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2221 Neonatal alloimmune thrombocytopenia (NAIT) is a life-threatening bleeding disorder in the fetus/ neonate caused by maternal alloantibodies directed against fetal platelet antigens inherited from the father. Of the 21 allonatigens described up to date http://www.ebi.ac.uk/ipd/hpa/table2.html, the human platelet antigen (HPA) −1 defined as a leucine /proline polymorphism at residue 33 in b3 integrin is the immune-dominant antigen leading to severe NAIT. Immunization to HPA-1a occurs only in 10% of HPA-1bb pregnant women, 90% of them carrying histocompatibility leukocyte antigen (HLA) DRB3*0101. The aims of the present study were: 1. to prospectively study whether in addition to HLA DR B3*0101 there other potential HLA DR antigens involved in the immune process. 2. To analyse whether the response to IVIgG treatment correlates with maternal HLA DR genotype 3. to determine whether, anti HLA antibodies in addition to HPA1a antibodies, resulted in a more severe thrombocytopenia. We enrolled 21 pregnant women who had previously given birth to newborns with NAIT due to HPA1 incompatibility and had antibodies directed to their spouses HPA1 phenotype (leucine or proline polymorphism ) at the Sheba Medical Center from May 2001 to January 2011. The control group consisted of 21 women who delivered at term newborns with thrombocytopenia and a diagnosis of NAIT was ruled out. Twelve women of 21 (57%) in the study group carried both HLADRB3*0101 and DRB4*0101phenotype. But in none of the women in the control group such combination was detected. Interestingly is the observation that of 20 women who gave birth once more following IVIgG treatment, four did not respond to IVIgG and 3 (75%) of them harbor both DRB3*0101 and DRB4*0101. When lymphocytotoxic cross match analysis was performed in eighteen couples of the study group seven (39%) of them had positive lymphocytotoxic cross match. However the presence of both HLA and HPA1 antibodies against their partner phenotype did not affect platelets' counts in the newborn. Taken together we postulate that the presence of both HLADRB3*0101 and HLADRB4*0101 in the mother increases the risk of NAIT development when HPA1 incompatibility between the couples is found and can serve as a diagnostic tool. The presence of HLA antibodies against the spouse did not alter response to IgG treatment. Disclosures: No relevant conflicts of interest to declare.

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This technique may be useful in the prenatal diagnosis of conotruncal anomalies and in the assessment of the spatial relationships of abnormal vascular connections in the upper mediastinum. P01.34Maternal lipopolysaccharide depresses fetal cardiovascular function in mouse S. Rounioja, J. Räsänen, H. Autio-Harmainen, M. Ojaniemi, V. Glumoff, K. Mäkikallio, M. Hallman University of Oulu, FinlandBackground: Intra-amniotic lipopolysaccharide (LPS) causes a fetal inflammatory response and cardiac dysfunction in mice. We hypothesized that the placenta serves as a barrier against bacterial toxins delaying the onset of a fetal inflammatory response and cardiac failure. Methods: At 14-15 days of gestation DBA strain mice were randomized to receive LPS (∼ 70 µg) or vehicle intraperitoneally. Doppler ultrasonography of fetal cardiovascular hemodynamics was performed before and six hours after LPS. The expression and production of cytokines and other inflammatory mediators were determined using ribonuclease protection assay and cytometric bead array. Histopathology and immunostaining of toll-like receptor (TLR) in placenta were carried out. Results: Six hours after LPS injection, there was no evidence of stasis in maternal lung or liver, although tumor necrosis factoralpha (TNF-á) and interleukin (IL)-6 were increased in serum (p < 0.05). In contrast, placenta showed severe dilatation and stasis most distinctly in maternal vessels. The expression of TNF-á, IL-1á and IL-6 (p < 0.05) increased in placenta, whereas no inflammatory activation was evident in fetal tissues, and amniotic fluid revealed no increase in cytokines. The expression of TLR2 (p < 0.05) was increased in labyrinthine macrophages, which could serve as target for LPS. The fetal cardiac outflow mean velocity, was lowered (p < 0.005) in the LPS group. The pulsatility indices (PI) of the umbilical artery and the descending aorta and the PI for veins from the ductus venosus were higher after LPS. In the LPS group 65% of the fetuses had atrioventricular valve regurgitation, compared to only 4% in the vehicle group. Conclusions: Maternally administered LPS acutely induced cytokine expressions in placental tissue with histologic lesions. Inflammatory response was not evident in the fetal compartment. However, placental congestion increased the cardiac afterload, leading to fetal cardiovascular dysfunction.