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652: 3D-power Doppler quantification of placental vascularity in pregnancy complicated with hypertensive disorders
www.AJOG.org
Academic Issues, Antepartum Fetal, Clinical Ob, Fetus, Genetics, Hypertension, Med-Surg-Diseases, Operative Ob, U/S
PlGF levels. Other analysis, such as fetal m-RNA dosage for each marker, appeared to be useful in order to better explain our results.
Poster Session IV
651 Prospective evaluation of circulating angiogenic factors in the prediction of early- versus late-onset pre-eclampsia Rebecca Jessel1, Ann Thomas2, Kee-Hak Lim3, Samuel Parry4, Thomas McElrath2
Spearman correlation
1 Brigham and Women’s Hospital; Harvard Medical School, Department of Obstetrics and Gynecology, Boston, MA, 2Brigham and Women’s Hospital; Harvard Medical School, Department of Obstetrics and Gynecology; Division of Maternal Fetal Medicine, Boston, MA, 3Boston MFM; BIDMC; Harvard Medical School, Boston Maternal-Fetal Medicine, Boston, MA, 4Hospital of the University of Pennsylvania, Division of Maternal-Fetal Medicine, Hospital of the University of Pennsylvania, PA
Spearman correlation
6..5
650 sTRAIL, a prognostic marker for future death from cardiovascular disease, is decreased in maternal plasma of patients with preeclampsia Piya Chaemsaithong1, Tinnakorn Chaiworapongsa2, Tamara Stampalija1, Nandor Gabor Than1, Zhong Dong1, Lami Yeo2, Sonia Hassan2, Roberto Romero1 1 NICHD/NIH/DHHS, Perinatology Research Branch, Detroit, MI, 2Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, MI
OBJECTIVE: Women who develop preeclampsia (PE) are at increased risk of cardiovascular disease later in life. Tumor necrosis factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL), a potent inducer of apoptosis, has anti-atherosclerotic effects on endothelial cells. Patients with acute coronary artery disease have lower serum concentrations of the soluble TRAIL (sTRAIL), with higher C-reactive protein (CRP) concentrations. sTRAIL and CRP confer a risk for future death (Hazard Ratio 0.93 and 2.2, respectively). The aim of this study was to determine if maternal plasma concentrations of sTRAIL and CRP change in pregnancies with preeclampsia. STUDY DESIGN: A cross-sectional study was conducted in the following groups: 1) normal pregnant women (n⫽93); and 2) women with PE (n⫽52). Patients with PE were sub-classified into preterm (n⫽38) and term (⬎37 weeks) PE (n⫽14). Maternal plasma concentrations of sTRAIL and C-reactive protein (CRP) were determined by ELISA. RESULTS: 1) The median plasma concentration of sTRAIL was significantly lower in patients with PE than in normal pregnant women (25.6 pg/mL vs. 29.2 pg/mL; p⫽0.03); 2) the preterm (but not term) preeclampsia group had a significantly lower median plasma concentration of sTRAIL than the normal pregnancy group (24.8 pg/mL vs. 30.5 pg/mL; p⫽0.03 and 26.5 pg/mL vs. 26.8 pg/mL; p⫽0.7, respectively); and 3) the median plasma concentration of CRP was significantly higher in patients with PE (n⫽32) than in normal pregnant women (n⫽53) (8 ng/mL vs. 4.1 ng/mL; p⫽0.001); however, there was no significant correlation between maternal plasma concentrations of sTRAIL and CRP in either PE (p⫽0.1) or normal pregnancy (p⫽0.3). CONCLUSION: Preeclampsia was associated with a lower sTRAIL and a higher CRP concentration in maternal plasma. Both proteins may be involved in the mechanisms of predisposing patients with preeclampsia to future cardiovascular disease.
OBJECTIVE: Circulating angiogenic factors play a role in pathogenesis of preeclampsia (PE) but we have previously demonstrated that they have limited predictive capacity if PE is considered a single entity. However, PE is a heterogeneous disease with early (⬍34w) and late onest PE possibly representing different entities. We tested the hypothesis that sequential measurement of sFlt-1 and PlGF in a longitudinal cohort of patients can distinguish patients who are more likely to develop and require delivery for early PE. STUDY DESIGN: 2,241 singleton pregnancies were followed prospectively from the initiation of prenatal care at three regional academic centers. Plasma sFlt-1 and PlGF levels were collected prospectively and quantified by immunoassay at approximately 10, 17, and 24 weeks gestation. Patients were followed through delivery. PE was diagnosed by ACOG criteria. Patients with chronic hypertension and diabetes were excluded from this analysis. RESULTS: Median analyte concentrations for early and late and testing characteristics for the prediction of early PE are presented in the table. Twenty patients developed PE before 34 weeks compared to 182 patients with late PE. Incidence of early PE was ⬍1%. PlGF concentrations are significantly lower among early PE patients at all time points and magnitude of increase with gestation was lower than those with late PE. sFlt-1 concentrations and the ratio are significantly different at 26 weeks. However, the testing characteristics do not suggest clinical utility in the prediction of early PE. CONCLUSION: Our results support the suggestion that PE is a heterogeneous disease with early and late PE possibly representing different disease processes. Despite low incidence, the significant differences in analytes in early versus late suggests a more homogenous cohort. However, the analytes, do not appear to be clinically useful in the prediction of early PE.
Differences in analytes and ROC analysis for early and late preeclampsia
652 3D-power Doppler quantification of placental vascularity in pregnancy complicated with hypertensive disorders Eduardo Pimenta1, Rodrigo Ruano2, Rossana Francisco1, Marcelo Zugaib1 1 Medical School, University of Sao Paulo, Obstetrics and Gynecology, Sao Paulo, Brazil, 2Baylor College of Medicine, Obstetrics and Gynecology, Houston, TX
OBJECTIVE: To evaluate if pregnancies complicated with hypertensive disorders have reduced placental vascularity than healthy pregnancies. STUDY DESIGN: Between April 2011 and July 2012, a prospective casecontrol study was conducted in one center. Sixty-one pregnant
Supplement to JANUARY 2013 American Journal of Obstetrics & Gynecology
S275
Poster Session IV
Academic Issues, Antepartum Fetal, Clinical Ob, Fetus, Genetics, Hypertension, Med-Surg-Diseases, Operative Ob, U/S
women with hypertensive disorder (19 with pure preeclampsia, 23 with chronic hypertension and 20 with superimposed preeclampsia) and 66 healthy pregnant women underwent 3DUS examination once during the pregnancy. Case and controls were a match according to maternal age, gestational age at ultrasound examination and parity. Placental vascularity was calculated using the 3D-power Doppler histogram using pre-established power Doppler settings. Comparison among groups and subgroups were analyzed using t-student and ANOVA tests. RESULTS: The population demographics and characteristics were similar in both groups. Mean gestational age at evaluation was 32.6⫾3.4 weeks. The placental vascularity index was significantly reduced in cases with hypertension (11.1⫾0.8%) in comparison with healthy pregnancies (15.2⫾1.1%; p⬍0.01); but with similar reduction in those with pure preeclampsia (10.7⫾1.1%), chronic hypertension (11.5⫾1.3%) and superimposed preeclampsia (11.2⫾1.2%; p⫽0.89). CONCLUSION: Pregnancies complicated with hypertensive disorders have reduced placental vascularity than healthy pregnancies, independently of the classification of the disorder.
653 Evidence for excessive feto-placental activation of the polyol pathway: implications for hyperuricemia of preeclampsia (PE) Sami Makaroun1, Catalin Buhimschi1, Guomao Zhao1, Megan McCarthy1, John Hardy1, Antonette Dulay1, Christine Laky1, Irina Buhimschi1 1
Yale University, Ob/Gyn & Reprod. Sci., New Haven, CT
OBJECTIVE: Uric acid (UA) can result from fructose (FRU) metabo-
lism. Aside from ingestion, FRU is endogenously produced from glucose (GLU) via the polyol pathway: aldose reductase (ARD) converts GLU to sorbitol (SOR) and SOR-dehydrogenase (SORD) converts SOR to FRU. We hypothesized that overactivation of an existing polyol pathway in the feto-placental unit contributes to hyperuricemia of PE. STUDY DESIGN: FRU, SOR, GLU, and UA were assayed in serum and urine of 65 pregnant healthy controls (CRL: GA: ⬍20w, n⫽4; GA: 20-34w, n⫽15; GA: ⬎37w, n⫽46) and 29 women with severe PE (sPE, GA: 29⫾2w). Same analytes were assayed in cord blood (CB) of fetuses delivered in the setting of sPE (n⫽23, GA: 30⫾1), idiopathic preterm birth (iPTB, n⫽23, GA: 31⫾1), and normal healthy term gestation (n⫽22). Placental and amniochorion ARD & SORD expression was studied in sPE, iPTB and term gestation (n⫽4/group) by RT-PCR and IHC. Placenta and membrane explants were employed to test their ability to generate SOR in vitro. RESULTS: In normal gestation, serum UA increased with GA (P⬍.001) in relationship with SOR (r⫽.67, P⬍.001) and FRU (r⫽.32, P⫽.03) but not GLU (P⬎.05). Fractional excretion (FE) of FRU and UA decreased with GA (P⬍.001). sPE increased serum UA (P⬍.001) and SOR (P⬍0.001) but not FRU & GLU (P⬎0.05). FE of UA, FRU and SOR but not of GLU were decreased in sPE (P⬍.001). In sPE, UA level was predicted by the combination of SOR and serum creatinine (P⬍.001 for both), accounting for 53% of variability. SOR & UA in CB of healthy term newborns exceed maternal levels. sPE further increased CB SOR and UA vs iPTB group (P⬍.05). PCR and IHC demonstrated preferential expression of ARD in trophoblasts and of SORD in decidual cells. Fetal membranes release 3-fold SOR compared to placenta in vitro. CONCLUSION: An active polyol pathway is present and functional in the feto-placental unit. Decidual dysfunction and accumulation of SOR at this site could be an alternative explanation for the increased UA in PE.
S276
www.AJOG.org
654 Endocan (ESM-1): a novel soluble endothelial cell injury marker in preeclampsia (PE) and intrauterine growth restriction (IUGR) Sarah Cross1, Irina Buhimschi1, Christina Duzyj1, Lydia Shook1, Megan McCarthy1, John Hardy1, Guomao Zhao1, Catalin Buhimschi1 1
Yale University, Ob/Gyn & Reprod. Sci., New Haven, CT
OBJECTIVE: ESM-1 is a newly discovered soluble endothelial cell pro-
teoglycan, released by damaged vascular endothelium in response to inflammatory cytokines and angiogenic stimuli. Recent data show ESM-1 regulates angiogenesis and its bioactivity is mediated via interaction with hepatocyte growth factor (HGF). Vascular endothelial dysfunction and injury plays a key role in the pathogenesis of PE and IUGR. We hypothesized that soluble ESM-1 is upregulated in women with severe PE (sPE), and its circulatory levels relate to the timing and clinical manifestation of the disease. STUDY DESIGN: We analyzed 211 serum samples from: normotensive healthy pregnant controls (CRL, GA ⬍20w, n⫽29; GA 20-34w, n⫽31; GA ⬎37w, n⫽18), early-onset sPE (GA 20-34w, n⫽28), early onset sPE⫹IUGR (GA ⬍37w, n⫽16), late-onset sPE (GA ⬎37w, n⫽39), chronic hypertension (crHTN, GA ⬍37w, n⫽39) and idiopathic IUGR (GA ⬍37w, n⫽18). ESM-1 and HGF were measured by ELISA and validated by Western blotting. Placental ESM-1 mRNA expression and localization were studied by RT-PCR, IHC and image analysis. RESULTS: Maternal serum levels of ESM-1 were GA-regulated with a significant decrease toward term (R⫽⫺.43, P⬍.001). Compared to GA-matched CRLs, women with early-onset sPE had higher ESM-1 serum concentrations (P⫽.003) that varied independent of maternal circulatory levels of HGF. Late-onset sPE, crHTN and idiopathic IUGR did not significantly impact circulating ESM-1 levels (P⬎.05). ESM-1 mRNA was detected in villous trophoblast and had high immunostaining in endothelial, cytotrophoblast and decidual cells. There was an increase in the expression of ESM-1 in the peri-infarct areas of IUGR placentas (P⫽.016), independent of sPE. CONCLUSION: Women with preterm sPE have elevated serum ESM-1 levels, likely reflecting advanced degree of endothelial activation and injury at earlier GA. Enhanced expression at sites of major placental damage suggests ESM-1 may play a role in the pathophysiology of trophoblast injury in IUGR.
655 Relationship between urinary tract infection and circulating angiogenic factors in patients with preeclampsia Sarah Rae Easter1, Kee-Hak Lim2, Samuel Parry3, Thomas McElrath4 1 Brigham and Women’s Hospital, Massachusetts General Hospital, Harvard Medical School, Department of Obstetrics and Gynecology, Boston, MA, 2 Beth Israel Deaconess Medical Center, Harvard Medical School, Division of Maternal-Fetal Medicine, Boston, MA, 3Hospital of the University of Pennsylvania, Division of Maternal-Fetal Medicine, Philadelphia, PA, 4 Brigham and Women’s Hospital, Harvard Medical School, Division of Maternal-Fetal Medicine, Boston, MA
OBJECTIVE: The association between preeclampsia (PE) and urinary tract infection (UTI) has been described. Aberrancies in circulating angiogenic factors, specifically sFlt-1 and P1GF, are associated with development of preeclampsia. We tested the hypothesis that UTI and the resulting inflammation causes changes in these markers leading to the development of PE. STUDY DESIGN: Pregnancies (n⫽2,619) were followed prospectively from the initiation of prenatal care through delivery at three U.S., regional academic centers. Plasma sFlt-1 and PlGF concentrations were quantified at 10, 17, 25 and 35 weeks gestational age (GA). Presence of UTI was abstracted from the medical record. PE was defined by ACOG criteria. Median sFlt-1 and PlGF concentrations were compared in early-onset (⬍34 weeks GA, n⫽29), late-onset (34⫹ weeks
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2013
Academic Issues, Antepartum Fetal, Clinical Ob, Fetus, Genetics, Hypertension, Med-Surg-Diseases, Operative Ob, U/S
PlGF levels. Other analysis, such as fetal m-RNA dosage for each marker, appeared to be useful in order to better explain our results.
Poster Session IV
651 Prospective evaluation of circulating angiogenic factors in the prediction of early- versus late-onset pre-eclampsia Rebecca Jessel1, Ann Thomas2, Kee-Hak Lim3, Samuel Parry4, Thomas McElrath2
Spearman correlation
1 Brigham and Women’s Hospital; Harvard Medical School, Department of Obstetrics and Gynecology, Boston, MA, 2Brigham and Women’s Hospital; Harvard Medical School, Department of Obstetrics and Gynecology; Division of Maternal Fetal Medicine, Boston, MA, 3Boston MFM; BIDMC; Harvard Medical School, Boston Maternal-Fetal Medicine, Boston, MA, 4Hospital of the University of Pennsylvania, Division of Maternal-Fetal Medicine, Hospital of the University of Pennsylvania, PA
Spearman correlation
6..5
650 sTRAIL, a prognostic marker for future death from cardiovascular disease, is decreased in maternal plasma of patients with preeclampsia Piya Chaemsaithong1, Tinnakorn Chaiworapongsa2, Tamara Stampalija1, Nandor Gabor Than1, Zhong Dong1, Lami Yeo2, Sonia Hassan2, Roberto Romero1 1 NICHD/NIH/DHHS, Perinatology Research Branch, Detroit, MI, 2Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, MI
OBJECTIVE: Women who develop preeclampsia (PE) are at increased risk of cardiovascular disease later in life. Tumor necrosis factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL), a potent inducer of apoptosis, has anti-atherosclerotic effects on endothelial cells. Patients with acute coronary artery disease have lower serum concentrations of the soluble TRAIL (sTRAIL), with higher C-reactive protein (CRP) concentrations. sTRAIL and CRP confer a risk for future death (Hazard Ratio 0.93 and 2.2, respectively). The aim of this study was to determine if maternal plasma concentrations of sTRAIL and CRP change in pregnancies with preeclampsia. STUDY DESIGN: A cross-sectional study was conducted in the following groups: 1) normal pregnant women (n⫽93); and 2) women with PE (n⫽52). Patients with PE were sub-classified into preterm (n⫽38) and term (⬎37 weeks) PE (n⫽14). Maternal plasma concentrations of sTRAIL and C-reactive protein (CRP) were determined by ELISA. RESULTS: 1) The median plasma concentration of sTRAIL was significantly lower in patients with PE than in normal pregnant women (25.6 pg/mL vs. 29.2 pg/mL; p⫽0.03); 2) the preterm (but not term) preeclampsia group had a significantly lower median plasma concentration of sTRAIL than the normal pregnancy group (24.8 pg/mL vs. 30.5 pg/mL; p⫽0.03 and 26.5 pg/mL vs. 26.8 pg/mL; p⫽0.7, respectively); and 3) the median plasma concentration of CRP was significantly higher in patients with PE (n⫽32) than in normal pregnant women (n⫽53) (8 ng/mL vs. 4.1 ng/mL; p⫽0.001); however, there was no significant correlation between maternal plasma concentrations of sTRAIL and CRP in either PE (p⫽0.1) or normal pregnancy (p⫽0.3). CONCLUSION: Preeclampsia was associated with a lower sTRAIL and a higher CRP concentration in maternal plasma. Both proteins may be involved in the mechanisms of predisposing patients with preeclampsia to future cardiovascular disease.
OBJECTIVE: Circulating angiogenic factors play a role in pathogenesis of preeclampsia (PE) but we have previously demonstrated that they have limited predictive capacity if PE is considered a single entity. However, PE is a heterogeneous disease with early (⬍34w) and late onest PE possibly representing different entities. We tested the hypothesis that sequential measurement of sFlt-1 and PlGF in a longitudinal cohort of patients can distinguish patients who are more likely to develop and require delivery for early PE. STUDY DESIGN: 2,241 singleton pregnancies were followed prospectively from the initiation of prenatal care at three regional academic centers. Plasma sFlt-1 and PlGF levels were collected prospectively and quantified by immunoassay at approximately 10, 17, and 24 weeks gestation. Patients were followed through delivery. PE was diagnosed by ACOG criteria. Patients with chronic hypertension and diabetes were excluded from this analysis. RESULTS: Median analyte concentrations for early and late and testing characteristics for the prediction of early PE are presented in the table. Twenty patients developed PE before 34 weeks compared to 182 patients with late PE. Incidence of early PE was ⬍1%. PlGF concentrations are significantly lower among early PE patients at all time points and magnitude of increase with gestation was lower than those with late PE. sFlt-1 concentrations and the ratio are significantly different at 26 weeks. However, the testing characteristics do not suggest clinical utility in the prediction of early PE. CONCLUSION: Our results support the suggestion that PE is a heterogeneous disease with early and late PE possibly representing different disease processes. Despite low incidence, the significant differences in analytes in early versus late suggests a more homogenous cohort. However, the analytes, do not appear to be clinically useful in the prediction of early PE.
Differences in analytes and ROC analysis for early and late preeclampsia
652 3D-power Doppler quantification of placental vascularity in pregnancy complicated with hypertensive disorders Eduardo Pimenta1, Rodrigo Ruano2, Rossana Francisco1, Marcelo Zugaib1 1 Medical School, University of Sao Paulo, Obstetrics and Gynecology, Sao Paulo, Brazil, 2Baylor College of Medicine, Obstetrics and Gynecology, Houston, TX
OBJECTIVE: To evaluate if pregnancies complicated with hypertensive disorders have reduced placental vascularity than healthy pregnancies. STUDY DESIGN: Between April 2011 and July 2012, a prospective casecontrol study was conducted in one center. Sixty-one pregnant
Supplement to JANUARY 2013 American Journal of Obstetrics & Gynecology
S275
Poster Session IV
Academic Issues, Antepartum Fetal, Clinical Ob, Fetus, Genetics, Hypertension, Med-Surg-Diseases, Operative Ob, U/S
women with hypertensive disorder (19 with pure preeclampsia, 23 with chronic hypertension and 20 with superimposed preeclampsia) and 66 healthy pregnant women underwent 3DUS examination once during the pregnancy. Case and controls were a match according to maternal age, gestational age at ultrasound examination and parity. Placental vascularity was calculated using the 3D-power Doppler histogram using pre-established power Doppler settings. Comparison among groups and subgroups were analyzed using t-student and ANOVA tests. RESULTS: The population demographics and characteristics were similar in both groups. Mean gestational age at evaluation was 32.6⫾3.4 weeks. The placental vascularity index was significantly reduced in cases with hypertension (11.1⫾0.8%) in comparison with healthy pregnancies (15.2⫾1.1%; p⬍0.01); but with similar reduction in those with pure preeclampsia (10.7⫾1.1%), chronic hypertension (11.5⫾1.3%) and superimposed preeclampsia (11.2⫾1.2%; p⫽0.89). CONCLUSION: Pregnancies complicated with hypertensive disorders have reduced placental vascularity than healthy pregnancies, independently of the classification of the disorder.
653 Evidence for excessive feto-placental activation of the polyol pathway: implications for hyperuricemia of preeclampsia (PE) Sami Makaroun1, Catalin Buhimschi1, Guomao Zhao1, Megan McCarthy1, John Hardy1, Antonette Dulay1, Christine Laky1, Irina Buhimschi1 1
Yale University, Ob/Gyn & Reprod. Sci., New Haven, CT
OBJECTIVE: Uric acid (UA) can result from fructose (FRU) metabo-
lism. Aside from ingestion, FRU is endogenously produced from glucose (GLU) via the polyol pathway: aldose reductase (ARD) converts GLU to sorbitol (SOR) and SOR-dehydrogenase (SORD) converts SOR to FRU. We hypothesized that overactivation of an existing polyol pathway in the feto-placental unit contributes to hyperuricemia of PE. STUDY DESIGN: FRU, SOR, GLU, and UA were assayed in serum and urine of 65 pregnant healthy controls (CRL: GA: ⬍20w, n⫽4; GA: 20-34w, n⫽15; GA: ⬎37w, n⫽46) and 29 women with severe PE (sPE, GA: 29⫾2w). Same analytes were assayed in cord blood (CB) of fetuses delivered in the setting of sPE (n⫽23, GA: 30⫾1), idiopathic preterm birth (iPTB, n⫽23, GA: 31⫾1), and normal healthy term gestation (n⫽22). Placental and amniochorion ARD & SORD expression was studied in sPE, iPTB and term gestation (n⫽4/group) by RT-PCR and IHC. Placenta and membrane explants were employed to test their ability to generate SOR in vitro. RESULTS: In normal gestation, serum UA increased with GA (P⬍.001) in relationship with SOR (r⫽.67, P⬍.001) and FRU (r⫽.32, P⫽.03) but not GLU (P⬎.05). Fractional excretion (FE) of FRU and UA decreased with GA (P⬍.001). sPE increased serum UA (P⬍.001) and SOR (P⬍0.001) but not FRU & GLU (P⬎0.05). FE of UA, FRU and SOR but not of GLU were decreased in sPE (P⬍.001). In sPE, UA level was predicted by the combination of SOR and serum creatinine (P⬍.001 for both), accounting for 53% of variability. SOR & UA in CB of healthy term newborns exceed maternal levels. sPE further increased CB SOR and UA vs iPTB group (P⬍.05). PCR and IHC demonstrated preferential expression of ARD in trophoblasts and of SORD in decidual cells. Fetal membranes release 3-fold SOR compared to placenta in vitro. CONCLUSION: An active polyol pathway is present and functional in the feto-placental unit. Decidual dysfunction and accumulation of SOR at this site could be an alternative explanation for the increased UA in PE.
S276
www.AJOG.org
654 Endocan (ESM-1): a novel soluble endothelial cell injury marker in preeclampsia (PE) and intrauterine growth restriction (IUGR) Sarah Cross1, Irina Buhimschi1, Christina Duzyj1, Lydia Shook1, Megan McCarthy1, John Hardy1, Guomao Zhao1, Catalin Buhimschi1 1
Yale University, Ob/Gyn & Reprod. Sci., New Haven, CT
OBJECTIVE: ESM-1 is a newly discovered soluble endothelial cell pro-
teoglycan, released by damaged vascular endothelium in response to inflammatory cytokines and angiogenic stimuli. Recent data show ESM-1 regulates angiogenesis and its bioactivity is mediated via interaction with hepatocyte growth factor (HGF). Vascular endothelial dysfunction and injury plays a key role in the pathogenesis of PE and IUGR. We hypothesized that soluble ESM-1 is upregulated in women with severe PE (sPE), and its circulatory levels relate to the timing and clinical manifestation of the disease. STUDY DESIGN: We analyzed 211 serum samples from: normotensive healthy pregnant controls (CRL, GA ⬍20w, n⫽29; GA 20-34w, n⫽31; GA ⬎37w, n⫽18), early-onset sPE (GA 20-34w, n⫽28), early onset sPE⫹IUGR (GA ⬍37w, n⫽16), late-onset sPE (GA ⬎37w, n⫽39), chronic hypertension (crHTN, GA ⬍37w, n⫽39) and idiopathic IUGR (GA ⬍37w, n⫽18). ESM-1 and HGF were measured by ELISA and validated by Western blotting. Placental ESM-1 mRNA expression and localization were studied by RT-PCR, IHC and image analysis. RESULTS: Maternal serum levels of ESM-1 were GA-regulated with a significant decrease toward term (R⫽⫺.43, P⬍.001). Compared to GA-matched CRLs, women with early-onset sPE had higher ESM-1 serum concentrations (P⫽.003) that varied independent of maternal circulatory levels of HGF. Late-onset sPE, crHTN and idiopathic IUGR did not significantly impact circulating ESM-1 levels (P⬎.05). ESM-1 mRNA was detected in villous trophoblast and had high immunostaining in endothelial, cytotrophoblast and decidual cells. There was an increase in the expression of ESM-1 in the peri-infarct areas of IUGR placentas (P⫽.016), independent of sPE. CONCLUSION: Women with preterm sPE have elevated serum ESM-1 levels, likely reflecting advanced degree of endothelial activation and injury at earlier GA. Enhanced expression at sites of major placental damage suggests ESM-1 may play a role in the pathophysiology of trophoblast injury in IUGR.
655 Relationship between urinary tract infection and circulating angiogenic factors in patients with preeclampsia Sarah Rae Easter1, Kee-Hak Lim2, Samuel Parry3, Thomas McElrath4 1 Brigham and Women’s Hospital, Massachusetts General Hospital, Harvard Medical School, Department of Obstetrics and Gynecology, Boston, MA, 2 Beth Israel Deaconess Medical Center, Harvard Medical School, Division of Maternal-Fetal Medicine, Boston, MA, 3Hospital of the University of Pennsylvania, Division of Maternal-Fetal Medicine, Philadelphia, PA, 4 Brigham and Women’s Hospital, Harvard Medical School, Division of Maternal-Fetal Medicine, Boston, MA
OBJECTIVE: The association between preeclampsia (PE) and urinary tract infection (UTI) has been described. Aberrancies in circulating angiogenic factors, specifically sFlt-1 and P1GF, are associated with development of preeclampsia. We tested the hypothesis that UTI and the resulting inflammation causes changes in these markers leading to the development of PE. STUDY DESIGN: Pregnancies (n⫽2,619) were followed prospectively from the initiation of prenatal care through delivery at three U.S., regional academic centers. Plasma sFlt-1 and PlGF concentrations were quantified at 10, 17, 25 and 35 weeks gestational age (GA). Presence of UTI was abstracted from the medical record. PE was defined by ACOG criteria. Median sFlt-1 and PlGF concentrations were compared in early-onset (⬍34 weeks GA, n⫽29), late-onset (34⫹ weeks
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2013