Weight Velocity Percentiles in Children Aged 4-17 Years from Pune During 2007-2013.

OBJECTIVE: To assess weight velocity and the age at peak weight velocity and to construct weight velocity percentiles in 4-17-year-old apparently healthy Indian children. METHOD: This longitudinal study enrolled 1045 children (588 boys) from Pune belonging to middle and upper socioeconomic class aged 4-17 years. The study parameters included annual height and weight measurements recorded longitudinally from 2007 to 2013. A total of 5225 weight velocity measurements (2940 on boys) were computed. Age- and gender-specific smoothened weight velocity percentiles (3rd, 10th, 25th, 50th, 75th, 90th and 97th) were constructed using LMS chart maker. RESULTS: The median weight velocity was low in boys and girls at 4 years, thereafter it increased to a peak of 4.6 kg/year at 13 years in boys, then declined to 1.1 kg/year at 17.5 years. In girls, median weight velocity peaked to 4.0 kg/year at 11 years, then declined to 0.8 kg/year at 17.5 years. Peak velocity-centred analysis revealed higher peak velocities of 7.5 kg/year at 13.1 years and 6.6 kg/year at 12 years in boys and girls respectively. CONCLUSION: Weight velocity percentiles are presented for 4-17-year-old apparently healthy Indian children.

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.

Long term clinical follow up of four patients with Wolfram syndrome and urodynamic abnormalities.

OBJECTIVES: Wolfram syndrome is characterised by insulin-dependent diabetes (IDDM), diabetes insipidus (DI), optic atrophy, sensorineural deafness and neurocognitive disorders. The DIDMOAD acronym has been recently modified to DIDMOAUD suggesting the rising awareness of the prevalence of urinary tract dysfunction (UD). End stage renal disease is the commonest cause of mortality in Wolfram syndrome. We present a case series with main objective of long term follow up in four children having Wolfram syndrome with evaluation of their urodynamic profile. METHODS: A prospective follow up of four genetically proven children with Wolfram syndrome presenting to a tertiary care pediatric diabetes clinic in Pune, India was conducted. Their clinical, and urodynamic parameters were reviewed. RESULTS: IDDM, in the first decade, was the initial presentation in all the four children (three male and one female). Three children had persistent polyuria and polydipsia despite having optimum glycemic control; hence were diagnosed to have DI and treated with desmopressin. All four patients entered spontaneous puberty. All patients had homozygous mutation in WFS1 gene; three with exon 8 and one with exon 6 novel mutations. These children with symptoms of lower urinary tract malfunction were further evaluated with urodynamic studies; two of them had hypocontractile detrusor and another had sphincter-detrusor dyssynergia. Patients with hypocontractile bladder were taught clean intermittent catheterization and the use of overnight drain. CONCLUSIONS: We report a novel homozygous deletion in exon 6 of WFS-1 gene. The importance of evaluation of lower urinary tract malfunction is highlighted by our case series. The final bladder outcome in our cases was a poorly contractile bladder in three patients.

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.

Natural history of Wolcott-Rallison syndrome: A systematic review and follow-up study.

BACKGROUND AND AIMS: To systematically review the literature for reports on Wolcott-Rallison syndrome, focusing on the spectrum and natural history, genotype-phenotype correlations, patient and native liver survival, and long-term outcomes. METHODS: PubMed, Livio, Google Scholar, Scopus and Web of Science databases were searched. Data on genotype, phenotype, therapy, cause of death and follow-up were extracted. Survival and correlation analyses were performed. RESULTS: Sixty-two studies with 159 patients met the inclusion criteria and additional 30 WRS individuals were collected by personal contact. The median age of presentation was 2.5 months (IQR 2) and of death was 36 months (IQR 50.75). The most frequent clinical feature was neonatal diabetes in all patients, followed by liver impairment in 73%, impaired growth in 72%, skeletal abnormalities in 59.8%, the nervous system in 37.6%, the kidney in 35.4%, insufficient haematopoiesis in 34.4%, hypothyroidism in 14.8% and exocrine pancreas insufficiency in 10.6%. Episodes of acute liver failure were frequently reported. Liver transplantation was performed in six, combined liver-pancreas in one and combined liver-pancreas-kidney transplantation in two individuals. Patient survival was significantly better in the transplant cohort (p = .0057). One-, five- and ten-year patient survival rates were 89.4%, 65.5% and 53.1%, respectively. Liver failure was reported as the leading cause of death in 17.9% of cases. Overall survival was better in individuals with missense mutations (p = .013). CONCLUSION: Wolcott-Rallison syndrome has variable clinical courses. Overall survival is better in individuals with missense mutations. Liver- or multi-organ transplantation is a feasible treatment option to improve survival.

Development of a simplified new method of bone age estimation using three bones of the hand and wrist.

Though the Greulich and Pyle (GP) method is easy, inter-observer variability, differential maturation of hand bones influences ratings. The Tanner-Whitehouse (TW) method is more accurate, but cumbersome. A simpler method combining the above, such that it utilizes fewer bones without affecting accuracy, would be widely used and more applicable in clinical practice. OBJECTIVES: 1. Devising a simplified method utilizing three bones of the hand and wrist for bone age (BA) assessment. 2. Testing whether the 3 bone method gives comparable results to standard methods (GP,TW2,TW3) in Indian children. METHODS: Developmental stages and corresponding BA for radius, hamate, terminal phalanx (left middle finger) epiphyses combining stages from GP,TW3 atlases were described; BA were rated by two blinded observers. 3 bone method ratings were compared with the same dataset analyzed earlier using GP,TW2,TW3 (4 raters). RESULTS: Radiographs analysed:493 (Girls=226). Mean chronological age:9.4 ± 4.6 yrs, mean BA 3 bone:9.8 ± 4.8 yrs, GP:9.6 ± 4.8 yrs, TW3:9.3 ± 4.5 yrs, TW2:9.9 ± 5.0 yrs. The 3 bone method demonstrated no significant inter-observer variability (p = 0.3, mean difference = 0.02 ± 0.6 yrs); a strong positive correlation (p < 0.0001) with GP (r = 0.985), TW3 (r = 0.983) and TW2 (r = 0.982) was noted. Bland-Altman plots demonstrated good agreement; the root mean square errors between 3 bone and GP,TW3,TW2 ratings were 0.6,0.7,0.6 years; mean differences were 0.19,0.49,-0.14 years respectively. Greatest proportion of outliers (beyond ±1.96 SD of mean difference) was between 6 and 8 years age for difference in 3 bone and GP, and between 4-6 years for difference in 3 bone and TW3,TW2. CONCLUSION: The 3 bone method has multiple advantages; it is easier, tackles differential maturation of wrist and hand bones, has good reproducibility, without compromising on accuracy rendering it suitable for office practice.

Effect of Yoga or Physical Exercise on Muscle Function in Rural Indian Children: A Randomized Controlled Trial.

BACKGROUND: Synergistic effects of yoga or physical exercise (PE) along with protein supplementation on children's muscle function in rural India have not been studied. Hence, we aimed to study the effect of yoga and PE along with protein supplementation on muscle function in healthy 6- to 11-year-old rural Indian children post 6 months of intervention. METHODS: A randomized controlled trial on 232 children, recruited into 3 groups, each receiving 1 protein-rich ladoo (148 kcal, 7 g protein/40 g ladoo-an Indian sweet snack) daily and performing (1) yoga (n = 78) for 30 minutes 5 times per week, (2) PE (n = 76) for 30 minutes 5 times per week, or (3) control group (n = 78) no additional exercise. Maximum power, maximum voluntary force (Fmax), and grip strength (GS) were measured. Data were analyzed using paired t tests and a 2-way mixed analysis of variance with post hoc Bonferroni adjustment. RESULTS: GS, maximum power, and Fmax within yoga group increased significantly (P < .05) from baseline to endline. GS and Fmax increased significantly within PE group postintervention (P < .001). In controls, GS increased (P < .05) at endline. No significant effect of the intervention was observed on the change in maximum power (P > .05) postintervention. The 2 exercise groups showed significant increase in Fmax compared with the control group (P < .05). Similarly, increase in GS was significantly higher in both the exercise groups compared with the control group (P < .05). No significant difference was observed in change in muscle function between the 2 exercise groups (P > .05). CONCLUSIONS: Structured physical activity along with protein supplementation resulted in improved muscle function in children. Yoga and PE showed a comparable impact on muscle force.

Longitudinal assessment of auxological parameters, adult height outcome and its determinants in leuprolide-treated Indian girls with idiopathic central precocious puberty.

OBJECTIVES: To assess auxological parameters, adult height outcome and its determinants in Indian girls with idiopathic central precocious puberty (iCPP) treated with gonadotropin-releasing hormone analogues (GnRHa). METHODS: Retrospective study. Inclusion: data on girls with iCPP from initiation to stopping GnRHa (n=179). Exclusion: boys, peripheral, organic central precocity. RESULTS: Mean age of starting GnRHa: 8.2± 1.1 years, duration: 2.8± 1.2 years. 11.7 % had attained menarche at first presentation. The difference between bone (BA) and chronological (CA) ages reduced significantly from 2.6± 0.9 years (onset) to 1.6± 0.8 years (cessation). Weight, BMI Z-scores increased (p<0.01), height Z-scores decreased (0.8 vs. 0.6; p<0.01), predicted adult height (PAH) and Z-scores improved by 3.5 cm, 0.5 SDS following treatment (p<0.01). Overweight/obese girls (vs. normal BMI) were taller, with more advanced BA at starting (height Z-score: 0.7 vs. 1.0, BA-CA: 2.2 vs. 2.9 years), stopping (height Z-score: 0.5 vs. 0.9, BA-CA: 1.4 vs. 1.9 years) treatment, but showed no difference in PAH at starting, stopping treatment. Adult height data (n=58) revealed 1.9 cm gain above target height. Adult height Z-scores significantly exceeded target height Z-scores (p<0.01). Mean adult height (157.1± 5.8 cm) crossed PAH at starting treatment (155.9± 6.4 cm) but remained 1.6 cm lesser than PAH at cessation. Adult weight, BMI Z-scores (-0.2± 1.3, -0.1± 1.2) were significantly lower (p<0.01) than those at stopping GnRHa. Height gain adjusted for age at starting GnRHa correlated negatively with height, weight, BMI, Tanner-staging, BA, FSH, Estradiol at treatment onset, BA at cessation, and correlated positively with treatment duration. CONCLUSIONS: GnRHa treatment in Indian girls with iCPP resulted in improved PAH, decelerated bone age advancement and growth velocity. Most girls achieved adult height within target range, surpassing PAH at treatment initiation. Lesser anthropometric, sexual, skeletal maturity, lower baseline FSH, estradiol, longer treatment duration, less advanced BA at stopping GnRHa may translate into better adult height outcomes.

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.

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.

The interplay between air pollution, built environment, and physical activity: Perceptions of children and youth in rural and urban India.

The role of physical inactivity as a contributor to non-communicable disease risk in children and youth is widely recognized. Air pollution and the built environment can limit participation in physical activity and exacerbate non-communicable disease risk; however, the relationships between perceptions of air pollution, built environment, and health behaviours are not fully understood, particularly among children and youth in low and middle-income countries. Currently, there are no studies capturing how child and youth perceptions of air pollution and built environment are associated with physical activity in India, thus, this study investigated the association between perceived air pollution and built environment on moderate-to-vigorous physical activity (MVPA) levels of Indian children and youth. Online surveys captured MVPA, perception of air pollution as a problem, built environment factors, as well as relevant sociodemographic characteristics from parents and children aged 5-17 years in partnership with 41 schools across 28 urban and rural locations during the Coronavirus disease lockdowns in 2021. After adjusting for age, gender, and location, a significant association was found between the perception of air pollution as a problem and MVPA levels (ß = -18.365, p < 0.001). Similarly, the perception of a high crime rate was associated with lower MVPA levels (ß = -23.383, p = 0.002). Reporting the presence of zebra crossings, pedestrian signals, or attractive natural sightings were associated with higher MVPA levels; however, this association varied across sociodemographic groups. These findings emphasize the importance of addressing air pollution and improving the built environment to facilitate outdoor active living, including active transportation, among children and youth - solutions that are particularly relevant not only for preventing non-communicable disease risk but also for climate change mitigation.

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.

Rare case of central congenital hypothyroidism due to a TSHß mutation presenting with macro-orchidism.

A male infant was brought to our paediatric endocrine unit with typical clinical features of congenital hypothyroidism (CH) and striking macro-orchidism. On evaluation, free T3, free T4 and thyroid stimulating hormone (TSH) were found to be low, suggestive of congenital CH. Cortisol was within reference range and prolactin was mildly elevated. No suspicious lesions were encountered on neurosonography. On commencing treatment with thyroxine, clinical features of hypothyroidism showed dramatic improvement with regression of testicular enlargement. Genetic analysis revealed deletion of the TSHß gene.Our case highlights a rare presentation of central CH with macro-orchidism in a genetically proven deletion of TSHß gene. Macro-orchidism has been widely reported in IGSF-1 mutations leading to central CH; however, central CH and macro-orchidism have not been reported in association with TSHß deletions.

A Cross-Sectional Multicentre Study to Validate Insulin Sensitivity Index Cut-Offs for Detection of Metabolic Syndrome in Indian Adolescents with Type-1 Diabetes.

Background: A previous study compared insulin sensitivity indices for the detection of double diabetes (DD) in Indian adolescents with type-1 diabetes (T1D) and derived a cut-off to predict future risk for the development of metabolic syndrome (MS) in adolescents with T1D. We conducted the current study with the aim to validate these cut-offs for detecting DD among Indian subjects with T1D from various geographical locations. Methods: This multicentric cross-sectional study included 161 Indian adolescents with T1D. Demographic, anthropometric, clinical, and biochemical data were collected using standard protocols. Insulin sensitivity (IS) was calculated using various equations developed to determine insulin sensitivity in subjects with T1D. Metabolic syndrome was diagnosed using International Diabetes Federation (IDF) Consensus Definition 2017. Results: We report 4.3% prevalence of MS in Indian adolescents with T1D with an additional 29.8% of study participants at risk of development of MS. Low High density lipoprotein (HDL) (23.6%) was the commonest abnormal component of the MS definition. Insulin sensitivity calculated by an equation derived by the SEARCH group was the most appropriate index to identify MS and metabolic risk in Indian adolescents with T1D. The proposed cut-off of 5.48 had high specificity, positive predictive value, and negative predictive value in identifying the risk of the development of DD. Conclusions: Insulin sensitivity calculated by the equation proposed by the SEARCH group together with cut-offs derived in earlier study may be used effectively to identify risk of development of MS/DD in Indian adolescents with T1D from various geographical locations.

Insulin Resistance in Adolescents and Youth With Type 1 Diabetes: A Review of Problems and Solutions.

Though insulin resistance (IR) was previously considered a feature of only type 2 Diabetes (T2DM), its development in type 1 Diabetes (T1DM) is not an uncommon occurrence, the causes of which are multifactorial (gender, pubertal status, diabetes duration, ethnicity, genetics, adiposity, glycemic control, chronic inflammation). Despite improvements in glucose, blood pressure and lipid profile, vascular complications (coronary artery disease and nephropathy) continue to remain common causes of morbidity and mortality in T1DM. Aggressive glycemic control reduces but does not eliminate the risk of IR. IR accelerates the development of micro and macrovascular complications, many of which can be potentially reversed if diagnosed and managed early. Lack of endogenous insulin production makes estimation of insulin sensitivity in T1DM difficult. As hyperinsulinemic-euglycemic clamp studies are cumbersome and invasive, the use of prediction equations for calculating estimated insulin sensitivity may prove to be useful. Along with intensive insulin therapy, dietary modifications and increasing physical activity, the role of Metformin in managing IR in T1DM is becoming increasingly popular. Metformin adjunct therapy in T1DM has been shown to improve insulin sensitivity, glycemic control, lipid profile, body composition, vascular smooth muscle function, thereby reducing the risk of vascular complications, as well as reversal of early vascular dysfunction. However, further studies to assess long-term efficacy and safety of Metformin use in adolescents and youth with T1DM are needed. This review aims at revisiting the pathophysiology of IR in T1DM and techniques of identifying those at risk so as to put into action various strategies for management of the same.

Comparison of Nutritional Status of Healthy Under-Five Indian Children Using Composite Index of Anthropometric Failure on WHO 2006 versus 2019 Indian Synthetic Growth Charts.

OBJECTIVES: To assess nutritional status of apparently-healthy under-five Indian children using Composite Index of Anthropometric Failure (CIAF) and to compare anthropometric failure prevalence using conventional indices and CIAF on World Health Organization (WHO) vs. synthetic Indian growth charts. METHODS: This observational study was conducted over 2 y. The inclusion criteria was apparently-healthy children (0-60 mo) and the exclusion criteria were acute/chronic illness and small for gestational age. RESULTS: A total of 1557 children (762 girls) were included in the study. The mean age of the subjects was 21 mo. The Z-scores for height, weight, body mass index (BMI) for age and weight for height in children were lower on WHO vs. synthetic charts (p = 0.0001). Significantly higher proportion of children were moderately and severely underweight, stunted and wasted on WHO charts. Synthetic charts identified significantly higher proportion as normal for weight, height, BMI for age, weight for height, overweight (overall), and a higher prevalence of severe stunting, and severe acute malnutrition (SAM) was noted among girls compared to boys. Using CIAF, 54.1% children were normal on WHO charts vs. 78.0% on synthetic (p = 0.0001). Larger proportion of girls (8.8%) were stunted+underweight (category-E) vs. boys (4.3%) on synthetic charts (p = 0.0003). Significantly higher proportion of children demonstrated failure (single/dual/multiple) on WHO charts except category-Y (higher proportion of underweight on synthetic charts). Maximum difference in CIAF (WHO vs. synthetic) was observed between 0-24 mo age. Of 1215 children normal on synthetic charts, 837 (68.9%) were normal on WHO charts. Of 116 underweight children (category-Y) on synthetic charts, 20 (17.2%) were underweight on WHO charts; remaining had compound failure (wasting+underweight = 49.1%, wasting+stunting+underweight = 14.7%, stunting+underweight = 12.1%) on WHO charts. Among those stunted+underweight (category-E) on synthetic charts, WHO charts classified 1/4th as wasted+stunted+underweight (category-D). CONCLUSIONS: Synthetic references are more representative of Indian growth patterns, and seem more appropriate for monitoring growth of Indian children to avoid mislabelling as malnourished.

Vitamin D supplementation for improving bone density in vitamin D-deficient children and adolescents: systematic review and individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin D supplements are widely used for improving bone health in children and adolescents, but their effects in vitamin D-deficient children are unclear. OBJECTIVES: This study aimed to examine whether the effect of vitamin D supplementation on bone mineral density (BMD) in children and adolescents differs by baseline vitamin D status and estimate the effect in vitamin D-deficient individuals. METHODS: This is a systematic review and individual participant data (IPD) meta-analysis. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, MBASE, CINAHL, AMED, and ISI Web of Science (until May 27, 2020) for randomized controlled trials (RCTs) of vitamin D supplementation reporting bone density outcomes after ≥6 mo in healthy individuals aged 1-19 y. We used two-stage IPD meta-analysis to determine treatment effects on total body bone mineral content and BMD at the hip, femoral neck, lumbar spine, and proximal and distal forearm after 1 y; examine whether effects varied by baseline serum 25-hydroxyvitamin D [25(OH)D] concentration, and estimate treatment effects for each 25(OH)D subgroup. RESULTS: Eleven RCTs were included. Nine comprising 1439 participants provided IPD (86% females, mean baseline 25(OH)D = 36.3 nmol/L). Vitamin D supplementation had a small overall effect on total hip areal BMD (weighted mean difference = 6.8; 95% confidence interval: 0.7, 12.9 mg/cm2; I2 = 7.2%), but no effects on other outcomes. There was no clear evidence of linear or nonlinear interactions between baseline 25(OH)D and treatment; effects were similar in baseline 25(OH)D subgroups (cutoff of 35 or 50 nmol/L). The evidence was of high certainty. CONCLUSIONS: Clinically important benefits for bone density from 1-y vitamin D supplementation in healthy children and adolescents, regardless of baseline vitamin D status, are unlikely. However, our findings are mostly generalizable to White postpubertal girls and do not apply to those with baseline 25(OH)D outside the studied range or with symptomatic vitamin D deficiency (e.g., rickets). This study was preregistered at PROSPERO as CRD42017068772. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017068772.

Assessment of pubertal onset and disorders of puberty in Indian children and youth with type-1 diabetes.

OBJECTIVES: Disorders of pubertal development are enlisted as associated conditions in children and adolescents with type-1 diabetes (T1D). We conducted this study with objective (1) To estimate the median age at onset of puberty and luteinizing hormone (LH) and sex-steroid concentrations in Indian adolescents with T1D and (2) To assess the impact of puberty on glycemic control and insulin resistance (IR). METHODS: This cross-sectional study included 399 children and youth aged 6-23 years with T1D. Demographic, anthropometric, biochemical and pelvic ultrasound data were collected using standard protocols. IR was calculated using estimated glucose disposal rate and puberty was assessed using Tanner staging. RESULTS: Median age at onset of thelarche, pubarche and menarche were 11.3, 11.4 and 12.8 years in girls and that of gonadarche and pubarche were 10.6 and 12.7 years for boys. The mean LH and sex-steroid concentrations of subjects with T1D were similar to healthy subjects at each stage of puberty. The cut-offs of LH and sex-steroids derived from healthy Indian children yielded high sensitivity and specificity in determining pubertal onset. The prevalence of precocity, delayed puberty, ovarian cysts and polycystic ovaries was 0.9 , 5.1, 5.1 and 8.6 %, respectively. Glycaemic control and insulin sensitivity was poor in pubertal subjects. CONCLUSIONS: The age at onset of puberty, LH, and sex-steroid concentrations in subjects with T1D were like otherwise healthy Indian children with poor glycemic control and IR in pubertal subjects. Although most complications of T1D are associated with poor glycemic control, pubertal disorders were significantly low despite the less-than-optimal glycemic control.

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.

Pre-pregnancy weight, the rate of gestational weight gain, and the risk of early gestational diabetes mellitus among women registered in a tertiary care hospital in India.

BACKGROUND: The impact of pre-pregnancy weight and the rate of gestational weight gain (GWG) together on the risk of early GDM (< 24 weeks gestation; eGDM) has not been studied in the Indian context. We aimed to study the influence of (1) pre-pregnancy weight on the risk of eGDM diagnosed in two time intervals; and (2) in addition, the rate of GWG by 12 weeks on the risk of eGDM diagnosed in 19-24 weeks. METHOD: Our study utilized real-world clinical data on pregnant women routinely collected at an antenatal care clinic at a private tertiary hospital, in Pune, India. Women registering before 12 weeks of gestation (v1), with a singleton pregnancy, and having a follow-up visit between 19-24 weeks (v2) were included (n = 600). The oral glucose tolerance test was conducted universally as per Indian guidelines (DIPSI) at v1 and v2 for diagnosing eGDM. The data on the onset time of eGDM were interval censored; hence, we modeled the risk of eGDM using binomial regression to assess the influence of pre-pregnancy weight on the risk of eGDM in the two intervals. The rate of GWG by 12 weeks was added to assess its impact on the risk of eGDM diagnosed in v2. RESULT: Overall, 89 (14.8%) women (age 32 ± 4 years) were diagnosed with eGDM by 24 weeks, of which 59 (9.8%) were diagnosed before 12 weeks and 30 of 541 (5.5%) women were diagnosed between 19-24 weeks. Two-thirds (66%) of eGDM were diagnosed before 12 weeks of gestation. Women's pre-pregnancy weight was positively associated with the risk of GDM in both time intervals though the lower confidence limit was below zero in v1. The rate of GWG by 12 weeks was not observed to be associated with the risk of eGDM diagnosed between 19-24 weeks of gestation. These associations were independent of age, height, and parity. CONCLUSION: Health workers may focus on pre-pregnancy weight, a modifiable risk factor for eGDM. A larger community-based study measuring weight and GDM status more frequently may be warranted to deepen the understanding of the role of GWG as a risk factor for GDM.