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

Novel Insights into Obesity in Preschool Children with Autism Spectrum Disorder

Obesity is present in 8–32% of the children with Autism Spectrum Disorder (ASD). However, most studies are performed in school-aged children from the USA. The current study compares obesity rates of Dutch preschoolers with ASD with children from the Dutch general population and explores which child- and parental factors are related to obesity in children with ASD. This cross-sectional study is part of the ongoing Tandem Study (Dutch Trial register: NL7534). Seventy-eight children with ASD aged 3–7 years and their parents (77 mothers, 67 fathers) participated. Child factors are: Body Mass Index (by physical measurement), child eating behavior (Child Eating Behavior Questionnaire), child problem behavior (Child Behavior Checklist), and ASD severity (Autism Diagnostic Observation Scale 2). Parental factors are: BMI (by physical measurement), parental eating behavior (Dutch Eating Behavior Inventory), parenting stress (The Parenting Stress Questionnaire) and highest completed educational level (SES). Children with ASD were 8 times more often obese (16.8%) than children from the general population (2.0%). Child BMI correlated positively with child food approach behavior and maternal BMI, and correlated negatively with child ‘Slowness in eating’. There was no correlation between child BMI and ASD severity, problem behavior, parental eating behavior, parental stress and SES. Thus, Dutch, preschool children with ASD have 8 times higher obesity rates than children from the general population. More attention to obesity risk in research and clinical care could contribute to the quality of life of individuals with ASD and their families. Clinical Trial Registration: Dutch Trial register, NL7534, https://trialsearch.who.int/Trial2.aspx?TrialID=NL7534 .</p

Novel Insights into Obesity in Preschool Children with Autism Spectrum Disorder

Obesity is present in 8–32% of the children with Autism Spectrum Disorder (ASD). However, most studies are performed in school-aged children from the USA. The current study compares obesity rates of Dutch preschoolers with ASD with children from the Dutch general population and explores which child- and parental factors are related to obesity in children with ASD. This cross-sectional study is part of the ongoing Tandem Study (Dutch Trial register: NL7534). Seventy-eight children with ASD aged 3–7 years and their parents (77 mothers, 67 fathers) participated. Child factors are: Body Mass Index (by physical measurement), child eating behavior (Child Eating Behavior Questionnaire), child problem behavior (Child Behavior Checklist), and ASD severity (Autism Diagnostic Observation Scale 2). Parental factors are: BMI (by physical measurement), parental eating behavior (Dutch Eating Behavior Inventory), parenting stress (The Parenting Stress Questionnaire) and highest completed educational level (SES). Children with ASD were 8 times more often obese (16.8%) than children from the general population (2.0%). Child BMI correlated positively with child food approach behavior and maternal BMI, and correlated negatively with child ‘Slowness in eating’. There was no correlation between child BMI and ASD severity, problem behavior, parental eating behavior, parental stress and SES. Thus, Dutch, preschool children with ASD have 8 times higher obesity rates than children from the general population. More attention to obesity risk in research and clinical care could contribute to the quality of life of individuals with ASD and their families. Clinical Trial Registration: Dutch Trial register, NL7534, https://trialsearch.who.int/Trial2.aspx?TrialID=NL7534 .</p

Novel Insights into Autism Knowledge and Stigmatizing Attitudes Toward Mental Illness in Dutch Youth and Family Center Physicians

Education and Child Studie

The impact of raising a child with a developmental or physical health condition in Ethiopia

Objective Raising a child with a developmental disability or physical health condition can have a major impact on the lives of their families, especially in low-income countries. We explored the impact on such families in Ethiopia. Study design A total of 241 child-caregiver dyads were recruited from two public hospitals in Addis Ababa, Ethiopia. Of these, 139 children were diagnosed with a developmental disability (e.g. autism, intellectual disability) and 102 children with a physical health condition (e.g. malnutrition, severe HIV infection). The family quality of life was assessed using caregiver reports on the Pediatric Quality of Life Inventory™ (PedsQL-FIM™). The disability weight score, which is a Global Burden of Disease measure to quantify health loss, was estimated for each child. Results Families with a child with a developmental disability reported lower quality of life than families caring for a child with a physical health condition (p

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

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