P. Barja

Prediction of early and late pre-eclampsia from maternal characteristics, uterine artery Doppler and markers of vasculogenesis during first trimester of pregnancy.

To develop a predictive model for pre‐eclampsia using clinical, biochemical and ultrasound markers during the first trimester of pregnancy.

Endothelial cell markers in chronic uremia: relationship with hemostatic defects and severity of renal failure.

Plasma von Willebrand factor antigen, soluble thrombomodulin, and tissue factor were increased in 31 patients with severe chronic renal failure (creatinine clearance <20 ml/min) under conservative treatment, whereas plasminogen activator inhibitor antigen did not differ significantly from healthy controls. No correlation among plasma levels of these proteins was found. Three patterns of relationship between endothelial cell markers and hemostatic defects were identified: 1) Plasma thrombomodulin, a marker of endothelium damage, was found an independent predictor of bleeding time and platelet aggregation, and secretion defects, and was also related to the severity of renal failure; 2) von Willebrand factor antigen, an index of endothelial cell activation and secretion, was significantly correlated with intravascular markers of thrombin and plasmin generation and with platelet adenosine triphosphate content, but not with plasma creatinine levels; and 3) tissue factor and plasminogen activator inhibitor antigen levels were not statistically correlated with the diverse hemostatic defects. Activation of coagulation and fibrinolysis, secondary to endothelial cell activation, appearing early during the evolution of chronic renal failure, is pathogenically related to the platelet dysfunction, and probably to development of atherosclerosis and thrombotic events in this disease. The progression of chronic renal failure, through endothelial cell damage, would lead to aggravation of the platelet functional defect potentiating the hemorrhagic risk.

Effects of Loxosceles laeta spider venom on blood coagulation.

The hematologic effects of intradermal injection of Loxosceles laeta venom in rabbits were studied with special reference to partial thromboplastin time, prothrombin time, platelet count and fibrinogen-fibrin degradation products. The in vitro effect of Loxesceles laeta venom on human platelet aggregation was also studied. Fibrinogen and platelet count decreased and fibrinogen-fibrin degradation products increased at 12 hr.

Oxidative damage to pre-eclamptic placenta: immunohistochemical expression of VEGF, nitrotyrosine residues and von Willebrand factor

Objective: To determine the relationship of biomarkers of placental damage by oxidative stress in pre-eclamptic placenta. Methods: A case-control study was performed on a population of 14 pregnant women with PE and 12 women with normal pregnancies. Immunohistochemical expressions of VEGF, vWF distribution, (Na + K)-ATPase activity, and abundance of nitrotyrosine residues, were assessed in the placental tissue. Results: Women with pre-eclampsia showed increased VEGF expression and abundance of nitrotyrosine residues in placental villous, and plasma vWF levels (p < 0.05), whereas placental (Na + K)-ATPase activity were significantly reduced. The syncytiotrophoblast and the maternal space of pre-eclamptic placenta showed diminished and increased vWF expression, respectively, but no significant differences in its expression were found in the placental endothelium and stroma (p < 0.05). Conclusions: It could be suggested that increased oxidative stress and VEGF contribute to enhance the impairment of placental perfusion by increasing peroxynitrite formation, product of the NO and superoxide reaction, thereby partly contributing to account for the pathophysiology of this disease. The presence of vWF in the maternal space and its diminished expression in syncytiotrophoblast of pre-eclamptic placenta also might have pathogenic implications.

First-Trimester Adiponectin and Subsequent Development of Preeclampsia or Fetal Growth Restriction

Background/Aims: The evidence regarding the utility of assessing first-trimester adiponectin (ApN) serum levels in early prediction of preeclampsia (PE) and fetal growth restriction (FGR) is contradictory. This study aims to determine the role of maternal serum ApN levels as an early predictor of PE and FGR. Methods: A prospective case-control study among a pregnant population who attended their 11- to 14-week ultrasound scan at the University of Chile’s Clinical Hospital’s Fetal Medicine Unit. We included patients who developed PE or FGR (10 cases per group) and 35 healthy controls. We determined ApN levels in blood samples from these 55 patients using a commercial ELISA kit and assessed the relationship of ApN levels with variables like development of PE, FGR, weight at birth and maternal BMI. Results: There were no significant differences among first-trimester ApN serum levels in the groups. Average concentrations were 8, 6.8 and 10.8 ng/ml for the control, PE and FGR groups, respectively. Conclusion: In our study, maternal serum ApN levels were not useful in predicting subsequent development of PE and FGR. However, maternal serum ApN concentration adjusted by BMI was significantly higher during the first trimester in women who later developed FGR.

OP37.01: First trimester maternal serum PP13 as screening test for preeclampsia and small gestational age

Methods: The Mod-MPI was measured prospectively between June 2009 and February 2010, in addition to the more commonly used indices of systolic cardiac function (EF) in 61 healthy fetuses (gestational age range, 16–37 weeks) and in 31 fetuses suspected of having cardiovascular dysfunction due to the presence of CCAM. An unsupervised classification analysis was conducted to identify groups of fetuses according to the location of the mass. Doppler flow-derived measures of Mod-MPI was performed as described by Hernandez-Andrate, and the ejection fraction was obtained from two-dimensional M-mode images in a transverse four-chamber view. Results: In the CCAM group, the systolic performance, as indicated by the ejection fraction, was decreased and the ventricular Mod-MPI was increased, thus suggesting diastolic dysfunction and poor filling secondary to cardiac compression. In the right-sided mass group, fetuses had abnormal EF and MPI, reflecting increased after-load on the ventricle with the vena cava as well as cardiac compression. In the left-sided mass group, fetuses had abnormal RV and LV MPI with isovolumic contraction time lengthening and preserved left systolic performance. Conclusions: In both rightand left-sided CCAM, diastolic dysfunction has a significant role in the pathophysiology of each disorder and precedes changes in systolic performance. Measures of ventricular performance can help to elucidate the poorly understood mechanisms of cardiovascular compromise in the developing fetus.

OC93: Effect of antioxidant vitamins in the prevention of pre-eclampsia in women with abnormal uterine artery Doppler during the second trimester of pregnancy

The differential diagnosis of hypertensive disorders in pregnancy is based in clinical, laboratorial and fundoscopic findings. The role of the ophthalmologist in the diagnosis of pre-eclampsia appears to be subjective and limited. Ophthalmic artery Doppler is an objective exam that can improve the diagnosis of hypertension in pregnancy. The study aims to analyze the ophthalmic artery Doppler indices in pregnancies with chronic hypertension and pre-eclampsia. Methods: Cross-sectional study that analysed 30 women with chronic hypertension and 44 preeclamptic women (National High Blood Pressure Education Program 2000 criteria) during the third trimester of pregnancy. Right and left eyes indices means and standard deviation were evaluated to the resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), end diastolic velocity (EDV) and peak ratio (PR). Mann-Whitney test were applied to compare the two groups of hipertensive woman and p-values < 0.05 were considerd statistically significant. Results: The ophthalmic arteries Doppler averages indices in chronic hypertension and pre-eclampsia were respectively RI: 0.74 ± 0.06; 0.63 ± 0.17, PI: 1.68 ± 0.41; 1.12 ± 0.28, PSV: 34.01 ± 10.3; 38.60 ± 9.67, DVF: 9.0 ± 4.12; 14.26 ± 4.74 and PR: 0.64 ± 0.13; 0.82 ± 0.09. The Doppler indices demonstrated ophthalmic artery lower impedance in preeclamptic women compared with chronic hypertension women. All the Doppler indices were accurate in the diferential diagnosis of chronic hypertension and pre-eclampsia demonstrated by p = 0.0001 (RI, PI, EDV, PR) and p = 0.0171 (PSV). The best parameter to establish a cut of point to differentiate chronic hypertension to pre-eclampsia was 0.75 to PR index. Conclusions: The ophthalmic artery Doppler is a new parameter that can be used in the differential diagnosis and classification of hypertensive disorders in pregnancy.

P209: Endothelial dysfunction is correlated with preeclampsia and fetal growth

lean mass (MAFM and MALM, scm), the mid-thigh fat mass and lean mass (MTFM and MTLM, scm), the abdominal fat mass (AFM, mm) and the subscapular fat mass (SSFM, mm). The Mann-Withney U-test and the Student t test were used to compare the two groups. Results: The abdominal circumference and the humerus were statistically lower among the GR fetuses. Most of the SCTT values were different in the two groups; particularly the SSFM (3.6 ± 1.1 vs 2.6 ± 0.7 mm; p = 0.011), the AFM (5.1 ± 0.7 vs 4 ± 1 mm; p = 0.01), the MAFM (3.5 ± 0.9 vs 2.2 ± 0.8 scm; p < 0.01) and MALM (2.1 ± 0.4 vs 1.7 ± 0.5 scm; p = 0.029) were statistically higher in fetuses with a normal development respect to the GR fetuses. Conclusions: We observed that, at mid-gestation, the whole set of SCTT, excluding the MTFM, is reduced among fetuses later developing an intrauterine growth restriction. Moreover we also found that the MALM was lower in GR fetuses, testifying that fat free mass and not only fat mass is involved in the incorrect fetal development. Therefore, the evaluation of SCTT allows us to understand that the whole fetal body compartments are involved in a ‘‘intrauterine dismantlement’’ that, if not recognized by time, might lead the fetus to death.

P017: Biochemical markers and uterine artery Doppler as predictors of complicated pregnancies

Walker-Warburg syndrome (WWS) is an autosomal recessive condition characterized by diffuse neurodysplasia, resulting in brain and eye abnormalities. We report on a prenatally diagnosed case of this syndrome born to a consanguineous couple. The patient was referred at 24 weeks following prenatal diagnosis of hydrocephalus at a 22 weeks routine scan. Major hydrocephalus was confirmed. In addition, abnormalities of the eye were found: an unilateral congenital cataract and a parasagital intra ocular structure in both eyes between the lens and the posterior wall of the eye. These structures were interpreted as bilateral hyperplasia of a persistent primary vitreous (PHPV). The parents elected to continue the pregnancy. Amniocentesis documented a normal male karyotype. MRI performed at 32 weeks confirmed hydrocephalus and lissencephaly II consistent with WWS, but was not contributive regarding the eye abnormalities. Ultrasonographic follow-up showed unchanged eye structures up to 34 weeks, when target like images suggestive of retinal detachment were found. The baby died immediately after birth. Autopsy showed dilated ventricles, thin cortex, type II lissencephaly and retinal dysplasia associated with retinal nonattachment, confirming the diagnosis of Walker-Warburg syndrome. The case we report demonstrates that prenatal sonographic diagnosis of retinal non attachment and of PHPV is feasible. It may have implications for prenatal diagnosis of conditions involving such abnormalities. Moreover, we report for the first time, on the prenatal occurrence of a retinal detachment following the presence of PHPV. It suggests that retinal dysplasia associated with WWS could be secondary to a retinal nonattachment due to PHPV, rather than resulting from a ‘‘primary’’ malformative process as classically accepted.

OC206: Assessment of adverse perinatal outcome using transvaginal uterine artery doppler between 22 to 25 week's gestation in an unselected chilean population

Objective: The purpose of this study was to evaluate the clinical value of the uterine artery color Doppler at 23 week’s gestation in predicting adverse perinatal outcomes in unselected population. Methods: Uterine artery Doppler assessment was carried out at 22–25 week’s gestation in singleton pregnancies attending routine antenatal care. The mean pulsatility index (PI) was calculated and the predictive value of an average PI above 95th centiles in the detection of poor outcome was determined. Results: Transvaginal color Doppler examination was performed in 1350 consecutive singleton pregnancies and a complete outcome information was obtained in 1110 (83%) pregnancies. The median PI was 1.02 and the 95th centile was 1.57. Poor outcome, defined as preeclampsia, fetal growth restriction (FGR), abruption placenta and preterm delivery before 34 week’s, occurred in 143 (12.9%) pregnant women. The incidence of preeclampsia and FGR was 4.6% and 5.2%, respectively. The sensitivity of the mean PI above 95th centile for poor perinatal outcome was 26%, and for preeclampsia was 33%. Although, there were few cases with adverse perinatal outcome born before 35 week’s in our series (20 cases with just 6 preeclamptic pregnancies), the respective sensitivities for total adverse outcome and preeclampsia requiring delivery before 34 week’s was 45% (9 out of 20 cases) and 67% (4 out of 6 cases), respectively. Conclusions: Transvaginal uterine artery Doppler using as a screening test between 22–25 week’s identifies most of the pregnant women who develop severe adverse perinatal outcomes before 34 week’s of gestation. Supported by Fondecyt No 1020080.