effect of serum from women with abnormal uterine artery doppler resistance on extravillous...

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West Ballroom, Fontainebleau Hotel 574 UTERINE ARTERY DOPPLER MEASUREMENT AND PRO-INFLAMMATORY CYTOKINES IN NORMAL PREGNANCY JENNIFER DONNELLY 1 , SHARON COOLEY 1 , JOANNA BALDING 2 , CIARAN MURPHY 2 , TOM WALSH 3 , OWEN SMITH 4 , CORRINA MCMAHON 5 , MICHAEL GEARY 1 , 1 Rotunda Hospital, Obstetrics and Gynaecology, Dublin 1, Ireland, 2 Institute of Molecular Medicine, Dept of Haematology, Trinity College, Dublin, Dublin 8, Ireland, 3 Royal College of Surgeons, Obstet- rics and Gynaecology, Dublin 1, Ireland, 4 National Centre for Hereditary Coag- ulation Disorders, Dublin 8, Ireland, 5 Our Lady’s Hospital for Sick Children, Haematology, Dublin 12, Ireland OBJECTIVE: Differences in the inflammatory response between normal pregnancy and the non-pregnant state are more marked than that between normal pregnancy and pre-eclampsia. Doppler studies of the uterine arteries in the second trimester have reported an increased pulsatility index (PI) in women at high risk for pre-eclampsia. We aimed to examine the relationship between certain pro-inflammatory cytokines and uterine artery Dopplers in normal pregnancy. STUDY DESIGN: 500 primiparous, caucasian women with no chronic medical conditions and no current drug therapy were recruited prospectively at their booking visit (!20 weeks gestation). Tumor necrosis factor-alpha (TNF-a), Interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) levels were taken at booking and at 34-36 weeks and were measured using Duoset ELISA Development system. Doppler studies of the uterine arteries were performed using colour flow mapping and pulsed wave Doppler at 23 weeks gestation. The mean PI of the two uterine arteries was calculated. Eighty-two women were excluded from analysis as they developed maternal or fetal pregnancy complications. Correlation between groups was evaluated using Pearson Chi-Square. RESULTS: No significant relationship was found between high levels of TNF-alpha or VEGF at booking or at 34-36 weeks and a high mean PI in the second trimester. However, women with levels of IL-6 greater than 5 pg/ml at booking were found to have a significant association with a high mean PI (p!0.05). CONCLUSION: Despite increased impedance to flow in the uterine arteries of women with high levels of the pro-inflammatory cytokine IL-6, these women had a normal pregnancy outcome. This supports the theory that normal pregnancy and pre-eclampsia are part of the same continuum of the maternal inflammatory response to pregnancy. 575 EFFECT OF SERUM FROM WOMEN WITH ABNORMAL UTERINE ARTERY DOPPLER RESISTANCE ON EXTRAVILLOUS TROPHOBLAST INVASION IN THE FIRST TRIMESTER RAMESH GANAPATHY 1 , LAURA AYLING 2 , GUY WHITLEY 2 , JUDITH CARTWRIGHT 2 , BASKY THILAGANATHAN 1 , 1 St. George’s Hospital Medical School, Fetal Medicine, London, United Kingdom, 2 St. Georges Medical School London, Biochemistry and Immunology, Division of Basic Medical Sciences, London, United Kingdom OBJECTIVE: To evaluate in-vitro trophoblast function following exposure to first trimester serum from pregnancies with high uterine artery Doppler resistance indices. STUDY DESIGN: Doppler ultrasound examination of the maternal uterine arteries was performed on women at 10-14 weeks’ gestation. Serum was collected from women with high uterine artery resistance (bilateral uterine artery notches and mean RI above the 95th centile). Samples were also obtained from patients with normal uterine artery indices and a male volunteer. The effect of serum on trophoblast invasion was determined using an established in-vitro model from the extravillous trophoblast-derived cell line SGHPL-4. RESULTS: Trophoblastic invasion was significantly reduced when treated with serum from women with high resistance compared to normal resistance uterine artery Doppler indices. CONCLUSION: Maternal serum in the first trimester of pregnancy from patients with high resistance uterine artery Doppler indices appears to inhibit trophoblast invasion. This experimental model allows the further investigation of the factors responsible and the evaluation of therapeutic strategies. 576 THE RELATIONSHIP BETWEEN ABNORMAL FETAL TESTING AND ADVERSE PERI- NATAL OUTCOMES IN INTRAUTERINE GROWTH RESTRICTION (IUGR) JUAN GONZALEZ 1 , ANTHONY ODIBO 2 , DAVID STAMILIO 3 , SERDAR URAL 2 , GEORGE MACONES 2 , 1 Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, 2 University of Pennsylvania, Obstetrics and Gynecology, Phila- delphia, Pennsylvania, 3 University of Pennsylvania Medical Center, Philadel- phia, Pennsylvania OBJECTIVE: To compare the efficacy of non-stress test (NST), biophysical profile (BPP) or abnormal Dopplers (AbnDopp) in predicting adverse perinatal outcomes in IUGR. STUDY DESIGN: Retrospective cohort study of IUGR (birth weight !5th percentile for gestation) over a seven year period. We excluded twins or fetuses with aneuploidy or congenital malformations. Abnormal antenatal testing were defined as: NST which was non-reactive or with late decelerations; BPP ¡U ¨ 6 and AbnDopp as umbilical artery with absent or reversed end diastolic flow. The outcomes studied included: umbilical artery pH ! 7; respiratory distress syndrome (RDS); periventricular leukomalacia (PVL); grades 3-4 intraventricular hemorrhage (IVH); perinatal mortality (PNM); necrotizing enterocolitis (NEC) and a composite of at least one adverse outcome. Statistical analysis included bivariate and multivariable techniques. RESULTS: We identified 151 singleton pregnancies with IUGR meeting the inclusion criteria. On bivariate analysis significant variables associated with adverse outcomes were: history of chronic hypertension, steroid administra- tion and gestational age of delivery. These were adjusted for using logistic regression. Of the testing modalities compared only AbnDopp significantly predicted RDS and the composite of adverse outcome. Using the Kaplan- Meier survival plot there was significant association between the interval from abnormal doppler to delivery in the cases with adverse outcomes (p ! 0.002). CONCLUSION: In cases of IUGR the presence of abnormal Doppler is the best predictor of adverse perinataloutcome. pH!7 N=3 RDS N = 25 PVL N=2 IVH N=3 PNM N=9 NEC N=6 Composite N = 36 NST 0 (0%) 9 (36%) 0 (0%) 0 (0%) 2 (22%) 3 (50%) 12 (33%) AOR (95%CI) d 1.7 (0.5-5.8) d d 0.7 (0.1-7.0) 2.6 (0.4-17.3) 1.6 (0.4-6.0) BPP 0 (0%) 4 (16%) 0 (0%) 0 (0%) 2 (22%) 2 (33%) 7 (19%) AOR (95%CI) d 0.8 (0.2-4.1) d d 2.4 (0.3-20) 2.8 (0.4-21.8) 1.2 (0.2-5.8) AbnDopp 0 (0%) 9 (36%) 0 (0%) 1 (33%) 1 (11%) 1 (17%) 10 (28%) AOR (95%CI) d 6.5 (1.8-23.3) d 2.8 (0.2-40.3) 0.3 (.01-5.6) 1 (0.1-9.8) 4.3 (1.0-17.8) AOR = Adjusted odds ratio. 577 MIDDLE CEREBRAL ARTERY PEAK SYSTOLIC VELOCITY AND DUCTUS VENOSUS PULSATILITY INDEX – WHICH IS BEST IN PREDICTING PERINATAL MORTALITY OF SGA FETUSES WITH ABNORMAL UMBILICAL ARTERY? GIANCARLO MARI 1 , MAMTHA BALASUBRAMANIAM 2 , ELEAZAR SOTO 1 , JIMMY ESPINOZA 1 , JYH KAE NIEN 3 , KARINA RICHANI 1 , MARJORIE TREADWELL 1 , 1 Wayne State University, Obstetrics & Gyne- cology, Detroit, Michigan, 2 Beaumont Hospital, Royal Oak, Michigan, 3 Perina- tology Research Branch, NICHD, NIH, DHHS, Detroit, Michigan OBJECTIVE: It has been suggested that abnormal ductus venosus (DV) pulsatility index (PI) is a better predictive parameter of adverse perinatal outcome than umbilical artery (UA) PI. Recently, it has been reported that middle cerebral artery (MCA) peak systolic velocity (PSV) predicts perinatal mortality better than MCA-PI. The aim of this study was to compare the performance of MCA-PSV and DV-PI in predicting perinatal mortality. STUDY DESIGN: The study population consisted of patients diagnosed to have SGA (EFW or AC ! 10th percentile) and an UA PI outside the reference range. MCA-PSV and DV-PI for each fetus were considered abnormal when they fell outside the reference range. The presence or absence of DV reversed flow SMFM Abstracts S165

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Page 1: Effect of serum from women with abnormal uterine artery Doppler resistance on extravillous trophoblast invasion in the first trimester

West Ballroom, Fontainebleau Hotel574 UTERINE ARTERY DOPPLER MEASUREMENT AND PRO-INFLAMMATORY CYTOKINES

IN NORMAL PREGNANCY JENNIFER DONNELLY1, SHARON COOLEY1, JOANNABALDING2, CIARAN MURPHY2, TOM WALSH3, OWEN SMITH4, CORRINAMCMAHON5, MICHAEL GEARY1, 1Rotunda Hospital, Obstetrics and Gynaecology,Dublin 1, Ireland, 2Institute of Molecular Medicine, Dept of Haematology,Trinity College, Dublin, Dublin 8, Ireland, 3Royal College of Surgeons, Obstet-rics andGynaecology,Dublin 1, Ireland, 4National Centre forHereditaryCoag-ulation Disorders, Dublin 8, Ireland, 5Our Lady’s Hospital for Sick Children,Haematology, Dublin 12, Ireland

OBJECTIVE: Differences in the inflammatory response between normalpregnancy and the non-pregnant state are more marked than that betweennormal pregnancy and pre-eclampsia. Doppler studies of the uterine arteries inthe second trimester have reported an increased pulsatility index (PI) in womenat high risk for pre-eclampsia. We aimed to examine the relationship betweencertain pro-inflammatory cytokines and uterine artery Dopplers in normalpregnancy.

STUDY DESIGN: 500 primiparous, caucasian women with no chronicmedical conditions and no current drug therapy were recruited prospectivelyat their booking visit (!20 weeks gestation). Tumor necrosis factor-alpha(TNF-a), Interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF)levels were taken at booking and at 34-36 weeks and were measured usingDuoset ELISA Development system. Doppler studies of the uterine arterieswere performed using colour flow mapping and pulsed wave Doppler at 23weeks gestation. The mean PI of the two uterine arteries was calculated.Eighty-two women were excluded from analysis as they developed maternal orfetal pregnancy complications. Correlation between groups was evaluatedusing Pearson Chi-Square.

RESULTS: No significant relationship was found between high levels ofTNF-alpha or VEGF at booking or at 34-36 weeks and a high mean PI in thesecond trimester. However, women with levels of IL-6 greater than 5 pg/ml atbooking were found to have a significant association with a high mean PI(p!0.05).

CONCLUSION: Despite increased impedance to flow in the uterine arteries ofwomen with high levels of the pro-inflammatory cytokine IL-6, these womenhad a normal pregnancy outcome. This supports the theory that normalpregnancy and pre-eclampsia are part of the same continuum of the maternalinflammatory response to pregnancy.

576 THE RELATIONSHIP BETWEEN ABNORMAL FETAL TESTING AND ADVERSE PERI-NATAL OUTCOMES IN INTRAUTERINE GROWTH RESTRICTION (IUGR)JUAN GONZALEZ1, ANTHONY ODIBO2, DAVID STAMILIO3, SERDAR URAL2,GEORGE MACONES2, 1Hospital of the University of Pennsylvania, Philadelphia,Pennsylvania, 2University of Pennsylvania, Obstetrics and Gynecology, Phila-delphia, Pennsylvania, 3University of Pennsylvania Medical Center, Philadel-phia, Pennsylvania

OBJECTIVE: To compare the efficacy of non-stress test (NST), biophysicalprofile (BPP) or abnormal Dopplers (AbnDopp) in predicting adverseperinatal outcomes in IUGR.

STUDY DESIGN: Retrospective cohort study of IUGR (birth weight !5thpercentile for gestation) over a seven year period. We excluded twins or fetuseswith aneuploidy or congenital malformations. Abnormal antenatal testingwere defined as: NST which was non-reactive or with late decelerations; BPP¡U 6 and AbnDopp as umbilical artery with absent or reversed end diastolicflow. The outcomes studied included: umbilical artery pH ! 7; respiratorydistress syndrome (RDS); periventricular leukomalacia (PVL); grades 3-4intraventricular hemorrhage (IVH); perinatal mortality (PNM); necrotizingenterocolitis (NEC) and a composite of at least one adverse outcome.Statistical analysis included bivariate and multivariable techniques.

RESULTS: We identified 151 singleton pregnancies with IUGR meeting theinclusion criteria. On bivariate analysis significant variables associated withadverse outcomes were: history of chronic hypertension, steroid administra-tion and gestational age of delivery. These were adjusted for using logisticregression. Of the testing modalities compared only AbnDopp significantlypredicted RDS and the composite of adverse outcome. Using the Kaplan-Meier survival plot there was significant association between the interval fromabnormal doppler to delivery in the cases with adverse outcomes (p ! 0.002).

CONCLUSION: In cases of IUGR the presence of abnormal Doppler is thebest predictor of adverse perinataloutcome.

pH!7N = 3

RDSN = 25

PVLN = 2

IVHN = 3

PNMN = 9

NECN = 6

CompositeN = 36

NST 0 (0%) 9 (36%) 0 (0%) 0 (0%) 2 (22%) 3 (50%) 12 (33%)AOR (95%CI) d 1.7

(0.5-5.8)d d 0.7

(0.1-7.0)2.6(0.4-17.3)

1.6(0.4-6.0)

BPP 0 (0%) 4 (16%) 0 (0%) 0 (0%) 2 (22%) 2 (33%) 7 (19%)AOR (95%CI) d 0.8

(0.2-4.1)d d 2.4

(0.3-20)2.8(0.4-21.8)

1.2(0.2-5.8)

AbnDopp 0 (0%) 9 (36%) 0 (0%) 1 (33%) 1 (11%) 1 (17%) 10 (28%)AOR (95%CI) d 6.5

(1.8-23.3)d 2.8

(0.2-40.3)0.3(.01-5.6)

1 (0.1-9.8) 4.3(1.0-17.8)

AOR = Adjusted odds ratio.

577 MIDDLE CEREBRAL ARTERY PEAK SYSTOLIC VELOCITY AND DUCTUS VENOSUSPULSATILITY INDEX – WHICH IS BEST IN PREDICTING PERINATAL MORTALITY OFSGA FETUSES WITH ABNORMAL UMBILICAL ARTERY? GIANCARLO MARI1, MAMTHABALASUBRAMANIAM2, ELEAZAR SOTO1, JIMMY ESPINOZA1, JYH KAE NIEN3, KARINARICHANI1, MARJORIE TREADWELL1, 1Wayne State University, Obstetrics & Gyne-cology, Detroit, Michigan, 2Beaumont Hospital, Royal Oak, Michigan, 3Perina-tology Research Branch, NICHD, NIH, DHHS, Detroit, Michigan

OBJECTIVE: It has been suggested that abnormal ductus venosus (DV)pulsatility index (PI) is a better predictive parameter of adverse perinataloutcome than umbilical artery (UA) PI. Recently, it has been reported thatmiddle cerebral artery (MCA) peak systolic velocity (PSV) predicts perinatalmortality better than MCA-PI. The aim of this study was to compare theperformance of MCA-PSV and DV-PI in predicting perinatal mortality.

STUDY DESIGN: The study population consisted of patients diagnosed tohave SGA (EFW or AC! 10th percentile) and an UA PI outside the referencerange. MCA-PSV and DV-PI for each fetus were considered abnormal whenthey fell outside the reference range. The presence or absence ofDV reversed flow

SMFM Abstracts S165

575 EFFECT OF SERUM FROM WOMEN WITH ABNORMAL UTERINE ARTERY DOPPLERRESISTANCE ON EXTRAVILLOUS TROPHOBLAST INVASION IN THE FIRST TRIMESTERRAMESH GANAPATHY1, LAURA AYLING2, GUY WHITLEY2, JUDITH CARTWRIGHT2,BASKY THILAGANATHAN1, 1St.George’sHospitalMedical School, FetalMedicine,London, United Kingdom, 2St. GeorgesMedical School London, Biochemistryand Immunology, Division of Basic Medical Sciences, London, UnitedKingdom

OBJECTIVE: To evaluate in-vitro trophoblast function following exposureto first trimester serum from pregnancies with high uterine artery Dopplerresistance indices.

STUDY DESIGN: Doppler ultrasound examination of the maternal uterinearteries was performed on women at 10-14 weeks’ gestation. Serum wascollected from women with high uterine artery resistance (bilateral uterineartery notches and mean RI above the 95th centile). Samples were alsoobtained from patients with normal uterine artery indices and a malevolunteer. The effect of serum on trophoblast invasion was determined usingan established in-vitro model from the extravillous trophoblast-derived cellline SGHPL-4.

RESULTS: Trophoblastic invasion was significantly reduced when treatedwith serum from women with high resistance compared to normal resistanceuterine artery Doppler indices.

CONCLUSION: Maternal serum in the first trimester of pregnancy frompatients with high resistance uterine artery Doppler indices appears to inhibittrophoblast invasion. This experimental model allows the further investigationof the factors responsible and the evaluation of therapeutic strategies.