Sarah H. Kehoe

Intrauterine exposure to maternal diabetes is associated with higher adiposity and insulin resistance and clustering of cardiovascular risk markers in Indian children

OBJECTIVE To test the hypothesis that maternal gestational diabetes increases cardiovascular risk markers in Indian children. RESEARCH DESIGN AND METHODS Anthropometry, blood pressure, and glucose/insulin concentrations were measured in 514 children at 5 and 9.5 years of age (35 offspring of diabetic mothers [ODMs], 39 offspring of diabetic fathers [ODFs]). Children of nondiabetic parents were control subjects. RESULTS At age 9.5 years, female ODMs had larger skinfolds (P < 0.001), higher glucose (30 min) and insulin concentrations, and higher homeostasis model assessment (HOMA) of insulin resistance and systolic blood pressure (P < 0.05) than control subjects. Male ODMs had higher HOMA (P < 0.01). Associations were stronger than at age 5 years. Female ODFs had larger skinfolds and male ODFs had higher HOMA (P < 0.05) than control subjects; associations were weaker than for ODMs. Associations between outcomes in control subjects and parental BMI, glucose, and insulin concentrations were similar for mothers and fathers. CONCLUSIONS The intrauterine environment experienced by ODMs increases diabetes and cardiovascular risk over genetic factors; the effects strengthen during childhood.

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.

Diet patterns are associated with demographic factors and nutritional status in south Indian children

Abstract 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 childs 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.

Relationship between physical activity measured using accelerometers and energy expenditure measured using doubly labelled water in Indian children

Background/Objectives:To test the association between physical activity measured using accelerometer counts (Actigraph) and energy expenditure (EE) measured using the doubly labelled water (DLW) method in free-living children in India. The aim of this study was to explore the usefulness of Actigraphs in estimating EE.Subjects/Methods:Total EE (TEE) was measured in 58 children aged 8–9 years over a period of 2 weeks using the DLW technique. Physical activity level (PAL) was estimated from TEE, and the basal metabolic rate was predicted from weight. Physical activity was measured simultaneously using the Actigraph accelerometers (MTI AM7164 and GT1M). TEE was also calculated from the Actigraph counts using a published equation.Results:TEE (mean: 6.6 vs 5.7 MJ, P=0.04) and Actigraph counts (counts/minute: 557 vs 465, P=0.02; total counts: 445 534 vs 354 748, P=0.004) were higher in boys than in girls. There were no significant correlations between either total Actigraph counts (r=0.15, P=0.3) or counts/minute (r=0.18, P=0.2), and TEE estimated using DLW. Similarly, there were no significant correlations between Actigraph counts and PAL (r=0.10, P=0.5; r=0.17, P=0.2, respectively). The Bland–Altman analysis showed poor agreement between TEE estimated using the DLW method and TEE derived from the Actigraph equation.Conclusions:Activity measured using Actigraph accelerometers was not related to TEE and PAL derived using the DLW technique in children in Mysore. Actigraphs may not be useful in predicting EE in this setting, but may be better used for judging activity patterns.

A Daily Snack Containing Leafy Green Vegetables, Fruit, and Milk before and during Pregnancy Prevents Gestational Diabetes in a Randomized, Controlled Trial in Mumbai, India.

Background: Prospective observational studies suggest that maternal diets rich in leafy green vegetables and fruit may help prevent gestational diabetes mellitus (GDM). Objective: Our objective was to test whether increasing women’s dietary intake of leafy green vegetables, fruit, and milk before conception and throughout pregnancy reduced their risk of GDM. Methods: Project SARAS (“excellent”) (2006–2012) was a nonblinded, individually randomized, controlled trial in women living in slums in the city of Mumbai, India. The interventions included a daily snack made from leafy green vegetables, fruit, and milk for the treatment group or low-micronutrient vegetables (e.g., potato and onion) for the control group, in addition to the usual diet. Results for the primary outcome, birth weight, have been reported. Women were invited to take an oral-glucose-tolerance test (OGTT) at 28–32 wk gestation to screen for GDM (WHO 1999 criteria). The prevalence of GDM was compared between the intervention and control groups, and Kernel density analysis was used to compare distributions of 120-min plasma glucose concentrations between groups. Results: Of 6513 women randomly assigned, 2291 became pregnant; of these, 2028 reached a gestation of 28 wk, 1008 (50%) attended for an OGTT, and 100 (9.9%) had GDM. In an intention-to-treat analysis, the prevalence of GDM was reduced in the treatment group (7.3% compared with 12.4% in controls; OR: 0.56; 95% CI: 0.36, 0.86; P = 0.008). The reduction in GDM remained significant after adjusting for prepregnancy adiposity and fat or weight gain during pregnancy. Kernel density analysis showed that this was explained by the fact that fewer women in the treatment group had a 2-h glucose concentration in the range 7.5–10.0 mmol/L. Conclusions: In low-income settings, in which women have a low intake of micronutrient-rich foods, improving dietary micronutrient quality by increasing intake of leafy green vegetables, fruit, and/or milk may have an important protective effect against the development of GDM. This trial was registered at www.controlled-trials.com as ISRCTN62811278.

Effects of a food-based intervention on markers of micronutrient status among Indian women of low socio-economic status.

Intakes of micronutrient-rich foods are low among Indian women of reproductive age. We investigated whether consumption of a food-based micronutrient-rich snack increased markers of blood micronutrient concentrations when compared with a control snack. Non-pregnant women (n 222) aged 14–35 years living in a Mumbai slum were randomised to receive a treatment snack (containing green leafy vegetables, dried fruit and whole milk powder), or a control snack containing foods of low micronutrient content such as wheat flour, potato and tapioca. The snacks were consumed under observation 6 d per week for 12 weeks, compliance was recorded, and blood was collected at 0 and 12 weeks. Food-frequency data were collected at both time points. Compliance (defined as the proportion of women who consumed ≥ 3 snacks/week) was >85 % in both groups. We assessed the effects of group allocation on 12-week nutrient concentrations using ANCOVA models with respective 0-week concentrations, BMI, compliance, standard of living, fruit and green leafy vegetable consumption and use of synthetic nutrients as covariates. The treatment snack significantly increased β-carotene concentrations (treatment effect: 47·1 nmol/l, 95 % CI 6·5, 87·7). There was no effect of group allocation on concentrations of ferritin, retinol, ascorbate, folate or vitamin B12. The present study shows that locally sourced foods can be made into acceptable snacks that may increase serum β-carotene concentrations among women of reproductive age. However, no increase in circulating concentrations of the other nutrients measured was observed.

Birth size and physical activity in a cohort of Indian children aged 6-10 years.

There is evidence of a reduction in childrens 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.

Effect of a micronutrient-rich snack taken preconceptionally and throughout pregnancy on ultrasound measures of fetal growth: The Mumbai Maternal Nutrition Project (MMNP)

Abstract Improving micronutrient intakes of under‐nourished mothers in low‐ and middle‐income countries increases birth weight, but there is little data on the nature and timing during gestation of any effects on fetal growth. Ultrasound measures of fetal size were used to determine whether and when a food‐based supplement affected fetal growth. Non‐pregnant women living in Mumbai slums, India (N = 6,513), were randomly assigned to receive either a daily micronutrient‐rich snack containing green leafy vegetables, fruit, and milk (treatment) or a snack made from lower‐micronutrient vegetables (control) in addition to their usual diet from before pregnancy until delivery. From 2,291 pregnancies, the analysis sample comprised 1,677 fetuses (1,335 fetuses of women supplemented for ≥3 months before conception). First‐trimester (median: 10 weeks, interquartile range: 9–12 weeks) fetal crown‐rump length was measured. Fetal head circumference, biparietal diameter, femur length, and abdominal circumference were measured during the second (19, 19–20 weeks) and third trimesters (29, 28–30 weeks). The intervention had no effect on fetal size or growth at any stage of pregnancy. In the second trimester, there were interactions between parity and allocation group for biparietal diameter (p = .02) and femur length (p = .04) with both being smaller among fetuses of primiparous women and larger among those of multiparous women, in the treatment group compared with the controls. Overall, a micronutrient‐rich supplement did not increase standard ultrasound measures of fetal size and growth at any stage of pregnancy. Additional ultrasound measures of fetal soft tissues (fat and muscle) may be informative.

The relationship of birthweight, muscle size at birth and postnatal growth to grip strength in 9 year-old Indian children: findings from the Mysore Parthenon Study: Birthweight and grip strength at 9

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.

Life course programming of stress responses in adolescents and young adults in India: Protocol of the Stress Responses in Adolescence and Vulnerability to Adult Non-communicable disease (SRAVANA) Study

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.