war. METHODS: One hundred and sixty-seven mothers of preschoolers (aged 4.0-6.5 years) were interviewed regarding PTSD and psychosomatic symptomatology of their children, as well as their own reactions to trauma. RESULTS: Fourteen mothers (8.4%) and 35 children (21.0%) screened positive for PTSD. Sociodemographic characteristics were not associated with PTSD among mothers or children. Among children, the only significant risk factor was having a mother with PTSD (OR = 12.22, 95% CI 2.75-54.28). Compared to children who did not screen positive for PTSD, those who did screen positive displayed significantly higher rates of psychosomatic reactions to trauma, most notably constipation or diarrhea (OR = 4.36, 95% CI 1.64-11.60) and headaches (OR = 2.91, 95% CI 1.07-7.94). CONCLUSIONS: Results of this study add to the burgeoning literature on child PTSD, emphasizing the important role of maternal anxiety and the psychosomatic reactions associated with exposure to ongoing traumatic experiences in young children.

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.