Comparison of regional fat measurements by dual-energy X-ray absorptiometry and conventional anthropometry and their association with markers of diabetes and cardiovascular disease risk.

BACKGROUND/OBJECTIVES: Fat distribution is a strong and independent predictor of type 2 diabetes (T2D) and cardiovascular disease (CVD) and is usually determined using conventional anthropometry in epidemiological studies. Dual-energy X-ray absorptiometry (DXA) can measure total and regional adiposity more accurately. Nonetheless, whether DXA provides more precise estimates of cardiovascular risk in relation to total and regional adiposity is not known. We determined the strength of the associations between DXA- and conventional anthropometry determined fat distribution and T2D and CVD risk markers. SUBJECTS/METHODS: Waist (WC) and hip circumference (HC) and DXA was used to measure total and regional adiposity in 4950 (2119 men) participants aged 29-55 years from the Oxford Biobank without pre-existing T2D or CVD. Cross-sectional associations were compared between WC and HC vs. DXA-determined regional adiposity (all z-score normalised) with impaired fasting glucose, hypertriglyceridemia, hypertension and insulin resistance (IR). RESULTS: Following adjustment for total adiposity, upper body adiposity measurements showed consistently increased risk of T2D and CVD risk markers except for abdominal subcutaneous fat in both sexes, and arm fat in men, which showed protective associations. Among upper adiposity depots, visceral fat mass showed stronger odds ratios (OR) ranging from 1.69 to 3.64 compared with WC 1.07-1.83. Among lower adiposity depots, HC showed modest protection for IR in both sexes (men: OR 0.80 (95% confidence interval 0.67, 0.96); women: 0.69 (0.56, 0.86)), whereas gynoid fat and in particular leg fat showed consistent and strong protective effects for all outcomes in both men and women. The differential effect of body fat distribution on CVD and T2D were more pronounced at higher levels of total adiposity. CONCLUSIONS: Compared with DXA, conventional anthropometry underestimates the associations of regional adiposity with T2D and CVD risk markers. After correcting for overall adiposity, greater subcutaneous fat mass in particular in the lower body is protective relative to greater android or visceral adipose tissue mass.

Associations of infant feeding and timing of linear growth and relative weight gain during early life with childhood body composition.

BACKGROUND: Growth and feeding during infancy have been associated with later life body mass index. However, the associations of infant feeding, linear growth and weight gain relative to linear growth with separate components of body composition remain unclear. METHODS: Of 5551 children with collected growth and infant-feeding data in a prospective cohort study (Amsterdam Born Children and their Development), body composition measured using bioelectrical impedance analysis at the age of 5-6 years was available for 2227 children. We assessed how feeding (duration of full breastfeeding and timing of introduction of complementary feeding) and conditional variables representing linear growth and relative weight gain were associated with childhood fat-free mass (FFM) and fat mass (FM). RESULTS: Birth weight was positively associated with both FFM and FM in childhood, and more strongly with FFM than FM. Faster linear growth and faster relative weight gain at all ages in infancy were positively associated with childhood FFM and FM. The associations with FM were stronger for relative weight gain than for linear growth (FM z score: ß coefficient 0.23 (95% con 0.19 to 0.26), P<0.001 and 0.14 (0.11 to 0.17), P<0.001 per s.d. change in relative weight gain and linear growth between 1 and 3 months, respectively). Compared with full breastfeeding <1 month, full breastfeeding >6 months was associated with lower FM (FM z score: -0.17 (-0.28 to -0.05), P=0.005) and lower FFM (FFM z score: -0.13 (-0.23 to -0.03), P=0.015), as was the introduction of complementary feeding >6 months (FM z score: -0.22 (-0.38 to -0.07), P=0.004), compared with <4 months. CONCLUSIONS: Faster infant weight gain is associated with a healthier childhood body composition when it is caused by faster linear growth. Full breastfeeding >6 months and introduction of complementary feeding >6 months are associated with lower childhood FM.

Parental childhood growth and offspring birthweight: pooled analyses from four birth cohorts in low and middle income countries.

OBJECTIVE: Associations between parental and offspring size at birth are well established, but the relative importance of parental growth at different ages as predictors of offspring birthweight is less certain. Here we model parental birthweight and postnatal conditional growth in specific age periods as predictors of offspring birthweight. METHODS: We analyzed data from 3,392 adults participating in four prospective birth cohorts and 5,506 of their offspring. RESULTS: There was no significant heterogeneity by study site or offspring sex. 1SD increase in maternal birthweight was associated with offspring birthweight increases of 102 g, 1SD in maternal length growth 0-2 year with 46 g, and 1SD in maternal height growth Mid-childhood (MC)-adulthood with 27 g. Maternal relative weight measures were associated with 24 g offspring birth weight increases (2 year- MC) and 49 g for MC-adulthood period but not with earlier relative weight 0-2 year. For fathers, birthweight, and linear/length growth from 0-2 year were associated with increases of 57 and 56 g in offspring birthweight, respectively but not thereafter. CONCLUSIONS: Maternal and paternal birthweight and growth from birth to 2 year each predict offspring birthweight. Maternal growth from MC-adulthood, relative weight from 2-MC and MC-adulthood also predict offspring birthweight. These findings suggest that shared genes and/or adequate nutrition during early life for both parents may confer benefits to the next generation, and highlight the importance of maternal height and weight prior to conception. The stronger matrilineal than patrilineal relationships with offspring birth weight are consistent with the hypothesis that improving the early growth conditions of young females can improve birth outcomes in the next generation.

Size at birth, morning cortisol and cardiometabolic risk markers in healthy Indian children.

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

Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians.

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

Growth from birth to adulthood and peak bone mass and density data from the New Delhi Birth Cohort.

UNLABELLED: Growth in early life may predict adult bone health. Our data showed that greater height and body mass index (BMI) gain in utero and infancy are associated with higher peak bone mass, and greater BMI gain in childhood/adolescence with higher peak bone density. These associations are mediated by attained adult height and BMI. INTRODUCTION: To study the relationship of height and BMI during childhood with adult bone mineral content (BMC), areal density (aBMD) and apparent density (BMAD, estimated volumetric density). METHODS: Participants comprised 565 men and women aged 33-39 years from the New Delhi Birth Cohort, India, whose weight and height were recorded at birth and annually during infancy (0-2 years), childhood (2-11 years) and adolescence (11 years-adult). Lumbar spine, femoral neck and forearm BMC and aBMD were measured using dual X-ray absorptiometry; lumbar spine and femoral neck BMAD were calculated. RESULTS: Birth length, and height and height gain during infancy, childhood and adolescence were positively correlated with adult BMC (p≤0.01 all sites except birth length with femoral neck). Correlations increased with height from birth to 6 years, then remained constant for later height measurements. There were no associations with BMAD. BMI at birth, and during childhood and adolescence was also positively correlated with BMC (p < 0.01 all sites). BMI at 11 years, and BMI gain in childhood and adolescence, were correlated with aBMD and BMAD (p < 0.001 for all); these correlations strengthened with increasing age of BMI measurement. The associations with height and BMI in early life became non-significant after adjustment for adult height and BMI. CONCLUSIONS: Greater skeletal growth and BMI gain in utero and during infancy are associated with higher peak BMC, and greater BMI gain in childhood and adolescence is associated with higher peak aBMD and BMAD. These associations are mediated by the attainment of adult height and BMI, respectively.

Childhood Head Growth and Educational Attainment in an Indian Cohort.

BACKGROUND: There is minimal information about the association of head growth at different stages of childhood with cognitive ability. OBJECTIVE: To determine the relationship of newborn head size and head growth during infancy, childhood and adolescence with attained education, a proxy for cognitive ability. STUDY DESIGN: Prospective birth cohort study. SETTING: Married women living in South Delhi between 1969 and 1973. PARTICIPANTS: The New Delhi Birth Cohort study followed up 8030 newborns born in 1969-1973 with head circumference, weight and height measurements at birth and 6-12 monthly until adulthood. Of these, 1526 men and women were followed up at the age of 26-32 years. OUTCOMES: Association between years of schooling, as an indicator of cognitive ability, and newborn head circumference and conditional measures of head growth during infancy, childhood and adolescence. RESULTS: In unadjusted analyses, newborn head size was positively associated with years of education [(b (95% CI)=0.30 (0.14 to 0.47) years per SD head circumference], as was head growth from birth to 6 months [b (95% CI)=0.44 (0.28 to 0.60) years per SD conditional head growth], 6 months to 2 years [b (95% CI)=0.31 (0.15 to 0.47) years per SD conditional head growth] and 2 to 11 years [b (95% CI)=0.20 (0.03 to 0.36) years per SD conditional head growth]. There were similar findings for height and body mass index (BMI). In the adjusted model containing all growth measures, gestational age, and socio-economic status (SES) at birth as predictors, only SES was positively associated with educational attainment. CONCLUSION: Educational attainment in this population is positively associated with socioeconomic status and its influence on inter-related early life (fetal, infant and childhood) factors like nutritional status and brain growth.

Glucose tolerance and insulin resistance in Indian children: relationship to infant feeding pattern.

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

Childhood cognitive ability: relationship to gestational diabetes mellitus in India.

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

Low plasma vitamin B12 in pregnancy is associated with gestational 'diabesity' and later diabetes.

AIMS/HYPOTHESIS: This study was designed to test the hypothesis that low plasma vitamin B(12) concentrations combined with high folate concentrations in pregnancy are associated with a higher incidence of gestational diabetes (GDM) and later diabetes. METHODS: Women (N = 785) attending the antenatal clinics of one hospital in Mysore, India, had their anthropometry, insulin resistance (homeostasis model assessment-2) and glucose tolerance assessed at 30 weeks' gestation (100 g oral glucose tolerance test; Carpenter-Coustan criteria) and at 5 years after delivery (75 g OGTT; WHO, 1999). Gestational vitamin B(12) and folate concentrations were measured in stored plasma samples. RESULTS: Low vitamin B(12) concentrations (<150 pmol/l, B(12) deficiency) were observed in 43% of women and low folate concentrations (<7 nmol/l) in 4%. B(12)-deficient women had higher body mass index (p < 0.001), sum of skinfold thickness (p < 0.001), insulin resistance (p = 0.02) and a higher incidence of GDM (8.7% vs 4.6%; OR 2.1, p = 0.02; p = 0.1 after adjusting for BMI) than non-deficient women. Among B(12)-deficient women, the incidence of GDM increased with folate concentration (5.4%, 10.5%, 10.9% from lowest to highest tertile, p = 0.04; p for interaction = 0.2). Vitamin B(12) deficiency during pregnancy was positively associated with skinfold thickness, insulin resistance (p < 0.05) and diabetes prevalence at 5 year follow-up (p = 0.009; p = 0.008 after adjusting for BMI). The association with diabetes became non-significant after excluding women with previous GDM (p = 0.06). CONCLUSIONS/INTERPRETATION: Maternal vitamin B(12) deficiency is associated with increased adiposity and, in turn, with insulin resistance and GDM. Vitamin B(12) deficiency may be an important factor underlying the high risk of 'diabesity' in south Asian Indians.

FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians.

AIMS AND HYPOTHESIS: Variants of the FTO (fat mass and obesity associated) gene are associated with obesity and type 2 diabetes in white Europeans, but these associations are not consistent in Asians. A recent study in Asian Indian Sikhs showed an association with type 2 diabetes that did not seem to be mediated through BMI. We studied the association of FTO variants with type 2 diabetes and measures of obesity in South Asian Indians in Pune. METHODS: We genotyped, by sequencing, two single nucleotide polymorphisms, rs9939609 and rs7191344, in the FTO gene in 1,453 type 2 diabetes patients and 1,361 controls from Pune, Western India and a further 961 population-based individuals from Mysore, South India. RESULTS: We observed a strong association of the minor allele A at rs9939609 with type 2 diabetes (OR per allele 1.26; 95% CI 1.13-1.40; p = 3 x 10(-5)). The variant was also associated with BMI but this association appeared to be weaker (0.06 SDs; 95% CI 0.01-0.10) than the previously reported effect in Europeans (0.10 SDs; 95% CI 0.09-0.12; heterogeneity p = 0.06). Unlike in the Europeans, the association with type 2 diabetes remained significant after adjusting for BMI (OR per allele for type 2 diabetes 1.21; 95% CI 1.06-1.37; p = 4.0 x 10(-3)), and also for waist circumference and other anthropometric variables. CONCLUSIONS: Our study replicates the strong association of FTO variants with type 2 diabetes and similar to the study in North Indians Sikhs, shows that this association may not be entirely mediated through BMI. This could imply underlying differences between Indians and Europeans in the mechanisms linking body size with type 2 diabetes.

Neonatal anthropometry: thin-fat phenotype in fourth to fifth generation South Asian neonates in Surinam.

We assessed whether the earlier described 'thin-fat phenotype' is present in Surinam South Asian babies of the fourth to fifth generation after migration from India. In this observational study we collected data from 39 South Asian term neonates and their mothers in Paramaribo, Surinam. We compared the following data with data from an earlier study in Southampton, UK (338 neonates) and in Pune, India (631 neonates): maternal body mass index, neonatal weight, length, head, mid-upper arm and abdominal circumferences and subscapular skinfold thickness. The mothers in Paramaribo were older than the Southampton mothers; their body mass index was comparable. Mean birth weight was 3159 g (Southampton: 3494 g; Pune: 2666 g). Compared with Southampton babies, the Paramaribo babies were smaller in nearly all body measurements, the smallest being abdominal circumference at the umbilicus level (s.d. score: -1.62; 95% confidence interval (CI): -2.07 to -1.16) and mid-upper arm circumference (s.d. score: -1.08; 95% CI: -1.46 to -0.69). In contrast, subscapular skinfold thickness was similar (s.d. score: +0.08; 95% CI: -0.24 to +0.55). Except for subscapular skinfold thickness and length, all neonatal measurements were intermediate between those from Southampton and Pune. The thin-fat phenotype is preserved in Surinam South Asian neonates of the fourth to fifth generation after migration from India.

Bone mass in Indian children--relationships to maternal nutritional status and diet during pregnancy: the Pune Maternal Nutrition Study.

CONTEXT/OBJECTIVE: Bone mass is influenced by genetic and environmental factors. Recent studies have highlighted associations between maternal nutritional status during pregnancy and bone mass in the offspring. We hypothesized that maternal calcium intakes and circulating micronutrients during pregnancy are related to bone mass in Indian children. DESIGN/SETTING/PARTICIPANTS/MAIN OUTCOME MEASURES: Nutritional status was measured at 18 and 28 wk gestation in 797 pregnant rural Indian women. Measurements included anthropometry, dietary intakes (24-h recall and food frequency questionnaire), physical workload (questionnaire), and circulating micronutrients (red cell folate and plasma ferritin, vitamin B12, and vitamin C). Six years postnatally, total body and total spine bone mineral content and bone mineral density (BMD) were measured using dual-energy x-ray absorptiometry (DXA) in the children (n = 698 of 762 live births) and both parents. RESULTS: Both parents' DXA measurements were positively correlated with the equivalent measurements in the children (P < 0.001 for all). The strength of these correlations was similar for fathers and mothers. Children of mothers who had a higher frequency of intake of calcium-rich foods during pregnancy (milk, milk products, pulses, non-vegetarian foods, green leafy vegetables, fruit) had higher total and spine bone mineral content and BMD, and children of mothers with higher folate status at 28 wk gestation had higher total and spine BMD, independent of parental size and DXA measurements. CONCLUSIONS: Modifiable maternal nutritional factors may influence bone health in the offspring. Fathers play a role in determining their child's bone mass, possibly through genetic mechanisms or through shared environment.

Truncal adiposity is present at birth and in early childhood in South Indian children.

OBJECTIVES: Muscle-thin but adipose ('thin-fat') body composition of south Asian adults contributes to their high risk of type 2 diabetes. Studies in Pune, India showed that this phenotype is present at birth. We aimed to determine if south Indian babies have a 'thin-fat' phenotype and if this persists in childhood. DESIGN: Prospective cohort study. SETTING: Holdsworth Memorial Hospital, Mysore, India. SUBJECTS: Children (n = 663) whose mothers were recruited from the antenatal clinics. METHODS: Weight, length, head, mid-upper-arm, abdominal circumferences; triceps and subscapular skinfolds were measured at birth, one and four years, and compared with white Caucasian babies born in Southampton, UK (birth), and UK and Dutch growth standards (one and four years). RESULTS: Mysore babies were lighter (2983 g vs 3472 g; -1.10 SD, CI -1.16, -1.02) and smaller in all body measurements than UK neonates (P < 0.001). The deficit was greatest for mid-upper-arm (-1.07 SD), head (-0.89 SD) and abdominal circumferences (-0.73 SD), and least for length (-0.25 SD) and subscapular skinfold thickness (-0.19 SD). Predictors of skinfold thickness were maternal body mass index (P < 0.001) and socio-economic status (P = 0.05). At four years, subscapular skinfold thickness was larger than UK (+0.18 SD, CI +0.11, +0.25; P < 0.001) and Dutch standards (+0.61 SD, CI +0.51, +0.71; P < 0.001), despite all other body measurements remaining smaller. Predictors of 4-year skinfold thickness were neonatal skinfold thickness (P = 0.001) and maternal insulin concentrations (P = 0.05). CONCLUSIONS: Mysore newborns have a 'thin-fat' phenotype. This may reflect the action of genes and/or the 'maternal environment'. The phenotype persists in childhood, and may be the forerunner of a diabetogenic adult phenotype.

Body size and body composition: a comparison of children in India and the UK through infancy and early childhood.

BACKGROUND: Indian babies are characterised by the 'thin-fat phenotype' which comprises a 'muscle-thin but adipose' body composition compared with European babies. This body phenotype is of concern because it is associated with an increased risk of diabetes and cardiovascular disease. We examined whether the 'thin-fat phenotype' persists through early childhood, comparing Indian children with white Caucasians in the UK at birth, infancy and childhood, using comparable measurement protocols. METHODS: We used data from two cohorts, the Pune Maternal Nutrition Study (N=631) and the Southampton Women's Survey (N=2643). Measurements of weight, head circumference, mid-upper arm circumference, height, triceps and subscapular skinfold thickness were compared at birth, 1, 2, 3 and 6 years of age. SD scores were generated for the Pune children, using the Southampton children as a reference. Generalised estimating equations were used to examine the changes in SD scores across the children's ages. RESULTS: The Indian children were smaller at birth in all body measurements than the Southampton children and became relatively even smaller from birth to 2 years, before 'catching up' to some extent at 3 years, and more so by 6 years. The deficit for both skinfolds was markedly less than for other measurements at all ages; triceps skinfold showed the least difference between the two cohorts at birth, and subscapular skinfold at all ages after birth. CONCLUSIONS: The 'thin-fat phenotype' previously found in Indian newborns, remains through infancy and early childhood. Despite being shorter and lighter than UK children, Indian children are relatively adipose.

Does birth weight predict adult serum cortisol concentrations? Twenty-four-hour profiles in the United kingdom 1920-1930 Hertfordshire Birth Cohort.

Low birth weight and weight in infancy are associated with adult insulin resistance and type 2 diabetes. A proposed mechanism is programming of the hypothalamic-pituitary-adrenal axis by intrauterine undernutrition, leading to persistently elevated cortisol concentrations. We examined 24-h serum cortisol profiles (samples every 20 min) in 83 healthy elderly men and women whose birth weight and infant weight were recorded. Variables derived from these profiles included trough, peak, and area under the curve concentrations; the time of onset, rate of rise, duration, and peak of the early morning cortisol rise; postprandial secretion; and regularity of secretion (approximate entropy). None of these parameters was related to birth weight, weight at 1 yr, or change in weight SD score between birth and 1 yr. Consistent with other studies, 0730-0900 h cortisol concentrations were higher in men and women of lower birth weight, although this was not statistically significant (P = 0.08). Our findings do not support the hypothesis that reduced intrauterine and infant growth are associated with continuously raised cortisol concentrations in old age. Programmed effects on the hypothalamic-pituitary-adrenal axis may influence reactivity rather than resting secretion.

Growth hormone predicts bone density in elderly women.

Evidence is accumulating that the risk of osteoporosis may be influenced by environmental factors during intrauterine and early postnatal life; such programming might be mediated through modification of the GH/IGF-1 axis during critical periods in its development. To address this issue, we explored the relationships among birth weight, circulating GH profile, bone density, and bone loss rate in a group of British women. The study population consisted of 38 women 60-75 years old resident in Hertfordshire for whom detailed birth records were available. Twenty-four-hour circulating GH profiles were obtained during an inpatient stay on a metabolic ward, after an overnight rest. The circulating profile of GH was characterised by estimating the peak, median, trough, and total concentrations from 72 samples measured sequentially over 24 h in each subject. Bone mineral density was assessed at the lumbar spine and femoral neck at baseline and at follow-up 4 years later. Lumbar spine bone mineral content (BMC) and density (BMD) were positively associated with all measures of GH concentration, although relationships were strongest for BMC with trough GH (r = 0.47, P < 0.01). Associations persisted after adjustment for age, body mass index, smoking, alcohol consumption, physical activity, and osteoarthritis score in multiple regression models. However, associations of GH concentration with femoral neck BMC were weak, and there was no association between any measure of GH concentration and bone loss at either site. Total (integrated) daily GH concentration tended to increase (P = 0.08) with rising birth weight, while IGF-1 concentration fell (P = 0.05) with rising birth weight, suggesting a role for the GH/IGF-1 axis in the programming of adult bone mass among women.

Contribution of the umbilical cord and membranes to untrimmed placental weight.

The extent of placental trimming before weighing varies within and between obstetric units. Quantification of the contribution of the umbilical cord and membranes to placental weight is required to enable measurements to be compared across populations. In a sample of 50 neonates born in Southampton, placentae of liveborn singletons were weighed three times; after removing any obvious blood clots, after cutting the umbilical cord, and after stripping both the foetal and maternal membranes. The correlation between untrimmed and trimmed placental weight was 0.98. Since the combined weight of the cord and membranes increased with increasing trimmed weight (correlation=0.54), the percentage rather than absolute difference between untrimmed and trimmed weight was calculated. The median difference between untrimmed and trimmed weight was 16 per cent. No association was found between the percentage difference and infant sex, duration of gestation, birthweight, maternal age, labour onset and duration, and presentation at delivery. However, the mode of delivery had a significant effect on this difference; medians for vaginal and Caesarean section deliveries were 19 per cent and 14 per cent respectively.

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

OBJECTIVE: To describe the relationship of the mother's 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.