Intellectual Disability in Children with Congenital Heart Defects in Western Australia

Introduction Congenital heart defects (CHD) are diagnosed up to age 6 in 8-12/1,000 births annually in Western Australia. Recent improvements in management of infants with CHDs has significantly increased survival; approximately 85\% of infants with CHDs live beyond childhood. However, children with CHDs may have increased risk of life-long intellectual disabilities. Objectives and Approach We conducted a study of 20,997 children to determine risk of intellectual disability (ID). All singleton, live born infants with CHDs born 1983-2010 were identified from the Western Australian Register for Developmental Anomalies, a statewide birth defects registry (n=6,968). Infants without CHDs born 1983-2010 were randomly selected from birth records (n=14,029). All data were linked to the Western Australia Midwives Notification System to obtain maternal and infant information. Children with ID were identified by linkage to the statewide Intellectual Disability Exploring Answers database. Risk ratios (RR) and 95% confidence intervals (CI) were calculated from multivariable logistic regression analyses. Results Of 20,997 children, 965 (4.6%) had an ID; 1.3% of children without CHDs and 11.2% of children with CHDs had an ID (P<0.001). 0.2% of children without CHDs and 0.4% of children with CHDs had autism. Three percent of children with CHDs had a known biomedical cause for ID (excluding trisomy 21) and 4.4% of children with CHDs had trisomy 21. Children with CHDs had 9 times the risk of ID compared to children without CHDs (RR=9.30; 95% CI: 7.91, 10.94). Children with CHDs almost had a twofold increased risk of autism compared to children without CHDs (RR=1.78; 95% CI: 1.07, 2.95). The greatest risk of ID among children with CHDs was associated with trisomy 21 (RR=166.0; 95% CI: 78.5, 350.8). Conclusion/Implications Children with CHDs have higher risk of ID than children without CHDs. Although the greatest risk for ID was for trisomy 21, children with CHDs still had increased risk of ID from other causes and all causes overall. Future research should elucidate the underlying etiology of ID in these children

Evaluation of the Western Australian population based data linkage Intellectual Disability Exploring Answers (IDEA) surveillance system

Introduction The IDEA system is a population-based data linkage system for intellectual disability (ID), which combines data from two government departments. Due to recent policy changes the future of the IDEA system is unknown. Understanding the IDEA system's strengths and limitations will provide data custodians with the opportunity to re-design the system. Objectives and Approach An evaluation of the IDEA surveillance system was undertaken to assess the quality, efficiency and usefulness of the system. The primary objectives were to evaluate systematically and objectively the attributes of the system and provide recommendations to data custodians and stakeholders to strengthen the surveillance system. The evaluation was based on the methods from the 2001 U.S. Centers for Disease Control and Prevention guidelines on evaluation of public health surveillance systems. We assessed the following system attributes: usefulness, simplicity, flexibility, data quality, acceptability, representativeness, timeliness, and stability. This was completed by process observation, semi-structured interviews and data analysis. Results Our results found the IDEA system was flexible, acceptable, representative, timely and stable. Given data linkage process and maintaining confidentiality the data linkage process was considered relatively simple. We compared individuals in the IDEA surveillance system to a sub-group of individuals, cerebral palsy with ID, to the mandatory reporting surveillance system WARDA-CP. There were 582 individuals identified in the WARDA-CP surveillance system as having cerebral palsy and ID. Of those identified 501 (86.1%) were also in the IDEA database and 81 (13.9%) were not. There were little differences in WARDA-CP cases that were not identified in the IDEA system between Indigenous status, sex and place of residence. Conclusion/Implications The IDEA system has successfully been used to understand prevalence rates and inform resource allocation. Advocacy organisations could play an important role in the sustainability of the system. Additional variables or enhanced surveillance for functional capacity could strengthen the system and provide important information to inform policy and practice

Costs of reproduction are present but latent in eusocial bumblebee queens

Background: The standard evolutionary theory of ageing proposes that ageing occurs because of a trade-off between reproduction and longevity. Eusocial insect queens exhibit positive fecundity-longevity associations and so have been suggested to be counter-examples through not expressing costs of reproduction and through remodelling conserved genetic and endocrine networks regulating ageing and reproduction. If so, eusocial evolution from solitary ancestors with negative fecundity-longevity associations must have involved a stage at which costs of reproduction were suppressed and fecundity and longevity became positively associated. Using the bumblebee (Bombus terrestris), we experimentally tested whether queens in annual eusocial insects at an intermediate level of eusocial complexity experience costs of reproduction, and, using mRNA-seq, the extent to which they exhibit a remodelling of relevant genetic and endocrine networks. Specifically, we tested whether costs of reproduction are present but latent, or whether a remodelling of relevant genetic and endocrine networks has already occurred allowing queens to reproduce without costs. Results: We experimentally increased queens’ costs of reproduction by removing their eggs, which caused queens to increase their egg-laying rate. Treatment queens had significantly reduced longevity relative to control queens whose egg-laying rate was not increased. Reduced longevity in treatment queens was not caused by increased worker-to-queen aggression or by increased overall activity in queens. In addition, treatment and control queens differed in age-related gene expression based on mRNA-seq in both their overall expression profiles and the expression of ageing-related genes. Remarkably, these differences appeared to occur principally with respect to relative age, not chronological age. Conclusions: This study represents the first simultaneously phenotypic and transcriptomic experimental test for a longevity cost of reproduction in eusocial insect queens. The results support the occurrence of costs of reproduction in annual eusocial insects of intermediate social complexity and suggest that reproductive costs are present but latent in queens of such species, i.e. that these queens exhibit condition-dependent positive fecundity-longevity associations. They also raise the possibility that a partial remodelling of genetic and endocrine networks underpinning ageing may have occurred in intermediately eusocial species such that, in unmanipulated conditions, age-related gene expression depends more on chronological than relative age

Developmental diet alters the fecundity-longevity relationship and age-related gene expression in Drosophila melanogaster

The standard evolutionary theory of aging predicts a negative relationship (trade-off) between fecundity and longevity. However, in principle, the fecundity-longevity relationship can become positive in populations in which individuals have unequal resources. Positive fecundity-longevity relationships also occur in queens of eusocial insects such as ants and bees. Developmental diet is likely to be central to determining trade-offs as it affects key fitness traits, but its exact role remains uncertain. For example, in Drosophila melanogaster, changes in adult diet can affect fecundity, longevity, and gene expression throughout life, but it is unknown how changes in developmental (larval) diet affect fecundity-longevity relationships and gene expression in adults. Using D. melanogaster, we tested the hypothesis that varying developmental diet alters the directionality of fecundity-longevity relationships in adults, and characterised associated gene expression changes. We reared larvae on low (20%), medium (100%), and high (120%) yeast diets, and transferred adult females to a common diet. We measured fecundity and longevity of individual adult females and profiled gene expression changes with age. Adult females raised on different larval diets exhibited fecundity-longevity relationships that varied from significantly positive to significantly negative, despite minimal differences in mean life-time fertility or longevity. Treatments also differed in age-related gene expression, including for aging-related genes. Hence the sign of fecundity-longevity relationships in adult insects can be altered and even reversed by changes in larval diet quality. By extension, larval diet differences may represent a key mechanistic factor underpinning positive fecundity-longevity relationships observed in species such as eusocial insects

Early mortality and primary causes of death in mothers of children with ID or ASD: a retrospective cohort study

INTRODUCTION: Mothers of children with intellectual disability or autism spectrum disorder (ASD) have poorer health than other mothers. Yet no research has explored whether this poorer health is reflected in mortality rates or whether certain causes of death are more likely. We aimed to calculate the hazard ratios for death and for the primary causes of death in mothers of children with intellectual disability or ASD compared to other mothers. METHODS: The study population comprised all mothers of live-born children in Western Australia from 1983-2005. We accessed state-wide databases which enabled us to link socio-demographic details, birth dates, diagnoses of intellectual disability or ASD in the children and dates and causes of death for all mothers who had died prior to 2011. Using Cox Regression with death by any cause and death by each of the three primary causes as the event of interest, we calculated hazard ratios for death for mothers of children intellectual disability or ASD compared to other mothers. RESULTS AND DISCUSSION: During the study period, mothers of children with intellectual disability or ASD had more than twice the risk of death. Mothers of children with intellectual disability were 40% more likely to die of cancer; 150% more likely to die of cardiovascular disease and nearly 200% more likely to die from misadventure than other mothers. Due to small numbers, only hazard ratios for cancer were calculated for mothers of children with ASD. These mothers were about 50% more likely to die from cancer than other mothers. Possible causes and implications of our results are discussed. CONCLUSION: Similar studies, pooling data from registries elsewhere, would improve our understanding of factors increasing the mortality of mothers of children with intellectual disability or ASD. This would allow the implementation of informed services and interventions to improve these mothers' longevity

Influence of the Environment on Participation in Social Roles for Young Adults with Down Syndrome

Background: The concept of disability is now understood as a result of the interaction between the individual, features related to impairment, and the physical and social environment. It is important to understand these environmental influences and how they affect social participation. The purpose of this study is to describe the social participation of young adults with Down syndrome and examine its relationship with the physical and social environment. Methods: Families ascertained from the Down syndrome ‘Needs Opinion Wishes’ database completed questionnaires during 2011. The questionnaires contained two parts, young person characteristics and family characteristics. Young adults’ social participation was measured using the Assessment of Life Habits (LIFE-H) and the influences of environmental factors were measured by the Measure of the Quality of the Environment (MQE). The analysis involved descriptive statistics and linear and logistic regression. Results: Overall, participation in daily activities was higher (mean 6.45) than in social roles (mean 5.17) (range 0 to 9). When the physical and/or social environment was reported as a facilitator, compared to being no influence or a barrier, participation in social roles was greater (coef 0.89, 95%CI 0.28, 1.52, coef 0.83, 95%CI 0.17, 1.49, respectively). The relationships between participation and both the physical (coef 0.60, 95% CI -0.40, 1.24) and social (coef 0.20, 95%CI -0.47, 0.87) environments were reduced when age, gender, behavior and functioning in ADL were taken into account. Conclusion: We found that young adults’ participation in social roles was influenced more by the physical environment than by the social environment, providing a potentially modifiable avenue for intervention

Impacts of caring for a child with the CDKL5 disorder on parental wellbeing and family quality of life

Background: Although research in this area remains sparse, raising a child with some genetic disorders has been shown to adversely impact maternal health and family quality of life. The aim of this study was to investigate such impacts in families with a child with the CDKL5 disorder, a newly recognised genetic disorder causing severe neurodevelopmental impairments and refractory epilepsy. Methods: Data were sourced from the International CDKL5 Disorder Database to which 192 families with a child with a pathogenic CDKL5 mutation had provided data by January 2016. The Short Form 12 Health Survey Version 2, yielding a Physical Component Summary and a Mental Component Summary score, was used to measure primary caregiver's wellbeing. The Beach Center Family Quality of Life Scale was used to measure family quality of life. Linear regression analyses were used to investigate relationships between child and family factors and the various subscale scores. Results: The median (range) age of the primary caregivers was 37.0 (24.6-63.7) years and of the children was 5.2 (0.2-34.1) years. The mean (SD) physical and mental component scores were 53.7 (8.6) and 41.9 (11.6), respectively. In mothers aged 25-54 years the mean mental but not the physical component score was lower than population norms. After covariate adjustment, caregivers with a tube-fed child had lower mean physical but higher mean mental component scores than those whose child fed orally (coefficient = -4.80 and 6.79; p = 0.009 and 0.012, respectively). Child sleep disturbances and financial hardship were negatively associated with the mental component score. The mean (SD) Beach Center Family Quality of Life score was 4.06 (0.66) and those who had used respite services had lower scores than those who had not across the subscales. Conclusions: Emotional wellbeing was considerably impaired in this caregiver population, and was particularly associated with increased severity of child sleep problems and family financial difficulties. Family quality of life was generally rated lowest in those using respite care extensively, suggesting that these families may be more burdened by daily caregiving

Day occupation is associated with psychopathology for adolescents and young adults with Down syndrome

Background: Young adults with Down syndrome experience increased rates of emotional and behavioural problems compared with the general population. Most adolescents with Down syndrome living in Western Australia participate in sheltered employment as their main day occupation. Relationship between day occupation and changes in behaviour has not been examined. Therefore, the aim of this research was to explore any relationship between post school day occupations and changes in the young person’s behaviour. Methods: The Down syndrome Needs Opinion Wishes database was used for case ascertainment of young adults aged 15 to 32 years with Down syndrome. Families of 118 young people in this population-based database completed questionnaires in 2004, 2009 and 2011. The questionnaires addressed both young person characteristics such as age, gender, presence of impairments, behaviour, functioning in activities of daily living, and family characteristics such as income and family functioning. Post-school day occupations in which the young people were participating included open and sheltered employment, training and day recreation programs. Change in behaviour of young adults who remained in the same post-school day occupation from 2009 to 2011 (n = 103) were examined in a linear regression model adjusting for confounding variables including age, gender, prior functioning and behaviour in 2004 and family income.Results: In comparison to those young adults attending open employment from 2009 to 2011, those attending day recreation programs were reported to experience worsening in behaviour both in the unadjusted (effect size -0.14, 95% CI -0.24, -0.05) and adjusted models (effect size -0.15, 95% CI -0.29, -0.01). Conclusions: We found that the behaviour of those participating in open employment improved compared to those attending other day occupations. Further examination of the direction of this association is required