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.

Pediatric Advanced Life Support Tape for Indian Children.

OBJECTIVE: To design a specific advanced life support (ALS) tape based on recent Indian multicenter height/length and weight data to accurately estimate the weight from the recumbent length. METHODS: We designed the new ALS tape by matching the median weights to median heights/lengths from the recently published Indian multicenter growth data, maintaining the same color codes as the Broselow tape. The accuracy of weight estimation for the newly designed ALS tape was validated and compared with the Broselow estimated weights at a tertiary care hospital. RESULTS: The color (weight) band matched median heights (cm) from the new ALS tape were higher (53.0 vs 53.9 for grey, 63.1 vs 67.4 for pink, 70.6 vs 76.4 for red, 79 vs 85.5 for purple, 89.6 vs 95.5 for yellow, 101.9 vs 107.5 for white, 126.1 vs 130.5 for orange and 137 vs 140.5 for green) than the Broselow tape. For every color band on the newly designed ALS tape, a sizable proportion of children (27% for grey, 78% for pink, 83% for red, 38% for purple, 63% for yellow, 41% for white, 35% for blue, 54% for orange) recorded a higher Broselow color band, suggesting overestimated weights at each color band. The percentage difference in the estimated weight from the actual weight was very small (-0.5% for under-5 years and 0.2% for older children) using the new ALS tape as compared to Broselow tape. CONCLUSION: This Indianized ALS tape estimated Indian children's weights more accurately. Use of the newly designed ALS tape may reduce the errors in calculating emergency medications, fluids and equipment sizes. Further studies are required to validate this tape in pediatric emergency departments in India.

Comparison of WHO 2006 Growth Standards and Synthetic Indian References in Assessing Growth in Normal Children and Children with Growth-Related Disorders.

Introduction: A good screening tool, such as a growth chart, should distinguish between children with normal growth and those with perturbed growth. Suitability of synthetic Indian growth references for diagnosing growth-related disorders for under-five children has not been evaluated. To assess the validity of World Health Organization (WHO) 2006 standards vs synthetic Indian references (2019) (by comparing weight, height, body mass index (BMI), standard deviation scores (SDS) and the composite index of anthropometric failure (CIAF)) in differentiating normal children and children with growth-related disorders. Methods: Records of 2188 children (0-60 months) attending a tertiary centre paediatric outpatient department (OPD) were retrospectively studied; 1854 children were healthy and 334 were diagnosed with growth-related disorders as per the European Society for Paediatric Endocrinology (ESPE) classification. The anthropometric parameters converted to Z-scores for weight-for-age (WAZ), height-for-age (HAZ), BMI-for-age (BAZ) and a CIAF were computed using WHO and synthetic charts; Student's t-test was used for assessing differences and Youden's index for validity. Results: Disease status of children and anthropometric failure on WAZ, HAZ, BAZ and CIAF on both WHO and synthetic charts had a significant association (P-value <0.05). WAZ, HAZ on both charts and CIAF on synthetic chart had a fair to moderate agreement (Kappa statistics) with disease status as per diagnosis (P-value <0.05). The sensitivity and negative predictive value for all anthropometric parameters were higher for synthetic charts. Conclusion: Indian charts were more sensitive for diagnosing growth-related disorders from birth to 60 months of age when compared to WHO growth standards.

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.

Assessment of Vitamin D Status, its Determinants and Relationship with Bone Health in Indian Children and Young Adults with Type-1 Diabetes.

Introduction: Recent evidence suggests that vitamin D deficiency and type-1 diabetes (T1D) have a bidirectional cause-effect relationship. The objective of this study is to estimate the prevalence and determinants of vitamin D deficiency in Indian children and young adults with T1D and assess the relationship between vitamin D status and their bone health. Methods: It was a single-centre, cross-sectional study. Inclusion: Children, young adults aged 5-25 years with T1D duration >1 year. Exclusion: Already on vitamin D supplementation, conditions affecting bone health. Data collected: Demographic, clinical, anthropometry, biochemical, body composition, DXA, pQCT measurements. Results: A total of 453 participants (251 girls) with T1D, mean age = 13.5 ± 4.0 years, disease duration = 5.7 ± 3.9 years. Mean 25-hydroxy vitamin D concentration of study group was 20.4 ± 11.3 ng/mL. One hundred and eleven (24.5%) were deficient in 25-hydroxy vitamin D, 141 (31.1%) were insufficient and 201 (44.4%) were sufficient. 25-Hydroxy vitamin D concentrations had significant negative correlation with BMI Z-score, diastolic blood pressure, fat percentage Z-score and positive correlation with physical activity, haemoglobin concentrations and trabecular density (P < 0.05). Risk of developing vitamin D deficiency and insufficiency was significantly lower in subjects with good/intermediate glycaemic control versus poor control (P = 0.008). Higher diastolic blood pressure and female gender were significant risk factors for development of vitamin D deficiency. Conclusion: Vitamin D deficiency has high prevalence in children and youth with T1D and has detrimental effect on bone geometry of these subjects. Weight reduction increased outdoor physical activity, good glycemic control are some modifiable factors that may prove useful in preventing vitamin D deficiency.

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.

Effectiveness of Supramaximal Angiotensin-converting Enzyme Inhibition in Controlling Proteinuria in Congenital Nephrotic Syndrome with Cytomegalovirus Infection and an NPHS1 Mutation.

Congenital nephrotic syndrome (NS) is characterized by early-onset heavy proteinuria. Most cases of congenital NS are associated with genetic mutations in the podocyte proteins. The causal relationship of perinatal infections with congenital NS has not yet been proven. Inadequate response to the treatment of such infections should prompt us to conduct genetic testing for congenital NS. The heavy proteinuria associated with congenital NS is usually difficult to control with conventional treatment. It often results in progressive kidney disease with a high risk of mortality in early life. Here, we describe an infant who developed congenital NS and was found to have a coexisting Cytomegalovirus infection and an underlying NPSH1 mutation. Proteinuria did not respond to a standard dose of enalapril. A supramaximal dose of enalapril was tried and was effective and safe in controlling the proteinuria. It was associated with improved growth, complete resolution of edema, normal serum albumin, and normal renal function beyond 2 years of age.

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.

A Rare Case of Salmonella meningitis and Hemophagocytic Lymphohistiocytosis.

Enteric fever is a common infectious disease of the tropical world. Common age group involved is children aged between 5 and 10 years. In addition to diarrhea, it may lead to extraintestinal infections including aseptic meningitis, hepatitis, cholecystitis, acute abdomen, intestinal perforation, pneumonia, psychosis, and ataxia. Hematologic complications leading to hemophagocytosis have a prevalence of < 1%. Salmonella meningitis has an incidence of 6% with poor prognosis neurological sequelae. We report a rare case of enteric fever that presented with hemophagocytic syndrome and S. meningitis. Response to third-generation cephalosporins is dramatic, eventually giving good prognosis.