Effect of Calcium and Vitamin D Supplementation (Dairy vs. Pharmacological) on Bone Health of Underprivileged Indian Children and Youth with Type-1 Diabetes: A Randomized Controlled Trial.

BACKGROUND: Bone health is affected by chronic childhood disorders including type-1 diabetes mellitus (T1DM). We conducted this randomized controlled trial with the objective of investigating the effect of 1-year supplementation of vitamin-D with milk or with pharmacological calcium on bone mass accrual in underprivileged Indian children and youth with T1DM. METHODS: 5 to 23year old (n = 203) underprivileged children and youth with T1DM were allocated to one of three groups: Milk (group A-received 200 ml milk + 1000 international unit (IU) vitamin-D3/day), Calcium supplement (group B-received 500 mg of calcium carbonate + 1000 IU of vitamin-D3/day) or standard of care/control (group C). Anthropometry, clinical details, biochemistry, diet (3-day 24-h recall), physical activity (questionnaires adapted for Indian children) and bone health parameters (using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography- DXA and pQCT respectively) were evaluated at enrolment and end of 12 month intervention. RESULTS: Total body less head(TBLH) bone mineral content (BMC(g)) and bone mineral density (BMD(gm/cm2)) were significantly higher at end of study in girls in both supplemented groups (TBLHBMC-A-1011.8 ±â€¯307.8, B-983.2 ±â€¯352.9, C-792.8 ±â€¯346.8. TBLHBMD-A-± 0.2, B-0.8 ±â€¯0.2, C-0.6 ±â€¯0.2, p < 0.05). Z score of lumbar spine bone mineral apparent density of supplemented participants of both sexes was significantly higher than controls (Boys- A-0.7 ±â€¯1.1, B-0.6 ±â€¯1.4, C- -0.7 ±â€¯1.1; Girls- A-1.1 ±â€¯1.1, B-0.9 ±â€¯3.4, C- -1.7 ±â€¯1.3, p < 0.05). A significantly higher percentage increase was found in cortical thickness in girls in both supplemented groups (A-17.9 ±â€¯28.6, B-15.3 ±â€¯16.5, C-7.6 ±â€¯26.2); the differences remained after adjusting for confounders. CONCLUSION: Supplementation with milk or pharmacological calcium (+vitaminD3) improved bone outcomes-particularly geometry in children with T1DM with more pronounced effect in girls. Pharmacological calcium may be more cost effective in optimising bone health in T1DM in resource limited settings.

BoneXpert-derived bone health index reference curves constructed on healthy Indian children and adolescents.

BACKGROUND: Artificial intelligence (AI)-based applications for the assessment of the paediatric musculoskeletal system like BoneXpert are not only useful to assess bone age (BA) but also to provide a bone health index (BHI) and a standard deviation score (SDS) for both. This allows comparison of the BHI with age- and sex-matched healthy Caucasian children. OBJECTIVE: We conducted this study with the objective of generating BHI curves using BoneXpert in healthy Indian children with BA between 2 and 17 years. METHOD: We retrospectively reviewed anthropometric parameters, BHI, and BHI SDS data of digitalized left-hand radiographs (joint photographic experts group [jpg] format) of a cohort of 788 paediatric patients from a previous study to which they were recruited to compare various methods of BA assessment. The recruited children represented all age groups for both sexes. The corrected BHI for jpg images was calculated using the formula corrected BHI=BHI*(stature/(avL*50))^0.33333 where stature is height of subject and avL is average length of metacarpal bones. The reference Indian BHI curves and centiles were generated using the Lambda-Mu-Sigma method. RESULT: The mean BHI and BHI SDS of the study group were 4.02±0.57 and -1.73±1.09, respectively. The average increase in median BHI from each age group was between 2.5% and 3% in both sexes up to age of 14 years after which it increased to 4.5% to 5%. The mean BHI of Indian children was lower than that of Caucasian children with maximum differences noted in boys at 16 years (21.7%) and girls at 14 years (16%). We report 8.4% SD of BHI for our study sample. Reference percentile curves for BHI according to BA were derived separately for boys and girls. CONCLUSION: Reference data has been provided for the screening of bone health status of Indian children and adolescents.

Impact of Adolescent Pregnancy on Bone Density in Underprivileged Pre-Menopausal Indian Women.

High prevalence (31.5%) of adolescent pregnancies (AP) have been reported in India. Reports suggest that pregnancy during adolescence may have deleterious effects on peak bone mass. Very few studies have described the long-term effects of a history of AP on bone mass. The objective of this study was to compare bone mineral density (BMD) and bone geometry of premenopausal women with first childbirth during adolescence (i.e., before age of 19 years) or after 20 years. A cross-sectional study was conducted in 242 women (age 28.0-54.5 years) from Pune, India (November, 2015 to November, 2017). Women were divided into 2-groups: Group-1: women-who had 1st-pregnancy and childbirth before 19 years of age (AP n = 131) and Group-2: women-who had 1st pregnancy after 20 years of age (non-AP n = 111). Demographic data, anthropometric measurements, and biochemical tests were performed using standard protocols. Physical activity and nutrient intakes were recorded using validated questionnaires. Areal BMD and bone geometry were measured using Dual-Energy-Absorptiometry-DXA (Lunar-iDXA, GE Healthcare) and peripheral-quantitative-computed-tomography-pQCT (XCT2000, Stratec Inc.). Mean age of the study group was 37 ± 4.6 years; in women from group-1 mean age at first delivery was 16.9 ± 1.6 years as against 22.6 ± 3.1 years in group-2. Both groups were similar in body mass index and socioeconomic status. pQCT measured radial diaphyseal cortical thickness (1.97 ± 0.3 mm vs 1.88 ± 0.3 mm resp., p = 0.016, periosteal circumference (38.0 ± 3.6 mm vs 36.7 ± 2.5 mm, resp. p = 0.016), total bone area (114.3 ± 24.8 mm2 vs 108.7 ± 14.7 mm2 resp. p = 0.026) and stress-strain index (SSI = 217 ± 75 vs 201 ± 40 mm3 resp. p = 0.042) were significantly higher in group-1 than group-2. After adjusting for anthropometric and lifestyle parameters, pQCT measured cortical thickness (1.98 ± 0.03 mm in group-1, 1.87 ± 0.03 mm group-2, p = 0.01, mean ± SE) and iDXA derived aBMD at forearm were still significantly higher (0.599 ± 0.006 g/cm3 vs 0.580 ± 0.006 g/cm3, p = 0.023) in Group-1. Our data suggest that women with a history of adolescent pregnancy had better bone geometry and higher aBMD at radius in later years. We speculate that early exposure to pregnancy resulted in higher aBMD at the radius and induced changes at radial diaphysis with bones becoming thicker and wider among these women.

A comparison of bone age assessments using automated and manual methods in children of Indian ethnicity.

BACKGROUND: Bone age is useful for pediatric endocrinologists in evaluating various disorders related to growth and puberty. Traditional methods of bone age assessment, namely Greulich and Pyle (GP) and Tanner-Whitehouse (TW), have intra- and interobserver variations. Use of computer-automated methods like BoneXpert might overcome these subjective variations. OBJECTIVE: The aim of our study was to assess the validity of BoneXpert in comparison to manual GP and TW methods for assessing bone age in children of Asian Indian ethnicity. MATERIALS AND METHODS: We extracted from a previous study the deidentified left hand radiographs of 920 healthy children aged 2-19 years. We compared bone age as determined by four well-trained manual raters using GP and TW methods with the BoneXpert ratings. We computed accuracy using root mean square error (RMSE) to assess how close the bone age estimated by BoneXpert was to the reference rating. RESULTS: The standard deviations (SDs) of rating among the four manual raters were 0.52 years, 0.52 years and 0.47 years for GP, TW2 and TW3 methods, respectively. The RMSEs between the automated bone age estimates and the true ratings were 0.39 years, 0.41 years and 0.36 years, respectively, for the same methods. The RMSE values were significantly lower in girls than in boys (0.53, 0.5 and 0.47 vs. 0.39, 0.47 and 0.4) by all the methods; however, no such difference was noted in classification by body mass index. The best agreement between BoneXpert and manual rating was obtained by using 50% weight on carpals (GP50). The carpal bone age was retarded in Indian children, more so in boys. CONCLUSION: BoneXpert was accurate and performed well in estimating bone age by both GP and TW methods in healthy Asian Indian children; the error was larger in boys. The GP50 establishes "backward compatibility" with manual rating.

Prevalence of Sarcopenia and Relationships Between Muscle and Bone in Indian Men and Women.

Both ethnicity and age are important determinants of musculoskeletal health. We aimed to determine the prevalence of sarcopenia, assess the suitability of current diagnostic guidelines, and explore muscle-bone relationships in adults from India. A total of 1009 young (20-35 years) and 1755 older (> 40 years) men and women from existing studies were collated and pooled for the analysis. Dual-energy x-ray absorptiometry measured areal bone mineral density (aBMD) at the hip and spine, and fat and lean mass; hand dynamometer measured hand grip strength (HGS). Indian-specific cut-points for appendicular lean mass (ALM), ALM index (ALMI) and HGS were calculated from young Indian (-2SD mean) populations. Sarcopenia was defined using cut-points from The Foundations for the National Institutes of Health (FNIH), revised European Working Group on Sarcopenia in Older People (EWGSOP2), Asian Working Group for Sarcopenia (AWGS), and Indian-specific cut-points. Low lean mass cut-points were then compared for their predictive ability in identifying low HGS. The relationship between muscle variables (ALM, ALMI, HGS) and aBMD was explored, and sex differences were tested. Indian-specific cut-points (men-HGS:22.93 kg, ALM:15.41 kg, ALMI:6.03 kg/m2; women-HGS:10.76 kg, ALM:9.95 kg, ALMI:4.64 kg/m2) were lower than existing definitions. The Indian-specific definition had the lowest, while EWGSOP2 ALMI had the highest predictive ability in detecting low HGS (men:AUC = 0.686, women:AUC = 0.641). There were sex differences in associations between aBMD and all muscle variables, with greater positive associations in women than in men. The use of appropriate cut-points for diagnosing low lean mass and physical function is necessary in ethnic populations for accurate sarcopenia assessment. Muscle-bone relationships are more tightly coupled during ageing in Indian women than men.

Paradoxical Response of Parathyroid Hormone to Vitamin D-Calcium Supplementation in Indian Children.

OBJECTIVES: To investigate the effect of oral vitamin D-calcium supplementation on serum intact parathyroid hormone (PTH), calcium, phosphorous, and alkaline phosphatase (ALK-P) concentrations in children with habitually low calcium intakes. STUDY DESIGN: In this follow-up study to a randomized controlled trial that aimed to assess the effect of vitamin D-calcium supplementation on immunity, data related to dietary intake, anthropometry, and biochemistry [serum 25(OH)D and bone profile] were collected from 178 children-79 in the vitamin D group and 99 in the non-vitamin D group. RESULTS: Dietary calcium to phosphorus intake ratio was 0.4:1. Baseline serum 25(OH)D concentration was 58.2 ± 10.9 nmol/L; 66% children were vitamin D sufficient and none deficient. After supplementation, vitamin D group, compared with the non-vitamin D group, had significantly (P < .05) greater 25(OH)D (83.9 ± 30.1 nmol/L vs 58.3 ± 15.7 nmol/L), significantly greater PTH (6.7 ± 3.6 pmol/L vs 5.5 ± 3.2 pmol/L), and positive correlation (rs = 0.24) between serum 25(OH)D and PTH (vs negative correlation [rs = -0.1] in non-vitamin D group). Mean concentrations of serum bone measures in the vitamin D group were calcium (2.2 ± 0.1 mmol/L), phosphorus (1.7 ± 0.2 mmol/L), and ALK-P (178.7 ± 40.7 IU/L). At follow-up, 1-year post-supplementation, in the vitamin D group, PTH concentrations continued to remain high (but not significantly different from levels at 6 months), with low normal serum calcium, high normal phosphate, and ALK-P in reference range. CONCLUSIONS: In children who are vitamin D sufficient but with habitually low dietary calcium intake, vitamin D-calcium supplementation paradoxically and significantly increased serum PTH concentrations with no apparent effect on other bone biochemistry. Chronic low dietary calcium to phosphorus ratio is likely to have caused this paradoxical response.

Sitting height percentiles in 3-17-year-old Indian children: a multicentre study.

Background: Sitting height (StH) percentiles are not described for the Indian paediatric population.Aim: To generate multicentre StH percentile values for Indian children.Subjects and methods: A total of 7961 apparently healthy children (3-17 years old, Boys: 4328) randomly selected from 10 schools from six states of India were measured for height (ht), StH and weight during July 2016-October 2017.Results: The StH:Ht ratio was 0.52 (0.02) and was similar between boys and girls (p > 0.1). The ratio decreased in boys until the age of 14 years and then slightly increased; the lowest ratio was observed during 13-15 years. In girls, however, the StH:Ht ratio decreased until the age of 9 years and then plateaued until 15 years of age with a slight increase at 16 years; the lowest ratio was observed at the age of 12-13 years. Sitting height percentiles (3rd, 10th, 25th, 50th, 75th, 90th and 97th) were computed using LMS chartmaker.Conclusions: The results indicate that, during the pubertal years, the lower limb growth is more predominant than trunk growth. Further, this study provides smoothened percentile curves for sitting height in Indian children for the first time.

Impact of dietary nutrient intake and physical activity on body composition and growth in Indian children.

BackgroundTo investigate interrelationships of dietary composition and physical activity (PA) with growth and body composition (BC) in urban Indian school children.MethodsA cross-sectional study was performed in 4,747 Indian school children (2,623 boys) aged 3-18 years. Weight, height, BC by body impedance analyzer, PA and dietary food intakes by questionnaire method were recorded.ResultsMean daily energy and protein intakes as recommended dietary allowance were significantly lower in both boys and girls (P<0.01) above 6 years, with 55% reduction in micronutrient intakes in older children. When compared with World Health Organization references, lower heights in pubertal boys and girls were related to dietary energy and protein intake. Multiple regression analysis showed positive association of height for age z-scores (HAZ) with midparental height z-scores (ß=0.45, P=0.0001) and protein density (ß=0.103, P=0.014). HAZ was negatively associated with inactivity (ß=-0.0001, P=0.049) in boys and girls (R2=0.104, P<0.01). Further, body fat percentage was negatively correlated with moderate or light activity and antioxidant intakes (P<0.01) but not with dietary fat intake. Percentage muscle mass was positively correlated with moderate activity and negatively with inactivity (P<0.05).ConclusionAdequacy of protein and antioxidant intakes, reducing inactivity and increasing moderate activity are essential for optimal growth and body composition in Indian children.

Establishing International Blood Pressure References Among Nonoverweight Children and Adolescents Aged 6 to 17 Years.

BACKGROUND: Several distributions of country-specific blood pressure (BP) percentiles by sex, age, and height for children and adolescents have been established worldwide. However, there are no globally unified BP references for defining elevated BP in children and adolescents, which limits international comparisons of the prevalence of pediatric elevated BP. We aimed to establish international BP references for children and adolescents by using 7 nationally representative data sets (China, India, Iran, Korea, Poland, Tunisia, and the United States). METHODS AND RESULTS: Data on BP for 52 636 nonoverweight children and adolescents aged 6 to 19 years were obtained from 7 large nationally representative cross-sectional surveys in China, India, Iran, Korea, Poland, Tunisia, and the United States. BP values were obtained with certified mercury sphygmomanometers in all 7 countries by using standard procedures for BP measurement. Smoothed BP percentiles (50th, 90th, 95th, and 99th) by age and height were estimated by using the Generalized Additive Model for Location Scale and Shape model. BP values were similar between males and females until the age of 13 years and were higher in males than females thereafter. In comparison with the BP levels of the 90th and 95th percentiles of the US Fourth Report at median height, systolic BP of the corresponding percentiles of these international references was lower, whereas diastolic BP was similar. CONCLUSIONS: These international BP references will be a useful tool for international comparison of the prevalence of elevated BP in children and adolescents and may help to identify hypertensive youths in diverse populations.

Waist circumference percentiles in 2-18 year old Indian children.

OBJECTIVES: To develop reference percentile curves in Indian children for waist circumference (WC), and to provide a cutoff of WC percentile to identify children at risk for metabolic syndrome (MS). STUDY DESIGN: A multicenter, cross-sectional study was performed in 5 major Indian cities. Height, weight, and blood pressure (BP) were measured in 10,842 children (6065 boys). Elevated BP was defined as either systolic BP or diastolic BP >95th percentile. WC was measured with the child standing using a stretch-resistant tape. Sex-specific reference percentiles were computed using the LMS method which constructs reference percentiles adjusted for skewness. To determine optimal cutoffs for WC percentiles, a validation sample of 208 children was assessed for MS risk factors (ie, anthropometry, BP, blood lipids), and receiver operating characteristic (ROC) curve analysis was performed. RESULTS: Age- and sex-specific WC percentiles (5th, 10th, 15th, 25th, 50th, 75th, 85th, 90th, and 95th) are presented. WC values increased with age in both the boys and the girls. The median WC at age >15 years was greater in boys compared with girls. ROC analysis suggested the 70th percentile as a cutoff for MS risk (sensitivity, 0.84 in boys and 0.82 in girls; specificity, 0.85 in both boys and girls; area under the ROC curve, 0.88 in boys and 0.92 in girls). CONCLUSION: Age- and sex-specific reference curves for WC for Indian children and cutoff values of 70th WC percentile for screening for MS risk are provided.

Effect of one-year growth hormone therapy on body composition and cardio-metabolic risk in Indian children with growth hormone deficiency.

Growth hormone (GH) deficiency in children manifests as short stature but is also associated with metabolic disturbances. Paucity of GH is also likely to be associated with increased intima media thickness. Data on body composition (BC) and carotid intima media thickness (cIMT) in children with growth hormone deficiency (GHD) from developing countries are very scarce. Therefore, objectives of present study were to assess effect of 1 year of rhGH therapy on (i) BC and lipid profile (LP) in a cohort of Indian GHD children and (ii) effect on atherosclerotic markers - cIMT in subsample. Anthropometry, BC [% body fat (BF), % lean body mass (LBM), bone mineral content (BMC)] (DXA) and LP were measured in 49 pre-pubertal GHD-children (9.3 ± 3.1 years) at baseline and after 1 year of rhGH therapy. On subset of 20 children, cIMT of right common carotid artery was also measured. Baseline BC parameters were compared with age-gender matched healthy controls (n = 49). At baseline % BF was 23 ± 9 %, LBM was 9 ± 3 kg and BMC was 0.306 ± 0.15 kg in GHD- children; BF was comparable, while lean and bone were less than controls (p < 0.05). Post therapy, significant reduction in fat (15%), and cIMT (7%) and increase in LBM and BMC by 40% and 44%, respectively (p < 0.05) was seen. Our cohort of untreated GHD children had abnormal BC and cIMT as compared to controls. rhGH therapy for 1 year had beneficial effect on BC and cardiovascular risk factors.

Adaptation and validation of an artificial intelligence based digital radiogrammetry tool for assessing bone health of indian children and youth with type-1 diabetes.

BACKGROUND AND OBJECTIVES: BoneXpert (BX) is an artificial intelligence software used primarily for bone age assessment. Besides, it can also be used to screen for bone health using the digital radiogrammetry tool called bone health index (BHI) for which normative reference values available are calculated from healthy European children. Due to ethnic difference in bone geometry, in a previous study, we generated reference curves based on healthy Indian children. The objectives of this study were: 1) To assess and compare bone health of Indian children with Type 1 diabetes (T1D) using both European and Indian BHI SDS reference data and 2) To identify determinants of poor bone health in Indian children and youth with T1D by using BHI tool (based on BHI-SDS Indian reference data) of BX. METHOD: The BHI was assessed retrospectively in 1159 subjects with T1D using digitalised left-hand x-rays and SDS were computed using European and Indian data. The demographic, anthropometric, clinical, biochemistry, dual x-ray absorptiometry (DXA) data and peripheral quantitative computed tomography (pQCT) data collection were performed using standard protocols and were extracted from hospital records. RESULTS: The BHI correlated well with DXA and pQCT parameters in subjects with T1D. BHI-SDS calculated using Indian reference data had better correlation with height and DXA parameters. 8.6% study participants had low (less than -2) BHI-SDS (Indian), with height SDS having significant effect. Subjects with low BHI-SDS were older, shorter and had higher duration of diabetes. They also had lower IGF1 and vitamin D concentrations, bone mineral density, and trabecular density. Female gender, increased duration of illness, poor glycaemic control, and vitamin D deficiency/insufficiency were significant predictors of poor BHI-SDS. CONCLUSION: Our study highlights the utility of digital radiogrammetry AI tool to screen for bone health of children with T1D and demonstrates and highlights the necessity of interpretation using ethnicity specific normative data.

Effect of metformin adjunct therapy on cardiometabolic parameters in Indian adolescents with type 1 diabetes: a randomized controlled trial.

Introduction: Insulin resistance is being increasingly reported in type-1 Diabetes (T1D) and is known to accelerate microvascular complications. The Asian Indian population has a higher risk of double diabetes development compared to Caucasians. Hence, we studied the effect of adding Metformin to standard insulin therapy on glycemic control, insulin sensitivity (IS), cardiometabolic parameters and body composition in Indian adolescents with T1D. Methods: A Randomized controlled trial was conducted spanning 9 months (Registration number:CTRI/2019/11/022126). Inclusion: Age 10-19 years, T1D duration>1year, HbA1c>8% Exclusion: Uncontrolled vascular complications/comorbidities, Metformin intolerance, concomitant drugs affecting insulin sensitivity. Participants were randomized to Metformin/Placebo (n=41 each) groups and age, sex, duration-matched. Assessments were performed at baseline, 3 and 9 months. Results: 82 participants aged 14.7 ± 3years (40 females) were enrolled, with a mean diabetes duration of 5.2 ± 2.3 years. Over 9 months, HbA1c decreased significantly by 0.8 (95% confidence interval: -1.2 to -0.3) from 9.8 ± 1.8% to 9.1 ± 1.7% on Metformin but remained largely unchanged (difference of 0.2, 95% confidence interval: -0.7 to 0.2) i.e. 9.9 ± 1.6% and 9.7 ± 2.2% on placebo. HbA1c improvement correlated negatively with baseline IS (EGDR:r= -0.3;SEARCH:r = -0.24, p<0.05) implying better HbA1c-lowering in those with decreased initial IS. CGM-based glycemic variability (standard deviation) reduced by 6.3 mg/dL (95% confidence interval: -12.9 to 0.2) from 100.2 ± 19.1 mg/dL to 93.7 ± 19.9 mg/dL in those on Metformin (p=0.05) but not placebo (94.0 ± 20.5; 90.0 ± 22.6 mg/dL). Insulin sensitivity: CACTIexa & SEARCH scores demonstrated no change with Metformin but significant worsening on placebo. Significant increase in LDL-C(42%), total cholesterol(133.6 to 151.1 mg/dL), triglyceride (60.0 to 88.0 mg/dL) and carotid intima-media thickness was noted on placebo but not Metformin. Weight, BMI, fat Z-scores increased significantly on placebo but not Metformin. Adverse events (AE) were minor; AE, compliance and safety parameters were similar between the two groups. Conclusion: Metformin as an adjunct to insulin in Asian Indian adolescents with T1D demonstrated beneficial effect on glycemic control, glycemic variability, IS, lipid profile, vascular function, weight and body fat, with a good safety profile when administered for 9 months.

The automated Greulich and Pyle: a coming-of-age for segmental methods?

The well-known Greulich and Pyle (GP) method of bone age assessment (BAA) relies on comparing a hand X-ray against templates of discrete maturity classes collected in an atlas. Automated methods have recently shown great success with BAA, especially using deep learning. In this perspective, we first review the success and limitations of various automated BAA methods. We then offer a novel hypothesis: When networks predict bone age that is not aligned with a GP reference class, it is not simply statistical error (although there is that as well); they are picking up nuances in the hand X-ray that lie "outside that class." In other words, trained networks predict distributions around classes. This raises a natural question: How can we further understand the reasons for a prediction to deviate from the nominal class age? We claim that segmental aging, that is, ratings based on characteristic bone groups can be used to qualify predictions. This so-called segmental GP method has excellent properties: It can not only help identify differential maturity in the hand but also provide a systematic way to extend the use of the current GP atlas to various other populations.

Standardization of Weightage Assigned to Different Segments of the Hand X-ray for Assessment of Bone Age by the Greulich-Pyle Method.

Introduction: Bone age (BA) assessment is important in evaluating disorders of growth and puberty; the Greulich and Pyle atlas method (GP) is most used. We aimed to determine the weightage to be attributed by raters to various segments of the hand x-ray, namely, distal end of radius-ulna (RU), carpals, and short bones for rating bone age using the GP atlas method. Methods: 692 deidentified x-rays from a previous study (PUNE-dataset) and 400 from the Radiological Society of North America (RSNA-dataset) were included in the study. Mean of BA assessed by experienced raters was termed reference rating. Linear regression was used to model reference age as function of age ratings of the three segments. The root-mean-square-error (RMSE) of segmental arithmetic mean and weighted mean with respect to reference rating were computed for both datasets. Results: Short bones were assigned the highest weightage. Carpals were assigned higher weightage in pre-pubertal PUNE participants as compared to RSNA, vice-versa in RU segment of post-pubertal participants. The RMSE of weighted mean ratings was significantly lower than for the arithmetic mean in the PUNE dataset. Conclusion: We thus determined weightage to be attributed by raters to segments of the hand x-ray for assessment of bone age by the GP method.

Influence of parental anthropometry and gestational weight gain on intrauterine growth and neonatal outcomes: Findings from the MAI cohort study in rural India.

Poor foetal growth and subsequent low birth weight are associated with an increased risk for disease later in life. Identifying parental factors that determine foetal growth are important to curbing intergenerational malnutrition, especially among disadvantaged populations in the global south where undernutrition rates are high. The objective of this study was to assess the relationships between parental biometry, intrauterine growth and neonatal outcomes, while factoring in socioeconomic status of historically disadvantaged households in rural India. Using data from the prospective longitudinal cohort, pregnant women from rural Pune, India (n = 134) were assessed between August 2020 and November 2022. Data on socio-demography, ultrasound measurements, parental and foetal anthropometry were collected. Multiple linear regression models were run to predict determinants of foetal intrauterine and neonatal growth (p value<0.05). The dependent variables were ultrasound measurements and neonatal biometry, and independent variables were gestational weight gain, parental and mid-parental height. Mean(±SD) maternal age, maternal height, paternal height and mid-parental height were 22.8±3.7 years, 153.6±5.5cm, 165.9±6.5cm and 159.1±8.7cm, respectively. Pre-pregnancy body mass index and gestational weight gain was 20.5±4.0 kg/m2 and 9.8±3.7kg respectively. Mid-parental height and gestational weight gain were strongly correlated with neonatal growth and foetal intrauterine growth (p<0.05); however, the correlation peaked at 28 weeks of gestation (p<0.05). Gestational weight gain (B = 28.7, p = 0.001) and mid-parental height (B = 14.3, p = 0.001) were identified as strong determinants of foetal-intrauterine growth and neonatal anthropometry at birth. Maternal height was found to influence length of male neonate (B = 0.18, p = 0.001), whereas, paternal height influenced length of the female neonate (B = 0.11, p = 0.01). Parental socio-economic status, biometry and maternal gestational weight gain influence growth of the child starting from the intrauterine period. Our study underlines the need for interventions during pre-pregnancy, as well as during pregnancy, for optimal weight gain and improved foetal and neonatal outcomes.

Pilot Study on Gut Microbiota Profile in Indian Children with Type 1 Diabetes.

Background: Non-genetic factors like microbial dysbiosis may be contributing to the increasing incidence/progression of type 1 diabetes mellitus (T1DM). Objectives: To analyse the gut microbiota profile in Indian children with T1DM and its effect on glycaemic control. Methodology: Faecal samples of 29 children with T1DM were collected and faecal microbial DNA was extracted and subjected to 16S rRNA (ribosomal RNA) sequencing and further analysis. Results: The dominant phyla in children with T1DM were Firmicutes and Bacteroidetes. Butyrate-producing bacteria Blautia and Ruminococcus showed a significant negative correlation with the glycosylated haemoglobin (HbA1C) levels (p < 0.05). Coprococcus and Propionibacterium were important negative predictors of glycaemic control (p < 0.05). Conclusion: Our study suggests that Indian children with T1DM have a distinct gut microbiome taxonomic composition and that short-chain fatty acid-producing bacteria like Ruminococcus and Blautia (butyrate-producing) may play an important role in the glycaemic control of subjects with T1DM.

Resting metabolic rate and its association with body composition parameters in 9- to 18-year-old Indian children and adolescents.

OBJECTIVES: Obesity is a disorder of energy balance with increasing prevalence in Indian children. Objectives were to study 1) resting metabolic rate (RMR), anthropometry, body composition (BC), and their relationships in Indian children and adolescents affected with overweight (OW) or obesity (OB) and in non-overweight (NOW) children and 2) factors influencing RMR, such as age, sex, and BC. METHODS: This cross-sectional, observational, multicentric study included 495 children (260 boys) of age 9-18 y who were assessed from six Indian states for sociodemographic and anthropometric parameters using standard protocols. Body composition was assessed by a body impedance analyzer technique (Tanita-BC-420), and RMR was assessed using indirect calorimetry. Data were analyzed using SPSS (version 26) with appropriate statistical tests. The level of significance was set at P < 0.05. RESULTS: Boys had higher absolute RMR values than did girls (1212±263 kcal/d versus 1066±204 kcal/d; P < 0.001). Weight-adjusted RMR was significantly lower among children classified as OW or OB than among NOW children of both sexes, respectively (P < 0.001). Linear regression analysis revealed fat-free mass, sex, age, and body mass index (BMI) as significant predictors of RMR (P < 0.05). CONCLUSIONS: We found lower weight-adjusted RMR in children classified as OW or OB as compared with NOW children. Our study underlines the importance of low RMR levels among children with a higher BMI, in girls, and with increasing age.

Impact of COVID-19 lockdown on idiopathic central precocious puberty - experience from an Indian centre.

OBJECTIVES: Owing to increase in referrals for precocity observed during COVID-19 lockdown, this study was conducted to estimate the proportion of patients referred for precocity and within these, those with idiopathic central precocious puberty (iCPP) before vs. during the COVID lockdown, and to assess the differences in anthropometric and clinical characteristics among iCPP patients in the two groups. METHODS: Retrospective study conducted at a tertiary level paediatric endocrinology centre (Western India) evaluating proportion of referrals for precocity and comparing demographics, anthropometry, pubertal staging and bone age at presentation among children with iCPP divided into two groups (pre-lockdown-group 1, lockdown-group 2). RESULTS: During lockdown, 155 (5.1%; 146 girls) of 3,053 referrals for precocity as opposed to 59 (1.4%; 54 girls) of 4,208 before the lockdown (p<0.05) were seen; increase was higher in girls (p<0.05). Proportion of referrals for iCPP was significantly higher in the lockdown (4.4%; 136 children vs. 1%; 44 children in group 2) among both genders. Mean age at first visit was 7.8 ± 1.3 and 8.2 ± 1.2 years in groups 1 and 2, respectively. Mean height, weight, BMI and height minus mid-parental height Z scores were not significantly different between the groups. Children in group 2 had a significantly advanced mean bone age (10.7 ± 2 years) and difference in bone and chronological ages (2.5 ± 1.2 years) as compared to group-1 (9.7 ± 1.9; 1.9 ± 1.2) and a larger proportion presented in late puberty. CONCLUSIONS: We found an increase in the referrals for precocious puberty and an increase in number of children diagnosed with iCPP during COVID lockdown.

Maternal early pregnancy body mass index, gestational weight gain and pregnancy outcomes among urban slum dwellers in Pune, India-A retrospective analysis.

Context: Studies on prepregnancy body mass index (BMI), gestational weight gain (GWG), and pregnancy outcomes among urban Indian slums are sparse. Aims: To study BMI during early pregnancy, GWG, and maternal and neonatal outcomes among slum-dwelling women in Pune, India. Design: A retrospective study among pregnant women attending antenatal care (ANC) facility. Methods and Material: Anthropometric and clinical data throughout pregnancy and pregnancy outcomes postdelivery were collected during hospitalization for delivery using ANC cards. Asian BMI cut-offs were used to define underweight (UW), normal weight (NW), overweight (OW), and obesity (OB). GWG was classified into insufficient, adequate, and excessive categories (2009 Institute of Medicine). Statistical analysis was performed using R (v 4.0). Results: Slum-dwelling pregnant women (n = 509, mean age 24 (3.6) years) were studied. Seventy-five percent of the women visited ANC clinics at least thrice during pregnancy. Only 17.5% (n = 89) of the women registered before 12 weeks of gestation, and higher education and being primiparous were the correlates. A total of 28% of the women were UW, whereas 25% of the women were OW/OB as per early pregnancy BMI. The highest percentage of preterm deliveries and cesarean/instrumental deliveries were observed in OW/OB categories. A total of 27% gained appropriate gestational weight. This cohort had 508 live births (mean BW- 2.8 kgs) and one stillbirth. One baby had macrosomia (BW >4 Kg), whereas 19% were low birth weight (LBW) (BW <2.5 Kg). Conclusions: Double burden of malnutrition (UW and OW) was observed among young slum-dwelling women. The proportion of slum-dwelling women attending ANC clinics during early pregnancy is still low. Increased uptake of government programs is required to enhance maternal and child health.