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CONTEXT The Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F) is used worldwide to screen for autism spectrum disorder (ASD). OBJECTIVE To calculate psychometric properties of the M-CHAT-R/F for subsequent diagnosis of ASD. DATA SOURCES Systematic searches of Medline, Embase, SCOPUS, and Trip Pro databases from January 2014 to November 2021. STUDY SELECTION Studies were included if they (1) used the M-CHAT-R/F (2) applied standard scoring protocol, (3) used a diagnostic assessment for ASD, and (4) reported at least 1 psychometric property of the M-CHAT-R/F. DATA EXTRACTION Two independent reviewers completed screening, full-text review, data extraction, and quality assessment, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A random-effects model was used to derive pooled estimates and assess for between-study heterogeneity. RESULTS Of 667 studies identified, 15 with 18 distinct samples from 10 countries (49 841 children) were used in the meta-analysis. Pooled positive predictive value (PPV), was 57.7% (95% confidence interval [CI] 48.6–66.8, τ2 = 0.031). PPV was higher among high-risk (75.6% [95% CI 66.0–85.2]) than low-risk samples (51.2% [95% CI 43.0–59.5]). Pooled negative predictive value was 72.5% (95% CI 62.5–82.4 τ2 = 0.031), sensitivity was 82.6% (95% CI 76.2–88.9) and specificity 45.7% (95% CI 25.0–66.4). LIMITATIONS Negative predictive value, sensitivity, and specificity were calculated based on small sample sizes because of limited or no evaluation of screen-negative children. CONCLUSIONS These results support use of the M-CHAT-R/F as a screening tool for ASD. Caregiver counseling regarding likelihood of an ASD diagnosis after positive screen should acknowledge the moderate PPV.

There is increasing recognition of the heterogeneity of origin of cases of autism spectrum disorder (ASD) with multiple forms of ASD having been identified over the decades. Among these, a genetic etiology can be identified in 20-40% of cases when a full genetic work-up is completed. The Fragile X premutation state (characterized by the presence of 55-200 CGG repeats in the FMR1 gene) is a relatively newly identified disease state that has since been associated with several disorders including fragile X-associated tremor ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI) and most recently, fragile X-associated neurodevelopmental disorders (FXAND) which commonly includes anxiety and depression. In addition to these associated disorders, extant literature and clinical observations have suggested an association between the premutation state and ASD. In this paper, we review the literature pertinent to this and discuss possible molecular mechanisms that may explain this association. This includes lowered levels of the FMR1 Protein (FMRP), GABA deficits, mitochondrial dysfunction and secondary genetic abnormalities that is seen in premutation carriers as well as their increased vulnerability to environmental stressors. Understanding these mechanisms can facilitate development of targeted treatment for specific sub-groups of ASD and premutation disorders in future.

Children with autism spectrum disorder (ASD) have challenges in home oral care, accessing a dentist and accepting dental treatment. Occupational therapists (OTs) and speech therapists (STs) are likely to be involved earlier in managing communication, behavioural and sensory processing issues.To determine perceived issues, barriers and potential solutions to dental care for children with ASD in Singapore from the perspective of OTs and STs.Semi-structured interviews and a focus group discussion involving OTs and STs who treat children with ASD were conducted. Audio recordings were transcribed and coded into themes using the NVivo 12 software.Emergent themes indicated that: (i) OTs and STs have important roles in recognition of issues with toothbrushing, oral pathology and harmful oral habits; (ii) OTs and STs were able to identify reasons for difficulties in oral home care for children with ASD and offer helpful strategies; and (iii) OTs and STs can play a role in pre-dental visit preparations but lack a clear dental referral pathway.OTs and STs exclusively assist in the early identification and referrals of children with ASD to the dentist. Interprofessional collaboration with dentists should be further explored to aid in the provision of preventive dental advice.

Background: The fragile X premutation carrier state (PM) (55–200 CGG repeats in the fragile X messenger ribonucleoprotein 1, FMR1 gene) is associated with several conditions, including fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor ataxia (FXTAS), with current literature largely primarily investigating older PM individuals. The aim of this study was to identify the prevalence of fragile X-associated neurodevelopmental disorders (FXAND) in a sample of young PM individuals. Methods: This was a retrospective study conducted through a medical record review of PM individuals who were seen either for clinical concerns (probands, 45.9%) or identified through the cascade testing (non-probands, 54.1%) of an affected sibling with fragile X syndrome. Information on the presence of autism spectrum disorder, attention deficit hyperactivity disorder, anxiety, depression, long-term psychiatric medication intake, and cognitive function, based on standardized assessments, was obtained. Molecular data, including CGG repeat number and FMR1 mRNA levels, were also available for a subset of participants. Analysis included descriptive statistics and a test of comparison to describe the clinical profile of PM individuals pertinent to FXAND. Results: Participants included 61 individuals (52 males and 9 females) aged 7.8 to 20.0 years (mean 12.6 ± 3.4) with a mean full-scale IQ of 90.9 ± 22.7. The majority (N = 52; 85.2%) had at least one mental health disorder, with anxiety being the most common (82.0% of subjects), followed by ADHD (66.5%), and ASD (32.8%). Twenty-seven (87.1%) of non-probands also had at least one mental health condition, with probands having lower cognitive and adaptive skills than non-probands. ASD was present in 20 participants (17/52 males and 3/9 females; 15 probands) with significantly lower FSIQ in those with ASD (mean 73.5 vs. 98.0, p < 0.001). Participants with ASD had a higher number of long-term medications compared to those without (2.32 vs. 1.3, p = 0.002). Conclusions: Our findings indicate a high rate of FXAND diagnoses within a cohort of young PM individuals, including those identified via cascade testing, although this was not a population sample. An awareness of the entity of FXAND and the early recognition of the symptoms of associated conditions may facilitate timely and appropriate care for PM individuals.

Children with autism spectrum disorders (ASD) face challenges in home oral care, accessing a dentist and accepting dental treatment.To determine the barriers to dental care for autistic children in Singapore through the experiences and opinions of their parents.A qualitative exploratory approach comprising semistructured interviews and a focus group discussion was used. Audio recordings were transcribed and coded into themes using NVivo 12 software.Participants were 23 parents of autistic children aged 3-12 years. The following barriers were identified: (1) Sensory, physical and parental knowledge issues are related to toothbrushing difficulties and use of nonoptimally fluoridated toothpaste in autistic children. (2) Accessing dental services was hindered by a lack of parental knowledge on the importance of an early dental home, parental apprehension about the child's acceptance of dental care, lack of information on specialised dentists and perceived high cost of dental visits. Parental suggestions for improvements included understanding the child's sensory profile, more information on finding a suitable dentist and subsidisation of costs for multiple acclimatisation visits.Caregivers' education, information about specialised dentists and the availability of specific dental care resources for autistic children in Singapore are needed for optimising their dental care.

We evaluated factors affecting psychological ill-effects and resilience of caregivers of children with developmental disabilities during the coronavirus pandemic. Depression, Anxiety, and Stress Scales (DASS-21) and Connor-Davidson Resilience Scale 25-item were administered. Logistic regression was used to identify factors associated with psychological ill-effects and resilience. DASS-21 depression, anxiety and stress scores were high; these were associated with difficulties with infection control measures, autism diagnosis, and need for early intervention services. For caregivers of children with ASD, our DASS-21 scores were significantly higher than non-pandemic scores locally and in other Asian sites. Resilience scores correlated inversely with DASS-21 scores. Targeted support to selected at-risk caregivers and improving resilience can help their coping.

This study aimed to identify potential modifiable factors prior to early intervention that are associated with better adaptive skills in children with autism spectrum disorder. This cross-sectional study recruited patients with autism spectrum disorder, aged 5–12 years from two tertiary developmental programmes in Singapore. Demographics, family socio-economic status and early intervention details were collected. The primary outcome was the Vineland Adaptive Behaviour Scales Adaptive Behaviour Composite score. Multivariate linear regression analysis was done. The sample ( N = 193) comprised 84% males with a mean age of 6 years and 7 months. Mean age at diagnosis was 35.5 months and mean Vineland Adaptive Behaviour Scales Adaptive Behaviour Composite standard score was 76.5. Mean waiting time for early intervention was 6.2 months with a mean intensity of 8.0 h/week. Waiting time for early intervention was a negative correlate of the Vineland Adaptive Behaviour Scales Adaptive Behaviour Composite score after controlling for other variables ( β = −0.74, p = 0.04). Significant correlates also included paternal education ( β = 5.44, p = 0.03) and the presence of financial difficulties in the family ( β = −5.98, p = 0.04). Waiting time for early intervention is a modifiable risk factor that may be addressed during service planning to potentially improve adaptive skills in autism spectrum disorder. Children from low socio-economic status families may be at risk for poor functional skills and will benefit from targeted intervention plans. Lay abstract Despite improving services and care for individuals with autism spectrum disorder, functional outcomes such as daily living skills tend to be suboptimal for many. This study wanted to identify modifiable early intervention factors that are associated with better outcomes and possible high-risk groups of children who are at risk of poorer outcomes. Participants included 193 children aged between 5 and 12 years of age whose parents provided information on their family background and early intervention characteristics. These children also had their adaptive behaviour skills examined by formal testing. Results indicated that shorter wait time for early intervention was associated with better adaptive behaviour scores. Children from families with financial difficulties and lower paternal education were also at risk of poorer adaptive skills. Designing services for children with autism such that wait times to enter early intervention services are minimised following initial diagnosis can improve their eventual functional outcomes. Changes in healthcare policy to allow expedited entry or targeted intervention to children from low socio-economic status families can also enhance their eventual adaptive skill gains.

This study aims to explore coping strategies of fathers of very low birth weight (VLBW) infants in the neonatal intensive care unit (NICU). A qualitative descriptive study among fathers of VLBW babies. Semi-structured interviews were conducted with 15 fathers until data saturation was achieved. The Consolidated Criteria for Reporting Qualitative Studies (COREQ) checklist was used for reporting. The overarching theme was an active pursuit of reassurance. Coping strategies revolved around identifying specific stressors and then making deliberate efforts to address them. Based on the main stressors identified, three subthemes were derived: pursuing information amidst uncertainty, bonding with the infant for normalcy and seeking emotional support in the midst of anxiety. Fathers took on a predominantly problem-focused approach. Empowering fathers with knowledge and emotional support, facilitating bonding with the infant and addressing their concerns are important in supporting them while having an infant in the NICU.

Amidst the ongoing novel Coronavirus disease pandemic, children with developmental disabilities warrant specific attention to minimise having disproportionate consequences. These children are especially vulnerable to the effects of the pandemic due to (1) Greater healthcare needs, (2) Dependency on community-based services and (3) Mental health concerns. Healthcare professionals, public health systems and the society needs to come together to advocate for these children by optimising access to healthcare and community intervention services, promoting mental well-being and caregiver welfare. The consequences of missed present-day opportunities might only be evident in the years to come in these children. Hence, despite the prolonged pandemic, with consequent limitations in availability of resources, children with developmental disabilities should continue to be supported.

Objective Parents of preterm, very low birthweight (VLBW) infants in neonatal intensive care units (NICU) undergo emotional turmoil. Studies on parent's experiences typically focus on the maternal perspective. The purpose of the study is to explore the emotional needs and experiences of fathers of VLBW neonates in the NICU and to identify ways to improve their experiences. Study Design This was a qualitative descriptive design study undertaken at the NICU of a tertiary university hospital. Convenience sampling with predefined inclusion and exclusion criteria was used to identify prospective participants. Semi-structured interviews were conducted with 15 fathers of infants until data saturation was reached. The COREQ (Consolidated Criteria for Reporting Qualitative Studies) checklist was used. Results Father's experiences were classified into the topics of concerns, roles, and perspectives. Uncertainty was a predominant theme in each of these. Fathers assume multiple roles toward the child, wife, self, and family. Their concerns were multifaceted involving the child, family, work, and finances; they experienced a myriad of emotions, but these evolved into resilience eventually. Conclusion Fathers have unique concerns pertinent to having an infant in the NICU. They juggle multiple roles and transition to emotions of resilience. It is imperative to acknowledge the uncertainty and diverse roles of fathers, provide them with customized information, and develop more balanced parent-support groups. Key Points

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the full mutation as well as highly localized methylation of the fragile X mental retardation 1 (FMR1) gene on the long arm of the X chromosome. Children with FXS are commonly co-diagnosed with Autism Spectrum Disorder, attention and learning problems, anxiety, aggressive behavior and sleep disorder, and early interventions have improved many behavior symptoms associated with FXS. In this review, we performed a literature search of original and review articles data of clinical trials and book chapters using MEDLINE (1990–2021) and ClinicalTrials.gov. While we have reviewed the biological importance of the fragile X mental retardation protein (FMRP), the FXS phenotype, and current diagnosis techniques, the emphasis of this review is on clinical interventions. Early non-pharmacological interventions in combination with pharmacotherapy and targeted treatments aiming to reverse dysregulated brain pathways are the mainstream of treatment in FXS. Overall, early diagnosis and interventions are fundamental to achieve optimal clinical outcomes in FXS.

While behavioral interventions remain the mainstay of treatment of autism spectrum disorder (ASD), several potential targeted treatments addressing the underlying neurophysiology of ASD have emerged in the last few years. These are promising for the potential to, in future, become part of the mainstay treatment in addressing the core symptoms of ASD. Although it is likely that the development of future targeted treatments will be influenced by the underlying heterogeneity in etiology, associated genetic mechanisms influencing ASD are likely to be the first targets of treatments and even gene therapy in the future for ASD. In this article, we provide a review of current psychopharmacological treatment in ASD including those used to address common comorbidities of the condition and upcoming new targeted approaches in autism management. Medications including metformin, arbaclofen, cannabidiol, oxytocin, bumetanide, lovastatin, trofinetide, and dietary supplements including sulforophane and N-acetylcysteine are discussed. Commonly used medications to address the comorbidities associated with ASD including atypical antipsychotics, serotoninergic agents, alpha-2 agonists, and stimulant medications are also reviewed. Targeted treatments in Fragile X syndrome (FXS), the most common genetic disorder leading to ASD, provide a model for new treatments that may be helpful for other forms of ASD.

Screen time in early childhood has been associated with children's prosocial and behavioral skills; however, the directionality of this relationship is unclear. We aimed to determine the direction of the relationship between screen time, social skills, and nonsocial behavioral traits in young children.This was a population-based, prospective cohort study with data across 5 time points. We examined the reciprocal relationships between caregiver-reported children's screen time at 12, 18, 24, 36, and 54 months and social behaviors collected using the Infant-Toddler Social-Emotional Assessment at 12 months; the Quantitative Checklist for Autism at 18, 24, and 36 months; and the Social Responsiveness Scale at 54 months. Cross-lagged path models were used for analysis.A multiple imputation data set and complete data from 229 participants were included in the analyses. Screen time at 12, 18, and 36 months predicted nonsocial behavioral traits at 54 months. Cross-lagged path models showed a clear direction from increased screen time at earlier time points to both poorer social skills and atypical behaviors at later time points (Akaike information criterion 18936.55, Bayesian information criterion 19210.73, root mean square error of approximation 0.037, and comparative fit index 0.943). Social skills or behavioral traits at a younger age did not predict later screen time at any of the time points.Screen time in early childhood has lagged influences on social skills and nonsocial behaviors; the reverse relationship is not found. Close monitoring of social behaviors may be warranted in the setting of excessive screen time during early childhood.

OBJECTIVE: To evaluate the effects of parental sleep and work arrangements on children's sleep duration during the national lockdown period, referred to as 'Circuit Breaker' (CB), due to COVID-19. METHODS: Cross-sectional, anonymous, online questionnaire to parents with school-going children aged between 3 and 16 years. Child and parental sleep duration in relation to change in parental work arrangements, housing type and number of individuals in the household as reported by parents were evaluated. Descriptive statistics and tests of comparison were used to evaluate data. RESULTS: School-going children (n = 593) had a mean age of 8.68 (SD = 3.65; median 7) years. Both, fathers and mothers had gains in sleep during CB (based on self-reported sleep data), compared to pre-CB. Change in both maternal and paternal sleep duration positively correlated with change in child sleep duration (based on parent-reported sleep data) among all children (r2 = 0.27, p

Aims and objective To explore the experiences and support needs of parents of children with recently diagnosed autism spectrum disorder (ASD) in Singapore. Background Raising a child with ASD is challenging for parents, especially in the initial period following the diagnosis. Limited studies have focused on parents' perspectives. Design A qualitative descriptive design study. Methods Thirteen parents were recruited from a developmental and behavioural paediatric outpatient clinic of a tertiary hospital in Singapore from October-December 2018. Adult parents, who were primary caregivers of 2-10-year-old children diagnosed with ASD in the preceding 3 months to 2 years, were recruited. Semi-structured individual face-to-face interviews were conducted based on an interview guide. Thematic analysis was used to analyse the data. Consolidated Criteria for Reporting Qualitative Studies (COREQ) checklist was used for reporting. Results Common themes were analysed using constant comparative method to generate results. Four themes emerged after 13 interviews: (1) adjusting psychologically, (2) changing lifestyle, (3) contending with hurdles to services and (4) needing informational, tangible and emotional support. Conclusions Findings suggested a need for more formal support networks, targeted resource platforms and accessibility of services to help support parents better after receiving a diagnosis of ASD in their child. Relevance to clinical practice Enhancing current healthcare and social policies to improve the provision of standardised and targeted information to parents, establishing formal support networks, facilitating access to childcare services, and involving domestic helpers/nannies as dedicated caregivers and trainers could better support parents.

Highlights • MMR vaccine uptake rates have dropped between 25.64% - 73.55% during COVID-19. • A measles epidemic is a possibility due to reduction in community herd immunity. • Urgent public health efforts are needed to maintain efficacious vaccine coverage., Although the direct health impact of Coronavirus disease (COVID-19) pandemic on child health is low, there are indirect impacts across many aspects. We compare childhood vaccine uptake in three types of healthcare facilities in Singapore - public primary care clinics, a hospital paediatric unit, and private paediatrician clinics - from January to April 2020, to baseline, and calculate the impact on herd immunity for measles. We find a 25.6% to 73.6% drop in Measles-Mumps-Rubella (MMR) uptake rates, 0.4 – 10.3% drop for Diphtheria-Tetanus-Pertussis-inactivated Polio-Haemophilus influenza (5-in-1), and 8.0-67.8% drop for Pneumococcal conjugate vaccine (PCV) across all 3 sites. Consequent herd immunity reduces to 74 - 84% among 12-month- to 2-year-olds, well below the 95% coverage that is protective for measles. This puts the whole community at risk for a measles epidemic. Public health efforts are urgently needed to maintain efficacious coverage for routine childhood vaccines during the COVID-19 pandemic.

Supplemental material, sj-pdf-1-aut-10.1177_1362361321997287 for Correlates of adaptive skills in children with autism spectrum disorder by Ramkumar Aishworiya, Tze Jui Goh, Min Sung and Stacey Kiat Hong Tay in Autism

Objective Prolonged home isolation may lead to long-term negative consequences for both children and caregivers’ psychological wellbeing, especially in families with children with neurodevelopmental disorders. Therefore, a scoping review was conducted to identify challenges faced by caregivers of children with neurodevelopmental disorders during the coronavirus disease 2019 (COVID-19) pandemic and to consolidate parenting interventions and guidelines. Methods A systematic search was conducted on Embase, PsycInfo, PubMed, Scopus, and LitCovid. All article types published between December 2019 and November 2020 which reported on intervention guidelines and experiences of families with children with neurodevelopmental disorders during the COVID-19 pandemic were included. Qualitative themes, quantitative data, and article summaries were charted, and a thematic analysis was conducted. Results Twenty-nine articles were included in the review. Three themes were generated: (a) behavioral issues and health concerns, (b) disruptions of lifelines and daily routines, and (c) existing programs, models, and guidelines to support families. Additionally, a list of caregiver strategies such as scheduling regular online consultations, maintaining online therapy, educating a child on COVID-19, and preventive behaviors, creating a structured daily schedule and reinforcement system, and selecting child-appropriate activities was consolidated. Conclusion This review revealed a lack of evidence-based studies and articles on children with other neurodevelopmental disorders apart from autism and attention-deficit hyperactivity disorder. It also places emphasis on the importance of telehealth services as major lifelines to parents during this pandemic and urges healthcare organizations to provide funding to increase telehealth services to afflicted families.

The Coronavirus Disease 2019 pandemic by virtue of its sudden, unprecedented and widespread nature, has led to a multitude of psychological effects on individuals across societies. This includes anxiety which has important implications on the daily functioning, physical and mental health of individuals. Children are a vulnerable group of the population who can experience anxiety which potentially can lead to long-lasting implications on their health for years to come. It is thus important that their caregivers, including parents and healthcare professionals be aware of strategies that can help with anxiety in children. This article discusses anxiety in children in the context of the COVID-19 pandemic and outlines strategies that may be helpful.

Background As the coronavirus 2019 pandemic continues, healthcare services need to adapt to continue providing optimal and safe services for patients. We detail our adaptive framework as a large Developmental and Behavioral Pediatrics service in a tertiary academic institution in Singapore. Methods The multidisciplinary team at our unit implemented various adaptations and workflow processes during this evolving pandemic in providing continued clinical care tailored to the challenges specific to our patient population. Services were continued via teleconsultation mode during the ‘Circuit Breaker’ (enhanced movement restriction) period. Specific workflow processes, IT infrastructure, and staff training were put in place to support smooth running of this service. Segregation of services into two teams based at two separate sites and implementation of stringent infection control measures surrounding the clinic visit by providers, patients and their families were incorporated to ensure safety. Measures were also taken to ensure providers' mental wellbeing. Results The clinical service was continued for the majority of our patients with a lowest reduction in patient consultations to half of baseline during the ‘Circuit Breaker’ period. We received positive feedback from families for teleconsultation services provided. Conclusion We have been able to continue services in our DBP clinics due to our dynamic reassessment of workflow processes and their prompt implementation in conjunction with the hospital and national public health response to the pandemic. Given that this pandemic is likely to be long drawn, our unit remains ready to constantly adjust these workflows and make adaptations as we go along, together with the support for mental health of patients, parents and staff. Continual improvements in workflows will be helpful even beyond the pandemic to ensure good continuity of care for our patients and families.

Objective To evaluate the sleep habits of school-going children before and during school closure in the national lockdown period (called ‘Circuit Breaker’ or CB in Singapore) due to the COVID-19 pandemic. Methods Cross-sectional, anonymous, online, population-based survey questionnaire was administered to parents aged 21 years and above with children aged between 3 and 16 years attending pre-school, primary or secondary school (equivalent to kindergarten, middle and-high school) and residing in Singapore. Sleep duration in relation to various daily activities including academic activities, physical exercise, and screen time was evaluated pre-CB and during CB. Results Data from 593 participants were analyzed. Pre-CB, the overall mean (SD) sleep duration of the study population was 9.01 (1.18) hours on weekdays and 9.99 (0.94) hours on weekends. During CB, mean (SD) sleep duration overall was 9.63 (1.18) hours. Although children generally went to bed later (mean 0.65 h later), they woke up even later during CB (mean 1.27 h later), resulting in longer sleep duration (mean increase of 0.35 h). This was most evident in secondary school children (mean increase of 0.70 h). Children attending private schools (which had later start times) had increased sleep duration (mean 10.01 (SD 0.89) hours pre-CB and 10.05 (SD 0.93) hours during CB) compared to public schools (mean 9.05 (SD 0.91) pre-CB and 9.49 (SD 1.22) hours during CB). Conclusions School closure from the COVID-19 pandemic resulted in longer sleep duration in school-going children. Early school/academic activity start times had a significant impact on limiting children's sleep duration.

This study aims to explore coping strategies of fathers of very low birth weight (VLBW) infants in the neonatal intensive care unit (NICU).A qualitative descriptive study among fathers of VLBW babies. Semi-structured interviews were conducted with 15 fathers until data saturation was achieved. The Consolidated Criteria for Reporting Qualitative Studies (COREQ) checklist was used for reporting.The overarching theme was an active pursuit of reassurance. Coping strategies revolved around identifying specific stressors and then making deliberate efforts to address them. Based on the main stressors identified, three subthemes were derived: pursuing information amidst uncertainty, bonding with the infant for normalcy and seeking emotional support in the midst of anxiety. Fathers took on a predominantly problem-focused approach.Empowering fathers with knowledge and emotional support, facilitating bonding with the infant and addressing their concerns are important in supporting them while having an infant in the NICU.