Autologous umbilical cord blood infusion for the treatment of autism in young children: A within-subjects open label study on safety (assessed via caregiver report) and efficacy.

This study aimed to document the safety and efficacy of a single infusion of autologous umbilical cord blood (UCB) in 20 autistic children aged 24-72 months. A pre-post treatment within-subjects open label design was used. At T = 0, 6, 12, and 18 months, participants underwent detailed and structured safety evaluations (via caregiver report), Vineland Adaptive Behavior Scale (Vineland-3), Stanford Binet Intelligence Scale (SB-5), Expressive One-Word Picture Vocabulary Test, Brief Observation of Social Communication Change (BOSCC), Pervasive Developmental Disorder-Behavior Inventory, Repetitive Behavior Scale-Revised, Sensory Experience Questionnaire (SEQ-2.1), Child Behavior Checklist, Clinical Global Impression-Severity and Improvement (CGI-I) Scales, and eye-gaze tracking. UCB infusion was conducted at T = 6 months, hence, 0-6 months was the control period, and 6-18 months the follow-up period. Of 20 children recruited, 19 completed the study and 1 was withdrawn due to UCB not meeting quality control criteria for infusion. There were 15 males and 4 females with an overall mean (SD) age of 4.15 (0.62) years. Mean (SD) cell dose administered was 38.16 (9.82) million cells/kg. None suffered serious adverse events although there were mild behavioral side effects and one unit grew coagulase negative staphylococcus from a post-thaw sample. There were no significant differences in Vineland-3, SB-5, BOSCC, and SEQ-2.1 scores at T = 12 and T = 18 months. Twelve participants had T = 18 CGI-I scores of 2-3 (minimally to much improved), seven participants had scores of 4 (no change). Autologous UCB infusion in autistic children is generally safe but not without risks, including that of infection. In this within-subjects study, some children showed global symptom improvements while others showed no change. Stem cell therapies for autism should only be conducted under strict clinical trial conditions with clear risk discussions.

2023 clinical practice guidelines on autism spectrum disorder in children and adolescents in Singapore.

Introduction: Autism is a neurodevelopmental condition that is increasing in prevalence worldwide. There has been an exponential increase in autism-related research since 2010, when the first Singapore Clinical Practice Guidelines (CPG) on autism was published. Understanding of autism has since evolved to adopt a lifespan approach beyond that of a childhood condition. The aim of this CPG was to provide an updated set of recommendations for children and adolescents to aid clinical practice for professionals. Method: A multidisciplinary workgroup that comprised representatives from various sectors worked on this CPG. Clinical questions were organised into 10 different sections, each with its own subgroup of members. Seventeen existing international guidelines were evaluated using the Appraisal of Guidelines for REsearch & Evaluation II (AGREE-II) framework, of which 4 met criteria to act as references. Literature review across multiple databases was conducted between January 2011 to 2023; Grading of Recommendations, Assessment, Development and Evaluation (GRADE-like) methodology was used to synthesise evidence. Recommendation statements were derived, following Delphi-style consensus surveys among the workgroup. The draft guidelines underwent external review and public consultation before being formalised. Results: Recommendation and good practice statements pertaining to care of children and adolescents on the autism spectrum across 10 different sections were developed. Evidence matrices complement these recommendations and detail relevant evidence behind each recommendation statement. Conclusion: It is intended for these guidelines to promote effective management and healthcare services for children and adolescents on the autism spectrum, by reinforcing good and evidence-based clinical practice within our national context.

2023 clinical practice guidelines on autism spectrum disorder in children and adolescents in Singapore

Autism is a neurodevelopmental condition that is increasing in prevalence worldwide. There has been an exponential increase in autism-related research since 2010, when the first Singapore Clinical Practice Guidelines (CPG) on autism was published. Understanding of autism has since evolved to adopt a lifespan approach beyond that of a childhood condition. The aim of this CPG was to provide an updated set of recommendations for children and adolescents to aid clinical practice for professionals. A multidisciplinary workgroup that comprised representatives from various sectors worked on this CPG. Clinical questions were organised into 10 different sections, each with its own subgroup of members. Seventeen existing international guidelines were evaluated using the Appraisal of Guidelines for REsearch & Evaluation II (AGREE-II) framework, of which 4 met criteria to act as references. Literature review across multiple databases was conducted between January 2011 to 2023; Grading of Recommendations, Assessment, Development and Evaluation (GRADE-like) methodology was used to synthesise evidence. Recommendation statements were derived, following Delphi-style consensus surveys among the workgroup. The draft guidelines underwent external review and public consultation before being formalised. Recommendation and good practice statements pertaining to care of children and adolescents on the autism spectrum across 10 different sections were developed. Evidence matrices complement these recommendations and detail relevant evidence behind each recommendation statement. It is intended for these guidelines to promote effective management and healthcare services for children and adolescents on the autism spectrum, by reinforcing good and evidence-based clinical practice within our national context.

A Direct Comparison of Three Screening Methods for Autism Spectrum Disorder in a High-Likelihood Sibling Population.

Targeted screening of children at increased likelihood of autism is recommended. However, autism screening tools are usually validated for use mainly in low-likelihood populations. This study compared the accuracy of the Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F), the ASDetect app, and the Social Attention and Communication Surveillance, Revised (SACS-R). Siblings of autistic children underwent autism screening at 12, 18 and 30 months old. At each visit, caregivers completed the M-CHAT-R/F and ASDetect while trained nurses tested the siblings using the SACS-R. At 36 to 48 months, the siblings underwent an Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) assessment. 189 siblings were screened, 141 completed the study, and 32 were confirmed to have autism. Although not validated for use at 12 months, the M-CHAT-R/F had the best sensitivity among the three tools for this age group, suggesting that early signs are already apparent to caregivers. The M-CHAT-R/F had overall better sensitivity (0.72-0.83) across all age groups, but with overall lower specificity (0.55-0.77). The SACS-R and ASDetect had better positive predictive values at 18 and 30 months (0.60-0.68), while the M-CHAT-R/F was 0.43-0.48. Negative predictive values were generally high across all three tools across all age groups (0.78-0.93). Targeted screening of children at high likelihood of autism yielded a detection rate of 22.7% and should therefore be implemented routinely to facilitate early detection and intervention. The performance of autism screening tools should be examined in higher-likelihood populations for targeted screening of these children.

Ethnic Group Differences in the Timing of Autism Diagnosis, Intellectual Disability, and Educational Placement of Autistic Children in Singapore.

AIM: Given Singapore's distinct multicultural identity, this study examined the hypotheses that there may be ethnic group differences in diagnosis and outcomes in autistic children in Singapore. METHODS: Retrospective data were obtained from medical records of all children born between 2008 and 2011 who were diagnosed with clinical or confirmed autism. One-way ANOVAs and regression analyses were used to analyze data. RESULTS: Data from 2577 medical records were extracted. There were more boys (82.5%) and ethnic group distribution was Chinese (67%), Malay (14%), Indian (10%), and Others (10%). Chinese children were more likely to present at a developmental clinic with concerns 3-4 months younger compared to Malay children and those from Other Races (F(3, 2038) = 9.58, p < .001, Cohen's F = 0.12). Chinese children were also more likely to receive an autism diagnosis approximately 3 months younger compared to Malay children. Fewer autistic Chinese children were diagnosed with co-occurring intellectual disability (13.1%) while there were almost twice more Malay children than expected with co-occurring intellectual disability (29.9%) (χ2 (3) = 55.17, p < .001). There are correspondingly more Malay children on the autism spectrum who attend special education schools. Possible confounding variables such as household income level and mother's level of education were identified in some of these findings. CONCLUSION: Several significant ethnic group differences in autistic children in Singapore exist that warrant more investigation into possible causes and support systems needed, with implications for other ethnically diverse nations.

Consensus statement on Singapore integrated 24-hour activity guide for early childhood.

Introduction: Early childhood is a critical period for growth and development. Adopting healthy lifestyle behaviours during this period forms the foundation for future well-being and offers the best protection against non-communicable diseases. Singapore studies have shown that many young children are not achieving the recommendations on physical activity, sedentary behaviour and sleep. A workgroup was set up to develop recommendations for caregivers of infants, toddlers and preschoolers (aged <7 years) on how to integrate beneficial activities within a daily 24-hour period for optimal development and metabolic health. Method: The Grading of Recommendations Assessment, Development and Evaluation (GRADE)- ADOLOPMENT approach was employed for adoption, adaption or de novo development of recommendations. International and national guidelines were used as references, and an update of the literature reviews up to September 2021 was conducted through an electronic search of PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Results: Four consensus statements were developed for each age group: infants, toddlers and preschoolers. The statements focus on achieving good metabolic health through regular physical activity, limiting sedentary behaviour, achieving adequate sleep and positive eating habits. The 13th consensus statement recognises that integration of these activities within a 24-hour period can help obtain the best results. Conclusion: This set of recommendations guides and encourages caregivers of Singapore infants, toddlers and preschoolers to adopt beneficial lifestyle activities within each 24-hour period.

Recognition and management of bladder bowel dysfunction in children with autism spectrum disorder.

Children with autism spectrum disorder (ASD) with rigidities, anxiety or sensory preferences may establish a pattern of holding urine and stool, which places them at high risk of developing bladder bowel dysfunction (BBD). BBD, despite being common, is often unrecognised in children with ASD. With this case report of a 7-year-old girl with ASD presenting with acute retention of urine, we attempt to understand the underlying factors which may contribute to the association between BBD and ASD. Literature review indicates a complex interplay of factors such as brain connectivity changes, maturational delay of bladder function, cognitive rigidities and psychosocial stressors in children with ASD may possibly trigger events which predispose some of them to develop BBD. Simple strategies such as parental education, maintaining a bladder bowel diary and treatment of constipation may result in resolution of symptoms.

Congenital blindness and autism spectrum disorder (ASD): diagnostic challenges and intervention options.

The case of a 6-year-old boy with congenital blindness and features suggestive of autism spectrum disorder (ASD) is reported. He presented to a developmental paediatrician with global developmental delay, worsening self-injurious behaviours and difficulties in social interaction, transitions and interactive play. He demonstrated poor response to his name, rigidity, repetitive behaviours and had a sensory profile suggestive of ASD. This paper discusses the challenges in diagnosing and managing ASD in visually impaired children.

Autism spectrum disorder: early identification and management in primary care.

Autism spectrum disorder (ASD) is characterised by persistent deficits in social communication and interaction as well as restricted, repetitive patterns of behaviour and interests. Early detection and early intervention programmes improve functional outcomes. Family physicians should screen for ASD opportunistically when children attend clinics for acute issues and during scheduled well-child assessments. Early warning signs of ASD include the lack of social gestures at 12 months, using no meaningful single words at 18 months, and having no interest in other children or no spontaneous two-word phrases at 24 months. Children with suspected ASD should be referred to appropriate specialist centres as early as possible for multidisciplinary assessment and diagnosis.

The Relationship Among Screen Use, Sleep, and Emotional/Behavioral Difficulties in Preschool Children with Neurodevelopmental Disorders.

OBJECTIVE: Despite evidence that excessive screen use may contribute to negative health, developmental, emotional, and behavioral outcomes, more children are engaging in increasing amounts of screen-related activities. For children with neurodevelopmental conditions, increased screen use could exacerbate emotional/behavioral difficulties (EBDs) by interfering with sleep quantity and quality. AIMS: This study examined the possible mediating role of sleep in the relationship between screen use and EBDs in preschool children with neurodevelopmental disorders (NDDs) clinically referred to a child development center in Singapore. METHODS: A screen use questionnaire developed for the purposes of the present study, the Children's Sleep Habits Questionnaire, and the Strengths and Difficulties Questionnaire were completed by 367 caregivers of 2- to 5-year-old children with NDDs (39.5% autism spectrum disorder; 36.8% speech-language disorders; 23.7% others). RESULTS: Average daily screen use duration was 3.98 hours, with 93.9% exceeding 1 hour of screen time daily. 57.7% of children had screen devices in their bedrooms, while 52% commenced screen use at the age of 18 months or earlier. Sleep problems fully mediated the relationship between the number of bedroom screen devices and children's EBDs, as well as between the age of first screen use and EBDs, but not between hours of screen use and EBDs. Controlling for age, developmental level, and family income, children who started using screens earlier than 18 months and who had screen devices in their bedrooms had significantly more sleep problems and EBDs than those without. CONCLUSION: Children with neurodevelopmental conditions may have more difficulties disengaging from screen devices in their bedrooms, and an earlier age of screen exposure may contribute to more chronic disruption of sleep.

Brief Report: Investigating the Implications of Applying the New DSM-5 Criteria for Diagnosing Autism Spectrum Disorder in a Preschool Population in Singapore.

Diagnostic reports for 206 children who underwent an assessment for autism spectrum disorder (ASD) using the DSM-IV-TR criteria, were re-evaluated using the DSM-5 criteria. Mean age of the children at time of diagnosis was 3 years 10 months. Of the 202 children diagnosed with ASD on the DSM-IV-TR, 184 (91.1 %) also met the DSM-5 criteria for ASD. The overall concordance rate of ASD diagnosis on the DSM-IV-TR and DSM-5 was higher than that reported in other studies. Of the 18 children who did not meet DSM-5 criteria for ASD, 16 children met all social communication criteria but did not fulfil at least two restricted and repetitive behaviour (RRB) criteria. Six of those children had further RRBs emerging later on follow-up.

The Utility of Developmental Checklists in Parent-held Health Records in Singapore.

OBJECTIVE: The aim of this study was to investigate parents' perceptions of developmental checklists and the child development monitoring schedule in the Singapore health booklet. METHOD: Parents of children aged 2 years 6 months to 3 years 11 months with or without developmental concerns (n = 450) completed a structured interview, and their child's health booklets were reviewed. RESULTS: Most parents reported reading and using the developmental checklists. However, only about half of them attempted the checklists with minimal help from professionals. Approximately 7 in 10 parents of children with developmental concerns found the checklists useful for identifying concerns about their child. Despite positive feedback from parents about the checklists, only about 1 in 4 parents brought their child for a 2 to 3 years developmental monitoring visit at the time of the survey, and the completion rates of the checklists were less than desirable. CONCLUSIONS: Further revisions to the checklists can include simplifying the words and sentences and providing relevant pictures to aid understanding. If the checklists are to be used for screening, standardization of how the checklists are to be completed and how children at risk of developmental delays can be identified on the checklists need to be provided. Parents' awareness of the importance of evaluating their child's development at 9 months, 18 months, and particularly at 2.5 years, needs to be raised. Developmental screening for children at these critical ages can be made mandatory. An electronic version of the health booklet is likely to facilitate implementation of developmental screening in the health care system.