Cord IGF-I concentrations in Indian newborns: associations with neonatal body composition and maternal determinants.

BACKGROUND: Indian newborns have been described as 'thin-fat' compared with European babies, but little is known about how this phenotype relates to the foetal growth factor IGF-I (insulin-like growth factor I) or its binding protein IGFBP-3. OBJECTIVE: To assess cord IGF-I and IGFBP-3 concentrations in a sample of Indian newborns and evaluate their associations with neonatal adiposity and maternal factors. METHODS: A prospective cohort study of 146 pregnant mothers with dietary, anthropometric and biochemical measurements at 28 and 34 weeks gestation. Neonatal weight, length, skin-folds, circumferences, and cord blood IGF-I and IGFBP-3 concentrations were measured at birth. RESULTS: Average cord IGF-I and IGFBP-3 concentrations were 46.6 (2.2) and 1269.4 (41) ng mL(-1) , respectively. Girls had higher mean IGF-I than boys (51.4 ng mL(-1) vs. 42.9 ng mL(-1) ; P < 0.03), but IGFBP-3 did not differ. Cord IGF-I was positively correlated with all birth size measures except length, and most strongly with neonatal sum-of-skin-folds (r = 0.50, P < 0.001). IGFBP-3 was positively correlated with ponderal index, sum-of-skin-folds and placenta weight (r = 0.21, 0.19, 0.16, respectively; P < 0.05). Of maternal demographic and anthropometric characteristics, only parity was correlated with cord IGF-I (r = 0.27, P < 0.001). Among dietary behaviours, maternal daily milk intake at 34 weeks gestation predicted higher cord IGF-I compared to no-milk intake (51.8 ng mL(-1) vs. 36.5 ng mL(-1) , P < 0.01) after controlling for maternal characteristics, placental weight, and newborn gestational age, sex, weight and sum-of-skin-folds. Sum-of-skin-folds were positively associated with cord IGF-I in this multivariate model (57.3 ng mL(-1) vs. 35.1 ng mL(-1) for highest and lowest sum-of skin-fold quartile, P < 0.001). IGFBP-3 did not show significant relationships with these covariates. CONCLUSION: In this Indian study, cord IGF-I concentration was associated with greater adiposity among newborns. Maternal milk intake may play a role in this relationship.

Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study.

AIMS/HYPOTHESIS: Raised maternal plasma total homocysteine (tHcy) concentrations predict small size at birth, which is a risk factor for type 2 diabetes mellitus. We studied the association between maternal vitamin B12, folate and tHcy status during pregnancy, and offspring adiposity and insulin resistance at 6 years. METHODS: In the Pune Maternal Nutrition Study we studied 700 consecutive eligible pregnant women in six villages. We measured maternal nutritional intake and circulating concentrations of folate, vitamin B12, tHcy and methylmalonic acid (MMA) at 18 and 28 weeks of gestation. These were correlated with offspring anthropometry, body composition (dual-energy X-ray absorptiometry scan) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-R]) at 6 years. RESULTS: Two-thirds of mothers had low vitamin B12 (<150 pmol/l), 90% had high MMA (>0.26 micromol/l) and 30% had raised tHcy concentrations (>10 micromol/l); only one had a low erythrocyte folate concentration. Although short and thin (BMI), the 6-year-old children were relatively adipose compared with the UK standards (skinfold thicknesses). Higher maternal erythrocyte folate concentrations at 28 weeks predicted higher offspring adiposity and higher HOMA-R (both p < 0.01). Low maternal vitamin B12 (18 weeks; p = 0.03) predicted higher HOMA-R in the children. The offspring of mothers with a combination of high folate and low vitamin B12 concentrations were the most insulin resistant. CONCLUSIONS/INTERPRETATION: Low maternal vitamin B12 and high folate status may contribute to the epidemic of adiposity and type 2 diabetes in India.

Newborn size, infant and childhood growth, and body composition and cardiovascular disease risk factors at the age of 6 years: the Pune Maternal Nutrition Study.

OBJECTIVE: To study associations of size and body proportions at birth, and growth during infancy and childhood, to body composition and cardiovascular disease (CVD) risk factors at the age of 6 years. DESIGN: The Pune Maternal Nutrition Study, a prospective population-based study of maternal nutrition and CVD risk in rural Indian children. METHODS: Body composition and CVD risk factors measured in 698 children at 6 years were related to body proportions and growth from birth. MEASUREMENTS: Anthropometry was performed every 6 months from birth. At 6 years, fat and lean mass (dual X-ray absorptiometry) and CVD risk factors (insulin resistance, blood pressure, glucose tolerance, plasma lipids) were measured. RESULTS: Compared with international references (NCHS, WHO) the children were short, light and thin (mean weight <-1.0 s.d. at all ages). Larger size and faster growth in all body measurements from birth to 6 years predicted higher lean and fat mass at 6 years. Weight and height predicted lean mass more strongly than fat mass, mid-upper arm circumference (MUAC) predicted them both approximately equally and skinfolds predicted only fat mass. Neither birthweight nor the 'thin-fat' newborn phenotype, was related to CVD risk factors. Smaller MUAC at 6 months predicted higher insulin resistance (P<0.001) but larger MUAC at 1 year predicted higher systolic blood pressure (P<0.001). After infancy, higher weight, height, MUAC and skinfolds, and faster growth of all these parameters were associated with increased CVD risk factors. CONCLUSIONS: Slower muscle growth in infancy may increase insulin resistance but reduce blood pressure. After infancy larger size and faster growth of all body measurements are associated with a more adverse childhood CVD risk factor profile. These rural Indian children are growing below international 'norms' for body size and studies are required in other populations to determine the generalizability of the findings.

Characteristics of gestational diabetic mothers and their babies in an Indian diabetes clinic.

AIMS AND OBJECTIVES: To compare clinical and metabolic features of mothers with gestational diabetes (GDM) and their offspring with those in non-diabetic pregnancies at the King Edward Memorial Hospital, Pune, India. MATERIALS AND METHODS: Antenatal information was obtained from hospital records. GDM was diagnosed by 75 g OGTT (Oral Glucose Tolerance Test) in clinically high-risk women. Anthropometric measurements of mother and the babies were recorded within 24h of delivery and a maternal blood sample collected for hematological and biochemical measurements. RESULTS: Between the period Jan 1998 to December 2003,265 women with gestational diabetes were treated in our Unit. Forty nine percent had first-degree relatives with diabetes. Compared to non-diabetic mothers (n=215) GDM mothers were older (29.0 vs. 26.0y, p<0.001), more obese (body mass index- BMI 26.0 vs. 22.0 kg/m2, p<0.001), centrally obese (Waist hip ratio-WHR 0.89 vs 0.86, p<0.001), adipose (sum of 4 skinfolds 98.4 vs. 61.4 mm, p<0.001) and had higher blood pressure (127/80 vs. 122/70 mmHg, p<0.001). GDM mothers had higher concentrations of plasma triglycerides (195.0 vs. 153.0 mg/dl, p<0.01); blood hemoglobin (11.7 vs 10.9 g/dl, p<0.001) and higher platelet count but lower concentration of HDL cholesterol and albumin. Sixty percent GDM mothers and 34% of non-diabetic mothers were delivered by caesarean-section, 23% of GDM mothers delivered pre term (<37 wk). Despite the smaller gestation, babies of GDM mothers were heavier (BW 2950.0 vs. 2824.0g, p<0.001, adjusted for gender), longer (48.9 vs. 48.0 cm, p<0.01) and more adipose (sum of 2 skinfolds 10.5 vs. 8.5 mm). Only 5% of babies born to GDM mothers weighed > 4000 g but 30% were >90th centile of birth weight of babies born to non-diabetic mothers. Babies of GDM mothers suffered higher neonatal morbidity. CONCLUSIONS: GDM mothers in urban India are more obese and more adipose than non-diabetic mothers, frequently have a family history of diabetes and show metabolic features of insulin resistance syndrome, suggesting high cardiovascular risk. Neonates of GDM mothers are heavier, longer and more adipose than those born to non-diabetic mothers, and suffer higher neonatal morbidity.