King Edward Memorial Hospital and Research Center

Pune, India

King Edward Memorial Hospital and Research Center

Pune, India
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Yajnik C.S.,King Edward Memorial Hospital and Research Center | Chandak G.R.,CSIR - Central Electrochemical Research Institute | Chandak G.R.,Genome Institute of Singapore | Joglekar C.,King Edward Memorial Hospital and Research Center | And 10 more authors.
International Journal of Epidemiology | Year: 2014

Background: Disturbed one-carbon (1-C) metabolism in the mother is associated with poor fetal growth but causality of this relationship has not been established. Methods: We studied the association between maternal total homocysteine and offspring birthweight in the Pune Maternal Nutrition Study (PMNS, Pune, India) and Parthenon Cohort Study (Mysore, India). We tested for evidence of causality within a Mendelian randomization framework, using a methylenetetrahydrofolatereductase (MTHFR) gene variant rs1801133 (earlier known as 677C→T) by instrumental variable and triangulation analysis, separately and using meta-analysis. Results: Median (IQR) homocysteine concentration and mean (SD) birthweight were 8.6 μmol/l (6.7,10.8) and 2642 g (379) in the PMNS and 6.0 mmol/l (5.1,7.1) and 2871 g (443) in the Parthenon study. Offspring birthweight was inversely related to maternal homocysteine concentration-PMNS: -22 g/SD [95% confidence interval (CI): (-50, 5), adjusted for gestational age and offspring gender]; Parthenon: -57 g (-92, -21); meta-analysis: -40 g (-62, -17)]. Maternal risk genotype at rs1801133 predicted higher homocysteine concentration [PMNS: 0.30 SD/allele (0.14, 0.46); Parthenon: 0.21 SD (0.02, 0.40); meta-analysis: 0.26 SD (0.14, 0.39)]; and lower birthweight [PMNS: -46 g (-102, 11, adjusted for gestational age, offspring gender and rs1801133 genotype); Parthenon: -78 g (-170, 15); meta-analysis: -61 g (-111, -10)]. Instrumental variable and triangulation analysis supported a causal association between maternal homocysteine concentration and offspring birthweight. Conclusions: Our findings suggest a causal role for maternal homocysteine (1-C metabolism) in fetal growth. Reducing maternal homocysteine concentrations may improve fetal growth. © The Author 2014; all rights reserved.


Christian P.,Johns Hopkins University | Lee S.E.,Johns Hopkins University | Angel M.D.,Johns Hopkins University | Adair L.S.,University of North Carolina at Chapel Hill | And 32 more authors.
International Journal of Epidemiology | Year: 2013

Background Low- a nd middle-income countriescontinue 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. © The Author 2013; all rights reserved.


Krishnaveni G.V.,CSI Holdsworth Memorial Hospital | Yajnik C.S.,King Edward Memorial Hospital and Research Center
European Journal of Clinical Nutrition | Year: 2017

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. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.


Sukumar N.,University of Warwick | Rafnsson S.B.,University College London | Rafnsson S.B.,University of Edinburgh | Kandala N.-B.,Northumbria University | And 5 more authors.
American Journal of Clinical Nutrition | Year: 2016

Background: Vitamin B-12 and folate are micronutrients essential for normal embryogenesis. Vitamin B-12 insufficiency in pregnancy is high in certain parts of the world, such as India, and although this has been linked to low birth weight (LBW) in these populations, the relation between Vitamin B-12 and birth weight (BW) elsewhere is unknown. Objectives: We performed a systematic review to assess 1) the worldwide prevalence of Vitamin B-12 insufficiency in pregnancy and 2) its association with BW. Design: A search of 5 electronic databases was performed to identify eligible articles. Random-effects meta-analysis was conducted according to geographic regions and pregnancy trimesters for the prevalence subreview and by categorical measures of BW. Results: A total of 57 and 23 articles were included for the prevalence and BW subreviews, respectively. The pooled estimates of Vitamin B-12 insufficiency were 21%, 19%, and 29% in the first, second, and third trimesters, respectively, with high rates for the Indian subcontinent and the Eastern Mediterranean. The large heterogeneity between studies was partially addressed by creating a standardized score for each study (mean Vitamin B-12 insufficiency O cutoff value), which internally corrected for geographic region, trimester, and assay type. Twelve of the 13 longitudinal studies included showed a decrease in mean or median Vitamin B-12 across trimesters. Pooled analysis showed nonsignificantly lower maternal Vitamin B-12 concentrations in LBW than in normal-BW infants and higher odds of LBW with lower Vitamin B-12 values (adjusted OR: 1.70; 95% CI: 1.16, 2.50), but studies from India largely contributed to the latter. Conclusions: Our review indicates that Vitamin B-12 insufficiency during pregnancy is common even in nonvegetarian populations and that concentrations of Vitamin B-12 decrease from the first to the third trimester. There is no consistent association between Vitamin B-12 insufficiency and LBW. However, given the long-term risks of LBW, this observation warrants further cohort studies and randomized controlled trials.


PubMed | King Edward Memorial Hospital and Research Center, University of Edinburgh, University College London, University of Warwick and Northumbria University
Type: Journal Article | Journal: The American journal of clinical nutrition | Year: 2016

Vitamin B-12 and folate are micronutrients essential for normal embryogenesis. Vitamin B-12 insufficiency in pregnancy is high in certain parts of the world, such as India, and although this has been linked to low birth weight (LBW) in these populations, the relation between vitamin B-12 and birth weight (BW) elsewhere is unknown.We performed a systematic review to assess 1) the worldwide prevalence of vitamin B-12 insufficiency in pregnancy and 2) its association with BW.A search of 5 electronic databases was performed to identify eligible articles. Random-effects meta-analysis was conducted according to geographic regions and pregnancy trimesters for the prevalence subreview and by categorical measures of BW.A total of 57 and 23 articles were included for the prevalence and BW subreviews, respectively. The pooled estimates of vitamin B-12 insufficiency were 21%, 19%, and 29% in the first, second, and third trimesters, respectively, with high rates for the Indian subcontinent and the Eastern Mediterranean. The large heterogeneity between studies was partially addressed by creating a standardized score for each study (mean vitamin B-12 insufficiency cutoff value), which internally corrected for geographic region, trimester, and assay type. Twelve of the 13 longitudinal studies included showed a decrease in mean or median vitamin B-12 across trimesters. Pooled analysis showed nonsignificantly lower maternal vitamin B-12 concentrations in LBW than in normal-BW infants and higher odds of LBW with lower vitamin B-12 values (adjusted OR: 1.70; 95% CI: 1.16, 2.50), but studies from India largely contributed to the latter.Our review indicates that vitamin B-12 insufficiency during pregnancy is common even in nonvegetarian populations and that concentrations of vitamin B-12 decrease from the first to the third trimester. There is no consistent association between vitamin B-12 insufficiency and LBW. However, given the long-term risks of LBW, this observation warrants further cohort studies and randomized controlled trials.


Chauhan G.,CSIR - Central Electrochemical Research Institute | Spurgeon C.J.,CSIR - Central Electrochemical Research Institute | Tabassum R.,CSIR - Central Electrochemical Research Institute | Bhaskar S.,CSIR - Central Electrochemical Research Institute | And 11 more authors.
Diabetes | Year: 2010

OBJECTIVE - Common variants in PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 genes have been shown to be associated with type 2 diabetes in European populations by genome-wide association studies. We have studied the association of common variants in these eight genes with type 2 diabetes and related traits in Indians by combining the data from two independent case-control studies. RESEARCH DESIGN AND METHODS - We genotyped eight single nucleotide polymorphisms (PPARG-rs1801282, KCNJ11-rs5219, TCF7L2-rs7903146, SLC30A8-rs13266634, HHEX-rs1111875, CDKN2A-rs10811661, IGF2BP2-rs4402960, and CDKAL1-rs10946398) in 5,164 unrelated Indians of Indo-European ethnicity, including 2,486 type 2 diabetic patients and 2,678 ethnically matched control subjects. RESULTS - We confirmed the association of all eight loci with type 2 diabetes with odds ratio (OR) ranging from 1.18 to 1.89 (P = 1.6 × 10-3 to 4.6 × 10-34). The strongest association with the highest effect size was observed for TCF7L2 (OR 1.89 [95% CI 1.71-2.09], P = 4.6 × 10-34). We also found significant association of PPARG and TCF7L2 with homeostasis model assessment of β-cell function (P = 6.9 × 10-8 and 3 × 10 -4, respectively), which looked consistent with recessive and under-dominant models, respectively. CONCLUSIONS - Our study replicates the association of welle-stablished common variants with type 2 diabetes in Indians and shows larger effect size for most of them than those reported in Europeans. © 2010 by the American Diabetes Association.


Deshmukh U.,Government Medical College and Hospital | Brown N.,Salisbury District Hospital | Yajnik C.,King Edward Memorial Hospital and Research Center
Paediatrics and Child Health (United Kingdom) | Year: 2016

After long periods of vast child health disparities between industrialized countries and Resource-limited Settings (RLS) a wave of research has started to address and reduce the gap. Major global collaborations have been mutually rewarding and have established funding and career structures unthinkable even 25 years ago. Despite this progress, work remains to ensure academic and funding equity and ethical parity. This paper outlines the background to and history of research in RLS, illustrates the current situation and points to potential future developments. © 2015 Elsevier Ltd.


PubMed | King Edward Memorial Hospital and Research Center and CSIR - Central Electrochemical Research Institute
Type: Journal Article | Journal: Current obesity reports | Year: 2015

The prevalence of diabetes and adiposity has increased at an alarming rate and together they contribute to the rise in morbidity and mortality worldwide. Genetic studies till date have succeeded in explaining only a proportion of heritability, while a major component remains unexplained. Early life determinants of future risk of these diseases are likely contributors to the missing heritability and thus have a significant potential in disease prevention. Epidemiological and animal studies show the importance of intrauterine and early postnatal environment in programming of the fetus to adverse metabolic outcomes and support the notion of Developmental Origins of Health and Disease (DOHaD). Emerging evidence highlights the role of epigenetic mechanisms in mediating effects of environmental exposures, which in certain instances may exhibit intergenerational transmission even in the absence of exposure. In this article, we will discuss the complexity of diabetes and increased adiposity and mechanisms of programming of these adverse metabolic conditions.


Yajnik C.S.,King Edward Memorial Hospital and Research Center
Annals of Nutrition and Metabolism | Year: 2014

The conventional aetiological model of obesity and diabetes proposes a genetic predisposition and a precipitation by an unhealthy adult lifestyle. This hypothesis was challenged by David Barker who proposed that the intrauterine environment influences the risk of non-communicable diseases (NCDs). The original idea was based on fetal undernutrition because lower birth weight was associated with a higher risk of diabetes and heart disease. However, soon it was clear that the association was U shaped, and that the increased risk in large babies was driven by maternal obesity and diabetes. A number of human and animal studies have refined our ideas of 'fetal programming', which is now thought to be related to acquired chemical changes in DNA (methylation), histones (acetylation and other) and the role of non-coding miRNAs. Maternal nutritional disturbances are the major programming stimulus, in addition to a deranged metabolism, infections, maternal stress, extreme atmospheric temperature, etc. The first demonstration of a link between fetal 'starvation' and future ill-health was in the Dutch Hunger Winter studies. In the prospective Pune Maternal Nutrition Study, we found that small and thin Indian babies were more adipose compared to larger English babies, and their higher risk of future diabetes was reflected in higher insulin and leptin and lower adiponectin concentrations in the cord blood. This phenotype was partly related to a deranged 1-carbon metabolism due to an imbalance in vitamin B12 (low) and folate (high) nutrition, which was also related to insulin resistance in the offspring. Maternal obesity and diabetes have made an increasing contribution to childhood obesity and diabetes at a young age. This was prominently shown in Pima Indians but is now obvious in all other populations. The best window of opportunity to prevent fetal programming of NCDs is in the periconceptional period. This is the period when gametogenesis, fertilisation, implantation, embryogenesis and placentation occur. Improving the nutrition and the health of young girls could make a substantial contribution to reducing the rapidly rising epidemic of NCDs in the world. This is referred to as 'primordial' prevention. © 2014 S. Karger AG, Basel.


Yajnik C.S.,King Edward Memorial Hospital and Research Center | Deshmukh U.S.,King Edward Memorial Hospital and Research Center
Reviews in Endocrine and Metabolic Disorders | Year: 2012

India is world's capital for low birth weight (LBW), which is ascribed to intrauterine growth restriction (IUGR) rather than prematurity. An average Indian mother is short and thin and gives birth to a light and thin baby. Maternal undernutrition is thought to be a major factor in the aetiology of IUGR, and the undernutrition is usually thought to be a low macronutrient intake. The Pune Maternal Nutrition Study (PMNS) showed that the Indian babies were thin but fat (more adipose) compared to European babies, and that maternal intake of micronutrient-rich foods was a strong determinant of fetal size. Two thirds of the mothers had low vitamin B 12 concentrations, folate deficiency was rare, and high circulating concentrations of homocysteine predicted IUGR. Follow up of these children revealed that higher maternal folate in pregnancy predicted higher adiposity and insulin resistance at 6 years of age. The most insulin resistant children were born to mothers who were vitamin B 12 deficient and had high folate concentrations. Thus, PMNS suggests an important role for maternal onecarbon (1C) metabolism in fetal growth and programming of diabetes risk. This could be due to the role of 1C metabolism in synthesis of nucleic acids, genomic stability and the epigenetic regulation of gene function. In addition, methionine has important role in protein synthesis. These ideas are supported by animal studies. The next logical step in India will be to improve 1C metabolism in adolescents to effect intergenerational prevention of adiposity, diabetes and other related conditions. © Springer Science+Business Media, LLC 2012.

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