Childhood obesity triggers the onset of a broad array of chronic illnesses, and children are becoming overweight at increasingly younger ages. An important pathway to obesity is developmental overnutrition. This pathway reflects the effects of hypernutrition during fetal or early postnatal life and creates the conditions for the later pathophysiological effects of an obesogenic environment. While several studies have provided supporting evidence, there are many unanswered questions, including the potential joint effects of several prenatal factors and the relative contribution of the early postnatal environment. The Healthy Start study was funded in 2009 to establish and follow a large population cohort of ethnically diverse pregnant women until delivery in order to explore the hypothesis that fetal overnutrition driven by maternal obesity is associated with neonatal body size and composition. We propose to extend the longitudinal follow up of this population to ages 5-6 years to address important research questions:
Aim 1 : To determine the magnitude of the associations of potentially modifiable prenatal factors during pregnancy with offspring adiposity, vascular and metabolic function at ages 5-6 years in an ethnically diverse cohort. We hypothesize that higher maternal pre-pregnancy body mass index (BMI), greater gestational weight gain (GWG), smoking and unhealthy dietary patterns during pregnancy are each associated with childhood adiposity [higher BMI and fat mass (FM), increased visceral adipose tissue (VAT), excess liver fat accumulation], with poorer vascular function (higher blood pressure and markers of endothelial dysfunction) and poorer insulin-glucose and lipid metabolism. Similar associations are observed in all major racial/ethnic groups.
Aim 2 : To examine the role of offspring growth, postnatal nutrition, physical activity and sleeping patterns in mediating these associations. We hypothesize that, in part, the associations of maternal prenatal factors with offspring outcomes at ages 5-6 years are mediated by: 1) Postnatal growth assessed as changes in BMI and FM from birth to current age;2) Parental feeding practices;3) Childhood eating behaviors;4) Current diet, physical activity and sleeping patterns.
Aim 3 : To explore the hypothesis that exposure to maternal obesity in utero leads to impaired leptin action and increases the risk of obesity in children. At a time when we are contemplating investing in very large randomized controlled trials that would require long-term follow-up of offspring, one needs strong evidence from the best quality observational studies, such as proposed here, that modifiable factors during pregnancy and in early postnatal life have specific effects on future offspring adiposity, metabolic and vascular health. Identifying the answers to some of these questions represents the first necessary step towards early prevention of obesity, its metabolic and cardiovascular consequences.

Public Health Relevance

This proposal explores a highly significant topic of public health impact, that of whether and how pre-natal and early postnatal life contributes to the development of childhood adiposity and related vascular and metabolic outcomes. Furthermore, we will explore potential mechanisms responsible for these associations, both specific intrauterine effects and postnatal mediators. This study will provide much needed evidence and enhance our knowledge of primordial prevention, with potentially huge public health implications.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (ZRG1-PSE-D (02))
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Horlick, Mary
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University of Colorado Denver
Public Health & Prev Medicine
Schools of Medicine
United States
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Polinski, Kristen J; Dabelea, Dana; Hamman, Richard F et al. (2018) Distribution and predictors of urinary concentrations of phthalate metabolites and phenols among pregnant women in the Healthy Start Study. Environ Res 162:308-317
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
Dabelea, Dana (2018) Diabetes in Youth-Looking Backwards to Inform the Future: Kelly West Award Lecture 2017. Diabetes Care 41:233-240
Sauder, Katherine A; Kaar, Jill L; Starling, Anne P et al. (2017) Predictors of Infant Body Composition at 5 Months of Age: The Healthy Start Study. J Pediatr 183:94-99.e1
Shapiro, Allison L B; Ringham, Brandy M; Glueck, Deborah H et al. (2017) Infant Adiposity is Independently Associated with a Maternal High Fat Diet but not Related to Niacin Intake: The Healthy Start Study. Matern Child Health J 21:1662-1668
Baker 2nd, Peter R; Patinkin, Zachary; Shapiro, Allison Lb et al. (2017) Maternal obesity and increased neonatal adiposity correspond with altered infant mesenchymal stem cell metabolism. JCI Insight 2:
Baker 2nd, Peter R; Patinkin, Zachary W; Shapiro, Allison L B et al. (2017) Altered gene expression and metabolism in fetal umbilical cord mesenchymal stem cells correspond with differences in 5-month-old infant adiposity gain. Sci Rep 7:18095
Starling, A P; Shapiro, A L B; Sauder, K A et al. (2017) Blood pressure during pregnancy, neonatal size and altered body composition: the Healthy Start study. J Perinatol 37:502-506
Moore, B F; Sauder, K A; Starling, A P et al. (2017) Exposure to secondhand smoke, exclusive breastfeeding and infant adiposity at age 5 months in the Healthy Start study. Pediatr Obes 12 Suppl 1:111-119
Starling, Anne P; Sauder, Katherine A; Kaar, Jill L et al. (2017) Maternal Dietary Patterns during Pregnancy Are Associated with Newborn Body Composition. J Nutr 147:1334-1339

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