PRENATAL DIAGNOSIS Prenat Diagn 2010; 30: 571–574. Published online 5 May 2010 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/pd.2528 The association between preeclampsia and placental disruption induced by chorionic villous sampling Antonio Farina 1 * , Junichi Hasegawa 1 , Simonetta Raffaelli 2 , Chiara Ceccarini 1 , Giuseppina Rapacchia 1 , M. Carla Pittalis 1 , Lorena Brondelli 1 , Francesca Righetti 2 and Nicola Rizzo 1 1 Department of Obstetrics and Gynecology, St Orsola Malpighi Hospital, University of Bologna, Bologna, Italy 2 Department of Haematology, Oncology and Laboratory Medicine, St Orsola Hospital, Bologna, Italy Objectives The objectives of this study were (1) to evaluate if the elevation of maternal serum α-feto protein (MSAFP) and pregnancy-associated placental protein-A (PAPP-A) in the maternal blood after chorionic villous sampling (CVS) is associated with a higher preeclampsia (PE) rate and (2) to verify the clinical utility of the analytes elevation for predicting PE. Methods A prospective study on 106 subjects who underwent CVS was performed. At the time of CVS, two blood samples were obtained for MSAFP and PAPP-A dosage, the first just before the procedure, and the second one 30 min after the procedure. Cases with abnormal karyotype, major anomalies or preterm delivery were subsequently excluded. The ratio between the two samples was calculated as  (MSAFP or PAPP-A post-CVS/MSAFP or PAPP-A pre-CVS) and it was related to subsequent occurrence of PE. Results The rate of PE was 5.7% (6/106). Both MSAFP and PAPP-A levels were higher after than before CVS (median ratio = 8.33 and 1.08, respectively). Cases developing PE had significantly higher MSAFP ratio (11.6 vs 7.4, p -value = 0.04) and PAPP-A ratio (1.13 vs 1.08, p -value = 0.009) than those who did not develop PE. Receiver operating characteristic curve analysis showed that PAPP-A ratio was a better predictor of subsequent PE than MSAFP ratio: at a fixed false positive rate of 10%, the detection rates for MSAFP and PAPP-A ratios were 33 and 50%, respectively. Conclusion The elevation of MSAFP and PAPP-A observed with CVS is associated with increased risk of subsequent PE. The ability of such increases to predict PE appears to be modest. Copyright  2010 John Wiley & Sons, Ltd. KEY WORDS: preeclampsia; chorionic villous sampling; AFP; PAPP-A INTRODUCTION Chorionic villus sampling (CVS) allows first-trimester prenatal diagnosis of genetic disorders. CVS causes feto- maternal hemorrhage due to the iatrogenic breach in the placenta and, as an epiphenomenon, the passing of cir- culating fetal proteins and trophoblastic cells into the maternal circulation. Several studies have shown that CVS can be associated with a higher rate of preeclamp- sia (PE) than expected for the general population (Silver et al., 2005; Adusumalli et al., 2007; Grobman et al., 2009). α-Fetoprotein (AFP) is a fetal glycoprotein which passes into the maternal circulation by diffusion across the placental membranes (Brumfield et al., 1990). An abnormal elevation of AFP has been reported in maternal serum (MS), and such an elevation is commonly con- sidered an indicator of CVS-associated fetal–maternal transfusion (Shulman et al., 1990; Katiyar et al., 2007). A direct correlation between the amount of villi obtained at CVS and the magnitude of feto-maternal transfusion has been documented (Shulman et al., 1990). Mixing of *Correspondence to: Antonio Farina, Department of Obstetrics and Gynecology, St Orsola Malpighi Hospital, University of Bologna, Via Massarenti 13, 40138 Bologna, Italy. E-mail: antonio.farina@unibo.it AFP from the fetal blood with the maternal serum occurs within 15 min of CVS (Katiyar et al., 2007). Pregnancy- associated plasma protein-A (PAPP-A) is a metallopro- teinase produced by the trophoblast and decidua (Barnea et al., 1986) which plays an important role in the reg- ulation of trophoblast invasion. Because of its location, PAPP-A can also be released into the maternal circula- tion during villi disruption. One could thus expect an elevation of PAPP-A as a result of CVS, as it occurs for MSAFP. No studies to date have explored this hypoth- esis. The purposes of this study were: (1) to evaluate if the MSAFP and PAPP-A elevations observed after CVS are associated with an increased rate of subsequent PE in a selected population and (2) to verify whether the magnitude of such elevations can be a diagnostic tool to predict occurrence of PE. MATERIALS AND METHODS This prospective cohort study was conducted from January 2008 to September 2009. The study population comprised women attending the Division of Prenatal Medicine at the University of Bologna, Bologna, Italy. A total of 106 women who underwent CVS between 11 and 13 weeks of gestation were included in the Copyright  2010 John Wiley & Sons, Ltd. Received: 5 February 2010 Revised: 5 March 2010 Accepted: 5 March 2010 Published online: 5 May 2010