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Leptin as a second trimester marker for preeclampsia
SMFM Abstracts S77 237 LEPTIN AS A SECOND TRIMESTER MARKER FOR PREECLAMPSIA CHRISTOPHER ROBINSON (F)1, DONNA JOHNSON1, 1Medical University of South Carolina, Obstetrics and Gynecology, Charleston, South Carolina OBJECTIVE: Leptin, a hormone produced by placental trophoblasts, is recognized as a regulator of satiety and fetal growth. Placental changes associated with preeclampsia are known to alter leptin gene regulation. This study was undertaken to determine if serum leptin levels are altered in the second trimester prior to the onset of clinical symptoms of preeclampsia. STUDY DESIGN: Following IRB approval, serum was obtained from ÿ70(C storage for healthy controls and patients who developed preeclampsia defined by ACOG criteria. Patients were matched for age, gestational age at blood draw, and body mass index (BMI). Leptin concentration was quantitated by ELISA and reported as mean G SEM in pg/mL. Statistical analysis was performed with independent sample T test, chi square, and Fisher’s exact test where appropriate. RESULTS: 23 controls and 23 patients with preeclampsia were enrolled. Age (p=0.54), gestational age at blood draw (p=0.32), and BMI (p=0.96) were all similar between groups. However, leptin was not different in second trimester serum in patients who later developed preeclampsia compared to healthy normotensive patients (6044.2 G 304.6 vs. 6341 G 236.8, p=0.44). CONCLUSION: Although leptin has been reported to be altered in serum of patients who have clinical manifestations of preeclampsia, it does not appear to be altered earlier as measured in the second trimester. Leptin alone is not a candidate marker for early detection of preeclampsia.
239 THE TIME COURSE RESPONSE TO CORTICOSTEROIDS IN WOMEN WITH ANTEPARTUM HELLP SYNDROME JOHN O’BRIEN1, WADE SCHWENDEMANN2, JOHN R. BARTON3, 1Baptist Health Care System, Lexington, Kentucky, 2University of Kentucky, Clinical Science: Obstetrics & Gynecology, Lexington, Kentucky, 3Central Baptist Hospital, Perinatal Diagnostic Center, Lexington, Kentucky OBJECTIVE: Our purpose was to evaluate the time course for response to glucocorticoids in women with HELLP syndrome and assess variables associated with the response. STUDY DESIGN: Patients with the antepartum HELLP syndrome from 1996-2003 were included for analysis if serial laboratory studies were obtained prior to delivery. The change in platelet count, liver function tests (LFTs), and LDH was evaluated at 6 hour intervals after the diagnosis of HELLP syndrome and initiation of therapy. Women not exposed to steroid were compared to those receiving standard doses (24 mg/day) and to those receiving a high-dose regimen (O24 mg/day). Statistical analysis was performed using non-parametric and regression analysis. RESULTS: Sixty-one patients were eligible for analysis with 28 receiving high-dose, 20 standard-dose, and 13 patients did not receive therapy. Patients in these groups had no significant differences in LFTs and LDH at diagnosis; however the mean PLT count at diagnosis was lower in the high-dose group, 57G19 vs the standard dose group, 80G24, and the no treatment group, 81G17 !103/uL, P!.05. A significant, dose-dependent improvement in platelet count was first observed by 6-12 hrs after dosing between groups: the high-dose group demonstrating an improvement vs other groups, P=.005. A significant difference in treated patients persisted to 36 hours after dosing. The median increase in platelet count 24 hours after initiation of high-dose therapy was 18 !103/uL (range –25 to C106 !103/uL) and at 48 hours was 56 !103/uL (range –2 to C223 !103/uL). Regression analysis demonstrated a significant inverse relationship between platelet count at the start of therapy and quantitative increase in platelet count 24 hrs after treatment, P=.002. CONCLUSION: Glucocorticoid therapy can impact the pathophysiology of HELLP syndrome by altering laboratory testing diagnostic for the disease within 12 hours of administration of high-dose therapy this effect persists to 36 hours. This medication has a potential benefit even in more severe cases with lower initial platelet counts.
238 MOLECULAR AND CELLULAR IMPACTS OF PLACENTA-RELATED PATHOLOGIES ON PP13 IN COMPLICATED PREMATURE DELIVERIES MAREI SAMMAR1, OSCAR SADAN2, ZEHAVIT FLEISCHFARB2, HAMUTAL MEIRI1, BERTHOLD HUPPERTZ3, ABRAHAM GOLAN2, 1Diagnostic Technologies Ltd, Haifa, Israel, 2Department of Obstet & Gynecol, Wolfson Medical Center, Sackler University, Tel Aviv, Israel, 3University of Technology Aachen, Medical Faculty, Anatomy, Aachen, Germany OBJECTIVE: To study molecular and cellular pathways that placenta protein 13 (PP13) undergoes in premature pregnancies complicated by preeclampsia (PET), pregnancy induced hypertension (PIH) and preterm delivery (PTD). STUDY DESIGN: Ten parturient were enrolled. Four women with PET, two women with PIHCIUGR, two women with HELLP syndrome and two women with PTD. Gestational age at delivery was 26-34. They were matched to controls delivered at term. Placenta, amniotic fluid, umbilical cord blood and maternal blood were obtained at delivery. Placental tissues were used for cultivation of explants and analysis of PP13 by immunohistochemistry, PCR and Western blotting. RESULTS: Two forms of PP13 were identified: a 17.8 kDa form released from explants and a 15.6 kDa form which most likely resulted from posttranslational modification in the placenta. Analysis of PP13 mRNA level from placenta tissue by real-time PCR showed a significant reduction of 85.8% (SD=4.04%) (p=0.003) in PET, compared to normal. The level was reduced only by 21.2% (30.23) in PIHCIUGR, 17.9%(50.8) in HELLP, and was elevated 40.8% in PTD. Median maternal serum PP13 in normals was 336.9 pg/ml (CI 95%: C44.3), 440 pg/ml (40.6) in PET (p=0.09) compared to 247(44) in PTD (p=0.04), and 293.3(68) in PIH. Stronger labelling of the villous membrane in placenta sections labelled with PP13 antibodies was found in PET placentas compared to normal patients. CONCLUSION: The data for PP13 in this study suggests that the molecule undergoes different molecular and cellular processing in pregnancy affected by PET, PIH, HELLP and PTD.
240 MATERNAL THROMBOPHILIAS ARE NOT ASSOCIATED WITH ADVERSE PREGNANCY OUTCOME (APO): A PROSPECTIVE OBSERVATIONAL STUDY BAHA SIBAI1, 1for the NICHD MFMU Network, Bethesda, Maryland OBJECTIVE: Several studies reported an association between thrombophilia and APO. Recommendations are being made to screen such women and treat with heparin/aspirin in subsequent pregnancies. Our purpose of study was to determine whether thrombophilias are associated with APO in women without a prior history of thromboembolism. STUDY DESIGN: Secondary analysis of a multicenter, prospective observational study to evaluate Factor V Leiden mutation (FVL) status in women with no personal history of thromboembolism 93 (TE). Study population for this analysis consisted of 113 FVL carriers and controls matched 2:1 by center, race/ethnicity and age (G 5 years) for whom additional thrombophilia testing was performed. A positive test was presence of FVL mutation, prothrombin G20210A mutation, homozygote for the 5, 10 MTHFR mutation, or positive lupusanticoagulant, protein C, protein S, antithrombin III or activated protein C resistance defined as values 2SD below the mean for normal. Patients and providers were blinded to the results of the tests. APO was defined as pregnancy loss (fetal or neonatal death) or a composite of preeclampsia, abruptio placentae, or birth weight !5th %ile. Data analysis included RR and 95% C.I. Discrete and binary variables were assessed by Fisher´ s exact test. RESULTS: 173 women were positive for thrombophilias and 166 were negative. There were no differences between the groups regarding age, parity, rate of smoking, family history of thromboembolism, or race. There were no cases of TE in this cohort.. There were no differences regarding pregnancy loss or the composite APO. (Table). CONCLUSION: We found no association between thrombophilias and APO in women without personal history of thromboembolism. Routine screening for thrombophilias in the absence of a personal history of thromboembolism is not justified.
Pregnancy loss Composite outcome
Positive n=173
Negative n=166
RR (95% CI)
0% 8.1%
1.8% 9.0%
0 (0.0, 1.44) 0.89 (0.45, 1.80)
239 THE TIME COURSE RESPONSE TO CORTICOSTEROIDS IN WOMEN WITH ANTEPARTUM HELLP SYNDROME JOHN O’BRIEN1, WADE SCHWENDEMANN2, JOHN R. BARTON3, 1Baptist Health Care System, Lexington, Kentucky, 2University of Kentucky, Clinical Science: Obstetrics & Gynecology, Lexington, Kentucky, 3Central Baptist Hospital, Perinatal Diagnostic Center, Lexington, Kentucky OBJECTIVE: Our purpose was to evaluate the time course for response to glucocorticoids in women with HELLP syndrome and assess variables associated with the response. STUDY DESIGN: Patients with the antepartum HELLP syndrome from 1996-2003 were included for analysis if serial laboratory studies were obtained prior to delivery. The change in platelet count, liver function tests (LFTs), and LDH was evaluated at 6 hour intervals after the diagnosis of HELLP syndrome and initiation of therapy. Women not exposed to steroid were compared to those receiving standard doses (24 mg/day) and to those receiving a high-dose regimen (O24 mg/day). Statistical analysis was performed using non-parametric and regression analysis. RESULTS: Sixty-one patients were eligible for analysis with 28 receiving high-dose, 20 standard-dose, and 13 patients did not receive therapy. Patients in these groups had no significant differences in LFTs and LDH at diagnosis; however the mean PLT count at diagnosis was lower in the high-dose group, 57G19 vs the standard dose group, 80G24, and the no treatment group, 81G17 !103/uL, P!.05. A significant, dose-dependent improvement in platelet count was first observed by 6-12 hrs after dosing between groups: the high-dose group demonstrating an improvement vs other groups, P=.005. A significant difference in treated patients persisted to 36 hours after dosing. The median increase in platelet count 24 hours after initiation of high-dose therapy was 18 !103/uL (range –25 to C106 !103/uL) and at 48 hours was 56 !103/uL (range –2 to C223 !103/uL). Regression analysis demonstrated a significant inverse relationship between platelet count at the start of therapy and quantitative increase in platelet count 24 hrs after treatment, P=.002. CONCLUSION: Glucocorticoid therapy can impact the pathophysiology of HELLP syndrome by altering laboratory testing diagnostic for the disease within 12 hours of administration of high-dose therapy this effect persists to 36 hours. This medication has a potential benefit even in more severe cases with lower initial platelet counts.
238 MOLECULAR AND CELLULAR IMPACTS OF PLACENTA-RELATED PATHOLOGIES ON PP13 IN COMPLICATED PREMATURE DELIVERIES MAREI SAMMAR1, OSCAR SADAN2, ZEHAVIT FLEISCHFARB2, HAMUTAL MEIRI1, BERTHOLD HUPPERTZ3, ABRAHAM GOLAN2, 1Diagnostic Technologies Ltd, Haifa, Israel, 2Department of Obstet & Gynecol, Wolfson Medical Center, Sackler University, Tel Aviv, Israel, 3University of Technology Aachen, Medical Faculty, Anatomy, Aachen, Germany OBJECTIVE: To study molecular and cellular pathways that placenta protein 13 (PP13) undergoes in premature pregnancies complicated by preeclampsia (PET), pregnancy induced hypertension (PIH) and preterm delivery (PTD). STUDY DESIGN: Ten parturient were enrolled. Four women with PET, two women with PIHCIUGR, two women with HELLP syndrome and two women with PTD. Gestational age at delivery was 26-34. They were matched to controls delivered at term. Placenta, amniotic fluid, umbilical cord blood and maternal blood were obtained at delivery. Placental tissues were used for cultivation of explants and analysis of PP13 by immunohistochemistry, PCR and Western blotting. RESULTS: Two forms of PP13 were identified: a 17.8 kDa form released from explants and a 15.6 kDa form which most likely resulted from posttranslational modification in the placenta. Analysis of PP13 mRNA level from placenta tissue by real-time PCR showed a significant reduction of 85.8% (SD=4.04%) (p=0.003) in PET, compared to normal. The level was reduced only by 21.2% (30.23) in PIHCIUGR, 17.9%(50.8) in HELLP, and was elevated 40.8% in PTD. Median maternal serum PP13 in normals was 336.9 pg/ml (CI 95%: C44.3), 440 pg/ml (40.6) in PET (p=0.09) compared to 247(44) in PTD (p=0.04), and 293.3(68) in PIH. Stronger labelling of the villous membrane in placenta sections labelled with PP13 antibodies was found in PET placentas compared to normal patients. CONCLUSION: The data for PP13 in this study suggests that the molecule undergoes different molecular and cellular processing in pregnancy affected by PET, PIH, HELLP and PTD.
240 MATERNAL THROMBOPHILIAS ARE NOT ASSOCIATED WITH ADVERSE PREGNANCY OUTCOME (APO): A PROSPECTIVE OBSERVATIONAL STUDY BAHA SIBAI1, 1for the NICHD MFMU Network, Bethesda, Maryland OBJECTIVE: Several studies reported an association between thrombophilia and APO. Recommendations are being made to screen such women and treat with heparin/aspirin in subsequent pregnancies. Our purpose of study was to determine whether thrombophilias are associated with APO in women without a prior history of thromboembolism. STUDY DESIGN: Secondary analysis of a multicenter, prospective observational study to evaluate Factor V Leiden mutation (FVL) status in women with no personal history of thromboembolism 93 (TE). Study population for this analysis consisted of 113 FVL carriers and controls matched 2:1 by center, race/ethnicity and age (G 5 years) for whom additional thrombophilia testing was performed. A positive test was presence of FVL mutation, prothrombin G20210A mutation, homozygote for the 5, 10 MTHFR mutation, or positive lupusanticoagulant, protein C, protein S, antithrombin III or activated protein C resistance defined as values 2SD below the mean for normal. Patients and providers were blinded to the results of the tests. APO was defined as pregnancy loss (fetal or neonatal death) or a composite of preeclampsia, abruptio placentae, or birth weight !5th %ile. Data analysis included RR and 95% C.I. Discrete and binary variables were assessed by Fisher´ s exact test. RESULTS: 173 women were positive for thrombophilias and 166 were negative. There were no differences between the groups regarding age, parity, rate of smoking, family history of thromboembolism, or race. There were no cases of TE in this cohort.. There were no differences regarding pregnancy loss or the composite APO. (Table). CONCLUSION: We found no association between thrombophilias and APO in women without personal history of thromboembolism. Routine screening for thrombophilias in the absence of a personal history of thromboembolism is not justified.
Pregnancy loss Composite outcome
Positive n=173
Negative n=166
RR (95% CI)
0% 8.1%
1.8% 9.0%
0 (0.0, 1.44) 0.89 (0.45, 1.80)