The Kynurenine/Tryptophan Ratio Is a Sensitive Biomarker for the Diagnosis of Pediatric Tuberculosis Among Indian Children

ObjectivesPediatric tuberculosis (TB) remains difficult to diagnose. The plasma kynurenine to tryptophan ratio (K/T ratio) is a potential biomarker for TB diagnosis and treatment response but has not been assessed in children.MethodsWe performed a targeted diagnostic accuracy analysis of four biomarkers: kynurenine abundance, tryptophan abundance, the K/T ratio, and IDO-1 gene expression. Data were obtained from transcriptome and metabolome profiling of children with confirmed tuberculosis and age- and sex-matched uninfected household contacts of pulmonary tuberculosis patients. Each biomarker was assessed as a baseline diagnostic and in response to successful TB treatment.ResultsDespite non-significant between-group differences in unbiased analysis, the K/T ratio achieved an area under the receiver operator characteristic curve (AUC) of 0.667 and 81.5% sensitivity for TB diagnosis. Kynurenine, tryptophan, and IDO-1 demonstrated diagnostic AUCs of 0.667, 0.602, and 0.463, respectively. None of these biomarkers demonstrated high AUCs for treatment response. The AUC of the K/T ratio was lower than biomarkers identified in unbiased analysis, but improved sensitivity over existing commercial assays for pediatric TB diagnosis.ConclusionsPlasma kynurenine and the K/T ratio may be useful biomarkers for pediatric TB. Ongoing studies in geographically diverse populations will determine optimal use of these biomarkers worldwide.

Prenatal and Early Postnatal Exposure to A Natural Disaster and Attention-Deficit/Hyperactivity Disorder Symptoms in Indian Children

The aim of this study was to assess the relation between early exposure to stressful event and a level of Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms in children, based on outcomes from a natural experiment. It was hypothesized that children pre- and postnatally exposed to cyclone Aila have a higher level of ADHD symptoms compared to the controls, and the effect depends on timing of exposure. Indian children (8-11y) prenatally (N=336) and early postnatally (N=216) exposed to Aila were compared to non-exposed control group of their peers (N=285). ADHD symptoms were assessed using the Conner’s Teacher Rating Scale Revised. The main effect of exposure to the cyclone on total ADHD symptoms’ score, ADHD index, Hyperactivity and Oppositional symptoms was significant and independent of covariates. Both prenatally and postnatally exposed girls, and only postnatally exposed boys, showed significantly higher level of Oppositional symptoms compared to the controls. Cognitive problems/Inattention symptoms were increased in both prenatally and postnatally exposed boys, but not girls, compared to non-exposed children. The timing of programming the later behavior characteristics by stressful experiences due to natural disaster is not limited to fetal life but extends at least into infancy. Sex is a significant modulator of the early stress-ADHD symptoms association.

DNA methylation signatures associated with cardiometabolic risk factors in children from India and The Gambia: results from the EMPHASIS study

Background The prevalence of cardiometabolic disease (CMD) is rising globally, with environmentally induced epigenetic changes suggested to play a role. Few studies have investigated epigenetic associations with CMD risk factors in children from low- and middle-income countries. We sought to identify associations between DNA methylation (DNAm) and CMD risk factors in children from India and The Gambia. Results Using the Illumina Infinium HumanMethylation 850 K Beadchip array, we interrogated DNAm in 293 Gambian (7–9 years) and 698 Indian (5–7 years) children. We identified differentially methylated CpGs (dmCpGs) associated with systolic blood pressure, fasting insulin, triglycerides and LDL-Cholesterol in the Gambian children; and with insulin sensitivity, insulinogenic index and HDL-Cholesterol in the Indian children. There was no overlap of the dmCpGs between the cohorts. Meta-analysis identified dmCpGs associated with insulin secretion and pulse pressure that were different from cohort-specific dmCpGs. Several differentially methylated regions were associated with diastolic blood pressure, insulin sensitivity and fasting glucose, but these did not overlap with the dmCpGs. We identified significant cis-methQTLs at three LDL-Cholesterol-associated dmCpGs in Gambians; however, methylation did not mediate genotype effects on the CMD outcomes. Conclusion This study identified cardiometabolic biomarkers associated with differential DNAm in Indian and Gambian children. Most associations were cohort specific, potentially reflecting environmental and ethnic differences.

Deciphering the mutation spectrum in south Indian children with congenital anomalies of the kidney and urinary tract

Background Congenital anomalies of the kidney and urinary tract (CAKUT) cover a spectrum of structural malformations that result from aberrant morphogenesis of kidney and urinary tract. It is the most prevalent cause of kidney failure in children. Hence, it is important from a clinical perspective to unravel the molecular etiology of kidney and urinary tract malformations. Causal variants in genes that direct various stages of development of kidney and urinary tract in fetal life have been identified in 5–20% of CAKUT patients from Western countries. Recent advances in next generation sequencing technology and decreasing cost offer the opportunity to characterize the genetic profile of CAKUT in Indian population and facilitate integration of genetic diagnostics in care of children with CAKUT. Methods Customized targeted panel sequencing was performed to identify pathogenic variants in 31 genes known to cause human CAKUT in 69 south Indian children with CAKUT. The NGS data was filtered using standardized pipeline and the variants were classified using ACMG criteria. Genotype and phenotype correlations were performed. Results The cohort consisted of children mostly with posterior urethral valve (PUV) (39.1%), vesico-ureteric reflux (VUR) (33.3%) and multi-cystic dysplastic kidney (MCDK) (7.2%). No pathogenic or likely pathogenic variants were identified in the study. Most of our variants (n = 39, 60%) were variants of unknown significance with 25.6% (10/39) of them were identified as potentially damaging but were novel variants. Conclusions The present study did not identify any disease-causing monogenic variants in the cohort. The absence of genetic cause may be due to limitations of panel-based testing and also due to higher proportion of children with abnormalities in lower urinary tract than hypodysplasia of kidneys. Clinical, larger targeted panel or whole exome sequencing may be a better method to characterize the genetic profile of Indians patients with CAKUT.

Growth during times of fear and emotional stress

Twenty-one scientists met for this year’s virtual conference on Auxology held at the University Potsdam, Germany, to discuss child and adolescent growth during times of fear and emotional stress. Growth within the broad range of normal for age and sex is considered a sign of good general health whereas fear and emotional stress can lead to growth faltering. Stunting is a sign of social disadvantage and poor parental education. Adverse childhood experiences affect child development, particularly in families with low parental education and low socioeconomic status. Negative effects were also shown in Indian children exposed prenatally and in early postnatal life to the cyclone Aila in 2009. Distrust, fears and fake news regarding the current Corona pandemic received particular attention though the effects generally appeared weak. Mean birth weight was higher; rates of low, very and extremely low birth weight were lower. Other topics discussed by the participants, were the influences of economic crises on birth weight, the measurement of self-confidence and its impact on growth, the associations between obesity, peer relationship, and behavior among Turkish adolescents, height trends in Indonesia, physiological neonatal weight loss, methods for assessing biological maturation in sportsmen, and a new method for skeletal age determination. The participants also discussed the association between acute myocardial infarction and somatotype in Estonia, rural-urban growth differences in Mongolian children, socio-environmental conditions and sexual dimorphism, biological mortality bias, and new statistical techniques for describing inhomogeneity in the association of bivariate variables, and for detecting and visualizing extensive interactions among variables.

Influence of agriculture on child nutrition through child feeding practices in India: A district-level analysis

Malnutrition continues to be a primary concern for researchers and policymakers in India. There is limited scientific research on the effect of agriculture on child nutrition in the country using a large representative sample. To the best of our knowledge, no study has examined the spatial clustering of child malnutrition and its linkage with agricultural production at the district-level in the country. The present study aims to examine agricultural production’s role in improving the nutritional status of Indian children through child feeding practices. The nutritional indicators of children from the National Family Health Survey-4 (2015–16) and the agricultural production data for all the 640 districts of India obtained from the District-Wise Crop Production Statistics (2015–16), published by the Ministry of Agriculture, Government of India were used for the analysis. The statistical analysis was undertaken in STATA (version 14.1). ArcMap (version 10.3), and GeoDa (version 1.8) were used for the spatial analysis. The study found a higher prevalence of malnutrition among children who had not received Minimum Meal Frequency (MMF), Minimum Dietary Diversity (MDD), and Minimum Acceptable Diet (MAD). Further, child feeding practices- MMF, MDD, and MAD- were positively associated with high yield rates of spices and cereals. The yield rate of cash crops, on the contrary, harmed child feeding practices. Production of pulses had a significant positive effect on MDD and MAD. Districts with high cereal yield rates ensured that children receive MMF and MAD. There is a significant spatial association between child feeding practices and malnutrition across Indian districts. The study suggests that adopting nutrient-sensitive agriculture may be the best approach to improving children’s nutritional status.

Delta Variant SARS-CoV-2 infections in pediatric cases during the second wave in India

The aim of this study was to identify the SARS-CoV-2 lineages circulating in the pediatric population of India during the second wave of the pandemic. Clinical and demographic details linked with the nasopharyngeal/oropharyngeal swabs (NPS/OPS) collected from SARS-CoV-2 cases (n=583) aged 0-18 year and tested positive by real-time RT-PCR were retrieved from March to June 2021.Symptoms were reported among 37.2% of patients and 14.8% reported to be hospitalized. The E gene CT value had significant statistical difference at the point of sample collection when compared to that observed in the sequencing laboratory. Out of these 512 sequences 372 were VOCs, 51 were VOIs. Most common lineages observed were Delta, followed by Kappa, Alpha and B.1.36, seen in 65.82%, 9.96%, 6.83% and 4.68%, respectively in the study population. Overall, it was observed that Delta strain was the leading cause of SARS-CoV-2 infection in Indian children during the second wave of the pandemic. We emphasize on the need of continuous genomic surveillance in SARS-CoV-2 infection even amongst children.