Growth charts for weight and height of Indian children with Down syndrome.

Age and gender specific growth charts for Indian children with Down syndrome (DS) based on longitudinal data have not been published. To establish percentile growth charts for DS children inhabiting northwestern parts of India, body weight and length/height of 1125 (Male: 752, Female: 373) children with DS aged <1 month to 10 years, enrolled from the "Genetics Clinic" were measured at half yearly age intervals in the "Growth Clinic" of the Institute from August 1994 to November 2018. A total of 2089 observations were made on these children using standardized anthropometric techniques and instruments following a prospective mixed-longitudinal growth research design. Using the LMS method, age and sex-specific percentile growth charts (<1 month to 10 years) for weight, and length/ height were generated. Unpaired t-test was used to compare mean growth attainments of study children with those of DS patients representing other population groups as well as their normal Multicentre Growth Reference Study (MGRS and Indian Academy of Pediatrics (IAP) counterparts. The 50th percentile growth curves for both weight and length/height of Indian children with DS demonstrated a regular increase. As compared to their normal MGRS and Indian (IAP) counterparts, the children with DS had lower weight and height attainments. The boys and girls with Down syndrome showed short stature (height < 3rd centile) from the age of 1 year till 10 years and also became underweight beyond 5 years. As compared to their normal counterparts, children with Down syndrome exhibited compromised auxological attainments. The use of growth charts presented herein may be used to compare and monitor growth and nutritional status of Indian children with Down syndrome.

The Promise of Cilnidipine in Hypertension with Comorbidities: National Consensus Statement: National Consensus Group Comprises Cardiologists, Nephrologists, and Diabetologists from India in a National Meet at New Delhi held on 22nd May 2022.

The rapidly increasing burden of hypertension is responsible for premature deaths from cardiovascular disease (CVD), renal disease, and stroke, with a tremendous public health and financial burden. Hypertension detection, treatment, and control vary worldwide; it is still low, particularly in low- and middle-income countries (LMICs). High blood pressure (BP) and CVD risk have a strong, linear, and independent association. They contribute to alarming numbers of all-cause and CVD deaths. A major culprit for increased hypertension is sympathetic activity, and further complications of hypertension are heart failure, ischemic heart disease (IHD), stroke, and renal failure. Now, antihypertensive interventions have emerged as a global public health priority to reduce BP-related morbidity and mortality. Calcium channel blockers (CCB) are highly effective vasodilators. and the most common drugs used for managing hypertension and CVD. Cilnidipine, with both L- and N-type calcium channel blocking activity, is a promising 4th generation CCB. It causes vasodilation via L-type calcium channel blockade and inhibits the sympathetic nervous system (SNS) via N-type calcium channel blockade. Cilnidipine, which acts as a dual L/N-type CCB, is linked to a reduced occurrence of pedal edema compared to amlodipine, which solely blocks L-type calcium channels. The antihypertensive properties of cilnidipine are very substantial, with low BP variability and long-acting properties. It is beneficial for hypertensive patients to deal with morning hypertension and for patients with abnormal nocturnal BP due to exaggerated sympathetic nerve activation. Besides its BP-lowering effect, it also exhibits organ protection via sympathetic nerve inhibition and renin-angiotensin-aldosterone system inhibition; it controls heart rate and proteinuria. Reno-protective, neuroprotective, and cardioprotective effects of cilnidipine have been well-documented and demonstrated.

Prevalence, risk, and outcomes of venous thromboembolic events in kidney transplant recipients: a nested case-control study.

INTRODUCTION: Thromboembolism is more common in kidney transplant recipients (KTRs) than in the general population. Studies evaluating arterial and venous thromboembolism (VTE) in KTRs are scarce and the magnitude and risk factors are mostly undefined. METHODS: A nested control study was conducted from January 1, 2007, to December 31, 2019. Adult KTRs who were detected to have VTE events during this period were included. The primary outcome was to assess the prevalence of VTE in this population. Secondary outcomes were the assessment of the time to occurrence of the thromboembolic events after transplantation and assessing the risk factors and patient survival. For each subject studied, 4 controls were matched from the data set. RESULTS: Amongst 2158 patients, 97 (4.5%) were found to have VTE. The median follow-up time was 3.9 years (6-156 months). A total of 101 VTE events were recorded. The most common site of VTE was the lower limb deep vein thrombosis in 79 patients (0.03%)).In multivariate Cox regression analysis, serum creatinine of more than 3 mg/dl [HR 1.30, 95% CI (1.03-1.38)] was independently associated with increased VTE risk. Patients who developed a VTE had higher mortality as compared to patients who did not develop VTE. No increased risk of graft failure was found in VTE patients. CONCLUSION: This study suggests that kidney transplantation surgery is a moderate risk factor for VTE, and VTE is associated with higher morbidity and mortality. However, prospective studies are needed to establish a definite role of VTE in outcomes in KTRs.

Short- and long-term outcomes of early initiation of peritoneal dialysis following catheter insertion.

INTRODUCTION: Early-start peritoneal dialysis (PD) (use of PD catheter within 48 hours of insertion) is an innovative approach for prompt initiation of PD. AIM: This study was conducted to analyze the outcomes of early-start PD. MATERIALS AND METHODS: A total of 100 patients on PD were retrospectively analyzed. Patients were grouped according to the "break-in period": < 48 hours (PD1) and ≥ 14 days (PD2). PD was initiated with low dwell volumes (500 mL) in a recumbent position within 48 hours of surgery. PD prescription was gradually incremented over 10 days to minimize any complications. RESULTS: In our study, there were 48 patients in the PD1 group and 52 in the PD2 group. The most common cause of end-stage kidney disease (ESKD) was diabetes mellitus in both groups. Incidence of early mechanical complications (within 30 days of catheter insertion), such as catheter obstruction, early catheter leakage, catheter malposition, tip migration, and infectious complications, were not found to be higher in the PD1 group. 1- and 4-year catheter patency rates were 97.0% and 96.2% in the PD1 group, respectively. These rates were comparable with those in the PD2 group. Early-start PD was not associated with an increased incidence of catheter failure (HR = 1.0, 95% CI 0.28 - 3.47). CONCLUSION: An early break-in period of < 48 hours is a feasible option for ESKD patients without any significantly increased risk of mechanical or infectious complications. It offers a safe and efficacious option for renal replacement therapy.

Detection of ocular hypertelorism among Indian children.

Background & objectives: Ocular hypertelorism constitutes an important component of many clinical syndromes. It is typically recommended to use inter-pupillary distance (IPD) for objective evaluation of ocular hypo/hypertelorism. Barring infancy, there is a scarcity of data on this anthropometric parameter relating to the ocular apparatus. This study aims to study auxological dynamics of IPD in children of Indian origin. Methods: A total of 3622 ( 2239 males and, 1383 females) normal, healthy Indian children of North-western origin, aged one month to 14 yr comprised the sample for this study. Inner and outer-canthal distance were measured using standardized anthropometric techniques. None of the children who participated in this study had craniofacial dysmorphism or any body deformity. Mean (standard deviation SD) and percentiles were calculated for IPD in male and female subjects at different age levels. Results: IPD increased from 4.68±0.21 to 6.19±0.36 cm in males and from 4.59±0.26 to 6.08±0.25 cm in females between one month and 14 yr of age. Boys in general, possessed larger IPD than girls, however, the gender differences became significant (P≤0.05) at 10, 11, 16-18 and 22-24 months, respectively, and five and 10 yr of age, respectively. Interpretation & conclusions: The results of this study suggest that the patients having IPD less than the 3rd percentile should be treated as cases of hypotelorism while, those exceeding 97th percentile as cases of hypertelorism. The use of percentile grids presented for IPD may be used to detect ocular hypotelorism and hypertelorism in male and female children to corroborate diagnosis of different syndromes.

CMV presenting as a skin growth in renal transplant patient.

CMV infection is one of the most common opportunistic infection in kidney transplant patients. If not treated, it is associated with increased mortality and graft loss. It can present as viremia or CMV disease in the form of CMV syndrome or tissue invasive CMV disease. The cutaneous presentation of CMV disease is a rare finding. Its identification is vital as cutaneous CMV infection can signal systemic infection and poor prognosis. In our case, 46-year-old male who was a post renal allograft recipient (RAR) presented as a protuberant growth over the medial side of the left ankle. On skin biopsy, nucleomegaly and inclusion bodies were seen in the epithelial cells. Immunohistochemistry was positive for CMV infection. Patient was treated with Ganciclovir, however, he succumbed to death because of severe sepsis due to secondary bacterial infection. Thus, CMV disease should always be kept in mind in immunocompromised patients like post RAR patients who present with cutaneous features like ulcerative lesions or fungating growth.

Growth pattern of skinfold thicknesses in term symmetric & asymmetric small for gestational age infants.

Background & objectives: A etiologically symmetric and asymmetric small for gestational age (SGA) infants are two distinct entities. In view of absence of longitudinal information on growth pattern of skinfold thicknesses (SFTs) among Indian infants, this study was conducted to assess the auxological dynamics of SFTs (sub-cutaneous fat) of symmetric and asymmetric SGA infants. Methods: Triceps, sub-scapular, biceps, mid-axillary and anterior thigh SFTs among full-term, 100 symmetric SGA, 100 asymmetric SGA and 100 appropriate for gestational age (AGA) infants were measured at one, three, six, nine and 12 months. Ponderal Index (PI) was used to categorize infants into symmetric SGA (PI ≥2.2 g/cm3) and asymmetric SGA (PI <2.2 g/cm3). Intra-group (symmetric vs. asymmetric), inter-group (SGA vs. AGA) and gender differences were quantified. Results: SFTs among symmetric, asymmetric SGA infants increased to attain peak by six months. Maximum fat deposition in SGA infants was noticed for triceps, minimum for mid-axillary SFT. Mean triceps and sub-scapular skinfolds were measured higher in symmetric SGA than in asymmetric infants. SGA infants had significantly (P≤0.05) thinner SFTs than AGA. Growth velocity for SFTs, among symmetric and asymmetric SGA, was measured maximum between one and three months, threreafter it declined and relatively, steepness of fall was maximum for mid-axillary SFT followed by sub-scapular SFT. Interpretation & conclusions: Thinner SFTs obtained for symmetric and asymmetric SGA as compared to AGA infants reveal their compromised adiposity and nutritional status. Comparatively, higher SFTs in symmetric than in asymmetric SGA infants appear to suggest that the former have a tendency to accumulate more fat, than the latter during infancy.

Identification of PKD1 and PKD2 gene variants in a cohort of 125 Asian Indian patients of ADPKD.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) accounts for 2.6% of the patients with chronic kidney disease in India. ADPKD is caused by pathogenic variants in either PKD1 or PKD2 gene. There is no comprehensive genetic data from Indian subcontinent. We aimed to identify the pathogenic variants in the heterogeneous Indian population. PKD1 and PKD2 variants were identified by direct gene sequencing and/or multiplex ligation-dependent probe amplification (MLPA) in 125 unrelated patients of ADPKD. The pathogenic potential of the variants was evaluated computationally and were classified according to ACMG guidelines. Overall 300 variants were observed in PKD1 and PKD2 genes, of which 141 (47%) have been reported previously as benign. The remaining 159 variants were categorized into different classes based on their pathogenicity. Pathogenic variants were observed in 105 (84%) of 125 patients, of which 99 (94.3%) were linked to PKD1 gene and 6 (6.1%) to PKD2 gene. Of 159 variants, 97 were novel variants, of which 43 (44.33%) were pathogenic, and 10 (10.31%) were of uncertain significance. Our data demonstrate the diverse genotypic makeup of single gene disorders in India as compared to the West. These data would be valuable in counseling and further identification of probable donors among the relatives of patients with ADPKD.

Secular trends of body mass index in North Indian children with Type 1 diabetes do not support the Accelerator Hypothesis.

OBJECTIVE: The accelerator hypothesis, which proposes a link between Type 1 diabetes (T1D) and Type 2 diabetes (T2D) through weight-related insulin resistance, remains untested in developing countries with increasing rates of childhood obesity and T1D, and different ethnicities. We aimed to test the accelerator hypothesis in the context of a significant increase in T1D at our centre. DESIGN AND METHODS: Medical records of children diagnosed with T1D between January 2005 and December 2014 were retrospectively reviewed. The body mass index (BMI) standard deviation scores (SDSs) were calculated using height and weight measurements recorded 1-2 months after diagnosis of T1D and compared with age-matched anthropometric data. The rate of change in BMI SDSs over time was calculated. Analysis of BMI data was undertaken for the three age categories: <5, 5 to <10 and >10 years. RESULTS: The mean age at diagnosis of 467 children with T1D was 7·27 ± 0·32 years and showed no change over the study period. There was a yearly increase of 14·11% in patient numbers; this increase was similar in the three age categories (22·7%, 17·0%, 16·3%, respectively, P = 1·0). Comparison of patient numbers between the two time periods of 5 years each showed a marked increase during 2010-2014 (148 vs 319, % increase 115·5%). The mean BMI SDSs at diagnosis in the three age categories were similar (P = 1·0) and showed a yearly change of -0·36; the mean change in the three age categories was also similar (-0·35, -0·27, -0·46, respectively, P = 1·0). No correlation was found between age at diagnosis and BMI SDSs (correlation coefficient 0·010, P = 0·82). The mean BMI SDS in patients was significantly lower compared to controls (-0·54 vs -0·02, P = 0·001). CONCLUSION: There was no association between BMI SDS and age at diagnosis in children with new onset T1D. Further studies are needed to test whether the accelerator hypothesis is relevant in developing countries.

Evaluation of micronutrient profile of North Indian children with cystic fibrosis: a case-control study.

BACKGROUND: Data on the micronutrient levels in children with cystic fibrosis (CF) are not available from developing countries, wherein the nutritional profile of children is quite different from that of Western countries. METHODS: Levels of fat-soluble vitamins (A, D, and E) and trace metals (iron, copper, and zinc) were measured in 27 CF cases and 27 controls. RESULTS: CF cases had significantly low levels of all studied micronutrients compared with controls, and the levels were even lower in cases with exacerbation than in stable CF cases. Prevalence of deficiency of vitamin D, vitamin E, iron, copper, and zinc was significantly higher in cases than in controls, whereas vitamin A deficiency was almost equal in both the groups. CONCLUSION: The prevalence of deficiency of vitamins A, D, and E and iron, copper, and zinc was high in CF cases, and their levels were significantly lower in cases than controls. CF cases should be regularly monitored for these micronutrients, and appropriate supplementation should be considered.

ABO-Incompatible Renal Transplant: A Single-Center Experience from India.

Introduction: In view of ever-increasing end-stage renal disease (ESRD) population but inadequate availability of suitable donors, ABO-incompatible (ABOi) transplantation can be an important void filler. However, at present, ABOi transplantation is limited to a few centers in India and there is a lack of adequate experience and expertise to guide this program to other centers in the country. Methods: Data of all the ABOi transplants performed from 2012 to 2021 in a tertiary care hospital was retrospectively analyzed. The anti-ABO antibody (IgG) titers (≤1:4) were considered safe before transplantation. Desensitization included rituximab, plasma exchange, or selective immunoadsorption column. Tacrolimus and mycophenolate mofetil were initiated at day -7. Induction agents included ATG, ATLG, basiliximab, or no induction. Postoperatively, anti-ABO titers were done daily for 2 weeks. Results: A total of 202 patients underwent transplantation; of these, 195 patients whose data were for available for 12 months were included in the study. Mean duration of follow-up was 28.9 ± 21.7 months. UTI was the most common source of infection, occurring in almost half (46.1%) of the patients. Antibody-mediated rejection (ABMR; 15%) was common in the first year. Patient survival was 86.6% (169/195) at 1 year. Sepsis was the most common of death in more than two-thirds of the population, including coronavirus disease 2019 (COVID-19)-associated mortality in nine patients (4.6%). Death-censored graft survival was 89.3% (174/195). AMR was the leading cause of graft loss in almost half of the patients. Conclusion: ABOi should be considered in ESRD patients for whom suitable ABO-compatible donor is not available. Higher rate of rejection and infection are still a major concern.

A boy with prepubertal gynecomastia, hyperprolactinemia, and hypothyroidism.

Non-physiologic prepubertal gynecomastia with an identifiable cause is an uncommon condition. Hyperprolactinemia due to hypothyroidism is known to result in gynecomastia in adults, but this observation has not been reported in children. We discuss here a boy who developed gynecomastia after the first year of age and was later diagnosed with congenital hypothyroidism.

Growth Pattern and Use of Inter-pupillary Distance in the Detection of Ocular Hypertelorism and Hypotelorism in Indian Down Syndrome Children.

Use of inter-pupillary distance (IPD) for objective evaluation of ocular hypertelorism and hypotelorism is recommended to corroborate diagnosis of syndromic conditions. In view of complete absence of serial data on growth of IPD, this study aims to unfold auxological dynamics of IPD in Down syndrome (DS) children of Indian origin. Inner canthal distance (ICD) and outer canthal distance (OCD) were measured on a total of 1,125 (male: 752, female: 373) DS children, aged 0 to 3 months to 10 years at 6 monthly age intervals using a "Digimatic Sliding Caliper" in the Growth Laboratory/Growth Clinic of the Institute. Using Feingold and Bossert (1974) formula, IPD at each age was calculated from ICD and OCD measured among male and female DS children. IPD, like OCD and ICD increased un-interruptedly among DS children. IPD grew rapidly up to 5 years thereafter, its rapidity became slower. Boys in general, possessed larger IPD than girls, however, gender differences became statistically significant up to first 4 years of life. Our study children possessed significantly smaller IPD as compared with their normal Indian counterparts. None of our DS children depicted ocular hypertelorism while hypotelorism, was noticed amongst 4.9% male and 16.8% female DS patients. Comparison with normative IPD data failed to establish existence of ocular hypertelorism in DS children (<10 years) of north-western Indian origin. Use of age and gender-specific data presented for IPD of DS children may be made for comparative purpose to ascertain inter-population variability.

Donor-Derived Cell-Free DNA as a Non-Invasive Biomarker for Graft Rejection in Kidney Transplant Recipients: A Prospective Study among the Indian Population.

Monitoring graft health and detecting graft rejection is crucial for the success of post-transplantation outcomes. In Western countries, the use of donor-derived cell-free DNA (dd-cfDNA) has gained widespread recognition as a diagnostic tool for kidney transplant recipients. However, the role of dd-cfDNA among the Indian population remains unexplored. The recipients were categorized into two groups: the post-transplant recipient (PTR) group (n = 16) and the random recipient (RR) group (n = 87). Blood samples were collected daily from the PTR group over a 7-day period, whereas the RR group's samples were obtained at varying intervals. In this study, we used a targeted approach to identify dd-cfDNA, which eliminated the need for genotyping, and is based on the minor allele frequency of SNP assays. In the PTR group, elevated dd-cfDNA% levels were observed immediately after transplantation, but returned to normal levels within five days. Within the RR group, heightened serum creatinine levels were directly proportional to increased dd-cfDNA%. Sixteen recipients were advised to undergo biopsy due to elevated serum creatinine and other pathological markers. Among these sixteen recipients, six experienced antibody-mediated rejection (ABMR), two exhibited graft dysfunctions, two had active graft injury, and six (37.5%) recipients showed no rejection (NR). In cases of biopsy-proven ABMR and NR, recipients displayed a mean ± SD dd-cfDNA% of 2.80 ± 1.77 and 0.30 ± 0.35, respectively. This study found that the selected SNP assays exhibit a high proficiency in identifying donor DNA. This study also supports the use of dd-cfDNA as a routine diagnostic test for kidney transplant recipients, along with biopsies and serum creatinine, to attain better graft monitoring.

Nutritional status and complications in children with diabetic ketoacidosis.

OBJECTIVE: Diabetic ketoacidosis in children continues to be an important cause of morbidity and mortality, especially in developing economies as a result of malnutrition, a high rate of infections, and delay in seeking timely medical care. Malnutrition also increases the risk of diabetic ketoacidosis-related complications. The objective of this study was to assess the nutritional status of patients presenting with diabetic ketoacidosis and correlate it with the incidence of complications at presentation and those encountered during the course of illness. DESIGN: Prospective study. SETTING: Pediatric emergency and intensive care units, Advanced Pediatrics Centre, PGIMER, Chandigarh, India. PATIENTS: Thirty-three children between 1 month and 12 yrs of age presenting with diabetic ketoacidosis between July 2008 and June 2009 were enrolled consecutively and assessed for nutritional status by anthropometric parameters (body weight, crown-heel length/height, mid-upper arm circumference, triceps and subscapular skin fold thicknesses), biochemical parameters (serum albumin, zinc, magnesium, vitamin A levels), and preillness dietary history (by pretested Food Frequency Questionnaire). Patients were classified as malnourished or normally nourished based on the weight for age criteria matched for Indian standards. The incidence of complications (electrolyte imbalances, hypoglycemia, sepsis, cerebral edema, etc.) and outcome in terms of survival or death in both the groups were compared with Student's t-test for parametric data, Mann-Whitney U test for nonparametric data, and chi-square test for categorical variables. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Anthropometric assessment showed that 11 of 33 (33.3%) were malnourished. Preillness dietary history revealed that 16 (48.5%) were calorie- and protein-deficient (known diabetic n = 7; new onset n = 9), whereas 11 (33.3%) were only calorie-deficient (known diabetic n = 2). Hypoalbuminemia was seen in 21 (63.6%), hypovitaminosis A in eight (24.2%), and low zinc levels in three (9%). The malnourished and normally nourished groups were similar with respect to demographics, precipitating factors, severity of diabetic ketoacidosis, treatment received, and outcome. However, the incidence and severity of therapy-related hypokalemia (100% vs. 72.7%; p = .05) and hypoglycemia (63.6 vs. 13.6%; p = .004) were significantly higher in the former as compared with the latter. The mean ± SD admission serum potassium levels were similar in both the groups (3.4 ± 0.8 mEq/L in the malnourished vs. 3.5 ± 0.7 mEq/L in the normally nourished) with the malnourished group showing a significant fall at 6 hrs after start the of diabetic ketoacidosis protocol (2.8 ± 0.8 mEq/L vs. 3.6 ± 0.7 mEq/L; p = .033), although the mean rate and dose of insulin infusion were similar. The fall in blood glucose (mean ± SD mg/dL) at 12, 24, and 36 hrs after onset of the diabetic ketoacidosis protocol was also significantly greater in the malnourished group as compared with the normally nourished diabetic ketoacidosis (195 ± 69.1 and 272.61 ± 96.3, p = .02; 171 ± 58.5 and 257 ± 96.3, p = .05; and 153.75 ± 49.6 and 241.71 ± 76.3, p = .04, respectively). The incidence of hypophosphatemia, hypomagnesemia, cerebral edema, renal failure, sepsis, and septic shock was similar in both the groups. There were two deaths, both resulting from complicating cerebral edema and renal failure and unrelated to the nutritional status of the patients. CONCLUSIONS: The incidence and severity of therapy-related hypokalemia and hypoglycemia were significantly higher in the malnourished as compared to the normally nourished diabetic ketoacidosis. Other diabetic ketoacidosis-related complications and outcome were similar in both the groups.

Postnatal percentile growth charts for Indian appropriate for gestational age (AGA) very low birth weight babies.

AIMS: To develop postnatal percentile growth charts for Indian very low birth weight (VLBW) appropriate for gestational age (AGA) babies till 37 weeks post conceptional age (PCA). METHODS: Prospective, mixed longitudinal study in 105 VLBW AGA (male 73 and female 32) babies weighing <1500 g and <34 weeks gestation born over 1 year. All were weighed daily until discharge and then weekly till 37 weeks of PCA. The percentile weight curves were computed in four categories : ≤28 weeks, 29-30, 31-32 and 33 weeks, and a total of seven percentile distributions (3rd, 10th, 25th, 50th, 75th, 90th& 97th) were generated. Entire data were subjected to Tanner's 1951 method to compute mean and standard deviation for body weight. The arithmetic mean served the 50(th) percentile. RESULTS: All babies at birth were <50th centile as per Lubchenco's intrauterine growth chart. This pattern was more evident in higher gestation (31-32 and 33 weeks) than lower gestation (≤28 and 29-30 weeks). At 37 weeks PCA, all were <10th centile and the lowest was in ≤28 weeks gestation. CONCLUSIONS: Our babies are born smaller, and growth rate is slower than their western counterparts. Babies at lowest gestation had slowest postnatal growth. Hence, we need a separate growth chart for our babies.