Spontaneous preterm birth and genetics

Preterm birth (PTB) is the main cause of perinatal mortality and short- and long-term morbidity. The pathophysiology of spontaneous PTB remains poorly understood. Infection and inflammation, fetal growth, uterine distention and decidual haemorrhage are be lieved to be part of the mechanisms resulting in preterm delivery. The genetic aspects of the mechanisms of spontaneous PTB will be the main focus of this research project, and it will be conducted as part of the Norwegian Mother and Child cohort study. Biological material, in the form of maternal serum, has been sampled at 18th gestational week and at delivery. Paternal serum has also been sampled. Umbilical cord blood (fetal blood) has been sampled at delivery. At present more than 50 000 deliveries ar e included. DNA is extracted and stored. The Norwegian Mother and Child cohort study has prospectively stored a huge amount of epidemiological data from questionnaires regarding the included deliveries. These data can be linked to the Norwegian Medical Bi rth Register as well. The study will be conducted using a triad-design with contol trios. We will use a candidate gene approach defined from a thoroughly review of the literature with regard to plausible pathways and available data on the protein le vel from women with threatening PTB. New high throughput technologies within the genetic field will be used. A new analytical model developed at Vanderbilt University, Nashville Tenessee will be used in the analyses after genotyping. Other analytical tool s applicable in trios will also be used. The significance of the project will be an increased understanding of PTB and its mechanisms at the genetic level. Furthermore, it will contribute to our growing knowledge of the preterm low-risk population. This will make it possible to find strategies for treatment and prevention of PTB. An intermediate aim will be development of biomarkers for PTB in women without symptoms of threatening preterm delivery.