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132. Epigenetic changes of endothelial progenitor cells in preeclampsia
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 13 (2018) S16–S49
showed asymmetric growth, while 5.5% of neonates with a customised birthweight >90th percentile (p < 0.000) showed asymmetric growth. Asymmetric growth restriction was predominant in males [22.5% vs 18.4%, p < 0.000]. Abnormal (>90th percentile) umbilical Doppler resistance index (RI) at 20 weeks’ gestation was more common in SGA females (9.6% vs 17.8% p = 0.003) but did not differ between symmetric and asymmetric SGA neonates. The presence of abnormal uterine artery Doppler RI at 20 weeks’ gestation did not differ between SGA subgroups. In each SGA subgroup PE incidence was increased (28.2% in symmetric SGA, 26.1% in asymmetric SGA, 27.2% in SGA male and 25.3% in SGA female bearing pregnancies) compared to non-SGA pregnancies (4.2%). The incidence of PE did not differ between SGA subgroups. Discussion: A quarter of asymmetric neonates are SGA. Asymmetric SGA associates with male neonates. In contrast with literature, PE was associated with both symmetric and asymmetric growth in SGA neonates. doi:10.1016/j.preghy.2018.08.074
128. Detection of predictive makers for preeclampsia using NMR and GC–MS/MS metabolomics Junichi Sugawara a, Daisuke Saigusa a, Matsuyuki Shirota a, Yasuhiro Kurosawa b, Maiko Wagata a, Satoshi Mizuno a, Ikuko Motoike a, Soichi Ogishima a, Hirohito Metoki c, Shinichi Kuriyama a, Seizo Koshiba a, Kengo Kinoshita a, Shigeo Kure a, Nobuo Yaegashi b, Masayuki Yamamoto a (a Tohoku University, Sendai, Japan, b Tohoku University Hospital, Sendai, Japan, c Tohoku Medical and Pharmaceutical University, Sendai, Japan) Introduction: The Birth and Three Generation Cohort Study was initiated by Tohoku Medical Megabank Organization (ToMMo), Tohoku University, Japan. A total of 73 085 participants, spanning 3 generations and including 22 493 pregnant women, have been recruited as of January 18, 2018. This cohort study was designed to establish methods for personalized early prediction of multifactorial diseases using cutting-edge technology and an integrated biobank, with a focus on genetic and environmental interactions. Objectives: Our aim is to discover early predictors of preeclampsia using nuclear magnetic resonance (NMR) spectroscopy and gas chromatography-tandem mass spectrometry (GC–MS/MS) metabolomics to evaluate maternal plasma samples from the first trimester of pregnancy. Methods: Plasma samples collected during the first trimester from pregnant women who later developed preeclampsia were obtained from the ToMMo biobank. There were 298 patients who developed preeclampsia, including 45 with early onset and 253 with late onset; these patients were compared with 338 patients with normal pregnancies, randomly selected from the database. We performed NMR and GC–MS/MS to detect circulating metabolites which could be candidates for early predictors of preeclampsia. The present study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of ToMMo. Results: Using NMR metabolomics, 36 metabolites were identified and quantified from each plasma sample. A total of 5 early-onset and 8 late-onset metabolites had significantly different values between the case- and control groups. On GC–MS/MS analysis, 155 metabolites were quantified satisfactorily; 15 early-onset and 31 lateonset metabolites had statistically significant differences between groups. Conclusions: We identified several candidate predictors using NMR and GC–MS/MS metabolomics in pregnant women who later developed preeclampsia. These results might bring new insights into
S25
the establishment of early-prediction formulae, in combination with additional genetic and epidemiologic information. doi:10.1016/j.preghy.2018.08.075
131. EGFR and the mitochondria; two parallel pathways regulating sFLT-1 secretion from placenta Tu’Uhevaha Kaitu’U-Lino, Roxanne Hastie, Fiona Brownfoot, Ping Cannon, Tuong-Vi Nguyen, Natalie Hannan, Stephen Tong (University of Melbourne, Australia) Introduction: Although discovered more than a decade ago, the molecular pathways regulating sFLT-1 release in preeclampsia are still poorly understood. We have discovered the EGFR superhighway and the mitochondria (either via inhibiting the electron transport chain (ETC) or increasing molecules associated with mitochondrial biogenesis) independently regulate sFLT-1 secretion from placenta. The aim of this study was to assess whether targeting both pathways simultaneously additively reduced sFLT-1. Methods: Isolated primary trophoblast were used for all studies. Metformin is a mitochondrial ETC inhibitor and resveratrol stimulates expression of mitochondrial biogenesis molecules SIRT1, AMPK and PGC1a. We initially assessed their effects on EGFR expression and activation using western blot. Gefitinib is an EGFR inhibitor, PD98059 a MEK-1 inhibitor and AG490 a STAT3 inhibitor (pathways downstream of the EGFR). We assessed their effects on mitochondrial respiration using a seahorse flux analyser. Having identified molecules that were either ‘‘EGFR-specific” or ‘‘Mitochondrial specific” we subsequently treated primary trophoblast simultaneously with drugs targeting both pathways and measured the effect on sFLT-1 secretion. Results: Treatment of primary trophoblast with metformin or resveratrol significantly reduced sFLT-1 secretion and increased down-stream mitochondrial biogenesis molecules but had no significant effect on EGFR, pEGFR or downstream adaptor molecules ERK, pERK, STAT-3 or pSTAT-3. Although inhibitors targeting the EGFR super-highway also significantly reduced sFLT-1 secretion, none significantly altered mitochondrial respiration, or ATP production. When we targeted the two pathways simultaneously (combining gefitinib and metformin, gefitinib and resveratrol, metformin and PD980 or metformin and AG490) we found the reduction in sFLT-1 was additive compared to targeting either pathway alone. Conclusions: Our study identifies EGFR signalling and the mitochondria as two parallel pathways that both regulate sFLT-1 secretion and which, when targeted simultaneously, can additively reduce sFLT-1. These pathways provide new therapeutic targets to reduce excess sFLT-1 secretion in pathological conditions and improve vascular homeostasis. doi:10.1016/j.preghy.2018.08.076
132. Epigenetic changes of endothelial progenitor cells in preeclampsia Lars Brodowski, Tristan Zindler, Sandra von Hardenberg, Constantin von Kaisenberg, Bianca Schröder-Heurich, Helge Frieling, Frauke von Versen-Höynck (Hannover Medical School, Hannover, Germany) Objective: The obstetrical history is an important component of the risk profile of women and their offspring for future cardiovascular diseases (CVD). The pregnancy-specific disease preeclampsia (PE) represents a separate, independent risk factor. Our research shows a
S26
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 13 (2018) S16–S49
diminished function of fetal endothelial progenitor cells (EPCs) in PE pregnancies. The aim of our study was to investigate whether the development of PE leads to changes in DNA methylation of fetal EPCs. Methods: Endothelial colony-forming cells (ECFCs), a proliferative subgroup of EPCs, were isolated from umbilical cord blood of healthy and PE-affected pregnancies. Subsequently, the genomic methylation pattern of fetal EFCFs was examined and compared using the Illumina Infinium EPIC BeadChip Kit. Furthermore, the genomic methylation pattern of fetal EFCFs from low and advanced cell culture passages were compared to assess if culturing fetal ECFCs leads to changes in global methylation status and therefore cultured ECFCs are subject to ‘‘evolutionary” regulation across different passages. Results: Overall, a differential methylation pattern of fetal ECFCs from PE was detected for a total of 1266 sites and has been assigned to different genes. The online platform Ingenuity Pathway Analysis classified the genes into 25 gene networks. These gene networks mainly affect endothelial health and the cell cycle. Discussion: An epigenetically modified endothelial precursor may influence both normal morphogenesis and postnatal vascular repair capacity during embryo- and fetogenesis. Considering the potential of cell therapies based on EPCs, further studies on epigenetic modifications due to complicated pregnancies are urgently needed to develop epigenetically-based therapeutics for the prevention and treatment of cardiovascular alterations. doi:10.1016/j.preghy.2018.08.077
134. Molecular and functional memory in decidual NK cells of parous women Moriya Gamliel a, Debra Goldman-Wohl b, Ofer Mandelboim a, Simcha Yagel b (a Hebrew University Faculty of Medicine, Jerusalem, Israel, b Hadassah Hebrew University Medical Center, Jerusalem, Israel) Introduction: Natural killer (NK) cells are abundant in the human decidua. These decidual NKs (dNK) produce cytokines, growth and angiogenic factors beneficial for the development of the placental bed. Preeclampsia and several of the ‘‘Great Obstetrical Syndromes” with a basis of poor placental development, are associated with first pregnancies. Thus, we investigated differences in dNKs in pregnancies of primigravid vs parous women. Hypothesis: Human dNK cells remember pregnancy, thus better supporting subsequent pregnancies. Methods: dNKs isolated from elective pregnancy terminations of primigravid and parous women (450 samples) were characterized by assays including FACs, RNA-seq and epigenetic analysis (ATACseq, CHIP-seq) followed by angiogenic and growth factor functional experiments. Endometrial NK cells from menstrual blood were also tested before and following pregnancies. Results: We discovered a dNK population unique to pregnancies of parous women, possessing a novel transcriptome and epigenetic signature, characterized with high expression levels of the receptors NKG2C and LILRB1. Activation of these receptors leads to increased production per cell and secretion of IFNc and VEGFa, the latter found to support vascular sprouting and trophoblast-tumor growth. Higher expression of these receptors was found on endometrial NK cells following first pregnancy. Discussion: We propose that this population termed as Pregnancy Trained decidual NK cells (PTdNKs) represents NK ‘‘memory” of pregnancy. We further suggest that the precursors of PTdNKs are found in the endometrium. These findings lend molecular and functional support for the observation that pregnancy is more robust in parous women. Our study offers an explanation of first pregnancy
as a risk factor for development of preeclampsia. PTdNKs may prove useful in understanding and treating disorders of poor placentation. doi:10.1016/j.preghy.2018.08.078
138. Placental growth factor to assess and diagnose hypertensive pregnant women: A stepped wedge randomised controlled trial (PARROT) Kate Duhig, Jessica Lowe, Jennifer Fetherston, Rachna Bahl, Gabrielle Bambridge, Sonia Barnfield, Joanna Ficquet, Joanna Girling, Asma Khalil, Jenny Myers, Andrew Sharp, Nigel Simpson, Derek Tuffnell, Paul Seed, Andrew Shennan, Lucy Chappell (King’s College London, United Kingdom) Introduction: Angiogenic factor measurements have shown potential for assisting in the diagnosis of pre-eclampsia in prospective cohort studies, but their diagnostic ability and clinical impact when revealed to clinicians remains uncertain. Hypothesis: In women presenting with suspected pre-eclampsia, use of placental growth factor (PlGF) testing decreases time to clinician-recognised diagnosis of pre-eclampsia (primary outcome) and decreases maternal and perinatal morbidity, and has an impact on health resource use (secondary outcomes). Methods: Design: Multi-centre, pragmatic, stepped-wedge cluster randomised controlled trial. Setting: Eleven UK maternity units (size range 3000–9000 deliveries per annum). Intervention: PlGF measurement with result revealed to clinical team and management guidance. Randomisation: Hospitals were randomly allocated to the order in which the intervention was implemented. Population: Women who presented to maternity services with suspected preeclampsia between 20 + 0 and 36 + 6 weeks’ gestation, providing individual-level consent. Results: Between June 2016 and October 2017, 1023 women with suspected pre-eclampsia were recruited. The median time to diagnosis of pre-eclampsia was from 4.1 days (usual care) to 1.9 days with PlGF testing (time ratios 0.39 (95% CI 0.17–0.91) by parametric survival analysis). There was a reduction in maternal severe adverse outcomes (as defined in the fullPIERS consensus) from 5.4% (concealed PlGF group) to 3.8% (revealed PlGF group) adjusted OR 0.32 (95% CI 0.11–0.96) with no evidence of a significant difference in perinatal adverse outcomes. Discussion: PlGF testing has been shown to be acceptable and clinically useful in substantially reducing the time to clinical recognition of pre-eclampsia. Where PlGF is implemented there is a reduction in maternal adverse outcomes, consistent with targeted enhanced surveillance as recommended in the trial management guidance for clinicians. Adoption of PlGF testing in women with suspected pre-eclampsia is supported by the results of this study. doi:10.1016/j.preghy.2018.08.079
139. Disease flares during pregnancy and postpartum in patients with systemic lupus erythematosus Amanda Eudy a, Anna Maria Siega-Riz b, Stephanie Engel c, Nora Franceschini c, Annie Green Howard c, Megan Clowse a, Michelle Petri d (a Duke University Medical Center, Durham, United States, b University of Virginia School of Nursing, Charlottesville, United States, c University of North Carolina Chapel Hill, Chapel Hill, United States, d Johns Hopkins University School of Medicine, Baltimore, United States) Introduction: Prior studies found conflicting results about whether lupus is likely to flare during or after pregnancy. Understanding the
showed asymmetric growth, while 5.5% of neonates with a customised birthweight >90th percentile (p < 0.000) showed asymmetric growth. Asymmetric growth restriction was predominant in males [22.5% vs 18.4%, p < 0.000]. Abnormal (>90th percentile) umbilical Doppler resistance index (RI) at 20 weeks’ gestation was more common in SGA females (9.6% vs 17.8% p = 0.003) but did not differ between symmetric and asymmetric SGA neonates. The presence of abnormal uterine artery Doppler RI at 20 weeks’ gestation did not differ between SGA subgroups. In each SGA subgroup PE incidence was increased (28.2% in symmetric SGA, 26.1% in asymmetric SGA, 27.2% in SGA male and 25.3% in SGA female bearing pregnancies) compared to non-SGA pregnancies (4.2%). The incidence of PE did not differ between SGA subgroups. Discussion: A quarter of asymmetric neonates are SGA. Asymmetric SGA associates with male neonates. In contrast with literature, PE was associated with both symmetric and asymmetric growth in SGA neonates. doi:10.1016/j.preghy.2018.08.074
128. Detection of predictive makers for preeclampsia using NMR and GC–MS/MS metabolomics Junichi Sugawara a, Daisuke Saigusa a, Matsuyuki Shirota a, Yasuhiro Kurosawa b, Maiko Wagata a, Satoshi Mizuno a, Ikuko Motoike a, Soichi Ogishima a, Hirohito Metoki c, Shinichi Kuriyama a, Seizo Koshiba a, Kengo Kinoshita a, Shigeo Kure a, Nobuo Yaegashi b, Masayuki Yamamoto a (a Tohoku University, Sendai, Japan, b Tohoku University Hospital, Sendai, Japan, c Tohoku Medical and Pharmaceutical University, Sendai, Japan) Introduction: The Birth and Three Generation Cohort Study was initiated by Tohoku Medical Megabank Organization (ToMMo), Tohoku University, Japan. A total of 73 085 participants, spanning 3 generations and including 22 493 pregnant women, have been recruited as of January 18, 2018. This cohort study was designed to establish methods for personalized early prediction of multifactorial diseases using cutting-edge technology and an integrated biobank, with a focus on genetic and environmental interactions. Objectives: Our aim is to discover early predictors of preeclampsia using nuclear magnetic resonance (NMR) spectroscopy and gas chromatography-tandem mass spectrometry (GC–MS/MS) metabolomics to evaluate maternal plasma samples from the first trimester of pregnancy. Methods: Plasma samples collected during the first trimester from pregnant women who later developed preeclampsia were obtained from the ToMMo biobank. There were 298 patients who developed preeclampsia, including 45 with early onset and 253 with late onset; these patients were compared with 338 patients with normal pregnancies, randomly selected from the database. We performed NMR and GC–MS/MS to detect circulating metabolites which could be candidates for early predictors of preeclampsia. The present study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of ToMMo. Results: Using NMR metabolomics, 36 metabolites were identified and quantified from each plasma sample. A total of 5 early-onset and 8 late-onset metabolites had significantly different values between the case- and control groups. On GC–MS/MS analysis, 155 metabolites were quantified satisfactorily; 15 early-onset and 31 lateonset metabolites had statistically significant differences between groups. Conclusions: We identified several candidate predictors using NMR and GC–MS/MS metabolomics in pregnant women who later developed preeclampsia. These results might bring new insights into
S25
the establishment of early-prediction formulae, in combination with additional genetic and epidemiologic information. doi:10.1016/j.preghy.2018.08.075
131. EGFR and the mitochondria; two parallel pathways regulating sFLT-1 secretion from placenta Tu’Uhevaha Kaitu’U-Lino, Roxanne Hastie, Fiona Brownfoot, Ping Cannon, Tuong-Vi Nguyen, Natalie Hannan, Stephen Tong (University of Melbourne, Australia) Introduction: Although discovered more than a decade ago, the molecular pathways regulating sFLT-1 release in preeclampsia are still poorly understood. We have discovered the EGFR superhighway and the mitochondria (either via inhibiting the electron transport chain (ETC) or increasing molecules associated with mitochondrial biogenesis) independently regulate sFLT-1 secretion from placenta. The aim of this study was to assess whether targeting both pathways simultaneously additively reduced sFLT-1. Methods: Isolated primary trophoblast were used for all studies. Metformin is a mitochondrial ETC inhibitor and resveratrol stimulates expression of mitochondrial biogenesis molecules SIRT1, AMPK and PGC1a. We initially assessed their effects on EGFR expression and activation using western blot. Gefitinib is an EGFR inhibitor, PD98059 a MEK-1 inhibitor and AG490 a STAT3 inhibitor (pathways downstream of the EGFR). We assessed their effects on mitochondrial respiration using a seahorse flux analyser. Having identified molecules that were either ‘‘EGFR-specific” or ‘‘Mitochondrial specific” we subsequently treated primary trophoblast simultaneously with drugs targeting both pathways and measured the effect on sFLT-1 secretion. Results: Treatment of primary trophoblast with metformin or resveratrol significantly reduced sFLT-1 secretion and increased down-stream mitochondrial biogenesis molecules but had no significant effect on EGFR, pEGFR or downstream adaptor molecules ERK, pERK, STAT-3 or pSTAT-3. Although inhibitors targeting the EGFR super-highway also significantly reduced sFLT-1 secretion, none significantly altered mitochondrial respiration, or ATP production. When we targeted the two pathways simultaneously (combining gefitinib and metformin, gefitinib and resveratrol, metformin and PD980 or metformin and AG490) we found the reduction in sFLT-1 was additive compared to targeting either pathway alone. Conclusions: Our study identifies EGFR signalling and the mitochondria as two parallel pathways that both regulate sFLT-1 secretion and which, when targeted simultaneously, can additively reduce sFLT-1. These pathways provide new therapeutic targets to reduce excess sFLT-1 secretion in pathological conditions and improve vascular homeostasis. doi:10.1016/j.preghy.2018.08.076
132. Epigenetic changes of endothelial progenitor cells in preeclampsia Lars Brodowski, Tristan Zindler, Sandra von Hardenberg, Constantin von Kaisenberg, Bianca Schröder-Heurich, Helge Frieling, Frauke von Versen-Höynck (Hannover Medical School, Hannover, Germany) Objective: The obstetrical history is an important component of the risk profile of women and their offspring for future cardiovascular diseases (CVD). The pregnancy-specific disease preeclampsia (PE) represents a separate, independent risk factor. Our research shows a
S26
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 13 (2018) S16–S49
diminished function of fetal endothelial progenitor cells (EPCs) in PE pregnancies. The aim of our study was to investigate whether the development of PE leads to changes in DNA methylation of fetal EPCs. Methods: Endothelial colony-forming cells (ECFCs), a proliferative subgroup of EPCs, were isolated from umbilical cord blood of healthy and PE-affected pregnancies. Subsequently, the genomic methylation pattern of fetal EFCFs was examined and compared using the Illumina Infinium EPIC BeadChip Kit. Furthermore, the genomic methylation pattern of fetal EFCFs from low and advanced cell culture passages were compared to assess if culturing fetal ECFCs leads to changes in global methylation status and therefore cultured ECFCs are subject to ‘‘evolutionary” regulation across different passages. Results: Overall, a differential methylation pattern of fetal ECFCs from PE was detected for a total of 1266 sites and has been assigned to different genes. The online platform Ingenuity Pathway Analysis classified the genes into 25 gene networks. These gene networks mainly affect endothelial health and the cell cycle. Discussion: An epigenetically modified endothelial precursor may influence both normal morphogenesis and postnatal vascular repair capacity during embryo- and fetogenesis. Considering the potential of cell therapies based on EPCs, further studies on epigenetic modifications due to complicated pregnancies are urgently needed to develop epigenetically-based therapeutics for the prevention and treatment of cardiovascular alterations. doi:10.1016/j.preghy.2018.08.077
134. Molecular and functional memory in decidual NK cells of parous women Moriya Gamliel a, Debra Goldman-Wohl b, Ofer Mandelboim a, Simcha Yagel b (a Hebrew University Faculty of Medicine, Jerusalem, Israel, b Hadassah Hebrew University Medical Center, Jerusalem, Israel) Introduction: Natural killer (NK) cells are abundant in the human decidua. These decidual NKs (dNK) produce cytokines, growth and angiogenic factors beneficial for the development of the placental bed. Preeclampsia and several of the ‘‘Great Obstetrical Syndromes” with a basis of poor placental development, are associated with first pregnancies. Thus, we investigated differences in dNKs in pregnancies of primigravid vs parous women. Hypothesis: Human dNK cells remember pregnancy, thus better supporting subsequent pregnancies. Methods: dNKs isolated from elective pregnancy terminations of primigravid and parous women (450 samples) were characterized by assays including FACs, RNA-seq and epigenetic analysis (ATACseq, CHIP-seq) followed by angiogenic and growth factor functional experiments. Endometrial NK cells from menstrual blood were also tested before and following pregnancies. Results: We discovered a dNK population unique to pregnancies of parous women, possessing a novel transcriptome and epigenetic signature, characterized with high expression levels of the receptors NKG2C and LILRB1. Activation of these receptors leads to increased production per cell and secretion of IFNc and VEGFa, the latter found to support vascular sprouting and trophoblast-tumor growth. Higher expression of these receptors was found on endometrial NK cells following first pregnancy. Discussion: We propose that this population termed as Pregnancy Trained decidual NK cells (PTdNKs) represents NK ‘‘memory” of pregnancy. We further suggest that the precursors of PTdNKs are found in the endometrium. These findings lend molecular and functional support for the observation that pregnancy is more robust in parous women. Our study offers an explanation of first pregnancy
as a risk factor for development of preeclampsia. PTdNKs may prove useful in understanding and treating disorders of poor placentation. doi:10.1016/j.preghy.2018.08.078
138. Placental growth factor to assess and diagnose hypertensive pregnant women: A stepped wedge randomised controlled trial (PARROT) Kate Duhig, Jessica Lowe, Jennifer Fetherston, Rachna Bahl, Gabrielle Bambridge, Sonia Barnfield, Joanna Ficquet, Joanna Girling, Asma Khalil, Jenny Myers, Andrew Sharp, Nigel Simpson, Derek Tuffnell, Paul Seed, Andrew Shennan, Lucy Chappell (King’s College London, United Kingdom) Introduction: Angiogenic factor measurements have shown potential for assisting in the diagnosis of pre-eclampsia in prospective cohort studies, but their diagnostic ability and clinical impact when revealed to clinicians remains uncertain. Hypothesis: In women presenting with suspected pre-eclampsia, use of placental growth factor (PlGF) testing decreases time to clinician-recognised diagnosis of pre-eclampsia (primary outcome) and decreases maternal and perinatal morbidity, and has an impact on health resource use (secondary outcomes). Methods: Design: Multi-centre, pragmatic, stepped-wedge cluster randomised controlled trial. Setting: Eleven UK maternity units (size range 3000–9000 deliveries per annum). Intervention: PlGF measurement with result revealed to clinical team and management guidance. Randomisation: Hospitals were randomly allocated to the order in which the intervention was implemented. Population: Women who presented to maternity services with suspected preeclampsia between 20 + 0 and 36 + 6 weeks’ gestation, providing individual-level consent. Results: Between June 2016 and October 2017, 1023 women with suspected pre-eclampsia were recruited. The median time to diagnosis of pre-eclampsia was from 4.1 days (usual care) to 1.9 days with PlGF testing (time ratios 0.39 (95% CI 0.17–0.91) by parametric survival analysis). There was a reduction in maternal severe adverse outcomes (as defined in the fullPIERS consensus) from 5.4% (concealed PlGF group) to 3.8% (revealed PlGF group) adjusted OR 0.32 (95% CI 0.11–0.96) with no evidence of a significant difference in perinatal adverse outcomes. Discussion: PlGF testing has been shown to be acceptable and clinically useful in substantially reducing the time to clinical recognition of pre-eclampsia. Where PlGF is implemented there is a reduction in maternal adverse outcomes, consistent with targeted enhanced surveillance as recommended in the trial management guidance for clinicians. Adoption of PlGF testing in women with suspected pre-eclampsia is supported by the results of this study. doi:10.1016/j.preghy.2018.08.079
139. Disease flares during pregnancy and postpartum in patients with systemic lupus erythematosus Amanda Eudy a, Anna Maria Siega-Riz b, Stephanie Engel c, Nora Franceschini c, Annie Green Howard c, Megan Clowse a, Michelle Petri d (a Duke University Medical Center, Durham, United States, b University of Virginia School of Nursing, Charlottesville, United States, c University of North Carolina Chapel Hill, Chapel Hill, United States, d Johns Hopkins University School of Medicine, Baltimore, United States) Introduction: Prior studies found conflicting results about whether lupus is likely to flare during or after pregnancy. Understanding the