Genetic and Environmental Factors in Pre- and Postnatal Growth Disorders: Studies in children born small for gestational age (SGA), with and without postnatal short stature

Th is thesis describes genetic and environmental factors which are important in pre- and postnatal growth disorders and specifi cally focuses on children born small for gestational age (SGA) with or without postnatal catch-up growth. It also presents a subclassifi cation of short SGA subjects according to length, weight and head circumference at birth. In addition, it reports investigations in three genes which have been found to play a central role in growth regulation: the insulinlike growth factor 1 (IGF1), the insulin-like growth factor 1 receptor (IGF1R) and the insulin (INS) gene and their associations with short SGA and SGA catch-up subjects. In addition, the thesis describes the results of a study into relatively large deletions and duplications (also called “copy number changes”) in 18 growth-related genes, performed in short SGA subjects. Th e last chapter describes phenotypic data of a large group of subjects participating in the Network of European Studies in Genes in growth (NESTEGG). Th is group consisted of subjects born SGA, either with persistent short or normal stature, idiopathic short stature (ISS) and controls. Finally, the aims of the study and outline of this thesis are described

How do primary care providers and autistic adults want to improve their primary care?: a Delphi-study

Autistic adults often experience health problems and a range of healthcare barriers. Therefore, the aim of this study was to evaluate barriers and explore how primary care providers and autistic adults want to improve their primary healthcare. Semi-structured interviews with three autistic adults, two parents of autistic children and six care providers, were performed to evaluate barriers in Dutch healthcare. Next, in a three-round Delphi-study, 21 autistic adults and 20 primary care providers rated barriers in primary healthcare and assessed recommendations based on usefulness and feasibility. In the thematically analysed interviews, 20 barriers in Dutch healthcare for autistic people were identified. In the Delphi-study, the primary care providers rated the negative impact of most barriers lower than the autistic adults. The Delphi-study resulted in 22 recommendations to improve primary healthcare for autistic adults, focused on: primary care providers (i.e. education in collaboration with autistic people), autistic adults (i.e. improvement of preparation for general practitioner-appointments) and organization of general practice (i.e. enhancement of continuity in care). In conclusion, primary care providers seem to assess healthcare barriers as less impactful than autistic adults. With the use of the Delphi-method, useful and feasible recommendations to improve primary healthcare for autistic adults were identified, based on the needs of autistic adults and primary care providers. Lay abstract Autistic adults often encounter different types of healthcare barriers. Because autistic adults also have an increased risk for health problems, the aim of this study was to evaluate barriers and to explore how primary care providers and autistic adults want to improve their primary healthcare. In this co-created study, semi-structured interviews with three autistic adults, two parents of autistic children and six care providers were performed to evaluate barriers in Dutch healthcare. Next, in the survey-study (using the Delphi-method including controlled feedback in three consecutive questionnaires), 21 autistic adults and 20 primary care providers rated the impact of barriers and the usefulness and feasibility of recommendations to improve primary healthcare. In the interviews, 20 barriers in Dutch healthcare for autistic people were found. In the survey-study, the primary care providers rated the negative impact of most barriers lower than the autistic adults. This survey-study resulted in 22 recommendations to improve primary healthcare focused on: primary care providers (including education in collaboration with autistic people), autistic adults (including improvement of preparation for general practitioner-appointments) and organization of general practice (including improvement of continuity in care). In conclusion, primary care providers seem to view healthcare barriers as less impactful than autistic adults. In this co-created study, recommendations to improve primary healthcare for autistic adults were identified, based on the needs of autistic adults and primary care providers. These recommendations provide a basis for primary care providers, autistic adults and their support network to start conversations about, for example, strategies to improve primary care providers' knowledge, autistic adults' preparation for a general practitioner-appointment and organization of primary care.New methods for child psychiatric diagnosis and treatment outcome evaluatio

Subclassification of small for gestational age children with persistent short stature: Growth patterns and response to GH treatment

Aim: We determined whether subclassification of short small for gestational age (SGA) children according to birth anthropometrics could delineate differen

Effectivity of play-based interventions in children with autism spectrum disorder and their parents: a systematic review

Education and Child Studie

Risperidone plasma concentrations are associated with side effects and effectiveness in children and adolescents with autism spectrum disorder

Aim: Risperidone is the most commonly prescribed antipsychotic drug to children and adolescents worldwide, but it is associated with serious side effects, including weight gain. This study assessed the relationship of risperidone and 9-hydroxyrisperidone trough concentrations, maximum concentrations and 24-hour area under the curves (AUCs) with body mass index (BMI) z-scores in children and adolescents with autism spectrum disorder (ASD) and behavioural problems. Secondary outcomes were metabolic, endocrine, extrapyramidal and cardiac side effects and effectiveness. Methods: Forty-two children and adolescents (32 males) aged 6-18 years were included in a 24-week prospective observational trial. Drug plasma concentrations, side effects and effectiveness were measured at several time points during follow-up. Relevant pharmacokinetic covariates, including medication adherence and CYP2D6, CYP3A4, CYP3A5 and P-glycoprotein (ABCB1) genotypes, were measured. Nonlinear mixed-effects modelling (NONMEM®) was used for a population pharmacokinetic analysis with 205 risperidone and 205 9-hydroxyrisperidone concentrations. Subsequently, model-based trough concentrations, maximum concentrations and 24-hour AUCs were analysed to predict outcomes using generalized and linear mixed-effects models. Results: A risperidone two-compartment model combined with a 9-hydroxyrisperidone one-compartment model best described the measured concentrations. Of all the pharmacokinetic parameters, higher risperidone sum trough concentrations best predicted higher BMI z-scores during follow-up (P <.001). Higher sum trough concentrations also predicted more sedation (P <.05), higher prolactin levels (P <.001) and more effectiveness measured with Aberrant Behavior Checklist irritability score (P <.01). Conclusion: Our results indicate a therapeutic window exists, which suggests that therapeutic drug monitoring of risperidone might increase safety and effectiveness in children and adolescents with ASD and behavioural problems

Recommendations to improve primary healthcare for people with autism: a Delphi-study

Autistic people often experience health problems and a range of healthcare barriers. Therefore, the aim of this study was to evaluate barriers and identify recommendations to improve primary healthcare for autistic people. Semi-structured interviews with 11 adults ((parents of) autistic people and healthcare providers (HCPs)) were performed to evaluate barriers in Dutch healthcare. Next, in the Delphi-study, a panel of 21 autistic adults and 20 primary HCPs rated barriers in primary healthcare and assessed recommendations based on usefulness and feasibility. In the thematically analysed interviews, 20 barriers in Dutch healthcare for autistic people were identified. In the Delphi-study, primary HCPs rated the negative impact of most barriers relatively lower than the autistic participants. The Delphi-study resulted in 22 recommendations to improve primary healthcare for autistic people: focused on primary HCPs (i.e., education with input from autistic people), on autistic people (i.e., improvement of preparation for GP-appointments), and on organization of general practice (i.e., improvement of continuity in care). Primary HCPs seem to assess healthcare barriers as less impactful than autistic adults. With use of the Delphi-method, useful and feasible recommendations to improve primary healthcare for autistic people were identified, based on the needs of autistic adults and primary HCPs

Stress, Eating Behavior and Adverse Health in Parents of Young Children with Autism Spectrum Disorder

Mothers of children with Autism Spectrum Disorder (ASD) often experience chronic stress and are at risk for adverse health. However, little is known about fathers, especially when their child is in early childhood. Parenting stress, eating behavior and physical health was evaluated in mothers (n = 48) and fathers (n = 43) of young children (3-7 years) with ASD by questionnaires and physical measurements. Mother's prevalence rates of obesity (39.1%), abdominal obesity (59.6%) and metabolic syndrome (21.6%) were higher than the norm. In fathers, the prevalence rate of clinical parenting stress (33%) was higher than the norm. Parenting stress was positively related to disinhibited eating in mothers, not in fathers. It is crucial to monitor stress and health of parents of children with ASD.New methods for child psychiatric diagnosis and treatment outcome evaluatio