OP005. Preeclampsia is associated with the presence oftranscriptionally active placental fragments in thematernal lungBuurma Aletta, Penning Marlies, Prins Frans, SchutteJoke, Bruijn Jan Antonie, Rajakumar Augustine, Blo-emenkamp Kitty, Karumanchi Ananth, Baelde Hans

Introduction: Preeclampsia is associated with increasedlevels of the circulating anti-angiogenic factor sFlt-1 as wellas with an excessive shedding of placenta-derived multinu-cleated syncytial aggregates into the maternal circulation.However, it remains unclear whether these aggregates aretranscriptionally active in the maternal organs and cantherefore contribute to the systemic manifestations ofpreeclampsia.

Objectives: We hypothesized that in preeclampsia,syncytial knots are the primary placental site of sFlt-1production and that increased numbers of sFlt-1-containingsyncytial aggregates are retained in the maternal lungs.

Methods: In this study, we measured placental sFlt-1mRNA levels in preeclamptic- and control placentas andperformed RNA in situ hybridization to localize the mainplacental expression site of sFlt-1 mRNA. Because thematernal lung is the first capillary bed that circulatingsyncytial aggregates traverse, we studied the presenceand persistence of placental material in lungs of preeclamp-tic women and control subjects. To confirm the placentalorigin of suspected syncytial aggregates in these lungs,immunohistochemistry for the placenta-specific markerhCG and Y-chromosome in situ hybridization wereperformed.

Results: Using human placental tissue, we found that syn-cytial knots are the principal site of expression of the anti-angiogenic factor sFlt-1. In addition, in autopsy materialobtained from women with preeclampsia (n = 9), weobserved significantly more placenta-derived syncytialaggregates in the lungs than in control subjects (n = 26).Importantly, these placental aggregates still contained theanti-angiogenic factor sFlt-1 following their entrapment inthe maternal lungs.

Conclusion: The current study confirms the important roleof syncytial knots in placental sFlt-1 mRNA production.Additionally, it shows a significant association between pre-eclampsia and larger quantities of sFlt-1 containing syncy-tial aggregates in maternal lungs, suggesting that thetransfer of syncytial aggregates to the maternal compart-ment may contribute to the systemic endothelial dysfunc-tion that characterizes preeclampsia.

doi:10.1016/j.preghy.2013.04.021

OP006. A preeclampsia genome-wide linkage scan inNorwegian familiesLinda Tømmerdal Roten, Matthew P. Johnson, Liv CecilieV. Thompsen, Astrid S. Gundersen, Per Solberg, KjerstiTollaksen, Ingvill Lyslo, Christian Tappert, Maria LisaOdland, Kristin M. Strand, Mona H. Fenstad, Finn Drabløs,Frank Skorpen, Eric K. Moses, Rigmor Austgulen, LineBjørge

Introduction: Several maternal susceptibility loci for pre-eclampsia (PE) have been discovered amongst Icelandic,Australian/New Zealand, Dutch and Finnish family cohorts,implicating locus heterogeneity. Through candidate genestudies, allele-specific heterogeneity in different populationsis also evident. It is therefore likely that numerous popula-tion specific PE susceptibility variants exist, differing in theireffect size. Despite on-going efforts to identify susceptibilitygenes for PE, the causal genetic variants still remain obscure.

Objectives: The aim of this study is to interrogate thegenetic architecture of PE susceptibility by performing agenome-wide linkage scan in a novel familial cohort fromNorway.

Methods: A total of 480 DNA samples from The NorwegianPE Family Biobank were genotyped at Genomic Core Facilityat NTNU. Genome-wide genotyping was performed with theInfinium HumanExome BeadChip (>240,000 markers) (Illu-mina, USA) that delivers focused coverage of exonic regionsof the human genome.

Results: A total of 137 families are represented with 222women with a valid PE diagnosis (SBP P 140 mmHg DBP P90 mmHg, P2 measurements at least 4 h apart with docu-mented proteinuria at P2 occasions occurring after 20 weeksof pregnancy), 44 with self-reported PE and 72 women with ahealthy pregnancy. The genotyping has just recently beencompleted with an average call rate of 99.96%. Data andstatistical analysis is now underway using MERLIN, R andSOLAR. A description of the Norwegian PE familial cohort pluspreliminary results will be presented at the Congress.

Conclusion: To our knowledge this is the first SNP-basedgenome-wide linkage study on PE, and the first performedin a novel Norwegian PE family cohort. By using an approachfocusing on functionally relevant markers we anticipate theidentification of susceptibility loci that are of substantialimportance for disease development.

doi:10.1016/j.preghy.2013.04.022

Clinical research

OP007. PLGF in combination with other commonly uti-lised tests and other biomarkers for predicting need fordelivery for pre-eclampsia within 14 days in womenpresenting prior to 35 weeks’ gestationChappell Lucy, Duckworth Suzy, Griffin Melanie, SeedPaul, Redman Christopher, Shennan Andrew

Introduction: Current means of assessing women present-ing with suspected pre-eclampsia using BP and proteinuriaare of limited use in predicting need for imminent delivery.

Objectives/Method/Design: We undertook a prospectivemulticentre study to determine diagnostic accuracy of PlGF<5th centile (Triage assay) and other candidate biomarkersin women presenting with suspected pre-eclampsia at 20–35 weeks’ gestation, in determining need for delivery forpre-eclampsia within 14 days. We calculated ROC curvesfor predictive potential and undertook principal factor anal-ysis to determine additional predictive ability for biomarkercombinations.

64 Oral Presentations / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 3 (2013) 62–66