- Email: [email protected]
PlGF on late onset preeclampsia
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Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 13 (2018) S50–S150
Discussion: Our data demonstrate for the first time that the ECM of the placenta and therefore the microenvironment has great impact on trophoblast signaling. Preeclampsic ECM alters the trophoblast phenotype and LLLT restored the phenotype to the phenotype found in trophoblasts cultured on control ECM. doi:10.1016/j.preghy.2018.08.283
196. The P4 study: Postpartum maternal and infant faecal microbiome 6 months after hypertensive versus normotensive pregnancy D. Susic, L. Roberts, A. Henry, G. Davis, A. Gia, E. El-Omar (University of New South Wales, Sydney, Australia) Introduction: There is increasing evidence inside and outside pregnancy of the importance of the microbiome to human health, including hypertension and cardiovascular health. How the microbiome changes and affects pregnancy outcomes including hypertensive disorders (HDP) is still unclear, and postpartum data is lacking. Objective/hypothesis: To explore differences in faecal microbiome six months post-partum between women and their infants who had normotensive pregnancies (NP) versus those who had gestational hypertension or preeclampsia (HP). Methods: Subgroup pilot study within the P4 study (Postpartum Physiology, Psychology, and Paediatrics Study) of 18 mother-infant pairs 6 months postpartum after NP or HP Mothers collected a stool sample from themselves and their infants, with samples aliquoted and stored at 80°C. DNA was extracted from samples at the same time point using the PSP Spin Stool DNA Plus Kit, and 16S sequencing analysis performed. Results: Ten NP and 8 HP (6 preeclampsia, 2 gestational hypertension) mother-infant pairs participated. They were predominantly primiparous (n = 16) with vaginal birth (n = 14). Apart from one HP woman with cholestasis, no other pregnancy complications, or medical history was present in the remaining cohort. At the time of faecal microbiome analysis 8 women were using a form of hormonal contraception (oral or implantable), and one HP woman remained on an antihypertensive. All women had blood pressures in the normal range, systolic 90–124, diastolic 60–76. Ten women had high BMI (eight 25–29.9, two 30+), and their gestational weight gain had ranged from 1 to 23 kg (average 11.1 kg). At the time of assessment all infants had started solids. Eight were exclusively breastfed, one bottle fed and nine mixed. Three infants had been exposed to a course of antibiotics and one had a multivitamin. Sequencing results in process and to be presented. Discussion: Postpartum microbiome analysis may provide additional insight into HDP, particularly relationship to long-term cardiovascular disease. doi:10.1016/j.preghy.2018.08.284
197. Markers of maternal cardiac dysfunction in pre-eclampsia and superimposed pre-eclampsia Frances Conti-Ramsden, Carolyn Gill, Paul Seed, Kate Bramham, Lucy Chappell, Fergus McCarthy (King’s College London, London, United Kingdom) Introduction: Women who experience hypertensive disorders of pregnancy have an increased risk of developing cardiovascular disease in later life. The mechanism underlying this association unknown. Objectives: To determine whether elevated glycogen phosphorylase isoenzyme B (GPBB) and/or brain natriuretic peptide (BNP)
concentrations suggestive of cardiac dysfunction are observed in pre-eclampsia and superimposed pre-eclampsia (SPE). Method: Four groups of women were selected from an existing cohort study: healthy controls (n = 21), pre-eclampsia (n = 19), preexisting chronic hypertension (CHT) and/or chronic kidney disease (CKD) without (n = 20), or with SPE (n = 19). Plasma samples taken in the third trimester or at time of disease were assayed using Diagenics DianeonatalÒ Glycogen phosphorylase Isoenzyme BB (GP-BB)-ELISA in vitro diagnostic device kits and Alere Triage Ó CardioRenal assays (BNP). Log transformed GPBB and BNP concentrations were compared using interval regression as ratios of the geometric means with 95% confidence intervals. Results: No difference was observed in GPBB plasma concentrations between the control and pre-eclampsia groups (mean [95% C. I.]: 4.72 [2.49–8.94] ng/mL vs 4.98 [2.52–9.84] ng/mL; N = 40, p = 0.91), or between CHT and/or CKD and SPET groups (mean [95% C. I.]: 9.49 [4.93–18.25] ng/mL vs 10.24 [5.27–19.92] ng/mL; N = 39, p = 0.87). BNP plasma concentrations were significantly raised in the pre-eclampsia group compared to the control group (mean [95% C.I.]: 31.75 [19.21–52.49] pg/mL vs 11.31 [7.00–18.25] pg/mL; N = 40, p = 0.004), but did not reach statistical significance between the SPET and CHT and/or CKD groups (GM [95% C.I.]: 20.66 [12.40– 34.44] pg/mL vs 16.06 [9.83–26.23] pg/mL; N = 39, p = 0.486). Discussion: There was no difference in GPBB concentration between groups. BNP concentrations were elevated in cases of preeclampsia compared to controls. This suggests cardiac dysfunction at the time of pre-eclampsia but through a mechanism other than cardiac ischaemia, and little role for the use of GPBB as a biomarker in hypertensive disorders of pregnancy. doi:10.1016/j.preghy.2018.08.285
198. The usefulness of sFlt-1/PlGF on late onset preeclampsia Risa Yoshimoto a, Taro Fukuta b, Takuji Ueno b, Takuma Yamada b, Takehiko Takeda b, Sho Tano b, Kaname Uno b, Mayu Ukai b, Teppei Suzuki b, Toko Harata b, Yasuyuki Kishigami b, Hidenori Oguchi b (a TOYOTA Memorial Hospital, Japan, b Japan) Introduction: Endothelial cell dysfunction is thought to be the main pathophysiological condition of preeclampsia(PE). Increased production of soluble Fms-like tyrosinekinase-1(sFlt-1) and decrease on placental growth factor(PlGF) in PE patients lead to be an established biomarker for early onset PE at 1st trimester. Other hand, the utility of this angiogenic biomarker for predicting late onset PE has not been clarified. Objectives: We performed this study to assess the usefulness of sFlt-1/PlGF at late weeks of gestation as a predictive biomarker for late-onset PE. Methods: This is a single-center, retrospective cohort study conducted between April 2016 and June 2017 using the records of the Department of Obstetrics at Perinatal Medical Center of TOYOTA Memorial Hospital, Japan. We examined this biomarker for patients who had or were expected to develop PE. We defined sFlt-1/PlGF < 38 as low-risk, 38 < sFlt-1/PlGF < 85 as intermediate risk and 85 < sFlt-1/PlGF as high-risk respectively. Age at delivery, rate of PE, duration of pregnancy from blood sampling to termination, rate of Cesarean section, gestational age at delivery and fetal birth weight were collected. Results: 36 patients were included in the study and the mean age was 31.5 years old and median gestational weeks at blood sampling were 35 weeks of gestation. High risk group included 23 patients, middle risk group included 7 patients and low risk group included 6 patients. The rates of PE in each group were 73.9%, 28.5% and 16.7%. The rate of Cesarean section was significantly higher in high risk group compared with low risk group (70.0% vs 16.7%, p =
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 13 (2018) S50–S150
0.018). Gestational age at delivery was much shorter in high risk group than intermediate (35w vs 37w p = 0.003) and low risk group (35w vs 39w p = 0.002). Discussion: sFlt-1/PlGF at late weeks of gestation can be useful on predicting late onset PE. Further clinical research is needed to make this biomarker established. doi:10.1016/j.preghy.2018.08.286
200. Clinical trial of metformin to treat preterm preeclampsia: pharmacokinetics and biomarker studies Stephen Tong a, Eric Decloedt b, Tu’Uhevaha Kaitu’U-Lino b, Brownfoot Fiona b, David Hall b, Sue Walker b, Cathy Cluver b (a University of Melbourne, Heidelberg, Victoria, Australia, b Australia) Introduction: Metformin is a potential therapeutic for preeclampsia as it decreases sFlt-1 and soluble endoglin and rescues endothelial dysfunction. Metformin pharmacokinetics in preeclampsia, where there is increased renal clearance and proteinuria, has not been established. Objective/Hypothesis: To evaluate metformin XR (extended release) pharmacokinetics in preterm preeclampsia, obtain data on pregnancy prolongation and circulating levels of biomarkers associated with endothelial dysfunction. Methods: 15 women with preterm preeclampsia were treated with 1.5 g metformin XR twice daily. Pharmacokinetic sampling was performed on day 1 at 2,4,5,6,7,8,24 h, and concentrations measured using liquid chromatography-tandem mass spectrometry. Given steady state is reached at 24–48 h, trough concentrations were measured at day 1 and 5 to assess the increase in Cmin over time. Plasma was taken twice weekly and biomarkers of endothelial dysfunction measured. Results: Gestation at recruitment ranged from 27 to 31 weeks, and median prolongation was 11.5 days [IQR 5.8–23.8]. Pharmacokinetic studies confirmed excellent circulating levels at 0–12 h exposure, with Cmax [median (IQR)] 1.6 (1.3–1.9) mg/l, AUC 0–12 11.7 (8.9–13.5) mg.h/l and AUC 0-infinity 17.0 (10.7–36.6) mg.h/l. Day 1 and 5 trough concentrations were 0.55 (0.34–1.22) mg/l and 0.01 (0.01–0.70) mg/l suggesting steady state exposure is similar to day 1. Umbilical cord blood:plasma ratios taken 4 (3–9.5) hours after dosing were 0.67 (0.2–0.86). None of the following circulating biomarkers increased across pregnancy among those who remain undelivered: sFlt1, soluble endoglin, Vascular Cell Adhesion Molecule 1, Endothelin-1 and placental growth factor. Discussion: 1.5 g of metformin XL twice daily in preterm preeclampsia resulted in at least the same exposure as 2 g daily in healthy controls, despite pregnancy and preeclampsia related changes. Metformin potentially stabilised levels of circulating biomarkers of endothelial dysfunction. Randomised trials to treat preterm preeclampsia should be performed. doi:10.1016/j.preghy.2018.08.287
201. Higher levels of memory T-cell subsets in decidua parietalis compared to basalis tissue of uncomplicated term pregnancies Anne Laskewitz, Lisanne Zijlker, Annege Vledder, Sicco Scherjon, Marijke Faas, Jelmer Prins (University Medical Center Groningen, Groningen, The Netherlands) Introduction: During pregnancy, tolerance towards the fetus is induced by adaptations in the maternal immune system.
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Maladaptation of the maternal immune system is associated with pregnancy complications like preeclampsia and fetal growth restriction. Memory T-cells might play an important role in fetal-maternal tolerance. It is at the fetal-maternal interface where the maternal immune system especially needs to create tolerance towards the fetus. Decidua basalis is the maternal part of the basal plate whereas decidua parietalis is the maternal part of the fetal membranes. Decidual distribution pattern of memory T-cells during pregnancy is not known. Objective: Since it is unknown how memory T-cells are distributed in decidual tissue, memory T-cells in decidua basalis and decidua parietalis were evaluated. Methods: Lymphocytes were isolated from decidua basalis and decidua parietalis from uncomplicated term pregnancies. Using flowcytometry, subsets of memory T-cells (central, effector, regulatory, and tissue resident) of uncomplicated term pregnancies were analysed (n = 27). To compare different subsets of memory T-cells between decidual tissues, a student’s t-test (p < 0,05) was used. Results: Levels of memory T-cells (CD45RO+) were higher in decidua parietalis compared to decidua basalis in both CD4+ and CD8+ cells. Moreover, CD8+ central memory cells (CD45RO+CCR7+) and CD8+ tissue resident cells (CD45RO+CD103+) were higher in decidua parietalis compared to decidua basalis. Lastly, activation status (CD69+) was higher for all memory subsets (except for CD4+ effector memory T-cells) in decidua parietalis compared to decidua basalis. Discussion: This study shows that memory T-cell subsets are differently distributed in decidua parietalis and basalis, with higher percentages of memory T-cell subsets as well as more activated memory T-cell subsets found in decidua parietalis compared to decidua basalis. Since memory T-cells are found to be present at higher percentages in decidua parietalis, this could suggest that these cells are especially important for creating tolerance to the fetal membranes. doi:10.1016/j.preghy.2018.08.288
202. Joint exposure to antiangiogenesis and inflammation in pregnant mice results in sex specific growth restriction patterns Violeta Stojanovska a, Dorieke J. Dijkstra a, Rebekka Vogtmann b, Alexandra Gellhaus b, Sicco A. Scherjon a, Torsten Plosch a (a University Medical Center Groningen, Groningen, The Netherlands, b University Hospital Essen, Essen, Germany) Introduction: Preeclampsia is a multifactorial pregnancy disorder presented with angiogenic imbalance and low-grade systemic inflammation. However, animal models which represent these variety of pathophysiological conditions are missing. Objective/hypothesis: We aimed to establish a novel double hit preeclampsia animal model in order to mimic the complex multifactorial conditions that are present during preeclampsia and to investigate the early consequences to the fetus. Methods: C57Bl/6 mice on gestational day GD 8.5 were injected with adenovirus overexpressing sFlt-1 (1 109 PFU in 100 ml) or empty adenovirus. On GD 10, a second hit was introduced with a low dose of lipopolysaccharide (LPS, 25 lg/kg, i.p.) or PBS. Between GD 16.5 and 17.5, 24-h urine was collected. Blood pressure and blood analysis were performed on GD 18.5. Fetuses and placentas were collected at GD 18.5. Results: Animals exposed to sFlt-1 and LPS showed increased blood pressure and albumins in 24-h urine. sFlt-1 concentrations were 2higher in the double hit preeclampsia group. Blood pressure values were positively correlated with the sFlt-1 concentrations. Fetuses were growth restricted and subclassification based on sex showed that females have symmetrical growth restriction
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 13 (2018) S50–S150
Discussion: Our data demonstrate for the first time that the ECM of the placenta and therefore the microenvironment has great impact on trophoblast signaling. Preeclampsic ECM alters the trophoblast phenotype and LLLT restored the phenotype to the phenotype found in trophoblasts cultured on control ECM. doi:10.1016/j.preghy.2018.08.283
196. The P4 study: Postpartum maternal and infant faecal microbiome 6 months after hypertensive versus normotensive pregnancy D. Susic, L. Roberts, A. Henry, G. Davis, A. Gia, E. El-Omar (University of New South Wales, Sydney, Australia) Introduction: There is increasing evidence inside and outside pregnancy of the importance of the microbiome to human health, including hypertension and cardiovascular health. How the microbiome changes and affects pregnancy outcomes including hypertensive disorders (HDP) is still unclear, and postpartum data is lacking. Objective/hypothesis: To explore differences in faecal microbiome six months post-partum between women and their infants who had normotensive pregnancies (NP) versus those who had gestational hypertension or preeclampsia (HP). Methods: Subgroup pilot study within the P4 study (Postpartum Physiology, Psychology, and Paediatrics Study) of 18 mother-infant pairs 6 months postpartum after NP or HP Mothers collected a stool sample from themselves and their infants, with samples aliquoted and stored at 80°C. DNA was extracted from samples at the same time point using the PSP Spin Stool DNA Plus Kit, and 16S sequencing analysis performed. Results: Ten NP and 8 HP (6 preeclampsia, 2 gestational hypertension) mother-infant pairs participated. They were predominantly primiparous (n = 16) with vaginal birth (n = 14). Apart from one HP woman with cholestasis, no other pregnancy complications, or medical history was present in the remaining cohort. At the time of faecal microbiome analysis 8 women were using a form of hormonal contraception (oral or implantable), and one HP woman remained on an antihypertensive. All women had blood pressures in the normal range, systolic 90–124, diastolic 60–76. Ten women had high BMI (eight 25–29.9, two 30+), and their gestational weight gain had ranged from 1 to 23 kg (average 11.1 kg). At the time of assessment all infants had started solids. Eight were exclusively breastfed, one bottle fed and nine mixed. Three infants had been exposed to a course of antibiotics and one had a multivitamin. Sequencing results in process and to be presented. Discussion: Postpartum microbiome analysis may provide additional insight into HDP, particularly relationship to long-term cardiovascular disease. doi:10.1016/j.preghy.2018.08.284
197. Markers of maternal cardiac dysfunction in pre-eclampsia and superimposed pre-eclampsia Frances Conti-Ramsden, Carolyn Gill, Paul Seed, Kate Bramham, Lucy Chappell, Fergus McCarthy (King’s College London, London, United Kingdom) Introduction: Women who experience hypertensive disorders of pregnancy have an increased risk of developing cardiovascular disease in later life. The mechanism underlying this association unknown. Objectives: To determine whether elevated glycogen phosphorylase isoenzyme B (GPBB) and/or brain natriuretic peptide (BNP)
concentrations suggestive of cardiac dysfunction are observed in pre-eclampsia and superimposed pre-eclampsia (SPE). Method: Four groups of women were selected from an existing cohort study: healthy controls (n = 21), pre-eclampsia (n = 19), preexisting chronic hypertension (CHT) and/or chronic kidney disease (CKD) without (n = 20), or with SPE (n = 19). Plasma samples taken in the third trimester or at time of disease were assayed using Diagenics DianeonatalÒ Glycogen phosphorylase Isoenzyme BB (GP-BB)-ELISA in vitro diagnostic device kits and Alere Triage Ó CardioRenal assays (BNP). Log transformed GPBB and BNP concentrations were compared using interval regression as ratios of the geometric means with 95% confidence intervals. Results: No difference was observed in GPBB plasma concentrations between the control and pre-eclampsia groups (mean [95% C. I.]: 4.72 [2.49–8.94] ng/mL vs 4.98 [2.52–9.84] ng/mL; N = 40, p = 0.91), or between CHT and/or CKD and SPET groups (mean [95% C. I.]: 9.49 [4.93–18.25] ng/mL vs 10.24 [5.27–19.92] ng/mL; N = 39, p = 0.87). BNP plasma concentrations were significantly raised in the pre-eclampsia group compared to the control group (mean [95% C.I.]: 31.75 [19.21–52.49] pg/mL vs 11.31 [7.00–18.25] pg/mL; N = 40, p = 0.004), but did not reach statistical significance between the SPET and CHT and/or CKD groups (GM [95% C.I.]: 20.66 [12.40– 34.44] pg/mL vs 16.06 [9.83–26.23] pg/mL; N = 39, p = 0.486). Discussion: There was no difference in GPBB concentration between groups. BNP concentrations were elevated in cases of preeclampsia compared to controls. This suggests cardiac dysfunction at the time of pre-eclampsia but through a mechanism other than cardiac ischaemia, and little role for the use of GPBB as a biomarker in hypertensive disorders of pregnancy. doi:10.1016/j.preghy.2018.08.285
198. The usefulness of sFlt-1/PlGF on late onset preeclampsia Risa Yoshimoto a, Taro Fukuta b, Takuji Ueno b, Takuma Yamada b, Takehiko Takeda b, Sho Tano b, Kaname Uno b, Mayu Ukai b, Teppei Suzuki b, Toko Harata b, Yasuyuki Kishigami b, Hidenori Oguchi b (a TOYOTA Memorial Hospital, Japan, b Japan) Introduction: Endothelial cell dysfunction is thought to be the main pathophysiological condition of preeclampsia(PE). Increased production of soluble Fms-like tyrosinekinase-1(sFlt-1) and decrease on placental growth factor(PlGF) in PE patients lead to be an established biomarker for early onset PE at 1st trimester. Other hand, the utility of this angiogenic biomarker for predicting late onset PE has not been clarified. Objectives: We performed this study to assess the usefulness of sFlt-1/PlGF at late weeks of gestation as a predictive biomarker for late-onset PE. Methods: This is a single-center, retrospective cohort study conducted between April 2016 and June 2017 using the records of the Department of Obstetrics at Perinatal Medical Center of TOYOTA Memorial Hospital, Japan. We examined this biomarker for patients who had or were expected to develop PE. We defined sFlt-1/PlGF < 38 as low-risk, 38 < sFlt-1/PlGF < 85 as intermediate risk and 85 < sFlt-1/PlGF as high-risk respectively. Age at delivery, rate of PE, duration of pregnancy from blood sampling to termination, rate of Cesarean section, gestational age at delivery and fetal birth weight were collected. Results: 36 patients were included in the study and the mean age was 31.5 years old and median gestational weeks at blood sampling were 35 weeks of gestation. High risk group included 23 patients, middle risk group included 7 patients and low risk group included 6 patients. The rates of PE in each group were 73.9%, 28.5% and 16.7%. The rate of Cesarean section was significantly higher in high risk group compared with low risk group (70.0% vs 16.7%, p =
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 13 (2018) S50–S150
0.018). Gestational age at delivery was much shorter in high risk group than intermediate (35w vs 37w p = 0.003) and low risk group (35w vs 39w p = 0.002). Discussion: sFlt-1/PlGF at late weeks of gestation can be useful on predicting late onset PE. Further clinical research is needed to make this biomarker established. doi:10.1016/j.preghy.2018.08.286
200. Clinical trial of metformin to treat preterm preeclampsia: pharmacokinetics and biomarker studies Stephen Tong a, Eric Decloedt b, Tu’Uhevaha Kaitu’U-Lino b, Brownfoot Fiona b, David Hall b, Sue Walker b, Cathy Cluver b (a University of Melbourne, Heidelberg, Victoria, Australia, b Australia) Introduction: Metformin is a potential therapeutic for preeclampsia as it decreases sFlt-1 and soluble endoglin and rescues endothelial dysfunction. Metformin pharmacokinetics in preeclampsia, where there is increased renal clearance and proteinuria, has not been established. Objective/Hypothesis: To evaluate metformin XR (extended release) pharmacokinetics in preterm preeclampsia, obtain data on pregnancy prolongation and circulating levels of biomarkers associated with endothelial dysfunction. Methods: 15 women with preterm preeclampsia were treated with 1.5 g metformin XR twice daily. Pharmacokinetic sampling was performed on day 1 at 2,4,5,6,7,8,24 h, and concentrations measured using liquid chromatography-tandem mass spectrometry. Given steady state is reached at 24–48 h, trough concentrations were measured at day 1 and 5 to assess the increase in Cmin over time. Plasma was taken twice weekly and biomarkers of endothelial dysfunction measured. Results: Gestation at recruitment ranged from 27 to 31 weeks, and median prolongation was 11.5 days [IQR 5.8–23.8]. Pharmacokinetic studies confirmed excellent circulating levels at 0–12 h exposure, with Cmax [median (IQR)] 1.6 (1.3–1.9) mg/l, AUC 0–12 11.7 (8.9–13.5) mg.h/l and AUC 0-infinity 17.0 (10.7–36.6) mg.h/l. Day 1 and 5 trough concentrations were 0.55 (0.34–1.22) mg/l and 0.01 (0.01–0.70) mg/l suggesting steady state exposure is similar to day 1. Umbilical cord blood:plasma ratios taken 4 (3–9.5) hours after dosing were 0.67 (0.2–0.86). None of the following circulating biomarkers increased across pregnancy among those who remain undelivered: sFlt1, soluble endoglin, Vascular Cell Adhesion Molecule 1, Endothelin-1 and placental growth factor. Discussion: 1.5 g of metformin XL twice daily in preterm preeclampsia resulted in at least the same exposure as 2 g daily in healthy controls, despite pregnancy and preeclampsia related changes. Metformin potentially stabilised levels of circulating biomarkers of endothelial dysfunction. Randomised trials to treat preterm preeclampsia should be performed. doi:10.1016/j.preghy.2018.08.287
201. Higher levels of memory T-cell subsets in decidua parietalis compared to basalis tissue of uncomplicated term pregnancies Anne Laskewitz, Lisanne Zijlker, Annege Vledder, Sicco Scherjon, Marijke Faas, Jelmer Prins (University Medical Center Groningen, Groningen, The Netherlands) Introduction: During pregnancy, tolerance towards the fetus is induced by adaptations in the maternal immune system.
S97
Maladaptation of the maternal immune system is associated with pregnancy complications like preeclampsia and fetal growth restriction. Memory T-cells might play an important role in fetal-maternal tolerance. It is at the fetal-maternal interface where the maternal immune system especially needs to create tolerance towards the fetus. Decidua basalis is the maternal part of the basal plate whereas decidua parietalis is the maternal part of the fetal membranes. Decidual distribution pattern of memory T-cells during pregnancy is not known. Objective: Since it is unknown how memory T-cells are distributed in decidual tissue, memory T-cells in decidua basalis and decidua parietalis were evaluated. Methods: Lymphocytes were isolated from decidua basalis and decidua parietalis from uncomplicated term pregnancies. Using flowcytometry, subsets of memory T-cells (central, effector, regulatory, and tissue resident) of uncomplicated term pregnancies were analysed (n = 27). To compare different subsets of memory T-cells between decidual tissues, a student’s t-test (p < 0,05) was used. Results: Levels of memory T-cells (CD45RO+) were higher in decidua parietalis compared to decidua basalis in both CD4+ and CD8+ cells. Moreover, CD8+ central memory cells (CD45RO+CCR7+) and CD8+ tissue resident cells (CD45RO+CD103+) were higher in decidua parietalis compared to decidua basalis. Lastly, activation status (CD69+) was higher for all memory subsets (except for CD4+ effector memory T-cells) in decidua parietalis compared to decidua basalis. Discussion: This study shows that memory T-cell subsets are differently distributed in decidua parietalis and basalis, with higher percentages of memory T-cell subsets as well as more activated memory T-cell subsets found in decidua parietalis compared to decidua basalis. Since memory T-cells are found to be present at higher percentages in decidua parietalis, this could suggest that these cells are especially important for creating tolerance to the fetal membranes. doi:10.1016/j.preghy.2018.08.288
202. Joint exposure to antiangiogenesis and inflammation in pregnant mice results in sex specific growth restriction patterns Violeta Stojanovska a, Dorieke J. Dijkstra a, Rebekka Vogtmann b, Alexandra Gellhaus b, Sicco A. Scherjon a, Torsten Plosch a (a University Medical Center Groningen, Groningen, The Netherlands, b University Hospital Essen, Essen, Germany) Introduction: Preeclampsia is a multifactorial pregnancy disorder presented with angiogenic imbalance and low-grade systemic inflammation. However, animal models which represent these variety of pathophysiological conditions are missing. Objective/hypothesis: We aimed to establish a novel double hit preeclampsia animal model in order to mimic the complex multifactorial conditions that are present during preeclampsia and to investigate the early consequences to the fetus. Methods: C57Bl/6 mice on gestational day GD 8.5 were injected with adenovirus overexpressing sFlt-1 (1 109 PFU in 100 ml) or empty adenovirus. On GD 10, a second hit was introduced with a low dose of lipopolysaccharide (LPS, 25 lg/kg, i.p.) or PBS. Between GD 16.5 and 17.5, 24-h urine was collected. Blood pressure and blood analysis were performed on GD 18.5. Fetuses and placentas were collected at GD 18.5. Results: Animals exposed to sFlt-1 and LPS showed increased blood pressure and albumins in 24-h urine. sFlt-1 concentrations were 2higher in the double hit preeclampsia group. Blood pressure values were positively correlated with the sFlt-1 concentrations. Fetuses were growth restricted and subclassification based on sex showed that females have symmetrical growth restriction