High Hepatitis B Surface Antigen Levels Predict Insignificant Fibrosis in Hepatitis B e Antigen Positive Chronic Hepatitis B

Introduction

There is no data on the relationship between hepatitis B surface antigen (HBsAg) levels and liver fibrosis in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B (CHB).

Methods

Serum HBsAg and HBV DNA levels in HBeAg-positive CHB patients with liver biopsies were analyzed. The upper limit of normal (ULN) of alanine aminotransferase (ALT) was 30 and 19 U/L for men and women respectively. Histologic assessment was based on Ishak fibrosis staging for fibrosis and Knodell histologic activity index (HAI) for necroinflammation.

Results

140 patients (65% male, median age 32.7 years) were recruited. 56 (40%) had ALT ≤2×ULN. 72 (51.4%) and 42 (30%) had fibrosis score ≤1 and necroinflammation grading ≤4 respectively. Patients with fibrosis score ≤1, when compared to patients with fibrosis score >1, had significantly higher median HBsAg levels (50,320 and 7,820 IU/mL respectively, p<0.001). Among patients with ALT ≤2×ULN, serum HBsAg levels achieved an area under receiver operating characteristic curve of 0.869 in predicting fibrosis score ≤1. HBsAg levels did not accurately predict necroinflammation score. HBsAg ≥25,000 IU/mL was independently associated with fibrosis score ≤1 (p = 0.025, odds ratio 9.042).Using this cut-off HBsAg level in patients with ALT ≤2×ULN, positive and negative predictive values for predicting fibrosis score ≤1 were 92.7% and 60.0% respectively. HBV DNA levels had no association with liver histology.

Conclusion

Among HBeAg-positive patients with ALT ≤2×ULN, high serum HBsAg levels can accurately predict fibrosis score ≤1, and could potentially influence decisions concerning treatment commencement and reduce the need for liver biopsy.     

Inflammatory adipokines, high molecular weight adiponectin, and insulin resistance: a population-based survey in prepubertal schoolchildren

Background

The aim of this study was to investigate sex differences and associations of high molecular weight (HMW) adiponectin, leptin and proinflammatory adipokines, individually or in combinations, with adiposity and insulin resistance (IR) measures in prepubertal childhood.

Methodology

We studied 305 prepubertal children (boys/girls: 144/161; Tanner stage 1; age: 5-13 yr), included in a cohort of 44,231 adolescents who participated in an extensive Italian school-based survey. According to Cole''s criteria, 105 individuals were lean (L; boys/girls: 59/46), 60 overweight (OW; boys/girls: 32/28) and 140 obese (OB; boys/girls: 70/70). Measurements comprised total and HMW adiponectin, leptin, as well as a panel of proinflammatory adipokines/chemokines associated with diabetes risk.

Principal Findings

Leptin-, and the leptin-to-HMW adiponectin ratio (L/HMW)-, increased progressively (p<0.0001) from L to OW to OB boys and girls. When compared with L peers, OW and OB girls exhibited lower (p<0.001) HMW adiponectin levels, while in boys the HMW multimers did not differ significantly across the BMI-stratified groups. OB girls displayed higher (p<0.05) IL-8, IL-18, monocyte chemoattractant protein-1 (MCP-1) and soluble intercellular adhesion molecule-1 levels (sICAM-1) than L girls, whereas increased macrophage migration inhibitory factor (MIF) concentrations in OB vs OW boys were seen. HMW adiponectin (negatively), leptin or inflammatory markers (positively) correlated with adiposity and IR measures. In multivariate models, leptin represented a strong and independent determinant of HOMA-IR (R² 0.378; p<0.01). Adjustment for age, BMI_z-score, lipids and inflammatory mediators abolished the association between leptin and HOMA-IR in boys, while in girls leptin remained still a significant predictor of IR (R² 0.513; p<0.01). Finally, in both sexes, the joint effect of the L/HMW did not improve the prediction of basal IR as compared with leptin levels alone, which were mainly explained by the BMI_z-score.

Conclusions

In prepubertal children, leptin emerges as a sex-independent discrimination marker of adiposity degree and as a useful, sex-associated predictor of the systemic insulin resistance.     

A large population histology study showing the lack of association between ALT elevation and significant fibrosis in chronic hepatitis B

Objective

We determined the association between various clinical parameters and significant liver injury in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients.

Methods

From 1994 to 2008, liver biopsy was performed on 319 treatment-naïve CHB patients. Histologic assessment was based on the Knodell histologic activity index for necroinflammation and the Ishak fibrosis staging for fibrosis.

Results

211 HBeAg-positive and 108 HBeAg-negative patients were recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5%) HBeAg-positive patients with normal ALT had significant histologic abnormalities (necroinflammation grading ≥7 or fibrosis score ≥3). There was a significant difference in fibrosis scores among HBeAg-positive patients with an ALT level within the Prati criteria (30 U/L for men, 19 U/L for women) and patients with a normal ALT but exceeding the Prati criteria (p = 0.024). Age, aspartate aminotransferase and platelet count were independent predictors of significant fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis (p = 0.007, 0.047 and 0.045 respectively). HBV DNA and platelet count were predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015 respectively). An elevated ALT was not predictive of significant fibrosis for HBeAg-positive (p = 0.345) and -negative (p = 0.544) disease. There was no significant difference in fibrosis staging among ALT 1–2×upper limit of normal (ULN) and >×2 ULN for both HBeAg-positive (p = 0.098) and -negative (p = 0.838) disease.

Conclusion

An elevated ALT does not accurately predict significant liver injury. Decisions on commencing antiviral therapy should not be heavily based on a particular ALT threshold.     

Psychometric properties of the Danish Strength and Difficulties Questionnaire: the SDQ assessed for more than 70,000 raters in four different cohorts

Background

The Strength and Difficulties Questionnaire (SDQ) is a brief behavioural five factor instrument developed to assess emotional and behavioural problems in children and adolescents. The aim of the current study was to evaluate the psychometric properties for parent and teacher ratings in the Danish version of SDQ for different age groups of boys and girls.

Methods

The Danish versions of the SDQ were distributed to a total of 71,840 parent and teacher raters of 5-, 7- and 10- to 12-year-old children included in four large scale Danish cohorts. The internal reliability was assessed and exploratory factor analyses were carried out to replicate the originally proposed five factor structure. Mean scores and percentiles were examined in order to differentiate between low, medium and high levels of emotional and behavioural difficulties.

Results

The original five factor structure could be substantially confirmed. The Conduct items however did not solely load on the proposed Conduct scale and the Conduct scale was further contaminated by non-conduct items. Positively worded items tended to load on the Prosocial scale. This was more so the case for teachers than for parents. Parent and teacher means and percentiles were found to be lower compared to British figures but similar to or only slightly lower than those found in the other Nordic countries. The percentiles for girls were generally lower than for boys, markedly so for the teacher hyperactivity ratings.

Conclusions

The study supports the usefulness of the SDQ as a screening tool for boys and girls across age groups and raters in the general Danish population.     

Limited Utility of Plasma M30 in Discriminating Non-Alcoholic Steatohepatitis from Steatosis – A Comparison with Routine Biochemical Markers

Introduction

The utility of Cytokeratin-18 fragment, namely CK18Asp396 (M30), for the diagnosis of non-alcoholic steatohepatitis (NASH) is currently uncertain. We aimed to provide further data in this area among multi-ethnic Asian subjects with NAFLD.

Materials and Methods

The accuracy of M30 for detecting NASH was compared with serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transpeptidase (GGT) levels in consecutive adult subjects with biopsy-proven non-alcoholic fatty liver disease (NAFLD).

Results

Data for 93 NAFLD subjects (mean age 51.0±11.1 years old and 51.6% males) and 20 healthy controls (mean age 50.2±16.4 years old and 33.3% males) were analyzed. There were 39 NASH subjects (41.9%) and 54 non-NASH subjects (58.1%) among the NAFLD subjects. Plasma M30 (349 U/L vs. 162 U/L), and serum ALT (70 IU/L vs. 26 IU/L), AST (41 IU/L vs. 20 IU/L) and GGT (75 IU/L vs. 33 IU/L) were significantly higher in NAFLD subjects than in healthy controls. Serum ALT (86 IU/L vs. 61 IU/L), AST (58 IU/L vs. 34 IU/L) and GGT (97 IU/L vs. 56 IU/L) were significantly higher in NASH subjects compared to non-NASH subjects, but no significant difference was observed with plasma M30 (435 U/L vs. 331 U/L). The accuracy of plasma M30, and serum ALT, AST and GGT was good for predicting NAFLD (AUROC 0.91, 0.95, 0.87 and 0.85, respectively) but less so for NASH (AUROC 0.59, 0.64, 0.75 and 0.68, respectively). Serum ALT and AST, but not plasma M30 showed a significant trend with increasing grades of ballooning and lobular inflammation.

Conclusion

The utility of M30 in the detection of NASH in clinical practice appears limited, in comparison to routine biochemical markers.     

Alanine aminotransferase decreases with age: the Rancho Bernardo Study

Background

Serum alanine aminotransferase (ALT) is a marker of liver injury. The 2005 American Gastroenterology Association Future Trends Committee report states that serum ALT levels remain constant with age. This study examines the association between serum ALT and age in a community-dwelling cohort in the United States.

Methods

A cross-sectional study of 2,364 (54% female) participants aged 30–93 years from the Rancho Bernardo Study cohort who attended a research clinic visit in 1984–87. Demographic, metabolic co-variates, ALT, bilirubin, gamma glutamyl transferase (GGT), albumin, and adiposity signaling biomarkers (leptin, IL-6, adiponectin, ghrelin) were measured. Participants were divided into four-groups based upon age quartile, and multivariable-adjusted least squares of means (LSM) were examined (p for trend <0.05).

Results

ALT decreased with increasing age, with mean ALT levels (IU/L) of 23, 21, 20, and 17 for those between quartile ages 30–62, 63–71, 72–77, and 78–93 years (p<0.0001). Trends of decreasing LSM ALT with age and the decreasing prevalence of categorically defined elevated serum ALT with age remained robust after adjusting for sex, alcohol use, metabolic syndrome components, and biomarkers of adiposity (p-value <0.0001), and was not materially changed after adjusting for bilirubin, GGT, and albumin.

Conclusions

ALT levels decrease with age in both men and women independent of metabolic syndrome components, adiposity signaling biomarkers, and other commonly used liver function tests. Further studies are needed to understand the mechanisms responsible for a decline in ALT with age, and to establish the optimal cut-point of normal ALT in the elderly.     

Development, problem behavior, and quality of life in a population based sample of eight-year-old children with Down syndrome

Objective

Children with Down syndrome (DS) have delayed psychomotor development. We investigated levels of development, problem behavior, and Health-Related Quality of Life (HRQoL) in a population sample of Dutch eight-year-old children with DS. Developmental outcomes were compared with normative data of eight-year-old children from the general population.

Method

Over a three-year-period all parents with an eight-year-old child with DS were approached by the national parent organization. Developmental skills were assessed by means of the McCarthy Scales of Children''s Ability. To measure emotional and behavioral problems we used the Child Behavior Checklist. HRQoL was assessed with the TNO-AZL Children''s Quality of Life questionnaire. Analyses of variance were applied to compare groups.

Results

A total of 337 children participated. Mean developmental age was substantially lower than mean calendar age (3.9 years, SD 0.87 and 8.1 years, SD 0.15 respectively). Mean developmental age was significantly lower among boys than girls (3.6 (SD 0.85) and 4.2 years (SD 0.82) respectively; p<0.001). Compared with the general population, children with DS had more emotional and behavioral problems (p<0.001). However on the anxious/depressed scale, they scored significantly more favorably (p<0.001). Significantly lower HRQoL scores for the scales gross motor skills, autonomy, social functioning and cognitive functioning were found (p-values<0.001). Hardly any differences were observed for the scales physical complaints, positive and negative emotions.

Conclusion

Eight-year-old children with DS have an average developmental delay of four years, more often have emotional and behavioral problems, and have a less favorable HRQoL compared with children from the general population.     

The association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat

Background and Aims

A polymorphism in adiponutrin/patatin-like phospholipase-3 gene (PNPLA3), rs738409 C->G, encoding for the I148M variant, is the strongest genetic determinant of liver fat and ALT levels in adulthood and childhood obesity. Aims of this study were i) to analyse in a large group of obese children the role of the interaction of not-genetic factors such as BMI, waist circumference (W/Hr) and insulin resistance (HOMA-IR) in exposing the association between the I148M polymorphism and ALT levels and ii) to stratify the individual risk of these children to have liver injury on the basis of this gene-environment interaction.

Methods

1048 Italian obese children were investigated. Anthropometric, clinical and metabolic data were collected and the PNPLA3 I148M variant genotyped.

Results

Children carrying the 148M allele showed higher ALT and AST levels (p = 0.000006 and p = 0.0002, respectively). Relationships between BMI-SDS, HOMA-IR and W/Hr with ALT were analysed in function of the different PNPLA3 genotypes. Children 148M homozygous showed a stronger correlation between ALT and W/Hr than those carrying the other genotypes (p: 0.0045) and, therefore, 148M homozygotes with high extent of abdominal fat (W/Hr above 0.62) had the highest OR (4.9, 95% C. I. 3.2–7.8, p = 0.00001) to develop pathologic ALT.

Conclusions

We have i) showed for the first time that the magnitude of the association of PNPLA3 with liver enzymes is driven by the size of abdominal fat and ii) stratified the individual risk to develop liver damage on the basis of the interaction between the PNPLA3 genotype and abdominal fat.     

Increase in prevalence of overweight in Dutch children and adolescents: a comparison of nationwide growth studies in 1980, 1997 and 2009

Objective

To assess the prevalence of overweight and obesity among Dutch children and adolescents, to examine the 30-years trend, and to create new body mass index reference charts.

Design

Nationwide cross-sectional data collection by trained health care professionals.Participants: 10,129 children of Dutch origin aged 0–21 years.

Main Outcome Measures

Overweight (including obesity) and obesity prevalences for Dutch children, defined by the cut-off values on body mass index references according to the International Obesity Task Force.

Results

In 2009, 12.8% of the Dutch boys and 14.8% of the Dutch girls aged 2–21 years were overweight and 1.8% of the boys and 2.2% of the girls were classified as obese. This is a two to three fold higher prevalence in overweight and four to six fold increase in obesity since 1980. Since 1997, a substantial rise took place, especially in obesity, which increased 1.4 times in girls and doubled in boys. There was no increase in mean BMI SDS in the major cities since 1997.

Conclusions

Overweight and obesity prevalences in 2009 were substantially higher than in 1980 and 1997. However, the overweight prevalence stabilized in the major cities. This might be an indication that the rising trend in overweight in the Netherlands is starting to turn.     

Relationship of body fat and cardiorespiratory fitness with cardiovascular risk in Chinese children

Backgrounds/Objectives

Cardiorespiratory fitness (CRF) and body fat play an important role in elevated risk for cardiovascular disease (CVD). However, the combined effects of CRF and obesity on metabolic health in Chinese children are unclear. The purpose of this study was to investigate the independent and combined associations between body fat, CRF, and CVD risk in Chinese schoolchildren.

Methods

The study subjects comprised 676 schoolchildren (392 boys and 284 girls, aged 9.6±0.7 yrs old) in Wuhan, China. Their body mass index (BMI), waist circumference (WC), CRF, blood pressure (BP), lipids, glucose, and pubertal status were assessed. Children were categorized into different groups based on their BMI, WC, and CRF using Chinese obesity cut-off points and CRF sex-specific median points. Metabolic Risk Score (MRS) was computed based on the standardized scores of BP, lipids, and glucose.

Results

Multiple linear regression models showed that, in the separate models, body fat was positively associated with MRS while CRF was inversely associated with MRS (p<0.001). However, when assessed simultaneously, only body fat had a significant association with MRS (p<0.001). In general, low-fit children had a lower MRS compared to their counterparts, and a significant difference between the two extreme groups was observed (low CRF and high fat vs. high CRF and low fat, p<0.001).

Conclusions

These findings suggest that both body fat and CRF should be considered when interpreting CVD risk in Chinese children, while body fat may be correlated with CVD risk more than CRF.     

Factors associated with elevated ALT in an international HIV/HBV co-infected cohort on long-term HAART

Background

Previous studies have demonstrated that hepatitis B virus (HBV) infection increases the risk for ALT elevations in HIV-HBV co-infected patients during the first year of HAART; however, there is limited data on the prevalence of ALT elevations with prolonged HAART in this patient group.

Methods/Principal findings

To identify factors associated with ALT elevations in an HIV-HBV co-infected cohort receiving prolonged HAART, data from 143 co-infected patients on HAART enrolled in an international HIV-HBV co-infected cohort where ALT measurements were obtained every 6 months was analysed. A person-visit analysis was used to determine frequency of ALT elevation (≥2.5×ULN) at each visit. Factors associated with ALT elevation were determined using multivariate logistic regression with generalized estimating equations to account for correlated data. The median time on HAART at the end of follow-up was 5.6 years (range 0.4–13.3) years. During follow-up, median ALT was 36 U/L with 10.6% of person-visits classified as having ALT elevation. Most ALT elevations were grade 2 (86.5%), with only 13.5% of all ALT elevations grade 3 or higher. Univariate associations with ALT elevation (p<0.05) included history of AIDS, HBV DNA ≥2,000 IU/ml, HBeAg positive, study visit CD4 <200 cells/ml and nadir CD4 <200 cells/ml. In the multivariate analysis, only study visit CD4 <200 cells/ml (OR 2.07, 95%CI 1.04–4.11, p = 0.04) and HBeAg positive status (OR 2.22, 95%CI 1.03–4.79, p = 0.04) were independently associated with ALT elevation.

Conclusions

In this HIV-HBV co-infected cohort, elevated ALT after >1 year of HAART was uncommon, and severe ALT elevations were rare. HIV-HBV co-infected patients on long-term HAART who are either HBeAg positive or have a CD4 count of <200 cells/ml are at increased risk for ALT elevations.     

Prevalence of Abdominal Obesity in Spanish Children and Adolescents. Do We Need Waist Circumference Measurements in Pediatric Practice?

Background

Evidence indicates that central adiposity has increased to a higher degree than general adiposity in children and adolescents in recent decades. However, waist circumference is not a routine measurement in clinical practice.

Objective

This study aimed to determine the prevalence of abdominal obesity based on waist circumferences (WC) and waist to height ratio (WHtR) in Spanish children and adolescents aged 6 to 17 years. Further, the prevalence of abdominal obesity (AO) among normal and overweight individuals was analyzed.

Design

Data were obtained from a study conducted from 1998 to 2000 in a representative national sample of 1521 children and adolescents aged 6 to 17 years (50.0% female) in Spain. WC and WHtR measurements were obtained in addition to BMI. AO was defined as WHtR ≥0.50 (WHtR-AO), sex and age specific WC≥90^th percentile (WC-AO1), and sex and age specific WC cut-off values associated with high trunk fat measured by by dual-energy X-ray absorptiometry (WC-AO2).

Results

IOTF- based overweight and obsity prevalence was 21.5% and 6.6% in children and 17.4% and 5.2% in adolescents, respectively. Abdominal obesity (AO) was defined as WHtR≥0.50 (WHtR-AO), sex- and age-specific WC≥90th percentile (WC-AO1), and sex- and age-specific WC cut-off values associated with high trunk fat measured by dual-energy X-ray absorptiometry (WC-AO2). The respective prevalence of WHtR-AO, WC-AO1, and WC-AO2 was 21.3% (24.6% boys; 17.9% girls), 9.4% (9.1% boys; 9.7% girls), and 26.8% (30.6% boys;22.9% girls) in children and 14.3% (20.0% boys; 8.7% girls), 9.6% (9.8% boys; 9.5% girls), and 21.1% (28.8% boys; 13.7% girls) in adolescents.

Conclusion

The prevalence of AO in Spanish children and adolescents is of concern. The high proportion of AO observed in young patients who are normal weight or overweight indicates a need to include waist circumference measurements in routine clinical practice.     

Reasons for (non)participating in a telephone-based intervention program for families with overweight children

Objective

Willingness to participate in obesity prevention programs is low; underlying reasons are poorly understood. We evaluated reasons for (non)participating in a novel telephone-based obesity prevention program for overweight children and their families.

Method

Overweight children and adolescents (BMI>90^th percentile) aged 3.5–17.4 years were screened via the CrescNet database, a representative cohort of German children, and program participation (repetitive computer aided telephone counseling) was offered by their local pediatrician. Identical questionnaires to collect baseline data on anthropometrics, lifestyle, eating habits, sociodemographic and psychosocial parameters were analyzed from 433 families (241 participants, 192 nonparticipants). Univariate analyses and binary logistic regression were used to identify factors associated with nonparticipation.

Results

The number of overweight children (BMI>90^th percentile) was higher in nonparticipants than participants (62% vs. 41.1%,p<0.001), whereas the number of obese children (BMI>97^th percentile) was higher in participants (58.9% vs.38%,p<0.001). Participating girls were younger than boys (8.8 vs.10.4 years, p<0.001). 87.3% and 40% of participants, but only 72.2% and 24.7% of nonparticipants, respectively, reported to have regular breakfasts (p = 0.008) and 5 regular daily meals (p = 0.003). Nonparticipants had a lower household-net-income (p<0.001), but higher subjective physical wellbeing than participants (p = 0.018) and believed that changes in lifestyle can be made easily (p = 0.05).

Conclusion

An important reason for nonparticipation was non-awareness of their child''s weight status by parents. Nonparticipants, who were often low-income families, believed that they already perform a healthy lifestyle and had a higher subjective wellbeing. We hypothesize that even a low-threshold intervention program does not reach the families who really need it.     

Soluble serum CD81 is elevated in patients with chronic hepatitis C and correlates with alanine aminotransferase serum activity

Aim

Cellular CD81 is a well characterized hepatitis C virus (HCV) entry factor, while the relevance of soluble exosomal CD81 in HCV pathogenesis is poorly defined. We performed a case-control study to investigate whether soluble CD81 in the exosomal serum fraction is associated with HCV replication and inflammatory activity.

Patients and Methods

Four cohorts were investigated, patients with chronic hepatitis C (n = 37), patients with chronic HCV infection and persistently normal ALT levels (n = 24), patients with long term sustained virologic response (SVR, n = 7), and healthy volunteers (n = 23). Concentration of soluble CD81 was assessed semi-quantitatively after differential centrifugation ranging from 200 g to 100,000 g in the fifth centrifugation fraction by immunoblotting and densitometry.

Results

Soluble CD81 was increased in patients with chronic hepatitis C compared to healthy subjects (p = 0.03) and cured patients (p = 0.017). Patients with chronic HCV infection and persistently normal ALT levels and patients with long term SVR had similar soluble CD81 levels as healthy controls (p>0.2). Overall, soluble CD81 levels were associated with ALT levels (r = 0.334, p = 0.016) and severe liver fibrosis (p = 0.027).

Conclusion

CD81 is increased in the exosomal serum fraction in patients with chronic hepatitis C and appears to be associated with inflammatory activity and severity of fibrosis.     

Sex ratio at birth in India, its relation to birth order, sex of previous children and use of indigenous medicine

Objective

Sex-ratio at birth in families with previous girls is worse than those with a boy. Our aim was to prospectively study in a large maternal and child unit sex-ratio against previous birth sex and use of traditional medicines for sex selection.

Main Outcome Measures

Sex-ratio among mothers in families with a previous girl and in those with a previous boy, prevalence of indigenous medicine use and sex-ratio in those using medicines for sex selection.

Results

Overall there were 806 girls to 1000 boys. The sex-ratio was 720∶1000 if there was one previous girl and 178∶1000 if there were two previous girls. In second children of families with a previous boy 1017 girls were born per 1000 boys. Sex-ratio in those with one previous girl, who were taking traditional medicines for sex selection, was 928∶1000.

Conclusion

Evidence from the second children clearly shows the sex-ratio is being manipulated by human interventions. More mothers with previous girls tend to use traditional medicines for sex selection, in their subsequent pregnancies. Those taking such medication do not seem to be helped according to expectations. They seem to rely on this method and so are less likely use more definitive methods like sex selective abortions. This is the first such prospective investigation of sex ratio in second children looked at against the sex of previous children. More studies are needed to confirm the findings.     

Associations of Physical Activity and Sedentary Behavior with Academic Skills – A Follow-Up Study among Primary School Children

Background

There are no prospective studies that would have compared the relationships of different types of physical activity (PA) and sedentary behavior (SB) with academic skills among children. We therefore investigated the associations of different types of PA and SB with reading and arithmetic skills in a follow-up study among children.

Methods

The participants were 186 children (107 boys, 79 girls, 6–8 yr) who were followed-up in Grades 1–3. PA and SB were assessed using a questionnaire in Grade 1. Reading fluency, reading comprehension and arithmetic skills were assessed using standardized tests at the end of Grades 1–3.

Results

Among all children more recess PA and more time spent in SB related to academic skills were associated with a better reading fluency across Grades 1–3. In boys, higher levels of total PA, physically active school transportation and more time spent in SB related to academic skills were associated with a better reading fluency across the Grades 1–3. Among girls, higher levels of total PA were related to worse arithmetic skills across Grades 1–3. Moreover, total PA was directly associated with reading fluency and arithmetic skills in Grades 1–3 among girls whose parents had a university degree, whereas these relationships were inverse in girls of less educated parents.

Conclusions

Total PA, physically active school transportation and SB related to academic skills may be beneficial for the development of reading skills in boys, whereas factors that are independent of PA or SB may be more important for academic skills in girls.

Trial Registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01803776","term_id":"NCT01803776"}}NCT01803776     

Effects of Changes in Adiposity and Physical Activity on Preadolescent Insulin Resistance: The Australian LOOK Longitudinal Study

Background

In a previous longitudinal analysis of our cohort as 8 to 10 year-olds, insulin resistance (IR) increased with age, but was not modified by changes in percent body fat (%BF), and was only responsive to changes in physical activity (PA) in boys. We aimed to determine whether these responses persisted as the children approached adolescence.

Methods

In this prospective cohort study, 256 boys and 278 girls were assessed at ages 8, 10 and 12 years for fasting blood glucose and insulin, %BF (dual energy X-ray absorptiometry); PA (7-day pedometers), fitness (multistage run); and pubertal development (Tanner stage).

Results

From age 8 to 12 years, the median homeostatic model of IR (HOMA-IR) doubled in boys and increased 250% in girls. By age 12, 23% of boys and 31% of girls had elevated IR, as indicated by HOMA-IR greater than 3. Longitudinal relationships, with important adjustments for covariates body weight, PA, %BF, Tanner score and socioeconomic status showed that, on average, for every 1 unit reduction of %BF, HOMA-IR was lowered by 2.2% (95% CI 0.04–4) in girls and 1.6% (95% CI 0–3.2) in boys. Furthermore, in boys but not girls, HOMA-IR was decreased by 3.5% (95%CI 0.5–6.5) if PA was increased by 2100 steps/day.

Conclusion

Evidence that a quarter of our apparently healthy 12 year-old Australians possessed elevated IR suggests that community-based education and prevention strategies may be warranted. Responsiveness of IR to changes in %BF in both sexes during late preadolescence and to changes in PA in the boys provides a specific basis for targeting elevated IR. That body weight was a strong covariate of IR, independent of %BF, points to the importance of adjusting for weight in correctly assessing these relationships in growing children.     

Physical Education and Blood Lipid Concentrations in Children: The LOOK Randomized Cluster Trial

Background and Objectives

Elevated blood lipids during childhood are predictive of dyslipidemia in adults. Although obese and inactive children have elevated values, any potentially protective role of elementary school physical education is unknown. Our objective was to determine the effect of a modern elementary school physical education (PE) program on the blood lipid concentrations in community-based children.

Methods

In this cluster-randomized controlled trial, 708 healthy children (8.1±0.3 years, 367 boys) in 29 schools were allocated to either a 4-year intervention program of specialist-taught PE (13 schools) or to a control group of the currently practiced PE conducted by generalist classroom teachers. Fasting blood lipids were measured at ages 8, 10, and 12 years and intervention and control class activities were recorded.

Results

Intervention classes included more fitness work and more moderate and vigorous physical activity than control classes (both p<0.001). With no group differences at baseline, the percentage of 12 year-old boys and girls with elevated low density lipoprotein cholesterol (LDL-C, >3.36mmol.L⁻¹,130 mg/dL) was lower in the intervention than control group (14% vs. 23%, p = 0.02). There was also an intervention effect on mean LDL-C across all boys (reduction of 9.6% for intervention v 2.8% control, p = 0.02), but not girls (p = 0.2). The intervention effect on total cholesterol mirrored LDL-C, but there were no detectable 4-year intervention effects on high-density lipoprotein cholesterol or triglycerides.

Conclusions

The PE program delivered by specialist teachers over four years in elementary school reduced the incidence of elevated LDL-C in boys and girls, and provides a means by which early preventative practices can be offered to all children.

Trial Registration

Australia New Zealand Clinical Trial Registry ANZRN12612000027819 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=347799.     

Efficacy, safety, and tolerability of three regimens for prevention of malaria: a randomized, placebo-controlled trial in Ugandan schoolchildren

Background

Intermittent preventive treatment (IPT) is a promising malaria control strategy; however, the optimal regimen remains unclear. We conducted a randomized, single-blinded, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of a single course of sulfadoxine-pyrimethamine (SP), amodiaquine + SP (AQ+SP) or dihydroartemisinin-piperaquine (DP) among schoolchildren to inform IPT.

Methods

Asymptomatic girls aged 8 to 12 years and boys aged 8 to 14 years enrolled in two primary schools in Tororo, Uganda were randomized to receive one of the study regimens or placebo, regardless of presence of parasitemia at enrollment, and followed for 42 days. The primary outcome was risk of parasitemia at 42 days. Survival analysis was used to assess differences between regimens.

Results

Of 780 enrolled participants, 769 (98.6%) completed follow-up and were assigned a treatment outcome. The risk of parasitemia at 42 days varied significantly between DP (11.7% [95% confidence interval (CI): 7.9, 17.1]), AQ+SP (44.3% [37.6, 51.5]), and SP (79.7% [95% CI: 73.6, 85.2], p<0.001). The risk of parasitemia in SP-treated children was no different than in those receiving placebo (84.6% [95% CI: 79.1, 89.3], p = 0.22). No serious adverse events occurred, but AQ+SP was associated with increased risk of vomiting compared to placebo (13.0% [95% CI: 9.1, 18.5] vs. 4.7% [95% CI: 2.5, 8.8], respectively, p = 0.003).

Conclusions

DP was the most efficacious and well-tolerated regimen tested, although AQ+SP appears to be a suitable alternative for IPT in schoolchildren. Use of SP for IPT may not be appropriate in areas with high-level SP resistance in Africa.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00852371","term_id":"NCT00852371"}}NCT00852371