Inflammatory Markers in the Second Trimester Prior to Clinical Onset of Preeclampsia, Intrauterine Growth Restriction, and Spontaneous Preterm Birth Sofie Haedersdal, 1,5 Jannie D. Salvig, 3 Martine Aabye, 2 Christian W. Thorball, 2 Morten Ruhwald, 2 Steen Ladelund, 2 Jesper Eugen-Olsen, 2 and Niels J. Secher 4 Abstract—Low-grade inflammation has been associated with pregnancy complications including preeclampsia (PE), intrauterine growth restriction (IUGR), and spontaneous preterm birth (SPB). In an unmatched, nested case–control study, we assessed the possible predictive association of mate- rnal C-reactive protein (CRP), interferon-γ-inducible protein 10 (IP-10), and soluble urokinase pl- asminogen activator receptor (suPAR) in second trimester plasma samples in relation to later development of PE (n 0 29), IUGR (n 0 53), and SPB (n 0 9). Inflammatory marker levels in these groups were compared to normotensive healthy pregnant controls (n 0 127). We found no statistic- ally significant difference in CRP, IP-10, or suPAR in second trimester plasma samples from pre- gnant women with later PE, IUGR, and SPB when compared to normotensive healthy controls. Second trimester plasma samples of CRP, IP-10, and suPAR cannot be used as a prognostic marker for PE, IUGR, and SPB. KEY WORDS: inflammatory markers; intrauterine growth restriction; preeclampsia; spontaneous preterm birth; suPAR. INTRODUCTION Preeclampsia (PE), intrauterine growth restriction (IUGR), and spontaneous preterm birth (SPB) are some of the most common obstetric complications, causing relevant public health concerns due to the fact that effective preventive strategies remain unavailable [1–3]. PE is a hypertensive disorder that complicates 3–5% of pregnancies and contributes significantly to maternal and perinatal morbidity and mortality [4]. PE is associated with an increased risk of IUGR, although most preeclamptic patients do not give birth to growth- restricted infants [5]. PE and IUGR share common pathophysiological traits of abnormal placentation due to inadequate trophoblast modification of spiral arteries, resulting in oxidative and inflammatory stress [6, 7]. Preterm birth, defined as birth before 37 weeks of gestation, accounts for approximately 75 % of perinatal mortality and more than half of long-term morbidity [8]. The most severe complications are observed at delivery before 34 weeks of gestation [9]. Several pathophysiological aspects have been exam- ined as potential key factors for developing PE, IUGR, and SPB; one of these is the importance of inflammation [2, 10, 11]. In recent years, the term “low-grade inflammation” has commonly been used to describe a state of a slightly elevated number of immune cells and elevated levels of pro-inflammatory proteins and acute phase proteins in 1 Department of Obstetrics and Gynaecology, Hvidovre Hospital, Univer- sity of Copenhagen, Kettegaard Allé 30, 2650 Hvidovre, Denmark 2 Clinical Research Center, Hvidovre Hospital, University of Copen- hagen, Hvidovre, Denmark 3 Department of Obstetrics and Gynaecology, University Hospital of Aarhus, Skejby, Denmark 4 The Research Unit Women’s and Children’s Health, The Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Copenha- gen, Denmark 5 To whom correspondence should be addressed at Department of Obstetrics and Gynaecology, Hvidovre Hospital, University of Copen- hagen, Kettegaard Allé 30, 2650 Hvidovre, Denmark. E-mail: sofiehaedersdal@gmail.com Abbreviations: PE, Preeclampsia; IUGR, Intrauterine growth restric- tion; SPB, Spontaneous preterm birth; CRP, C-reactive protein; IP-10, Interferon-γ-inducible protein 10; suPAR, Soluble urokinase plasmin- ogen activator receptor 0360-3997/13/0000-0001/0 # 2013 Springer Science+Business Media New York Inflammation ( # 2013) DOI: 10.1007/s10753-013-9619-x