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1.  Patterns of fetal growth in a rural Indian cohort and a comparison with a western European population, data from the Pune Maternal Nutrition Study 
Objective
To describe fetal size in a rural Indian population and compare it with European and urban Indian populations using ultrasound.
Methods
Participants were from the Pune Maternal Nutrition Study, India. Fetal growth curves were constructed from serial ultrasound scans at ~18, 30 and 36 weeks gestation in 653 singleton pregnancies. Measurements included femur length (FL) and abdominal circumference (AC), and biparietal diameter (BPD) and occipito-frontal diameter (OFD) from which head circumference (HC) was estimated. Measurements were compared with data from a large population-based study in France and a study of urban mothers in Vellore, South India.
Results
Fetal AC and BPD were smaller than the French reference at 18 weeks gestation (−1.38 SD and −1.30 SD respectively), while FL and HC were more comparable (−0.77 SD and −0.59 SD). The deficit remained similar at 36 weeks for AC (−0.97 SD), FL (−0.43 SD) and HC (−0.52 SD) and increased for BPD (−2.3 SD). Ultrasound at 18 weeks under-estimated gestational age, compared with LMP date, by a median of −1.4 (IQR −4.6, 1.8) days. The Pune fetuses were smaller, even at the 1st scan, than the urban Vellore sample.
Conclusions
Fetal size is smaller in a rural Indian population than in European or urban Indian populations, even in mid pregnancy. The deficit varied for different fetal measurements; it was greatest for abdominal circumference and biparietal diameter and least for femur length and head circumference.
PMCID: PMC3537223  PMID: 20103791
Fetal ultrasound; fetal growth; population differences; India
2.  Vitamin D insufficiency is common in Indian mothers but is not associated with gestational diabetes or variation in newborn size 
Background/objectives:
Vitamin D is required for bone growth and normal insulin secretion. Maternal hypovitaminosis D may impair fetal growth and increase the risk of gestational diabetes. We related maternal vitamin D status in pregnancy to maternal and newborn glucose and insulin concentrations, and newborn size, in a South Indian population.
Subjects/methods:
Serum 25 hydroxy vitamin D (25(OH)D) concentrations, glucose tolerance, and plasma insulin, proinsulin and 32-33 split proinsulin concentrations were measured at 30 weeks gestation in 559 women who delivered at the Holdsworth Memorial Hospital, Mysore. The babies' anthropometry and cord plasma glucose, insulin and insulin precursor concentrations were measured.
Results:
66% of women had hypovitaminosis D [25(OH)D concentrations <50 nmol/l] and 31% were below 28 nmol/l. There was seasonal variation in 25(OH)D concentrations (P<0.0001). There was no association between maternal 25(OH)D and gestational diabetes (incidence 7% in women with and without hypovitaminosis D). Maternal 25(OH)D concentrations were unrelated to newborn anthropometry or cord plasma variables. In mothers with hypovitaminosis D, higher 25(OH)D concentrations were associated with lower 30-minute glucose concentrations (p=0.03) and higher fasting proinsulin concentrations (p=0.04).
Conclusions:
Hypovitaminosis D at 30 weeks gestation is common in Mysore mothers. It is not associated with an increased risk of gestational diabetes, impaired fetal growth, or altered neonatal cord plasma insulin secretory profile.
doi:10.1038/ejcn.2008.14
PMCID: PMC2678985  PMID: 18285809
Vitamin D; Prenatal nutrition; Pregnancy outcome; Birth weight; India; Gestational diabetes; Glucose tolerance; Insulin secretion; Cord blood insulin
3.  Adult metabolic syndrome and impaired glucose tolerance are associated with different patterns of body mass index gain during infancy; Data from the New Delhi birth cohort 
Diabetes care  2008;31(12):2349-2356.
Objective:
To describe patterns of infant, childhood and adolescent body mass index (BMI) and weight associated with adult metabolic risk factors for cardiovascular disease.
Research Design and Methods:
We measured waist circumference, blood pressure, glucose, insulin and lipid concentrations, and the prevalence of metabolic syndrome (NCEP-ATPIII definition) in 1,492 men and women aged 26-32 years in Delhi, India, whose weight and height were recorded 6-monthly throughout infancy (0-2 years), childhood (2-11 years) and adolescence (11 years-adult).
Results:
Men and women with metabolic syndrome (29% overall), any of its component features, or higher (>upper quartile) insulin resistance (HOMA) had more rapid BMI or weight gain than the rest of the cohort throughout infancy, childhood and adolescence. Glucose intolerance (impaired glucose tolerance or diabetes) was, like metabolic syndrome, associated with rapid BMI gain in childhood and adolescence, but with lower BMI in infancy.
Conclusions:
In this Indian population, patterns of infant BMI and weight gain differed for people who developed metabolic syndrome (rapid gain) compared with those who developed glucose intolerance (low infant BMI). Rapid BMI gain during childhood and adolescence was a risk factor for both disorders.
doi:10.2337/dc08-0911
PMCID: PMC2584194  PMID: 18835958
Metabolic syndrome; diabetes; birthweight; infant weight; child growth
4.  Risk of childhood undernutrition related to small-for-gestational age and preterm birth in low- and middle-income countries 
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.
doi:10.1093/ije/dyt109
PMCID: PMC3816349  PMID: 23920141
Foetal growth restriction; preterm birth; stunting; wasting; childhood
5.  Improving women's diet quality preconceptionally and during gestation: effects on birth weight and prevalence of low birth weight—a randomized controlled efficacy trial in India (Mumbai Maternal Nutrition Project)12345 
Background: Low birth weight (LBW) is an important public health problem in undernourished populations.
Objective: We tested whether improving women's dietary micronutrient quality before conception and throughout pregnancy increases birth weight in a high-risk Indian population.
Design: The study was a nonblinded, individually randomized controlled trial. The intervention was a daily snack made from green leafy vegetables, fruit, and milk (treatment group) or low-micronutrient vegetables (potato and onion) (control group) from ≥90 d before pregnancy until delivery in addition to the usual diet. Treatment snacks contained 0.69 MJ of energy (controls: 0.37 MJ) and 10–23% of WHO Reference Nutrient Intakes of β-carotene, riboflavin, folate, vitamin B-12, calcium, and iron (controls: 0–7%). The primary outcome was birth weight.
Results: Of 6513 women randomly assigned, 2291 women became pregnant, 1962 women delivered live singleton newborns, and 1360 newborns were measured. In an intention-to-treat analysis, there was no overall increase in birth weight in the treatment group (+26 g; 95% CI: −15, 68 g; P = 0.22). There was an interaction (P < 0.001) between the allocation group and maternal prepregnant body mass index (BMI; in kg/m2) [birth-weight effect: −23, +34, and +96 g in lowest (<18.6), middle (18.6–21.8), and highest (>21.8) thirds of BMI, respectively]. In 1094 newborns whose mothers started supplementation ≥90 d before pregnancy (per-protocol analysis), birth weight was higher in the treatment group (+48 g; 95% CI: 1, 96 g; P = 0.046). Again, the effect increased with maternal BMI (−8, +79, and +113 g; P-interaction = 0.001). There were similar results for LBW (intention-to-treat OR: 0.83; 95% CI: 0.66, 1.05; P = 0.10; per-protocol OR = 0.76; 95% CI: 0.59, 0.98; P = 0.03) but no effect on gestational age in either analysis.
Conclusions: A daily snack providing additional green leafy vegetables, fruit, and milk before conception and throughout pregnancy had no overall effect on birth weight. Per-protocol and subgroup analyses indicated a possible increase in birth weight if the mother was supplemented ≥3 mo before conception and was not underweight. This trial was registered at www.controlled-trials.com/isrctn/ as ISRCTN62811278.
doi:10.3945/ajcn.114.084921
PMCID: PMC4196482  PMID: 25332324
6.  The case for establishing a Holocaust survivors cohort in Israel 
In this issue, Keinan-Boker summarises the main studies that have followed up offspring of women exposed to famine during pregnancy and calls for the establishment of a national cohort of Holocaust survivors and their offspring to study inter-generational effects. She suggests that the study would consolidate the fetal origins theory and lead to translational applications to deal with the inter-generational effects of the Holocaust. Barker suggested that alterations in the nutritional supply during critical stages of intra-uterine development permanently alter the structure and metabolism of fetal organs which he termed ‘fetal programming’ (now known as developmental origins of health and disease). The famine studies have played an important role in refining the hypothesis by allowing a ‘quasi-experimental’ setting that would otherwise have been impossible to recreate. The developmental origins hypothesis provides a framework to link genetic, environmental and social factors across the lifecourse and offers a primordial preventive strategy to prevent non-communicable disease. Although the famine studies have provided valuable information, the results from various studies are inconsistent. It is perhaps unsurprising given the problems with collecting and interpreting data from famine studies. Survival bias and information bias are key issues. With mortality rates being high, survivors may differ significantly from non-survivors in factors which influence disease development. Most of the data is at ecological level; a lack of individual-level data and poor records make it difficult to identify those affected and assess the severity of effect. Confounding is also possible due to the varying periods and degrees of food deprivation, physical punishment and mental stress undergone by famine survivors. Nonetheless, there would be value in setting up a cohort of Holocaust survivors and their offspring and Keinan-Boker correctly argues that they deserve special attention. National support is essential as the study may re-open old wounds. The study will need to be appropriately planned and resourced. If properly designed, it may provide further insight into the developmental origins hypothesis and suggest translational applications. It may also influence provision of support to women and children affected by man-made wars and famines that continue to happen across the world.
doi:10.1186/2045-4015-3-22
PMCID: PMC4077117  PMID: 24987516
7.  Relationship between adiposity and cognitive performance in 9-10 year old children in south India 
Archives of disease in childhood  2013;99(2):126-134.
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 bio-impedance. Cognitive function was assessed using 3 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’ socio-economic status, education, occupation and income were collected.
Results
According to WHO definitions, 3.5% of the children were overweight/obese (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 to 0.20 SD; p<0.05 for all). The effects, though attenuated, remained mainly significant after adjustment for age, sex and socio-economic 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 socio-economic 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 socio-economic factors.
doi:10.1136/archdischild-2013-304478
PMCID: PMC3982043  PMID: 24146284
Adiposity; Children; Cognitive function; India; Birth cohort
8.  Risk of childhood undernutrition related to small-for-gestational age and preterm birth in low- and middle-income countries 
International journal of epidemiology  2013;42(5):10.1093/ije/dyt109.
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 birth-weight, 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.
doi:10.1093/ije/dyt109
PMCID: PMC3816349  PMID: 23920141
Foetal growth restriction; preterm birth; stunting; wasting; childhood
9.  Fetal Programming and the Risk of Non-communicable Disease 
Indian journal of pediatrics  2012;80(0 1):S13-S20.
The “developmental origins of health and disease” (DOHaD) hypothesis proposes that environmental conditions during fetal and early post-natal development influence lifelong health and capacity through permanent effects on growth, structure and metabolism. This has been called ‘programming’. The hypothesis is supported by epidemiological evidence in humans linking newborn size, and infant growth and nutrition, to adult health outcomes, and by experiments in animals showing that maternal under- and over-nutrition and other interventions (eg. glucocorticoid exposure) during pregnancy lead to abnormal metabolism and body composition in the adult offspring. Early life programming is now thought to be important in the aetiology of obesity, type 2 diabetes, and cardiovascular disease, opening up the possibility that these common diseases could be prevented by achieving optimal fetal and infant development. This is likely to have additional benefits for infant survival and human capital (eg improved cognitive performance and physical work capacity). Fetal nutrition is influenced by the mother’s diet and body size and composition, but hard evidence that the nutrition of the human mother programmes chronic disease risk in her offspring is currently limited. Recent findings from follow-up of children born after randomised nutritional interventions in pregnancy are mixed, but show some evidence of beneficial effects on vascular function, lipid concentrations, glucose tolerance and insulin resistance. Work in experimental animals suggests that epigenetic phenomena, whereby gene expression is modified by DNA methylation, and which are sensitive to the nutritional environment in early life, may be one mechanism underlying programming.
doi:10.1007/s12098-012-0834-5
PMCID: PMC3793300  PMID: 22829248
Fetal programming; developmental origins of health and disease (DOHaD); birthweight; childhood growth; epidemiologic transition; non-communicable chronic disease
10.  Predictors of carotid intima-media thickness and carotid plaque in young Indian adults: results from the New Delhi Birth Cohort 
International journal of cardiology  2012;167(4):1322-1328.
Background
Carotid intima-media thickness (CIMT) and carotid plaques represent preclinical markers of atherosclerosis. We sought to describe predictors of CIMT and carotid plaques, including early life growth, in a young urban Indian cohort free of clinical cardiovascular disease (CVD).
Methods
In 2006-2009, we performed B-mode carotid ultrasound on 600 participants (mean [SD] age 36 [1.1] years; 45% women) from the New Delhi Birth Cohort to evaluate CIMT and carotid plaques (> 1mm). Height and weight were recorded at birth, 2 and 11 years of age. Data on CVD risk factors, anthropometry, medical history, socio-economic position, and lifestyle habits were collected in 1998-2002.
Results
Mean (SD) CIMT for men and women was 0.91 (0.12) and 0.86 (0.13) mm, respectively. Carotid plaque was present in 33% of men and 26% of women. Waist circumference in 1998-2002 was positively associated with CIMT (β coefficient 0.26 mm [0.17, 0.36] per SD) and carotid plaque (OR 1.27 [1.06,1.52] per SD) in 2006-2009. Higher triglycerides, PAI-1, insulin resistance, and diastolic blood pressure, metabolic syndrome, and lower HDL-cholesterol and physical activity predicted higher CIMT and/or plaque (p<0.05). Longer length at 2 years was associated with higher CIMT (p<0.05). These associations were attenuated after adjusting for adult waist circumference.
Conclusions
These are the first prospective data from India showing that early life growth, adult socio-demographics, and CVD risk factors predict future CIMT and /or carotid plaque. These relationships appear primarily mediated through central adiposity, highlighting the importance of maintaining a healthy weight in early adulthood to prevent CVD.
doi:10.1016/j.ijcard.2012.03.180
PMCID: PMC3622714  PMID: 22537976
carotid intima media thickness; carotid plaque; India; cohort; birth weight; infant and childhood growth
11.  Testing the fetal overnutrition hypothesis; the relationship of maternal and paternal adiposity to adiposity, insulin resistance and cardiovascular risk factors in Indian children 
Public health nutrition  2012;16(9):1656-1666.
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 30 ± 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.
doi:10.1017/S1368980012003795
PMCID: PMC3622715  PMID: 22895107
Adiposity; Cardiovascular risk factors; Children; India; Insulin resistance; Intergeneration; Maternal and paternal effects
12.  Associations of linear growth and relative weight gain during early life with adult health and human capital in countries of low and middle income: findings from five birth cohort studies 
Lancet  2013;382(9891):525-534.
Summary
Background
Fast weight gain and linear growth in children in low-income and middle-income countries are associated with enhanced survival and improved cognitive development, but might increase risk of obesity and related adult cardiometabolic diseases. We investigated how linear growth and relative weight gain during infancy and childhood are related to health and human capital outcomes in young adults.
Methods
We used data from five prospective birth cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa. We investigated body-mass index, systolic and diastolic blood pressure, plasma glucose concentration, height, years of attained schooling, and related categorical indicators of adverse outcomes in young adults. With linear and logistic regression models, we assessed how these outcomes relate to birthweight and to statistically independent measures representing linear growth and weight gain independent of linear growth (relative weight gain) in three age periods: 0–2 years, 2 years to mid-childhood, and mid-childhood to adulthood.
Findings
We obtained data for 8362 participants who had at least one adult outcome of interest. A higher birthweight was consistently associated with an adult body-mass index of greater than 25 kg/m2 (odds ratio 1·28, 95% CI 1·21–1·35) and a reduced likelihood of short adult stature (0·49, 0·44–0·54) and of not completing secondary school (0·82, 0·78–0·87). Faster linear growth was strongly associated with a reduced risk of short adult stature (age 2 years: 0·23, 0·20–0·52; mid-childhood: 0·39, 0·36–0·43) and of not completing secondary school (age 2 years: 0·74, 0·67–0·78; mid-childhood: 0·87, 0·83–0·92), but did raise the likelihood of overweight (age 2 years: 1·24, 1·17–1·31; mid-childhood: 1·12, 1·06–1·18) and elevated blood pressure (age 2 years: 1·12, 1·06–1·19; mid-childhood: 1·07, 1·01–1·13). Faster relative weight gain was associated with an increased risk of adult overweight (age 2 years: 1·51, 1·43–1·60; mid-childhood: 1·76, 1·69–1·91) and elevated blood pressure (age 2 years: 1·07, 1·01–1·13; mid-childhood: 1·22, 1·15–1·30). Linear growth and relative weight gain were not associated with dysglycaemia, but a higher birthweight was associated with decreased risk of the disorder (0·89, 0·81–0·98).
Interpretation
Interventions in countries of low and middle income to increase birthweight and linear growth during the first 2 years of life are likely to result in substantial gains in height and schooling and give some protection from adult chronic disease risk factors, with few adverse trade-offs.
Funding
Wellcome Trust and Bill & Melinda Gates Foundation.
doi:10.1016/S0140-6736(13)60103-8
PMCID: PMC3744751  PMID: 23541370
13.  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 
Fetal 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 hand-grip 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 (SD)) birthweight was 2863 (446) g. At 9 years, the children were short (mean height SD −0.6) and light (mean weight SD −1.1) compared with the World Health Organization growth reference. Mean (SD) 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 per standard deviation increase in birthweight, p<0.001; and β=0.41 kg per standard deviation 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.
doi:10.1017/S2040174410000309
PMCID: PMC3672832  PMID: 23750316
Grip strength; birthweight; children; arm muscle area
14.  Higher maternal plasma folate but not vitamin B-12 concentrations during pregnancy are associated with better cognitive function scores in 9-10 year old children in South-India1-3 
The Journal of nutrition  2010;140(5):1014-1022.
Folate and vitamin B-12 (B-12) are essential for normal brain development. Few studies have examined the relationship of maternal folate and B-12 status during pregnancy to offspring cognitive function. To test the hypothesis that lower maternal plasma folate and B-12 concentrations and higher plasma homocysteine concentrations during pregnancy, are associated with poorer neurodevelopment, cognitive function was assessed during 2007-2008 among 536 children (aged 9-10 y) from the Mysore Parthenon birth cohort. Maternal folate, B-12 and homocysteine concentrations were measured in stored plasma samples taken at 30±2 wk gestation. The children’s cognitive function was measured using 3 core tests from the Kaufman Assessment Battery and additional tests measuring learning ability, long-term storage/retrieval, attention and concentration, visuo-spatial and verbal abilities. During pregnancy 4% of mothers had low folate concentrations (<7 nmol/L), 42.5% had low B-12 concentrations (<150 pmol/L) and 3% had hyperhomocysteinemia (>10 μmol/L). There was a 0.1-0.2 SD increase in the children’s cognitive scores per SD increase in maternal folate concentration (p<0.001 for all tests). The associations with learning ability and long-term storage/retrieval, visuo-spatial ability, attention and concentration were independent of maternal age, BMI, parity, the parents’ education, socio-economic status, rural/urban residence, religion, the child’s gestational age, birth size, sex and the children’s size, educational level and folate and B-12 concentrations at 9.5 y. There were no consistent associations of maternal B-12 and homocysteine concentrations with childhood cognitive performance.
Conclusions
In this Indian population higher maternal folate, but not vitamin B-12 concentrations during pregnancy, predicted better childhood cognitive ability.
doi:10.3945/jn.109.118075
PMCID: PMC3672847  PMID: 20335637
16.  Socio-economic status and Cardiovascular Risk Factors in Rural and Urban Areas of Vellore, Tamilnadu, South India 
Background
We examined associations between socio-economic (SES) indicators and cardiovascular disease (CVD) risk factors among urban and rural South Indians.
Methods
Data from a population-based birth cohort of 2,218 men and women aged 26-32 years from Vellore, Tamilnadu were used. SES indicators included a household possessions score, attained education, and paternal education. CVD risk factors included body mass index, waist circumference, blood pressure, glucose tolerance, plasma cholesterol and triglyceride levels, and consumption of tobacco and alcohol. Multiple logistic regression analysis was used to assess associations between SES indicators and CVD risk factors.
Results
Most risk factors were positively associated with possessions score in urban and rural men and women, except for tobacco use, which was negatively associated. Trends were similar with the participants’ own education, and paternal education, though weaker and less consistent. In a concurrent analysis of all three SES indicators adjusted for gender and urban/rural residence, independent associations were observed only for the possessions score; compared with those in the lowest fifth of the possessions score, participants in the highest fifth had a higher risk of abdominal obesity (OR=6.4, 95%CI 3.4, 11.6), high total cholesterol to HDL ratio (OR=2.4, 95%CI 1.6, 3.5) and glucose intolerance (OR=2.8, 95%CI 1.9, 4.1). Their tobacco use (OR=0.4, 95%CI 0.2, 0.6) was lower. Except hypertension and glucose intolerance, risk factors were higher in urban than rural participants independently of SES.
Conclusion
In rural and urban populations, higher SES, as reflected by household possessions, was associated (apart from tobacco use) with a more adverse CVD risk factor profile.
doi:10.1093/ije/dys001
PMCID: PMC3541500  PMID: 22366083
Socio-economic indicators; CVD risk factors; India; Birth cohort studies
17.  Evidence for the intra-uterine programming of adiposity in later life 
Annals of human biology  2011;38(4):410-428.
Research in animals has shown that altering fetal nutrition by under-nourishing or over-nourishing the mother or rendering her diabetic, or fetal exposure to glucocorticoids and toxins, can programme obesity in later life. The increased adiposity is mediated by permanent changes in appetite, food choices, physical activity and energy metabolism. In humans, increased adiposity has been shown in people who experienced fetal under-nutrition due to maternal famine, or over-nutrition due to maternal diabetes. Lower birth weight (a proxy for fetal under-nutrition) is associated with a reduced adult lean mass and increased intra-abdominal fat. Higher birthweight caused by maternal diabetes is associated with increased total fat mass and obesity in later life. There is growing evidence that maternal obesity, without diabetes, is also a risk factor for obesity in the child, due to fetal over-nutrition effects. Maternal smoking is associated with an increased risk of obesity in the children, though a causal link has not been proven. Other fetal exposures associated with increased adiposity in animals include glucocorticoids and endocrine disruptors. Reversing the current obesity epidemic will require greater attention to, and better understanding of, these inter-generational (mother-offspring) factors that programme body composition during early development.
doi:10.3109/03014460.2011.592513
PMCID: PMC3428869  PMID: 21682572
18.  Infant feeding practice and childhood cognitive performance in South India 
Archives of disease in childhood  2009;95(5):347-354.
Aim
Several studies have suggested a beneficial effect of infant breast-feeding on childhood cognitive function. Our main objective was to examine whether duration of breast-feeding and age at introduction of complementary foods are related to cognitive performance in 9-10 year old school going children in South-India.
Methods
We examined 514 children from the Mysore Parthenon birth cohort for whom breast-feeding duration (6 categories from <3 to ≥18 months) and age at introduction of complementary foods (4 categories from <4 to ≥6 months) were collected at the 1st, 2nd and 3rd year annual follow-up visits. Their cognitive function was assessed at a mean age of 9.7 years using 3 core tests from the Kaufman Assessment Battery for children and additional tests measuring long-term retrieval/storage, attention and concentration, visuo-spatial and verbal abilities.
Results
All the children were initially breast-fed. The mode for duration of breast-feeding was 12-17 months (45.7%) and for age at introduction of complementary foods 4 months (37.1%). There were no associations between longer duration of breast-feeding, or age of introduction of complementary foods, and cognitive function at 9-10 years, either unadjusted or after adjustment for age, sex, gestation, birth size, maternal age, parity, socio-economic status, parents’ attained schooling, and rural/urban residence.
Conclusions
Within this cohort, in which prolonged breast-feeding was the norm (90% breast-fed ≥6 months and 65% breast-fed for ≥12 months), there was no evidence suggesting a beneficial effect of longer duration of breast-feeding on later cognitive ability.
doi:10.1136/adc.2009.165159
PMCID: PMC3428883  PMID: 19946010
Breast-feeding; Complementary foods; Children; Cognitive performance; India
19.  CHILDHOOD BODY MASS INDEX AND ADULT PRO-INFLAMMATORY AND PRO-THROMBOTIC RISK FACTORS; DATA FROM THE NEW DELHI BIRTH COHORT 
Objective
Weight gain and growth in early life may influence adult pro-inflammatory and pro-thrombotic cardiovascular risk factors.
Methods
Follow-up of a birth cohort in New Delhi, India, whose weight and height were measured 6-monthly until age 21 years. BMI at birth, during infancy (2 years), childhood (11 years) and adulthood (26-32 years) and BMI gain between these ages were analyzed in 886 men and 640 women in relation to adult fibrinogen, high-sensitivity C-reactive protein (hsCRP) and plasminogen activator inhibitor (PAI-1) concentrations.
Results
All the pro-inflammatory/pro-thrombotic risk factors were higher in participants with higher adiposity. In women, BMI at birth and age 2 years was inversely related to fibrinogen (p=0.002 and 0.05) and, after adjusting for adult adiposity, to hsCRP (p=0.02 and 0.009). After adjusting for adult adiposity, BMI at 2 years was inversely related to hsCRP and PAI-1 concentrations (p<0.001 and p=0.02) in men. BMI gain between 2-11 years and/or 11 years to adulthood was positively associated with fibrinogen and hsCRP in women and with hsCRP and PAI-1 in men.
Conclusions
Thinness at birth or during infancy, and accelerated BMI gain during childhood/adolescence are associated with a pro-inflammatory/pro-thrombotic state in adult life. An altered inflammatory state could be one link between small newborn/infant size and adult cardiovascular disease. Associations between pro-inflammatory markers and childhood/adolescent BMI gain are probably mediated through adult adiposity.
doi:10.1093/ije/dyq121
PMCID: PMC3428891  PMID: 20660641
Birthweight; growth; C-reactive protein; fibrinogen; plasminogen activator inhibitor-1
20.  Glucose tolerance, insulin resistance and insulin secretion in young south Indian adults; relationships to parental size, neonatal size and childhood body mass index 
Objective
To study the relationship of newborn size and post-natal growth to glucose intolerance in south Indian adults.
Research design and Methods
2,218 men and women (mean age 28 years) were studied from a population-based birth cohort born in a large town and adjacent rural villages. The prevalence of adult diabetes mellitus [DM] and impaired glucose tolerance [IGT], and insulin resistance and insulin secretion (calculated) were examined in relation to BMI and height at birth, and in infancy, childhood and adolescence and changes in BMI and height between these stages.
Results
Sixty-two (2.8%) subjects had type 2 diabetes (DM) and 362 (16.3%) had impaired glucose tolerance (IGT). IGT and DM combined (IGT/DM) and insulin resistance were associated with low childhood body mass index (BMI) (p<0.001 for both) and above-average BMI gain between childhood or adolescence and adult life (p<0.001 for both). There were no direct associations between birthweight or infant size and IGT/DM; however, after adjusting for adult BMI, lower birthweight was associated with an increased risk.
Conclusions
The occurrence of IGT and Type 2 DM is associated with thinness at birth and in childhood followed by accelerated BMI gain through adolescence.
doi:10.1016/j.diabres.2009.11.015
PMCID: PMC3428893  PMID: 20115937
Type 2 diabetes mellitus; impaired glucose tolerance; insulin resistance; childhood body mass index; young adulthood
21.  Maternal vitamin D status during pregnancy and body composition and cardiovascular risk markers in Indian children: the Mysore Parthenon study 
Background
Metabolic consequences of vitamin D deficiency have become a recent research focus. Maternal vitamin D status is thought to influence musculo-skeletal health in children, but its relationship with offspring metabolic risk is not known.
Objective
We aimed to examine the association between maternal vitamin D status and anthropometry, body composition and cardiovascular risk markers in Indian children.
Design
Serum 25-hydroxy D (25(OH)D ) concentrations were measured at 28-32 weeks gestation in 568 women who delivered at Holdsworth Memorial Hospital, Mysore. Anthropometry, glucose and insulin concentrations, blood pressure (BP) and fasting lipid concentrations were measured in the offspring at 5 and 9.5 years of age. Muscle-grip strength was measured using a hand held dynamometer at 9.5 years. Arm-muscle-area was calculated as a measure of muscle mass. Fasting insulin resistance was calculated using the HOMA equation.
Results
67% of women had vitamin D deficiency (serum 25(OH)D concentration <50 nmol/l). At 5 and 9.5 years, children born to vitamin D deficient mothers had smaller arm-muscle-area compared to 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 years, children of vitamin D deficient mothers had higher fasting insulin resistance than children of non-deficient women (P=0.04). There were no associations between maternal vitamin D status and other offspring risk factors at either age.
Conclusions
Intra-uterine exposure to low 25(OH)D concentrations is associated with lower muscle mass and higher insulin resistance in children.
doi:10.3945/ajcn.110.003921
PMCID: PMC3407368  PMID: 21228264
22.  Infant-feeding patterns and cardiovascular risk factors in young adulthood: data from five cohorts in low- and middle-income countries 
Background Infant-feeding patterns may influence lifelong health. This study tested the hypothesis that longer duration of breastfeeding and later introduction of complementary foods in infancy are associated with reduced adult cardiovascular risk.
Methods Data were pooled from 10 912 subjects in the age range of 15–41 years from five prospective birth-cohort studies in low-/middle-income countries (Brazil, Guatemala, India, Philippines and South Africa). Associations were examined between infant feeding (duration of breastfeeding and age at introduction of complementary foods) and adult blood pressure (BP), plasma glucose concentration and adiposity (skinfolds, waist circumference, percentage body fat and overweight/obesity). Analyses were adjusted for maternal socio-economic status, education, age, smoking, race and urban/rural residence and infant birth weight.
Results There were no differences in outcomes between adults who were ever breastfed compared with those who were never breastfed. Duration of breastfeeding was not associated with adult diabetes prevalence or adiposity. There were U-shaped associations between duration of breastfeeding and systolic BP and hypertension; however, these were weak and inconsistent among the cohorts. Later introduction of complementary foods was associated with lower adult adiposity. Body mass index changed by −0.19 kg/m2 [95% confidence interval (CI) −0.37 to −0.01] and waist circumference by −0.45 cm (95% CI −0.88 to −0.02) per 3-month increase in age at introduction of complementary foods.
Conclusions There was no evidence that longer duration of breastfeeding is protective against adult hypertension, diabetes or overweight/adiposity in these low-/middle-income populations. Further research is required to determine whether ‘exclusive’ breastfeeding may be protective. Delaying complementary foods until 6 months, as recommended by the World Health Organization, may reduce the risk of adult overweight/adiposity, but the effect is likely to be small.
doi:10.1093/ije/dyq155
PMCID: PMC3043278  PMID: 20852257
Infant feeding; breastfeeding; complementary feeding; blood pressure; diabetes; body composition
24.  A principal components approach to parent-to-newborn body composition associations in South India 
BMC Pediatrics  2009;9:16.
Background
Size at birth is influenced by environmental factors, like maternal nutrition and parity, and by genes. Birth weight is a composite measure, encompassing bone, fat and lean mass. These may have different determinants. The main purpose of this paper was to use anthropometry and principal components analysis (PCA) to describe maternal and newborn body composition, and associations between them, in an Indian population. We also compared maternal and paternal measurements (body mass index (BMI) and height) as predictors of newborn body composition.
Methods
Weight, height, head and mid-arm circumferences, skinfold thicknesses and external pelvic diameters were measured at 30 ± 2 weeks gestation in 571 pregnant women attending the antenatal clinic of the Holdsworth Memorial Hospital, Mysore, India. Paternal height and weight were also measured. At birth, detailed neonatal anthropometry was performed. Unrotated and varimax rotated PCA was applied to the maternal and neonatal measurements.
Results
Rotated PCA reduced maternal measurements to 4 independent components (fat, pelvis, height and muscle) and neonatal measurements to 3 components (trunk+head, fat, and leg length). An SD increase in maternal fat was associated with a 0.16 SD increase (β) in neonatal fat (p < 0.001, adjusted for gestation, maternal parity, newborn sex and socio-economic status). Maternal pelvis, height and (for male babies) muscle predicted neonatal trunk+head (β = 0. 09 SD; p = 0.017, β = 0.12 SD; p = 0.006 and β = 0.27 SD; p < 0.001). In the mother-baby and father-baby comparison, maternal BMI predicted neonatal fat (β = 0.20 SD; p < 0.001) and neonatal trunk+head (β = 0.15 SD; p = 0.001). Both maternal (β = 0.12 SD; p = 0.002) and paternal height (β = 0.09 SD; p = 0.030) predicted neonatal trunk+head but the associations became weak and statistically non-significant in multivariate analysis. Only paternal height predicted neonatal leg length (β = 0.15 SD; p = 0.003).
Conclusion
Principal components analysis is a useful method to describe neonatal body composition and its determinants. Newborn adiposity is related to maternal nutritional status and parity, while newborn length is genetically determined. Further research is needed to understand mechanisms linking maternal pelvic size to fetal growth and the determinants and implications of the components (trunk v leg length) of fetal skeletal growth.
doi:10.1186/1471-2431-9-16
PMCID: PMC2649926  PMID: 19236724
25.  Gestational Diabetes and the Incidence of Diabetes in the 5 Years following the Index Pregnancy in South Indian Women 
This study was carried out to examine the incidence of diabetes and the factors associated with this in a cohort of south Indian women five years after they were examined for gestational diabetes (GDM). Women (N=630) whose GDM status was determined (Carpenter-Coustan criteria; GDM: N=41) delivered live babies without major anomalies at the Holdsworth Memorial Hospital, Mysore. Of these, 526 women (GDM: N=35) available for follow-up after 5 years underwent a 2-hour oral glucose tolerance test and detailed anthropometry. Diabetes was determined using WHO criteria, and Metabolic Syndrome using IDF criteria recommended for south Asian women. The incidence of diabetes (37% vs. 2%) and Metabolic Syndrome (60% vs. 26%) was considerably higher in women with previous GDM compared to non-GDM women. GDM women who developed diabetes had lower gestational insulin area-under-the-curve (P=0.05). They had larger waist-to-hip ratio, skinfolds, body mass index, and lower 30-minute insulin increment at follow-up than other GDM women. In all, history of diabetes in first-degree relatives was independently associated with higher incidence of diabetes (P<0.001). Our findings suggest high diabetes and cardiovascular risks in women with previous GDM. Follow-up of these women after delivery would provide opportunities to modify adverse lifestyle factors.
doi:10.1016/j.diabres.2007.06.002
PMCID: PMC2358951  PMID: 17640759
Gestational diabetes; type 2 diabetes; follow-up; India; Metabolic Syndrome

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