Exploring the Fuel-Mediated Programming of Neonatal Growth

 描述（由申请人提供）：儿童肥胖症引发了一系列慢性疾病的发病，儿童在越来越年轻的年龄变得超重。肥胖的一个重要途径是发育性营养过剩。该途径反映了胎儿或出生后早期营养过剩的影响，并为致肥胖环境的后期病理生理学影响创造了条件。虽然有几项研究提供了支持性证据，但仍有许多问题没有得到解答，包括几个产前因素的潜在联合影响和出生后早期环境的相对贡献。2009年资助了健康开始研究，以建立和跟踪一个由不同种族的孕妇组成的大型人群队列，直到分娩，以探索由母体肥胖引起的胎儿营养过剩与新生儿体型和组成相关的假设。我们建议将这一人群的纵向随访延长至5-6岁，以解决重要的研究问题：目的1：在一个种族多样的队列中，确定妊娠期间可能改变的产前因素与5-6岁时后代肥胖、血管和代谢功能的相关性。我们假设母亲孕前体重指数（BMI）较高，妊娠期体重增加（GWG）较大，怀孕期间吸烟和不健康的饮食模式均与儿童肥胖相关[BMI和脂肪量（FM）较高，内脏脂肪组织（VAT）增加，肝脏脂肪堆积过多]，血管功能较差（血压和内皮功能障碍的标志物较高）和胰岛素-葡萄糖和脂质代谢较差。在所有主要种族/族裔群体中都观察到类似的关联。目的2：研究后代生长、产后营养、体力活动和睡眠模式在介导这些关联中的作用。我们假设，母亲产前因素与5-6岁后代结局的相关性部分由以下因素介导：1）产后生长评估为从出生到当前年龄的BMI和FM变化; 2）父母喂养习惯; 3）儿童饮食行为; 4）当前饮食，体育活动和睡眠模式。目标3：探讨母亲在子宫内肥胖导致瘦素作用受损并增加儿童肥胖风险的假设。 当我们考虑投资于需要长期随访后代的大型随机对照试验时，我们需要来自最佳质量观察性研究的强有力证据，例如这里提出的，怀孕期间和出生后早期生活中的可改变因素对未来后代的肥胖，代谢和血管健康有特定影响。确定其中一些问题的答案是早期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.