effect of low dose heparin, unfractionated heparin and aspirin on trophoblast invasion

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Page 1: Effect of low dose heparin, unfractionated heparin and aspirin on trophoblast invasion

257 NICOTINE SUPPRESSES PRO-INFLAMMATORY RESPONSES BY HUMAN PLACENTALCELLS OONAGH DOWLING1, BURTON ROCHELSON2, CHRISTINE N. METZ1, 1Institutefor Medical Research at North Shore-LIJ, Center for Patient OrientedResearch, Manhasset, New York, 2North Shore University Hospital, Divisionof Maternal-Fetal Medicine, Manhasset, New York

OBJECTIVE: Pregnancy-Induced Hypertension (PIH) a leading causes ofperinatal morbidity and mortality. Although the pathogenesis of PIH is poorlyunderstood, numerous reports support the hypothesis that aberrant pro-inflammatory cytokine production and endothelial dysfunction within theplacenta mediate PIH development. While smoking during pregnancy isassociated with many adverse effects, several studies show that smokingprotects against the development of PIH. Based on recent studies revealingthe anti-inflammatory properties of nicotine, we have examined the effectof nicotine on inflammatory cytokine production by human placenta cellsin vitro.

STUDY DESIGN: Anonymous human placentas (free of gross abnormalities)were processed within 3 hr of delivery to isolate placenta cells. Placenta cells(2! 10-6 cells/ml in 96 well plates) were treated with nicotine 10�4M to 10�8Mfor 30 min prior to LPS stimulation (1-100 ng/ml). After an overnight incuba-tion, cell culture supernatants were collected and assayed for TNF productionby ELISA. Statistical significance was determined by ANOVA followed by Tu-key post hoc analysis to make pairwise comparisons.

RESULTS: LPS (1-1000 ng/ml) stimulation induced a dose-dependentproduction of the pro-inflammatory mediator, TNF, by human placenta cells.Nicotine (10�4M to 10�5M) significantly reduced TNF production by placentacells, with the greatest reduction (up to 45%) observed at 10�4M nicotine.

CONCLUSION: Our observations reveal that nicotine inhibits pro-inflam-matory cytokine production by placenta cells in vitro. This finding is consistentwith studies demonstrating the anti-inflammatory effects of nicotine innumerous pathological conditions, including ulcerative colitis, experimentalsepsis, and experimental ileus. Our results suggest a mechanism by whichsmoking may protect against the development of PIH.

258 OUTCOMES OF MATERNAL FRACTURES IN PREGNANCY DINA EL KADY (F)1,LLOYD SMITH1, GUIBO XING1, WILLIAM M. GILBERT1, 1University of California,Davis, Medical Center, OB/GYN, Sacramento, California

OBJECTIVE: To examine maternal, fetal and neonatal outcomes of pregnantwomen hospitalized for fracture injuries in a large obstetric population.

STUDY DESIGN: This is a large retrospective cohort analysis using a com-puterized database of maternal and newborn hospital discharge records linkedto vital certificate birth records. Pregnant women hospitalized for an injuryin California from 1991-1999 were included in the study. Fractures wereidentified using International Classification of Diseases, ninth revision, clinicalmodification codes. Perinatal outcomes were analyzed, including demograph-ics, risk factors for injury, and maternal and fetal outcomes. Statistical analysiswere perfomed using odds ratios with 95% Confidence Intervals. Multivariateregression analysis was perfomed to assess the effects of gestational age andsubstance abuse on low birth weight.

RESULTS: A total of 3292 fractures were identified among 4,833,386deliveries. The most common mechanism of fracture was by motor vehicleaccidents (44%) followed by falls (25%). Demographics reveal higher per-centages of white, non-hispanic women, and a higher percentage of olderwomen age 35-41C. Women sustaining a fracture who delivered at the injuryhospitalization had significantly increased risks of adverse outcomes, includingabruption, OR 7.8 (95%CI 7.2, 11.8) blood transfusions, OR 10.4 (95%CI9.5, 19.5) stillbirth OR 6.3 (95%CI 3.3, 11.7), uterine rupture OR 35.7 (95%CI5, 255) and maternal mortality OR 169 (95%CI 83.2, 346.4). Womensustaining a fracture discharged home undelivered continue to have increasedrisks when presenting for delivery, including increased risk of low birth weightinfants OR 1.46 (95%CI 1.28, 1.66), and thrombotic events OR 9.2 (95%CI1.3, 65). Pelvic Fractures had the worst maternal and neonatal outcomes.

CONCLUSION: Fracture Injuries during pregnancy, are associated with signi-ficant immediate and long term increases in maternal and perinatal morbidityand mortality. Our data supports the close observation of these undeliveredhigh risk women.

259 ECHOCARDIOGRAPIC ASSESSMENT OF THE OBESE GRAVIDA CONSTANCE FARO1,MILDRED RAMIREZ1, JOAN MASTROBATTISTA1, MANJU MONGA1, 1University ofTexas Health Science Center at Houston, Obstetrics, Gynecology and Repro-ductive Science, Houston, Texas

OBJECTIVE: Obesity is increasing in prevalence in America. Obese womenare at increased risk of adverse maternal and perinatal outcome. Limitedinformation is available about cardiac function in this patient population. Ourobjective was to prospectively evaluate the echocardiographic findings in agroup of obese pregnant women.

STUDY DESIGN: Prospective observational study of maternal echocardio-grams (ECHO) 2D, M-mode, Doppler and color flow performed from 10/02 to5/05 in women with body mass index (BMI) of 40 or greater. Results wereavailable for clinical management. We excluded patients with known cardiacdisease and those with AHA symptoms at the time of ECHO. All ECHO wereperformed at one location. Data recorded were maternal age, BMI, medicalco-morbidities, gestational age at the time of the ECHO, ECHO findings anddelivery outcomes. Data was analyzed using descriptive statistics and corre-lation analysis when indicated.

RESULTS: 24 patients were evaluated. The median maternal age was 32years (range 22-45), the median BMI was 53.6 (range 40-68). The mediangravidity was 4 (range 1-12). 33% of the patients had hypertension, 8% haddiabetes and 42% had both. Gestational age at delivery was 36.1G3.1 weekswith a mean birth weight of 3198G913 grams. Superimposed preeclampsiawas diagnosed in 42% with 68% were delivered by cesarean. ECHO wasperformed after the first trimester in 96%. The mean left ventricle (LV) enddiastolic cavity dimension was 5.0G0.48 cm while the end systolic cavitydimension was 3.4G0.7 cm. The mean left posterior wall thickness was1.0G.15 cm. The left ventricular ejection (LVEF) was normal (O55%) in 23 of24 patients. LV dimensions were not correlated with BMI. The systolicpulmonary artery pressure (PAP) was not measurable in 58%. Three patients(12%) showed evidence of mild concentric left ventricular hypertrophy.

CONCLUSION: Despite BMI of greater than 40, asymptomatic morbidlyobese gravidas maintain normal left ventricular function. Maternal transtho-racic ECHO was of limited value in evaluating PAP.

260 EFFECT OF LOW DOSE HEPARIN, UNFRACTIONATED HEPARIN AND ASPIRIN ONTROPHOBLAST INVASION RAMESH GANAPATHY1, BASKY THILAGANATHAN2,LAURA AYLING2, JUDITH CARTWRIGHT3, GUY WHITLEY3, 1St. George’s HospitalMedical School, Fetal Medicine, London, United Kingdom, 2St. George’sHospital Medical School, London, United Kingdom, 3St. Georges MedicalSchool London, Biochemistry and Immunology, Division of Basic MedicalSciences, London, United Kingdom

OBJECTIVE: To evaluate trophoblast invasion in a cell line and placentaltissue when exposed to unfractionated and fractionated Heparin and Aspirin.

STUDY DESIGN: An established cell Line of trophoblasts SGHPL4 was usedto study invasion on a fibrin gel in the presence of varying concentrations ofHeparin and fractionated heparin and Aspirin. Placental tissue was collectedfrom patients after termination with their consent. Villous tissue growth wasmeasured on a time lapse microscope and the area of invasion analysed in thepresence of Heparin and fractionated Heparin.

RESULTS: Fractionated heparin reduced invasion in the cell line and inplacental tissue in a dose dependant fashion. Heparin effected a uniform doseindependent reduction in invasion in the cell linemodel and in placental samples.Aspirin showed a reduction in invasion but the results were inconsistent.

CONCLUSION: Heparin in the unfractionated form and fractionated formreduces trophoblast invasion in cell lines and first trimester trophoblastspecimens. Aspirin doesnt appear to have a consistent response. This studyhighlights the need for further evaluation of these medications in-vitro andin-vivo; especially when they are used in the absence of any thrombophilicdisorders.

S82 SMFM Abstracts