Identification of biological/biochemical marker(s) for preterm delivery

Fetal and neonatal mortality and morbidity rates are strongly associated wi th gestational age for delivery: the risk for poor outcome increases as ges tational age decreases. Attempts to predict preterm delivery (PTD, spontane ous delivery before 37 weeks' gestation) have been largely unsuccessful, an d rates of PTD have not improved in recent decades. More recently, the repo rted associations between infections in pregnancy and PTD suggest preventiv e initiatives that could be taken. The overall objective of the current study is to assess whether specific ma rkers of infection (primarily interleukin (IL) 1 beta, tumour necrosis fact or (TNF) alpha, IL-6, and IL-10) obtained from maternal blood during pregna ncy, alone or in combination with other risk factors for PTD, permit identi fication of women at risk for spontaneous PTD. To achieve this objective, d ata are obtained from two Danish prospective cohort studies involving seria l collection of maternal blood samples, newborn cord blood samples, and rel evant confounders and other risk factors for PTD. The first study consists of a completed Danish regional cohort of 3000 pregnant women enrolled in a study of microbiological causes of PTD, upon which a nested case-control st udy of PTD in 84 cases and 400 controls has been performed. The second stud y is a nested case-control study of 675 PTD cases (equally divided into thr ee gestational age categories of 24-29 weeks' gestation, 30-33 weeks' gesta tion, and 34-36 weeks' gestation) and 675 controls drawn from the ongoing D anish National Birth Cohort study of 100000 pregnant women enrolled during 1997-2001. The second study will provide the opportunity to refine and rete st hypotheses from the first study, as well as to explore new hypotheses. O ur preliminary work suggests that a single predictive marker effectively ac counting for a large proportion of PTD is unlikely to be found. Rather, a s earch for multiple markers indicative of the multifactorial aetiology of PT D is likely to be more successful. Knowledge gained from the proposed studies will be implemented in a third, clinical intervention study against PTD. The first phase of the clinical in tervention study will be to establish a risk-assessment model based on the 'best' combination of biological/biochemical measures and other factors ass ociated with PTD in order to identify pregnant women at very high risk of P TD. The second phase will be to apply an intervention model of tailored obs tetric care to the very high-risk pregnant women for PTD identified in phas e one. The intervention will be carried out against each specific risk fact or associated with PTD identified for the individual. The aim is to reduce the risk for PTD attributed to the combination of risk factors included in the clinical intervention study.