Childhood adversities characterize the heterogeneity in the brain pattern of individuals during neurodevelopment.

BACKGROUND: Several factors shape the neurodevelopmental trajectory. A key area of focus in neurodevelopmental research is to estimate the factors that have maximal influence on the brain and can tip the balance from typical to atypical development. METHODS: Utilizing a dissimilarity maximization algorithm on the dynamic mode decomposition (DMD) of the resting state functional MRI data, we classified subjects from the cVEDA neurodevelopmental cohort (n = 987, aged 6-23 years) into homogeneously patterned DMD (representing typical development in 809 subjects) and heterogeneously patterned DMD (indicative of atypical development in 178 subjects). RESULTS: Significant DMD differences were primarily identified in the default mode network (DMN) regions across these groups (p < 0.05, Bonferroni corrected). While the groups were comparable in cognitive performance, the atypical group had more frequent exposure to adversities and faced higher abuses (p < 0.05, Bonferroni corrected). Upon evaluating brain-behavior correlations, we found that correlation patterns between adversity and DMN dynamic modes exhibited age-dependent variations for atypical subjects, hinting at differential utilization of the DMN due to chronic adversities. CONCLUSION: Adversities (particularly abuse) maximally influence the DMN during neurodevelopment and lead to the failure in the development of a coherent DMN system. While DMN's integrity is preserved in typical development, the age-dependent variability in atypically developing individuals is contrasting. The flexibility of DMN might be a compensatory mechanism to protect an individual in an abusive environment. However, such adaptability might deprive the neural system of the faculties of normal functioning and may incur long-term effects on the psyche.

Risk clustering and psychopathology from a multi-center cohort of Indian children, adolescents, and young adults.

Developmental adversities early in life are associated with later psychopathology. Clustering may be a useful approach to group multiple diverse risks together and study their relation with psychopathology. To generate risk clusters of children, adolescents, and young adults, based on adverse environmental exposure and developmental characteristics, and to examine the association of risk clusters with manifest psychopathology. Participants (n = 8300) between 6 and 23 years were recruited from seven sites in India. We administered questionnaires to elicit history of previous exposure to adverse childhood environments, family history of psychiatric disorders in first-degree relatives, and a range of antenatal and postnatal adversities. We used these variables to generate risk clusters. Mini-International Neuropsychiatric Interview-5 was administered to evaluate manifest psychopathology. Two-step cluster analysis revealed two clusters designated as high-risk cluster (HRC) and low-risk cluster (LRC), comprising 4197 (50.5%) and 4103 (49.5%) participants, respectively. HRC had higher frequencies of family history of mental illness, antenatal and neonatal risk factors, developmental delays, history of migration, and exposure to adverse childhood experiences than LRC. There were significantly higher risks of any psychiatric disorder [Relative Risk (RR) = 2.0, 95% CI 1.8-2.3], externalizing (RR = 4.8, 95% CI 3.6-6.4) and internalizing disorders (RR = 2.6, 95% CI 2.2-2.9), and suicidality (2.3, 95% CI 1.8-2.8) in HRC. Social-environmental and developmental factors could classify Indian children, adolescents and young adults into homogeneous clusters at high or low risk of psychopathology. These biopsychosocial determinants of mental health may have practice, policy and research implications for people in low- and middle-income countries.

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.

Body Composition and Cardiometabolic Risk Markers in Children of Women who Took Part in a Randomized Controlled Trial of a Preconceptional Nutritional Intervention in Mumbai, India.

BACKGROUND: Maternal nutrition influences fetal development and may permanently alter ("program") offspring body composition and metabolism, thereby influencing later risk of diabetes and cardiovascular (cardiometabolic) disease. The prevalence of cardiometabolic disease is rising rapidly in India. OBJECTIVES: To test the hypothesis that supplementing low-income Indian women with micronutrient-rich foods preconceptionally and during pregnancy has a beneficial impact on the children's body composition and cardiometabolic risk marker profiles. METHODS: Follow-up of 1255 children aged 5-10 y whose mothers took part in the Mumbai Maternal Nutrition Project [Project "SARAS"; International Standard Randomised Controlled Trial Number (ISRCTN)62811278]. Mothers were randomly assigned to receive a daily micronutrient-rich snack or a control snack of lower micronutrient content, both made from local foods, in addition to normal diet, from before pregnancy until delivery. Children's body composition was assessed using anthropometry and DXA. Their blood pressure, plasma glucose, insulin, and lipid concentrations were measured. Outcomes were compared between allocation groups with and without adjustment for confounding factors. RESULTS: Overall, 15% of children were stunted, 34% were wasted, and 3% were overweight. In the intention-to-treat analysis, there were no differences in body composition or risk markers between children in the intervention and control groups. Among children whose mothers started supplementation ≥3 mo before conception (the "per protocol" sample) the intervention increased adiposity among girls, but not boys. BMI in girls was increased relative to controls by 2% (95% CI: 1, 4; P = 0.01); fat mass index by 10% (95% CI: 3, 18; P = 0.004); and percent fat by 7% (95% CI: 1, 13; P = 0.01) unadjusted, with similar results in adjusted models. CONCLUSIONS: Overall, supplementing women with micronutrient-rich foods from before pregnancy until delivery did not alter body composition or cardiometabolic risk markers in the children. Subgroup analyses showed that, if started ≥3 mo before conception, supplementation may increase adiposity among female children.

Body Composition and Cardiometabolic Risk Markers in Children of Women who Took Part in a Randomized Controlled Trial of a Preconceptional Nutritional Intervention in Mumbai, India.

BACKGROUND: Maternal nutrition influences fetal development and may permanently alter ("program") offspring body composition and metabolism, thereby influencing later risk of diabetes and cardiovascular (cardiometabolic) disease. The prevalence of cardiometabolic disease is rising rapidly in India. OBJECTIVES: To test the hypothesis that supplementing low-income Indian women with micronutrient-rich foods preconceptionally and during pregnancy has a beneficial impact on the children's body composition and cardiometabolic risk marker profiles. METHODS: Follow-up of 1255 children aged 5-10 y whose mothers took part in the Mumbai Maternal Nutrition Project [Project "SARAS"; International Standard Randomised Controlled Trial Number (ISRCTN)62811278]. Mothers were randomly assigned to receive a daily micronutrient-rich snack or a control snack of lower micronutrient content, both made from local foods, in addition to normal diet, from before pregnancy until delivery. Children's body composition was assessed using anthropometry and DXA. Their blood pressure, plasma glucose, insulin, and lipid concentrations were measured. Outcomes were compared between allocation groups with and without adjustment for confounding factors. RESULTS: Overall, 15% of children were stunted, 34% were wasted, and 3% were overweight. In the intention-to-treat analysis, there were no differences in body composition or risk markers between children in the intervention and control groups. Among children whose mothers started supplementation ≥3 mo before conception (the "per protocol" sample) the intervention increased adiposity among girls, but not boys. BMI in girls was increased relative to controls by 2% (95% CI: 1, 4; P = 0.01); fat mass index by 10% (95% CI: 3, 18; P = 0.004); and percent fat by 7% (95% CI: 1, 13; P = 0.01) unadjusted, with similar results in adjusted models. CONCLUSIONS: Overall, supplementing women with micronutrient-rich foods from before pregnancy until delivery did not alter body composition or cardiometabolic risk markers in the children. Subgroup analyses showed that, if started ≥3 mo before conception, supplementation may increase adiposity among female children.

Peri-conceptional diet patterns and the risk of Gestational diabetes mellitus in South Indian women.

OBJECTIVE: To identify peri-conceptional diet patterns among women in Bangalore, and examine their associations with risk of gestational diabetes mellitus. DESIGN: BANGLES, started in June 2016, was a prospective observational study, in which women were recruited at 5-16 weeks' gestation. Peri-conceptional diet was recalled at recruitment, using a validated 224-item food frequency questionnaire. GDM was assessed by a 75-gram oral glucose tolerance test at 24-28 weeks' gestation, applying WHO 2013 criteria. Diet patterns were identified using principal component analysis and diet pattern-GDM associations were examined using multivariate logistic regression, adjusting for 'a priori' confounders. SETTING: Antenatal clinics of two hospitals, Bangalore, South India. PARTICIPANTS: 785 pregnant women of varied socio-economic status. RESULTS: GDM prevalence was 22%. Three diet patterns were identified: a) High-diversity, urban (HDU) characterised by diverse, home-cooked and processed foods was associated with older, more affluent, better-educated and urban women; b) Rice-fried snacks-chicken-sweets (RFCS), characterised by low diet-diversity, was associated with younger, less-educated, and lower income, rural and joint families; c) Healthy, traditional vegetarian (HTV), characterised by home-cooked-vegetarian and non-processed foods was associated with less-educated, more affluent, and rural and joint families. The HDU pattern was associated with a lower GDM risk (aOR: 0.80 per SD, 95% CI: 0.64, 0.99, p=0.04) after adjusting for confounders. BMI was strongly related to GDM risk and possibly mediated diet-GDM associations. CONCLUSIONS: The findings support global recommendations to encourage women to attain a healthy pre-pregnancy BMI and increase diet-diversity. Both healthy and unhealthy foods in the patterns indicate low-awareness about healthy foods and a need for public-education.

The Consortium on Vulnerability to Externalizing Disorders and Addictions (c-VEDA): an accelerated longitudinal cohort of children and adolescents in India.

The global burden of disease attributable to externalizing disorders such as alcohol misuse calls urgently for effective prevention and intervention. As our current knowledge is mainly derived from high-income countries such in Europe and North-America, it is difficult to address the wider socio-cultural, psychosocial context, and genetic factors in which risk and resilience are embedded in low- and medium-income countries. c-VEDA was established as the first and largest India-based multi-site cohort investigating the vulnerabilities for the development of externalizing disorders, addictions, and other mental health problems. Using a harmonised data collection plan coordinated with multiple cohorts in China, USA, and Europe, baseline data were collected from seven study sites between November 2016 and May 2019. Nine thousand and ten participants between the ages of 6 and 23 were assessed during this time, amongst which 1278 participants underwent more intensive assessments including MRI scans. Both waves of follow-ups have started according to the accelerated cohort structure with planned missingness design. Here, we present descriptive statistics on several key domains of assessments, and the full baseline dataset will be made accessible for researchers outside the consortium in September 2019. More details can be found on our website [cveda.org].

A scoping review of literature describing the nutritional status and diets of adolescents in Côte d'Ivoire.

OBJECTIVE: Adolescents living in resource-limited settings remain a neglected population regarding their nutritional health. We reviewed what studies on nutrition have been conducted for adolescents living in Côte d'Ivoire. DESIGN: A scoping literature review, searching for any quantitative studies published from 1 January 2000 to 1 May 2019, referenced in PubMed and grey literature, related to adolescent nutritional status and diet, written in English or French. SETTING: Côte d'Ivoire, West Africa. SUBJECTS: Adolescent girls and boys (aged 10-19 years). RESULTS: We used three search strategies to explore studies related to (1) diet and nutritional practices, (2) anthropometry and (3) micronutrient intakes/status. Each identified 285, 108 and 84 titles and abstracts, respectively, resulting in 384 full-text articles to review. Finally, after adding five relevant studies from the grey literature, thirty articles were included. Two-thirds were cross-sectional observation studies. The main topics were anaemia and parasitic diseases. Among seven intervention studies, most focused on micronutrient supplementation or deworming. No studies on macronutrients or food supplementation were found. Overall, studies showed a high prevalence of undernutrition, along with emerging overweight and obesity. Anaemia and Fe deficiency were highly prevalent, with Fe supplementation showing modest improvements. Malaria and gut parasite infections remain a major burden, affecting adolescents' nutritional status. CONCLUSIONS: Few specific relevant studies have been published regarding adolescent nutrition in Côte d'Ivoire, and most studies being focused on younger children. There are knowledge gaps about many nutritional aspects in this population, which urgently need to be addressed.

Anthropometric nutritional status, and social and dietary characteristics of African and Indian adolescents taking part in the TALENT (Transforming Adolescent Lives through Nutrition) qualitative study.

OBJECTIVE: To describe the anthropometry, socioeconomic circumstances, diet and screen time usage of adolescents in India and Africa as context to a qualitative study of barriers to healthy eating and activity. DESIGN: Cross-sectional survey, including measured height and weight and derived rates of stunting, low BMI, overweight and obesity. Parental schooling and employment status, household assets and amenities, and adolescents' dietary diversity, intake of snack foods, mobile/smartphone ownership and TV/computer time were obtained via a questionnaire. SETTING: Four settings each in Africa (rural villages, West Kiang, The Gambia; low-income urban communities, Abidjan, Cote D'Ivoire; low/middle-class urban communities, Jimma, Ethiopia; low-income township, Johannesburg, South Africa) and India (rural villages, Dervan; semi-rural villages, Pune; city slums, Mumbai; low-middle/middle-class urban communities, Mysore). PARTICIPANTS: Convenience samples (n 41-112 per site) of boys and girls, half aged 10-12 years and another half aged 15-17 years, were recruited for a qualitative study. RESULTS: Both undernutrition (stunting and/or low BMI) and overweight/obesity were present in all settings. Rural settings had the most undernutrition, least overweight/obesity and greatest diet diversity. Urban Johannesburg (27 %) and Abidjan (16 %), and semi-rural Pune (16 %) had the most overweight/obesity. In all settings, adolescents reported low intakes of micronutrient-rich fruits and vegetables, and substantial intakes of salted snacks, cakes/biscuits, sweets and fizzy drinks. Smartphone ownership ranged from 5 % (West Kiang) to 69 % (Johannesburg), higher among older adolescents. CONCLUSIONS: The 'double burden of malnutrition' is present in all TALENT settings. Greater urban transition is associated with less undernutrition, more overweight/obesity, less diet diversity and higher intakes of unhealthy/snack foods.

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.

Before the beginning: nutrition and lifestyle in the preconception period and its importance for future health.

A woman who is healthy at the time of conception is more likely to have a successful pregnancy and a healthy child. We reviewed published evidence and present new data from low-income, middle-income, and high-income countries on the timing and importance of preconception health for subsequent maternal and child health. We describe the extent to which pregnancy is planned, and whether planning is linked to preconception health behaviours. Observational studies show strong links between health before pregnancy and maternal and child health outcomes, with consequences that can extend across generations, but awareness of these links is not widespread. Poor nutrition and obesity are rife among women of reproductive age, and differences between high-income and low-income countries have become less distinct, with typical diets falling far short of nutritional recommendations in both settings and especially among adolescents. Several studies show that micronutrient supplementation starting in pregnancy can correct important maternal nutrient deficiencies, but effects on child health outcomes are disappointing. Other interventions to improve diet during pregnancy have had little effect on maternal and newborn health outcomes. Comparatively few interventions have been made for preconception diet and lifestyle. Improvements in the measurement of pregnancy planning have quantified the degree of pregnancy planning and suggest that it is more common than previously recognised. Planning for pregnancy is associated with a mixed pattern of health behaviours before conception. We propose novel definitions of the preconception period relating to embryo development and actions at individual or population level. A sharper focus on intervention before conception is needed to improve maternal and child health and reduce the growing burden of non-communicable diseases. Alongside continued efforts to reduce smoking, alcohol consumption, and obesity in the population, we call for heightened awareness of preconception health, particularly regarding diet and nutrition. Importantly, health professionals should be alerted to ways of identifying women who are planning a pregnancy.

Size at birth and cognitive ability in late life: A systematic review.

INTRODUCTION: Recent evidence suggests that growth restriction in utero may lead to neurocognitive disorders in late life, either through impaired brain development or adverse metabolic programming. METHODS: Systematic review of literature investigating the relationship between size at birth and cognitive abilities in late life. The search, data extraction, and rating for the quality of reporting were conducted independently by two researchers. RESULTS: Of 533 selected studies, 11 were included in this systematic review and 10 of these were from high-income setting. Of these 11 studies, eight indicated that lower birth weight is a risk factor for lower cognitive function in late life, at least in high-income countries. The reported effect sizes were small and it was not possible to conduct meta-analyses because of clinical heterogeneity DISCUSSION: A modest association of lower birth weight with lower cognitive abilities in late life is consistent with persisting effects of the prenatal environment on brain function. As with all observational studies, confounding is an alternative explanation. Further studies are required to elucidate the mechanisms.

Cognitive function and disability in late life: an ecological validation of the 10/66 battery of cognitive tests among community-dwelling older adults in South India.

BACKGROUND: The 10/66 Dementia Research Group developed and validated a culture and education fair battery of cognitive tests for diagnosis of dementia in population-based studies in low-income and middle-income countries including India. AIMS: This study examined the association between individual domains of the 10/66 battery of cognitive tests and 'disability' and 'functional impairment' in community-dwelling older adults in South India. METHODS: One hundred twenty-nine adults aged 60-90 years residing in Karunapura, in the city of Mysore, were interviewed in their own homes. Cognitive functioning was measured by administering the 10/66 battery of cognitive tests that composes of Community Screening Instrument for Dementia (CSI'D' COGSCORE), verbal fluency (VF) and word list memory recall (WLMR). A reliable informant was interviewed to ascertain if the subject's cognitive problems have resulted in functional impairment. Disability was measured by WHO Disability Schedule-II (DAS). RESULTS: The women had significantly lower CSI'D' COGSCORE score when compared with men (p = 0.002). The presence of 'functional impairment' resulting from cognitive decline was significantly associated with lower scores on VF (p = 0.03), WLMR (p = 0.03) and CSI'D' COGSCOREs (p < 0.01). There was a significant inverse association between WHO DAS II score and WLMR (p = 0.004), VF (0.006) and CSI'D' COGSCORE scores (p ≤ 0.001) even after adjusting for self-reported ischaemic heart disease, stroke, chronic obstructive airway disease, hypertension and diabetes. CONCLUSIONS: Lower scores on individual domains of the 10/66 battery of cognitive tests are associated with higher levels of disability and functional impairment in community-dwelling older adults. These culture and education fair tests are suitable for use in population-based research in India. Copyright © 2015 John Wiley & Sons, Ltd.

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.

Periconceptional diet and the risk of gestational diabetes in south Indian women: findings from the BAngalore Nutrition Gestational diabetes LiFEstyle Study (BANGLES).

BACKGROUND: Gestational diabetes can predispose two generations-a mother and her child-to a higher risk of obesity and type 2 diabetes. Culture-specific strategies to prevent gestational diabetes are required. BANGLES investigated the associations between women's periconceptional diet and gestational diabetes risk. METHODS: BANGLES was a prospective observational study (n=785), in which women of various socioeconomic status were recruited at 5-16 weeks' gestation in Bangalore, India. Periconceptional diet was recalled at recruitment, using a validated 224-item food frequency questionnaire, that was reduced to 21 food groups for the food group-gestational diabetes analysis, and 68 food groups for the principal component analysis for a diet pattern-gestational diabetes analysis. Diet-gestational diabetes associations were examined using multivariate logistic regression, adjusting for a priori confounders determined from the literature. Gestational diabetes was assessed by a 75 g oral glucose tolerance test at 24-28 weeks' gestation, applying 2013 WHO criteria. FINDINGS: Women who consumed whole-grain cereals (adjusted odds ratio [OR] 0·58, 95% CI 0·34-0·97, p=0·03); had moderate egg consumption (>1-3 times per week) compared with less than once per week (adjusted OR 0·54, 95% CI 0·34-0·86, p=0·01); and a higher weekly intake of pulses and legumes (adjusted OR 0·81, 95% CI 0·66-0·98, p=0·03), nuts and seeds (adjusted OR 0·77, 95% CI 0·63-0·94, p=0·01), and fried and fast food (adjusted OR 0·72, 95% CI 0·59-0·89, p=0·002) had a lower gestational diabetes. None of these associations was significant after correction for multiple testing. A high-diversity, urban diet pattern characterised by diverse home-cooked and processed foods and associated with older, affluent, educated, urban women was associated with a lower risk (adjusted OR 0·80, 95% CI 0·64-0·99, p=0·04). BMI was the strongest risk factor for gestational diabetes and possibly mediated the diet pattern-gestational diabetes associations. INTERPRETATION: The same food groups that were associated with a lower gestational diabetes risk were components of the high-diversity, urban diet pattern. One healthy diet pattern might not be relevant to India. Findings support global recommendations to encourage women to attain a healthy pre-pregnancy BMI, increase diet diversity to prevent gestational diabetes, and have policies to increase food affordability. FUNDING: Schlumberger Foundation.

An intergenerational life-course approach to address early childhood obesity and adiposity: the Healthy Life Trajectories Initiative (HeLTI).

BACKGROUND: Interactions between genes and early-life exposures during conception, fetal life, infancy, and early childhood have been shown to affect an individual's health later in life. Maternal undernutrition and obesity, gestational diabetes, and impaired growth in utero and in early life are associated with adiposity and overweight and obesity in childhood, which are risk factors for poor health trajectories and non-communicable diseases. In Canada, China, India, and South Africa, 10-30% of children aged 5-16 years are overweight or obese. METHODS: The application of developmental origins of health and disease principles offers a novel approach to prevention of overweight and obesity and reduction of adiposity by delivering integrated interventions across the life course, starting before conception and continuing through early childhood. The Healthy Life Trajectories Initiative (HeLTI) was established in 2017 through a unique collaboration between national funding agencies in Canada, China, India, South Africa, and WHO. The aim of HeLTI is to evaluate the effect of an integrated four-phase intervention starting preconceptionally and continuing through pregnancy, infancy, and early childhood on reducing childhood adiposity (fat mass index) and overweight and obesity, and optimising early child development, nutrition, and other healthy behaviours. FINDINGS: Approximately 22 000 women are being recruited in Shanghai (China), Mysore (India), Soweto (South Africa), and across various provinces of Canada. Women who conceive (an expected 10 000) and their children will be followed up until the child reaches the age of 5 years. INTERPRETATION: HeLTI has harmonised the intervention, measures, tools, biospecimen collection, and analysis plans for the trial to be run across four countries. HeLTI will help establish whether an intervention aimed at addressing maternal health behaviours, nutrition, and weight; providing psychosocial support to reduce maternal stress and prevent mental illness; optimising infant nutrition, physical activity, and sleep; and promoting parenting skills can reduce the intergenerational risk of excess childhood adiposity and overweight and obesity across diverse settings. FUNDING: Canadian Institutes of Health Research; National Science Foundation of China; Department of Biotechnology, India; and South African Medical Research Council.

Differential expression of genes influencing mitotic processes in cord blood mononuclear cells after a pre-conceptional micronutrient-based randomised controlled trial: Pune Rural Intervention in Young Adolescents (PRIYA).

In The Pune Maternal Nutrition Study, vitamin B12 deficiency was seen in 65% of pregnant women, folate deficiency was rare. Maternal total homocysteine concentrations were inversely associated with offspring birthweight, and low vitamin B12 and high folate concentrations predicted higher offspring adiposity and insulin resistance. These findings guided a nested pre-conceptional randomised controlled trial 'Pune Rural Intervention in Young Adolescents'. The interventions included: (1) vitamin B12+multi-micronutrients as per the United Nations International Multiple Micronutrient Antenatal Preparation, and proteins (B12+MMN), (2) vitamin B12 (B12 alone), and (3) placebo. Intervention improved maternal pre-conceptional and in-pregnancy micronutrient nutrition. Gene expression analysis in cord blood mononuclear cells in 88 pregnancies revealed 75 differentially expressed genes between the B12+MMN and placebo groups. The enriched biological processes included G2/M phase transition, chromosome segregation, and nuclear division. Enriched pathways included, mitotic spindle checkpoint and DNA damage response while enriched human phenotypes were sloping forehead and decreased head circumference. Fructose-bisphosphatase 2 (FBP2) and Cell Division Cycle Associated 2 (CDCA2) genes were under-expressed in the B12 alone group. The latter, involved in chromosome segregation was under-expressed in both intervention groups. Based on the role of B-complex vitamins in the synthesis of nucleotides and S-adenosyl methionine, and the roles of vitamins A and D on gene expression, we propose that the multi-micronutrient intervention epigenetically affected cell cycle dynamics. Neonates in the B12+MMN group had the highest ponderal index. Follow-up studies will reveal if the intervention and the altered biological processes influence offspring diabesity.

DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood.

Human height is strongly influenced by genetics but the contribution of modifiable epigenetic factors is under-explored, particularly in low and middle-income countries (LMIC). We investigate links between blood DNA methylation and child height in four LMIC cohorts (n = 1927) and identify a robust association at three CpGs in the suppressor of cytokine signaling 3 (SOCS3) gene which replicates in a high-income country cohort (n = 879). SOCS3 methylation (SOCS3m)-height associations are independent of genetic effects. Mendelian randomization analysis confirms a causal effect of SOCS3m on height. In longitudinal analysis, SOCS3m explains a maximum 9.5% of height variance in mid-childhood while the variance explained by height polygenic risk score increases from birth to 21 years. Children's SOCS3m is associated with prenatal maternal folate and socio-economic status. In-vitro characterization confirms a regulatory effect of SOCS3m on gene expression. Our findings suggest epigenetic modifications may play an important role in driving child height in LMIC.

Growth trajectories for executive and social cognitive abilities in an Indian population sample: Impact of demographic and psychosocial determinants.

Cognitive abilities are markers of brain development and psychopathology. Abilities, across executive, and social domains need better characterization over development, including factors that influence developmental change. This study is based on the cVEDA [Consortium on Vulnerability to Externalizing Disorders and Addictions] study, an Indian population based developmental cohort. Verbal working memory, visuo-spatial working memory, response inhibition, set-shifting, and social cognition (faux pas recognition and emotion recognition) were cross-sectionally assessed in > 8000 individuals over the ages 6-23 years. There was adequate representation across sex, urban-rural background, psychosocial risk (psychopathology, childhood adversity and wealth index, i.e. socio-economic status). Quantile regression was used to model developmental change. Age-based trajectories were generated, along with examination of the impact of determinants (sex, childhood adversity, and wealth index). Development in both executive and social cognitive abilities continued into adulthood. Maturation and stabilization occurred in increasing order of complexity, from working memory to inhibitory control to cognitive flexibility. Age related change was more pronounced for low quantiles in response inhibition (ß∼4 versus  -1 versus -0.25 for lower quantiles). Wealth index had the largest influence on developmental change across cognitive abilities. Sex differences were prominent in response inhibition, set-shifting and emotion recognition. Childhood adversity had a negative influence on cognitive development. These findings add to the limited literature on patterns and determinants of cognitive development. They have implications for understanding developmental vulnerabilities in young persons, and the need for providing conducive socio-economic environments.

Neurocognitive Analysis of Low-level Arsenic Exposure and Executive Function Mediated by Brain Anomalies Among Children, Adolescents, and Young Adults in India.

Importance: Arsenic, a contaminant of groundwater and irrigated crops, is a global public health hazard. Exposure to low levels of arsenic through food extends well beyond the areas with high arsenic content in water. Objective: To identify cognitive impairments following commonly prevalent low-level arsenic exposure and characterize their underlying brain mechanisms. Design, Setting, and Participants: This multicenter population-based cohort study analyzed cross-sectional data of the Indian Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA) cohort, recruited between November 4, 2016, and May 4, 2019. Participants aged 6 to 23 years were characterized using deep phenotyping measures of behavior, neuropsychology, psychopathology, brain neuroimaging, and exposure to developmental adversities and environmental neurotoxins. All analyses were performed between June 1, 2020, and December 31, 2021. Exposure: Arsenic levels were measured in urine as an index of exposure. Main Outcomes and Measures: Executive function measured using the cVEDA neuropsychological battery, gray matter volume (GMV) from T1-weighted magnetic resonance imaging, and functional network connectivity measures from resting state functional magnetic resonance imaging. Results: A total of 1014 participants aged 6 to 23 years (589 male [58.1%]; mean [SD] age, 14.86 [4.79] years) were included from 5 geographic locations. Sparse-partial least squares analysis was used to describe a negative association of arsenic exposure with executive function (r = -0.12 [P = 5.4 × 10-4]), brain structure (r = -0.20 [P = 1.8 × 10-8]), and functional connectivity (within network, r = -0.12 [P = 7.5 × 10-4]; between network, r = -0.23 [P = 1.8 × 10-10]). Alterations in executive function were partially mediated by GMV (b = -0.004 [95% CI, -0.007 to -0.002]) and within-network functional connectivity (b = -0.004 [95% CI, -0.008 to -0.002]). Socioeconomic status and body mass index moderated the association between arsenic and GMV, such that the association was strongest in participants with lower socioeconomic status and body mass index. Conclusions and Relevance: The findings of this cross-sectional study suggest that low-level arsenic exposure was associated with alterations in executive functioning and underlying brain correlates. These results indicate potential detrimental consequences of arsenic exposure that are below the currently recommended guidelines and may extend beyond endemic risk areas. Precision medicine approaches to study global mental health vulnerabilities highlight widespread but potentially modifiable risk factors and a mechanistic understanding of the impact of low-level arsenic exposure on brain development.