Nicole D Ford1, Jere R Behrman2, John F Hoddinott3, John A Maluccio4, Reynaldo Martorell1, Manuel Ramirez-Zea5, Aryeh D Stein6. 1. Hubert Department of Global Health, Rollins School of Public Health Emory University, Atlanta, GA, USA. 2. Departments of Economics and Sociology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA. 3. Division of Nutritional Sciences and Charles H Dyson School of Applied Economics and Management, Cornell University, Ithaca, NY, USA. 4. Department of Economics, Middlebury College, Middlebury, VT, USA. 5. Institute of Nutrition of Central America and Panama Research Center for the Prevention of Chronic Diseases, Institute of Nutrition of Central America and Panama, Guatemala City, Guatemala. 6. Hubert Department of Global Health, Rollins School of Public Health Emory University, Atlanta, GA, USA. Electronic address: aryeh.stein@emory.edu.
Abstract
BACKGROUND: Low-income and middle-income countries with populations that are chronically undernourished in early life are undergoing a nutrition transition and are experiencing an epidemic of cardiometabolic disease. These dual burdens are thought to be causally related; therefore, the extent to which improvements in early-life nutrition can offset adult-onset disease is important. The aim of this study was to examine whether improvement of protein-energy nutrition from conception to age 2 years can attenuate the risk of cardiometabolic disease. METHODS: We followed up a cohort of 2392 individuals born between Jan 1, 1962, and Feb 28, 1977, in four villages in Guatemala who had participated in a cluster-randomised protein-energy nutritional supplementation (Atole) trial. Of 1661 participants available for follow-up from Feb 26, 2015, to April 29, 2017, we studied 684 women and 455 men. We assessed cardiometabolic disease riskat ages 37-54 years using anthropometry, fasting and post-challenge glucose, fasting lipid concentrations, and blood pressure. We used generalised linear and logistic regression modelling to estimate the effect of Atole from conception to age 2 years (the first 1000 days) on cardiometabolic disease risk. FINDINGS: Exposure to Atole from conception to age 2 years was associated with increased fatness (body-mass index [1·29 kg/m2, 95% CI 0·08 to 2·50], body fat [1·73%, 0·20 to 3·26], and obesity [odds ratio 1·94, 1·11 to 3·40]), diastolic blood pressure (1·59 mm Hg, -0·74 to 3·92), and blood lipids (total cholesterol [10·10 mg/dL, 0·80 to 19·40] and non-HDL cholesterol [10·41 mg/dL, 1·51 to 19·31]), reduced post-challenge glucose (-5·84 mg/dL, -12·51 to 0·83), and reduced odds of diabetes (odds ratio 0·46, 0·21 to 0·97). We found stratum heterogeneity by sex in pooled models for non-HDL cholesterol (4·34 mg/dL, 95% CI -6·86 to 15·55 for women vs 19·84 mg/dL, 5·86 to 33·82 for men) and post-challenge glucose (-0·19 mg/dL, -8·63 to 8·24 for women vs -13·10 mg/dL, -23·64 to -2·56 for men). p values for interaction of sex and exposure to Atole from conception to age 2 years were 0·09 and 0·04, respectively. INTERPRETATION: Improved protein-energy nutrition from conception to the 2nd birthday reduced the odds of diabetes at ages 37-54 years; however, this protein-energy supplementation also increased the risk of obesity and several obesity-related conditions. Our findings suggest a mixed ability of protein-energy nutritional supplementation in early life to prevent adult cardiometabolic disease incidence in the context of high childhood stunting and high adult overweight and obesity. FUNDING: National Institutes of Health.
RCT Entities:
BACKGROUND: Low-income and middle-income countries with populations that are chronically undernourished in early life are undergoing a nutrition transition and are experiencing an epidemic of cardiometabolic disease. These dual burdens are thought to be causally related; therefore, the extent to which improvements in early-life nutrition can offset adult-onset disease is important. The aim of this study was to examine whether improvement of protein-energy nutrition from conception to age 2 years can attenuate the risk of cardiometabolic disease. METHODS: We followed up a cohort of 2392 individuals born between Jan 1, 1962, and Feb 28, 1977, in four villages in Guatemala who had participated in a cluster-randomised protein-energy nutritional supplementation (Atole) trial. Of 1661 participants available for follow-up from Feb 26, 2015, to April 29, 2017, we studied 684 women and 455 men. We assessed cardiometabolic disease risk at ages 37-54 years using anthropometry, fasting and post-challenge glucose, fasting lipid concentrations, and blood pressure. We used generalised linear and logistic regression modelling to estimate the effect of Atole from conception to age 2 years (the first 1000 days) on cardiometabolic disease risk. FINDINGS: Exposure to Atole from conception to age 2 years was associated with increased fatness (body-mass index [1·29 kg/m2, 95% CI 0·08 to 2·50], body fat [1·73%, 0·20 to 3·26], and obesity [odds ratio 1·94, 1·11 to 3·40]), diastolic blood pressure (1·59 mm Hg, -0·74 to 3·92), and blood lipids (total cholesterol [10·10 mg/dL, 0·80 to 19·40] and non-HDL cholesterol [10·41 mg/dL, 1·51 to 19·31]), reduced post-challenge glucose (-5·84 mg/dL, -12·51 to 0·83), and reduced odds of diabetes (odds ratio 0·46, 0·21 to 0·97). We found stratum heterogeneity by sex in pooled models for non-HDL cholesterol (4·34 mg/dL, 95% CI -6·86 to 15·55 for women vs 19·84 mg/dL, 5·86 to 33·82 for men) and post-challenge glucose (-0·19 mg/dL, -8·63 to 8·24 for women vs -13·10 mg/dL, -23·64 to -2·56 for men). p values for interaction of sex and exposure to Atole from conception to age 2 years were 0·09 and 0·04, respectively. INTERPRETATION: Improved protein-energy nutrition from conception to the 2nd birthday reduced the odds of diabetes at ages 37-54 years; however, this protein-energy supplementation also increased the risk of obesity and several obesity-related conditions. Our findings suggest a mixed ability of protein-energy nutritional supplementation in early life to prevent adult cardiometabolic disease incidence in the context of high childhood stunting and high adult overweight and obesity. FUNDING: National Institutes of Health.
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