Brain structure, executive function and appetitive traits in adolescent obesity.

BACKGROUND: Children with obesity show differences in brain structure, executive function and appetitive traits when compared with lean peers. Little is known on the relationship between brain structure and these traits. OBJECTIVES: To investigate the relationship between differences in brain structure and executive function and appetitive traits, in obese and lean adolescents. METHODS: MRI was used to measure cortical thickness and subcortical volumes. Executive function was measured by a Stop Signal-and a Choice Delay Task. Appetitive traits were measured using the Child Eating Behaviour Questionnaire. RESULTS: Adolescents with obesity had greater volumes of the pallidum; 1.78 mL (SE 0.03, p=0.014), when compared with controls; 1.65 mL (SE 0.02). In the group with obesity, greater pallidum volume was positively associated with the ability to delay reward in the Choice Delay Task (p=0.012). CONCLUSION: The association between pallidum volumes and Choice Delay Task in obese adolescents supports the hypothesis that the pallidum plays an important role in executive dysfunction in obese children.

Disturbed phase relations in white matter hyperintensity based vascular dementia: an EEG directed connectivity study.

OBJECTIVE: White matter hyperintensities (WMH), a feature seen on magnetic resonance imaging (MRI) and regarded to reflect small vessel disease, can lead to vascular dementia (WMH-VaD). In WMH-VaD, cognitive deficits typically consist of executive function disturbances, and reduced information processing speed, regarded as a result of cerebral hypoperfusion. We aimed to investigate whether this patient group has typical functional differences from controls. METHODS: Resting-state encephalography studies of 17 VaD patients and 17 age- and gender matched non-demented controls were analysed in the delta, theta, alpha1 and 2, and beta frequency bands. Undirected functional connectivity between electrodes was established with the Phase Lag Index (PLI) and directed functional connectivity with the directed Phase Lag Index (dPLI). PLI and dPLI were related to performance in cognitive testing. RESULTS: Mean PLI did not differ between patients and controls. In the control group dPLI showed anterior to posterior phase gradients in all bands except the delta band. In the VaD patient group this pattern was significantly different without a clear directional pattern. No relationship with cognition was demonstrated. CONCLUSIONS: This study shows a clear front-to-back direction of connectivity in non-demented controls. In VaD patients with extensive WMH, this pattern is disturbed. SIGNIFICANCE: Structural damage at the regions of long distance white matter tracts may induce changes in the direction of phase relationships of distinct brain regions.

Health outcomes of children born after IVF/ICSI: a review of current expert opinion and literature.

The Sixth Evian Annual Reproduction (EVAR) Workshop Group Meeting was held to evaluate the impact of IVF/intracytoplasmic sperm injection on the health of assisted-conception children. Epidemiologists, reproductive endocrinologists, embryologists and geneticists presented data from published literature and ongoing research on the incidence of genetic and epigenetic abnormalities and congenital malformations in assisted-conception versus naturally conceived children to reach a consensus on the reasons for potential differences in outcomes between these two groups. IVF-conceived children have lower birthweights and higher peripheral fat, blood pressure and fasting glucose concentrations than controls. Growth, development and cognitive function in assisted-conception children are similar to controls. The absolute risk of imprinting disorders after assisted reproduction is less than 1%. A direct link between assisted reproduction and health-related outcomes in assisted-conception children could not be established. Women undergoing assisted reproduction are often older, increasing the chances of obtaining abnormal gametes that may cause deviations in outcomes between assisted-conception and naturally conceived children. However, after taking into account these factors, it is not clear to what extent poorer outcomes are due to the assisted reproduction procedures themselves. Large-scale, multicentre, prospective epidemiological studies are needed to investigate this further and to confirm long-term health consequences in assisted-conception children. Assisted reproduction treatment is a general term used to describe methods of achieving pregnancy by artificial means and includes IVF and sperm implantation. The effect of assisted reproduction treatment on the health of children born using these artificial methods is not fully understood. In April 2011, fertility research experts met to give presentations based on research in this area and to look carefully at the evidence for the effects of assisted reproduction treatment on children's health. The purpose of this review was to reach an agreement on whether there are differences in the health of assisted-conception children with naturally conceived children. The researchers discovered no increased risk in birth defects in assisted-conception children compared with naturally conceived children. They found that IVF-conceived children have lower birth weights and higher fat under the skin, higher blood pressure and higher fasting glucose concentrations than naturally conceived children; however, growth, development and cognitive function are similar between groups. A very low risk of disorders of genetic control was observed in assisted-conception children. Overall, there did not appear to be a direct link between assisted reproduction treatment and children's health. The researchers concluded that the cause of some differences in the health of children conceived using assisted reproduction treatment may be due to the age of the woman receiving treatment. Large-scale, research studies are needed to study the long-term health of children conceived using assisted reproduction treatment.

Long-term effect of the Go4it group treatment for obese adolescents: a randomised controlled trial.

BACKGROUND & AIMS: Few studies evaluating treatment of adolescent obesity have been published. Therefore, long-term effects of the Go4it group treatment for obese adolescents were examined. METHODS: Obese adolescents (11-18 years) visiting an outpatient paediatric obesity clinic were randomly assigned to 1) intervention group (Go4it) or 2) current regular care i.e. referral to a dietician in the home care setting (controls). Linear mixed models analysis was performed to evaluate intervention effects. Effect modification by sex, age and ethnicity was checked. Outcome measures included body mass index standard deviation score (BMIsds), body composition and metabolic components at 6 and 18 months follow-up. RESULTS: 122 adolescents, 71 Go4it and 51 controls, with a mean BMIsds of 2.9 ± 0.5 were randomised. At 18 months a modest significant reduction in BMIsds (between group difference: -0.16; 95%CI: -0.30, -0.02; p = .028) was observed. None of the other body composition or metabolic components showed significant treatment effects. Ethnicity was a significant effect modifier. Posthoc analysis showed a large significant reduction on BMIsds (between group difference: -0.35; 95%CI: -0.64, -0.07) at 18 months for obese adolescents from western descent, while no effect was observed for adolescents from non-western descent. Significant treatment effects were also observed for systolic and diastolic blood pressure, as well as HDL cholesterol level, but only for obese adolescents from western descent. CONCLUSIONS: Go4it showed promising long-term effects on BMIsds compared with regular care in obese adolescents. Larger benefits were achieved for adolescents of western ethnicity. This trial was registered at www.trialregister.nl with the Netherlands Trial Register as ISRCTN27626398.

The concurrent validity between leptin, BMI and skin folds during pregnancy and the year after.

BACKGROUND: From a public health perspective it is important to know which of the currently used methods to estimate changes in maternal body fat during pregnancy and the year thereafter is the most adequate. OBJECTIVES: To evaluate the concurrent validity between leptin and surrogates of fat measures: body mass index (BMI) and the sum of four skin folds. DESIGN: Data from the New Life(style) intervention study were analysed as a cohort study. SETTING: Midwife practices in The Netherlands. POPULATION: Healthy pregnant nulliparous women. METHODS: Anthropometric measurements were done and blood was collected at 15, 25 and 35 weeks of pregnancy and at 6, 26 and 52 weeks after delivery. Data were used if at least 4 out of the 6 measurements were available, leaving 87 women in the analyses. Spearman's correlation coefficients between leptin and BMI and between leptin and the sum of skin folds were calculated for each time point and for the changes between the time points. RESULTS: Correlations between leptin and BMI varied from 0.69 to 0.81. Correlations between leptin and the sum of skin folds were comparable, varying between 0.65 and 0.81.Correlations between changes in leptin and changes in BMI and the sum of skin folds, respectively, were much lower compared with cross-sectional correlations. CONCLUSION: Because of the high correlation among the three methods and because of the overlapping intervals, all methods seem to be equally adequate to estimate changes in maternal body fat during pregnancy and the year thereafter.

Longitudinal study of hormonal and physical development in young twins.

CONTEXT AND OBJECTIVE: Information on the correlation of normative reproductive hormone levels with physical development (Tanner stages) during puberty and on the influences of genes and environment on variation in these hormones and Tanner stages is limited. DESIGN, SETTING, AND PARTICIPANTS: One hundred twelve healthy 9-year-old twin pairs (n = 224) took part in a longitudinal study, of which 89 pairs participated again at age 12 years (n = 178). MAIN OUTCOME MEASURES: Morning urinary LH, FSH, estradiol, and salivary testosterone levels, determined by competitive immunoassays, were measured. Tanner stages were determined through physical examination. RESULTS: Over the 3-year interval, all hormone levels showed a 2- to 9-fold increase. LH and FSH at age 9 years predicted sex-specific Tanner stages at age 12 years in both boys and girls. Most of the associations between hormone levels at age 9 years and physical development at 12 years were explained by genetic influences. FSH in 9-year-old boys correlated with all hormone levels and Tanner stages at age 12 years. Moderate to high heritability estimates were found for hormone levels at both ages and in both sexes. In girls a shift from environmental (age 9 years) to genetic influences (age 12 years) was found for estradiol and pubic hair development, and for breast development a shift in the opposite direction was seen. CONCLUSIONS: During development LH and FSH (and testosterone in boys) levels predict secondary sexual characteristics in boys and girls 3 years later. These correlations are largely due to genes that are involved in both early pubertal hormone levels and subsequent physical development.

Increased somatic morbidity in the first year after leaving opioid maintenance treatment: results from a Norwegian cohort study.

BACKGROUND/AIMS: Some patients on opioid maintenance treatment (OMT) leave treatment temporarily or permanently. This study investigated whether patients interrupting their OMT differed from non-interrupters in sociodemographic and drug-use characteristics and examined acute/sub-acute somatic morbidity among the interrupters, prior to, during, and after OMT. METHODS: Cohort design. OBSERVATION PERIOD: 5 years prior to, up to first 5 years during, and up to 5 years after interruption of OMT. PARTICIPANTS: The sample (n = 200) comprised 51 OMT interrupters and 149 non-interrupters. Data on patient characteristics were obtained from interviews and OMT register information. Data on somatic morbidity were gathered from hospital records. MEASUREMENTS: Key patient characteristics among OMT interrupters and non-interrupters. Incidence rates of acute and sub-acute somatic disease incidents leading to hospital treatment (drug-related/non-drug-related/injuries) prior to/during/after OMT. RESULTS: Interrupters and non-interrupters did not differ in sociodemographic characteristics, while longer duration of amphetamine and benzodiazepine dependence predicted OMT interruption. Interrupters scored significantly higher on drug-taking and overdose during OMT but still had a significant 41% reduction in drug-related treatment, episodes. After interruption of treatment, such episodes increased markedly and were 3.6 times more frequent during the first post-OMT year compared to the pre-OMT period (p < 0.001). This increase was highest during the first months after OMT interruption. 2-5 years after interruption there was no significant increase. CONCLUSIONS: Increased somatic morbidity was found among OMT interrupters during the first year after OMT, and especially during the immediate post-treatment period.

Genetic analysis of short children with apparent growth hormone insensitivity.

BACKGROUND/AIMS: In short children, a low IGF-I and normal GH secretion may be associated with various monogenic causes, but their prevalence is unknown. We aimed at testing GH1, GHR, STAT5B, IGF1, and IGFALS in children with GH insensitivity. SUBJECTS AND METHODS: Patients were divided into three groups: group 1 (height SDS <-2.5, IGF-I <-2 SDS, n = 9), group 2 (height SDS -2.5 to -1.9, IGF-I <-2 SDS, n = 6) and group 3 (height SDS <-1.9, IGF-I -2 to 0 SDS, n = 21). An IGF-I generation test was performed in 11 patients. Genomic DNA was used for direct sequencing, multiplex ligation-dependent probe amplification and whole-genome SNP array analysis. RESULTS: Three patients in group 1 had two novel heterozygous STAT5B mutations, in two combined with novel IGFALS variants. In groups 2 and 3 the association between genetic variants and short stature was uncertain. The IGF-I generation test was not predictive for the growth response to GH treatment. CONCLUSION: In severely short children with IGF-I deficiency, genetic assessment is advised. Heterozygous STAT5B mutations, with or without heterozygous IGFALS defects, may be associated with GH insensitivity. In children with less severe short stature or IGF-I deficiency, functional variants are rare.

Association between impulsivity, reward responsiveness and body mass index in children.

BACKGROUND: Childhood obesity is a major health problem. An association between children's body mass index (BMI) and overeating has been established, but mechanisms leading to overeating are poorly understood. The personality characteristics impulsivity and reward responsiveness may be involved in the tendency to overeat. Impulsivity might relate to overeating through poor inhibition of food intake; reward responsiveness through the rewarding value of food. OBJECTIVE: This study aimed to reveal the relationships between impulsivity, reward responsiveness, overeating and BMI in a sample of 346 Dutch children aged 6-13 years. The BMI distribution in the sample was representative of the BMI distribution in the Dutch pediatric population. METHODS: Impulsivity and reward responsiveness were measured with the Dutch version of the parent-report Sensitivity to Punishment and Sensitivity to Reward Questionnaire for children. Overeating was assessed with the Dutch translation of the parent-report Children's Eating Behaviour Questionnaire. RESULTS: Overeating, impulsivity and reward responsiveness were significantly associated with childhood BMI. Mediation analysis revealed that impulsivity and reward responsiveness equally and significantly predicted BMI indirectly through overeating. CONCLUSIONS: The personality characteristics impulsivity and reward responsiveness predict childhood BMI indirectly through overeating. This suggests that these personality characteristics are risk factors for obesity.

Normative values for testicular volume measured by ultrasonography in a normal population from infancy to adolescence.

BACKGROUND/AIMS: We obtained reference data for testicular volume measured by ultrasound in asymptomatic boys aged 0.5-18 years. In addition, we assessed the validity of the Prader orchidometer per age group by correlating it with the volume measurement by ultrasound. METHODS: The study only included healthy boys with two scrotal testes at birth and at the time of the examination. For each boy the testicular volume of both testes was measured by ultrasound and the Prader orchidometer. Testicular volumes were measured for boys aged from 1 to 18 years. The boys' ages were rounded down to the last birthday if it had occurred less than 6 months previously or rounded up to the next birthday if it was going to be within 6 months. RESULTS: The volume measurement by the Prader orchidometer according to reference curves showed a statistically significant correlation. Moreover, the testicular volumes measured by the Prader orchidometer showed an accurate goodness of fit with US measurements (R(2) = 0.956). CONCLUSION: Normative values are provided for testicular volume measured by ultrasound in boys aged 0.5-18 years. An accurate correlation was found between volume measurements by ultrasound and by the Prader orchidometer (R(2) = 0.956). Therefore, volume measurement by the Prader orchidometer, as generally used in the practice by doctors, can be used as a valid parameter for monitoring testicular growth.

Oral fluid is a viable alternative for monitoring drug abuse: detection of drugs in oral fluid by liquid chromatography-tandem mass spectrometry and comparison to the results from urine samples from patients treated with Methadone or Buprenorphine.

Oral fluid is an alternative biological matrix that might have advantages over urine for drug analysis in treatment programs. A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method has been used for screening 32 of the most commonly abused drugs and their metabolites in 0.5 mL preserved oral fluid, and the results were compared to results obtained from urine samples taken at the same time. In all, 164 pairs of oral fluid and urine were obtained from 45 patients stabilized on either methadone or buprenorphine. The total number of detections of drugs other than buprenorphine or methadone was 535 in oral fluid and 629 in urine. Morphine was found more often in urine (n = 66) than in oral fluid (n = 48), whereas the opposite was the case for 6-monoacetylmorphine (n = 20 in urine and n = 48 in oral fluid). Methadone showed the same detection frequency in urine and oral fluid (n = 75), whereas amphetamine (n = 45 in urine and n = 51 in oral fluid), methamphetamine (n = 39 in urine and n = 45 in oral fluid), and N-desmethyldiazepam (n = 37 in urine and n = 51 in oral fluid) were detected slightly more often in oral fluid. The other benzodiazepines, cannabis and cocaine were found more frequently in urine samples. If using a sensitive LC-MS-MS technique, oral fluid might be a good alternative to urine for detection of relatively recent use of drugs.

Insulin resistance and the metabolic syndrome in obese children referred to an obesity center.

OBJECTIVE: The aim of this study was to describe insulin resistance and the metabolic syndrome in obese children and adolescents. SUBJECTS: The cohort consisted of 518 patients, 250 boys, 268 girls, age +/- sd: 11.8 +/- 3.2 years, BMIsds +/- sd: 2.94 +/- 0.5. A standard OGTT was performed. RESULTS: Impaired glucose tolerance was found in 9.4% of the boys and 5.5% of the girls. Impaired fasting glucose was found in 12.4% of the boys and 11.6% of the girls. The metabolic syndrome was present in 13.9% of children of 10 years or older. The proportion in which the metabolic syndrome was diagnosed was essentially not altered when pubertal groups were used instead of age groups. CONCLUSION: Both impaired fasting glucose and impaired glucose tolerance as well as the metabolic syndrome are highly prevalent among obese children and adolescents.

Neurological signs in relation to white matter hyperintensity volumes in memory clinic patients.

PURPOSE: To determine the frequency of neurological signs in a memory clinic population and to explore their associations with white matter hyperintensity (WMH). METHODS: We included patients with Alzheimer disease (AD; n = 210), vascular dementia (VaD; n = 34), mild cognitive impairment (MCI; n = 86) and subjective complaints (n = 153). The presence of extrapyramidal and unilateral signs was assessed from medical charts. On MRI, WMH volumes were extracted automatically. RESULTS: Extrapyramidal signs were found in 10% and unilateral signs in 12% of the patients. Age- and sex-adjusted extrapyramidal signs occurred more often in VaD compared to patients with subjective complaints. Unilateral signs were more prevalent in all groups compared to patients with subjective complaints. Two-way analysis of variance (ANOVA) with WMH as the dependent variable showed a main effect of diagnosis (p < 0.001), but not of extrapyramidal signs (p = 0.62). In contrast, 2-way ANOVA showed main effects of diagnosis (p < 0.001) and unilateral signs (p = 0.001). Furthermore, there was an interaction between these factors (p = 0.04); if unilateral signs were present, patients with subjective complaints and VaD showed more WMH, whereas there was no relation in AD and MCI. CONCLUSION: Extrapyramidal and unilateral signs are common in memory clinic patients, but are only modestly related to WMH.

Brain development, intelligence and cognitive outcome in children born small for gestational age.

Intrauterine growth restriction (IUGR) can lead to infants being born small for gestational age (SGA). SGA is associated with increased neonatal morbidity and mortality as well as short stature, cardiovascular disease, insulin resistance, diabetes mellitus type 2, dyslipidemia and end-stage renal disease in adulthood. In addition, SGA children have decreased levels of intelligence and cognition, although the effects are mostly subtle. The overall outcome of each child is the result of a complex interaction between intrauterine and extrauterine factors. Animal and human studies show structural alterations in the brains of individuals with IUGR/SGA. The presence of growth hormone (GH) receptors in the brain implies that the brain is also a target for GH. Exogenous GH theoretically has the ability to act on the brain. This is exemplified by the effects of GH on cognition in GH-deficient adults. In SGA children, data on the effect of exogenous GH on intelligence and cognition are scant and contradictory.

High-dose GH treatment limited to the prepubertal period in young children with idiopathic short stature does not increase adult height.

OBJECTIVE: To assess the long-term effect of prepubertal high-dose GH treatment on growth in children with idiopathic short stature (ISS). DESIGN AND METHODS: Forty children with no signs of puberty, age at start 4-8 years (girls) or 4-10 years (boys), height SDS <-2.0 SDS, and birth length >-2.0 SDS, were randomly allocated to receive GH at a dose of 2 mg/m(2) per day (equivalent to 75 microg/kg per day at start and 64 microg/kg per day at stop) until the onset of puberty for at least 2 years (preceded by two 3-month periods of treatment with low or intermediate doses of GH separated by two washout periods of 3 months) or no treatment. In 28 cases, adult height (AH) was assessed at a mean (S.D.) age of 20.4 (2.3) years. RESULTS: GH-treated children (mean treatment period on high-dose GH 2.3 years (range 1.2-5.0 years)) showed an increased mean height SDS at discontinuation of the treatment compared with the controls (-1.3 (0.8) SDS versus -2.6 (0.8) SDS respectively). However, bone maturation was significantly accelerated in the GH-treated group compared with the controls (1.6 (0.4) versus 1.0 (0.2) years per year, respectively), and pubertal onset tended to advance. After an untreated interval of 3-12 years, AH was -2.1 (0.7) and -1.9 (0.6) in the GH-treated and control groups respectively. Age was a positive predictor of adult height gain. CONCLUSION: High-dose GH treatment restricted to the prepubertal period in young ISS children augments height gain during treatment, but accelerates bone maturation, resulting in a similar adult height compared with the untreated controls.

Information processing, attention and visual-motor function of adolescents born after in vitro fertilization compared with spontaneous conception.

BACKGROUND: Adverse conditions during prenatal life are associated with changes in physical and mental functioning in later life, as shown in children born preterm or small for gestational age. While recently in IVF children cardiometabolic differences have been demonstrated, there might also be risks for disturbance in cognitive functions. Therefore, this study examined information processing, attention and visual-motor function in pubertal IVF children compared with spontaneously conceived controls from subfertile parents. Results of these cognitive functions were then related to cardiometabolic measures to explore whether both can be explained by changes in fetal programming due to IVF. METHODS: A total of 139 IVF and 143 control adolescents underwent various neuropsychological tests to measure information processing, attention and visual-motor function. The results were then related to data on blood pressure and glucose levels previously obtained from the same groups. RESULTS: No differences between IVF and control adolescents were found in the various test results for information processing and attention. A slight difference was found between the groups for motor speed, but these scores were within the normal range for the test. No direct relation was found between cognitive measures and cardiometabolic outcome. CONCLUSIONS: Comparison of IVF adolescents and controls revealed no disturbances in information processing, attention and visual-motor function. In addition, these cognitive functions were not directly related to cardiometabolic outcome. Therefore, these results do not support the hypothesis that cognition is influenced by IVF conception or an altered programming of metabolic systems due to IVF, and indicate that cognitive abilities in IVF children, as measured by the tasks assessed, appear to develop normally.

[First favourable results of the group education programme Go4it for overweight and obese adolescents]. / Eerste gunstige bevindingen van het groepseducatieprogramma Go4it voor adolescenten met overgewicht of obesitas.

OBJECTIVE: To evaluate the effect of Go4it, a multidisciplinary group education programme for adolescents with overweight or obesity. DESIGN: Uncontrolled intervention study. METHOD: At the obesity outpatient clinic of the Transmural Research and Treatment Centre for Overweight and Obese Children of the VU University Medical Center, Amsterdam, The Netherlands, a group education programme was developed for adolescents (age 12-18 year) who are overweight or obese. Obese adolescents who were referred to the obesity outpatient clinic were asked to participate. During 7 sessions (one session every two weeks) the adolescents were educated on the health consequences of obesity, diet, physical activity, energy balance, improving self-esteem and how to handle bullying and other difficult situations. All sessions were held in groups of 8-10 adolescents. In addition, two sessions were organised for the parents concerning the health consequences of obesity, diet, and physical activity. Body weight and height, glucose tolerance (by an oral glucose tolerance test; OGTT), and insulin resistance were measured at enrolment into the Go4it programme and 6 months later. RESULTS: In total, 93 adolescents (39 boys, 54 girls) were included with a mean age of 3.9 (SD: 1.7) years. Of those, 69 adolescents (74%) attended at least 6 out of 7 sessions of the education programme. Stabilisation or reduction in obesity levels following completion of Go4it was achieved in 51 (74%) of these participants. 50 adolescents had a second OGTT. The BMI standard deviation score (BMI-sds) decreased by 4.3% for boys (p = 0.020) and 3.3% for girls (p = 0.017). Among girls, fasting blood glucose levels decreased by an average of 0.37 mmol/l (95% CI: 0.14-0.60) and insulin concentrations decreased by an average of 299 pmol/l (95% CI: 71-528). CONCLUSION: Participation in the Go4it education programme is accompanied by a stabilisation or reduction in the level of obesity and has favourable effects on glucose and insulin metabolism.