Population Pharmacokinetics of Prednisolone in Relation to Clinical Outcome in Children With Nephrotic Syndrome.

Background: The relapse frequency in children with nephrotic syndrome (NS) is highly variable despite standardized prednisolone treatment regimens. Existing evidence on the relationship between prednisolone pharmacokinetics (PK) and clinical response in children with NS is scarce and limited. The aim of this study was to develop a pediatric popPK model for prednisolone based on our previous model based on healthy adults using salivary measurements in children with NS and to correlate clinical outcome with between-subject variability in prednisolone exposure.

Childhood kidney outcomes in relation to fetal blood flow and kidney size.

Impaired fetal abdominal blood flow may lead to smaller kidneys and subsequent impaired kidney function in later life. In a prospective cohort study among 923 pregnant women and their children, we measured fetal growth, kidney volumes, and umbilical and cerebral artery blood flow (median gestational age of 30.3 weeks; 95% range, 28.

Fetal and infant growth patterns and kidney function at school age.

Low birth weight is associated with ESRD. To identify specific growth patterns in early life that may be related to kidney function in later life, we examined the associations of longitudinally measured fetal and infant growth with kidney function in school-aged children. This study was embedded in a population-based prospective cohort study among 6482 children followed from fetal life onward.

Kidney size and function in a multi-ethnic population-based cohort of school-age children.

Background: Subclinical impaired kidney growth and function in childhood may lead to kidney diseases and high blood pressure in adulthood. We assessed the cross-sectional associations of childhood characteristics with kidney size and function in a multi-ethnic cohort.

Methods: This study was embedded in a population-based cohort study of 6,397 children with a median age of 6.

Genetic and in vivo determinants of glucocorticoid sensitivity in relation to clinical outcome of childhood nephrotic syndrome.

Following initial glucocorticoid treatment, the clinical course in children with nephrotic syndrome is highly variable. Intrinsic sensitivity to glucocorticoids might be a determinant of this variability. Functional polymorphisms of the glucocorticoid receptor gene NR3C1 have been associated with either relatively impaired (GR-9β) or increased (BclI) glucocorticoid sensitivity.

Parental smoking during pregnancy and cardiovascular structures and function in childhood: the Generation R Study.

Background: Foetal smoke exposure might lead to foetal developmental adaptations that permanently affect the cardiovascular system. We assessed the associations of both maternal and paternal smoking during pregnancy with childhood cardiovascular structures and function.

Method: In a prospective cohort study among 5565 children, we examined whether maternal and paternal smoking during pregnancy are associated with blood pressure, carotid-femoral pulse wave velocity and left cardiac structures and function in 6-year-old children.

Maternal first-trimester dietary intake and childhood blood pressure: the Generation R Study.

Suboptimal maternal dietary intake during pregnancy might lead to fetal cardiovascular adaptations and higher blood pressure in the offspring. The aim of the present study was to investigate the associations of maternal first-trimester dietary intake with blood pressure in children at the age of 6 years. We assessed first-trimester maternal daily dietary intake by a FFQ and measured folate, homocysteine and vitamin B₁₂ concentrations in the blood, in a population-based prospective cohort study among 2863 mothers and children.

Parental psychological distress during pregnancy and childhood cardiovascular development. The Generation R Study.

Background: Maternal psychological distress during pregnancy might lead to higher fetal cortisol exposure, which subsequently leads to fetal cardiovascular developmental adaptations and cardiovascular dysfunction in later life.

Aims: We examined whether maternal and paternal psychological distress was associated with the cardiovascular outcome measurements in school age children.

Study Design And Subjects: In a population-based prospective cohort study among 4831 children, we assessed maternal and paternal psychological distress during pregnancy by questionnaire, using the Brief Symptom Inventory (see Fig.

Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome.

Prolonged prednisolone treatment for the initial episode of childhood nephrotic syndrome may reduce relapse rate, but whether this results from the increased duration of treatment or a higher cumulative dose remains unclear. We conducted a randomized, double-blind, placebo-controlled trial in 69 hospitals in The Netherlands. We randomly assigned 150 children (9 months to 17 years) presenting with nephrotic syndrome to either 3 months of prednisolone followed by 3 months of placebo (n=74) or 6 months of prednisolone (n=76), and median follow-up was 47 months.

The Generation R Study: design and cohort update 2012.

The Generation R Study is a population-based prospective cohort study from fetal life until adulthood. The study is designed to identify early environmental and genetic causes and causal pathways leading to normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on six areas of research: (1) maternal health; (2) growth and physical development; (3) behavioural and cognitive development; (4) respiratory health and allergies; (5) diseases in childhood; and (6) health and healthcare for children and their parents.

Common variants at 12q15 and 12q24 are associated with infant head circumference.

To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 × 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.

Genetic variants associated with adult blood pressure and kidney function do not affect fetal kidney volume. The Generation R Study.

Background: Smaller kidneys with reduced number of nephrons in early life lead to impaired kidney function and risk for hypertension and chronic kidney disease. These associations might be partly explained by common genetic variation.

Aims: To assess the associations between common genetic variants, which have recently shown to be associated with blood pressure or kidney function, with fetal kidney volume.

Genome-wide profiling of blood pressure in adults and children.

Hypertension is an important determinant of cardiovascular morbidity and mortality and has a substantial heritability, which is likely of polygenic origin. The aim of this study was to assess to what extent multiple common genetic variants contribute to blood pressure regulation in both adults and children and to assess overlap in variants between different age groups, using genome-wide profiling. Single nucleotide polymorphism sets were defined based on a meta-analysis of genome-wide association studies on systolic blood pressure and diastolic blood pressure performed by the Cohort for Heart and Aging Research in Genome Epidemiology (n=29 136), using different P value thresholds for selecting single nucleotide polymorphisms.

Maternal smoking during pregnancy and kidney volume in the offspring: the Generation R Study.

An adverse fetal environment leads to smaller kidneys, with fewer nephrons, which might predispose an individual to the development of kidney disease and hypertension in adult life. In a prospective cohort study among 1,072 children followed from early fetal life onward, we examined whether maternal smoking during pregnancy, as a significant adverse fetal exposure, is associated with fetal (third trimester of pregnancy, n = 1,031) and infant kidney volume (2 years of age, n = 538) measured by ultrasound. Analyses were adjusted for various potential confounders.

The Generation R Study: design and cohort update 2010.

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children.

Kidney growth curves in healthy children from the third trimester of pregnancy until the age of two years. The Generation R Study.

Information about growth of kidney structures in early life is limited. In a population-based prospective cohort study, from foetal life onwards, we constructed reference curves for kidney growth from the third trimester of pregnancy until early childhood, using data from 1,158 healthy children. Kidney size, defined as length, width, depth and volume, was measured in the third trimester of pregnancy and at the postnatal ages of 6 months and 24 months.

Cardiac structures track during the first 2 years of life and are associated with fetal growth and hemodynamics: the Generation R Study.

Background: The aim of this study is to examine whether cardiac size and function track in early childhood and are associated with fetal and early postnatal growth and blood flow characteristics.

Methods: This study was embedded in a population-based prospective cohort study from fetal life onward. Fetal growth and fetal and placental blood flow parameters in second and third trimester of pregnancy were measured by ultrasound and Doppler.

Reliability of renal ultrasound measurements in children.

The aim of the investigation reported here was to assess the intraobserver and interobserver variability of renal measurements in children. The study comprised 56 paired measurements in 28 children (median age 7.5 years, range 3.

[The practice guideline 'Children with fever' (second revision) from the Dutch College of General Practitioners; a response from the perspective of paediatricians].

The new version of the practice guideline 'Children with fever' was recently published by the Dutch College of General Practitioners and is commented on from the perspective of paediatricians. Whether or not general practitioners should refer feverish children to the paediatrician depends on the age of the patient and the severity of the illness. All children younger than 1 month and children with warning symptoms should be referred to a paediatrician at once.

The Generation R Study: design and cohort update until the age of 4 years.

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health from fetal life until young adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children.

Tracking and determinants of kidney size from fetal life until the age of 2 years: the Generation R Study.

Background: An adverse fetal environment may lead to smaller kidneys and subsequently kidney disease and hypertension in adulthood. The aims of this study are to examine whether kidney size tracks from fetal life to childhood and whether maternal and fetal characteristics are associated with kidney size at the age of 2 years.

Study Design: Prospective cohort study from fetal life onward.

Nephrocalcinosis in preterm neonates.

The prevalence of nephrocalcinosis (NC) in preterm neonates in recent reports is 7-41%. The wide range in prevalence is a consequence of different study populations and ultrasound equipment and criteria, in addition to a moderate interobserver variation. NC in preterm neonates has a multifactorial aetiology, consisting of low gestational age and birth weight, often in combination with severe respiratory disease, and occurs as a result of an imbalance between stone-promoting and stone-inhibiting factors.

Mycophenolate mofetil versus cyclosporine for remission maintenance in nephrotic syndrome.

We performed a multi-centre randomized controlled trial to compare the efficacy of mycophenolate mofetil (MMF) to that of cyclosporine A (CsA) in treating children with frequently relapsing nephrotic syndrome and biopsy-proven minimal change disease. Of the 31 randomized initially selected patients, seven were excluded. The remaining 24 children received either MMF 1200 mg/m(2) per day (n = 12) or CsA 4-5 mg/kg per day (n = 12) during a 12-month period.

The Generation R Study Biobank: a resource for epidemiological studies in children and their parents.

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health from fetal life until young adulthood. In total, 9,778 mothers were enrolled in the study.