The REVAMP study: research exploring various aspects and mechanisms in preeclampsia: study protocol.

BACKGROUND: Preeclampsia is a major cause of maternal, fetal and neonatal morbidity and mortality, particularly in developing countries. Considering the burden of preeclampsia and its associated complications, it is important to understand the underlying risk factors and mechanisms involved in its etiology. There is considerable interest in the potential for dietary long chain polyunsaturated fatty acids (LCPUFA) as a therapeutic intervention to prevent preeclampsia, as they are involved in angiogenesis, oxidative stress, and inflammatory pathways. METHODS: The REVAMP study (Research Exploring Various Aspects and Mechanisms in Preeclampsia) follows a cohort of pregnant women from early pregnancy until delivery to examine longitudinally the associations of maternal LCPUFA with clinical outcome in preeclampsia. A multisite centre for advanced research was established and pregnant women coming to Bharati hospital and Gupte hospital, Pune, India for their first antenatal visit are recruited and followed up at 11-14 weeks, 18-22 weeks, 26-28 weeks, and at delivery. Their personal, obstetric, clinical, and family history are recorded. Anthropometric measures (height, weight), food frequency questionnaire (FFQ), physical activity, socioeconomic status, fetal ultrasonography, and color Doppler measures are recorded at different time points across gestation. Maternal blood at all time points, cord blood, and placenta at delivery are collected, processed and stored at - 80 °C. The children's anthropometry is assessed serially up to the age of 2 years, when their neurodevelopmental scores will be assessed. DISCUSSION: This study will help in early identification of pregnant women who are at risk of developing preeclampsia. The prospective design of the study for the first time will establish the role of LCPUFA in understanding the underlying biochemical and molecular mechanisms involved in preeclampsia and their association with developmental programming in children.

Higher glucose, insulin and insulin resistance (HOMA-IR) in childhood predict adverse cardiovascular risk in early adulthood: the Pune Children's Study.

AIMS/HYPOTHESIS: The Pune Children's Study aimed to test whether glucose and insulin measurements in childhood predict cardiovascular risk factors in young adulthood. METHODS: We followed up 357 participants (75% follow-up) at 21 years of age who had undergone detailed measurements at 8 years of age (glucose, insulin, HOMA-IR and other indices). Oral glucose tolerance, anthropometry, plasma lipids, BP, carotid intima-media thickness (IMT) and arterial pulse wave velocity (PWV) were measured at 21 years. RESULTS: Higher fasting glucose, insulin and HOMA-IR at 8 years predicted higher glucose, insulin, HOMA-IR, BP, lipids and IMT at 21 years. A 1 SD change in 8 year variables was associated with a 0.10-0.27 SD change at 21 years independently of obesity/adiposity at 8 years of age. A greater rise in glucose-insulin variables between 8 and 21 years was associated with higher cardiovascular risk factors, including PWV. Participants whose HOMA-IR measurement remained in the highest quartile (n = 31) had a more adverse cardiovascular risk profile compared with those whose HOMA-IR measurement remained in the lowest quartile (n = 28). CONCLUSIONS/INTERPRETATION: Prepubertal glucose-insulin metabolism is associated with adult cardiovascular risk and markers of atherosclerosis. Our results support interventions to improve glucose-insulin metabolism in childhood to reduce cardiovascular risk in later life.

Arterial stiffness in obese children: Role of adiposity and physical activity.

OBJECTIVE: To explore association of adiposity and physical activity with arterial stiffness and to propose optimal waist circumference cutoffs, corresponding to 90(th) percentile of NHANES (National Health and Nutrition Examination Survey) for Indian children and adolescents. MATERIALS AND METHODS: Data on weight, height, waist circumference, physical activity and right Carotid artery Intima-Media-Thickness (CIMT), pulse wave velocity (PWV), elasticity modulus (Ep), stiffness index(ß), arterial compliance (AC) were assessed in 250 children (72 normal-weight and 178 overweight/obese) aged 6-17 years from Pune city, India. Body composition was measured using Dual energy X-ray absorptiometry. RESULTS: Total, 37.1% normal-weight and 98.2% overweight/obese children had high adiposity (>95(th) body fat percentile). Positive association of PWV and Ep (r = 0.5) also ß(r = 0.25) with BMI (Body Mass Index), waist circumference and body fat (P < 0.05) was observed. Physical activity was inversely associated with PWV (r =-0.2), ß(r =-0.13), Ep (r =-0.12) and positively with AC (r = 0.12) (P < 0.05). PWV significantly increased with increasing body fat for each tertile of physical activity (P < 0.05). Regression analysis revealed waist circumference, BMI, body fat and physical activity as independent associates for PWV after adjusting for age (P < 0.05). The cutoff of waist circumference yielding sensitivity and specificity for predicting the risk of high PWV was (-0.43, -0.44) for boys and girls with sensitivity in boys (girls) of 78% (87%) and specificity in boys (girls) 51% (70%). The observed cutoffs are less than the NHANES-III cutoff values of waist circumference for 90(th) percentiles according to age and sex. CONCLUSION: High adiposity and low physical activity are adversely related to arterial stiffness in Indian children.

Metabolic risk factors and arterial stiffness in Indian children of parents with metabolic syndrome.

OBJECTIVE: To investigate the possible association between metabolic syndrome (MS) and arterial stiffness in Indian children with parental MS status. METHODS: A cross-sectional study was conducted in 140 overweight/obese and 60 normal-weight Indian children (mean age, 11.4 ± 2.8 years) along with one of their parents during 2008-2009. Data on weight, height, blood pressure, serum lipids, zinc, insulin, and glucose were collected. Intima media thickness (CIMT) and stiffness parameters were assessed in the right carotid artery. Physical activity and diet were assessed using structured questionnaires. Body composition was measured using dual-energy x-ray absorptiometry. RESULTS: A gradual increase in the percentage of MS children with an increasing number of MS components in parents was observed. Mean values for arterial stiffness, pulse wave velocity, and elastic modulus were significantly higher in MS children of MS parents than in MS children of normal parents (p < 0.05). A significant correlation was observed for lifestyle, metabolic, and arterial parameters among child-parent pairs (p < 0.05). Multiple logistic regression revealed that children's CIMT and arterial stiffness were significantly associated (p < 0.01) with their serum levels of triglycerides, high-density lipoprotein, and zinc, as well as with parental MS-CIMT. CONCLUSION: Parental MS status and lifestyle factors increase the risk of MS and arterial abnormalities in children.

Diet and exercise intervention, with special reference to micronutrients, reduces cardiometabolic risk in overweight children.

OBJECTIVE: To study the effect of lifestyle intervention in the presence of multivitamin-zinc supplementation in improving the cardiometabolic status of overweight children. MATERIALS AND METHODS: Data were evaluated in 74 overweight children (11.3 ± 2.9 years) randomly assigned to three groups of intervention for 4 months as follows: group A: diet-exercise counseling with multivitamin-zinc supplementation; group B: diet-exercise counseling; and group C: placebo. Anthropometric, biochemical, carotid arterial and lifestyle parameters were assessed. RESULTS: Lifestyle counseling resulted in significant reduction in inactivity, energy and fat intakes and increase in micronutrient density of diets and physical activity in groups A and B in comparison to group C. Percent decline in body fat was more in group A than in groups B and C. Percent change in triglycerides (-13.7%) was significantly higher in group A than in groups B (-5.9%) and C (5.7%). Pulse wave velocity and elasticity modulus reduced and arterial compliance improved significantly in group A than in group B. CONCLUSION: Multivitamin-zinc supplementation with lifestyle intervention has a positive effect of on the cardiometabolic status of overweight children.

Macroorchidism in an Indian boy with McCune-Albright syndrome.

McCune-Albright syndrome (MAS) is defined by the clinical triad of fibrous dysplasia of bone (FD), café-au-lait spots and precocious puberty (PP). It is a rare disease with estimated prevalence between 1/100,000 and 1/1,000,000. The authors report a case of MAS in an Indian boy who had history of unilateral macroorchidism (but no other signs of MAS) since birth, then presented with PP, FD and café-au-lait spots at 6 years of age. On examination he had asymmetry of the face, café-au-lait spots and signs of sexual precocity with a right testicular volume of 25 ml (left 8 ml). Investigations revealed suppressed gonadotropins with elevated testosterone levels. Skeletal survey showed dysplastic changes involving multiple bones and advanced bone age. Reports of MAS in a boy with unilateral macroorchidism are scarce. Thus, unilateral macroorchidism at birth in a baby may be a feature of MAS and should be followed up with care.

Maternal and paternal height and BMI and patterns of fetal growth: the Pune Maternal Nutrition Study.

We examined the differential associations of each parent's height and BMI with fetal growth, and examined the pattern of the associations through gestation. Data are from 557 term pregnancies in the Pune Maternal Nutrition Study. Size and conditional growth outcomes from 17 to 29 weeks to birth were derived from ultrasound and birth measures of head circumference, abdominal circumference, femur length and placental volume (at 17 weeks only). Parental height was positively associated with fetal head circumference and femur length. The associations with paternal height were detectible earlier in gestation (17-29 weeks) compared to the associations with maternal height. Fetuses of mothers with a higher BMI had a smaller mean head circumference at 17 weeks, but caught up to have larger head circumference at birth. Maternal but not paternal BMI, and paternal but not maternal height, were positively associated with placental volume. The opposing associations of placenta and fetal head growth with maternal BMI at 17 weeks could indicate prioritisation of early placental development, possibly as a strategy to facilitate growth in late gestation. This study has highlighted how the pattern of parental-fetal associations varies over gestation. Further follow-up will determine whether and how these variations in fetal/placental development relate to health in later life.

Patterns of fetal growth in a rural Indian cohort and comparison with a Western European population: data from the Pune maternal nutrition study.

OBJECTIVE: The purpose of this study was to describe fetal size on sonography in a rural Indian population and compare it with those in European and urban Indian populations. Methods. Participants were from the Pune Maternal Nutrition Study of India. Fetal growth curves were constructed from serial ultrasound scans at approximately 18, 30, and 36 weeks' gestation in 653 singleton pregnancies. Measurements included femur length (FL), abdominal circumference (AC), biparietal diameter (BPD), and occipitofrontal diameter, 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 and -1.30 SD, respectively), whereas FL and HC were more comparable (-0.77 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). Sonography at 18 weeks underestimated gestational age compared with the last menstrual period date by a median of -1.4 (interquartile range, -4.6, 1.8) days. The Pune fetuses were smaller, even at the first scan, than the urban Vellore sample. CONCLUSIONS: Fetal size was smaller in a rural Indian population than in European and urban Indian populations, even in mid pregnancy. The deficit varied for different fetal measurements; it was greatest for AC and BPD and least for FL and HC.