Prediction of m6A and m5C at single-molecule resolution reveals a transcriptome-wide co-occurrence of RNA modifications.

The epitranscriptome embodies many new and largely unexplored functions of RNA. A significant roadblock hindering progress in epitranscriptomics is the identification of more than one modification in individual transcript molecules. We address this with CHEUI (CH3 (methylation) Estimation Using Ionic current). CHEUI predicts N6-methyladenosine (m6A) and 5-methylcytosine (m5C) in individual molecules from the same sample, the stoichiometry at transcript reference sites, and differential methylation between any two conditions. CHEUI processes observed and expected nanopore direct RNA sequencing signals to achieve high single-molecule, transcript-site, and stoichiometry accuracies in multiple tests using synthetic RNA standards and cell line data. CHEUI's capability to identify two modification types in the same sample reveals a co-occurrence of m6A and m5C in individual mRNAs in cell line and tissue transcriptomes. CHEUI provides new avenues to discover and study the function of the epitranscriptome.

Efficacy and Safety of a Tetravalent Dengue Vaccine (TAK-003) in Children With Prior Japanese Encephalitis or Yellow Fever Vaccination.

BACKGROUND: We explored the impact of prior Yellow fever (YF) or Japanese encephalitis (JE) vaccination on the efficacy of Takeda's dengue vaccine candidate, TAK-003 (NCT02747927). METHODS: Children 4-16 years of age were randomized 2:1 to receive TAK-003 or placebo and were under active febrile surveillance. Symptomatic dengue was confirmed by serotype-specific RT-PCR. YF and JE vaccination history was recorded. RESULTS: Of the 20,071 children who received TAK-003 or placebo, 21.1% had a YF and 23.9% had a JE vaccination history at randomization. Fifty-seven months after vaccination, vaccine efficacy was 55.7% (95% CI, 39.7%-67.5%) in those with YF vaccination, 77.8% (70.8%-83.1%) for JE vaccination, and 53.5% (45.4%-60.4%) for no prior YF/JE vaccination. Regional differences in serotype distribution confound these results. The apparent higher vaccine efficacy in the JE vaccination subgroup could be largely explained by serotype-specific efficacy of TAK-003. Within 28 days of any vaccination, the proportions of participants with serious adverse events in the YF/JE prior vaccination population were comparable between the TAK-003 and placebo groups. CONCLUSIONS: The available data do not suggest a clinically relevant impact of prior JE or YF vaccination on TAK-003 performance. Overall, TAK-003 was well-tolerated and efficacious in different epidemiological settings.

Long-term efficacy and safety of a tetravalent dengue vaccine (TAK-003): 4·5-year results from a phase 3, randomised, double-blind, placebo-controlled trial.

BACKGROUND: About half of the world's population lives in dengue-endemic areas. We aimed to evaluate the long-term efficacy and safety of two doses of the tetravalent dengue vaccine TAK-003 in preventing symptomatic dengue disease of any severity and due to any dengue virus (DENV) serotypes in children and adolescents. METHODS: In this ongoing double-blind, randomised, placebo-controlled trial, we enrolled healthy participants aged 4-16 years at 26 medical and research centres across eight dengue-endemic countries (Brazil, Colombia, Dominican Republic, Nicaragua, Panama, Philippines, Sri Lanka, and Thailand). The main exclusion criteria were febrile illness (body temperature ≥38°C) at the time of randomisation, hypersensitivity or allergy to any of the vaccine components, pregnancy or breastfeeding, serious chronic or progressive disease, impaired or altered immune function, and previous receipt of a dengue vaccine. Participants were randomly assigned 2:1 (stratified by age and region) using an interactive web response system and dynamic block assignment to receive two subcutaneous doses of TAK-003 or placebo 3 months apart. Investigators, participants, and their parents or legal guardians were blinded to group assignments. Active febrile illness surveillance and RT-PCR testing of febrile illness episodes were performed for identification of virologically confirmed dengue. Efficacy outcomes were assessed in the safety analysis set (all randomly assigned participants who received ≥1 dose) and the per protocol set (all participants who had no major protocol violations), and included cumulative vaccine efficacy from first vaccination to approximately 4·5 years after the second vaccination. Serious adverse events were monitored throughout. This study is registered with ClinicalTrials.gov, NCT02747927. FINDINGS: Between Sept 7, 2016, and March 31, 2017, 20 099 participants were randomly assigned (TAK-003, n=13 401; placebo, n=6698). 20 071 participants (10 142 [50·5%] males; 9929 [49·5%] females; safety set) received TAK-003 or placebo, with 18 257 (91·0%) completing approximately 4·5 years of follow-up after the second vaccination (TAK-003, 12 177/13 380; placebo, 6080/6687). Overall, 1007 (placebo: 560; TAK-003: 447) of 27 684 febrile illnesses reported were virologically confirmed dengue, with 188 cases (placebo: 142; TAK-003: 46) requiring hospitalisation. Cumulative vaccine efficacy was 61·2% (95% CI 56·0-65·8) against virologically confirmed dengue and 84·1% (77·8-88·6) against hospitalised virologically confirmed dengue; corresponding efficacies were 53·5% (41·6-62·9) and 79·3% (63·5-88·2) in baseline seronegative participants (safety set). In an exploratory analysis, vaccine efficacy was shown against all four serotypes in baseline seropositive participants. In baseline seronegative participants, vaccine efficacy was shown against DENV-1 and DENV-2 but was not observed against DENV-3 and low incidence precluded evaluation against DENV-4. During part 3 of the trial (approximately 22-57 months after the first vaccination), serious adverse events were reported for 664 (5·0%) of 13 380 TAK-003 recipients and 396 (5·9%) of 6687 placebo recipients; 17 deaths (6 in the placebo group and 11 in the TAK-003 group) were reported, none were considered study-vaccine related. INTERPRETATION: TAK-003 demonstrated long-term efficacy and safety against all four DENV serotypes in previously exposed individuals and against DENV-1 and DENV-2 in dengue-naive individuals. FUNDING: Takeda Vaccines. TRANSLATIONS: For the Portuguese, Spanish translations and plain language summary of the abstract see Supplementary Materials section.

Infant body composition at 6 and 24 months: what are the driving factors?

BACKGROUND/OBJECTIVE: Available evidence on infant body composition is limited. This study aimed to investigate factors associated with body composition at 6 and 24 months. SUBJECTS/METHODS: Multicenter study with data from a 0 to 6-mo cohort (Australia, India and South Africa) and a 3 to 24-mo cohort (Brazil, Pakistan, South Africa, and Sri Lanka). For the 0-6-mo cohort, body composition was assessed by air-displacement plethysmography (ADP) and for the 3-24-month cohort by the deuterium dilution (DD) technique. Fat mass (FM), fat-free mass (FFM), FM index (FMI), and FFM index (FFMI) were calculated. Independent variables comprised the Gini index of the country, maternal and infant characteristics, and breastfeeding pattern at 3 months. For the 3-24-mo cohort, breastfeeding, and minimum dietary diversity (MDD) at 12 months were also included. Crude and adjusted analyses stratified by sex were conducted by multilevel modelling using mixed models. RESULTS: At 6 months, every 1 kg increase in birth weight was associated with an increase of 0.716 kg in FFM and 0.582 kg/m2 in FFMI in girls, whereas in boys, the increase was of 0.277 kg in FFM. At 24 months, compared to those weaned before 12 months, girls still breastfed at 12 months presented a decrease of 0.225 kg in FM, 0.645 kg in FFM and 0.459 kg/m2 in FFMI, and in boys the decreases were of 0.467 kg in FM, 0.603 kg in FFM and 0.628 kg/m2 in FFMI. CONCLUSION: Birth weight and breastfeeding are independent predictors of body composition in early life, irrespective of sex.

Body composition from birth to 2 years.

Providing all infants with the best start to life is a universal but challenging goal for the global community. Historically, the size and shape of infants, quantified by anthropometry and commencing with birthweight, has been the common yardstick for physical growth and development. Anthropometry has long been considered a proxy for nutritional status during infancy when, under ideal circumstances, changes in size and shape are most rapid. Developed from data collected in the Multicentre Growth Reference Study (MGRS), WHO Child Growth Standards for healthy infants and children have been widely accepted and progressively adopted. In contrast, and somewhat surprisingly, much less is understood about the 'quality' of growth as reflected by body composition during infancy. Recent advances in body composition assessment, including the more widespread use of air displacement plethysmography (ADP) across the first months of life, have contributed to a progressive increase in our knowledge and understanding of growth and development. Along with stable isotope approaches, most commonly the deuterium dilution (DD) technique, the criterion measure of total body water (TBW), our ability to quantify lean and fat tissue using a two-compartment model, has been greatly enhanced. However, until now, global reference charts for the body composition of healthy infants have been lacking. This paper details some of the historical challenges associated with the assessment of body composition across the first two years of life, and references the logical next steps in growth assessments, including reference charts.

Body composition reference charts for infants from birth to 24 months: Multicenter Infant Body Composition Reference Study.

BACKGROUND: Body composition assessment in the first 2 y of life provides important insights into child nutrition and health. The application and interpretation of body composition data in infants and young children have been challenged by a lack of global reference data. OBJECTIVES: We aimed to develop body composition reference charts of infants aged 0-6 mo based on air displacement plethysmography (ADP) and those aged 3-24 mo based on total body water (TBW) by deuterium dilution (DD). METHODS: Body composition was assessed by ADP in infants aged 0-6 mo from Australia, India, and South Africa. TBW using DD was assessed for infants aged 3-24 mo from Brazil, Pakistan, South Africa, and Sri Lanka. Reference charts and centiles were constructed for body composition using the lambda-mu-sigma method. RESULTS: Sex-specific reference charts were produced for FM index (FMI), FFM index (FFMI), and percent FM (%FM) for infants aged 0-6 mo (n = 470 infants; 1899 observations) and 3-24 mo (n = 1026 infants; 3690 observations). When compared with other available references, there were observable differences but similar patterns in the trajectories of FMI, FFMI, and %FM. CONCLUSIONS: These reference charts will strengthen the interpretation and understanding of body composition in infants across the first 24 mo of life.

Serum Triglyceride to High-Density Lipoprotein Ratio as a Marker of Insulin Resistance Among 5-15-Year-Old Sri Lankan Children in an Urban Setting.

Objective: Prevalence of insulin resistance (IR) among South Asian populations is relatively high. It increases with the obesity epidemic. Since determining IR is costly, triglyceride to high-density lipoprotein (TG/HDL) ratio has shown to be a good proxy marker for IR in adults. However, it is not yet well established in children. This study aimed to assess TG/HDL ratio as a marker of IR in 5-15-year-old children in Colombo District of Sri Lanka. Methods: A cross-sectional descriptive study was conducted among 309 school children 5-15 years of age, selected using two-stage probability-proportionate-to-size cluster sampling technique. Sociodemographic data, and anthropometric and biochemical parameters were obtained. After a 12-hr overnight fast, blood was taken for biochemical investigations. Results: Three hundred nine children (173 girls) were recruited. Mean age of girls was 9.9 years and boys 10.3 years. Based on body mass index (BMI) z-score, 15.3% were overweight and 6.1% were obese. Metabolic syndrome was present in 2.3% of children and IR based on Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) ≥2.5 in 7.5%. Mean TG/HDL ratio, waist circumference (WC), hip circumference (HC), BMI, waist-to-height-ratio (WHtR), and body fat percentage were significantly higher (P < 0.01) among children with IR compared with non-IR children. TG/HDL ratio significantly correlated with BMI, % fat mass, WC, HC, WHtR, and HOMA-IR. TG/HDL ratio is an independent risk factor in determining IR. The cutoff value of TG/HDL ratio ≥3 had higher specificity (89.8%) but lower sensitivity (47.8%) for detection of IR. TG/HDL ratio >1.5 had a higher sensitivity (82.6%) but lower specificity (47.7%). Conclusions: TG/HDL ratio is a good proxy marker of IR among 5-15-year-old children. A cutoff value of ≥1.5 had satisfactory sensitivity and specificity.

The effect of foetal and early childhood growth on metabolic derangements of Sri Lankan children.

BACKGROUND: Previous studies have shown that delayed prenatal growth followed by accelerated postnatal growth plays a significant role on the onset of adult metabolic diseases. The present study aimed to identify the effects of intrauterine and later growth on metabolic derangements among children in Colombo, Sri Lanka. METHODS: A school-based cross-sectional study was conducted among 5-15-year-old children selected using a two-stage probability-proportionate-to-size cluster sampling technique. Birth-weight (BW) was extracted from records (denotes prenatal growth) and body mass index(BMI)-Z score and fat mass(FM) measured to denote the current growth of children. Fasting and random blood glucose, lipid profile and blood pressure(BP) were measured. The sample was stratified by age (5-< 10 and 10-15 years); was further categorized into tertiles of BW and BMI-Z scores. Based on these two parameters, metabolic parameters were evaluated within each age category. RESULTS: The sample comprised 833(494 boys) healthy school children. Metabolic parameters did not significantly differ by sex or across BW tertiles of each BMI-Z score tertile. However, significant changes in some metabolic parameters were noted across the BMI-Z score tertiles of each BW tertile. Children belonging to the lowest BW and highest BMI-Z score tertiles had worst metabolic profiles, while those in the lowest BW as well as BMI-Z score tertile were protected. Excessive fat deposition seemed to move children to higher BMI-Z score tertiles. CONCLUSION: Poor prenatal growth is not the sole risk factor for abnormal metabolic profile found in childhood. Those who gain fat, denoted by weight, during early childhood are at a higher risk of developing metabolic abnormalities than those who do not. This favours the accelerated postnatal growth hypothesis.

The Long-Term Consequences of Early Life Exposure to Tsunami and Conflict on Adolescents in Sri Lanka.

The consequences for adolescent health due to early life exposure to natural disasters combined with war are not known. We collected data from adolescents aged 12-13 years in Sri Lanka whose mothers were pregnant during the Indian Ocean tsunami in 2004 in a tsunami-affected region (n = 22), conflict-affected region (n = 35), conflict-plus-tsunami-affected region (n = 29), or controls in areas unaffected by either (n = 24). Adjusted body mass index (BMI)-for-age z-scores were 1.3, 1.0 and 2.0 for conflict, tsunami, and conflict-plus-tsunami, respectively, compared with the control group. Greater skinfold thickness and higher diastolic blood pressure were found in adolescents born in the conflict zone but no differences were found in height, head circumference, and waist circumference, or blood results, with the exception of serum insulin. Being born after a natural disaster or during conflict was associated with increased BMI and body fat during adolescent, which are associated with longer-term risk of noncommunicable disease.

External validation of a prediction model for estimating fat mass in children and adolescents in 19 countries: individual participant data meta-analysis.

OBJECTIVE: To evaluate the performance of a UK based prediction model for estimating fat-free mass (and indirectly fat mass) in children and adolescents in non-UK settings. DESIGN: Individual participant data meta-analysis. SETTING: 19 countries. PARTICIPANTS: 5693 children and adolescents (49.7% boys) aged 4 to 15 years with complete data on the predictors included in the UK based model (weight, height, age, sex, and ethnicity) and on the independently assessed outcome measure (fat-free mass determined by deuterium dilution assessment). MAIN OUTCOME MEASURES: The outcome of the UK based prediction model was natural log transformed fat-free mass (lnFFM). Predictive performance statistics of R2, calibration slope, calibration-in-the-large, and root mean square error were assessed in each of the 19 countries and then pooled through random effects meta-analysis. Calibration plots were also derived for each country, including flexible calibration curves. RESULTS: The model showed good predictive ability in non-UK populations of children and adolescents, providing R2 values of >75% in all countries and >90% in 11 of the 19 countries, and with good calibration (ie, agreement) of observed and predicted values. Root mean square error values (on fat-free mass scale) were <4 kg in 17 of the 19 settings. Pooled values (95% confidence intervals) of R2, calibration slope, and calibration-in-the-large were 88.7% (85.9% to 91.4%), 0.98 (0.97 to 1.00), and 0.01 (-0.02 to 0.04), respectively. Heterogeneity was evident in the R2 and calibration-in-the-large values across settings, but not in the calibration slope. Model performance did not vary markedly between boys and girls, age, ethnicity, and national income groups. To further improve the accuracy of the predictions, the model equation was recalibrated for the intercept in each setting so that country specific equations are available for future use. CONCLUSION: The UK based prediction model, which is based on readily available measures, provides predictions of childhood fat-free mass, and hence fat mass, in a range of non-UK settings that explain a large proportion of the variability in observed fat-free mass, and exhibit good calibration performance, especially after recalibration of the intercept for each population. The model demonstrates good generalisability in both low-middle income and high income populations of healthy children and adolescents aged 4-15 years.

Timing and pattern of growth faltering in children up-to 18 months of age and the associated feeding practices in an urban setting of Sri Lanka.

BACKGROUND: Growth faltering is commonly encountered in breastfed infants during 4-6 months of age in low socioeconomic communities. The objective of this study was to describe the changes of growth indices with age, timing of growth faltering and its association with the feeding practices in children up-to 18 months of age. METHODS: A cross sectional descriptive study was conducted in 254 children aged 12 and 18 months attending an immunization clinic. Data on growth were extracted from the Child Health Development Record. Weight and length were measured using standard methods. Feeding practices were assessed using interviewer-administered questionnaire. A drop of > 0.25 in weight-for-age Standard Deviation Score (SDS) from birth SDS was defined as weight faltering. RESULTS: Weight faltering occurred at some point in 64.2% (n = 163) during first 18 months of life, and 78.5% of whom, had the onset ≤ 4 months of age. Majority (76.6%, n = 98) with weight for age faltering by 4 months remained so at 12 months (p = 0.497), while 29.7% (n = 38) had a weight-for-length below-2SD (p < 0.001). Prevalence of weight faltering was 50.4%, 46.1%, 48.4% and 48% at 4, 6, 9 and 12 months respectively. Exclusive breastfeeding was given at least until 4 months in 88% (n = 223) and up to 6 months in 60% (n = 153) while 92.9% (n = 236) were breastfed at 12 months, with 38.2% (n = 97) were breastfed on demand after six months. Complementary feeding (CF) was started before 6 months in 40.6% (n = 52) with early weight faltering, but only 20.3% received it with proper consistency. Breastfeeding throughout the night was significantly associated with current weight-for-length being < -1SD (OR = 1.89, CI, 1.04-3.45; p = 0.037). CONCLUSIONS: Early growth faltering was found in this population with high exclusive breastfeeding rates and persisting growth faltering was associated with poor feeding practices. Therefore, timely individualized interventions need to be taken to improve long term growth.

Levels and Correlates of Objectively Measured Sedentary Behavior in Young Children: SUNRISE Study Results from 19 Countries.

PURPOSE: There is a paucity of global data on sedentary behavior during early childhood. The purpose of this study was to examine how device-measured sedentary behavior in young children differed across geographically, economically, and sociodemographically diverse populations, in an international sample. METHODS: This multinational, cross-sectional study included data from 1071 children 3-5 yr old from 19 countries, collected between 2018 and 2020 (pre-COVID). Sedentary behavior was measured for three consecutive days using activPAL accelerometers. Sedentary time, sedentary fragmentation, and seated transport duration were calculated. Linear mixed models were used to examine the differences in sedentary behavior variables between sex, country-level income groups, urban/rural settings, and population density. RESULTS: Children spent 56% (7.4 h) of their waking time sedentary. The longest average bout duration was 81.1 ± 45.4 min, and an average of 61.1 ± 50.1 min·d-1 was spent in seated transport. Children from upper-middle-income and high-income countries spent a greater proportion of the day sedentary, accrued more sedentary bouts, had shorter breaks between sedentary bouts, and spent significantly more time in seated transport, compared with children from low-income and lower-middle-income countries. Sex and urban/rural residential setting were not associated with any outcomes. Higher population density was associated with several higher sedentary behavior measures. CONCLUSIONS: These data advance our understanding of young children's sedentary behavior patterns globally. Country income levels and population density appear to be stronger drivers of the observed differences, than sex or rural/urban residential setting.

Effects of probiotics combined with dietary and lifestyle modification on clinical, biochemical, and radiological parameters in obese children with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis: a randomized clinical trial.

BACKGROUND: Childhood obesity is a global problem associated with metabolic abnormalities. The gut-liver axis is thought to play a major role in its pathogenesis. Probiotics are known to alter the gut microbiota and, therefore, could be a therapeutic option in the management of childhood obesity-related complications. PURPOSE: This double-blind randomized placebo-controlled trial evaluated the effects of probiotics on metabolic derangement in obese children with nonalcoholic fatty liver disease/ nonalcoholic steatohepatitis (NAFLD/NASH). METHODS: Obese children with NAFLD/NASH treated at the nutrition clinic of the University Paediatric Unit at Lady Ridgeway Hospital, Colombo, were recruited. Anthropometry, body fat, metabolic derangement, and liver ultrasound scan (USS) results were evaluated at baseline and after 6 months. Transient elastography (FibroScan) was performed on a subsample of these patients. Eighty-four patients were recruited and randomized into the probiotics (n=43) and placebo (n= 41) groups. The mean age was 11.3±1.9 versus 12.1±1.5 years in the probiotic and placebo groups, respectively. Baseline parameters including liver disease stage on USS, body fat percentage, fasting blood sugar, lipid profile, liver function, and C-reactive protein showed no significant intergroup differences. RESULTS: In the probiotic group, a statistically significant reduction in body mass index was noted from the baseline value. However, the reduction was not significant compared with the placebo group. There was a significant reduction in triglycerides, aspartate transaminase (AST), alanine aminotransferase (ALT), AST/ALT ratio, and alkaline phosphatase in the placebo group over the treatment period. Although the liver disease stage on USS improved from stage II-III to stage I in a small number of patients in the probiotic-treated group, transient elastography performed in a subsample did not demonstrate significant improvement in either group. CONCLUSION: Our results indicate that probiotics have no advantage over lifestyle modification for improving obesityassociated metabolic derangement in children.

Global effect of COVID-19 pandemic on physical activity, sedentary behaviour and sleep among 3- to 5-year-old children: a longitudinal study of 14 countries.

BACKGROUND: The restrictions associated with the 2020 COVID-19 pandemic has resulted in changes to young children's daily routines and habits. The impact on their participation in movement behaviours (physical activity, sedentary screen time and sleep) is unknown. This international longitudinal study compared young children's movement behaviours before and during the COVID-19 pandemic. METHODS: Parents of children aged 3-5 years, from 14 countries (8 low- and middle-income countries, LMICs) completed surveys to assess changes in movement behaviours and how these changes were associated with the COVID-19 pandemic. Surveys were completed in the 12 months up to March 2020 and again between May and June 2020 (at the height of restrictions). Physical activity (PA), sedentary screen time (SST) and sleep were assessed via parent survey. At Time 2, COVID-19 factors including level of restriction, environmental conditions, and parental stress were measured. Compliance with the World Health Organizations (WHO) Global guidelines for PA (180 min/day [≥60 min moderate- vigorous PA]), SST (≤1 h/day) and sleep (10-13 h/day) for children under 5 years of age, was determined. RESULTS: Nine hundred- forty-eight parents completed the survey at both time points. Children from LMICs were more likely to meet the PA (Adjusted Odds Ratio [AdjOR] = 2.0, 95%Confidence Interval [CI] 1.0,3.8) and SST (AdjOR = 2.2, 95%CI 1.2,3.9) guidelines than their high-income country (HIC) counterparts. Children who could go outside during COVID-19 were more likely to meet all WHO Global guidelines (AdjOR = 3.3, 95%CI 1.1,9.8) than those who were not. Children of parents with higher compared to lower stress were less likely to meet all three guidelines (AdjOR = 0.5, 95%CI 0.3,0.9). CONCLUSION: PA and SST levels of children from LMICs have been less impacted by COVID-19 than in HICs. Ensuring children can access an outdoor space, and supporting parents' mental health are important prerequisites for enabling pre-schoolers to practice healthy movement behaviours and meet the Global guidelines.

Development of a New Equation for the Prediction of Resting Metabolic Rate in Sri Lankan Adults.

Resting metabolic rate (RMR) is the key determinant of the energy requirement of an individual. Measurement of RMR by indirect calorimetry is not feasible in field settings and therefore equation-based calculations are used. Since a valid equation is not available for Sri Lankans, it is important to develop a new population-specific equation for field use. The study objective was to develop a new equation for the prediction of RMR in healthy Sri Lankans using a reference method, indirect calorimetry. RMR data were collected from fifty-seven (male 27) adults aged 19 to 60 years. They were randomly assigned to validation (n = 28) and cross-validation (n = 19) groups using the statistical package R (version 3.6.3). Height, weight, and RMR were measured. Multivariable fractional polynomials (MFP) were used to determine explanatory variables and their functional forms for the model. A variable shrinkage method was used to find the best fit predictor coefficients of the equation. The developed equation was cross-validated on an independent group. Weight and sex code (male = 1; female = 0) were identified as reliable independent variables. The new equation developed was RMR (kcal/day) = 284.5 + (13.2 x weight) + (133.0 x sex code). Independent variables of the prediction equation were able to predict 88.5% of the variance. Root mean square error (RMSE) of the prediction equation in validation and cross-validation was 88.11 kcal/day and 79.03 kcal/day, respectively. The equation developed in this study is suitable for predicting RMR in Sri Lankan adults.

Nutritional status of school children living in Northern part of Sri Lanka.

BACKGROUND: Nutritional status is an important indicator for measuring quality of life in children. A region that is recovering from war will face many problems related to nutrition. Very few studies have addressed the nutritional problems in school children. This study was undertaken to identify the prevalence of wasting, stunting and obesity among school children from Northern Sri Lanka and associated socio-demographic factors. METHODS: A community based cross-sectional study was carried out using multistage stratified proportionate cluster among healthy children attending schools in the Northern part of the country. Height and weight were measured, and Body Mass Index (BMI) calculated [weight (kg)/Height (m) 2]. BMI-for-age z-score (BAZ) and Height for age Z (HAZ) scores were determined and WHO growth references were used to categorise the nutritional status. Correlation between various nutritional problems with Maternal education, household income, number of family members and the residential area was assessed. RESULTS: A total of 1012 children were recruited, and the mean age and standard deviation were 11.12±1.77 yrs. Girls in the age ranges of 9-14 were heavier and taller when compared to the boys compatible with the pubertal growth spurt. Stunting based on the height for age was seen in 10.9% of boys and 11.8% of girls. Wasting based on BMI for age WHO standard (WHO 2007) was seen in 30.6% of boys and 29.1% of the girls. The prevalence of overweight was 11% and Obesity was 6.3% of the population. Obesity was predominantly seen in boys (4.2%) and it was significantly higher when compared to the girls (2.1%) (p < 0.001). Obesity in older boys (> 10 years) was significantly more than the younger ones (p < 0.01). Maternal education and family income had a significant impact on the prevalence of wasting, stunting and obesity whereas the family size contributed to the wasting and obesity (p< 0.001). CONCLUSION: Findings suggest that stunting, wasting, overweight and obesity are prevalent among 6-16-year-old leading to concerns in public health. The nutritional status significantly varies according to the geographical location, maternal education and the household income.

Association between early weight gain and later adiposity in Sri Lankan adolescents.

Early growth pattern is increasingly recognized as a determinant of later obesity. This study aimed to identify the association between weight gain in early life and anthropometry, adiposity, leptin, and fasting insulin levels in adolescence. A cross-sectional study was conducted in 366 school children aged 11-13 years. Weight, height, and waist circumference (WC) were measured. Fat mass (FM) was assessed using bioelectrical impedance analysis. Blood was drawn after a 12-h fast for insulin and leptin assay. Birth weight and weight at 6 months and at 18 months were extracted from Child Health Development Records. An increase in weight SD score (SDS) by ≥0.67 was defined as accelerated weight gain. Linear mixed-effects modeling was used to predict anthropometry, adiposity, and metabolic outcomes using sex, pubertal status, accelerated weight gain as fixed factors; age, birth weight, and family income as fixed covariates, and school as a random factor. Children with accelerated weight gain between birth and 18 months had significantly higher body mass index (BMI) SDS, WC SDS, height SDS, %FM, fat mass index (FMI), fat free mass index (FFMI), and serum leptin levels in adolescence. Accelerated weight gain between 6 and 18 months was associated with higher BMI SDS, WC SDS, %FM, and FMI, but not with height SDS or FFMI. Accelerated weight gain at 0-6 months, in children with low birth weight, was associated with higher height SDS, BMI SDS, WC SDS, %FM, and FMI; in children with normal birth weight, it was associated with BMI SDS, WC SDS, height SDS, and FFMI, but not with %FM or FMI. Effects of accelerated weight gain in early life on anthropometry and adiposity in adolescence varied in different growth windows. Accelerated weight gain during 6-18 months was associated with higher FM rather than linear growth. Effects of accelerated weight gain between 0 and 6 months varied with birth weight.

Baseline iron and low-grade inflammation modulate the effectiveness of iron supplementation: evidence from follow-up of pregnant Sri Lankan women.

PURPOSE: We evaluated the effectiveness of iron supplementation in relation to baseline iron and inflammatory status of pregnant women and their offspring in Sri Lanka. METHODS: Apparently healthy women aged 18-36 years at < 12 weeks of gestation prior to receiving any supplementation were randomly recruited at the antenatal clinics. They received 60 mg of elemental iron in combined iron-folic acid pills from 12 weeks of gestation until delivery via the National Maternal Supplementation Programme. Serum ferritins (SF), hemoglobin and high-sensitive C-reactive protein (hs-CRP) were assessed. The women were grouped as iron sufficient-inflammation (+), iron sufficient-inflammation (-), iron deficient-inflammation (+) and iron deficient-inflammation (-) based on their baseline iron stores and low-grade inflammation (hs-CRP > 5 < 10 mg/L) at baseline and late pregnancy. RESULTS: Despite supplementation, SF in the iron sufficient-inflammation (+) women reduced significantly (p = 0.037) to deficiency state (SF < 30 µg/L) at mid-pregnancy. Whereas no significant changes were noted in the SF in iron sufficient-inflammation (-) women (p > 0.05). They maintained their stores at sufficient state until delivery. The cord SF was higher (p < 0.001) in iron sufficient-inflammation (-) than the inflammation (+) women. 96.4% of the iron deficient women remained deficient until delivery regardless of their inflammatory state. Low-grade inflammation was higher (p < 0.001) in women with baseline BMI > 25 kg/m2. Whereas inflammation at late pregnancy was higher (p < 0.001) in women who gained weight in excess of the recommended, regardless of their baseline BMI. CONCLUSION: Iron status prior to supplementation and low-grade inflammation associated with BMI > 25 kg/m2 and excess weight gain during pregnancy appear to modulate the effectiveness of iron supplementation.

Prevalence of different states of glucose intolerance in Sri Lankan children and adolescents with obesity and its relation to other comorbidities.

BACKGROUND: South Asian adults have higher prevalence of obesity comorbidities than other ethnic groups. Whether this also is true for Sri Lankan children with obesity has rarely been investigated. OBJECTIVE: To investigate prevalence of glucose intolerance and other comorbidities in Sri Lankan children with obesity and compare them with Swedish children. To identify risk factors associated with glucose intolerance. SUBJECTS: A total of 357 Sri Lankan children (185 boys), aged 7 to 17 years with BMI-SDS ≥2.0 from a cross-sectional school screening in Negombo. A total of 167 subjects from this study population were matched for sex, BMI-SDS and age with 167 Swedish subjects from the ULSCO cohort for comparison. METHODS: After a 12 hour overnight fast, blood samples were collected and oral glucose tolerance test was performed. Body fat mass was assessed by bioelectrical impedance assay. Data regarding medical history and socioeconomic status were obtained from questionnaires. RESULTS: Based on levels of fasting glucose (FG) and 2 hours-glucose (2 hours-G), Sri Lankan subjects were divided into five groups: normal glucose tolerance (77.5%, n = 276), isolated impaired fasting glucose according to ADA criteria (9.0%, n = 32), isolated impaired glucose tolerance (8.4%, n = 30), combined impaired fasting glucose (IFG) + impaired glucose tolerance (IGT) (3.1%, n = 11) and type 2 diabetes mellitus (2.0%, n = 7). FG, 2 hours-insulin and educational status of the father independently increased the Odds ratio to have elevated 2 hours-G. Sri Lankan subjects had higher percentage of body fat, but less abdominal fat than Swedish subjects. CONCLUSION: High prevalence in Sri Lankan children with obesity shows that screening for glucose intolerance is important even if asymptomatic.