GENETIC EPIDEMIOLOGY OF HUMAN FETAL GROWTH

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Fetal growth represents a fundamental biological parameter for all mammalian species. In the human species, the distribution of fetal growth assumes an added dimension of great public health importance because it defines the frequency of babies most likely to die during infancy - the intra uterine growth retarded (IUGR) baby. Despite the importance of fetal growth as a primary determinant of health during infancy and early childhood, we known very little about the intrinsic factors that modify the distribution of fetal growth in populations. In particular, we lack a clear understanding of how genetic factors influence fetal growth in Man, and the extent to which maternal and environmental variables constrain the genetic growth potential of the fetus. This study aims to carry out the first comprehensive investigation of the interactions between genetic, maternal and environmental factors which influence the distribution of fetal growth in an entire, defined, U.S. population -the state of Utah. First, a data base of linked Utah birth records will be created for the approximately 318,814 live and still births born between 1940- 55 (parental cohort) and the approximately 581,447 births born between 1970-85. Record linking within each cohort will form parental sibships and offspring sibships, while record linking between cohorts will form nuclear families and cousin sets. We anticipate forming about 100,000 nuclear families with birth records (of which nearly 30,000 will have completed reproduction) and 200,000 cousin sets. Second, this data base will be analyzed to: a) evaluate the effect of various environmental and demographic concomitants on fetal growth. b) determine the impact of fetal growth constraints on mortality. c) identify the relative contribution of genetic, maternal and environmental factors on fetal growth using path analysis and segregation analysis. d) test hypotheses concerning the mechanism of maternal influences on fetal growth, and evaluate the magnitude of natural selection due to fetal growth.