BIRTHWEIGHT AND GESTATIONAL AGE AND CHRONIC DISEASE RISK

一些研究表明，出生矮小或苗条的人成年后患胰岛素抵抗综合征(IRS)、非胰岛素依赖型糖尿病(NIDDM)和心血管疾病(CVD)的风险增加。这些观察结果导致了“胎儿起源”假说，即对这些慢性成人疾病的易感性可能是在子宫中编程的。妊娠期间发生的深刻的代谢和血流动力学变化使怀孕成为葡萄糖耐量异常、高血压和其他与IRS相关的异常的生理应激测试。妊娠期糖尿病(GDM)和妊娠高血压综合征(PIH)是两种常见的妊娠并发症，它们具有许多IRS的特征，也预测了妇女未来发展为NIDDM和CVD的风险。我们建议调查女性在自己出生前的生长发育(由她自己的出生体重和胎龄表示)对她年轻成年后患妊高征或妊娠期糖尿病的风险的影响。除了我们最近在科罗拉多州完成的有希望的初步工作外，这是一个以前从未探索过的调查领域。这项提议是根据纽约州和纽约市的出生登记和出院数据进行一项病例对照研究，并将这一代人的数据通过计算机连接起来。研究对象将是1959年后出生在纽约，并在1990至1996年间在纽约生下一个活着的单身婴儿的女性。病例将是在最近一次怀孕期间(1990-1996年)被诊断为妊高征和/或妊娠期糖尿病的受试者，而对照组将是与住院和分娩年份相匹配的受试者，但没有被诊断为妊高征或妊娠期糖尿病。每个受试者最近怀孕的记录(1990-1996年)将与她自己出生的记录(12-36年前)相匹配。我们将使用多元Logistic回归来估计母亲自身早期生长的独立影响，如出生体重和胎龄，对其日后患妊娠期糖尿病或妊高征风险的独立影响。这项分析将考虑到潜在的混杂和影响因素，包括种族/民族、产妇年龄和吸烟。我们还将对出生记录中诊断为妊娠期糖尿病和妊高征的有效性进行一项子研究。因此，这项研究将提供一种强大而经济高效的方式来调查妊娠期糖尿病和妊高征的胎儿起源假说，这两种常见但仍鲜为人知的妊娠并发症与晚年患慢性病的风险增加有关。

Several studies have shown that people born small or thin have increased risk for developing Insulin Resistance Syndrome (IRS), non-insulin dependent diabetes mellitus (NIDDM), and cardiovascular disease (CVD) as adults. These observations have led to the "fetal origins" hypothesis - that susceptibility to these chronic adult conditions may be programmed in utero. The profound metabolic and hemodynamic changes that occur in gestation make pregnancy a physiologic stress test for glucose intolerance, hypertension, and other IRS-related abnormalities. Gestational diabetes (GDM) and pregnancy-induced hypertension (PIH) are two common complications of pregnancy that share many characteristics of IRS, and also predict a woman's risk for the later development of NIDDM and CVD. We propose to investigate the effects of a woman's growth before her own birth (indicated by her own birthweight and gestational age) on her risk in young adulthood for PIH or GDM. Apart from promising preliminary work we have recently completed in Colorado, this is an area of investigation that has not previously been explored. The proposal is to conduct a case-control study based on birth registry and hospital discharge data from New York State and New York City, computer-linked across a generation. Subjects will be women who were born in NY after 1959 and delivered a live singleton infant in New York between 1990 and 1996. Cases will be subjects who had PIH and/or GDM diagnosed during a recent pregnancy (1990-1996), while controls will be subjects frequency matched to cases on hospital and year of delivery, but without a diagnosis of PIH or GDM. The records of each subject's recent pregnancy (1990-1996) will be matched to those of her own birth (12-36 years earlier). We will use multiple logistic regression to estimate the independent effects of a mother's own early growth, as indicated by birth weight and gestational age, on her later risk of developing GDM or PIH. The analysis will account for potential confounding and effect-modifying factors, including race/ethnicity, maternal age, and smoking. We will also conduct a sub-study of the validity of the diagnoses of GDM and PIH on the birth records. This study will thus offer a powerful and cost-efficient way to investigate the hypothesis of the fetal origins of GDM and PIH, two common but still poorly understood complications of pregnancy which are associated with increased risk for chronic disease later in life.