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Background Clustering of observations is a common phenomenon in epidemiological and clinical research. Previous studies have highlighted the importance of using multilevel analysis to account for such clustering, but in practice, methods ignoring clustering are often employed. We used simulated data to explore the circumstances in which failure to account for clustering in linear regression could lead to importantly erroneous conclusions. Methods We simulated data following the random-intercept model specification under different scenarios of clustering of a continuous outcome and a single continuous or binary explanatory variable. We fitted random-intercept (RI) and ordinary least squares (OLS) models and compared effect estimates with the “true” value that had been used in simulation. We also assessed the relative precision of effect estimates, and explored the extent to which coverage by 95% confidence intervals and Type I error rates were appropriate. Results We found that effect estimates from both types of regression model were on average unbiased. However, deviations from the “true” value were greater when the outcome variable was more clustered. For a continuous explanatory variable, they tended also to be greater for the OLS than the RI model, and when the explanatory variable was less clustered. The precision of effect estimates from the OLS model was overestimated when the explanatory variable varied more between than within clusters, and was somewhat underestimated when the explanatory variable was less clustered. The cluster-unadjusted model gave poor coverage rates by 95% confidence intervals and high Type I error rates when the explanatory variable was continuous. With a binary explanatory variable, coverage rates by 95% confidence intervals and Type I error rates deviated from nominal values when the outcome variable was more clustered, but the direction of the deviation varied according to the overall prevalence of the explanatory variable, and the extent to which it was clustered. Conclusions In this study we identified circumstances in which application of an OLS regression model to clustered data is more likely to mislead statistical inference. The potential for error is greatest when the explanatory variable is continuous, and the outcome variable more clustered (intraclass correlation coefficient is ≥ 0.01).

Fast weight gain and linear growth in children in low-income and middle-income countries are associated with enhanced survival and improved cognitive development, but might increase risk of obesity and related adult cardiometabolic diseases. We investigated how linear growth and relative weight gain during infancy and childhood are related to health and human capital outcomes in young adults. We used data from five prospective birth cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa. We investigated body-mass index, systolic and diastolic blood pressure, plasma glucose concentration, height, years of attained schooling, and related categorical indicators of adverse outcomes in young adults. With linear and logistic regression models, we assessed how these outcomes relate to birthweight and to statistically independent measures representing linear growth and weight gain independent of linear growth (relative weight gain) in three age periods: 0–2 years, 2 years to mid-childhood, and mid-childhood to adulthood. We obtained data for 8362 participants who had at least one adult outcome of interest. A higher birthweight was consistently associated with an adult body-mass index of greater than 25 kg/m2 (odds ratio 1·28, 95% CI 1·21–1·35) and a reduced likelihood of short adult stature (0·49, 0·44–0·54) and of not completing secondary school (0·82, 0·78–0·87). Faster linear growth was strongly associated with a reduced risk of short adult stature (age 2 years: 0·23, 0·20–0·52; mid-childhood: 0·39, 0·36–0·43) and of not completing secondary school (age 2 years: 0·74, 0·67–0·78; mid-childhood: 0·87, 0·83–0·92), but did raise the likelihood of overweight (age 2 years: 1·24, 1·17–1·31; mid-childhood: 1·12, 1·06–1·18) and elevated blood pressure (age 2 years: 1·12, 1·06–1·19; mid-childhood: 1·07, 1·01–1·13). Faster relative weight gain was associated with an increased risk of adult overweight (age 2 years: 1·51, 1·43–1·60; mid-childhood: 1·76, 1·69–1·91) and elevated blood pressure (age 2 years: 1·07, 1·01–1·13; mid-childhood: 1·22, 1·15–1·30). Linear growth and relative weight gain were not associated with dysglycaemia, but a higher birthweight was associated with decreased risk of the disorder (0·89, 0·81–0·98). Interventions in countries of low and middle income to increase birthweight and linear growth during the first 2 years of life are likely to result in substantial gains in height and schooling and give some protection from adult chronic disease risk factors, with few adverse trade-offs. Wellcome Trust and Bill & Melinda Gates Foundation.

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.

Low birth weight is a risk factor for the subsequent development of coronary disease. The effect of childhood growth on coronary risk was evaluated in a cohort of persons born in Finland between 1934 and 1944. On average, children who had a coronary event as adults were small at birth but grew rapidly from 2 to 11 years of age. This growth pattern was also associated with elevated fasting insulin concentrations. The effect of childhood growth on coronary risk was evaluated. On average, children who had a coronary event as adults were small at birth but grew rapidly from 2 to 11 years of age. People with a low birth weight are at increased risk for the development of coronary heart disease. 1 – 6 There is uncertainty about the effects of growth during early childhood, a time when rapid weight gain may predispose to later overweight. 7 We used data from a cohort of subjects in Helsinki to examine associations between growth in early childhood and later coronary events. We have previously analyzed this cohort for the association between annual changes in body size up to 11 years of age and subsequent coronary events. 5 , 8 We found that rapid weight gain after two years of age increased . . .

Birth weight and post-natal growth are important predictors of adult health. Preeclampsia (PE) is associated with low birth weight and may have long term effects on the health of the children. The current study aims to compare anthropometry and blood pressure between children of mothers with and without PE in an Indian cohort. We studied children born to women with (PE; n = 211) and without preeclampsia (non-PE; n = 470) at Bharati Hospital, Pune, India. Anthropometry and blood pressure were measured in children at 3-7 years of age. Weight and height Z-scores were calculated using the WHO 2006 growth reference. Independent t-tests were used to compare means between the two groups, and associations between preeclampsia and child outcomes were analyzed using multiple linear regression, adjusting for potential confounders. Weight and height Z-scores (p = 0.04 and 0.008), and subscapular skinfold thickness (p = 0.03) were higher among children of PE compared with children of non-PE mothers. Systolic blood pressure was also higher in children of PE mothers (1.70 mmHg [95% CI 0.05, 2.90] p = 0.006). BMI and diastolic blood pressure did not differ between groups. In regression models adjusted for newborn weight and gestational age, current age and sex, and maternal height, BMI and socio-economic status, children of PE mothers had higher weight Z-score (0.27 SD [95%CI 0.06, 0.48] p = 0.01), height Z-score (0.28 SD [95%CI 0.09, 0.47] p = 0.005), and subscapular skinfold thickness (0.38 mm [95%CI 0.00, 0.76] p = 0.049). A trend for higher systolic blood pressure (1.59 mmHg [95%CI -0.02, 3.20] p = 0.053) in the children was also observed in the adjusted model. The difference in systolic blood pressure was attenuated after adjusting further for the child's weight and height (1.09 mmHg [95%CI -0.48, 2.67] p = 0.17). There was no evidence of differences in effects between boys and girls. Children of PE mothers were taller and heavier, and had higher systolic blood pressure, partly explained by their increased body size, than children of non-PE mothers. In utero exposure to preeclampsia may increase the risk of future cardiovascular disease.

This study from Delhi, India, assessed 1442 men and women 26 to 32 years of age who had been evaluated at birth and throughout childhood in a prospective, population-based study. Subjects who currently had impaired glucose tolerance or diabetes typically had a low body-mass index up to the age of two years, followed by an early, accelerated increase in body-mass index. Diabetics typically had a low body-mass index up to two years of age, followed by an accelerated increase. The prevalence of type 2 diabetes mellitus is increasing rapidly in developing countries such as India. 1 – 3 This epidemic has been attributed to what has been called “nutritional transition” (increased availability of food, reduced physical activity, and increases in obesity) — changes that are most marked in urban populations. Type 2 diabetes may originate from events initiated during fetal development and in patterns of childhood weight gain. Studies have consistently shown high rates of this disease in people who were born small but became overweight as adults. 4 – 8 It is unclear whether the crucial phase of postnatal weight gain is . . .

To identify peri-conceptional diet patterns among women in Bangalore and examine their associations with risk of gestational diabetes mellitus (GDM). BAngalore Nutrition Gestational diabetes LifEstyle Study, 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 FFQ. GDM was assessed by a 75-g 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 ' ' confounders. Antenatal clinics of two hospitals, Bangalore, South India. Seven hundred and eighty-five pregnant women of varied socio-economic status. 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; and (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 (adjusted odds ratio (aOR): 0·80/sd, 95 % CI (0·64, 0·99), = 0·04) after adjusting for confounders. BMI was strongly related to GDM risk and possibly mediated diet-GDM associations. 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.

A key factor in the use of assisted reproductive technologies (ART) for diverse species is the safety of procedures for long-term health. By using a mouse model, we have investigated the effect of in vitro culture and embryo transfer (ET) of superovulated embryos on postnatal growth and physiological activity compared with that of embryos developing in vivo. Embryo culture from two-cell to blastocyst stages in T6 medium either with or without a protein source reduced blastocyst trophectoderm and inner cell mass cell number compared with that of embryos developing in vivo. Embryo culture and ET had minimal effects on postnatal growth when compared with in vivo development with an equivalent litter size. However, embryo culture, and to a lesser extent ET, led to an enhanced systolic blood pressure at 21 weeks compared with in vivo development independent of litter size, maternal origin, or body weight. Moreover, activity of enzymatic regulators of cardiovascular and metabolic physiology, namely, serum angiotensin-converting enzyme and the gluconeogenesis controller, hepatic phosphoenolpyruvate carboxykinase, were significantly elevated in response to embryo culture and/or ET in female offspring at 27 weeks, independent of maternal factors and postnatal growth. These animal data indicate that postnatal physiological criteria important in cardiovascular and metabolic health may be more sensitive to routine ART procedures than growth.

We aimed to determine how linear growth and fat and lean tissue gain during discrete age periods from birth to adolescence are related to adolescent cardiometabolic risk factors and cognitive ability. Adolescents born to mothers with normal glucose tolerance during pregnancy from an Indian birth cohort (N = 486, age 13.5 years) had detailed anthropometry and measurements of body fat (fat%), fasting plasma glucose, insulin and lipid concentrations, blood pressure and cognitive function. Insulin resistance (HOMA-IR) was calculated. These outcomes were examined in relation to birth measurements and statistically independent measures (conditional SD scores) representing linear growth, and fat and lean tissue gain during birth-1, 1-2, 2-5, 5-9.5 and 9.5-13.5 years in 414 of the children with measurements at all these ages. Birth length and linear growth at all ages were positively associated with current height. Fat gain, particularly during 5-9.5 years was positively associated with fat% at 13.5 years (0.44 SD per SD [99.9% confidence interval: 0.29,0.58]). Greater fat gain during mid-late childhood was associated with higher systolic blood pressure (5-9.5 years: 0.23 SD per SD [0.07,0.40]) and HOMA-IR (5-9.5 years: 0.24 [0.08,0.40], 9.5-13.5 years: 0.22 [0.06,0.38]). Greater infant growth (up to age 2 years) in linear, fat or lean components was unrelated to cardiometabolic risk factors or cognitive function. This study suggests that factors that increase linear, fat and lean growth in infancy have no adverse cardiometabolic effects in this population. Factors that increase fat gain in mid-late childhood may increase cardiometabolic risk, without any benefit to cognitive abilities.