Exploring the Fuel-Mediated Programming of Neonatal Growth

 描述(申请人提供)：儿童肥胖会引发一系列慢性疾病，儿童在越来越小的年龄就变得超重。导致肥胖的一个重要途径是发育过度营养。这一途径反映了胎儿或出生后早期高营养的影响，并为后来的肥胖环境的病理生理影响创造了条件。虽然一些研究已经提供了佐证，但仍有许多问题没有得到回答，包括几个产前因素的潜在联合作用以及早期出生后环境的相对贡献。Healthy Start研究是在2009年资助的，目的是建立和跟踪一大批不同种族的孕妇，直到分娩，以探索母亲肥胖导致的胎儿营养过剩与新生儿的身体尺寸和组成有关的假设。我们建议将这一人群的纵向随访扩展到5-6岁，以解决重要的研究问题：目标1：在一个不同种族的队列中，确定怀孕期间潜在的可改变的产前因素与5-6岁的后代肥胖、血管和代谢功能的关联程度。我们假设，孕前较高的体重指数(BMI)、较大的孕期体重增加(GWG)、吸烟和孕期不健康的饮食结构都与儿童肥胖症[较高的BMI和脂肪质量(FM)、内脏脂肪组织(VAT)增加、过度的肝脏脂肪堆积]、较差的血管功能(较高的血压和内皮功能障碍的标志物)以及较差的胰岛素-葡萄糖和脂代谢相关。在所有主要种族/族裔群体中都观察到了类似的联系。目的2：研究后代生长、出生后营养、体力活动和睡眠模式在调节这些联系中的作用。我们假设，在一定程度上，母亲产前因素与5-6岁子女结局的关系是由以下因素调节的：1)出生后生长发育评估为从出生到现在年龄的BMI和FM变化；2)父母喂养习惯；3)儿童饮食行为；4)当前饮食、体力活动和睡眠模式。目的：探讨宫内暴露于母体肥胖导致瘦素作用受损并增加儿童肥胖风险的假说。在我们考虑投资于需要对后代进行长期随访的大型随机对照试验的时候，人们需要从最高质量的观察性研究中获得强有力的证据，证明怀孕期间和出生后早期的可修改因素对未来的后代肥胖、代谢和血管健康有特定的影响。找出其中一些问题的答案，是及早预防肥胖及其代谢和心血管后果的第一个必要步骤。

 DESCRIPTION (provided by applicant): 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.