The 2022 India Report Card on physical activity for children and adolescents.

Background: With strong evidence of physical inactivity's link to chronic disease and economic burden - particularly with childhood active living behaviors tracking into adulthood - it is imperative to promote physical activity among children and adolescents in India. Objectives: To evaluate active living patterns among Indian children and adolescents. Methods: The India Report Card (IRC) team, which consists of experts in India and Canada, systematically collected and appraised evidence on 11 indicators of active living, including 5 behavioral (Overall Physical Activity, Organized Sport Participation, Active Play, Active Transportation, Sedentary Behavior), 2 individual-level (Physical Fitness, Yoga) and 4 sources of influence (Family and Peers, School, Community and Built Environment, Government). Peer-reviewed articles were appraised based on national representativeness, sample size, and data quality. Grey literature was appraised based on comprehensiveness, validity of the sources, and representativeness. All indicators were assessed against parameters provided by the Active Healthy Kids Global Alliance. Results: Active Transportation and Government Strategies were ranked highest with a B- and C+ grade, respectively. Overall Physical Activity and Schools were assigned a C grade, while Sedentary Behavior and Community and Built Environment were given D grades. Yoga was the lowest ranking indicator with a D- grade. Organized Sport Participation, Active Play, Family and Peers, and Physical Fitness were all graded incomplete. Conclusions: Active Transportation, Government Strategies, and Overall Physical Activity have improved since the 2018 IRC, a positive trend that needs to be translated to other indicators. However, Sedentary Behavior has consistently worsened, with grades C, C-, and D-, in 2016, 2018, and 2022, respectively. Evidence generated by the 2022 IRC suggests opportunities for improvement not only in India, but also the 56 other countries taking part in Global Matrix 4.0.

Size at birth, lifecourse factors, and cognitive function in late life: findings from the MYsore study of Natal effects on Ageing and Health (MYNAH) cohort in South India.

OBJECTIVE: To examine if smaller size at birth, an indicator of growth restriction in utero, is associated with lower cognition in late life, and whether this may be mediated by impaired early life brain development and/or adverse cardiometabolic programming. DESIGN: Longitudinal follow-up of a birth cohort. SETTING: CSI Holdsworth Memorial Hospital (HMH), Mysore South India. PARTICIPANTS: 721 men and women (55-80 years) whose size at birth was recorded at HMH. Approximately 20 years earlier, a subset (n = 522) of them had assessments for cardiometabolic disorders in mid-life. MEASUREMENTS: Standardized measurement of cognitive function, depression, sociodemographic, and lifestyle factors; blood tests and assessments for cardiometabolic disorders. RESULTS: Participants who were heavier at birth had higher composite cognitive scores (0.12 SD per SD birth weight [95% CI 0.05, 0.19] p = 0.001) in late life. Other lifecourse factors independently positively related to cognition were maternal educational level and participants' own educational level, adult leg length, body mass index, and socioeconomic position, and negatively were diabetes in mid-life and current depression and stroke. The association of birth weight with cognition was independent cardiometabolic risk factors and was attenuated after adjustment for all lifecourse factors (0.08 SD per SD birth weight [95% CI -0.01, 0.18] p = 0.07). CONCLUSIONS: The findings are consistent with positive effects of early life environmental factors (better fetal growth, education, and childhood socioeconomic status) on brain development resulting in greater long-term cognitive function. The results do not support a pathway linking poorer fetal development with reduced late life cognitive function through cardiometabolic programming.

GWAS identifies population-specific new regulatory variants in FUT6 associated with plasma B12 concentrations in Indians.

Vitamin B12 is an important cofactor in one-carbon metabolism whose dysregulation is associated with various clinical conditions. Indians have a high prevalence of B12 deficiency but little is known about the genetic determinants of circulating B12 concentrations in Indians. We performed a genome-wide association study in 1001 healthy participants in the Pune Maternal Nutrition Study (PMNS), replication studies in 3418 individuals from other Indian cohorts and by meta-analysis identified new variants, rs3760775 (P = 1.2 × 10-23) and rs78060698 (P = 8.3 × 10-17) in FUT6 to be associated with circulating B12 concentrations. Although in-silico analysis replicated both variants in Europeans, differences in the effect allele frequency, effect size and the linkage disequilibrium structure of credible set variants with the reported variants suggest population-specific characteristics in this region. We replicated previously reported variants rs602662, rs601338 in FUT2, rs3760776, rs708686 in FUT6, rs34324219 in TCN1 (all P < 5 × 10-8), rs1131603 in TCN2 (P = 3.4 × 10-5), rs12780845 in CUBN (P = 3.0 × 10-3) and rs2270655 in MMAA (P = 2.0 × 10-3). Circulating B12 concentrations in the PMNS and Parthenon study showed a significant decline with increasing age (P < 0.001), however, the genetic contribution to B12 concentrations remained constant. Luciferase reporter and electrophoretic-mobility shift assay for the FUT6 variant rs78060698 using HepG2 cell line demonstrated strong allele-specific promoter and enhancer activity and differential binding of HNF4α, a key regulator of expression of various fucosyltransferases. Hence, the rs78060698 variant, through regulation of fucosylation may control intestinal host-microbial interaction which could influence B12 concentrations. Our results suggest that in addition to established genetic variants, population-specific variants are important in determining plasma B12 concentrations.

Active children are less adipose and insulin resistant in early adolescence; evidence from the Mysore Parthenon Cohort.

BACKGROUND: The aim of this study was to determine whether physical activity volume and intensity in mid-childhood and early adolescence were associated with cardiometabolic risk factors at 13.5 years. METHODS: Participants were recruited from the Mysore Parthenon observational birth cohort. At ages 6-10 and 11-13 years, volume and intensity of physical activity were assessed using AM7164 or GT1M actigraph accelerometers worn for ≥4 days, and expressed as mean counts per day and percentage time spent in light, moderate and vigorous physical activity according to criteria defined by Evenson et al. At 13.5 years, fasting blood samples were collected; lipids, glucose and insulin concentrations were measured and insulin resistance (HOMA) was calculated. Systolic and diastolic blood pressure were measured at the left arm using a Dinamap (Criticon). Anthropometry and bio-impedance analysis were used to assess body size and composition. Metabolic and anthropometric measures were combined to produce a metabolic syndrome risk score. RESULTS: At 6-10 years, boys and girls respectively spent a median (IQR) of 1.1 (0.5, 2.0) % and 0.8 (0.4, 1.3) % of recorded time vigorously active. At 11-13 years, boys and girls respectively spent a median (IQR) of 0.8 (0.4, 1.7) % and 0.3 (0.1, 0.6) % of time vigorously active. All of the physical activity parameters were positively correlated between the 6-10 year and the 11-13 year measurements indicating that physical activity tracked from childhood to early adolescence. There were no associations between physical activity at 6-10 years and individual 13.5 year risk factors but % time vigorously active was inversely associated with metabolic syndrome score (B = -0.40, 95% CI -0.75, 0.05). Volume of physical activity at 11-13 years was inversely associated with 13.5 year HOMA and fat percentage and vigorous physical activity was associated with HOMA, fat percentage, sum of skinfolds, waist circumference and total: HDL cholesterol ratio. Vigorous physical activity was inversely associated with metabolic syndrome score (B = -0.51, 95% CI -0.94, -0.08). CONCLUSIONS: Volume and intensity of physical activity in early adolescence were negatively associated with metabolic and anthropometric risk factors. Interventions that aim to increase adolescent physical activity, especially vigorous, may prevent cardiometabolic disease in later life.

Associations of Maternal Vitamin B12 Concentration in Pregnancy With the Risks of Preterm Birth and Low Birth Weight: A Systematic Review and Meta-Analysis of Individual Participant Data.

Vitamin B12 (hereafter referred to as B12) deficiency in pregnancy is prevalent and has been associated with both lower birth weight (birth weight <2,500 g) and preterm birth (length of gestation <37 weeks). Nevertheless, current evidence is contradictory. We performed a systematic review and a meta-analysis of individual participant data to evaluate the associations of maternal serum or plasma B12 concentrations in pregnancy with offspring birth weight and length of gestation. Twenty-two eligible studies were identified (11,993 observations). Eighteen studies were included in the meta-analysis (11,216 observations). No linear association was observed between maternal B12 levels in pregnancy and birth weight, but B12 deficiency (<148 pmol/L) was associated with a higher risk of low birth weight in newborns (adjusted risk ratio = 1.15, 95% confidence interval (CI): 1.01, 1.31). There was a linear association between maternal levels of B12 and preterm birth (per each 1-standard-deviation increase in B12, adjusted risk ratio = 0.89, 95% CI: 0.82, 0.97). Accordingly, B12 deficiency was associated with a higher risk of preterm birth (adjusted risk ratio = 1.21, 95% CI: 0.99, 1.49). This finding supports the need for randomized controlled trials of vitamin B12 supplementation in pregnancy.

Association between maternal nutritional status in pregnancy and offspring cognitive function during childhood and adolescence; a systematic review.

BACKGROUND: The mother is the only source of nutrition for fetal growth including brain development. Maternal nutritional status (anthropometry, macro- and micro-nutrients) before and/or during pregnancy is therefore a potential predictor of offspring cognitive function. The relationship of maternal nutrition to offspring cognitive function is unclear. This review aims to assess existing evidence linking maternal nutritional status with offspring cognitive function. METHODS: Exposures considered were maternal BMI, height and weight, micronutrient status (vitamins D, B12, folate and iron) and macronutrient intakes (carbohydrate, protein and fat). The outcome was any measure of cognitive function in children aged <18 years. We considered observational studies and trials with allocation groups that differed by single nutrients. We searched Medline/PubMed and the Cochrane Library databases and reference lists of retrieved literature. Two reviewers independently extracted data from relevant articles. We used methods recommended by the Centre for Reviews and Dissemination, University of York and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Of 16,143 articles identified, 38 met inclusion criteria. Most studies were observational, and from high-income settings. There were few randomized controlled trials. There was consistent evidence linking maternal obesity with lower cognitive function in children; low maternal BMI has been inadequately studied. Among three studies of maternal vitamin D status, two showed lower cognitive function in children of deficient mothers. One trial of folic acid supplementation showed no effects on the children's cognitive function and evidence from 13 observational studies was mixed. Among seven studies of maternal vitamin B12 status, most showed no association, though two studies in highly deficient populations suggested a possible effect. Four out of six observational studies and two trials (including one in an Iron deficient population) found no association of maternal iron status with offspring cognitive function. One trial of maternal carbohydrate/protein supplementation showed no effects on offspring cognitive function. CONCLUSIONS: Current evidence that maternal nutritional status during pregnancy as defined by BMI, single micronutrient studies, or macronutrient intakes influences offspring cognitive function is inconclusive. There is a need for more trials especially in populations with high rates of maternal undernutrition. SYSTEMATIC REVIEW REGISTRATION: Registered in PROSPERO CRD42013005702 .

Contribution of food sources to the vitamin B12 status of South Indian children from a birth cohort recruited in the city of Mysore.

OBJECTIVE: There is evidence that subclinical vitamin B12 (B12) deficiency is common in India. Vegetarianism is prevalent and therefore meat consumption is low. Our objective was to explore the contribution of B12-source foods and maternal B12 status during pregnancy to plasma B12 concentrations. DESIGN: Maternal plasma B12 concentrations were measured during pregnancy. Children's dietary intakes and plasma B12 concentrations were measured at age 9.5 years; B12 and total energy intakes were calculated using food composition databases. We used linear regression to examine associations between maternal B12 status and children's intakes of B12 and B12-source foods, and children's plasma B12 concentrations. SETTING: South Indian city of Mysore and surrounding rural areas. SUBJECTS: Children from the Mysore Parthenon Birth Cohort (n 512, 47.1 % male). RESULTS: Three per cent of children were B12 deficient (<150 pmol/l). A further 14 % had 'marginal' B12 concentrations (150-221 pmol/l). Children's total daily B12 intake and consumption frequencies of meat and fish, and micronutrient-enriched beverages were positively associated with plasma B12 concentrations (P=0.006, P=0.01 and P=0.04, respectively, adjusted for socio-economic indicators and maternal B12 status). Maternal pregnancy plasma B12 was associated with children's plasma B12 concentrations, independent of current B12 intakes (P<0.001). Milk and curd (yoghurt) intakes were unrelated to B12 status. CONCLUSIONS: Meat and fish are important B12 sources in this population. Micronutrient-enriched beverages appear to be important sources in our cohort, but their high sugar content necessitates care in their recommendation. Improving maternal B12 status in pregnancy may improve Indian children's status.

Association between maternal folate concentrations during pregnancy and insulin resistance in Indian children.

AIMS/HYPOTHESIS: In an Indian birth cohort, higher maternal homocysteine concentration in pregnancy was associated with lower birthweight of the offspring. Lower maternal vitamin B12 and higher folate concentrations were associated with higher offspring insulin resistance. Disordered one-carbon metabolism during early development may increase later metabolic risk. We explored these associations in another birth cohort in India at three age points. METHODS: We measured plasma vitamin B12, folate and homocysteine concentrations at 30 ± 2 weeks' gestation in 654 women who delivered at one hospital. Neonatal anthropometry was recorded, and the children's glucose and insulin concentrations were measured at 5, 9.5 and 13.5 years of age. Insulin resistance was estimated using HOMA of insulin resistance (HOMA-IR). RESULTS: Maternal homocysteine concentrations were inversely associated with all neonatal anthropometric measurements (p < 0.05), and positively associated with glucose concentrations in the children at 5 (30 min; p = 0.007) and 9.5 years of age (120 min; p = 0.02). Higher maternal folate concentrations were associated with higher HOMA-IR in the children at 9.5 (p = 0.03) and 13.5 years of age (p = 0.03). Maternal vitamin B12 concentrations were unrelated to offspring outcomes. CONCLUSIONS/INTERPRETATION: Maternal vitamin B12 status did not predict insulin resistance in our cohort. However, associations of maternal homocysteine and folate concentrations with birth size, and with childhood insulin resistance and glycaemia in the offspring, suggest a role for nutritionally driven disturbances in one-carbon metabolism in fetal programming of diabetes.

Diet patterns are associated with demographic factors and nutritional status in South Indian children.

The burden of non-communicable chronic disease (NCD) in India is increasing. Diet and body composition 'track' from childhood into adult life and contribute to the development of risk factors for NCD. Little is known about the diet patterns of Indian children. We aimed to identify diet patterns and study associations with body composition and socio-demographic factors in the Mysore Parthenon Study cohort. We collected anthropometric and demographic data from children aged 9.5 years (n = 538). We also administered a food frequency questionnaire and measured fasting blood concentrations of folate and vitamin B12. Using principal component analysis, we identified two diet patterns. The 'snack and fruit' pattern was characterised by frequent intakes of snacks, fruit, sweetened drinks, rice and meat dishes and leavened breads. The 'lacto-vegetarian' pattern was characterised by frequent intakes of finger millet, vegetarian rice dishes, yoghurt, vegetable dishes and infrequent meat consumption. Adherence to the 'snack and fruit' pattern was associated with season, being Muslim and urban dwelling. Adherence to the lacto-vegetarian pattern was associated with being Hindu, rural dwelling and a lower maternal body mass index. The 'snack and fruit' pattern was negatively associated with the child's adiposity. The lacto-vegetarian pattern was positively associated with blood folate concentration and negatively with vitamin B12 concentration. This study provides new information on correlates of diet patterns in Indian children and how diet relates to nutritional status. Follow-up of these children will be important to determine the role of these differences in diet in the development of risk factors for NCD including body composition.

Testing the fetal overnutrition hypothesis; the relationship of maternal and paternal adiposity to adiposity, insulin resistance and cardiovascular risk factors in Indian children.

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 3±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.

Breastfeeding duration, age of starting solids and high BMI risk and adiposity in Indian children.

This study utilized data from a prospective birth cohort study on 568 Indian children, to determine whether a longer duration of breastfeeding and later introduction of solid feeding were associated with a reduced higher body mass index (BMI) and less adiposity. Main outcomes were high BMI (>90th within-cohort sex-specific BMI percentile) and sum of skinfold thickness (triceps and subscapular) at age 5. Main exposures were breastfeeding (six categories from 1-4 to ≥21 months) and age of starting regular solid feeding (four categories from ≤3 to ≥6 months). Data on infant-feeding practices, socio-economic and maternal factors were collected by questionnaire. Birthweight, maternal and child anthropometry were measured. Multiple regression analysis that accounted for potential confounders demonstrated a small magnitude of effect for breastfeeding duration or introduction of solid feeds on the risk of high BMI but not for lower skinfold thickness. Breastfeeding duration was strongly negatively associated with weight gain (0-2 years) [adjusted ß = -0.12 standard deviation, 95% confidence interval (CI): -0.19 to -0.05 per category change in breastfeeding duration, P = 0.001], and weight gain (0-2 years) was strongly associated with high BMI at 5 years (adjusted odds ratio = 3.8, 95% CI: 2.53-5.56, P < 0.001). In our sample, findings suggest that longer breastfeeding duration and later introduction of solids has a small reduction on later high BMI risk and a negligible effect on skinfold thickness. However, accounting for sampling variability, these findings cannot exclude the possibility of no effect at the population level.

Sexual dimorphism in the relationship between brain complexity, volume and general intelligence (g): a cross-cohort study.

Changes in brain morphology have been reported during development, ageing and in relation to different pathologies. Brain morphology described by the shape complexity of gyri and sulci can be captured and quantified using fractal dimension (FD). This measure of brain structural complexity, as well as brain volume, are associated with intelligence, but less is known about the sexual dimorphism of these relationships. In this paper, sex differences in the relationship between brain structural complexity and general intelligence (g) in two diverse geographic and cultural populations (UK and Indian) are investigated. 3D T1-weighted magnetic resonance imaging (MRI) data and a battery of cognitive tests were acquired from participants belonging to three different cohorts: Mysore Parthenon Cohort (MPC); Aberdeen Children of the 1950s (ACONF) and UK Biobank. We computed MRI derived structural brain complexity and g estimated from a battery of cognitive tests for each group. Brain complexity and volume were both positively corelated with intelligence, with the correlations being significant in women but not always in men. This relationship is seen across populations of differing ages and geographical locations and improves understanding of neurobiological sex-differences.

Babies of South Asian and European Ancestry Show Similar Associations With Genetic Risk Score for Birth Weight Despite the Smaller Size of South Asian Newborns.

Size at birth is known to be influenced by various fetal and maternal factors, including genetic effects. South Asians have a high burden of low birth weight and cardiometabolic diseases, yet studies of common genetic variations underpinning these phenotypes are lacking. We generated independent, weighted fetal genetic scores (fGSs) and maternal genetic scores (mGSs) from 196 birth weight-associated variants identified in Europeans and conducted an association analysis with various fetal birth parameters and anthropometric and cardiometabolic traits measured at different follow-up stages (5-6-year intervals) from seven Indian and Bangladeshi cohorts of South Asian ancestry. The results from these cohorts were compared with South Asians in UK Biobank and the Exeter Family Study of Childhood Health, a European ancestry cohort. Birth weight increased by 50.7 g and 33.6 g per SD of fGS (P = 9.1 × 10-11) and mGS (P = 0.003), respectively, in South Asians. A relatively weaker mGS effect compared with Europeans indicates possible different intrauterine exposures between Europeans and South Asians. Birth weight was strongly associated with body size in both childhood and adolescence (P = 3 × 10-5 to 1.9 × 10-51); however, fGS was associated with body size in childhood only (P < 0.01) and with head circumference, fasting glucose, and triglycerides in adults (P < 0.01). The substantially smaller newborn size in South Asians with comparable fetal genetic effect to Europeans on birth weight suggests a significant role of factors related to fetal growth that were not captured by the present genetic scores. These factors may include different environmental exposures, maternal body size, health and nutritional status, etc. Persistent influence of genetic loci on size at birth and adult metabolic syndrome in our study supports a common genetic mechanism that partly explains associations between early development and later cardiometabolic health in various populations, despite marked differences in phenotypic and environmental factors in South Asians.

Placental programming of blood pressure in Indian children.

AIM: To determine whether the size and shape of the placental surface predict blood pressure in childhood. METHODS: We studied blood pressure in 471 nine-year-old Indian children whose placental length, breadth and weight were measured in a prospective birth cohort study. RESULTS: In the daughters of short mothers (

Validation of EURO-D, a geriatric depression scale in South India: Findings from the Mysore study of Natal effects on Ageing and Health (MYNAH).

INTRODUCTION: Many of the assessment tools used to study depression amongst older people in low- and middle- income countries (LMICs) are adaptations of instruments developed in other cultural settings. There is a need to validate those instruments in LMICs. METHODS: 721 men and women aged 55-80 years from the Mysore Birth Records Cohort underwent standardised assessments for sociodemographic characteristics, cardiometabolic risk factors, cognitive function and mental health. Sensitivity, specificity and level of agreement of EURO-D diagnosis of depression with diagnosis of depression derived by the Geriatric Mental State (GMS) examination were calculated. To validate the EURO-D score against GMS depressive episode, we used maximum Youden's index as the criterion for each cut-off point. Concurrent validity was assessed by measuring correlations with the WHO Disability Assessment Schedule (WHO DAS II). RESULTS: Of the 721 (408 men and 313 women) who participated in this study, 138 (54 men and 84 women) were diagnosed with depression. Women had higher depression scores on the EURO-D scale and disability on the WHO DAS II scale. A maximum Youden's Index of 0.60 was observed at a EURO-D cut-off of 6, which corresponded to 95% sensitivity, 64% specificity, kappa value of 0.6 and area under the curve (AUC) of 80%. There was significant and positive correlation between EURO-D and WHO DAS II scores. LIMITATIONS: Future independent validation studies in other settings are required. DISCUSSION: This study supports the use of the EURO-D scale for diagnosing depression amongst older adults in South India.

Protocol for a cluster randomised trial evaluating a multifaceted intervention starting preconceptionally-Early Interventions to Support Trajectories for Healthy Life in India (EINSTEIN): a Healthy Life Trajectories Initiative (HeLTI) Study.

INTRODUCTION: The Healthy Life Trajectories Initiative is an international consortium comprising four harmonised but independently powered trials to evaluate whether an integrated intervention starting preconceptionally will reduce non-communicable disease risk in their children. This paper describes the protocol of the India study. METHODS AND ANALYSIS: The study set in rural Mysore will recruit ~6000 married women over the age of 18 years. The village-based cluster randomised design has three arms (preconception, pregnancy and control; 35 villages per arm). The longitudinal multifaceted intervention package will be delivered by community health workers and comprise: (1) measures to optimise nutrition; (2) a group parenting programme integrated with cognitive-behavioral therapy; (3) a lifestyle behaviour change intervention to support women to achieve a diverse diet, exclusive breast feeding for the first 6 months, timely introduction of diverse and nutritious infant weaning foods, and adopt appropriate hygiene measures; and (4) the reduction of environmental pollution focusing on indoor air pollution and toxin avoidance.The primary outcome is adiposity in children at age 5 years, measured by fat mass index. We will report on a host of intermediate and process outcomes. We will collect a range of biospecimens including blood, urine, stool and saliva from the mothers, as well as umbilical cord blood, placenta and specimens from the offspring.An intention-to-treat analysis will be adopted to assess the effect of interventions on outcomes. We will also undertake process and economic evaluations to determine scalability and public health translation. ETHICS AND DISSEMINATION: The study has been approved by the institutional ethics committee of the lead institute. Findings will be published in peer-reviewed journals. We will interact with policy makers at local, national and international agencies to enable translation. We will also share the findings with the participants and local community through community meetings, newsletters and local radio. TRIAL REGISTRATION NUMBER: ISRCTN20161479, CTRI/2020/12/030134; Pre-results.

Higher maternal plasma folate but not vitamin B-12 concentrations during pregnancy are associated with better cognitive function scores in 9- to 10- year-old children in South India.

Folate and vitamin B-12 are essential for normal brain development. Few studies have examined the relationship of maternal folate and vitamin B-12 status during pregnancy and offspring cognitive function. To test the hypothesis that lower maternal plasma folate and vitamin B-12 concentrations and higher plasma homocysteine concentrations during pregnancy are associated with poorer neurodevelopment, 536 children (aged 9-10 y) from the Mysore Parthenon birth cohort underwent cognitive function assessment during 2007-2008 using 3 core tests from the Kaufman Assessment Battery, and additional tests measuring learning, long-term storage/retrieval, attention and concentration, and visuo-spatial and verbal abilities. Maternal folate, vitamin B-12, and homocysteine concentrations were measured at 30 +/- 2 wk gestation. During pregnancy, 4% of mothers had low folate concentrations (<7 nmol/L), 42.5% had low vitamin B-12 concentrations (<150 pmol/L), and 3% had hyperhomocysteinemia (>10 micromol/L). The children's cognitive test scores increased by 0.1-0.2 SD per SD increase across the entire range of maternal folate concentrations (P < 0.001 for all), with no apparent associations at the deficiency level. The associations with learning, long-term storage/retrieval, visuo-spatial ability, attention, and concentration were independent of the parents' education, socioeconomic status, religion, and the child's sex, age, current size, and folate and vitamin B-12 concentrations. There were no consistent associations of maternal vitamin B-12 and homocysteine concentrations with childhood cognitive performance. In this Indian population, higher maternal folate, but not vitamin B-12, concentrations during pregnancy predicted better childhood cognitive ability. It also suggests that, in terms of neurodevelopment, the concentration used to define folate deficiency may be set too low.

Association of birthweight and head circumference at birth to cognitive performance in 9- to 10-year-old children in South India: prospective birth cohort study.

To examine whether birthweight and head circumference at birth are associated with childhood cognitive ability in South India, cognitive function was assessed using three core tests from the Kaufman Assessment Battery for children and additional tests measuring long-term retrieval/storage, attention and concentration, and visuospatial and verbal abilities among 505 full-term born children (mean age 9.7 y). In multiple linear regression adjusted for age, sex, gestation, socioeconomic status, parent's education, maternal age, parity, body mass index, height, rural/urban residence, and time of testing, Atlantis score (learning ability/long-term storage and retrieval) rose by 0.1 SD per SD increase in newborn weight and head circumference, respectively (p < 0.05 for all), and Kohs' block design score (visuospatial ability) increased by 0.1 SD per SD increase in birthweight (p < 0.05). The associations were reduced after further adjustment for current head circumference. There were no associations of birthweight and/or head circumference with measures of short-term memory, fluid reasoning, verbal abilities, and attention and concentration. In conclusion, higher birthweight and larger head circumference at birth are associated with better childhood cognitive ability. The effect may be specific to learning, long-term storage and retrieval, and visuospatial abilities, but this requires confirmation by further research.

Maternal B12, Folate and Homocysteine Concentrations and Offspring Cortisol and Cardiovascular Responses to Stress.

CONTEXT: Imbalances in maternal 1-carbon nutrients (vitamin B12, folate) have been shown to be associated with higher offspring cardiometabolic risk markers in India. OBJECTIVE: We examined the hypothesis that low plasma vitamin B12 (B12) and high folate and homocysteine concentrations in the mother are associated with higher hypothalamic-pituitary-adrenal axis (cortisol) and cardiovascular responses during the Trier Social Stress Test for Children (TSST-C) in an Indian birth cohort. METHODS: Adolescents (n = 264; mean age: 13.6 years), whose mothers' plasma B12, folate and total homocysteine concentrations had been measured during pregnancy, completed 5-minutes each of public speaking and mental arithmetic tasks in front of 2 unfamiliar "judges" (TSST-C). Baseline and poststress salivary cortisol concentrations were measured. Heart rate, blood pressure, stroke volume, cardiac output, and total peripheral resistance were measured continuously at baseline, during the TSST-C, and for 10 minutes after the TSST-C using a finger cuff; beat-to-beat values were averaged for these periods, respectively. RESULTS: Maternal low B12 status (plasma B12 < 150 pmol/L) was associated with greater cortisol responses to stress in the offspring (P < .001). Higher homocysteine concentrations were associated with greater offspring heart rate response (P < .001). After adjustment for multiple comparisons, there were nonsignificant associations between higher maternal folate concentrations and offspring total peripheral resistance response (P = .01). CONCLUSION: Our findings suggest that maternal 1-carbon nutritional status may have long-term programming implications for offspring neuroendocrine stress responses.