Himangi Lubree

Maternal activity in relation to birth size in rural India. The Pune Maternal Nutrition Study.

Objective: To describe the relationship of the mothers physical activity to the birth size of her baby in a rural Indian population.Design: Prospective observational study.Setting: Six villages near Pune, Maharashtra, India.Subjects: A total of 797 women were studied after excluding abortions and termination of pregnancies (112), foetal anomalies (8), multiple pregnancies (3), incomplete pre-pregnancy anthropometry (14) and pregnancies detected later than 21 weeks of gestation (168).Method: An activity questionnaire was developed after focus group discussions and incorporated community-specific activities. It was validated against an observer-maintained diary. Activity scores were derived using published data on energy costs to weight the contributions of various activities. It was then administered to assess physical activity at 18 (±2) and 28 (±2) weeks of gestation.Outcome measures: Birth outcome, maternal weight gain and neonatal anthropometry.Results: The activity questionnaire was used to classify women into light, moderate and heavy activity categories. Maternal activity did not influence the incidence of prematurity or stillbirth, or the duration of gestation. It was inversely related to maternal weight gain up to 28 weeks of gestation (P=0.002). Higher maternal activity in early, as well as mid gestation, was associated with lower mean birth weight (P=0.05 and 0.02, respectively), and smaller neonatal head circumference (P=0.005 and 0.009) and mid-arm circumference (P=0.03 and 0.01) after adjusting for the effect of major confounding factors.Conclusions: The Findings suggest that excessive maternal activity during pregnancy is associated with smaller foetal size in rural India, The approach described for developing an activity questionnaire has potential for adoption in other settings.Sponsorship: Wellcome Trust, London, UK, and the Medical Research Council, UK.

Spuriously High Prevalence of Prediabetes Diagnosed by HbA1c in Young Indians Partly Explained by Hematological Factors and Iron Deficiency Anemia

OBJECTIVE To examine the influence of glycemic and nonglycemic parameters on HbA1c concentrations in young adults, the majority of whom had normal glucose tolerance. RESEARCH DESIGN AND METHODS We compared the diagnosis of normal glucose tolerance, prediabetes, and diabetes between a standard oral glucose tolerance test (OGTT; World Health Organization 2006 criteria) and HbA1c concentrations (American Diabetes Association [ADA] 2009 criteria) in 116 young adults (average age 21.6 years) from the Pune Children’s Study. We also studied the contribution of glycemic and nonglycemic determinants to HbA1c concentrations. RESULTS The OGTT showed that 7.8% of participants were prediabetic and 2.6% were diabetic. By ADA HbA1c criteria, 23.3% were prediabetic and 2.6% were diabetic. The negative predictive value of HbA1c was 93% and the positive predictive value was 20% (only 20% had prediabetes or diabetes according to the OGTT; this figure was 7% in anemic participants). Of participants, 34% were anemic, 37% were iron deficient (ferritin <15 ng/mL), 40% were vitamin B12 deficient (<150 pmol/L), and 22% were folate deficient (<7 nmol/L). On multiple linear regression analysis, HbA1c was predicted by higher 2-h glucose (R2 = 25.6%) and lower hemoglobin (R2 = 7.7%). When hematological parameters were replaced by ferritin, vitamin B12, and folate, HbA1c was predicted by higher glycemia (R2 = 25.6%) and lower ferritin (R2 = 4.3%). CONCLUSIONS The use of HbA1c to diagnose prediabetes and diabetes in iron-deficient populations may lead to a spuriously exaggerated prevalence. Further investigation is required before using HbA1c as a screening tool in nutritionally compromised populations.

Effect of physiological doses of oral vitamin B12 on plasma homocysteine – A randomized, placebo-controlled, double-blind trial in India

Background/Objectives:Vitamin B12 (B12) deficiency is common in Indians and a major contributor to hyperhomocysteinemia, which may influence fetal growth, risk of type II diabetes and cardiovascular disease. The purpose of this paper was to study the effect of physiological doses of B12 and folic acid on plasma total homocysteine (tHcy) concentration.Subjects/Methods:A cluster randomized, placebo-controlled, double-blind, 2 × 3 factorial trial, using the family as the randomization unit. B12 was given as 2 or 10 μg capsules, with or without 200 μg folic acid, forming six groups (B0F0, B2F0, B10F0, B0F200, B2F200 and B10F200). Plasma tHcy concentration was measured before and after 4 and 12 months of supplementation.Results:From 119 families in the Pune Maternal Nutrition Study, 300 individuals were randomized. There was no interaction between B12 and folic acid (P=0.14) in relation to tHcy concentration change and their effects were analyzed separately: B0 vs. B2 vs. B10; and F0 vs. F200. At 12 months, tHcy concentration reduced by a mean 5.9 (95% CI: −7.8, −4.1) μmol/l in B2, and by 7.1 (95% CI: −8.9, −5.4) μmol/l in B10, compared to nonsignificant rise of 1.2 (95% CI: −0.5, 2.9) μmol/l in B0. B2 and B10 did not differ significantly. In F200, tHcy concentration decreased by 4.8 (95% CI: −6.3, −3.3) μmol/l compared to 2.8 (95% CI: −4.3, −1.2) μmol/l in F0.Conclusion:Daily oral supplementation with physiological doses of B12 is an effective community intervention to reduce tHcy. Folic acid (200 μg per day) showed no additional benefit, neither had any unfavorable effects.

Molecular Characterization and Meta-Analysis of Gut Microbial Communities Illustrate Enrichment of Prevotella and Megasphaera in Indian Subjects

The gut microbiome has varied impact on the wellbeing of humans. It is influenced by different factors such as age, dietary habits, socio-economic status, geographic location, and genetic makeup of individuals. For devising microbiome-based therapies, it is crucial to identify population specific features of the gut microbiome. Indian population is one of the most ethnically, culturally, and geographically diverse, but the gut microbiome features remain largely unknown. The present study describes gut microbial communities of healthy Indian subjects and compares it with the microbiota from other populations. Based on large differences in alpha diversity indices, abundance of 11 bacterial phyla and individual specific OTUs, we report inter-individual variations in gut microbial communities of these subjects. While the gut microbiome of Indians is different from that of Americans, it shared high similarity to individuals from the Indian subcontinent i.e., Bangladeshi. Distinctive feature of Indian gut microbiota is the predominance of genus Prevotella and Megasphaera. Further, when compared with other non-human primates, it appears that Indians share more OTUs with omnivorous mammals. Our metagenomic imputation indicates higher potential for glycan biosynthesis and xenobiotic metabolism in these subjects. Our study indicates urgent need of identification of population specific microbiome biomarkers of Indian subpopulations to have more holistic view of the Indian gut microbiome and its health implications.

Iron Fortification of Whole Wheat Flour Reduces Iron Deficiency and Iron Deficiency Anemia and Increases Body Iron Stores in Indian School-Aged Children

Wheat is the primary staple food for nearly one-third of the worlds population. NaFeEDTA is the only iron (Fe) compound suitable for fortifying high extraction flours. We tested the hypothesis that NaFeEDTA-fortified, whole wheat flour reduces Fe deficiency (ID) and improves body Fe stores (BIS) and cognitive performance in Indian children. In a randomized, double-blind, controlled, school feeding trial, 6- to 15-y-old, Fe-depleted children (n = 401) were randomly assigned to either a daily wheat-based lunch meal fortified with 6 mg of Fe as NaFeEDTA or an otherwise identical unfortified control meal. Hemoglobin (Hb) and Fe status were measured at baseline, 3.5 mo, and 7 mo. Cognitive performance was evaluated at baseline and 7 mo in children (n = 170) at one of the study sites. After 7 mo, the prevalence of ID and ID anemia in the treatment group significantly decreased from 62 to 21% and 18 to 9%, respectively. There was a time x treatment interaction for Hb, serum ferritin, transferrin receptor, zinc protoporphyrin, and BIS (all P < 0.0001). Changes in BIS differed between the groups; it increased in the treatment group (0.04 ± 0.04 mmol/kg body weight) and decreased in the control group (-0.02 ± 0.04 mmol/kg body weight) (P < 0.0001). In sensory tests, NaFeEDTA-fortified flour could not be differentiated from unfortified flour. There were no significant differences in cognitive performance tests between the groups. NaFeEDTA-fortified wheat flour markedly improved BIS and reduced ID in Fe-depleted children. It may be recommended for wider use in national school feeding programs.

Prediction of body-fat percentage from skinfold and bio-impedance measurements in Indian school children

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 18O 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 manufacturers 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.

Increases in Plasma Holotranscobalamin Can Be Used to Assess Vitamin B-12 Absorption in Individuals with Low Plasma Vitamin B-12

Low plasma concentrations of vitamin B-12 are common in Indians, possibly due to low dietary intakes of animal-source foods. Whether malabsorption of the vitamin contributes to this has not been investigated. A rise in the plasma holotranscobalamin (holo-TC) concentration after a standard dose of oral vitamin B-12 has been proposed as a measure of gastrointestinal absorption in people with normal plasma vitamin B-12 concentrations. We studied 313 individuals (children and parents, 109 families) in the Pune Maternal Nutrition Study. They received 3 doses of 10 microg (n = 191) or 2 microg (n = 122) of cyanocobalamin at 6-h intervals. A rise in plasma holo-TC of > or =15% and >15 pmol/L above baseline was considered normal vitamin B-12 absorption. The baseline plasma vitamin B-12 concentration was <150 pmol/L in 48% of participants; holo-TC was <35 pmol/L in 98% and total homocysteine was high in 50% of participants (>10 micromol/L in children and >15 micromol/L in adults). In the 10 microg group, the plasma holo-TC concentration increased by 4.8-fold from (mean +/- SD) 9.3 +/- 7.0 pmol/L to 53.8 +/- 25.9 pmol/L and in the 2 microg group by 2.2-fold from 11.1 +/- 8.5 pmol/L to 35.7 +/- 19.3 pmol/L. Only 10% of the participants, mostly fathers, had an increase less than the suggested cut-points. Our results suggest that an increase in plasma holo-TC may be used to assess vitamin B-12 absorption in individuals with low vitamin B-12 status. Because malabsorption is unlikely to be a major reason for the low plasma vitamin B-12 concentrations in this population, increasing dietary vitamin B-12 should improve their status.

Fetal programming of type 2 diabetes : Is sex important?

Hales and Barker (1) caused a paradigm shift in our thinking about diabetes prevention when they demonstrated that low birth weight (due to growth retardation) predicted type 2 diabetes (the “thrifty phenotype” or “fetal origins” hypothesis). On the other hand, larger babies of diabetic mothers are also at higher risk of diabetes, apart from their genetic susceptibility (“fuel mediated teratogenesis”) (2,3). A concept evolved that the intrauterine experiences mold the fetal systems (“programming”) and influence future health (4). If the postnatal experiences are at variance with the intrauterine ones, the programmed fetus is susceptible to disease (5). For example, low birth weight babies who put on excess weight in later life are at a higher risk of type 2 diabetes than those who continue to be low weight (6). In the programming hypothesis, the focus is on the role of intrauterine environment and on gene-environment interaction rather than the differences in gene structure, which are the basis of conventional genetics. Genes are clearly important, and their role in intrauterine development and risk of diabetes was highlighted by Hattersley and Tooke (the “fetal insulin hypothesis”) (7). The most exciting thought in fetal programming is that intrauterine environment may modify gene expression permanently. A heritable change in gene expression without a change in DNA sequence is called “epigenetic” (8), a term first used by Waddington in developmental biology. Epigenetic changes alter gene function and can be silencing …

Vitamin B12 and folate during pregnancy and offspring motor, mental and social development at 2 years of age

Insufficiency of vitamin B12 (B12) and folate during pregnancy can result in low concentrations in the fetus and have adverse effects on brain development. We investigated the relationship between maternal B12 and folate nutrition during pregnancy and offspring motor, mental and social development at two years of age (2 y). Mothers (n = 123) and their offspring (62 girls, 61 boys) from rural and middle-class urban communities in and around Pune city were followed through pregnancy up to 2 y. Maternal B12 and folate concentrations were measured at 28 and 34 weeks of gestation. At 2 y, the Developmental Assessment Scale for Indian Infants was used to determine motor and mental developmental quotients and the Vineland Social Maturity Scale for the social developmental quotient. Overall, 62% of the mothers had low B12 levels (<150 pmol/l) and one mother was folate deficient during pregnancy. Maternal B12 at 28 and 34 weeks of gestation was associated with offspring B12 at 2 y (r = 0.29, r = 0.32, P < 0.001), but folate was not associated with offspring folate. At 2 y, motor development was associated with maternal folate at 28 and 34 weeks of gestation. Mental and social development quotients were associated positively with head circumference and negatively with birth weight. In addition, pregnancy B12 and folate were positively associated with mental and social development quotients. Maternal B12 and folate during intrauterine life may favorably influence brain development and function. Pregnancy provides a window of opportunity to enhance fetal psychomotor (motor and mental) development.

Marked Gender Difference in Plasma Total Homocysteine Concentrations in Indian Adults with low Vitamin B12

CONTEXT Plasma total homocysteine (tHcy) is higher in men than women. OBJECTIVE To explore the gender differences in tHcy in relation to determinants of one-carbon metabolism in Indian people with low B₁₂ and adequate folate. SETTING The study took place in rural and urban areas of Pune, India. DESIGN AND PARTICIPANTS Participants were 441 men from the cross-sectional Coronary Risk of Insulin Sensitivity in Indian Subjects study (CRISIS) and premenopausal wives of 146 men (median ages 38 and 34 years, respectively). MAIN OUTCOME MEASURES Gender difference in fasting tHcy in relation to plasma albumin and creatinine concentrations, lifestyle factors, diet and lean mass, plasma B₁₂ and red cell folate (RCF) was assessed. RESULTS Prevalence of high tHcy (> 15 µmol/L, median 14.4 µM) was 40 %, low B12 (< 150 pmol/L, 114 pmol/L) 66 %, and low RCF (< 283 nmol/L, 525 nmol/L) 8 %. Men had higher (1.8x) plasma tHcy concentrations (16.2 µmol/L) than women (9.5 µmol/L). Only 50 % of the gender difference was explained by age, lean mass, B₁₂, and RCF. The difference remained after controlling for other explanatory variables. Women with a tHcy of 9.3 µM had the same B₁₂ concentration (129 pmol/L) as men with a tHcy of 15 µM; and for a tHcy of 10.0 µmol/L women had the same RCF concentration (533 nmol/L) as men with a tHcy of 15 µmol/L. CONCLUSIONS Adult Indian women have markedly lower tHcy concentrations compared to men. This suggests a lower threshold for supplementation to improve reproductive and cardiovascular outcomes.