Preterm birth is the most important cause of perinatal morbidity and mortality worldwide. In this thesis studies on spontaneous preterm birth are presented. The main objective was to investigate the predictive capacity of mid-trimester cervical length measurement for spontaneous preterm birth in a low-risk population and to assess the effect of progesterone for the prevention of preterm birth in women who had a short cervical length. We performed a prospective observational cohort study among women with a singleton pregnancy without a previous preterm birth with a randomised clinical trial embedded set in the Dutch Obstetric Consortium. The analysis focused on the ability of cervical length to identify women at increased risk of preterm birth before 32, 34 and 37 weeks of gestation. Women with a cervical length ≤ 30 mm were randomized and received vaginal progesterone or placebo. Primary outcome was adverse neonatal outcome. Between 2009 and 2013, 20,234 women were screened. A cervical length ≤ 30 mm was seen in 375 women (1.8%) of whom 80 agreed to participate in the trial. We could not show a significant benefit of progesterone in reducing adverse neonatal outcome and preterm birth <37 weeks. In women at low risk of preterm birth, we found the risk of preterm birth to be inversely related to mid-trimester cervical length for a cervical length ≤35 mm. However, the low sensitivity questions its isolated use as a screening tool to prevent preterm birth.