Search

Human height is strongly influenced by genetics but the contribution of modifiable epigenetic factors is under-explored, particularly in low and middle-income countries (LMIC). We investigate links between blood DNA methylation and child height in four LMIC cohorts (n = 1927) and identify a robust association at three CpGs in the suppressor of cytokine signaling 3 (SOCS3) gene which replicates in a high-income country cohort (n = 879). SOCS3 methylation (SOCS3m)-height associations are independent of genetic effects. Mendelian randomization analysis confirms a causal effect of SOCS3m on height. In longitudinal analysis, SOCS3m explains a maximum 9.5% of height variance in mid-childhood while the variance explained by height polygenic risk score increases from birth to 21 years. Children's SOCS3m is associated with prenatal maternal folate and socio-economic status. In-vitro characterization confirms a regulatory effect of SOCS3m on gene expression. Our findings suggest epigenetic modifications may play an important role in driving child height in LMIC., (© 2023. Springer Nature Limited.)

Background: Gestational diabetes can predispose two generations-a mother and her child-to a higher risk of obesity and type 2 diabetes. Culture-specific strategies to prevent gestational diabetes are required. BANGLES investigated the associations between women's periconceptional diet and gestational diabetes risk., Methods: BANGLES was a prospective observational study (n=785), in which women of various socioeconomic status were recruited at 5-16 weeks' gestation in Bangalore, India. Periconceptional diet was recalled at recruitment, using a validated 224-item food frequency questionnaire, that was reduced to 21 food groups for the food group-gestational diabetes analysis, and 68 food groups for the principal component analysis for a diet pattern-gestational diabetes analysis. Diet-gestational diabetes associations were examined using multivariate logistic regression, adjusting for a priori confounders determined from the literature. Gestational diabetes was assessed by a 75 g oral glucose tolerance test at 24-28 weeks' gestation, applying 2013 WHO criteria., Findings: Women who consumed whole-grain cereals (adjusted odds ratio [OR] 0·58, 95% CI 0·34-0·97, p=0·03); had moderate egg consumption (>1-3 times per week) compared with less than once per week (adjusted OR 0·54, 95% CI 0·34-0·86, p=0·01); and a higher weekly intake of pulses and legumes (adjusted OR 0·81, 95% CI 0·66-0·98, p=0·03), nuts and seeds (adjusted OR 0·77, 95% CI 0·63-0·94, p=0·01), and fried and fast food (adjusted OR 0·72, 95% CI 0·59-0·89, p=0·002) had a lower gestational diabetes. None of these associations was significant after correction for multiple testing. A high-diversity, urban diet pattern characterised by diverse home-cooked and processed foods and associated with older, affluent, educated, urban women was associated with a lower risk (adjusted OR 0·80, 95% CI 0·64-0·99, p=0·04). BMI was the strongest risk factor for gestational diabetes and possibly mediated the diet pattern-gestational diabetes associations., Interpretation: The same food groups that were associated with a lower gestational diabetes risk were components of the high-diversity, urban diet pattern. One healthy diet pattern might not be relevant to India. Findings support global recommendations to encourage women to attain a healthy pre-pregnancy BMI, increase diet diversity to prevent gestational diabetes, and have policies to increase food affordability., Funding: Schlumberger Foundation., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: With strong evidence of physical inactivity's link to chronic disease and economic burden - particularly with childhood active living behaviors tracking into adulthood - it is imperative to promote physical activity among children and adolescents in India., Objectives: To evaluate active living patterns among Indian children and adolescents., Methods: The India Report Card (IRC) team, which consists of experts in India and Canada, systematically collected and appraised evidence on 11 indicators of active living, including 5 behavioral ( Overall Physical Activity , Organized Sport Participation , Active Play , Active Transportation , Sedentary Behavior ), 2 individual-level ( Physical Fitness , Yoga ) and 4 sources of influence ( Family and Peers , School , Community and Built Environment , Government ). Peer-reviewed articles were appraised based on national representativeness, sample size, and data quality. Grey literature was appraised based on comprehensiveness, validity of the sources, and representativeness. All indicators were assessed against parameters provided by the Active Healthy Kids Global Alliance., Results: Active Transportation and Government Strategies were ranked highest with a B- and C+ grade, respectively. Overall Physical Activity and Schools were assigned a C grade, while Sedentary Behavior and Community and Built Environment were given D grades. Yoga was the lowest ranking indicator with a D- grade. Organized Sport Participation , Active Play , Family and Peers , and Physical Fitness were all graded incomplete., Conclusions: Active Transportation , Government Strategies , and Overall Physical Activity have improved since the 2018 IRC, a positive trend that needs to be translated to other indicators. However, Sedentary Behavior has consistently worsened, with grades C, C-, and D-, in 2016, 2018, and 2022, respectively. Evidence generated by the 2022 IRC suggests opportunities for improvement not only in India, but also the 56 other countries taking part in Global Matrix 4.0., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2022 The Society of Chinese Scholars on Exercise Physiology and Fitness. Published by Elsevier (Singapore) Pte Ltd.)

Changes in brain morphology have been reported during development, ageing and in relation to different pathologies. Brain morphology described by the shape complexity of gyri and sulci can be captured and quantified using fractal dimension (FD). This measure of brain structural complexity, as well as brain volume, are associated with intelligence, but less is known about the sexual dimorphism of these relationships. In this paper, sex differences in the relationship between brain structural complexity and general intelligence (g) in two diverse geographic and cultural populations (UK and Indian) are investigated. 3D T1-weighted magnetic resonance imaging (MRI) data and a battery of cognitive tests were acquired from participants belonging to three different cohorts: Mysore Parthenon Cohort (MPC); Aberdeen Children of the 1950s (ACONF) and UK Biobank. We computed MRI derived structural brain complexity and g estimated from a battery of cognitive tests for each group. Brain complexity and volume were both positively corelated with intelligence, with the correlations being significant in women but not always in men. This relationship is seen across populations of differing ages and geographical locations and improves understanding of neurobiological sex-differences., (© 2022. The Author(s).)

Size at birth is known to be influenced by various fetal and maternal factors, including genetic effects. South Asians have a high burden of low birth weight and cardiometabolic diseases, yet studies of common genetic variations underpinning these phenotypes are lacking. We generated independent, weighted fetal genetic scores (fGSs) and maternal genetic scores (mGSs) from 196 birth weight-associated variants identified in Europeans and conducted an association analysis with various fetal birth parameters and anthropometric and cardiometabolic traits measured at different follow-up stages (5-6-year intervals) from seven Indian and Bangladeshi cohorts of South Asian ancestry. The results from these cohorts were compared with South Asians in UK Biobank and the Exeter Family Study of Childhood Health, a European ancestry cohort. Birth weight increased by 50.7 g and 33.6 g per SD of fGS (P = 9.1 × 10-11) and mGS (P = 0.003), respectively, in South Asians. A relatively weaker mGS effect compared with Europeans indicates possible different intrauterine exposures between Europeans and South Asians. Birth weight was strongly associated with body size in both childhood and adolescence (P = 3 × 10-5 to 1.9 × 10-51); however, fGS was associated with body size in childhood only (P < 0.01) and with head circumference, fasting glucose, and triglycerides in adults (P < 0.01). The substantially smaller newborn size in South Asians with comparable fetal genetic effect to Europeans on birth weight suggests a significant role of factors related to fetal growth that were not captured by the present genetic scores. These factors may include different environmental exposures, maternal body size, health and nutritional status, etc. Persistent influence of genetic loci on size at birth and adult metabolic syndrome in our study supports a common genetic mechanism that partly explains associations between early development and later cardiometabolic health in various populations, despite marked differences in phenotypic and environmental factors in South Asians., (© 2022 by the American Diabetes Association.)

Introduction: Many of the assessment tools used to study depression amongst older people in low- and middle- income countries (LMICs) are adaptations of instruments developed in other cultural settings. There is a need to validate those instruments in LMICs., Methods: 721 men and women aged 55-80 years from the Mysore Birth Records Cohort underwent standardised assessments for sociodemographic characteristics, cardiometabolic risk factors, cognitive function and mental health. Sensitivity, specificity and level of agreement of EURO-D diagnosis of depression with diagnosis of depression derived by the Geriatric Mental State (GMS) examination were calculated. To validate the EURO-D score against GMS depressive episode, we used maximum Youden's index as the criterion for each cut-off point. Concurrent validity was assessed by measuring correlations with the WHO Disability Assessment Schedule (WHO DAS II)., Results: Of the 721 (408 men and 313 women) who participated in this study, 138 (54 men and 84 women) were diagnosed with depression. Women had higher depression scores on the EURO-D scale and disability on the WHO DAS II scale. A maximum Youden's Index of 0.60 was observed at a EURO-D cut-off of 6, which corresponded to 95% sensitivity, 64% specificity, kappa value of 0.6 and area under the curve (AUC) of 80%. There was significant and positive correlation between EURO-D and WHO DAS II scores., Limitations: Future independent validation studies in other settings are required., Discussion: This study supports the use of the EURO-D scale for diagnosing depression amongst older adults in South India., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Adolescent diet, physical activity and nutritional status are generally known to be sub-optimal. This is an introduction to a special issue of papers devoted to exploring factors affecting diet and physical activity in adolescents, including food insecure and vulnerable groups., Setting: Eight settings including urban, peri-urban and rural across sites from five different low- and middle-income countries., Design: Focus groups with adolescents and caregivers carried out by trained researchers., Results: Our results show that adolescents, even in poor settings, know about healthy diet and lifestyles. They want to have energy, feel happy, look good and live longer, but their desire for autonomy, a need to 'belong' in their peer group, plus vulnerability to marketing exploiting their aspirations, leads them to make unhealthy choices. They describe significant gender, culture and context-specific barriers. For example, urban adolescents had easy access to energy dense, unhealthy foods bought outside the home, whereas junk foods were only beginning to permeate rural sites. Among adolescents in Indian sites, pressure to excel in exams meant that academic studies were squeezing out physical activity time., Conclusions: Interventions to improve adolescents' diets and physical activity levels must therefore address structural and environmental issues and influences in their homes and schools, since it is clear that their food and activity choices are the product of an interacting complex of factors. In the next phase of work, the Transforming Adolescent Lives through Nutrition consortium will employ groups of adolescents, caregivers and local stakeholders in each site to develop interventions to improve adolescent nutritional status.

Objective: To examine if smaller size at birth, an indicator of growth restriction in utero, is associated with lower cognition in late life, and whether this may be mediated by impaired early life brain development and/or adverse cardiometabolic programming., Design: Longitudinal follow-up of a birth cohort., Setting: CSI Holdsworth Memorial Hospital (HMH), Mysore South India., Participants: 721 men and women (55-80 years) whose size at birth was recorded at HMH. Approximately 20 years earlier, a subset (n = 522) of them had assessments for cardiometabolic disorders in mid-life., Measurements: Standardized measurement of cognitive function, depression, sociodemographic, and lifestyle factors; blood tests and assessments for cardiometabolic disorders., Results: Participants who were heavier at birth had higher composite cognitive scores (0.12 SD per SD birth weight [95% CI 0.05, 0.19] p = 0.001) in late life. Other lifecourse factors independently positively related to cognition were maternal educational level and participants' own educational level, adult leg length, body mass index, and socioeconomic position, and negatively were diabetes in mid-life and current depression and stroke. The association of birth weight with cognition was independent cardiometabolic risk factors and was attenuated after adjustment for all lifecourse factors (0.08 SD per SD birth weight [95% CI -0.01, 0.18] p = 0.07)., Conclusions: The findings are consistent with positive effects of early life environmental factors (better fetal growth, education, and childhood socioeconomic status) on brain development resulting in greater long-term cognitive function. The results do not support a pathway linking poorer fetal development with reduced late life cognitive function through cardiometabolic programming.

Background: In India, stress levels are increasing steadily among youth. We aimed to explore the factors that contribute to psychological stress and coping strategies among adolescents in Mysore, India to inform the development of an intervention. Methods: We recruited 16 volunteers in Mysore, India including 6 younger (12-15 years; 3 girls) and 10 older adolescents/ young adults (17-25 years; 5 girls) using a purposive sampling technique. Older adolescents were recruited from ongoing birth cohort study, and the younger adolescents by word-of-mouth from the community. Individual in-depth interviews were carried out based on a semi-structured interview guide comprising open-ended questions. The interviews were analysed to derive themes and emerging constructs related to stress and coping strategies.  Results: Adolescents generally perceived stress in their daily lives. Family conflicts and academic pressures were the main triggers for increased stress. Issues around peer relationships, and social position were also important contributors. Adolescents reported that they had robust coping strategies. These included stress release through rationalising and acceptance of the situation, distraction activities, spirituality, and self-comforting methods. However, they felt the need for further support from their family, and the society in general. In particular they expressed the need for a space to share their concerns and obtain guidance through healthy discussions with adults.      Conclusions: Our study indicates that adolescents in India are exposed to a wide range of stressors in their daily lives. The conflict between 'traditional' society's opinions of what adolescents should do and the new age adolescents' aspirations for autonomy to find 'informed' solutions for their issues may hinder the stress management efforts. Moving forward, we propose to develop a culturally acceptable intervention tool that accommodates adolescents' perspectives and psychosocial context., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Nagabharana T et al.)

Introduction: The Healthy Life Trajectories Initiative is an international consortium comprising four harmonised but independently powered trials to evaluate whether an integrated intervention starting preconceptionally will reduce non-communicable disease risk in their children. This paper describes the protocol of the India study., Methods and Analysis: The study set in rural Mysore will recruit ~6000 married women over the age of 18 years. The village-based cluster randomised design has three arms (preconception, pregnancy and control; 35 villages per arm). The longitudinal multifaceted intervention package will be delivered by community health workers and comprise: (1) measures to optimise nutrition; (2) a group parenting programme integrated with cognitive-behavioral therapy; (3) a lifestyle behaviour change intervention to support women to achieve a diverse diet, exclusive breast feeding for the first 6 months, timely introduction of diverse and nutritious infant weaning foods, and adopt appropriate hygiene measures; and (4) the reduction of environmental pollution focusing on indoor air pollution and toxin avoidance.The primary outcome is adiposity in children at age 5 years, measured by fat mass index. We will report on a host of intermediate and process outcomes. We will collect a range of biospecimens including blood, urine, stool and saliva from the mothers, as well as umbilical cord blood, placenta and specimens from the offspring.An intention-to-treat analysis will be adopted to assess the effect of interventions on outcomes. We will also undertake process and economic evaluations to determine scalability and public health translation., Ethics and Dissemination: The study has been approved by the institutional ethics committee of the lead institute. Findings will be published in peer-reviewed journals. We will interact with policy makers at local, national and international agencies to enable translation. We will also share the findings with the participants and local community through community meetings, newsletters and local radio., Trial Registration Number: ISRCTN20161479, CTRI/2020/12/030134; Pre-results., Competing Interests: Competing interests: None of the authors declare any conflict of interest. The HeLTI Council of funders and WHO have required all Principal Investigators to complete annual Declarations of Interest and to commit to having no direct or indirect relations with the tobacco, arms and infant food industries during the course of the study., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: Imbalances in maternal 1-carbon nutrients (vitamin B12, folate) have been shown to be associated with higher offspring cardiometabolic risk markers in India., Objective: We examined the hypothesis that low plasma vitamin B12 (B12) and high folate and homocysteine concentrations in the mother are associated with higher hypothalamic-pituitary-adrenal axis (cortisol) and cardiovascular responses during the Trier Social Stress Test for Children (TSST-C) in an Indian birth cohort., Methods: Adolescents (n = 264; mean age: 13.6 years), whose mothers' plasma B12, folate and total homocysteine concentrations had been measured during pregnancy, completed 5-minutes each of public speaking and mental arithmetic tasks in front of 2 unfamiliar "judges" (TSST-C). Baseline and poststress salivary cortisol concentrations were measured. Heart rate, blood pressure, stroke volume, cardiac output, and total peripheral resistance were measured continuously at baseline, during the TSST-C, and for 10 minutes after the TSST-C using a finger cuff; beat-to-beat values were averaged for these periods, respectively., Results: Maternal low B12 status (plasma B12 < 150 pmol/L) was associated with greater cortisol responses to stress in the offspring (P < .001). Higher homocysteine concentrations were associated with greater offspring heart rate response (P < .001). After adjustment for multiple comparisons, there were nonsignificant associations between higher maternal folate concentrations and offspring total peripheral resistance response (P = .01)., Conclusion: Our findings suggest that maternal 1-carbon nutritional status may have long-term programming implications for offspring neuroendocrine stress responses., (© Endocrine Society 2020.)

Background: The aim of this study was to determine whether physical activity volume and intensity in mid-childhood and early adolescence were associated with cardiometabolic risk factors at 13.5 years., Methods: Participants were recruited from the Mysore Parthenon observational birth cohort. At ages 6-10 and 11-13 years, volume and intensity of physical activity were assessed using AM7164 or GT1M actigraph accelerometers worn for ≥4 days, and expressed as mean counts per day and percentage time spent in light, moderate and vigorous physical activity according to criteria defined by Evenson et al. At 13.5 years, fasting blood samples were collected; lipids, glucose and insulin concentrations were measured and insulin resistance (HOMA) was calculated. Systolic and diastolic blood pressure were measured at the left arm using a Dinamap (Criticon). Anthropometry and bio-impedance analysis were used to assess body size and composition. Metabolic and anthropometric measures were combined to produce a metabolic syndrome risk score., Results: At 6-10 years, boys and girls respectively spent a median (IQR) of 1.1 (0.5, 2.0) % and 0.8 (0.4, 1.3) % of recorded time vigorously active. At 11-13 years, boys and girls respectively spent a median (IQR) of 0.8 (0.4, 1.7) % and 0.3 (0.1, 0.6) % of time vigorously active. All of the physical activity parameters were positively correlated between the 6-10 year and the 11-13 year measurements indicating that physical activity tracked from childhood to early adolescence. There were no associations between physical activity at 6-10 years and individual 13.5 year risk factors but % time vigorously active was inversely associated with metabolic syndrome score (B = -0.40, 95% CI -0.75, 0.05). Volume of physical activity at 11-13 years was inversely associated with 13.5 year HOMA and fat percentage and vigorous physical activity was associated with HOMA, fat percentage, sum of skinfolds, waist circumference and total: HDL cholesterol ratio. Vigorous physical activity was inversely associated with metabolic syndrome score (B = -0.51, 95% CI -0.94, -0.08)., Conclusions: Volume and intensity of physical activity in early adolescence were negatively associated with metabolic and anthropometric risk factors. Interventions that aim to increase adolescent physical activity, especially vigorous, may prevent cardiometabolic disease in later life.

Psychological stress is recognized as a major modifiable risk factor for adult non-communicable disease (NCD) that includes depression, type 2 diabetes mellitus, and cardiovascular disease. Dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity resulting in either exaggerated or blunted cortisol responses, and altered autonomic cardiovascular control have been thought to underlie this association. The developmental origins hypothesis proposes that impaired nutrition during fetal and early postnatal growth is associated with a higher NCD risk later in life. Maternal nutrients are vital for fetal growth and development, and both maternal undernutrition and over nutrition as in the case of gestational diabetes are associated with higher NCD risk markers in the offspring. Recent studies suggest that fetal exposure to maternal nutritional imbalances may permanently alter cortisol and cardio-sympathetic stress-responsiveness, which may link early life nutrition with adult disease risk. A few recent studies that examined the association between low birth weight as a marker of fetal undernutrition and stress response in humans showed that lower birth weight was associated with an altered HPA axis and cardiovascular sympathetic nervous system responses to stress in adults as well as in children. In addition, altered stress responses in relation to gestational diabetes have been noted. In this paper, we present available evidence from India for the association between maternal nutrition and offspring stress responsiveness against the backdrop of global evidence, and discuss its role in the escalating NCD rates in this population. We also discuss the scope for future studies in India and other transitioning countries., (Copyright © 2019 Krishnaveni and Srinivasan.)

Background: Body mass index (BMI) reaches a nadir in mid-childhood, known as the adiposity rebound (AR). Earlier AR is associated with a higher risk of cardio-vascular diseases in later life. Skinfolds, which are a more direct measure of adiposity, may give better insight into the relationship between childhood adiposity and later obesity and cardio-metabolic risk., Objective: We aimed to assess whether AR corresponds to a rebound in skinfolds, and compare associations of BMI-derived AR and skinfold-derived AR with cardio-metabolic risk markers in adolescence., Methods: We used penalised splines with random coefficients to estimate BMI and skinfold trajectories of 604 children from the Mysore Parthenon Birth Cohort. Age at AR was identified using differentiation of the BMI and skinfold growth curves between 2 and 10 years of age. At 13.5 years, we measured blood pressure, and glucose, insulin and lipid concentrations., Results: BMI and skinfolds had different growth patterns. Boys reached BMI-derived AR earlier than skinfold-derived AR (estimated difference: 0.41 years; 95% CI:[0.23, 0.56]), whereas the opposite was observed in girls (estimated difference: -0.71 years; 95% CI:[-0.90, -0.54]). At 13.5 years, children with earlier BMI-derived AR had higher BMI (-0.58 SD per SD increase of AR; 95%CI:[-0.65, -0.52]), fat mass (-0.44; 95%CI:[-0.50, -0.37]), insulin resistance (HOMA-IR: -0.20; 95%CI:[-0.28, -0.12]) and systolic blood pressure (-0.20; 95%CI:[-0.28, -0.11]), and lower HDL-cholesterol (0.12; 95%CI:[0.04, 0.21]). The associations were independent of BMI at time of rebound, but were fully explained by fat mass at 13.5 years. Similar associations were found for skinfold-derived AR., Conclusion: BMI-derived adiposity rebound predicts later cardio-metabolic risk markers similarly to that derived from skinfolds, a direct measure of adiposity.

Background: Early life nutrition may affect individuals' susceptibility to adult non-communicable diseases (NCD). Psychological stress is a well-recognised NCD risk factor. Recent evidence suggests that impaired foetal nutrition alters neuro-endocrine pathways, and hypothalamic-pituitary-adrenal axis feedback systems, resulting in abnormal stress responses, and NCD risk. This study aims to examine adolescent cortisol and cardiovascular stress responses in relation to maternal nutrition and contemporaneous NCD risk markers. Methods : The study sample will be drawn from three well-established birth cohorts in India; the Parthenon cohort, Mysore (N=550, age~20y), the SARAS KIDS prenatal intervention cohort, Mumbai (N=300, age~10-12y) and the Pune Rural Intervention in Young Adults/ PRIYA cohort, Pune (N=100, age~22y). We will perform the 'Trier Social Stress Test (TSST)', a well-accepted stress-test module which involves participants performing 5-minutes each of public speaking and mental arithmetic tasks in front of unfamiliar 'judges' (stressor). Repeated measures of salivary cortisol and autonomic cardiovascular outcomes relative to the stressor will be assessed. Measures of psychological stress, cognitive function, blood pressure, glucose-insulin metabolism and depression will be carried out. Mechanistic studies including DNA methylation in gluco-corticoid receptor ( NR3C1 ) and 11β-HSD2 gene loci and neuroimaging will be carried out in a subsample. Qualitative interviews and focus group discussions in a subsample of the Parthenon cohort will explore the perception of stress and stressors among the youth. We will convert repeated measures into time-weighted averages before analysis. We will carry out multivariable regression analysis to test the associations. We will further refine the analyses using the mixed-model regression and conditional analyses for the association with repeated measures.   Ethics and dissemination: This study has been approved by the research ethics committee of CSI Holdsworth Memorial Hospital, Mysore. The findings will be disseminated locally and at international meetings, and reports will be submitted to open access peer reviewed journals., Competing Interests: No competing interests were disclosed.

Objective: We examined associations of different adiposity measures with cortisol responses during the Trier Social Stress Test for children (TSST-C)., Design: Descriptive study., Setting: Holdsworth Memorial Hospital, Mysore, India., Participants: Adolescents aged 13.5y from a birth cohort were recruited (N=269, 133 boys)., Methods: The stressor (TSST-C) was 5-minutes each of public speaking and mental arithmetic tasks in front of two unfamiliar 'judges'. Salivary cortisol concentrations were measured at baseline and at regular intervals after TSST-C. Weight, height, sub scapular and triceps skinfold thickness, and waist and hip circumference were measured, and percentage body fat was estimated (fat%; bioimpedance). Body mass index (BMI) and Waist-to-hip ratio (WHR) were calculated. All variables were converted into within-cohort SD scores before analysis. Stress-induced change in cortisol concentrations from baseline (cortisol response) was examined in relation to adiposity., Results: Stress increased cortisol concentrations significantly from baseline (mean (SD): 5.5 (6.4) ng/mL; P<0.001). Higher WHR was associated with lower cortisol response at 20 and 30-minutes after stress (~0.13 SD decrease in cortisol response per SD higher WHR, P<0.05). Higher fat% was also associated with lower cortisol response only in girls 20-minutes post-stress (0.23 SD lower response per SD higher fat%, P=0.004). Sum of skinfold thickness and BMI were not associated with cortisol responses., Conclusion: Abdominal adiposity is associated with reduced hypothalamic-pituitary-adrenal axis reactivity to stress in this adolescent population.

The developmental origins of health disease (DOHaD) hypothesis proposes that altered environmental influences (nutrition, metabolism, pollutants, stress and so on) during critical stages of fetal growth predisposes individuals to diabetes and other non-communicable disease in later life. This phenomenon is thought to reflect permanent effects ('programming') of unbalanced fetal development on physiological systems. Intrauterine programming may underlie the characteristic Indian 'thin-fat' phenotype and the current unprecedented epidemic of diabetes on the backdrop of multigenerational maternal undernutrition in the country. India has been at the forefront of the DOHaD research for over two decades. Both retrospective and prospective birth cohorts in India provide evidence for the role of impaired early-life nutrition on the later diabetes risk. These studies show that in a transitioning country such as India, maternal undernutrition (of micronutrients) and overnutrition (gestational diabetes) co-exist, and expose the offspring to disease risk through multiple pathways. Currently, the Indian scientists are embarking on complex mechanistic and intervention studies to find solutions for the diabetes susceptibility of this population. However, a few unresolved issues in this context warrant continued research and a cautious approach.

Vitamin B12 is an important cofactor in one-carbon metabolism whose dysregulation is associated with various clinical conditions. Indians have a high prevalence of B12 deficiency but little is known about the genetic determinants of circulating B12 concentrations in Indians. We performed a genome-wide association study in 1001 healthy participants in the Pune Maternal Nutrition Study (PMNS), replication studies in 3418 individuals from other Indian cohorts and by meta-analysis identified new variants, rs3760775 (P = 1.2 × 10-23) and rs78060698 (P = 8.3 × 10-17) in FUT6 to be associated with circulating B12 concentrations. Although in-silico analysis replicated both variants in Europeans, differences in the effect allele frequency, effect size and the linkage disequilibrium structure of credible set variants with the reported variants suggest population-specific characteristics in this region. We replicated previously reported variants rs602662, rs601338 in FUT2, rs3760776, rs708686 in FUT6, rs34324219 in TCN1 (all P < 5 × 10-8), rs1131603 in TCN2 (P = 3.4 × 10-5), rs12780845 in CUBN (P = 3.0 × 10-3) and rs2270655 in MMAA (P = 2.0 × 10-3). Circulating B12 concentrations in the PMNS and Parthenon study showed a significant decline with increasing age (P < 0.001), however, the genetic contribution to B12 concentrations remained constant. Luciferase reporter and electrophoretic-mobility shift assay for the FUT6 variant rs78060698 using HepG2 cell line demonstrated strong allele-specific promoter and enhancer activity and differential binding of HNF4α, a key regulator of expression of various fucosyltransferases. Hence, the rs78060698 variant, through regulation of fucosylation may control intestinal host-microbial interaction which could influence B12 concentrations. Our results suggest that in addition to established genetic variants, population-specific variants are important in determining plasma B12 concentrations., (© The Author 2017. Published by Oxford University Press.)

Background and Objectives: Animal studies have demonstrated poor cognitive outcomes in offspring in relation to maternal vitamin D deficiency before and/or during pregnancy. Human studies linking maternal vitamin D status during pregnancy with offspring cognitive function are limited. We aimed to test the hypothesis that lower maternal vitamin D status during pregnancy is associated with poor offspring cognitive ability in an Indian population., Methods and Study Design: Cognitive function was assessed in children from the Mysore Parthenon birth cohort during childhood (age 9-10 years; n=468) and adolescence (age 13-14 years; n=472) using 3 core tests from the Kaufman Assessment Battery for children and additional tests measuring learning, long-term retrieval/ storage, short-term memory, reasoning, verbal fluency, visuo-spatial ability, and attention and concentration. Maternal serum 25-hydroxyvitamin D concentration was measured at 30±2 weeks of gestation., Results: During pregnancy 320 (68%) women had 'vitamin D deficiency' (serum 25-hydroxyvitamin D concentration <50 nmol/L). Girls scored better than boys in tests of short-term memory, reasoning, verbal fluency, and attention (p<0.05 for all). Maternal vitamin D status (low as well as across the entire range) was unrelated to offspring cognitive function at both ages, either unadjusted or after adjustment for the child's current age, sex, maternal age, parity, season at the time of blood sampling, gestational age, the child's birth and current size, socio-economic status, parents' education, maternal intelligence and home environment., Conclusions: In this population, despite a high prevalence of vitamin D deficiency during pregnancy, there was no evidence of an association between maternal vitamin D status and offspring cognitive function.

Introduction: For late-life neurocognitive disorders, as for other late-life chronic diseases, much recent interest has focused on the possible relevance of Developmental Origins of Health and Disease (DOHaD). Programming by undernutrition in utero, followed by overnutrition in adult life may lead to an increased risk, possibly mediated through cardiovascular and metabolic pathways. This study will specifically examine, if lower birth weight is associated with poorer cognitive functioning in late life in a south Indian population., Methods and Analysis: From 1934 onwards, the birth weight, length and head circumference of all babies born in the CSI Holdsworth Memorial Hospital, Mysore, India, were recorded in obstetric notes. Approximately 800 men and women from the Mysore Birth Records Cohort aged above 55 years, and a reliable informant for each, will be asked to participate in a single cross-sectional baseline assessment for cognitive function, mental health and cardiometabolic disorders. Participants will be assessed for hypertension, type-2 diabetes and coronary heart disease, nutritional status, health behaviours and lifestyles, family living arrangements, economic status, social support and social networks. Additional investigations include blood tests (for diabetes, insulin resistance, dyslipidaemia, anaemia, vitamin B 12 and folate deficiency, hyperhomocysteinemia, renal impairment, thyroid disease and Apolipoprotein E genotype), anthropometry, ECG, blood pressure, spirometry and body composition (bioimpedance). We will develop an analysis plan, first using traditional univariate and multivariable analytical paradigms with independent, dependent and mediating/confounding/interacting variables to test the main hypotheses., Ethics and Dissemination: This study has been approved by the research ethics committee of CSI Holdsworth Memorial Hospital. The findings will be disseminated locally and at international meetings, and will be published in open access peer reviewed journals., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Vitamin B12 (hereafter referred to as B12) deficiency in pregnancy is prevalent and has been associated with both lower birth weight (birth weight <2,500 g) and preterm birth (length of gestation <37 weeks). Nevertheless, current evidence is contradictory. We performed a systematic review and a meta-analysis of individual participant data to evaluate the associations of maternal serum or plasma B12 concentrations in pregnancy with offspring birth weight and length of gestation. Twenty-two eligible studies were identified (11,993 observations). Eighteen studies were included in the meta-analysis (11,216 observations). No linear association was observed between maternal B12 levels in pregnancy and birth weight, but B12 deficiency (<148 pmol/L) was associated with a higher risk of low birth weight in newborns (adjusted risk ratio = 1.15, 95% confidence interval (CI): 1.01, 1.31). There was a linear association between maternal levels of B12 and preterm birth (per each 1-standard-deviation increase in B12, adjusted risk ratio = 0.89, 95% CI: 0.82, 0.97). Accordingly, B12 deficiency was associated with a higher risk of preterm birth (adjusted risk ratio = 1.21, 95% CI: 0.99, 1.49). This finding supports the need for randomized controlled trials of vitamin B12 supplementation in pregnancy., (© The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Physical inactivity in children and youth in India is a major public health problem. The 2016 Indian Report Card on Physical Activity for Children and Youth has been conceptualized to highlight this epidemic by appraising behaviors, contexts, strategies, and investments related to physical activity of Indian children and youth., Methods: An international research collaboration resulted in the formation of a Research Working Group (RWG). RWG determined key indicators; identified, synthesized, and analyzed existing evidence; developed criteria for assigning grades; and, finally, assigned grades to indicators based on consensus., Results: Overall Physical Activity Levels were assigned a grade of C-. Active Transportation and Sedentary Behaviors were both assigned a grade of C. Government Strategies and Investments was assigned a grade of D. Six other indicators, including the country-specific indicator Physical Fitness, were graded as INC (incomplete) due to the lack of nationally representative evidence., Conclusions: Based on existing evidence, it appears that most Indian children do not achieve recommended levels of physical activity and spend most of their day in sedentary pursuits. The report card identifies gaps in both investments and research that need to be addressed before understanding the complete picture of active living in children and youth in India.

Background: The mother is the only source of nutrition for fetal growth including brain development. Maternal nutritional status (anthropometry, macro- and micro-nutrients) before and/or during pregnancy is therefore a potential predictor of offspring cognitive function. The relationship of maternal nutrition to offspring cognitive function is unclear. This review aims to assess existing evidence linking maternal nutritional status with offspring cognitive function., Methods: Exposures considered were maternal BMI, height and weight, micronutrient status (vitamins D, B12, folate and iron) and macronutrient intakes (carbohydrate, protein and fat). The outcome was any measure of cognitive function in children aged <18 years. We considered observational studies and trials with allocation groups that differed by single nutrients. We searched Medline/PubMed and the Cochrane Library databases and reference lists of retrieved literature. Two reviewers independently extracted data from relevant articles. We used methods recommended by the Centre for Reviews and Dissemination, University of York and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement., Results: Of 16,143 articles identified, 38 met inclusion criteria. Most studies were observational, and from high-income settings. There were few randomized controlled trials. There was consistent evidence linking maternal obesity with lower cognitive function in children; low maternal BMI has been inadequately studied. Among three studies of maternal vitamin D status, two showed lower cognitive function in children of deficient mothers. One trial of folic acid supplementation showed no effects on the children's cognitive function and evidence from 13 observational studies was mixed. Among seven studies of maternal vitamin B12 status, most showed no association, though two studies in highly deficient populations suggested a possible effect. Four out of six observational studies and two trials (including one in an Iron deficient population) found no association of maternal iron status with offspring cognitive function. One trial of maternal carbohydrate/protein supplementation showed no effects on offspring cognitive function., Conclusions: Current evidence that maternal nutritional status during pregnancy as defined by BMI, single micronutrient studies, or macronutrient intakes influences offspring cognitive function is inconclusive. There is a need for more trials especially in populations with high rates of maternal undernutrition., Systematic Review Registration: Registered in PROSPERO CRD42013005702 .

Background: We aimed to determine how linear growth and fat and lean tissue gain during discrete age periods from birth to adolescence are related to adolescent cardiometabolic risk factors and cognitive ability., Methods: Adolescents born to mothers with normal glucose tolerance during pregnancy from an Indian birth cohort (N = 486, age 13.5 years) had detailed anthropometry and measurements of body fat (fat%), fasting plasma glucose, insulin and lipid concentrations, blood pressure and cognitive function. Insulin resistance (HOMA-IR) was calculated. These outcomes were examined in relation to birth measurements and statistically independent measures (conditional SD scores) representing linear growth, and fat and lean tissue gain during birth-1, 1-2, 2-5, 5-9.5 and 9.5-13.5 years in 414 of the children with measurements at all these ages., Results: Birth length and linear growth at all ages were positively associated with current height. Fat gain, particularly during 5-9.5 years was positively associated with fat% at 13.5 years (0.44 SD per SD [99.9% confidence interval: 0.29,0.58]). Greater fat gain during mid-late childhood was associated with higher systolic blood pressure (5-9.5 years: 0.23 SD per SD [0.07,0.40]) and HOMA-IR (5-9.5 years: 0.24 [0.08,0.40], 9.5-13.5 years: 0.22 [0.06,0.38]). Greater infant growth (up to age 2 years) in linear, fat or lean components was unrelated to cardiometabolic risk factors or cognitive function., Conclusion: This study suggests that factors that increase linear, fat and lean growth in infancy have no adverse cardiometabolic effects in this population. Factors that increase fat gain in mid-late childhood may increase cardiometabolic risk, without any benefit to cognitive abilities.

Context: Altered endocrinal and autonomic nervous system responses to stress may link impaired intra-uterine growth with later cardiovascular disease., Objective: To test the hypothesis that offspring of gestational diabetic mothers (OGDM) have high cortisol and cardiosympathetic responses during the Trier Social Stress Test for Children (TSST-C)., Design: Adolescents from a birth cohort in India (n = 213; mean age, 13.5 y), including 26 OGDM, 22 offspring of diabetic fathers (ODF), and 165 offspring of nondiabetic parents (controls) completed 5 minutes each of public speaking and mental arithmetic tasks in front of two unfamiliar "evaluators" (TSST-C). Salivary cortisol concentrations were measured at baseline and at regular intervals after the TSST-C. Heart rate, blood pressure (BP), stroke volume, cardiac output, and total peripheral resistance were measured continuously at baseline, during the TSST-C, and for 10 minutes after the test using a finger cuff; the beat-to-beat values were averaged for these periods., Results: Cortisol and cardiosympathetic parameters increased from baseline during stress (P < .001). OGDM had greater systolic BP (mean difference, 5.6 mm Hg), cardiac output (0.5 L/min), and stroke volume (4.0 mL) increases and a lower total peripheral resistance rise (125 dyn · s/cm(5)) than controls during stress. ODF had greater systolic BP responses than controls (difference, 4.1 mm Hg); there was no difference in other cardiosympathetic parameters. Cortisol responses were similar in all three groups., Conclusions: Maternal diabetes during pregnancy is associated with higher cardiosympathetic stress responses in the offspring, which may contribute to their higher cardiovascular disease risk. Further research may confirm stress-response programming as a predictor of cardiovascular risk in OGDM.

Objective: There is evidence that subclinical vitamin B12 (B12) deficiency is common in India. Vegetarianism is prevalent and therefore meat consumption is low. Our objective was to explore the contribution of B12-source foods and maternal B12 status during pregnancy to plasma B12 concentrations., Design: Maternal plasma B12 concentrations were measured during pregnancy. Children's dietary intakes and plasma B12 concentrations were measured at age 9.5 years; B12 and total energy intakes were calculated using food composition databases. We used linear regression to examine associations between maternal B12 status and children's intakes of B12 and B12-source foods, and children's plasma B12 concentrations., Setting: South Indian city of Mysore and surrounding rural areas., Subjects: Children from the Mysore Parthenon Birth Cohort (n 512, 47.1 % male)., Results: Three per cent of children were B12 deficient (<150 pmol/l). A further 14 % had 'marginal' B12 concentrations (150-221 pmol/l). Children's total daily B12 intake and consumption frequencies of meat and fish, and micronutrient-enriched beverages were positively associated with plasma B12 concentrations (P=0.006, P=0.01 and P=0.04, respectively, adjusted for socio-economic indicators and maternal B12 status). Maternal pregnancy plasma B12 was associated with children's plasma B12 concentrations, independent of current B12 intakes (P<0.001). Milk and curd (yoghurt) intakes were unrelated to B12 status., Conclusions: Meat and fish are important B12 sources in this population. Micronutrient-enriched beverages appear to be important sources in our cohort, but their high sugar content necessitates care in their recommendation. Improving maternal B12 status in pregnancy may improve Indian children's status.

The Mysore Parthenon Birth Cohort was established to examine the long-term effects of maternal glucose tolerance and nutritional status on cardiovascular disease risk factors in the offspring. During 1997-98, 830 of 1233 women recruited from the antenatal clinics of the Holdsworth Memorial Hospital (HMH), Mysore, India, underwent an oral glucose tolerance test. Of these, 667 women delivered live babies at HMH. Four babies with major congenital anomalies were excluded, and the remaining 663 were included for further follow-up. The babies had detailed anthropometry at birth and at 6-12-monthly intervals subsequently. Detailed cardiovascular investigations were done at ages 5, 9.5 and 13.5 years in the children, and in the parents at the 5-year and 9.5-year follow-ups. This ongoing study provides extensive data on serial anthropometry and body composition, physiological and biochemical measures, dietary intake, nutritional status, physical activity measures, stress reactivity measures and cognitive function, and socio-demographic parameters for the offspring. Data on anthropometry, cardiovascular risk factors and nutritional status are available for mothers during pregnancy. Anthropometry and risk factor measures are available for both parents at follow-up., (© The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objective: To test the Trier Social Stress Test for children (TSST-C) in a cohort of Indian adolescents., Design: Cohort study., Setting: Holdsworth Memorial Hospital, Mysore, India., Participants: Adolescent children (N=273, 134 males; mean age 13.6 yrs) selected from an ongoing birth cohort; 269 completed the test., Intervention: Performance of 5-minutes each of public- speaking and mental arithmetic tasks in front of two unfamiliar 'evaluators'., Outcome Measures: Salivary cortisol concentrations were measured at baseline and at regular intervals after the TSST-C. Continuous measurements of heart rate, finger blood pressure, stroke volume, cardiac output and systemic vascular resistance were carried out before, during and for 10 minutes after the TSST-C using a finger cuff., Results: Cortisol concentrations [mean increment (SD): 6.1 (6.9) ng/mL], heart rate [4.6 (10.1) bpm], systolic [24.2 (11.6) mmHg] and diastolic blood pressure [16.5 (7.3) mmHg], cardiac output [0.6 (0.7) L/min], stroke volume [4.0 (5.6) mL] and systemic vascular resistance [225 (282) dyn.s/cm5] increased significantly (P<0.001) from baseline after inducing stress., Conclusions: The TSST-C produces stress responses in Indian adolescents of a sufficient magnitude to be a useful tool for examining stress physiology and its relationships to disease outcomes in this population.

Background: Studies in high-income countries have shown inverse associations between adiposity and cognitive performance in children. We aimed to examine the relationship between adiposity and cognitive function in Indian children., Methods: At a mean age of 9.7 years, height, weight, triceps and subscapular skinfold thicknesses and waist circumference were recorded for 540 children born in Mysore, India. Body fat percentage was estimated using bioimpedance. Cognitive function was assessed using three core tests from the Kaufman Assessment Battery for children-II edition and additional tests measuring learning, short-term memory, reasoning, verbal and visuo-spatial abilities, attention and concentration. Data on the parents' socioeconomic status, education, occupation and income were collected., Results: According to WHO definitions, 3.5% of the children were overweight/obese (Body Mass Index (BMI)>+1SD) and 27% underweight (BMI<-2SD). Compared to normal children, overweight/obese children scored higher in tests of learning/long-term retrieval, reasoning and verbal ability (unadjusted p<0.05 for all). All the Cognitive Test scores increased with increase in BMI and skinfold thickness, (unadjusted β=0.10-0.20 SD; p<0.05 for all). The effects, though attenuated, remained mainly significant after adjustment for age, sex and socioeconomic factors. Similar associations were found for waist circumference and percentage body fat., Conclusions: In this Indian population, in which obesity was uncommon, greater adiposity predicted higher cognitive ability. These associations were only partly explained by socioeconomic factors. Our findings suggest that better nutrition is associated with better cognitive function, and that inverse associations between adiposity and cognitive function in high-income countries reflect confounding by socioeconomic factors.

Objective: Prenatal programming of the hypothalamic-pituitary-adrenal (HPA) axis may link reduced foetal growth with higher adult chronic disease risk. South Asians have a high prevalence of low birth weight and a thin-fat phenotype, which is associated with subsequent type 2 diabetes and the metabolic syndrome. Altered HPA activity could be one of the pathological processes underlying this link., Methods: Plasma morning cortisol and corticosteroid-binding globulin (CBG) concentrations were determined in 528 children aged 9·5 years from a prospective birth cohort in India. They had detailed anthropometry at birth, and current measurements of anthropometry, plasma glucose, insulin and lipid concentrations and blood pressure. Insulin resistance (Homeostasis Model Assessment) and insulin secretion (the 30-min insulin increment) were also assessed., Results: None of the birth measurements were associated with cortisol concentrations, but both birth weight (P = 0·03) and length (P = 0·004) were inversely associated with CBG concentrations. Cortisol concentrations were inversely associated with current body mass index (P = 0·02), and positively associated with glucose (fasting: P < 0·001; 30-min: P = 0·002) concentrations, and systolic blood pressure (P = 0·005), but not insulin resistance or the insulin increment., Conclusion: Higher morning cortisol is associated with higher cardiometabolic risk markers in Indian children. Although cortisol concentrations did not appear to be related to birth size, small size at birth was associated with higher CBG levels, and may be one of the processes by which foetal undernutrition affects adult health. The findings suggest a need for dynamic testing of HPA axis activity (such as measuring stress responses)., (© 2013 John Wiley & Sons Ltd.)

The burden of non-communicable chronic disease (NCD) in India is increasing. Diet and body composition 'track' from childhood into adult life and contribute to the development of risk factors for NCD. Little is known about the diet patterns of Indian children. We aimed to identify diet patterns and study associations with body composition and socio-demographic factors in the Mysore Parthenon Study cohort. We collected anthropometric and demographic data from children aged 9.5 years (n = 538). We also administered a food frequency questionnaire and measured fasting blood concentrations of folate and vitamin B12. Using principal component analysis, we identified two diet patterns. The 'snack and fruit' pattern was characterised by frequent intakes of snacks, fruit, sweetened drinks, rice and meat dishes and leavened breads. The 'lacto-vegetarian' pattern was characterised by frequent intakes of finger millet, vegetarian rice dishes, yoghurt, vegetable dishes and infrequent meat consumption. Adherence to the 'snack and fruit' pattern was associated with season, being Muslim and urban dwelling. Adherence to the lacto-vegetarian pattern was associated with being Hindu, rural dwelling and a lower maternal body mass index. The 'snack and fruit' pattern was negatively associated with the child's adiposity. The lacto-vegetarian pattern was positively associated with blood folate concentration and negatively with vitamin B12 concentration. This study provides new information on correlates of diet patterns in Indian children and how diet relates to nutritional status. Follow-up of these children will be important to determine the role of these differences in diet in the development of risk factors for NCD including body composition., (© 2013 The Authors. Maternal and Child Nutrition published by John Wiley & Sons Ltd.)

Aims/hypothesis: In an Indian birth cohort, higher maternal homocysteine concentration in pregnancy was associated with lower birthweight of the offspring. Lower maternal vitamin B12 and higher folate concentrations were associated with higher offspring insulin resistance. Disordered one-carbon metabolism during early development may increase later metabolic risk. We explored these associations in another birth cohort in India at three age points., Methods: We measured plasma vitamin B12, folate and homocysteine concentrations at 30 ± 2 weeks' gestation in 654 women who delivered at one hospital. Neonatal anthropometry was recorded, and the children's glucose and insulin concentrations were measured at 5, 9.5 and 13.5 years of age. Insulin resistance was estimated using HOMA of insulin resistance (HOMA-IR)., Results: Maternal homocysteine concentrations were inversely associated with all neonatal anthropometric measurements (p < 0.05), and positively associated with glucose concentrations in the children at 5 (30 min; p = 0.007) and 9.5 years of age (120 min; p = 0.02). Higher maternal folate concentrations were associated with higher HOMA-IR in the children at 9.5 (p = 0.03) and 13.5 years of age (p = 0.03). Maternal vitamin B12 concentrations were unrelated to offspring outcomes., Conclusions/interpretation: Maternal vitamin B12 status did not predict insulin resistance in our cohort. However, associations of maternal homocysteine and folate concentrations with birth size, and with childhood insulin resistance and glycaemia in the offspring, suggest a role for nutritionally driven disturbances in one-carbon metabolism in fetal programming of diabetes.

Background: Low- and middle-income countries continue to experience a large burden of stunting; 148 million children were estimated to be stunted, around 30-40% of all children in 2011. In many of these countries, foetal growth restriction (FGR) is common, as is subsequent growth faltering in the first 2 years. Although there is agreement that stunting involves both prenatal and postnatal growth failure, the extent to which FGR contributes to stunting and other indicators of nutritional status is uncertain., Methods: Using extant longitudinal birth cohorts (n=19) with data on birthweight, gestational age and child anthropometry (12-60 months), we estimated study-specific and pooled risk estimates of stunting, wasting and underweight by small-for-gestational age (SGA) and preterm birth., Results: We grouped children according to four combinations of SGA and gestational age: adequate size-for-gestational age (AGA) and preterm; SGA and term; SGA and preterm; and AGA and term (the reference group). Relative to AGA and term, the OR (95% confidence interval) for stunting associated with AGA and preterm, SGA and term, and SGA and preterm was 1.93 (1.71, 2.18), 2.43 (2.22, 2.66) and 4.51 (3.42, 5.93), respectively. A similar magnitude of risk was also observed for wasting and underweight. Low birthweight was associated with 2.5-3.5-fold higher odds of wasting, stunting and underweight. The population attributable risk for overall SGA for outcomes of childhood stunting and wasting was 20% and 30%, respectively., Conclusions: This analysis estimates that childhood undernutrition may have its origins in the foetal period, suggesting a need to intervene early, ideally during pregnancy, with interventions known to reduce FGR and preterm birth.

Objective: We aimed to test the fetal overnutrition hypothesis by comparing the associations of maternal and paternal adiposity (sum of skinfolds) with adiposity and cardiovascular risk factors in children., Design: Children from a prospective birth cohort had anthropometry, fat percentage (bio-impedance), plasma glucose, insulin and lipid concentrations and blood pressure measured at 9.5 years of age. Detailed anthropometric measurements were recorded for mothers (at 3±2 weeks’ gestation) and fathers (5 years following the index pregnancy)., Setting: Holdsworth Memorial Hospital, Mysore, India., Subjects: Children (n 504), born to mothers with normal glucose tolerance during pregnancy., Results: Twenty-eight per cent of mothers and 38% of fathers were overweight/ obese (BMI≥25.0 kg/m²), but only 4% of the children were overweight/obese (WHO age- and sex-specific BMI≥18.2 kg/m²). The children’s adiposity (BMI, sum of skinfolds, fat percentage and waist circumference), fasting insulin concentration and insulin resistance increased with increasing maternal and paternal sum of skinfolds adjusted for the child’s sex, age and socio-economic status. Maternal and paternal effects were similar. The associations with fasting insulin and insulin resistance were attenuated after adjusting for the child’s current adiposity., Conclusions: In this population, both maternal and paternal adiposity equally predict adiposity and insulin resistance in the children. This suggests that shared family environment and lifestyle, or genetic/epigenetic factors, influence child adiposity. Our findings do not support the hypothesis that there is an intrauterine overnutrition effect of maternal adiposity in non-diabetic pregnancies, although we cannot rule out such an effect in cases of extreme maternal obesity, which is rare in our population.

This study utilized data from a prospective birth cohort study on 568 Indian children, to determine whether a longer duration of breastfeeding and later introduction of solid feeding were associated with a reduced higher body mass index (BMI) and less adiposity. Main outcomes were high BMI (>90th within-cohort sex-specific BMI percentile) and sum of skinfold thickness (triceps and subscapular) at age 5. Main exposures were breastfeeding (six categories from 1-4 to ≥21 months) and age of starting regular solid feeding (four categories from ≤3 to ≥6 months). Data on infant-feeding practices, socio-economic and maternal factors were collected by questionnaire. Birthweight, maternal and child anthropometry were measured. Multiple regression analysis that accounted for potential confounders demonstrated a small magnitude of effect for breastfeeding duration or introduction of solid feeds on the risk of high BMI but not for lower skinfold thickness. Breastfeeding duration was strongly negatively associated with weight gain (0-2 years) [adjusted β = -0.12 standard deviation, 95% confidence interval (CI): -0.19 to -0.05 per category change in breastfeeding duration, P = 0.001], and weight gain (0-2 years) was strongly associated with high BMI at 5 years (adjusted odds ratio = 3.8, 95% CI: 2.53-5.56, P < 0.001). In our sample, findings suggest that longer breastfeeding duration and later introduction of solids has a small reduction on later high BMI risk and a negligible effect on skinfold thickness. However, accounting for sampling variability, these findings cannot exclude the possibility of no effect at the population level., (© 2011 Blackwell Publishing Ltd.)

Objective: We aimed to examine detailed neonatal measurements as predictors of later diabetes in both parents., Research Design and Methods: Babies (n = 617) born to nondiabetic parents in Holdsworth Memorial Hospital, Mysore, India, were measured at birth for weight; crown-to-heel length (CHL), crown-to-rump length (CRL), and leg length; skinfolds (triceps and subscapular); and circumferences (head, abdomen, and mid-upper-arm circumference [MUAC]). Nine and a half years later, glucose tolerance and fasting insulin were measured in their parents (469 mothers and 398 fathers)., Results: Sixty-two (15.6%) fathers and 22 (4.7%) mothers had developed diabetes. There were linear inverse associations of the children's birth weight, CHL, CRL, MUAC, and skinfolds with paternal diabetes and insulin resistance (P < 0.05 for all). Offspring birth weight and adiposity (MUAC, abdominal circumference, and skinfolds) showed U-shaped associations with maternal diabetes (P for quadratic association <0.05 for all). These associations persisted after adjusting for the parents' current adiposity and maternal glucose concentrations and adiposity during pregnancy. Newborn adiposity was positively related to maternal insulin resistance; this association was nonsignificant after adjusting for maternal current adiposity., Conclusions: Newborn size is a window into the future health of the parents. Small newborn size (especially soft-tissue body components) predicts an increased risk of later diabetes in both parents, suggesting a genetic or epigenetic link between parents' diabetes risk and reduced fetal growth in their children. The association of higher birth weight and newborn adiposity with later maternal diabetes suggests effects on fetal adiposity of the intrauterine environment in prediabetic mothers.

There is evidence of a reduction in children's physical activity in India in the last decade. Our objective was to assess whether size and body composition at birth are associated with physical activity in school-aged children. Children from a prospective observational cohort study born in Mysore, South India between 1997 and 1998 (n = 663) had neonatal anthropometric measurements made within 72 h of delivery [weight, mid-upper arm circumference (MUAC), chest, abdomen and head circumference, crown-heel, crown-buttock and leg length, triceps and subscapular skinfolds]. At 6-10 years, children (n = 449) were asked to wear AM7164 or GT1M Actigraph accelerometers for 7 days. Body composition was measured within 6 months of activity monitoring. Arm muscle area at birth and time of activity monitoring was calculated from MUAC and skinfold measurements. Activity outcome measures were: mean accelerometer counts per minute (cpm); counts per day and proportion of time spent in moderate and vigorous activity. The mean (S.D.) number of days with ≥500 min of recorded accelerometer data was 7.0 (1.1). Linear regression models showed no significant associations between any of the neonatal anthropometric measures and the activity variables. Body fat percentage at 7.5 years was negatively associated with all activity variables (B = -4.69, CI: -7.31, -2.07 for mean cpm). In conclusion, this study showed no associations between body size and skinfold thickness at birth and objectively measured physical activity in childhood.

Aims/hypothesis: FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians., Methods: All studies published on the association between FTO-rs9939609 (or proxy [r (2) > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes., Results: The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10(-19)), overweight by 1.13-fold/allele (p = 1.0 × 10(-11)) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10(-8)). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10(-5)). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m(2) per allele (p = 2.8 × 10(-17)), WHR by 0.003/allele (p = 1.2 × 10(-6)), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12-20%) than South Asians (30-33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations., Conclusions/interpretation: FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.

Objective: UK Indian adults have higher risks of coronary heart disease and type 2 diabetes than Indian and UK European adults. With growing evidence that these diseases originate in early life, we compared cardiometabolic risk markers in Indian, UK Indian and white European children., Methods: Comparisons were based on the Mysore Parthenon Birth Cohort Study (MPBCS), India and the Child Heart Health Study in England (CHASE), which studied 9-10 year-old children (538 Indian, 483 UK Indian, 1375 white European) using similar methods. Analyses adjusted for study differences in age and sex., Results: Compared with Mysore Indians, UK Indians had markedly higher BMI (% difference 21%, 95%CI 18 to 24%), skinfold thickness (% difference 34%, 95%CI 26 to 42%), LDL-cholesterol (mean difference 0.48, 95%CI 0.38 to 0.57 mmol/L), systolic BP (mean difference 10.3, 95% CI 8.9 to 11.8 mmHg) and fasting insulin (% difference 145%, 95%CI 124 to 168%). These differences (similar in both sexes and little affected by adiposity adjustment) were larger than those between UK Indians and white Europeans. Compared with white Europeans, UK Indians had higher skinfold thickness (% difference 6.0%, 95%CI 1.5 to 10.7%), fasting insulin (% difference 31%, 95%CI 22 to 40%), triglyceride (% difference 13%, 95%CI 8 to 18%) and LDL-cholesterol (mean difference 0.12 mmol/L, 95%CI 0.04 to 0.19 mmol/L)., Conclusions: UK Indian children have an adverse cardiometabolic risk profile, especially compared to Indian children. These differences, not simply reflecting greater adiposity, emphasize the need for prevention strategies starting in childhood or earlier.

Background/objectives: Few equations for calculating body-fat percentage (BF%) from field methods have been developed in South-Asian children. The objective of this study was to assess agreement between BF% derived from primary reference methods and that from skinfold equations and bio-impedance analysis (BIA) in Indian children., Subjects/methods: We measured BF% in two groups of Indian children. In Pune, 570 rural children aged 6-8 years underwent dual-energy X-ray absorptiometry (DXA) scans. In Mysore (18)O in doubly labeled water was administered to 59 urban children aged 7-9 years. We conducted BIA at 50 kHz and anthropometry, including sub-scapular and triceps skinfold thicknesses. We used the published equations of Wickramasinghe, Shaikh, Slaughter and Dezenburg to calculate BF% from anthropometric data and the manufacturer's equation for BIA measurements. We assessed agreement with values derived from DXA and doubly labeled water using Bland-Altman analysis., Results: Children were light and thin on average compared with international standards. There was poor agreement between the reference BF% values and those from all equations. Assumptions for Bland-Altman analysis were not met for Wickramasinghe, Shaikh and Slaughter equations. The Dezenberg equations under-predicted BF% for most children (mean difference in Pune -13.4, LOA -22.7, -4.0 and in Mysore -7.9, LOA (-13.7 and -2.2). The mean bias for the BIA equation in Pune was +5.0% and in Mysore +1.95%, and the limits of agreement were wide; -5.0, 15.0 and -7.8, 11.7 respectively., Conclusions: Currently available skinfold equations do not accurately predict BF% in Indian children. We recommend development of BIA equations in this population using a four-compartment model.

Background: Studies have shown that the shape and size of the placenta at birth predict blood pressure in later life. The influences that determine placental morphology are largely unknown. We have examined the role of mother's body size., Methods: We studied 522 neonates who were born in a maternity hospital in Mysore, South India. The weight of the placenta and the length and breadth of its surface, were measured after delivery., Results: Higher maternal fat mass predicted a larger placental surface (p = 0.02), while larger maternal head circumference predicted a more oval placental surface (p = 0.03). Higher maternal fat mass and larger maternal head circumference were associated with greater placental efficiency, indicated by lower ratios of the length (p = 0.0003 and p = 0.0001 respectively) and breadth (p = 0.0002 and p < 0.0001) of the surface to birthweight. In a sub-sample of 51 mothers whose own birthweight was available, higher maternal birthweight was related to lower ratios of the length and breadth of the surface to birthweight (p = 0.01 and 0.002). Maternal height was unrelated to placental size or shape., Conclusions: Higher maternal fat mass, reflecting the mother's current nutritional state, and larger maternal head circumference, reflecting the mother's fetal/infant growth, are associated with changes in the shape and size of the placental surface and greater placental efficiency. We suggest that these associations reflect effects of the mother's nutrition at different stages of her lifecourse on the development of the placenta and on materno-placento-fetal transfer of nutrients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Aims/hypothesis: Our objective was to examine whether longer duration of breast-feeding and later introduction of complementary foods are associated with lower glucose concentrations and insulin resistance (IR-HOMA) in Indian children., Methods: Breast-feeding duration (six categories from <3 to ≥18 months) and age at introduction of complementary foods (four categories from <4 to ≥6 months) were recorded at 1, 2 and 3 year follow-up of 568 children from a birth cohort in Mysore, India. At 5 and 9.5 years of age, 518 children were assessed for glucose tolerance and IR-HOMA., Results: All the children were initially breast-fed; 90% were breast-fed for ≥6 months and 56.7% started complementary foods at or before the age of 4 months. Each category increase in breast-feeding duration was associated with lower fasting insulin concentration (β = -0.05 pmol/l [95% CI -0.10, -0.004]; p = 0.03) and IR-HOMA (β = -0.05 [95% CI -0.10, -0.001]; p = 0.046) at 5 years, adjusted for the child's sex, age, current BMI, socioeconomic status, parent's education, rural/urban residence, birthweight and maternal gestational diabetes status. Longer duration of breastfeeding was associated with higher 120-min glucose concentration at 5 years (β = 0.08 mmol/l [95% CI 0.001, 0.15; p = 0.03]) but lower 120-min glucose concentration at 9.5 years (β = -0.09 [95% CI -0.16, -0.03]; p = 0.006). Age at starting complementary foods was unrelated to the children's glucose tolerance and IR-HOMA., Conclusions/interpretation: Within this cohort, in which prolonged breast-feeding was the norm, there was evidence of a protective effect of longer duration of breast-feeding against glucose intolerance at 9.5 years. At 5 years longer duration of breast-feeding was associated with lower IR-HOMA.

Aim: To determine whether the size and shape of the placental surface predict blood pressure in childhood., Methods: We studied blood pressure in 471 nine-year-old Indian children whose placental length, breadth and weight were measured in a prospective birth cohort study., Results: In the daughters of short mothers (

Background: Metabolic consequences of vitamin D deficiency have become a recent research focus. Maternal vitamin D status is thought to influence musculoskeletal health in children, but its relation with offspring metabolic risk is not known., Objective: We aimed to examine the association between maternal vitamin D status and anthropometric variables, body composition, and cardiovascular risk markers in Indian children., Design: Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured at 28-32 wk gestation in 568 women who delivered at Holdsworth Memorial Hospital, Mysore, India. Anthropometric variables, glucose and insulin concentrations, blood pressure, and fasting lipid concentrations were measured in the offspring at 5 and 9.5 y of age. Muscle-grip strength was measured by using a hand-held dynamometer at age 9.5 y. Arm-muscle area was calculated as a measure of muscle mass. Fasting insulin resistance was calculated by using the homeostasis model assessment equation., Results: Sixty-seven percent of women had vitamin D deficiency [serum 25(OH)D concentration <50 nmol/L]. At ages 5 and 9.5 y, children born to vitamin D-deficient mothers had smaller arm-muscle area in comparison with children born to mothers without deficiency (P < 0.05). There was no difference in grip strength between offspring of women with and without vitamin D deficiency. At 9.5 y, children of vitamin D-deficient mothers had higher fasting insulin resistance than did children of nondeficient women (P = 0.04). There were no associations between maternal vitamin D status and other offspring risk factors at either age., Conclusion: Intrauterine exposure to low 25(OH)D concentrations is associated with less muscle mass and higher insulin resistance in children.

Lower birthweight, and rapid childhood weight gain predict elevated cardiovascular risk factors in children. We examined associations between serial, detailed, anthropometric measurements from birth to 9.5 years of age and cardiovascular risk markers in Indian children. Children (n = 663) born at the Holdsworth Memorial Hospital, Mysore, India were measured at birth and 6-12 monthly thereafter. At 9.5 years, 539 (255 boys) underwent a 2-h oral glucose tolerance test, and blood pressure (BP) and fasting lipid concentrations were measured. Insulin resistance was calculated using the HOMA equation. These outcomes were examined in relation to birth measurements and changes in measurements (growth) during infancy (0-2 years), 2-5 years and 5-9.5 years using conditional s.d. scores. Larger current weight, height and skinfold thickness were associated with higher risk markers at 9.5 years (P < 0.05). Lower weight, smaller length and mid-arm circumference at birth were associated with higher fasting glucose concentrations at 9.5 years (P ⩽ 0.01). After adjusting for current weight/height, there were inverse associations between birthweight and/or length and insulin concentrations, HOMA, systolic and diastolic BP and plasma triglycerides (P < 0.05). Increases in conditional weight and height between 0-2, 2-5 and 5-9.5 years were associated with higher insulin concentrations, HOMA and systolic BP. In conclusion, in 9-10-year-old Indian children, as in other studies, cardiovascular risk factors were highest in children who were light or short at birth but heavy or tall at 9 years. Greater infant and childhood weight and height gain were associated with higher risk markers.

Foetal development may permanently affect muscle function. Indian newborns have a low mean birthweight, predominantly due to low lean tissue and muscle mass. We aimed to examine the relationship of birthweight, and arm muscle area (AMA) at birth and post-natal growth to handgrip strength in Indian children. Grip strength was measured in 574 children aged 9 years, who had detailed anthropometry at birth and every 6-12 months post-natally. Mean (standard deviation (s.d.)) birthweight was 2863 (446) g. At 9 years, the children were short (mean height s.d. -0.6) and light (mean weight s.d. -1.1) compared with the World Health Organization growth reference. Mean (s.d.) grip strength was 12.7 (2.2) kg (boys) and 11.0 (2.0) kg (girls). Weight, length and AMA at birth, but not skinfold measurements at birth, were positively related to 9-year grip strength (β = 0.40 kg/s.d. increase in birthweight, P < 0.001; and β = 0.41 kg/s.d. increase in AMA, P < 0.001). Grip strength was positively related to 9-year height, body mass index and AMA and to gains in these measurements from birth to 2 years, 2-5 years and 5-9 years (P < 0.001 for all). The associations between birth size and grip strength were attenuated but remained statistically significant for AMA after adjusting for 9-year size. We conclude that larger overall size and muscle mass at birth are associated with greater muscle strength in childhood, and that this is mediated mainly through greater post-natal size. Poorer muscle development in utero is associated with reduced childhood muscle strength.

Aims/hypothesis: Our aim was to test the hypothesis that gestational diabetes mellitus (GDM) in mothers is associated with poorer cognitive ability in their offspring in India., Methods: During 1997 to 1998 maternal GDM status was assessed by OGTT at 30 +/- 2 weeks of gestation. Between 2007 and 2008, at a mean age of 9.7 years, 515 children (32 offspring of GDM mothers [ODM]; 483 offspring of non-GDM mothers [controls]) from the Mysore Parthenon birth cohort underwent cognitive function assessment using tests from the Kaufman Assessment Battery for Children--Second Edition and additional tests measuring learning, long-term storage/retrieval, short-term memory, reasoning, attention and concentration, and visuo-spatial and verbal abilities., Results: Compared with controls, ODM scored higher in tests for learning, long-term retrieval/storage (p = 0.008), reasoning (p = 0.02), verbal ability (p = 0.01), and attention and concentration (p = 0.003). In multiple regression, adjusted for the child's age, sex, gestation, neonatal weight and head circumference, maternal age, parity and BMI, and the parent's socioeconomic status, education and rural/urban residence, this difference remained significant only for learning, long-term retrieval/storage (beta = 0.4 SD (95% CI 0.01-0.75); p = 0.04) and verbal ability (beta = 0.5 SD (95% CI 0.09-0.83); p = 0.02), and not with other test scores., Conclusions/interpretation: In this population of healthy Indian children, there was no evidence of lower cognitive ability in ODM. In fact some cognitive scores were higher in ODM.