CONCLUSION: Our results, in a large cohort of healthy, non-diabeticwomen have shown that insulin resistance, even at levels below thosediagnostic of gestational diabetes, is associated with maternal and fetalinflammatory response. These findings have important implicationsfor defining the pathway for fetal programming of later metabolicsyndrome and childhood obesity.

211 Cardiotonic steroids induce an anti-angiogenicprofile in first trimester cytotrophoblast cellsJessica Ehrig1, Kelsey Kelso1, Russell Fothergill1, Steven Allen1,Richard Jones1, Thomas Kuehl1, Mohammad Uddin1

1Scott & White Memorial Hospital / Texas A&M Health Science CenterCollege of Medicine, Department of Obstetrics & Gynecology, Temple, TXOBJECTIVE: Preeclampsia (preE), a hypertensive disorder unique topregnancy, is characterized by abnormal placentation. Our investiga-tive team has demonstrated that marinobufagenin (MBG), one of thecardiotonic steroids (CTSs), inhibits these critical steps for normalplacental development: proliferation, migration and invasion of cy-totrophoblast (CTB) cells. The aim of this study is to determinewhether CTSs induce anti-angiogenic effects in CTB cells.STUDY DESIGN: Cells from the human extravillous CTB cell line Sw.71,derived from first trimester chorionic villus tissue, were incubatedwith 0.1, 1, 10, and 100 nM of each of three types of CTS (MBG,Cinobufatalin and Ouabain) for 72 h. Thereafter, the levels of angio-genic factors, vascular endothelial growth factor (VEGF), placentalgrowth factor (PlGF) and anti-angiogenic factors, soluble fms-liketyrosine kinase-1 (sFlt-1), soluble endoglin (sEnd) were measured inthe cell culture media by commercially available ELISA kits. Addition-ally, the expression of three CTB receptors, VEGF-1, angiogenic an-giotensin type 1 receptor (AT1) and anti-angiogenic angiotensin type2 receptor (AT2) were assayed using immunoblotting (western blot)in cell lysates.RESULTS: sFlt-1 and sEnd secretion were significantly increased whileVEGF and PIGF were decreased in the culture media of CTB cellstreated with �1 nM of all three CTSs (*p�0.05 for each). The AT2

receptor expression was significantly up-regulated in � 1 nM CTS-treated CTB cells, whereas AT2 and VEGF-1 receptor expressions weredown-regulated (*p�0.05 in each case).CONCLUSION: Exposure of CTB cells to CTSs induces an anti-angio-genic profile by: (i) up-regulating AT2 receptor expression; (ii) down-regulating AT1 and VEGF-1 receptor expression; (iii) increasing se-cretion of sFlt-1 and sEnd; and (iv) decreasing secretion of VEGF andPlGF.

212 Circulating adipokines in twins and singletons - linkingthe bridge from plurality to restricted fetal growthJiga Haas1, Eyal Sivan1, Eyal Schiff1, Yoav Yinon1,Mordechai Dulitzky1, Eran Barzilay1, Rina Hemi2,Clara Pariente2, Hannah Kanety2, Shali Mazaki-Tovi1

1Sheba Medical Center, Tel-Hashomer, Department of Obstetrics andGynecology, Ramat Gan, Israel, 2Institute of Endocrinology, Sheba MedicalCenter, Tel-Hashomer, Department of Obstetrics and Gynecology, RamatGan, IsraelOBJECTIVE: The condensational view is that the uterine milieu is lim-ited in its ability to nurture more than one fetus. Yet, the mecha-nism(s) by which attenuated twins growth is achieved has eluded elu-cidation. Adipokines have been implicated in fetal growth anddevelopment. The aim of this study is to determine cord blood adi-ponectin and leptin in twins and singletons.STUDY DESIGN: This is a case-control study included 2 groups of new-borns, matched for gestational age and birthweight percentile: 1. sin-gleton (n�60) and 2. twins (n�44). Adiponectin and leptin weredetermined in arterial cord blood. Non-parametric and parametricstatistical methods were used.RESULTS: Median adiponectin (31.5 vs. 63 �g/dL) and leptin (2.5 vs.5.6 ng/dL) concentrations was lower in twins vs. singletons (p�0.001for both comparisons). Among SGA newborns, median concentra-

tion of adiponectin (p�0.02), but not leptin (p�0.1), was lower intwins compared to singleton. Cord blood adiponectin was stronglycorrelated with gestational age (p�0.001, r�0.55) and birthweight(p�0.001, r�0.59), as was cord blood leptin (gestational age:p�0.005, r�0.27; birthweight: p�0.001, r�0.44). Regression analysisrevealed that plurality, gestational age and birthweight were signifi-cantly and independently associated with cord blood adiponectinconcentrations after adjustment for maternal BMI, age and gender.Similar regression model did not revealed association between plural-ity and cord blood leptin concentrations.CONCLUSION: Twins pregnancies are associated with lower cord bloodconcentrations of adiponectin, but not leptin, compared with single-ton gestations. These findings suggest that alterations in adiponectinconcentrations may provide a molecular mechanism to account forthe growth disparity between twins and singleton. These findings sup-port the concept that adipokines, particularly adiponectin may play arole in the complex and intriguing process of fetal growth.

213 Acute ascending aorta occlusion leads to decreasedcerebral perfusion pressure in a fetal sheepHeikki Huhta1, Juha Räsänen4, Juulia Junno1, Mervi Haapsamo1,Tiina Erkinaro2, Roger Hohimer3, Lowell Davis3,Ganesh Acharya5

1Oulu University Hospital, Obstetrics and Gynecology, Oulu, Finland, 2OuluUniversity Hospital, Anesthesiology, Oulu, Finland, 3Oregon Health andScience University, Obstetrics and Gynecology, Portland, OR, 4KuopioUniversity Hospital, Obstetrics and Gynecology, Kuopio, Finland,5University Hospital of Northern Norway, Obstetrics and Gynecology,Tromso, NorwayOBJECTIVE: The fetal aortic isthmus (AoI) is the only arterial connec-tion between the fetal right (RV) and left (LV) ventricles. In LV out-flow obstruction, blood from the ductus arteriosus flows retrogradeacross the AoI to supply fetal brain. We hypothesized that in acuteascending aorta (AA) occlusion (AAO), RV cardiac output wouldincrease and maintain normal arterial pressure in the carotid artery.STUDY DESIGN: Nine ewes underwent surgery at 115-135 gestationaldays (term 145 days) for the placement of a vascular occluder aroundfetal AA between the aortic valve and brachiocephalic artery. Fetalcarotid artery (CA) and jugular vein, and descending aorta (DAo) viafemoral artery were cannulated. After a 4-day recovery, fetal heart rate(FHR), right (RVCO) and left (LVCO) ventricular cardiac outputswere measured by ultrasonography. Pulmonary (Qp) volume bloodflow and systemic CO (combined cardiac output-Qp) were calculatedat baseline, 15 and 60 minutes after AAO, and 15 minutes after releaseof AAO. Mean arterial blood pressures (mABP) from CA and DAo,central venous (CVP) pressure, and CA pO2 were monitored.RESULTS: All the data are presented as means (SD).* p�0.05, com-pared with baseline.CONCLUSION: In fetal sheep, acute occlusion of AA leads to increasedRV cardiac output and decreased LV and systemic cardiac outputs,and pulmonary volume blood flow. Fetal arterial blood pressure in thedescending aorta is maintained. However, carotid artery blood pres-sure decreases during AA occlusion. Our results suggest that, at leastin acute conditions, retrograde blood flow shunting across AoI is notable to maintain normal cerebral perfusion pressure.

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