GENEVA Study of Preterm Delivery (DNBC/Iowa)

Preterm labor resulting in the delivery of a premature child is a complex problem with an enormous impact on individuals, families and society. An estimated 500,000 children are born prematurely in the U.S. each year, and 5 million worldwide die annually of prematurity and its complications. Prematurity is also the single largest contributor to disability-adjusted life years, a measure of the lifetime impact of a disease. Despite the importance of the problem and its disproportionate occurrence in poor and minority populations, its underlying etiology (or etiologies) remains unknown; the single best predictor for preterm delivery is a previous preterm birth. The largest single cause of prematurity is spontaneous preterm labor, and suspected triggers for this include infection, stress, poor nutrition and genetic factors. Family and twin studies provide strong evidence that genetic factors underlie about 40% of the risk for prematurity. A major challenge in studying genetic factors in prematurity is maternal/uterine factors, fetal/placental factors, or both may influence risk. Thus, any approach to studying preterm birth should account for both infant and maternal risk, environmental covariates and interactions. The Danish National Birth Cohort (DNBC) is a well-established, prospective cohort that enrolled women early in pregnancy, prior to any adverse pregnancy outcomes, to minimize bias in data collection and sampling. See details at: http://www.ssi.dk/English. The DNBC followed over 100,000 pregnancies beginning in the first trimester and has extensive biological material and epidemiologic data on health outcomes in both mother and child. The current study posted on dbGaP contains data from a genome-wide case/control study using approximately 1,000 preterm mother-child pairs from the DNBC most with spontaneous onset of labor or preterm premature rupture of membranes (PPROM), along with 1,000 control pairs where the child was born at ~40 weeks' gestation. After data cleaning some small changes in case/control status and other variables resulted in minor changes in numbers of cases or controls in certain categories. Environmental variables are being used as covariates in the analysis. To replicate positive findings, we are using additional mother-child pairs from the DNBC and from the general Danish population, as well as 2200 samples coming primarily from an African-American population known to have high rates of preterm labor and delivery. This group includes over 1000 mostly very low birthweight infants, over 500 infant term controls, 326 term mother/baby pairs and 180 preterm mother/baby pairs. The data from these additional cohorts will be available in separate dbGaP postings. The study is expected to yield a better understanding of the biology of parturition, identify common genetic factors that play a role in preterm birth and its complications and suggest environmental modifications that can prolong gestation, with the goal of improving both neonatal and adult outcomes. This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to prematurity and its complications through large-scale genome-wide association studies of a well-characterized cohort of Danish mothers and babies. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.]]>
Application form for access to data and biological samplesBioethics Committee ApprovalThe Danish National Birth Cohort--its background, structure and aim.Informed Consent FormRecruitment Information LeafletVariable DescriptionsVariable Definitions and Guide to Variable Construction for Jeff Murray’s Preterm Delivery ProjectTRANSLATION OF QUESTIONS FROM THE DANISH NATIONAL BIRTH COHORT INTERVIEW QUESTIONNAIRES RELEVANT TO THE MURRAY PRETERM DELIVERY PHENOTYPE DATASETFamily and Population Approach to Gene Discovery for Preterm BirthConditions for Access to Data from the Danish National Birth Cohort (DNBC)Global inclusion criteria (applied to both cases and controls): Singleton gestation Live birth Child free of congenital abnormalities No maternal conditions known to be associated with preterm delivery or often requiring early delivery of the baby (placenta previa, placental abruption, hydramnios, isoimmunization, placental insufficiency, pre-eclampsia/eclampsia) Maternal blood sample (buffy coat) available in the Danish National Birth Cohort biobank Child's parents and all four grandparents born in Denmark (except in 24 cases with one or two grandparents from other Nordic countries) Global restriction: One child per eligible mother Additional restriction for case pairs: Child delivered before 37 completed weeks' gestation Additional restrictions for control pairs: Child delivered at 40 completed weeks' gestation Child blood sample (buffy coat) available in the Danish National Birth Cohort biobank ]]>