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
Research Project (R01)
Project #
4R01HD034568-15
Application #
9222311
Study Section
Special Emphasis Panel (NSS)
Program Officer
Grave, Gilman D
Project Start
2017-02-06
Project End
2022-01-31
Budget Start
2017-02-06
Budget End
2018-01-31
Support Year
15
Fiscal Year
2017
Total Cost
$1,024,170
Indirect Cost
$407,200
Name
Harvard Pilgrim Health Care, Inc.
Department
Type
Other Domestic Non-Profits
DUNS #
071721088
City
Boston
State
MA
Country
United States
Zip Code
02215
Farr, Olivia M; Rifas-Shiman, Sheryl L; Oken, Emily et al. (2017) Current child, but not maternal, snoring is bi-directionally related to adiposity and cardiometabolic risk markers: A cross-sectional and a prospective cohort analysis. Metabolism 76:70-80
Stratakis, Nikos; Roumeliotaki, Theano; Oken, Emily et al. (2017) Fish and seafood consumption during pregnancy and the risk of asthma and allergic rhinitis in childhood: a pooled analysis of 18 European and US birth cohorts. Int J Epidemiol 46:1465-1477
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
Taveras, Elsie M; Rifas-Shiman, Sheryl L; Bub, Kristen L et al. (2017) Prospective Study of Insufficient Sleep and Neurobehavioral Functioning Among School-Age Children. Acad Pediatr 17:625-632
Switkowski, Karen M; Jacques, Paul F; Must, Aviva et al. (2017) Higher Maternal Protein Intake during Pregnancy Is Associated with Lower Cord Blood Concentrations of Insulin-like Growth Factor (IGF)-II, IGF Binding Protein 3, and Insulin, but Not IGF-I, in a Cohort of Women with High Protein Intake. J Nutr 147:1392-1400
Perng, Wei; Rifas-Shiman, Sheryl L; McCulloch, Scott et al. (2017) Associations of cord blood metabolites with perinatal characteristics, newborn anthropometry, and cord blood hormones in project viva. Metabolism 76:11-22
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
Rifas-Shiman, Sheryl L; Fleisch, Abby; Hivert, Marie-France et al. (2017) First and second trimester gestational weight gains are most strongly associated with cord blood levels of hormones at delivery important for glycemic control and somatic growth. Metabolism 69:112-119
Fleisch, Abby F; Rifas-Shiman, Sheryl L; Rokoff, Lisa B et al. (2017) Associations of maternal prenatal smoking with umbilical cord blood hormones: the Project Viva cohort. Metabolism 72:18-26
Quante, Mirja; Wang, Rui; Weng, Jia et al. (2017) Seasonal and weather variation of sleep and physical activity in 12-14-year-old children. Behav Sleep Med :1-13

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