Programming of cardiac metabolism by miR-15b-5p, a miRNA released in cardiac extracellular vesicles following ischemia-reperfusion injury.

OBJECTIVE: We investigated the potential involvement of miRNAs in the developmental programming of cardiovascular diseases (CVD) by maternal obesity. METHODS: Serum miRNAs were measured in individuals from the Helsinki Birth Cohort (with known maternal body mass index), and a mouse model was used to determine causative effects of maternal obesity during pregnancy and ischemia-reperfusion on offspring cardiac miRNA expression and release. RESULTS: miR-15b-5p levels were increased in the sera of males born to mothers with higher BMI and in the hearts of adult mice born to obese dams. In an ex-vivo model of perfused mouse hearts, we demonstrated that cardiac tissue releases miR-15b-5p, and that some of the released miR-15b-5p was contained within small extracellular vesicles (EVs). We also demonstrated that release was higher from hearts exposed to maternal obesity following ischaemia/reperfusion. Over-expression of miR-15b-5p in vitro led to loss of outer mitochondrial membrane stability and to repressed fatty acid oxidation in cardiomyocytes. CONCLUSIONS: These findings suggest that miR-15-b could play a mechanistic role in the dysregulation of cardiac metabolism following exposure to an in utero obesogenic environment and that its release in cardiac EVs following ischaemic damage may be a novel factor contributing to inter-organ communication between the programmed heart and peripheral tissues.

Longitudinal Growth and Undernutrition Burden Among Term Low Birth Weight Newborns Reared in Adverse Socioeconomic Conditions in Delhi.

BACKGROUND: There is limited data in term low birth weight neonates from urban poor settings on the incidence of and recovery from undernutrition and co-existence of its different forms, under conditions of appropriate health and nutrition care counselling. OBJECTIVES: To determine the longitudinal growth and undernutrition burden among term low birth weight newborns reared in adverse conditions, but with appropriate counselling. METHODS: The study reports follow-up data from DIVIDS trial. 2079 term low birth weight (1800-2499 grams) newborns from an urban poor setting were followed-up for growth from 0 to 26 weeks (n=1282) and at 2.8-6.8 years (n=912). Using Cole LMS approach, age- and sex-specific internal z scores were computed and subsequently adjusted for the effect of a vitamin D intervention and potential bias due to attrition. Back-transformed measurements were then used to compute WHO z scores for height for age (HAZ), weight for age (WAZ), and BMI for age (BMIZ). RESULTS: HAZ remained fairly stable: mean changes from birth till 6 weeks, 26 weeks and 3-7 years were 0.07, 0.04 and 0.2 SD, respectively. BMIZ and WAZ showed considerable catch-up; 0.69 SD, 1.84 SD and 1.38 SD for BMIZ, and 0.25 SD, 0.89 SD and 0.60 SD for WAZ, respectively. 60-92% had at least one form of undernutrition and co-existence was frequent. Half the children remained stunted till 5 years, while underweight and wasting declined considerably from 0-6 months. CONCLUSION: With appropriate counselling of parents, term low birth weight infants reared under adverse socioeconomic conditions show substantial catch-up growth in BMIZ and WAZ but not in HAZ. The long-term consequences of this excess weight over length gain need focused evaluation.

Growth in Infancy and Childhood and Age at Menarche in Five Low- or Middle-Income Countries: Consortium of Health Orientated Research in Transitional Societies (COHORTS).

BACKGROUND: Earlier age at menarche is associated with behavioral and noncommunicable disease risks. The influence of birth weight (BW) (intrauterine) and postnatal growth on age at menarche is not well studied in low- and middle-income countries (LMICs). OBJECTIVE: Therefore, we investigated these associations in 5 LMIC birth cohorts. METHODS: We analyzed data from Brazil, Guatemala, India, the Philippines, and South Africa (n = 3983). We derived stunting (< -2 SD scores) at 24 mo using the WHO child growth standards. We generated interaction terms with categorized BW and conditional weight (lighter < 0 or heavier ≥ 0), and height (shorter < 0 or taller ≥ 0) z-scores. We categorized early-, modal-, and late-onset menarche and used multilevel ordinal regression. We used multilevel linear regression on continuous age at menarche. RESULTS: Mean age at menarche was 12.8 y (95% CI: 12.7 12.9). BW was not associated with age at menarche. Conditional height at 24 mo and mid-childhood (OR: 1.35; 95% CI: 1.27, 1.44 and 1.32; 1.25, 1.41, respectively) and conditional weight at 24 mo and mid-childhood (OR: 1.15; 1.08, 1.22 and 1.18; 1.11, 1.25, respectively) were associated with increased likelihood of early-onset menarche. Being heavier at birth and taller at 24 mo was associated with a 4-mo (95% CI: 0.8, 7.6) earlier age at menarche than being lighter at birth and shorter at 24 mo. Being heavier at birth but lighter in mid-childhood was associated with a 3-mo (95% CI: 0.8, 4.8) later age at menarche than being lighter at birth and mid-childhood. Age at menarche was 7 mo later in stunted than nonstunted girls. CONCLUSION: Age at menarche is inversely related to relative weight gain but also to rapid linear growth among those born shorter but remained stunted, and those born taller and grew excessively. These findings do not deter the global health goal to reduce growth faltering but emphasize the potential adverse effects of an obesogenic environment on adolescent development.

Echocardiography protocol and cardiometabolic phenotyping in Indian birth cohorts-the IndEcho study.

Background: Asian Indians are at higher risk of cardiometabolic disease compared to other ethnic groups, and the age of onset is typically younger. Cardiac structure and function are poorly characterized in this ethnic group. In this study, we describe image-acquisition methods and the reproducibility of measurements and detailed echocardiography characteristics in two large Indian population-based cohorts (the New Delhi and Vellore Birth Cohorts) from India. Methods: The IndEcho study captured transthoracic echocardiographic measurements of cardiac structure and function from 2,322 men and women aged 43-50 years. M-mode measurements in the parasternal long axis (PLAX) and 2-dimensional (2D) short axis recordings at the mitral valve, mid-papillary and apical level were recorded. Apical 2D recordings of two- three- and four-chamber (2C, 3C and 4C) views and Doppler images (colour, pulsed and continuous) were recorded in cine-loop format. Left ventricular (LV) mass, LV hypertrophy, and indices of LV systolic and diastolic function were derived. Results: Echocardiographic measurements showed good/excellent technical reproducibility. Hetero-geneity across sites, sex and rural/urban differences in cardiac structure and function were observed. Overall, this cohort of South Asian Indians had smaller LV mass and normal systolic and diastolic function when compared with published data on other Asian Indians and the West, (LV mass indexed for body surface area: Delhi men: 68 g/m2, women 63.9; Vellore men: 65.8, women 61.6) but were within ethnic-specific reference ranges. The higher prevalence of obesity, diabetes and hypertension is reflected by the higher proportion of LV remodelling and lesser hypertrophy. Conclusions: Our study adds to scarce population-based echocardiographic data for mid-life Asian Indians. Compared to published literature on other ethnic groups, the Asian Indian heart is characterised by smaller cardiac dimensions and normal range systolic and diastolic function on a background of a high prevalence of hypertension, diabetes and cardiac disease at a relatively young age. This data will form the basis for further analyses of lifecourse, metabolic and body composition predictors of cardiac structure and function, and echocardiographic predictors of future mortality. ISRCTN registration number: 13432279.

The Long-Term Consequences of Early Life Exposure to Tsunami and Conflict on Adolescents in Sri Lanka.

The consequences for adolescent health due to early life exposure to natural disasters combined with war are not known. We collected data from adolescents aged 12-13 years in Sri Lanka whose mothers were pregnant during the Indian Ocean tsunami in 2004 in a tsunami-affected region (n = 22), conflict-affected region (n = 35), conflict-plus-tsunami-affected region (n = 29), or controls in areas unaffected by either (n = 24). Adjusted body mass index (BMI)-for-age z-scores were 1.3, 1.0 and 2.0 for conflict, tsunami, and conflict-plus-tsunami, respectively, compared with the control group. Greater skinfold thickness and higher diastolic blood pressure were found in adolescents born in the conflict zone but no differences were found in height, head circumference, and waist circumference, or blood results, with the exception of serum insulin. Being born after a natural disaster or during conflict was associated with increased BMI and body fat during adolescent, which are associated with longer-term risk of noncommunicable disease.

Comparison of Weight for Height and BMI for Age for Estimating Overnutrition Burden in Under-Five Populations With High Stunting Prevalence.

BACKGROUND: Overnourished under-five children are anthro-pometrically classified as either being at possible risk of over-weight, overweight or obese and defined so, when either weight for height or body mass index for age (BMI-for-age) are >1SD to 2SD, >2SD to 3SD and >3SD, respectively of the analogous World Health Organization standards. AIM: To compare weight for height and BMI for age definitions for quantifying overnutrition burden. METHODS: Theoretical consequences of ignoring age were evaluated by comparing, at varying height for age z-scores, the age- and sex-specific cutoffs of BMI that would define overnutrition with these two metrics. Overnutrition prevalence was then compared in simulated populations (short, intermediate and tall) and real-life datasets from India. RESULTS: In short (-2SD) children, the BMI cutoffs with weight for height criteria were lower in comparison to BMI for age till 7-8 months, but higher at later ages. In National Family Health Survey-4, India dataset (short population), overnutrition (>1SD) prevalence with weight for height was higher from 0-0.5 years (exclusive breastfeeding age), but lower at subsequent ages. The prevalence difference (weight for height - BMI for age) in 0.5-5 years was -2.26% (6.57% vs 8.83%); this attenuated in 0-5 years (-1.55%; 7.23% vs 8.78%). The discrepancy was maxi-mal for stunted children and was lower in girls. A similar pattern, of lower magnitude, was observed for overweight (>2SD) com-parison. In intermediate and tall populations, there were no meaningful differences. CONCLUSION: The two definitions produce cutoffs, and hence estimates of overnutrition, that differ with the age, sex, and height of under-five children. The relative invariance, with age and height, of BMI for age, favors its use.

Conditional wealth to estimate association of wealth mobility with health and human capital in low- and middle-income country cohorts.

Temporally harmonized asset indices allow the study of changes in relative wealth (mean, variance, social mobility) over time and its association with adult health and human capital in cohort studies. Conditional measures are the unexplained residuals of an indicator regressed on its past values. Using such measures, previously used to study the relative importance of key life stages for anthropometric growth, we can identify specific life stages during which changes in relative wealth are important for adult health in longitudinal studies. We discuss the assumptions, strengths and limitations of this methodology as applied to relative wealth. We provide an illustrative example using a publicly-available longitudinal dataset and show how relative wealth changes at different life stages are differentially associated with body mass index in adulthood.

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.

Effects of early-life poverty on health and human capital in children and adolescents: analyses of national surveys and birth cohort studies in LMICs.

The survival and nutrition of children and, to a lesser extent, adolescents have improved substantially in the past two decades. Improvements have been linked to the delivery of effective biomedical, behavioural, and environmental interventions; however, large disparities exist between and within countries. Using data from 95 national surveys in low-income and middle-income countries (LMICs), we analyse how strongly the health, nutrition, and cognitive development of children and adolescents are related to early-life poverty. Additionally, using data from six large, long-running birth cohorts in LMICs, we show how early-life poverty can have a lasting effect on health and human capital throughout the life course. We emphasise the importance of implementing multisectoral anti-poverty policies and programmes to complement specific health and nutrition interventions delivered at an individual level, particularly at a time when COVID-19 continues to disrupt economic, health, and educational gains achieved in the recent past.

Health and development from preconception to 20 years of age and human capital.

Optimal health and development from preconception to adulthood are crucial for human flourishing and the formation of human capital. The Nurturing Care Framework, as adapted to age 20 years, conceptualises the major influences during periods of development from preconception, through pregnancy, childhood, and adolescence that affect human capital. In addition to mortality in children younger than 5 years, stillbirths and deaths in 5-19-year-olds are important to consider. The global rate of mortality in individuals younger than 20 years has declined substantially since 2000, yet in 2019 an estimated 8·6 million deaths occurred between 28 weeks of gestation and 20 years of age, with more than half of deaths, including stillbirths, occurring before 28 days of age. The 1000 days from conception to 2 years of age are especially influential for human capital. The prevalence of low birthweight is high in sub-Saharan Africa and even higher in south Asia. Growth faltering, especially from birth to 2 years, occurs in most world regions, whereas overweight increases in many regions from the preprimary school period through adolescence. Analyses of cohort data show that growth trajectories in early years of life are strong determinants of nutritional outcomes in adulthood. The accrual of knowledge and skills is affected by health, nutrition, and home resources in early childhood and by educational opportunities in older children and adolescents. Linear growth in the first 2 years of life better predicts intelligence quotients in adults than increases in height in older children and adolescents. Learning-adjusted years of schooling range from about 4 years in sub-Saharan Africa to about 11 years in high-income countries. Human capital depends on children and adolescents surviving, thriving, and learning until adulthood.

Preterm birth and infant diurnal cortisol regulation.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis adaptation is a potential mechanism linking early life exposures with later adverse health. This study tested the hypothesis that preterm birth is associated with adaptation of diurnal cortisol regulation across infancy. METHODS: A secondary analysis was conducted of saliva cortisol measured morning, midday and evening, monthly, across infancy, as part of a birth cohort conducted in Linköping, Sweden. Diurnal cortisol regulation of infants born extremely preterm (n=24), very preterm (n=27) and at term (n=130) were compared across infancy through random coefficients regression models. RESULTS: Compared with infants born at term, infants born extremely preterm (-17.2%, 95% CI: -30.7 to -1.2), but not very preterm (1.7%, 95% CI: -14.1 to 20.4), had a flattened diurnal slope across infancy. CONCLUSIONS: Extremely preterm birth is associated with a flattened diurnal slope in infancy. This pattern of cortisol regulation could contribute to adverse metabolic and neurodevelopmental phenotypes observed in this population.

The effect of wasting and stunting during severe acute malnutrition in infancy on insulin sensitivity and insulin clearance in adult life.

Adults who had non-edematous severe acute malnutrition (SAM) during infancy (i.e., marasmus) have worse glucose tolerance and beta-cell function than survivors of edematous SAM (i.e., kwashiorkor). We hypothesized that wasting and/or stunting in SAM is associated with lower glucose disposal rate (M) and insulin clearance (MCR) in adulthood.We recruited 40 nondiabetic adult SAM survivors (20 marasmus survivors (MS) and 20 kwashiorkor survivors (KS)) and 13 matched community controls. We performed 150-minute hyperinsulinaemic, euglycaemic clamps to estimate M and MCR. We also measured serum adiponectin, anthropometry, and body composition. Data on wasting (weight-for-height) and stunting (height-for-age) were abstracted from the hospital records.Children with marasmus had lower weight-for-height z-scores (WHZ) (-3.8 ± 0.9 vs. -2.2 ± 1.4; P < 0.001) and lower height-for-age z-scores (HAZ) (-4.6 ± 1.1 vs. -3.4 ± 1.5; P = 0.0092) than those with kwashiorkor. As adults, mean age (SD) of participants was 27.2 (8.1) years; BMI was 23.6 (5.0) kg/m2. SAM survivors and controls had similar body composition. MS and KS and controls had similar M (9.1 ± 3.2; 8.7 ± 4.6; 6.9 ± 2.5 mg.kg-1.min-1 respectively; P = 0.3) and MCR. WHZ and HAZ were not associated with M, MCR or adiponectin even after adjusting for body composition.Wasting and stunting during infancy are not associated with insulin sensitivity and insulin clearance in lean, young, adult survivors of SAM. These data are consistent with the finding that glucose intolerance in malnutrition survivors is mostly due to beta-cell dysfunction.

Saliva cortisol diurnal variation and stress responses in term and preterm infants.

OBJECTIVE: To determine if preterm birth is associated with adaptation of the hypothalamic-pituitary-adrenal (HPA) axis and whether HPA axis programming relates to the degree of prematurity (defined as extremely preterm birth at <28 weeks or very preterm birth at 28-32 weeks gestation). DESIGN: This study reports findings from a prospective birth cohort. Saliva cortisol concentrations were measured prevaccination and postvaccination, and in the morning and evening, at 4 months chronological age. SETTING: Infants born at a single Scottish hospital. PARTICIPANTS: 45 term-born, 42 very preterm and 16 extremely preterm infants. OUTCOMES: Cortisol stress response to vaccination (postvaccination minus prevaccination cortisol concentrations), diurnal slope (log-transformed morning minus log-transformed evening cortisol values) and mean log-transformed daily cortisol. RESULTS: Compared with infants born at term, infants born extremely preterm had a blunted cortisol response to vaccination (5.8 nmol/L vs 13.1 nmol/L, difference in means: -7.3 nmol/L, 95% CI -14.0 to -0.6) and a flattened diurnal slope (difference in geometric means: -72.9%, 95% CI -87.1 to -42.8). In contrast, the cortisol response to vaccination (difference in means -2.7 nmol/L, 95% CI -7.4 to 2.0) and diurnal slope at 4 months (difference in geometric means: -33.6%, 95% CI -62.0 to 16.0) did not differ significantly in infants born very preterm compared with infants born at term. CONCLUSIONS: Infants born extremely preterm have blunted cortisol reactivity and a flattened diurnal slope. These patterns of HPA axis regulation are commonly seen after childhood adversity and could contribute to later metabolic and neurodevelopmental phenotypes observed in this population.

Weight-for-height is associated with an overestimation of thinness burden in comparison to BMI-for-age in under-5 populations with high stunting prevalence.

BACKGROUND: Thinness at <5 years of age, also known as wasting, is used to assess the nutritional status of populations for programmatic purposes. Thinness may be defined when either weight-for-height or body-mass-index-for-age (BMI-for-age) are below -2 SD of the respective World Health Organization standards. These definitions were compared for quantifying the burden of thinness. METHODS: Theoretical consequences of ignoring age were evaluated by comparing, at varying height-for-age z-scores, the age- and sex-specific cut-offs of BMI that would define thinness with these two metrics. Thinness prevalence was then compared in simulated populations (short, intermediate and tall) and real-life data sets from research and the National Family Health Survey-4 (NFHS-4) in India. RESULTS: In short (-2 SD) children, the BMI cut-offs with weight-for-height criteria were higher in comparison to BMI-for-age after 1 year of age but lower at earlier ages. In Indian research and NFHS-4 data sets (short populations), thinness prevalence with weight-for-height was lower from 0.5 to 1 years but higher at subsequent ages. The absolute difference (weight-for-height - BMI-for-age) for 0.5-5 years was 4.6% (15.9-11.3%) and 2.2% (19.2-17.0%), respectively; this attenuated in the 0-5 years age group. The discrepancy was higher in boys and maximal for stunted children, reducing with increasing stature. In simulated data sets from intermediate and tall populations, there were no meaningful differences. CONCLUSIONS: The two definitions produce cut-offs, and hence estimates of thinness, that differ with the age, sex and height of children. The relative invariance, with age and stature, of the BMI-for-age thinness definition favours its use as the preferred index for programmatic purposes.

Early Life Influences on Hearing in Adulthood: a Systematic Review and Two-Step Individual Patient Data Meta-Analysis.

OBJECTIVES: Adverse prenatal and early childhood development may increase susceptibility of hearing loss in adulthood. The objective was to assess whether indices of early development are associated with adult-onset hearing loss in adults ≥18 years. DESIGN: In a systematic review and meta-analysis, four electronic databases were searched for studies reporting associations between indices of early development (birth weight and adult height) and adult-onset hearing loss in adults ≥18 years. We screened studies, extracted data, and assessed risk of bias. Authors were contacted to provide adjusted odds ratios from a logistic regression model for relationships between birth weight/adult height and normal/impaired hearing enabling a two-step individual patient data random-effects meta-analysis to be carried out. The study is registered with PROSPERO, CRD42020152214. RESULTS: Four studies of birth weight and seven of adult height were identified. Three studies reported smaller birth weight associated with poorer adult hearing. Six studies reported shorter height associated with poorer hearing. Risk of bias was low to moderate. Four studies provided data for two-step individual patient data random-effects meta-analysis. Odds of hearing impairment were 13.5% lower for every 1 kg increase in birth weight [OR: 0.865 (95% confidence interval: 0.824 to 0.909)] in adulthood over two studies (N=81,289). Every 1 cm increase in height was associated with a 3% reduction in the odds of hearing impairment [OR: 0.970 (95% confidence interval: 0.968 to 0.971)] over four studies (N=156,740). CONCLUSIONS: Emerging evidence suggests that adverse early development increases the likelihood of hearing impairment in adulthood. Research and public health attention should focus on the potential for prevention of hearing impairment by optimizing development in early life.

Cardiovascular disease in people born to unmarried mothers in two historical periods: The Helsinki Birth Cohort Study 1934-1944.

Aims:Socio-economic conditions in early life are important contributors to cardiovascular disease - the leading cause of mortality globally - in later life. We studied coronary heart disease (CHD) and stroke in adulthood among people born out of wedlock in two historical periods: before and during World War II in Finland. Methods: We compared offspring born out of wedlock before (1934-1939) and during (1940-1944) World War II with the offspring of married mothers in the Helsinki Birth Cohort Study. The war affected the position of unmarried mothers in society. We followed the study subjects from 1971 to 2014 and identified deaths and hospital admissions from CHD and stroke. Data were analysed using a Cox regression, adjusting for other childhood and adulthood socio-economic circumstances. Results: The rate of out-of-wedlock births was 240/4052 (5.9%) before World War II and 397/9197 (4.3%) during World War II. Among those born before World War II, out-of-wedlock birth was associated with an increased risk of stroke (hazard ratio (HR)=1.44; 95% confidence interval (CI) 1.00-2.07) and CHD (HR=1.37; 95% CI 1.02-1.86). Among those born out of wedlock during World War II, the risks of stroke (HR=0.89; 95% CI 0.58-1.36) and CHD (HR=0.70; 95% CI 0.48=1.03) were similar to those observed for the offspring of married mothers. The p-values for interaction of unmarried×World War II were (p=0.015) for stroke and (p=0.003) for CHD. Conclusions: In a society in which marriage is normative, being born out of wedlock is an important predictor of lifelong health disadvantage. However, this may change rapidly when societal circumstances change, such as during a war.

Intergenerational change in anthropometry of children and adolescents in the New Delhi Birth Cohort.

BACKGROUND: A comparison of the anthropometry of children and adolescents with that of their parents at the same age may provide a more precise measure of intergenerational changes in linear growth and body mass index (BMI). METHODS: New Delhi Birth Cohort participants (F1), born between 1969 and 1972, were followed up for anthropometry at birth and at 6-monthly intervals until 21 years of age. At variable intervals 1447 children, aged 0-19 years (F2) and born to 818 F1 participants, were measured (weight and height), providing 2236 sets of anthropometries. Intergenerational changes (F2-F1) in height and BMI [absolute and standard deviation (SD) units] were computed by comparing children with their parents at corresponding ages. RESULTS: F2 children were taller (P < 0.001) than their parents at corresponding ages; the increase {mean [95% confidence interval (CI)] World Health Organization SD units} was 0.97 (0.83, 1.11), 1.21 (1.10, 1.32), 1.09 (0.98, 1.19), 1.10 (1.00, 1.21) and 0.75 (0.65, 0.85) for age categories of 0-5, 5-7.5, 7.5-10, 10-12.5 and >12.5 years, respectively. In absolute terms, this increase ranged from 3.5 cm (0-5-year-olds) to 7.5 cm (10-12.5-year-olds). The corresponding increases in BMI SD scores were 0.32 (0.18, 0.47), 0.60 (0.45, 0.75), 1.13 (0.99, 1.27), 1.30 (1.15, 1.45) and 1.00 (0.85, 1.15), respectively. The absolute BMI increase ranged from 1-3 kg/m2 at >5 years age to ∼3 kg/m2 at >10-years of age. The intergenerational increases were comparable in both sexes, but were greater in children born and measured later. A positive change in socioeconomic status was associated with an increase in height across the generations. CONCLUSIONS: Children and adolescents, throughout the ages 0-19 years, have become considerably taller and have a higher BMI than their parents at corresponding ages in an urban middle-class Indian population undergoing socioeconomic improvements.

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.

Poor In Utero Growth, and Reduced ß-Cell Compensation and High Fasting Glucose From Childhood, Are Harbingers of Glucose Intolerance in Young Indians.

OBJECTIVE: India is a double world capital of early-life undernutrition and type 2 diabetes. We aimed to characterize life course growth and metabolic trajectories in those developing glucose intolerance as young adults in the Pune Maternal Nutrition Study (PMNS). RESEARCH DESIGN AND METHODS: PMNS is a community-based intergenerational birth cohort established in 1993, with serial information on parents and children through pregnancy, childhood, and adolescence. We compared normal glucose-tolerant and glucose-intolerant participants for serial growth, estimates of insulin sensitivity and secretion (HOMA and dynamic indices), and ß-cell compensation accounting for prevailing insulin sensitivity. RESULTS: At 18 years (N = 619), 37% of men and 20% of women were glucose intolerant (prediabetes n = 184; diabetes n = 1) despite 48% being underweight (BMI <18.5 kg/m2). Glucose-intolerant participants had higher fasting glucose from childhood. Mothers of glucose-intolerant participants had higher glycemia in pregnancy. Glucose-intolerant participants were shorter at birth. Insulin sensitivity decreased with age in all participants, and those with glucose intolerance had consistently lower compensatory insulin secretion from childhood. Participants in the highest quintile of fasting glucose at 6 and 12 years had 2.5- and 4.0-fold higher risks, respectively, of 18-year glucose intolerance; this finding was replicated in two other cohorts. CONCLUSIONS: Inadequate compensatory insulin secretory response to decreasing insulin sensitivity in early life is the major pathophysiology underlying glucose intolerance in thin rural Indians. Smaller birth size, maternal pregnancy hyperglycemia, and higher glycemia from childhood herald future glucose intolerance, mandating a strategy for diabetes prevention from early life, preferably intergenerationally.