Placental expression of heparan sulfate 3-O-sulfotransferase-3A1 in normotensive and pre-eclamptic pregnancies.

INTRODUCTION: The endothelial glycocalyx, consisting of membrane-bound proteoglycans and attached glycosaminoglycans plays an important role in vascular homeostasis. We aimed to assess whether glycocalyx mRNA transcripts are differentially expressed in placental tissue of pre-eclamptic and normotensive women. METHODS: We evaluated the expression of transcripts encoding for proteins involved in glycocalyx synthesis and degradation using a microarray analysis of placental mRNA obtained from pre-eclamptic and normotensive women. Participants were recruited from the department of obstetrics at a university hospital in Amsterdam, The Netherlands. The most prominent differentially expressed transcript was validated by qPCR on 112 additional placenta samples. RESULTS: Of 78 preselected genes involved in glycocalyx synthesis and degradation, only HS3ST3A1 mRNA was differentially expressed in placental tissue obtained from pre-eclamptic women (N = 12) compared to normotensive women (N = 12, fold change = 0.61, p = 0.02). Validation with qPCR in additional placental samples of 64 normotensive and 48 pre-eclamptic women confirmed that normalized mRNA expression of HS3ST3A1 was decreased by 27% (95% CI 14%-41%) in placental tissue obtained from pre-eclamptic compared to normotensive women (p < 0.001). HS3ST3A1 expression was positively correlated with neonatal birth weight in normotensive women (r = 0.35, p < 0.01) and inversely correlated with mean arterial pressure of women with pre-eclampsia (r = 0.32, p = 0.02). CONCLUSIONS: The mRNA expression of HS3ST3A1, which encodes for a 3-O sulfating enzyme of heparan sulfate (3-OST-3A1), is decreased in pre-eclamptic placental tissue. Expression of this glycocalyx synthesis transcript is correlated with maternal blood pressure and neonatal birth weight, suggesting a possible role in pre-eclampsia-associated placental dysfunction.

OS065. Placental growth factor as a diagnostic and prognostic test forplacental complications of pregnancy.

INTRODUCTION: Placental growth factor (PlGF) levels in maternal circulation are altered in pre-eclampsia and intrauterine growth restriction (IUGR) (Benton et al.) and may have utility in identifying cases associated with placental dysfunction and stratifying pregnancy survival. OBJECTIVES: We sought to determine if a positive PlGF test measured on the Triage PlGF rapid assay (Alere, San Diego) agrees with the clinical diagnosis and predicts preterm delivery. METHODS: EDTA-blood was collected from women admitted to the AMC Obstetrics Department after 20 weeks of gestation with informed consent and according to the protocol approved by the AMC Medical Ethical Board (10/127). Plasma free PlGF levels from women diagnosed with early-onset pre-eclampsia (n=28), normotensive IUGR (N=6) and pregnancy complications excluding pre-eclampsia and IUGR (n=18) were quantified using the Triage PlGF immunoassay. Samples were collected before GA 34+6 and analyzed in batch assay. Results were interpreted against GA-dependent cutoffs set at the 5th centile for gestational age in normal pregnancy (Knudsen et al). PlGF levels below the cutoffs were assigned "positive" according to the product insert. The proportion of subjects with a positive PlGF test result was calculated for each group, together with the proportion of subjects requiring preterm delivery. RESULTS: Twenty-eight women developed early-onset pre-eclampsia and, of these, 27/28 (96.4%) had a positive PlGF test. The woman with negative PlGF test presented to clinic at GA 34+3 with hypertension and suspected pre-eclampsia, but delivered at GA 39+4. Six women developed normotensive IUGR, of which 4 had a positive PlGF test, and in each the PlGF level was below the limit of detection of the test. The 2 women with a negative PlGF test had twin pregnancies. Eighteen women developed pregnancy complications excluding pre-eclampsia and IUGR. Six had at least one serial sample with a positive PlGF test. Of these, one woman had partial placental abruption, 3 had PPROM, one had spontaneous labour at GA 33+3, and one had bleeding after elective embryo reduction and neonatal death during delivery at 23+3. The proportion of women with a positive PlGF test, where the date of delivery is known, requiring preterm delivery was 34/37 (91.9%). CONCLUSION: These preliminary data suggest that a positive PlGF test by Triage may identify placentally-mediated pregnancy complications and that a very low level of PlGF identifies women at increased risk for preterm delivery.