Low birthweight and prematurity are the leading causes of perinatal morbidity and mortality in the United States today. While great emphasis has been placed on elucidating possible environmental causes of these problems in the past, the contribution of genetic and genetically determined maternal effects have largely been ignored. The objectives of the proposed study are to identify and resolve specific genetic, maternal and environmental contributions to the occurrence of low birthweight and prematurity, in addition to, other complications of pregnancy, such as toxemia/hypertension, utilizing detailed self-reported questionnaire data on the reproductive histories of a minimum of 3,500 doubly-fertile monozygotic and dizygotic twin pairs ranging in age from 17 to 70 years. Twin pairs included in this study will be ascertained from the population- based Virginia and Norwegian Twin Registries which currently contain over 21,000 adult twin pairs Reproductive history information will be collected on all twins in both registries. Specific information on the occurrence of infertility in study participants will also be obtained. This data will be used in analyses that attempt to elucidate the particular factors which might play a role in influencing family size (reproductive fitness). The unique family structure of the data set to be collected will permit the use of several different methodological approaches in evaluating the hypotheses put forth in this study. Classical twin studies, regression, correlation, path and multivariate analyses will be used to investigate the degree to which such factors as maternal age and smoking during pregnancy. In addition to, genotype, contribute to low birthweight, prematurity and pregnancy loss. The more detailed analyses of the genetic nature of maternal influences on birth weight, in general, and low birthweight, in particular, will be conducted using co-twin control studies and comprehensive maximum likelihood analyses. Specific complications of pregnancy, such as toxemia/hypertension and nausea/vomiting will also be examined using these techniques. Response surface analysis and logistic regression will be used to assess the degree to which genetic, maternal, and environmental factors influence fertility and reproductive fitness.
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