- Email: [email protected]
T11.1 Association between stillbirth, fetal growth restriction and hypertensive diseases in pregnancy
State of the Art Lectures, Plenary Presentations and Oral Communications / Pregnancy Hypertension 1, Supplement 1 (2010) S1–S41
T10.4 The role of oxidative stress, inflammation, endothelial dysfunction, metabolic factors, angiogenic and antiangiogenic factors in the pathophysiology of preeclampsia: randomized controlled clinical trial on the effect of antioxidant in the prevention of preeclampsia Noroyono Wibowo 1 , Ali Sungkar 1 , Yuditiya Purwosunu 1 , Akihiko Sekizawa 2 , Antonio Farina 3 . 1 Department of Obstetrics and Gynecology, University of Indonesia, Cipto Mangunkusumo National Hospital, Jakarta, Indonesia; 2 Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan; 3 Department of Histology and Embryology Division of Prenatal Medicine, University of Bologna, Bologna, Italy Objective: To investigate the effect of antioxidants-enriched milk for prevention of preeclampsia. Methods: 104 pregnant women were identified as being at increased risk of preeclampsia and having low antioxidant capacity by FRAP (ferric reducing ability of plasma) level 900 nmol/mg protein or less and were randomly assigned antioxidants-enriched milk formula or standard milk formula at 8-12 weeks’ gestation. The antioxidants-enriched milk formula contained various compound of nutrients, including, but not limited to, 200 g protein of whey cystein, 2 mg copper (Cu), 15 mg zinc (Zn), 0.5 mg manganese (Mg), 30 mg iron (Fe), 10000 IU vitamin A, 2.2 mg vitamin B6, 2.2 vitamin B12, 200 mg vitamin C, 400 IU vitamin E, 400 μg folic acid, 100 μg selenium, and 800 mg calcium (Ca). The milk was taken twice a day until 2-week-postpartum. Plasma FRAP, high sensitivity C-reactive protein (hs-CRP), glucose, insulin, triglyceride, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), asymmetric dimethylarginine (ADMA), and soluble endoglin (sEng); as well as blood mRNA extracelullar superoxide dismutase (ecSOD), heme oxygenase-1 (HO1), endoglin (Eng), fms-like tyrosine kinase-1 (Flt-1), and placental growth factor (PlGF) were measured at second and third trimester of pregnancy, and postpartum period. Results: Supplementation with antioxidants-enriched milk formula was associated with a decrease in preeclampsia incidence from 14.5% to 2% (p=0.034). Antioxidant status was found to be significantly lower in preeclampsia group (mRNA ecSOD p<0.001; mRNA HO-1 p<0.001), and higher in antioxidant group (mRNA ecSOD, p<0.001; mRNA HO-1, p<0.001). Angiogenic factor was significantly lower in preeclampsia group (mRNA PlGF, p<0,001) but higher in antioxidant group (mRNA PlGF, p<0.001). In contrast, antiangiogenic factors were significantly higher in preeclampsia group (mRNA sFlt-1, p<0.001), while lower in antioxidant group (mRNA sFlt-1, p<0.001). Insulin resistance (HOMA-IR, p=0.006; fasting insulin, p=0.006; post-load insulin, p=0.005) and inflammation factor (hs-CRP, p=0.025) was shown to have significant greater influence to preeclampsia. Conclusions: In this study, supplementation with antioxidants-enriched milk formula decreased the incidence of preeclampsia.
baseline showed significantly better CrCl in response to DIF compared with placebo (p=0.03). For the other clinical variables, numbers were few, but differences between treatments were generally greater in subgroups with SP inhibition Conclusions: These data suggest subjects with measurable EDLF activity, particularly high serum EDLF activity are more likely to respond to DIF. These results support further research in this area Reference(s) [1] Adair CD, et al., Digoxin Immune Fab Treatment for Severe Preeclampsia. Am J Perinatol 2010 [epub].
T11.1 Association between stillbirth, fetal growth restriction and hypertensive diseases in pregnancy Tony Odibo 1, Andre Francis 2 , Alison Cahill 1 , Roxanne Rampersad 1 , George Macones 1 , Jason Gardosi 2 . 1 Washington University, St Louis, USA; 2 West Midlands Perinatal Institute, West Midlands, UK Objective: Hypertensive diseases in pregnancy as well as smoking are associated with prematurity and intrauterine growth restriction (IUGR). However recent studies have suggested that smoking throughout pregnancy has a protective effect, reducing the incidence of preeclampsia and gestational hypertension (PE/GH). We set out to investigate the relative effects that PE/GH and smoking have on prematurity and IUGR. Method: The data were extracted from a routinely collected database of 39,728 women delivered between July 2009 and March 2010 in the West Midlands. Because of considerable ethnic heterogeneity associated with smoking rates, this analysis included British-European mothers only (n=27,645, 69.6%). Smoking throughout pregnancy was categorised as light (<10) or heavy (10+ cigarettes per day). Prematurity was defined as birth <37 weeks gestation, and IUGR as birthweight below the 10th customised centile, adjusted for maternal height, weight, parity as well as fetal sex and gestational age at birth. Results: The incidence of pre-eclampsia in this population was 1.2%, and gestational hypertension 4.5%. The two conditions were combined to allow sufficient numbers for subgroup analysis. 14.4% of women smoked throughout pregnancy, including 5.9% light (<10) and 8.9% heavy smokers (20+ cigarettes per day). The findings are summarised in the table. Compared to the PE/GH rate for non smokers, 6.1%, mothers who smoked throughout pregnancy had significantly lower rates of PE/GH, regardless of the number of cigarettes smoked. However, despite lower rates of hypertensive diseases in pregnancy, women who smoked had significantly increased rates of prematurity and IUGR than non-smokers, and these differences were dose dependent. PE/GH %
T10.5
OR
Preterm CI
& <37w OR
Digoxin Immune Fab treatment for severe preclampsia; relationship between response and baseline endogenous digitalis-like factor
Non-smolers 6.1 * Light smokers (<10) 4.0 0.6 0.4-0.9 Heavy smokers (10+) 4.0 0.6 0.5-0.9
C. David Adair, Vardaman Buckalew, Steven W. Graves, Nikhil Chauhan, Garrett Lam on behalf of the entire DEEP Study Group, USA
*Reference for OR. w = week, cc = customised centile.
Background: We previously reported positive results on the use of a Digoxin Immune Fab (DIF) for treatment of severe preeclampsia [1]. DIF, relative to placebo, prevented a decline in CrCl and lowered levels of endogenous digitalis-like factor (EDLF) activity as measured by sodium pump inhibition (SPI). Accordingly, we conducted a secondary subanalysis evaluating whether DIF response was dependent on pretreatment serum EDLF activity. Aim: Determine if subjects with baseline EDLF activity were more likely to respond to DIF Methods: The methods for this RCT were previously reported [1]. In this subanalysis, subjects were divided into three subgroups, baseline SPI 0%, > to <30%, and >30%. Change in circulating EDLF levels and CrCl in response to DIF or placebo was evaluated within subgroups using ANCOVA. Frequencies of other clinical symptoms sequelae were compared using Fisher’s Exact Test. Results: 45 subjects (23 DIF, 22 placebo) had baseline SPI evaluated: 22% had undetectable baseline SPI 33% had >0 to <30% and 44% had >30%. Subjects with EDLF levels showed significantly reduced levels of SPI in response to DIF at each time point (12, 24, 48 hr) whereas subjects with undetectable EDLF showed no significant change in response to DIF or placebo. For CrCl analysis, subjects having undetectable EDLF showed deterioration of CrCl with or without DIF. Those having high ELDF levels at
S21
6.3 7.3 9.8
IUGR CI
* 1.2 0.9-1.6 1.6 1.3-2.0
% <10th cc OR 11.8 22.9 29.4
CI
* 2.2 1.9-2.6 3.1 2.7-3.6
Conclusion: Smoking during pregnancy reduces the incidence of hypertensive diseases, or at least their clinical manifestation, regardless of the number of cigarettes smoked. Despite this effect, pregnancies with maternal smoking have a significantly increased, dose dependent risk of prematurity and intrauterine growth restriction.
T11.2 Evaluation of the oxidative state of maternal serum low density lipoproteins in intrauterine growth restriction and preeclampsia Ulrich Pecks 1 , Raphaela Caspers 1 , Barbara Schiessl 1 , Dirk Bauerschlag 1 , Daniela Piroth 2 , Nicolai Maass 1 , Werner Rath 1 . 1 University Hospital of the RWTH, Department of O&G, Aachen, Germany; 2 University Hospital of the RWTH, Neonatology, Aachen, Germany Introduction: Altered maternal lipid concentration and lipoprotein profile has been suggested to play a role in the pathogenesis of preeclampsia (PE) and intrauterine growth restriction (IUGR): LDL subfractions shift towards an atherogenic phenotype. The small and dense LDL particles exhibit enhanced oxidation susceptibility to free radicals. Assuming that maternal oxidative stress and an atherogenic lipid profile are involved in the pathogenesis of IUGR and PE we evaluated the oxidative state and
T10.4 The role of oxidative stress, inflammation, endothelial dysfunction, metabolic factors, angiogenic and antiangiogenic factors in the pathophysiology of preeclampsia: randomized controlled clinical trial on the effect of antioxidant in the prevention of preeclampsia Noroyono Wibowo 1 , Ali Sungkar 1 , Yuditiya Purwosunu 1 , Akihiko Sekizawa 2 , Antonio Farina 3 . 1 Department of Obstetrics and Gynecology, University of Indonesia, Cipto Mangunkusumo National Hospital, Jakarta, Indonesia; 2 Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan; 3 Department of Histology and Embryology Division of Prenatal Medicine, University of Bologna, Bologna, Italy Objective: To investigate the effect of antioxidants-enriched milk for prevention of preeclampsia. Methods: 104 pregnant women were identified as being at increased risk of preeclampsia and having low antioxidant capacity by FRAP (ferric reducing ability of plasma) level 900 nmol/mg protein or less and were randomly assigned antioxidants-enriched milk formula or standard milk formula at 8-12 weeks’ gestation. The antioxidants-enriched milk formula contained various compound of nutrients, including, but not limited to, 200 g protein of whey cystein, 2 mg copper (Cu), 15 mg zinc (Zn), 0.5 mg manganese (Mg), 30 mg iron (Fe), 10000 IU vitamin A, 2.2 mg vitamin B6, 2.2 vitamin B12, 200 mg vitamin C, 400 IU vitamin E, 400 μg folic acid, 100 μg selenium, and 800 mg calcium (Ca). The milk was taken twice a day until 2-week-postpartum. Plasma FRAP, high sensitivity C-reactive protein (hs-CRP), glucose, insulin, triglyceride, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), asymmetric dimethylarginine (ADMA), and soluble endoglin (sEng); as well as blood mRNA extracelullar superoxide dismutase (ecSOD), heme oxygenase-1 (HO1), endoglin (Eng), fms-like tyrosine kinase-1 (Flt-1), and placental growth factor (PlGF) were measured at second and third trimester of pregnancy, and postpartum period. Results: Supplementation with antioxidants-enriched milk formula was associated with a decrease in preeclampsia incidence from 14.5% to 2% (p=0.034). Antioxidant status was found to be significantly lower in preeclampsia group (mRNA ecSOD p<0.001; mRNA HO-1 p<0.001), and higher in antioxidant group (mRNA ecSOD, p<0.001; mRNA HO-1, p<0.001). Angiogenic factor was significantly lower in preeclampsia group (mRNA PlGF, p<0,001) but higher in antioxidant group (mRNA PlGF, p<0.001). In contrast, antiangiogenic factors were significantly higher in preeclampsia group (mRNA sFlt-1, p<0.001), while lower in antioxidant group (mRNA sFlt-1, p<0.001). Insulin resistance (HOMA-IR, p=0.006; fasting insulin, p=0.006; post-load insulin, p=0.005) and inflammation factor (hs-CRP, p=0.025) was shown to have significant greater influence to preeclampsia. Conclusions: In this study, supplementation with antioxidants-enriched milk formula decreased the incidence of preeclampsia.
baseline showed significantly better CrCl in response to DIF compared with placebo (p=0.03). For the other clinical variables, numbers were few, but differences between treatments were generally greater in subgroups with SP inhibition Conclusions: These data suggest subjects with measurable EDLF activity, particularly high serum EDLF activity are more likely to respond to DIF. These results support further research in this area Reference(s) [1] Adair CD, et al., Digoxin Immune Fab Treatment for Severe Preeclampsia. Am J Perinatol 2010 [epub].
T11.1 Association between stillbirth, fetal growth restriction and hypertensive diseases in pregnancy Tony Odibo 1, Andre Francis 2 , Alison Cahill 1 , Roxanne Rampersad 1 , George Macones 1 , Jason Gardosi 2 . 1 Washington University, St Louis, USA; 2 West Midlands Perinatal Institute, West Midlands, UK Objective: Hypertensive diseases in pregnancy as well as smoking are associated with prematurity and intrauterine growth restriction (IUGR). However recent studies have suggested that smoking throughout pregnancy has a protective effect, reducing the incidence of preeclampsia and gestational hypertension (PE/GH). We set out to investigate the relative effects that PE/GH and smoking have on prematurity and IUGR. Method: The data were extracted from a routinely collected database of 39,728 women delivered between July 2009 and March 2010 in the West Midlands. Because of considerable ethnic heterogeneity associated with smoking rates, this analysis included British-European mothers only (n=27,645, 69.6%). Smoking throughout pregnancy was categorised as light (<10) or heavy (10+ cigarettes per day). Prematurity was defined as birth <37 weeks gestation, and IUGR as birthweight below the 10th customised centile, adjusted for maternal height, weight, parity as well as fetal sex and gestational age at birth. Results: The incidence of pre-eclampsia in this population was 1.2%, and gestational hypertension 4.5%. The two conditions were combined to allow sufficient numbers for subgroup analysis. 14.4% of women smoked throughout pregnancy, including 5.9% light (<10) and 8.9% heavy smokers (20+ cigarettes per day). The findings are summarised in the table. Compared to the PE/GH rate for non smokers, 6.1%, mothers who smoked throughout pregnancy had significantly lower rates of PE/GH, regardless of the number of cigarettes smoked. However, despite lower rates of hypertensive diseases in pregnancy, women who smoked had significantly increased rates of prematurity and IUGR than non-smokers, and these differences were dose dependent. PE/GH %
T10.5
OR
Preterm CI
& <37w OR
Digoxin Immune Fab treatment for severe preclampsia; relationship between response and baseline endogenous digitalis-like factor
Non-smolers 6.1 * Light smokers (<10) 4.0 0.6 0.4-0.9 Heavy smokers (10+) 4.0 0.6 0.5-0.9
C. David Adair, Vardaman Buckalew, Steven W. Graves, Nikhil Chauhan, Garrett Lam on behalf of the entire DEEP Study Group, USA
*Reference for OR. w = week, cc = customised centile.
Background: We previously reported positive results on the use of a Digoxin Immune Fab (DIF) for treatment of severe preeclampsia [1]. DIF, relative to placebo, prevented a decline in CrCl and lowered levels of endogenous digitalis-like factor (EDLF) activity as measured by sodium pump inhibition (SPI). Accordingly, we conducted a secondary subanalysis evaluating whether DIF response was dependent on pretreatment serum EDLF activity. Aim: Determine if subjects with baseline EDLF activity were more likely to respond to DIF Methods: The methods for this RCT were previously reported [1]. In this subanalysis, subjects were divided into three subgroups, baseline SPI 0%, > to <30%, and >30%. Change in circulating EDLF levels and CrCl in response to DIF or placebo was evaluated within subgroups using ANCOVA. Frequencies of other clinical symptoms sequelae were compared using Fisher’s Exact Test. Results: 45 subjects (23 DIF, 22 placebo) had baseline SPI evaluated: 22% had undetectable baseline SPI 33% had >0 to <30% and 44% had >30%. Subjects with EDLF levels showed significantly reduced levels of SPI in response to DIF at each time point (12, 24, 48 hr) whereas subjects with undetectable EDLF showed no significant change in response to DIF or placebo. For CrCl analysis, subjects having undetectable EDLF showed deterioration of CrCl with or without DIF. Those having high ELDF levels at
S21
6.3 7.3 9.8
IUGR CI
* 1.2 0.9-1.6 1.6 1.3-2.0
% <10th cc OR 11.8 22.9 29.4
CI
* 2.2 1.9-2.6 3.1 2.7-3.6
Conclusion: Smoking during pregnancy reduces the incidence of hypertensive diseases, or at least their clinical manifestation, regardless of the number of cigarettes smoked. Despite this effect, pregnancies with maternal smoking have a significantly increased, dose dependent risk of prematurity and intrauterine growth restriction.
T11.2 Evaluation of the oxidative state of maternal serum low density lipoproteins in intrauterine growth restriction and preeclampsia Ulrich Pecks 1 , Raphaela Caspers 1 , Barbara Schiessl 1 , Dirk Bauerschlag 1 , Daniela Piroth 2 , Nicolai Maass 1 , Werner Rath 1 . 1 University Hospital of the RWTH, Department of O&G, Aachen, Germany; 2 University Hospital of the RWTH, Neonatology, Aachen, Germany Introduction: Altered maternal lipid concentration and lipoprotein profile has been suggested to play a role in the pathogenesis of preeclampsia (PE) and intrauterine growth restriction (IUGR): LDL subfractions shift towards an atherogenic phenotype. The small and dense LDL particles exhibit enhanced oxidation susceptibility to free radicals. Assuming that maternal oxidative stress and an atherogenic lipid profile are involved in the pathogenesis of IUGR and PE we evaluated the oxidative state and