**9. Acknowledgments**

I would like to thank Ingemar Kjellmer, Professor at the Department of Pediatrics, Sahlgrenska University Hospital, Gothenburg, for his enthusiasm and encouragement, Anders Odén, Adjunct Professor of Biostatistics, Chalmers University of Technology, Gothenburg, for his patience, and Ulf Fagerquist, Tech Lic, my brother and friend, who created the computer programs, which gave us the opportunity to approach the true volume of the fetal urinary bladder.

Moreover, I would like to express my sincere thanks to Hans Steyskal, Professor and Mathematics Consultant, Concord, MA, USA, for his advice, and Sture G. Blomberg, MD, PhD, for his valuable criticism and support.

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**9** 

*Greece* 

**Recent Insights into the Role of the Insulin-Like** 

Preeclampsia, a hypertensive disorder that complicates approximately 3-5% of first pregnancies and is usually clinically manifested after 20 weeks of gestation, is a major cause of perinatal morbidity and mortality; also, neonates of preeclamptic mothers are prone to preterm birth, low birth weight for gestational age and fetal growth restriction [Goldman-Wohl & Yagel, 2002]. Although the pathophysiologic process of preeclampsia is not fully elucidated, abnormal placentation, shallow endovascular invasion, placental hypoxia, maternal insulin resistance and diffuse endothelial dysfunction seem to be interconnected key events that may precede the clinical onset of the disease by weeks or months [Davison et al., 2004]. In particular, impaired placental perfusion is evident even from the first trimester as it has been documented by the findings of both histologic and Doppler ultrasound findings of the uterine arteries and the altered levels of placental derived biochemical markers as

pregnancy-associated plasma protein (PAPP-A) [Poon et al., 2009a; Poon et al., 2009b].

The insulin-like growth factor (IGF) system comprises the IGF peptides (IGF-I, IGF-II), the cellular IGF receptors (type I, type II), and a family of soluble high affinity IGF binding proteins (IGFBP-1 to IGFBP-6) which modulate the bioavailability and activity of the IGFs [Jones & Clemmons, 1994] (Figure 1). Since the discovery of the IGF system before 50 or so years, there is ample evidence for their role in cell proliferation, differentiation and migration and their anti-apoptotic properties as well; thus they are involved in several physiological and pathological processes during prenatal and postnatal life [Forbes & Westwood, 2008]. This review aims to critically evaluate the postulated role of IGF axis components in the pathogenesis of preeclampsia and to discuss the mechanisms through

During pregnancy, several alterations are noted regarding the expression pattern and function of IGFs. According to a recent longitudinal study, the maternal serum levels of IGF-I remain stable until 20 weeks and then increase whereas IGF-II values do not relatively change throughout gestation [Olausson et al., 2008]. Though in non-pregnant-individuals,

**1. Introduction** 

which these effects are mediated.

**1.1 The IGF system in pregnancy** 

*1Department of Obstetrics-Gynecology, University Hospital of Heraklion, Crete,* 

**Growth Factor Axis in Preeclampsia** 

Dimitra Kappou1, Nikos Vrachnis2 and Stavros Sifakis1

*22nd Department of Obstetrics & Gynecology, Aretaieion Hospital,* 

*University of Athens, Athens,* 

