PRENATAL DIAGNOSIS Prenat Diagn 2011; 31: 196–201. Published online 4 January 2011 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/pd.2682 Maternal serum insulin-like growth factor-binding protein-1 (IGFBP-1) at 11–13 weeks in pre-eclampsia Stavros Sifakis 1 , Ranjit Akolekar 2 , Dimitra Kappou 1 , Nikitas Mantas 2 and Kypros H. Nicolaides 2,3 * 1 Department of Obstetrics and Gynaecology, University Hospital of Heraklion, Crete, Greece 2 Department of Fetal Medicine, King’s College Hospital, London, UK 3 Department of Fetal Medicine, University College Hospital, London, UK Objective The aim of this study was to determine the maternal serum concentration of insulin-like growth factor-binding protein-1 (IGFBP-1) at 11–13 weeks’ gestation in pregnancies that subsequently develop pre-eclampsia (PE) and to examine the possible association with uterine artery pulsatility index (PI). Methods Maternal serum concentration of IGFBP-1 and uterine artery PI were measured in 60 cases that developed PE, including 20 that required delivery before 34 weeks (early-PE) and 120 unaffected controls. The measured IGFBP-1 concentration and uterine artery PI were converted into a multiple of the expected median (MoM) in unaffected pregnancies and median MoM values were compared in the outcome groups. Regression analysis was used to determine the significance of association of IGFBP-1 MoM with uterine artery PI MoM. Results In the early- and late-PE groups, the median IGFBP-1 was decreased (0.63 and 0.67 MoM, respectively) and uterine artery PI was increased (1.31 and 1.19 MoM, respectively). In the group that developed PE there were no significant associations between serum IGFBP-1 with uterine artery PI (p = 0.210). Conclusion In pregnancies that develop PE, the serum IGFBP-1 is decreased from the first trimester suggesting that IGFBP-1 may be implicated in the pathogenesis of PE in a mechanism unrelated to impaired placental perfusion. Copyright  2011 John Wiley & Sons, Ltd. KEY WORDS: first-trimester screening; insulin-like growth factor-binding protein-1; pre-eclampsia; pregnancy- associated plasma protein-A; uterine artery Doppler INTRODUCTION Pre-eclampsia (PE), which affects approximately 2% of pregnancies, is a major cause of maternal and perina- tal morbidity and death (ACOG, 2002). There is an emerging evidence that PE is a heterogeneous condition with early disease requiring delivery before 34 weeks, thought to be a consequence of impaired placentation (Meekins et al., 1994; Yu et al., 2005; Plascencia et al., 2007), whereas in late-PE the main pathophysiological processes resemble those of the metabolic syndrome with increased insulin resistance (Kaaja et al., 1995; Lorentzen et al., 1998; Vatten and Skjaerven, 2005; D’Anna et al., 2006). Several studies have demonstrated that in pregnancies complicated by PE, both during and before the clinical onset of the disease the circulating maternal concen- trations of insulin-like growth factor-binding protein-1 (IGFBP-1) are altered (Table 1), suggesting that IGFBP- 1 may be implicated in the pathogenesis of the disease. However, it is not clear whether the relation between IGFBP-1 and PE is the consequence of its actions on *Correspondence to: Kypros H. Nicolaides, Harris Birthright Research Centre for Fetal Medicine, King’s College Hospital, Denmark Hill, London SE5 9RS, UK. E-mail: kypros@fetalmedicine.com placentation or its effects on insulin resistance and the metabolic syndrome. During pregnancy IGFBP-1 is pro- duced by decidualized endometrial cells (Han et al., 1996; Giudice and Irwin, 1999) and has a direct effect on the interaction between the decidua and the invad- ing trophoblast (Han et al., 1996; Giudice and Irwin, 1999; Lee et al., 1997; Fowler et al., 2000). In addi- tion, IGFBP-1 is involved in placentation and insulin resistance indirectly through its effects on IGF-I. This binding protein prolongs the half-life of IGF-I in plasma (Rechler and Clemmons, 1998; Monzavi and Cohen, 2002), and previous studies reported that IGF-I regulates and enhances trophoblast invasion by stimulation of cell migration and proliferation (Aplin et al., 2000; Fowler et al., 2000; Lacey et al., 2002; Forbes and Westwood, 2008). In addition, IGFBP-1 plays a role in maternal metabolism and the maintenance of glucose levels by preventing glucose uptake by muscle and hepatic cells through its inhibitory effects on IGF-I (Baxter, 1995; Lee et al., 1997). The aims of our study were first, to investigate the maternal serum concentration of IGFBP-1 at 11– 13 weeks in pregnancies that subsequently develop PE and second, to examine whether the possible relation of IGFBP-1 to PE is mediated by an effect on placentation manifested in increased uterine artery pulsatility index (PI), which provides a measure of placental perfusion Copyright  2011 John Wiley & Sons, Ltd. Received: 1 August 2010 Revised: 8 November 2010 Accepted: 16 November 2010 Published online: 4 January 2011