As children enter early adolescence, cardiovascular and metabolic consequences of obesity become more apparent. Studies in older children show that obesity and central fat distribution are associated with these outcomes. But how did the children get there in the first place? This is a key question for chronic disease prevention. A now-vast animal experimental literature and a growing human counterpart demonstrate that factors operating at the earliest stages of human development-even before birth-can have lifelong consequences for obesity and cardiometabolic outcomes. Yet major questions still exist regarding how pre- and peri-natal factors operate, through gain in weight and adiposity, to influence these outcomes. In analyses from the previous cycle of """"""""Pre- and peri-natal predictors of childhood obesity, the findings imply both that the endocrine milieu at the time of birth is different from later in life, and that it is likely to be a key driver of weight gain in the first months of life, itself a strong predictor of later obesity and cormorbidities. While these observations are consistent with endocrine knowledge emerging from animal experiments, they raise several questions: 7 To what extent are prenatal factors such as maternal nutrition (e.g., fatty acids, vitamin D), smoking, gestational weight gain, and gestational diabetes associated with perinatal hormone levels? 7 What other hormones are involved in these pathways? In particular, what are the roles of insulin and insulin-like growth factors (IGFs), which are correlated with leptin levels? 7 If these hormones influence childhood weight gain, do they also influence gain in adiposity, fat distribution, components of the metabolic syndrome and vascular dysfunction in early adolescence? 7 To what extent are these influences mediated by adiposity-related inflammation? The overall goal of this renewal of R01 HD 034568-10 is to examine associations of potentially modifiable prenatal factors, hormone levels in umbilical cord blood, gains in weight and adiposity in childhood, adiposity- related inflammation, and cardiometabolic outcomes in early adolescence. including components of the metabolic syndrome, carotid intima-media thickness, and endothelial dysfunction. Extending the productive pre-birth cohort study Project Viva through the age of 11 years provides the opportunity to meet this challenge. The results of this research will lead to new scientific knowledge about the drivers of growth and adiposity in childhood and may very well lead to new avenues for prevention of obesity, diabetes, and cardiovascular disease.

Public Health Relevance

As children enter early adolescence, the harmful cardiovascular and metabolic effects of obesity become more apparent. The drivers of these health outcomes may exist very early in life, perhaps even before birth. In this renewal of the grant that originally funded the cohort study Project Viva, we will examine how maternal diet, smoking, weight gain and diabetes during pregnancy affect hormone levels around the time of birth, how these hormone levels are associated with patterns of growth and inflammation during childhood and in turn with heart disease and diabetes risk factors at the age of 11 years. Our results will lead to new scientific knowledge and may very well lead to new ways to prevent obesity, diabetes, and cardiovascular disease.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HD034568-12
Application #
8606752
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Grave, Gilman D
Project Start
1998-07-01
Project End
2017-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
12
Fiscal Year
2014
Total Cost
$1,111,514
Indirect Cost
$369,362
Name
Harvard Pilgrim Health Care, Inc.
Department
Type
DUNS #
071721088
City
Boston
State
MA
Country
United States
Zip Code
02215
Rice, Mary B; Rifas-Shiman, Sheryl L; Litonjua, Augusto A et al. (2018) Lifetime air pollution exposure and asthma in a pediatric birth cohort. J Allergy Clin Immunol 141:1932-1934.e7
Tian, Fu-Ying; Rifas-Shiman, Sheryl L; Cardenas, Andres et al. (2018) Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva. Int J Obes (Lond) :
Felix, Janine F; Joubert, Bonnie R; Baccarelli, Andrea A et al. (2018) Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium. Int J Epidemiol 47:22-23u
Sen, S; Rifas-Shiman, S L; Shivappa, N et al. (2018) Associations of prenatal and early life dietary inflammatory potential with childhood adiposity and cardiometabolic risk in Project Viva. Pediatr Obes 13:292-300
Cardenas, Andres; Rifas-Shiman, Sheryl L; Agha, Golareh et al. (2017) Persistent DNA methylation changes associated with prenatal mercury exposure and cognitive performance during childhood. Sci Rep 7:288
Mora, Ana MarĂ­a; Oken, Emily; Rifas-Shiman, Sheryl L et al. (2017) Prenatal Exposure to Perfluoroalkyl Substances and Adiposity in Early and Mid-Childhood. Environ Health Perspect 125:467-473
Chatzi, L; Rifas-Shiman, S L; Georgiou, V et al. (2017) Adherence to the Mediterranean diet during pregnancy and offspring adiposity and cardiometabolic traits in childhood. Pediatr Obes 12 Suppl 1:47-56
Fleisch, Abby F; Rifas-Shiman, Sheryl L; Mora, Ana M et al. (2017) Early-Life Exposure to Perfluoroalkyl Substances and Childhood Metabolic Function. Environ Health Perspect 125:481-487
Fleisch, A F; Luttmann-Gibson, H; Perng, W et al. (2017) Prenatal and early life exposure to traffic pollution and cardiometabolic health in childhood. Pediatr Obes 12:48-57
Ertel, Karen A; Huang, Tianyi; Rifas-Shiman, Sheryl L et al. (2017) Perinatal weight and risk of prenatal and postpartum depressive symptoms. Ann Epidemiol 27:695-700.e1

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