Higher Standard Deviation Score Research Articles

Development of disease-specific growth charts for Korean children with Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is an epigenetic overgrowth syndrome. Despite its distinctive growth pattern, the detailed growth trajectories of children with BWS remain largely unknown. We retrospectively analyzed 413 anthropometric measurements over an average of 4.4 years of follow-up in 51 children with BWS. We constructed sex-specific percentile curves for height, weight, and head circumference using a generalized additive model for location, scale, and shape. Males with BWS exhibited greater height at all ages evaluated, weight before the age of 10, and head circumference before the age of 9 than those of the general population. Females with BWS showed greater height before the age of 7, weight before the age of 4.5, and head circumference before the age of 7 than those of the general population. At the latest follow-up visit at a mean 8.4 years of age, bone age was significantly higher than chronological age. Compared to paternal uniparental disomy (pUPD), males with imprinting center region 2-loss of methylation (IC2-LOM) had higher standard deviation score (SDS) for height and weight, while females with IC2-LOM showed larger SDS for head circumference. These disease-specific growth charts can serve as valuable tools for clinical monitoring of children with BWS.

Genetically defined favourable adiposity is not associated with a clinically meaningful difference in clinical course in people with type 2 diabetes but does associate with a favourable metabolic profile.

Change in weight, HbA1c , lipids, blood pressure and cardiometabolic events over time is variable in individuals with type 2 diabetes. We hypothesised that people with a genetic predisposition to a more favourable adiposity distribution could have a less severe clinical course/progression. We involved people with type 2 diabetes from two UK-based cohorts: 11,914 individuals with GP follow-up data from the UK Biobank and 723 from Salford. We generated a 'favourable adiposity' genetic score and conducted cross-sectional and longitudinal studies to test its association with weight, BMI, lipids, blood pressure, medication use and risk of myocardial infarction and stroke using 15 follow-up time points with 1-year intervals. The 'favourable adiposity' genetic score was cross-sectionally associated with higher weight (effect size per 1 standard deviation higher genetic score: 0.91kg [0.59,1.23]) and BMI (0.30kg/m2 [0.19,0.40]), but higher high-density lipoprotein (0.02mmol/L [0.01,0.02]) and lower triglycerides (-0.04mmol/L [-0.07, -0.02]) in the UK Biobank at baseline, and this pattern of association was consistent across follow-up. There was a trend for participants with higher 'favourable adiposity' genetic score to have lower risk of myocardial infarction and/or stroke (odds ratio 0.79 [0.62, 1.00]) compared to those with lower score. A one standard deviation higher score was associated with lower odds of using lipid-lowering (0.91 [0.86, 0.97]) and anti-hypertensive medication (0.95 [0.91, 0.99]). In individuals with type 2 diabetes, having more 'favourable adiposity' alleles is associated with a marginally better lipid profile long-term and having lower odds of requiring lipid-lowering or anti-hypertensive medication in spite of relatively higher adiposity.

Conservatively treated Congenital Hyperinsulinism (CHI) due to K-ATP channel gene mutations: reducing severity over time.

BackgroundPatients with Congenital Hyperinsulinism (CHI) due to mutations in K-ATP channel genes (K-ATP CHI) are increasingly treated by conservative medical therapy without pancreatic surgery. However, the natural history of medically treated K-ATP CHI has not been described; it is unclear if the severity of recessively and dominantly inherited K-ATP CHI reduces over time. We aimed to review variation in severity and outcomes in patients with K-ATP CHI treated by medical therapy.MethodsTwenty-one consecutively presenting patients with K-ATP CHI with dominantly and recessively inherited mutations in ABCC8/KCNJ11 were selected in a specialised CHI treatment centre to review treatment outcomes. Medical treatment included diazoxide and somatostatin receptor agonists (SSRA), octreotide and somatuline autogel. CHI severity was assessed by glucose infusion rate (GIR), medication dosage and tendency to resolution. CHI outcome was assessed by glycaemic profile, fasting tolerance and neurodevelopment.ResultsCHI presenting at median (range) age 1 (1, 240) days resolved in 15 (71%) patients at age 3.1(0.2, 13.0) years. Resolution was achieved both in patients responsive to diazoxide (n = 8, 57%) and patients responsive to SSRA (n = 7, 100%) with earlier resolution in the former [1.6 (0.2, 13.0) v 5.9 (1.6, 9.0) years, p = 0.08]. In 6 patients remaining on treatment, diazoxide dose was reduced in follow up [10.0 (8.5, 15.0) to 5.4 (0.5, 10.8) mg/kg/day, p = 0.003]. GIR at presentation did not correlate with resolved or persistent CHI [14.9 (10.0, 18.5) v 16.5 (13.0, 20.0) mg/kg/min, p = 0.6]. The type of gene mutation did not predict persistence; resolution could be achieved in recessively-inherited CHI with homozygous (n = 3), compound heterozygous (n = 2) and paternal mutations causing focal CHI (n = 2). Mild developmental delay was present in 8 (38%) patients; adaptive functioning assessed by Vineland Adaptive Behavior Scales questionnaire showed a trend towards higher standard deviation scores (SDS) in resolved than persistent CHI [−0.1 (−1.2, 1.6) v −1.2 (−1.7, 0.03), p = 0.1].ConclusionsIn K-ATP CHI patients managed by medical treatment only, severity is reduced over time in the majority, including those with compound heterozygous and homozygous mutations in ABCC8/KCNJ11. Severity and treatment requirement should be assessed periodically in all children with K-ATP CHI on medical therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0547-3) contains supplementary material, which is available to authorized users.

Growth charts: do they reflect healthy growth in Sri Lankan children?

BackgroundAnthropometry has been used in the assessment of growth with “normal” range of growth being considered to span within ±2SD of median. Generally the practice is to make a child to grow within this standard deviation (SD) range. This study aims to investigate the hypothesis that all children with anthropometrical parameters within the designated “normal growth range” (within ±2SD of median), have a healthy body composition irrespective of the SD value.ResultsFive to 15-year-old apparently healthy Sri Lankan children were studied. SD scores for height, weight and BMI, for age were calculated based on WHO 2007 standards. Sample was stratified according to age, sex, and SD score. %FM (assessed by isotope dilution methods using D2O) was compared between each SD group of each anthropometric parameter for gender and age. There were 278 (M/F:154/124) children. Non-parametric Kruskal–Wallis test revealed that the %FM of children differed significantly between SD groups even when they were within the accepted “normal limits of growth” and had higher levels of %FM in the upper SD groups.ConclusionsThis study shows that Sri Lankan children have unacceptably high body fat at levels that have been designated by growth charts as “normal”. Children who are positioned at a higher SD score, +1 to +2SD, (within normal range) in the weight for age and BMI for age charts are mainly due to the deposition of fat rather than the growth in both fat and fat free compartments of body. Therefore the implication of using current cutoff values would be leading to the accumulation of excess fat in the body of those with higher SD values, but still considered to be within “normal” limits. Therefore in the absence of local standards, it would be important to revise the cutoff values of the WHO growth charts to suite Sri Lankan children which would be between −3SD and +1SD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-016-2016-4) contains supplementary material, which is available to authorized users.

Intelligence in youth and health at age 50

BackgroundThe link between intelligence in youth and all-cause mortality in later-life is well established. To better understand this relationship, the current study examines the links between pre-morbid intelligence and a number of specific health outcomes at age 50 using the NLSY-1979 cohort. MethodsParticipants were the 5793 participants in the NLSY-79 who responded to questions about health outcomes at age 50. Sixteen health outcomes were examined: two were summary measures (physical health and functional limitation), 9 were diagnosed illness conditions, 4 were self-reported conditions, and one was a measure of general health status. Linear and logistic regressions were used, as appropriate, to examine the relationship between intelligence in youth and the health outcomes. Age, sex and both childhood and adult SES, and its sub-components – income, education, & occupational prestige – are all adjusted for separately. Results & conclusionHigher pre-morbid intelligence is linked with better physical health at age 50, and a lower risk for a number of chronic health conditions. For example, a 1 SD higher score in IQ was significantly associated with increased odds of having good, very good, or excellent health, with an odds ratio of 1.70 (C.I. 1.55–1.86). Thirteen of the illness outcomes were significantly and negatively associated with IQ in youth; the odds ratios ranged from 0.85 for diabetes/high blood sugar to 0.65 for stroke, per one standard deviation higher score in IQ. Adjustment for childhood SES led to little attenuation but adult SES partially mediated the relationship for a number of conditions. Mediation by adult SES was not consistently explained by any one of its components—income, education, and occupation status. The current findings contribute to our understanding of lower intelligence as a risk factor for poor health and how this may contribute to health inequalities.

IQ in childhood and atherosclerosis in middle-age: 40 Year follow-up of the Newcastle Thousand Families Cohort Study

ObjectiveCarotid intima-media thickness (IMT) is a known precursor to coronary heart disease (CHD) and other relevant health outcomes such as stroke and cognitive impairment. In addition, higher childhood intelligence has been associated with lower risk of coronary heart disease events in later life, although the mechanisms of effect are unclear. We therefore examined the association between childhood intelligence and atherosclerosis using carotid IMT as a marker of the atherosclerotic process. ApproachParticipants were 412 members of the Newcastle Thousand Families Study, a prospective cohort study of all 1142 births in the city of Newcastle in May and June 1947, who took an IQ test and English and arithmetic tests at age 11 years. Study members participated in a medical examination and lifestyle assessment at age 49–51 years during which IMT was measured using ultrasound techniques. ResultsIndividuals with higher childhood IQ score had a lower mean IMT in middle-age. A standard deviation higher score in childhood overall IQ was associated with a 0.053 mm (95% CI −0.102, −0.004) lower IMT in men and a 0.039 mm (95% CI −0.080, −0.002) lower IMT in women. Similar levels of association were found for the English and arithmetic tests. After adjustment for a range of covariates including education, the size of effect was undiminished in men but increased in women. ConclusionsIn the present study, higher childhood IQ scores were associated with a lower degree of atherosclerosis by middle-age.

Identifying children at high risk for a child maltreatment report

Objective To help professionals identify factors that place families at risk for future child maltreatment, to facilitate necessary services and to potentially help prevent abuse and neglect. Method The data are from a prospective, longitudinal study of 332 low-income families recruited from urban pediatric primary care clinics, followed for over 10 years, until the children were approximately 12 years old. Children with prior child protective services involvement (CPS) were excluded. The initial assessment included sociodemographic, child, parent and family level variables. Child maltreatment was assessed via CPS reports. Risk ratios (RRs) and their 95% confidence intervals (CIs) were estimated using Cox regression models. Results Of the 224 children without a prior CPS report and with complete data who were followed for an average of 10 years, 97 (43%) later had a CPS report. In a multivariate survival analysis, 5 risk factors predicted CPS reports: child's low performance on a standardized developmental assessment (RR = 1.23, 95% CI = 1.01–1.49, p = .04), maternal education ≤ high school (RR = 1.55, CI = 1.01–2.38, p = .04), maternal drug use (RR = 1.71, CI = 1.01–2.90, p < .05), maternal depressive symptoms (RR per one standard deviation higher score = 1.28, CI = 1.09–1.51, p < .01), and more children in the family (RR per additional child = 1.26, CI = 1.07–1.47, p < .01). Conclusions Five risk factors were associated with an increased risk for later maltreatment. Child health care and other professionals can identify these risk factors and facilitate necessary services to strengthen families, support parents and potentially help prevent child maltreatment.

Long-term follow-up of patients with Bartter syndrome type I and II

Little information is available on a long-term follow-up in Bartter syndrome type I and II. Clinical presentation, treatment and long-term follow-up (5.0-21, median 11 years) were evaluated in 15 Italian patients with homozygous (n = 7) or compound heterozygous (n = 8) mutations in the SLC12A1 (n = 10) or KCNJ1 (n = 5) genes. Thirteen new mutations were identified. The 15 children were born pre-term with a normal for gestational age body weight. Medical treatment at the last follow-up control included supplementation with potassium in 13, non-steroidal anti-inflammatory agents in 12 and gastroprotective drugs in five patients. At last follow-up, body weight and height were within normal ranges in the patients. Glomerular filtration rate was <90 mL/min/1.73 m(2) in four patients (one of them with a pathologically increased urinary protein excretion). In three patients, abdominal ultrasound detected gallstones. The group of patients with antenatal Bartter syndrome had a lower renin ratio (P < 0.05) and a higher standard deviation score (SDS) for height (P < 0.05) than a previously studied group of patients with classical Bartter syndrome. Patients with Bartter syndrome type I and II tend to present a satisfactory prognosis after a median follow-up of more than 10 years. Gallstones might represent a new complication of antenatal Bartter syndrome.

Serum levels of type I procollagen C-terminal propeptide, insulin-like growth factor-I (IGF-I), and IGF binding protein-3 in obese children and adolescents: Relationship to gender, pubertal development, growth, insulin, and nutritional status

We measured fasting serum levels of type I procollagen C-terminal propeptide (PICP), insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3) in obese children and adolescents (obese subjects [OS]) to evaluate their relationship to growth, gender, pubertal stage, and weight excess (WE). The influence of insulin, growth hormone (GH), and weight loss was also studied. The study population consisted of 244 OS and 236 normal-weight subjects (NWS) matched for age, gender, and pubertal stage. At stage I, OS had a higher standard deviation score (SDS) for height than NWS of both genders. During the prepubertal phase, growth velocity (GV) was greater in OS than in NWS of both genders, but it was lower in female OS at stage II and male OS at stage III. PICP increased in puberty, with a more rapid decrease later in female OS and NWS; prepubertal values were higher in OS but were reduced at pubertal stage IV to V in comparison to NWS. Stepwise multiple regression analysis demonstrated that GV was the only anthropological variable correlating with PICP. IGF-I serum values increased significantly in puberty and were higher in OS than in NWS at stage I for both genders. IGFBP-3 values of OS exceeded those of NWS at stages I to III in males and I to II in females. No difference was observed for males versus females in each group, nor was any difference observed for the IGF-I IGFBP-3 molar ratio between the two groups. Using stepwise analysis, a positive correlation between IGF-I and IGFBP-3 was observed in prepubertal but not in pubertal NWS. Fasting insulin values correlated with IGFBP-3 in OS, accounting for 24.8% of the variation in prepubertal subjects and 17.1% in pubertal subjects. No such correlation was observed in NWS. In prepubertal NWS, PICP and SDS of body mass index (BMI) correlated with IGF-I, accounting for 12.9% of the variation, and SDS of BNII correlated with IGFBP-3, explaining 27.8% of the variation. In prepubertal OS, no such correlations could be observed, but PICP and SDS of BMI accounted for 14.3% of the variation in the IGF-I IGFBP-3 molar ratio. A significant reduction of IGFBP-3 and an increase of the IGF-I IGFBP-3 molar ratio were detected after weight loss in 40 OS. In conclusion, we demonstrated that IGF-I and IGFBP-3 are influenced by age, gender, sexual development, and nutritional status. Also, an influence of insulin on IGFBP-3 serum levels was observed in OS. The relations of IGF-I to PICP in NWS and of the IGF-I IGFBP-3 molar ratio to PICP in OS support the concept of IGF-I influence on skeletal growth. The increased IGFBP-3 serum values in OS suggest a possible role in controlling the growth stimulus induced by nutritional status.

Growth response to growth hormone therapy following cranial irradiation.

The growth response to growth hormone (GH) therapy has been studied in 12 children who received irradiation to the cranium alone either for brain gliomas, distant from the hypothalamic-pituitary axis, or as prophylaxis against CNS leukaemia. Seven children have completed GH treatment (mean duration 4 years) and five are presently on GH (mean duration 1.2 years). This response has been compared to that seen in 14 children with isolated idiopathic GH deficiency (IGHD), following GH therapy. Before treatment, the cranially irradiated patients (C-PRGHD) had higher standard deviation scores (SDS) for standing height, sitting height and leg length, and less bone age (BA) retardation, but started treatment at a similar age, and with a similar pre-treatment growth velocity and GH peak to standard provocative tests, compared to IGHD patients. GH produced a significant and similar increase in growth velocity (cm/year and SDS for BA) over the first 2 years' treatment in both groups. However C-PRGHD patients entered puberty and thus completed growth earlier than the IGHD group. As a result, cranially-irradiated children showed no change in height SDS with GH therapy, compared to catch-up growth in IGHD. Nevertheless, GH has enabled C-PRGHD patients to maintain their centile position and to achieve a more acceptable final height.