Co-occurring conditions in Down syndrome: Findings from a clinical database.

Individuals with Down syndrome (DS) experience a range of medical and neurodevelopmental conditions, necessitating systematic study of their occurrence and impact on neurodevelopmental outcomes. We describe the prevalence and relationships of medical, neurodevelopmental (ND), and mental health (MH) conditions in children with DS. We created a prospective clinical database of individuals with DS, integrated into the workflow of a specialty Down Syndrome Program at a specialty pediatric referral hospital. Conditions were collected through caregiver- and clinician report at clinical visits (N = 599). We calculated frequencies of medical, ND, and MH conditions and then assessed the relationship between medical, ND, and MH conditions using frequencies and comparative statistics. The most frequent co-occurring conditions were vision (72.5%), ear/hearing (71.0%), gastrointestinal (61.3%), respiratory (45.6%), and feeding (33.6%) problems, with variation in frequency by age. ND and MH conditions were reported in one quarter, most commonly autism spectrum disorder and attention-deficit/hyperactivity disorder. Those with ND and MH conditions had greater frequency of medical conditions, with highest rates of vision, ear/hearing, and gastrointestinal issues, and CHD. Systematically collected clinical data in a large cohort of children with DS reveals high prevalence of several co-occurring medical, ND, and MH conditions. Clinical care requires an understanding of the complex relationship between medical conditions and neurodevelopment.

Cardiometabolic profiles in children and adults with overweight and obesity and down syndrome.

Individuals with Down syndrome (DS) are at increased risk for being overweight/obese, but the associated cardiometabolic risk (CR) is not clear. Cross-sectional anthropometric and clinical laboratory data from a multi-site, international cohort of individuals with DS were analyzed to determine cardiometabolic risk by reporting observed distributions of cardiometabolic biomarkers in overweight/obese individuals with DS throughout the lifespan. Descriptive statistics and regression analyses by age categories determined the distributive percentiles for cardiometabolic biomarkers and tested for adiposity as a predictor of CR. Across seven DS clinics, data were collected on 240 patients between the ages of 3 and 63 years, with one quarter overweight and three quarters obese among children and nearly all adults being obese. In children and adults, most cardiometabolic biomarker profiles showed distributive values within normal ranges. Blood lipids were positively associated with body mass index (BMI) in children (high density lipid-cholesterol, p = 0.01; low density lipid-cholesterol, p = 0.02). Levels of hs-CRP were elevated in both children and adults, with BMI positively associated with hs-CRP in adults with DS (p = 0.04). Liver enzyme values were positively associated with BMI in children and adults. The data suggest that in contrast to the general population, in individuals with Down syndrome, being overweight and obese does not appear to confer a significantly increased risk for cardiometabolic disease by biomarker profile. Individuals with DS who are overweight/obese appear to have unique cardiometabolic profiles unrelated to adiposity, notable for increased hs-CRP and normal HA1c levels.

Development and implementation of a longitudinal clinical database for down syndrome in a large pediatric specialty clinic: Methodology and feasibility.

Down syndrome (DS) is a complex condition associated with multiple medical, developmental, and behavioral concerns. A prospective, longitudinal clinical database was integrated into a specialty Down Syndrome Program, with the goals of better understanding the incidence, course, and impact of co-occurring medical, neurodevelopmental, and mental health conditions in DS. We describe the process of developing the database, including a systematic approach to data collection and database infrastructure, and report on feasibility, challenges, and solutions of initial implementation. Between March 2018 and November 2021, data from 842 patients (ages 4.8 months to 26 years) was collected. Challenges included caregiver form completion as well as time and personnel required for successful implementation. With full integration into clinical visit flow, the database proved to be feasible. The database enables identification of patterns of development and health throughout the lifespan and it facilitates future data sharing and collaborative research to advance care.

Unexplained regression in Down syndrome: Management of 51 patients in an international patient database.

Research to guide clinicians in the management of the devastating regression which can affect adolescents and young adults with Down syndrome is limited. A multi-site, international, longitudinal cohort of individuals with a clinical diagnosis of Unexplained Regression in Down syndrome (URDS) was collated through seven Down syndrome clinics. Tiered medical evaluation, a 28-item core symptom list, and interim management are described naturalistically. Improvement-defined by the percentage of baseline function on a Parent-reported Functional Score, overall improvement in symptoms on a Clinician-administered Functional Assessment, or report of management type being associated with improvement-was analyzed. Improvement rates using ECT, IVIG, and others were compared. Across seven clinics, 51 patients with URDS had regression at age 17.6 years, on average, and showed an average 14.1 out of 28 symptoms. Longitudinal improvement in function was achieved in many patients and the medical management, types of treatment, and their impact on function are described. Management with intravenous immunoglobulin (IVIG) was significantly associated with higher rate of improvement in symptoms at the next visit (p = 0.001). Our longitudinal data demonstrates that URDS is treatable, with various forms of clinical management and has a variable course. The data suggests that IVIG may be an effective treatment in some individuals. Our description of the management approaches used in this cohort lays the groundwork for future research, such as development of standardized objective outcome measure and creation of a clinical practice guideline for URDS.

Is Developmental Regression in Down Syndrome Linked to Life Stressors?

OBJECTIVE: Unexplained regression in Down syndrome (URDS) involves a loss of acquired skills resulting in functional deterioration. Despite extensive workup and treatment, few individuals regain baseline function. This study aimed to understand the role of psychosocial stressors in URDS. METHODS: We describe psychosocial stressors in 14 cases of URDS. Specifically, we examined psychosocial stressors in the context of presentation and clinical symptoms. We also examined co-occurring neurodevelopmental disorders and medical and mental health conditions. RESULTS: All individuals experienced psychosocial stressors within one year of diagnosis of URDS. The most common psychosocial stressors were moving to a new home or school. CONCLUSION: Psychosocial stressors are commonly reported preceding URDS. Knowledge about psychosocial stressors' impact may lead to preventive interventions, improved monitoring, and earlier diagnosis. Future research should focus on understanding psychosocial stressors to help identify individuals at risk for URDS and contribute to treatment.

Autism Spectrum Disorder Parent Report for Outcome Monitoring: A Preliminary Report of Development and Clinical Utility.

OBJECTIVE: Children with autism spectrum disorder (ASD) face challenges across many functional domains. A tool that gathers relevant clinical information before visits, emphasizing symptoms that are likely to change over development and inform clinical interventions, could improve health care quality, allowing for more patient-centered and efficient care. This study evaluated the clinical utility and preliminary psychometrics of the ASD Parent Report for Outcome Monitoring (ASD-PROM), a web-based measure assessing competence in core features of ASD, along with the breadth of concerns and comorbidities that frequently co-occur with ASD. METHODS: An interdisciplinary team drafted the ASD-PROM and made iterative revisions based on parent feedback. Parents of 62 children completed the ASD-PROM before their autism-specialty clinical visit, 53 completed the ASD-PROM twice, and 48 completed the Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) concurrently. Parents (n = 25) and clinicians (n = 13) completed postvisit surveys to assess utility (phase 1). The ASD-PROM was then released for general clinical use (phase 2). RESULTS: On a Likert scale (1 = very poorly, 10 = very well), parents found that ASD-PROM items described their child's abilities well (median = 8.0; interquartile range [IQR]: 7.0-9.5) and had a positive effect on care (median = 8.0; IQR: 7.0-10.0). Clinicians found the ASD-PROM effective in assessing parent-reported patient abilities (median = 9.0, IQR: 7.0-9.0) and felt the ASD-PROM helped make their care more patient-centered and efficient (both median = 8.0, IQR: 6.0-9.0). Two-week test-retest reliability was acceptable (0.95). ASD-PROM scores correlated positively with scores from similar domains on the Vineland-II (Pearson r 0.30-0.50, medium to large effects). CONCLUSION: The ASD-PROM is a freely available tool to gather information on developmental and behavioral functioning in children with ASD before autism-specialty clinical visits. Clinical utility and preliminary psychometrics are promising, although limitations (including a low response rate during clinical use and a need for additional in-depth assessments and potential resulting modifications to the tool) remain to be addressed. Ultimately, the ASD-PROM may help promote patient-centered and efficient care for children across a wide range of ages and developmental levels.

International/Institutional Trauma in Developmental Pediatric Practice.

CASE: "Aabis" is a school-aged boy from a predominantly conservative Muslim nation who presented to a tertiary developmental-behavioral pediatric (DBP) clinic to seek "expert opinion" for significant social and learning difficulties in the context of a history of frequent falling and "clumsiness." He was seen by a psychiatrist in his home country, who ordered an electroencephalogram and "brain map" (both normal), and received occupational and physical therapies. Frequent tantrums and intense emotional reactions to minor events-revealed to be related to a history of repeated physical beatings from groups of his "friends"-prompted referral to the DBP clinic. When asked why he did not fight back, Aabis said that he did not want to lose his friends. He and his parents further explained that this kind of organized aggression is considered part of normative development in their country and that Aabis needed to "toughen up."Aabis was described by his parents as being very "sensitive" when others raised their voices, shivering when reprimanded and profusely apologizing for real and imagined mistakes. He bit his nails until they bled, washed his hands repetitively, and changed his clothes several times per day. On witnessing his parents arguing, Aabis threatened to harm himself with a decorative knife.The assessment presented with several procedural complications specifically the use of an interpreter and the cultural differences regarding many of the topics discussed. Aabis spoke very little English, and an interpreter was not available in person on the initial day of the assessment. Telephonic phone translation services were attempted, but there were concerns that Aabis would not feel comfortable with sharing his emotions over the phone with an unidentified individual. As feared, Aabis was resistant to discuss emotionally charged topics (e.g., feeling sad, being bullied, hearing or seeing things) and grew impatient and irritated with the phone interpreter. After some unsuccessful experimentation with a Google-based translation system (implemented at Aabi's request to help build comfort and rapport), a second telephonic interpreter was brought into the session, who Aabis later described to his parents as "mean." (Aabis clarified that the second interpreter had been brusque and insensitive to his tentative attempts to express his feelings, e.g., by telling him to "Speak up. Spit it out.")Toward the end of the interview, Aabis seemed to dissociate and insisted anxiously that he did not want to relay certain information without his parents present in the room. What would you do next in this situation?Details about this case, including name and age, have been altered to protect the child's identity.