The Pune Rural Intervention in Young Adolescents (PRIYA) study: design and methods of a randomised controlled trial

BACKGROUND: The Pune Maternal Nutrition Study (PMNS) was established to prospectively study the relationship of maternal nutrition to fetal growth and later cardiometabolic risk in the offspring. High homocysteine and low vitamin B12 levels in pregnancy predicted lower birthweight and higher insulin resistance at 6 years in the offspring. B12 deficiency was widespread in this population, due to low dietary intake. We therefore commenced a community-based intervention study with the underlying hypothesis that vitamin B12 supplementation of adolescent members of the PMNS cohort will improve birth weight, B12 status, and reduce future diabetes risk, in their offspring. METHODS: The individually randomised controlled trial commenced in September 2012, with boys and girls randomized into 3 groups, to receive daily for at least 3 years or until the birth of their first child: 1) vitamin B12 2 μg; or 2) vitamin B12 2 μg plus multiple micronutrients (MMN) plus 20 g of milk powder or 3) placebo. Iron and folic acid is given to all participants. Compliance is assessed by monthly supplement counts. Adverse events are recorded using a standardised questionnaire. The primary outcome is cord blood B12 concentration; based on 180–200 pregnancies in the girls, the study has ~80% power to detect a 0.5 SD change in newborn B12, in the B12 supplementation groups compared with controls, at the 5% significance level. Primary analysis will be by intention to treat. DISCUSSION: Our study tests a primordial prevention strategy through an intergenerational intervention started pre-conceptionally in both boys and girls using physiological doses of micronutrients to improve immediate pregnancy-related and long-term cardio metabolic outcomes. The results will have significant public health implications in a setting with widespread B12 deficiency but relative folate sufficiency. The randomised controlled trial design allows us to be confident that our findings will be causally relevant. TRIAL REGISTRATION: ISRCTN 32921044, applied on 14/09/2012. CTRI 2012/12/003212, registered on 02/12/2012. Retrospectively registered

What shapes adolescents’ diet and physical activity habits in rural Kokan, India? Adolescents’ and caregivers’ perspectives

Objective:To explore, adolescents’ and caregivers’ perspectives, about shaping of diet and physical activity habits in rural Konkan, India.Design:Five focus group discussions (FGD) were conducted with adolescents and two with caregivers. Data were analysed using thematic analysis.Setting:FGD were conducted in secondary schools located in remote rural villages in the Ratnagiri district, Konkan region, Maharashtra, India.Participants:Forty-eight adolescents were recruited including twenty younger (10–12 years) and twenty-eight older (15–17 years) adolescents. Sixteen caregivers (all mothers) were also recruited.Results:Three themes emerged from discussion: (i) adolescents’ and caregivers’ perceptions of the barriers to healthy diet and physical activity, (ii) acceptance of the status quo and (iii) salience of social and economic transition. Adolescents’ basic dietary and physical activity needs were rarely met by the resources available and infrastructure of the villages. There were few opportunities for physical activity, other than performing household chores and walking long distances to school. Adolescents and their caregivers accepted these limitations and their inability to change them. Increased use of digital media and availability of junk foods marked the beginning of a social and economic transition.Conclusion:FGD with adolescents and their caregivers provided insights into factors influencing adolescent diet and physical activity in rural India. Scarcity of basic resources limited adolescent diet and opportunities for physical activity. To achieve current nutritional and physical activity recommendations for adolescents requires improved infrastructure in these settings, changes which may accompany the current Indian social and economic transition

Patterns of fetal growth in a rural Indian cohort and 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 1(st) 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

Birth weight, childhood and adolescent growth and diabetes risk factors in 21-year old Asian Indians: The Pune Children’s Study

Our objective was to investigate associations of body size (birth weight and body mass index (BMI)) and growth in height, body fat (adiposity) and lean mass during childhood and adolescence, with risk markers for diabetes in young South Asian adults. We studied 357 men and women aged 21 years from the Pune Children’s Study birth cohort. Exposures were 1) birth weight, 21-year BMI, both of these mutually adjusted, and their interaction, and 2) uncorrelated conditional measures of growth in height and proxies for gain in adiposity and lean mass from birth to 8 years (childhood) and 8 to 21 years (adolescence) constructed from birth weight, and weight, height, and skinfolds at 8 and 21 years. Outcomes were plasma glucose and insulin concentrations during an oral glucose tolerance test and derived indices of insulin resistance and secretion. Higher 21-year BMI was associated with higher glucose and insulin concentrations and insulin resistance, and lower disposition index. After adjusting for 21-year BMI, higher birth weight was associated with lower 120-min glucose and insulin resistance, and higher disposition index. In the growth analysis, greater adiposity gain during childhood and adolescence was associated with higher glucose, insulin and insulin resistance, and lower disposition index, with stronger effects from adolescent gain. Greater childhood lean gain and adolescent height gain were associated with lower 120-min glucose and insulin. Consistent with other studies, lower birth weight and higher childhood weight gain increases diabetes risk. Disaggregation of weight gain showed that greater child/adolescent adiposity gain and lower lean and height gain may increase risk

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

Increases in plasma holotranscobalamin can be used to assess vitamin B-12 absorption in individuals with low plasma vitamin B-12

Low plasma concentrations of vitamin B-12 are common in Indians, possibly due to low dietary intakes of animal-source foods. Whether malabsorption of the vitamin contributes to this has not been investigated. A rise in the plasma holotranscobalamin (holo-TC) concentration after a standard dose of oral vitamin B-12 has been proposed as a measure of gastrointestinal absorption in people with normal plasma vitamin B-12 concentrations. We studied 313 individuals (children and parents, 109 families) in the Pune Maternal Nutrition Study. They received 3 doses of 10 µg (n = 191) or 2 µg (n = 122) of cyanocobalamin at 6-h intervals. A rise in plasma holo-TC of 15% and >15 pmol/L above baseline was considered normal vitamin B-12 absorption. The baseline plasma vitamin B-12 concentration was <150 pmol/L in 48% of participants; holo-TC was <35 pmol/L in 98% and total homocysteine was high in 50% of participants (>10 µmol/L in children and >15 µmol/L in adults). In the 10 µg group, the plasma holo-TC concentration increased by 4.8-fold from (mean ± SD) 9.3 ± 7.0 pmol/L to 53.8 ± 25.9 pmol/L and in the 2 µg group by 2.2-fold from 11.1 ± 8.5 pmol/L to 35.7 ± 19.3 pmol/L. Only 10% of the participants, mostly fathers, had an increase less than the suggested cut-points. Our results suggest that an increase in plasma holo-TC may be used to assess vitamin B-12 absorption in individuals with low vitamin B-12 status. Because malabsorption is unlikely to be a major reason for the low plasma vitamin B-12 concentrations in this population, increasing dietary vitamin B-12 should improve their status