Prediction of Spontaneous Preterm Birth : Clinical and Immunological Aspects

Abstract

Background: Preterm birth (PTB), defined as birth before 37 weeks of gestation, accounts for most neonatal death and morbidity. Accurate prediction is a pre-requisite for the prevention and proper management of PTB. However, methods for prediction are unsatisfactory, although sonographic cervical length has a moderate predictive value. For clinical utility, adding a biomarker could increase the predictive accuracy. The immune system has an important regulatory role during pregnancy. Thus, presumptive predictive biomarkers may be searched for among immune-related molecules, such as cytokines, chemokines and other inflammation-associated mediators.The aims of this thesis were to identify clinical risk factors and immunological prediction markers for PTB, both in women at increased risk of PTB because of preterm labour (PTL) or preterm prelabour rupture of the membranes (PPROM), and in asymptomatic women in early pregnancy. An additional aim was to explore immune reaction patterns in PTL and PPROM compared to normal pregnancy. Material and methods:In a retrospective registry study, including 20,643 women who delivered during a five-year period, risk factors for Apgar score <7 at five minutes and risk factors for PTB <32 weeks were investigated using univariate and multivariate logistic regression. Furthermore, in a multi-centre mixed case-control and prospective cohort study of women with PTL <34 weeks of gestation (n=80), PPROM (n=40), as well as antenatal controls (n=44) and controls in labour at term (n=40), plasma levels of cytokines and chemokines representing different types of immune responses were analysed with a multiplex bead assay. In addition, an extended protein analysis exploring 92 inflammation-associated plasma proteins using proximity extension assay (PEA) was performed, as well as analysis of 67 different oxylipins by liquid chromatography coupled to tandem mass spectrometry. Finally, the PEA technique was used also to explore plasma proteins in a case-control study including 46 women with PTB and 46 women with normal pregnancies and delivery at term. Results and conclusions:A number of partly preventable clinical risk factors for PTB <32 weeks were identified, for example smoking (odds ratio (OR) 1.61 (95% confidence interval (CI) 1.07-2.41)); preeclampsia )); and multiple gestation (OR 15 (95% CI 10-24)). The most evident risk factor for low Apgar scores was PTB; the more preterm the higher the risk. This provides important information for health care professionals, and offers motivations for preventive strategies regarding smoking cessation.