RESUMEN
Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR < 0.05). Eight of these CpGs were located near/in the MTNR1B gene, coding for a melatonin receptor. Regional analysis identified them together as a differentially methylated region consisting of 9 CpGs in/near MTNR1B, at which higher DNAm was associated with greater maternal age (PFDR = 6.92 × 10-8) in newborns. In childhood blood samples, these differences in blood DNAm of MTNR1B CpGs were nominally significant (p < 0.05) and retained the same positive direction, suggesting persistence of associations. Maternal age was also positively associated with higher DNA methylation at three CpGs in RTEL1-TNFRSF6B at birth (PFDR < 0.05) and nominally in childhood (p < 0.0001). Of the remaining 10 CpGs also persistent in childhood, methylation at cg26709300 in YPEL3/BOLA2B in external data was associated with expression of ITGAL, an immune regulator. While further study is needed to establish causality, particularly due to the small effect sizes observed, our results potentially support offspring DNAm as a mechanism underlying associations of maternal age with child health.
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Metilación de ADN , Edad Materna , Metilación de ADN/genética , Humanos , Femenino , Recién Nacido , Niño , Adulto , Masculino , Preescolar , Islas de CpG/genética , EmbarazoRESUMEN
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.
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Metilación de ADN , Proteínas Supresoras de la Señalización de Citocinas , Femenino , Embarazo , Humanos , Niño , Metilación de ADN/genética , Proteínas Supresoras de la Señalización de Citocinas/genética , Epigénesis Genética , Epigenómica , Citocinas , Proteína 3 Supresora de la Señalización de Citocinas/genéticaRESUMEN
Air pollution is a global public health threat. Evidence suggests that increased air pollution leads to increased cardiovascular morbidity and mortality. The aim of this review was to systematically review and synthesize scientific evidence to understand the effect of performing outdoor physical activity (PA) in a polluted environment on cardiovascular outcomes. This review was developed and reported in accordance with the PRISMA guidelines. Electronic searches in Embase, Web of Science, and PubMed were undertaken through March 2021 initially, and later updated through to 31st January 2022, for observational studies published in peer-reviewed journals that report cardiovascular mortality or morbidity due to outdoor PA in air polluted environment. These searches yielded 10,840 citations. Two reviewers independently reviewed each citation for its eligibility. Seven studies were found to be eligible. Of these, five were cohort studies and two were cross-sectional studies. Pollutants measured in the selected studies were Particulate Matter (PM)-PM10, PM2.5, nitrogen oxides (NOx), and ozone (O3). The most common study outcome was myocardial infarction, followed by cardiovascular mortality, hypertension and heart rate variability. Six studies emphasized that the PA has beneficial effects on cardiovascular outcomes, though air pollutants attenuate this effect to an extent. Two studies showed that walking, even in the polluted environment, significantly reduced the heart rate and heart rate variability indices. The beneficial effects of outdoor PA outweigh the harmful effects of air pollution on cardiovascular health, though the benefits reduce to an extent when PA is carried out in a polluted environment. Because a limited number of studies (n = 7) were eligible for inclusion, the review further emphasizes the critical need for more primary studies that differentiate between outdoor and indoor PA and its effect on cardiovascular health.
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Contaminantes Atmosféricos , Contaminación del Aire , Enfermedades Cardiovasculares , Sistema Cardiovascular , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Enfermedades Cardiovasculares/epidemiología , Exposición a Riesgos Ambientales/análisis , Ejercicio Físico , Humanos , Material Particulado/análisisRESUMEN
BACKGROUND: The prevalence of cardiometabolic disease (CMD) is rising globally, with environmentally induced epigenetic changes suggested to play a role. Few studies have investigated epigenetic associations with CMD risk factors in children from low- and middle-income countries. We sought to identify associations between DNA methylation (DNAm) and CMD risk factors in children from India and The Gambia. RESULTS: Using the Illumina Infinium HumanMethylation 850 K Beadchip array, we interrogated DNAm in 293 Gambian (7-9 years) and 698 Indian (5-7 years) children. We identified differentially methylated CpGs (dmCpGs) associated with systolic blood pressure, fasting insulin, triglycerides and LDL-Cholesterol in the Gambian children; and with insulin sensitivity, insulinogenic index and HDL-Cholesterol in the Indian children. There was no overlap of the dmCpGs between the cohorts. Meta-analysis identified dmCpGs associated with insulin secretion and pulse pressure that were different from cohort-specific dmCpGs. Several differentially methylated regions were associated with diastolic blood pressure, insulin sensitivity and fasting glucose, but these did not overlap with the dmCpGs. We identified significant cis-methQTLs at three LDL-Cholesterol-associated dmCpGs in Gambians; however, methylation did not mediate genotype effects on the CMD outcomes. CONCLUSION: This study identified cardiometabolic biomarkers associated with differential DNAm in Indian and Gambian children. Most associations were cohort specific, potentially reflecting environmental and ethnic differences.
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Biomarcadores , Factores de Riesgo Cardiometabólico , Metilación de ADN/genética , Epigénesis Genética , Predisposición Genética a la Enfermedad , Síndrome Metabólico/epidemiología , Síndrome Metabólico/genética , Niño , Preescolar , Estudios de Cohortes , Femenino , Gambia/epidemiología , Humanos , India/epidemiología , Masculino , PrevalenciaRESUMEN
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.
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Composición Corporal , Enfermedades Cardiovasculares , Antropometría , Composición Corporal/fisiología , Índice de Masa Corporal , Enfermedades Cardiovasculares/prevención & control , Niño , Preescolar , Femenino , Humanos , Fenómenos Fisiologicos Nutricionales Maternos , EmbarazoRESUMEN
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.
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Pueblo Asiatico , Desarrollo Fetal , Pueblo Asiatico/genética , Peso al Nacer/genética , Estudios de Cohortes , Humanos , Recién Nacido , Factores de RiesgoRESUMEN
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.
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Enfermedades Cardiovasculares , Obesidad , Embarazo , Humanos , Femenino , Niño , Obesidad/epidemiología , Composición Corporal , Madres , Micronutrientes , Enfermedades Cardiovasculares/prevención & control , Índice de Masa CorporalRESUMEN
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.
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Agentes Comunitarios de Salud , Población Rural , Adulto , Niño , Preescolar , Femenino , Humanos , India , Lactante , Persona de Mediana Edad , Madres , Estado Nutricional , Embarazo , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: To explore influences on the diet and physical activity of adolescents living in Mumbai slums, from the perspectives of adolescents and their caregivers. DESIGN: Three investigators from Mumbai conducted six focus group discussions. SETTING: The study was conducted in suburban Mumbai slums. PARTICIPANTS: Thirty-six adolescents (aged 10-12 and 15-17 years) and twenty-three caregivers were recruited through convenience sampling. RESULTS: The findings highlighted the complex negotiations between adolescent and caregivers surrounding adolescent junk food consumption and physical activity opportunities. Caregivers learned recipes to prepare popular junk foods to encourage adolescents to eat more home-cooked, and less 'outside', food, yet adolescents still preferred to eat outside. To adolescents, the social aspect of eating junk food with friends was an important and enjoyable experience. Caregivers felt that they had no control over adolescents' food choices, whereas adolescents felt their diets were dictated by their parents. Adolescents wanted to be physically active but were encouraged to focus on their academic studies instead. Gender was also a key driver of physical activity, with girls given less priority to use outside spaces due to cultural and religious factors, and parental fears for their safety. CONCLUSIONS: These findings show that adolescents and caregivers have different agendas regarding adolescent diet. Adolescent girls have less opportunity for healthy exercise, and are more sedentary, than boys. Adolescents and caregivers need to be involved in designing effective interventions such as making space available for girls to be active, and smartphone games to encourage healthy eating or physical activity.
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Cuidadores , Áreas de Pobreza , Adolescente , Dieta , Ejercicio Físico , Conducta Alimentaria , Femenino , Preferencias Alimentarias , Humanos , MasculinoRESUMEN
BACKGROUND: Maternal nutrition in pregnancy has been linked to offspring health in early and later life, with changes to DNA methylation (DNAm) proposed as a mediating mechanism. OBJECTIVE: We investigated intervention-associated DNAm changes in children whose mothers participated in 2 randomized controlled trials of micronutrient supplementation before and during pregnancy, as part of the EMPHASIS (Epigenetic Mechanisms linking Preconceptional nutrition and Health Assessed in India and sub-Saharan Africa) study (ISRCTN14266771). DESIGN: We conducted epigenome-wide association studies with blood samples from Indian (n = 698) and Gambian (n = 293) children using the Illumina EPIC array and a targeted study of selected loci not on the array. The Indian micronutrient intervention was food based, whereas the Gambian intervention was a micronutrient tablet. RESULTS: We identified 6 differentially methylated CpGs in Gambians [2.5-5.0% reduction in intervention group, all false discovery rate (FDR) <5%], the majority mapping to ESM1, which also represented a strong signal in regional analysis. One CpG passed FDR <5% in the Indian cohort, but overall effect sizes were small (<1%) and did not have the characteristics of a robust signature. We also found strong evidence for enrichment of metastable epialleles among subthreshold signals in the Gambian analysis. This supports the notion that multiple methylation loci are influenced by micronutrient supplementation in the early embryo. CONCLUSIONS: Maternal preconceptional and pregnancy micronutrient supplementation may alter DNAm in children measured at 7-9 y. Multiple factors, including differences between the nature of the intervention, participants, and settings, are likely to have contributed to the lack of replication in the Indian cohort. Potential links to phenotypic outcomes will be explored in the next stage of the EMPHASIS study.
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Metilación de ADN , Fenómenos Fisiologicos Nutricionales Maternos , Micronutrientes/administración & dosificación , Adulto , Niño , Preescolar , Femenino , Interacción Gen-Ambiente , Humanos , Masculino , Proteínas de Neoplasias/genética , Embarazo , Proteoglicanos/genética , Sitios de Carácter Cuantitativo , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Diets in rural India are cereal based with low intakes of micronutrient-rich foods. The value chains for nutrition approach aims to study supply and demand of such foods. This may aid in development of interventions to improve diets and livelihoods. OBJECTIVES: (1) To identify how fruit and vegetables are accessed, (2) to describe and map the structure of value chains for exemplar foods, (3) to understand how foods are priced, and (4) to explore factors that affect decisions about which crops are grown, marketed, and sold. METHODS: After stakeholder consultation, we identified 2 fruits (mango and guava) and 2 vegetables (shepu and spinach) as exemplar foods. Criteria for these exemplar foods were that they should be known to participants and there should be variability in intakes. We held 24 interviews with value chain actors including farmers, wholesalers, and vendors of the exemplar foods. Data collection was stopped when no new information emerged. We used inductive thematic coding for our analysis. RESULTS: The value chains for each of the exemplar foods were relatively simple and involved farmers, middlemen, and vendors at either city or village level. The main themes identified as being factors considered when making decisions about which foods to grow and sell were (1) farming resources and assets, (2) quality of produce, (3) environmental conditions, (4) financial factors, (5) transport availability, and (6) consumer demand. CONCLUSIONS: There are opportunities to intervene within fruit and vegetable value chains to increase availability, affordability, and access to produce in rural India. Future research is required to determine which interventions will be feasible, effective, and acceptable to the community and other stakeholders.
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Abastecimiento de Alimentos/estadística & datos numéricos , Frutas , Estado Nutricional , Población Rural , Verduras , Adolescente , Adulto , Agricultura/economía , Comercio/economía , Costos y Análisis de Costo , Dieta , Agricultores , Femenino , Abastecimiento de Alimentos/economía , Promoción de la Salud , Humanos , India , Micronutrientes/administración & dosificación , Micronutrientes/deficiencia , Investigación Cualitativa , Adulto JovenRESUMEN
OBJECTIVES: To (1) describe micronutrient intakes among women of reproductive age living in Mumbai slums; (2) assess the adequacy of these intakes compared with reference values; (3) identify important dietary sources of micronutrients. SUBJECTS/METHODS: Participants were 6426 non-pregnant women aged 16-39 years, registered in a randomised controlled trial of a food-based intervention set in the Bandra, Khar and Andheri areas of Mumbai, India. Cross-sectional quantified food frequency questionnaire (FFQ) data were collected. Vitamin (n = 9) and mineral (n = 6) intakes were calculated and analysed in relation to dietary reference values (DRVs). Important dietary sources were identified for each micronutrient. RESULTS: Median intakes of all micronutrients, except vitamin E, were below the FAO/WHO reference nutrient intake (RNI). Intakes of calcium, iron, vitamin A and folate were furthest from the RNI. For seven of the micronutrients, over half of the women had intakes below the lower reference nutrient intake (LRNI); this figure was over 75% for calcium and riboflavin. The majority of women (93%) had intakes below the EAR for 5 or more micronutrients, and 64% for 10 or more. Adolescents had lower intakes than women aged >19 years. Less than 1% of adult women and no adolescents met the EAR for all micronutrients. Animal source foods and micronutrient-rich fruit and vegetables were consumed infrequently. CONCLUSIONS: These women had low intakes of multiple micronutrients, increasing their risk of insufficiency. There is a need to determine the factors causing poor intakes, to direct interventions that improve diet quality and nutritional sufficiency.
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Dieta/estadística & datos numéricos , Ingestión de Energía/fisiología , Micronutrientes/sangre , Estado Nutricional/fisiología , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , India/epidemiología , Metales Pesados/sangre , Áreas de Pobreza , Adulto JovenRESUMEN
BACKGROUND: Micronutrient deficiencies have been a serious public health problem among women of reproductive age in low- and middle-income countries including India, adversely affecting maternal and child health and human capital outcomes. Fruit and vegetables are important sources of micronutrients, and consumption of these foods is less than recommendations. OBJECTIVE: The objective of this study was to identify perceived barriers and facilitators to fruit and vegetable consumption among women of reproductive age living in rural communities in the State of Maharashtra, India. METHODS: Women aged 18 to 40 years were recruited from 8 villages surrounding the city of Wardha, Maharashtra, India. We used qualitative methods and held 9 focus group discussions and 12 one-to-one interviews. The data collection was stopped when no new information emerged. We used inductive thematic coding to analyze the data. RESULTS: Women knew that fruit and vegetables were beneficial to health and expressed that they wanted to increase the intake of these foods for themselves and their children. Seven main themes were identified as being barriers or facilitators to fruit and vegetable consumption: (1) personal factors, (2) household dynamics, (3) social and cultural norms, (4) workload, (5) time pressures, (6) environmental factors, and (7) cost. CONCLUSIONS: Rural Indian women consumed fruit and vegetables infrequently and said they would like to consume more. Several potentially modifiable factors affecting the intake of fruit and vegetables were identified. Value chain analyses of fruit and vegetables in these communities will be important to identify opportunities to intervene and increase consumption.
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Dieta , Frutas , Verduras , Adolescente , Adulto , Femenino , Grupos Focales , Humanos , India , Factores de Riesgo , Población Rural , Factores Socioeconómicos , Adulto JovenRESUMEN
BACKGROUND: Young maternal age is associated with poorer birth outcomes, but the mechanisms are incompletely understood. Using data from a prospective cohort of pregnant women living in Mumbai slums, India, we tested whether lower maternal age was associated with adverse fetal growth. METHODS: Fetal crown-rump length (CRL) was recorded at a median (interquartile range, IQR) of 10 weeks' gestation (9-10 weeks). Head circumference (HC), biparietal diameter (BPD), femur length (FL), and abdominal circumference (AC) were recorded at 19 (19-20) and 29 (28-30) weeks. Newborns were measured at a median (IQR) of 2 days (1-3 days) from delivery. Gestation was assessed using prospectively collected menstrual period dates. RESULTS: The sample comprised 1653 singleton fetuses without major congenital abnormalities, of whom 1360 had newborn measurements. Fetuses of younger mothers had smaller CRL (0.01 standard deviation [SD] per year of maternal age; 95% confidence interval CI: 0.00-0.02 1 ; P = .04), and smaller HC, FL, and AC at subsequent visits. Fetal growth of HC (0.04 cm; 95% CI: 0.02-0.05; P < .001), BPD (0.01 cm; 95% CI: 0.00-0.01; P = .009), FL (0.04 cm; 95% CI: 0.02-0.06; P < .001), and AC (0.01 cm; 95% CI: 0.00-0.01; P = .003) up to the third trimester increased with maternal age. Skinfolds, head, and mid-upper arm circumferences were smaller in newborns of younger mothers. Adjusting for maternal prepregnancy socioeconomic status, body mass index, height, and parity attenuated the associations between maternal age and newborn size but did not change those with fetal biometry. CONCLUSION: Fetuses of younger mothers were smaller from the first trimester onward and grew slower, independently of known confounding factors.
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Desarrollo Infantil , Desarrollo Fetal , Retardo del Crecimiento Fetal/etiología , Edad Materna , Fenómenos Fisiologicos Nutricionales Maternos , Estado Nutricional , Abdomen/crecimiento & desarrollo , Adolescente , Adulto , Peso al Nacer , Largo Cráneo-Cadera , Femenino , Fémur/diagnóstico por imagen , Fémur/crecimiento & desarrollo , Retardo del Crecimiento Fetal/diagnóstico por imagen , Retardo del Crecimiento Fetal/fisiopatología , Edad Gestacional , Cabeza/diagnóstico por imagen , Cabeza/crecimiento & desarrollo , Humanos , India , Recién Nacido , Recien Nacido Prematuro , Recién Nacido Pequeño para la Edad Gestacional , Masculino , Embarazo , Nacimiento Prematuro/etiología , Nacimiento Prematuro/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Ultrasonografía Prenatal , Adulto JovenRESUMEN
Background: Early life nutrition may affect individuals' susceptibility to adult non-communicable diseases (NCD). Psychological stress is a well-recognised NCD risk factor. Recent evidence suggests that impaired foetal nutrition alters neuro-endocrine pathways, and hypothalamic-pituitary-adrenal axis feedback systems, resulting in abnormal stress responses, and NCD risk. This study aims to examine adolescent cortisol and cardiovascular stress responses in relation to maternal nutrition and contemporaneous NCD risk markers. Methods: The study sample will be drawn from three well-established birth cohorts in India; the Parthenon cohort, Mysore (N=550, age~20y), the SARAS KIDS prenatal intervention cohort, Mumbai (N=300, age~10-12y) and the Pune Rural Intervention in Young Adults/ PRIYA cohort, Pune (N=100, age~22y). We will perform the 'Trier Social Stress Test (TSST)', a well-accepted stress-test module which involves participants performing 5-minutes each of public speaking and mental arithmetic tasks in front of unfamiliar 'judges' (stressor). Repeated measures of salivary cortisol and autonomic cardiovascular outcomes relative to the stressor will be assessed. Measures of psychological stress, cognitive function, blood pressure, glucose-insulin metabolism and depression will be carried out. Mechanistic studies including DNA methylation in gluco-corticoid receptor ( NR3C1) and 11ß-HSD2 gene loci and neuroimaging will be carried out in a subsample. Qualitative interviews and focus group discussions in a subsample of the Parthenon cohort will explore the perception of stress and stressors among the youth. We will convert repeated measures into time-weighted averages before analysis. We will carry out multivariable regression analysis to test the associations. We will further refine the analyses using the mixed-model regression and conditional analyses for the association with repeated measures. Ethics and dissemination: This study has been approved by the research ethics committee of CSI Holdsworth Memorial Hospital, Mysore. The findings will be disseminated locally and at international meetings, and reports will be submitted to open access peer reviewed journals.
RESUMEN
BACKGROUND AND OBJECTIVES: There are few data on the fatty acid status of non-pregnant Indian women. Our objective was to investigate the effect of a snack containing green leafy vegetables (GLVs) on women's erythrocyte long chain polyunsaturated fatty acid status (LCPUFA). METHODS AND STUDY DESIGN: Non-pregnant women (n=222) aged 14-35 years from Mumbai slums were randomized to consume a snack containing GLVs, fruit and milk (treatment) or a control snack containing foods of low micronutrient content such as potato and onion, daily under observation. One treatment snack contained a mean (SD) of 54.1 (33.7) mg alpha-linolenic acid (ALA) and one control snack contained 4.1 (3.4) mg ALA. Blood was collected at baseline (0 weeks) and after 12 weeks of supplementation. Erythrocyte fatty acids were analyzed using gas chromatography and expressed as g/100g fatty acids. Plasma malondialdehyde, homocysteine, and erythrocyte superoxide dismutase and glutathione peroxidase were measured. The effect of the treatment on 12 week LCPUFA was assessed using ANCOVA models. RESULTS: Median (IQR) erythrocyte DHA in the treatment group increased from 1.50 (1.11, 2.03) at baseline to 1.86 (1.50, 2.43) (p<0.001) at 12 weeks, and fell in controls from 1.78 (1.37, 2.32) to 1.60 (1.32, 2.04) (p<0.001). The total n-3 fatty acids increased in the treatment group. There was no effect on malondialdehyde and antioxidant enzyme levels. Plasma homocysteine at 0 and 12 weeks was inversely associated with erythrocyte DHA at 12 weeks. CONCLUSION: Daily consumption of a snack containing GLV improved women's erythrocyte DHA levels without increasing oxidative stress.
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Ácidos Grasos/sangre , Bocadillos , Verduras , Adolescente , Adulto , Dieta , Eritrocitos , Ácidos Grasos/metabolismo , Femenino , Homocisteína , Humanos , India , Adulto JovenRESUMEN
Improving micronutrient intakes of under-nourished mothers in low- and middle-income countries increases birth weight, but there is little data on the nature and timing during gestation of any effects on fetal growth. Ultrasound measures of fetal size were used to determine whether and when a food-based supplement affected fetal growth. Non-pregnant women living in Mumbai slums, India (N = 6,513), were randomly assigned to receive either a daily micronutrient-rich snack containing green leafy vegetables, fruit, and milk (treatment) or a snack made from lower-micronutrient vegetables (control) in addition to their usual diet from before pregnancy until delivery. From 2,291 pregnancies, the analysis sample comprised 1,677 fetuses (1,335 fetuses of women supplemented for ≥3 months before conception). First-trimester (median: 10 weeks, interquartile range: 9-12 weeks) fetal crown-rump length was measured. Fetal head circumference, biparietal diameter, femur length, and abdominal circumference were measured during the second (19, 19-20 weeks) and third trimesters (29, 28-30 weeks). The intervention had no effect on fetal size or growth at any stage of pregnancy. In the second trimester, there were interactions between parity and allocation group for biparietal diameter (p = .02) and femur length (p = .04) with both being smaller among fetuses of primiparous women and larger among those of multiparous women, in the treatment group compared with the controls. Overall, a micronutrient-rich supplement did not increase standard ultrasound measures of fetal size and growth at any stage of pregnancy. Additional ultrasound measures of fetal soft tissues (fat and muscle) may be informative.
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Dieta , Desarrollo Fetal , Micronutrientes/administración & dosificación , Atención Prenatal/métodos , Ultrasonografía Prenatal , Adulto , Animales , Antropometría , Largo Cráneo-Cadera , Suplementos Dietéticos , Femenino , Feto/diagnóstico por imagen , Frutas , Edad Gestacional , Humanos , India , Masculino , Fenómenos Fisiologicos Nutricionales Maternos , Leche , Estado Nutricional , Áreas de Pobreza , Atención Preconceptiva/métodos , Embarazo , Bocadillos , VerdurasRESUMEN
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.
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Fucosiltransferasas/genética , Vitamina B 12/metabolismo , Adulto , Alelos , Pueblo Asiatico/genética , Niño , Preescolar , Femenino , Fucosiltransferasas/metabolismo , Frecuencia de los Genes/genética , Genética de Población , Estudio de Asociación del Genoma Completo , Humanos , India , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Vitamina B 12/sangre , Población Blanca/genéticaRESUMEN
BACKGROUND: Animal studies have shown that nutritional exposures during pregnancy can modify epigenetic marks regulating fetal development and susceptibility to later disease, providing a plausible mechanism to explain the developmental origins of health and disease. Human observational studies have shown that maternal peri-conceptional diet predicts DNA methylation in offspring. However, a causal pathway from maternal diet, through changes in DNA methylation, to later health outcomes has yet to be established. The EMPHASIS study (Epigenetic Mechanisms linking Pre-conceptional nutrition and Health Assessed in India and Sub-Saharan Africa, ISRCTN14266771) will investigate epigenetically mediated links between peri-conceptional nutrition and health-related outcomes in children whose mothers participated in two randomized controlled trials of micronutrient supplementation before and during pregnancy. METHODS: The original trials were the Mumbai Maternal Nutrition Project (MMNP, ISRCTN62811278) in which Indian women were offered a daily snack made from micronutrient-rich foods or low-micronutrient foods (controls), and the Peri-conceptional Multiple Micronutrient Supplementation Trial (PMMST, ISRCTN13687662) in rural Gambia, in which women were offered a daily multiple micronutrient (UNIMMAP) tablet or placebo. In the EMPHASIS study, DNA methylation will be analysed in the children of these women (~1,100 children aged 5-7 y in MMNP and 298 children aged 7-9 y in PMMST). Cohort-specific and cross-cohort effects will be explored. Differences in DNA methylation between allocation groups will be identified using the Illumina Infinium MethylationEPIC array, and by pyrosequencing top hits and selected candidate loci. Associations will be analysed between DNA methylation and health-related phenotypic outcomes, including size at birth, and children's post-natal growth, body composition, skeletal development, cardio-metabolic risk markers (blood pressure, serum lipids, plasma glucose and insulin) and cognitive function. Pathways analysis will be used to test for enrichment of nutrition-sensitive loci in biological pathways. Causal mechanisms for nutrition-methylation-phenotype associations will be explored using Mendelian Randomization. Associations between methylation unrelated to supplementation and phenotypes will also be analysed. CONCLUSION: The study will increase understanding of the epigenetic mechanisms underpinning the long-term impact of maternal nutrition on offspring health. It will potentially lead to better nutritional interventions for mothers preparing for pregnancy, and to identification of early life biomarkers of later disease risk.