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.
