The overarching goal of this proposal is to establish and follow a cohort of ethnically diverse pregnant women and their offspring in order to longitudinally explore the hypothesis that fetal over-nutrition is associated with obesity, metabolic and cardio- vascular abnormalities in offspring. As part of the current application, we propose to test the hypothesis that programming of neonatal adiposity is driven by maternal obesity per se, in the absence of frank gestational diabetes. To determine whether there are associations between specific maternal factors and neonatal outcomes we will examine the effects of maternal obesity, diet and weight gain during pregnancy, together with specific potential mediators measured prospectively throughout pregnancy (maternal fuels, markers of insulin-resistance and inflammation). These are factors that can be targeted by future interventions. We propose to enroll a total of 1,920 pregnant women before 15 weeks of gestation and follow them prospectively through delivery in order to explore the relationships between maternal body size and behaviors during pregnancy [pre-pregnant BMI, weight gain, diet], intra-partum fuels (glucose, lipids, FFA), markers of inflammation (IL-6, TNF-?) and insulin resistance (HOMA-IR)], and infant body size (birth weight for gestational age), fatness (determined by air displacement plethysmography) and fat deposition (skinfolds). All women will have two fasting in- person visits, in early pregnancy (15-16 weeks of gestation, IPV1) and mid pregnancy (24-28 weeks of gestation, IPV2). This well characterized cohort of pregnant women will not only permit us to test important hypotheses related to programming of neonatal fatness (Aims 1 and 2), but will also be informative for the planned follow-up of the cohort of offspring assembled. To explore the relationships between maternal factors and infant metabolic markers, a random sample (N=300) of mother/infant pairs, enriched in women with GDM, will be selected to undergo a neonatal fasting blood draw protocol. Biomarkers traditionally associated with an increased risk of future cardiovascular disease, such as glucose, lipids (triglyceride, total and HDL-cholesterol, FFA), markers of insulin resistance (HOMA-IR) and insulin secretion, and markers of inflammation (TNF-?, leptin) will be explored in these newborns (Aim 3).

Public Health Relevance

A substantial increase in the prevalence of overweight and obesity among obstetric populations of all ages, racial/ethnic and socio-economic backgrounds has been reported in the last decade. Hence, maternal obesity has become an important and potentially modifiable exposure with potential programming consequences. This project offers a unique opportunity to explore a timely public health problem by testing the hypothesis that maternal obesity programs neonatal growth, fatness and metabolism, and by identifying specific mediators of these effects that can be targeted by future interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK076648-04
Application #
8311773
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Horlick, Mary
Project Start
2009-08-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$705,931
Indirect Cost
$244,538
Name
University of Colorado Denver
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Sauder, K A; Starling, A P; Shapiro, A L et al. (2016) Diet, physical activity and mental health status are associated with dysglycaemia in pregnancy: the Healthy Start Study. Diabet Med 33:663-7
Shapiro, Allison L B; Boyle, Kristen E; Dabelea, Dana et al. (2016) Nicotinamide Promotes Adipogenesis in Umbilical Cord-Derived Mesenchymal Stem Cells and Is Associated with Neonatal Adiposity: The Healthy Start BabyBUMP Project. PLoS One 11:e0159575
Boyle, Kristen E; Patinkin, Zachary W; Shapiro, Allison L B et al. (2016) Mesenchymal Stem Cells From Infants Born to Obese Mothers Exhibit Greater Potential for Adipogenesis: The Healthy Start BabyBUMP Project. Diabetes 65:647-59
Harrod, Curtis S; Fingerlin, Tasha E; Chasan-Taber, Lisa et al. (2015) Exposure to prenatal smoking and early-life body composition: the healthy start study. Obesity (Silver Spring) 23:234-41
Starling, Anne P; Brinton, John T; Glueck, Deborah H et al. (2015) Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study. Am J Clin Nutr 101:302-9
Shapiro, Allison L B; Schmiege, Sarah J; Brinton, John T et al. (2015) Testing the fuel-mediated hypothesis: maternal insulin resistance and glucose mediate the association between maternal and neonatal adiposity, the Healthy Start study. Diabetologia 58:937-41
Sauder, K A; Starling, A P; Shapiro, A L et al. (2015) Exploring the association between maternal prenatal multivitamin use and early infant growth: The Healthy Start Study. Pediatr Obes :
Lemas, D J; Brinton, J T; Shapiro, A L B et al. (2015) Associations of maternal weight status prior and during pregnancy with neonatal cardiometabolic markers at birth: the Healthy Start study. Int J Obes (Lond) 39:1437-42
Friedman, Jacob E (2015) Obesity and Gestational Diabetes Mellitus Pathways for Programming in Mouse, Monkey, and Man—Where Do We Go Next? The 2014 Norbert Freinkel Award Lecture. Diabetes Care 38:1402-11
Crume, Tessa L; Shapiro, Allison L; Brinton, John T et al. (2015) Maternal fuels and metabolic measures during pregnancy and neonatal body composition: the healthy start study. J Clin Endocrinol Metab 100:1672-80

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