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Grant Abstract: Exploring the Fuel-Mediated Programming of Neonatal Growth

Grant Number: 5R01DK076648-08
PI Name: Dabelea
Project Title: Exploring the Fuel-Mediated Programming of Neonatal Growth

Abstract: 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.

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