Noroyono Wibowo

Lower Rate of Preeclampsia After Antioxidant Supplementation in Pregnant Women with Low Antioxidant Status

Objective: To investigate maternal and neonatal outcomes after antioxidant supplementation relatively early in pregnancy (8 to 12 weeks) for pregnant women with low antioxidant status. Methods: A randomized, double-blind, placebo-controlled trial of daily antioxidant supplementation was performed on pregnant women screening positive for low antioxidant status at 8 to 12 weeks of gestation. Low antioxidant status was defined as a superoxidedismutase (SOD) level below 1102 U/g Hb or 164 U/mL. The supplementation group received the following antioxidants daily: vitamins A (1000 IU), B6 (2.2 mg), B12 (2.2 μg), C (200 mg), and E (400 IU), folic acid (400 μg), N-acetylcysteine (200 mg), Cu (2 mg), Zn (15 mg), Mn (0.5 mg), Fe (30 mg), calcium (800 mg), and selenium (100 μg). The control group received Fe (30 mg) and folic acid (400 μg). Maternal (preeclampsia, abortion, and hypertension) and perinatal outcomes were assessed. Results: In the supplementation group (29 subjects), we observed 2 cases of preeclampsia (6.8%, 1 mild and 1 severe), 1 of IUGR (birth weight 2300 g at 38 weeks), and 1 preterm delivery. In the control group (31 subjects), there were 8 abortions, 9 cases of preeclampsia (29%, 6 mild and 3 severe) with perinatal outcome: 3 preterm delivery cases and 1 IUGR (birth weight 2030 g at 39 weeks). Preeclampsia was significantly less frequent in the supplementation group when compared to the control group (2 vs. 9 cases, p = 0.043, OR = 0.18 [95% CI: 0.03, 0.92]). Finally we focused on the prediction of preeclampsia at 8 to 12 weeks. Combined sensitivity of markers of antioxidant status (SOD slutathione peroxidase, [GPx], and total anti-oxidant status [TAS]) was 33% (false-positive rate of 4.5%). Conclusion: Antioxidant supplementation was associated with better maternal and perinatal outcome in pregnant women with low antioxidant status than control supplementation with iron and folate alone. In a selected population already screened positive for low SOD, preeclampsia can be detected in 33% of asymptomatic cases in the first trimester using SOD, GPx, and TAS. It seems feasible that panels of both biochemical and molecular markers may be clinically useful in the prediction of this disease.

Prediction of preeclampsia by analysis of cell-free messenger RNA in maternal plasma

OBJECTIVE The purpose of this study was to predict the occurrence of preeclampsia in a series of patients at gestational week 15-20 weeks, with the use of a panel of messenger RNA markers. STUDY DESIGN Data from 62 patients with preeclampsia who were asymptomatic at the time of blood testing and 310 control subjects were analyzed. Multivariable analysis was performed with discriminant analysis. RESULTS Univariable analysis identified vascular endothelial growth factor receptor 1 as the marker with the highest detection rate; placenta-specific 1 with the lowest. Mean estimated score for preeclampsia was 9.4 for control subjects and 72.5 for subjects who experienced preeclampsia. A receiver operating characteristic curve that was obtained with the estimated score for preeclampsia as a test variable yielded a detection rate of 84% (95% CI, 71.8-91.5) at a 5% false-positive rate with an area under the curve of 0.927 (P < .001). Again, detection rate and score for each patient for classification as preeclamptic correlated with severity. CONCLUSION A panel of messenger RNA is able to detect subjects who will experience preeclampsia.

Cellular mRNA expressions of anti-oxidant factors in the blood of preeclamptic women

To assess the alterations of mRNA expressions associated with oxidative stress in the cellular component of blood from pregnant women with pre‐eclampsia.

Placenta-derived, cellular messenger RNA expression in the maternal blood of preeclamptic women.

OBJECTIVE: To perform gene expression profiling and real-time quantitative reverse-transcription polymerase chain reaction (PCR) analysis to identify biomarkers of preeclampsia in cellular messenger RNA (mRNA) from maternal blood. METHODS: We performed a microarray analysis with five maternal blood samples from women with preeclampsia and five matched control subjects. Up-regulated gene expression was further analyzed through reverse-transcription PCR analysis with 28 consecutive blood samples from women affected with preeclampsia and 29 controls. RESULTS: Both pregnancy-specific &bgr;1 glycoprotein and trophoblast glycoprotein were selected based on microarray analysis. Reverse-transcription PCR analysis detected significantly increased mRNA concentrations among women in the preeclampsia group. When stratified according to mild or severe preeclampsia, 19.2-fold and 41.8-fold increases in pregnancy-specific &bgr;1 glycoprotein and 8.3-fold and 10.6-fold increases in trophoblast glycoprotein were observed, respectively. Among women with hemolysis, elevated liver enzymes, and low platelet count syndrome, 51.6-fold and 13.1-fold increases in pregnancy-specific &bgr;1 glycoprotein and trophoblast glycoprotein were observed, respectively. In the preeclampsia group, pregnancy-specific &bgr;1 glycoprotein correlated with severity of proteinuria (P<.001) and systolic blood pressure (P=.01). CONCLUSION: The mRNA expression of pregnancy-specific &bgr;1 glycoprotein and trophoblast glycoprotein is up-regulated in cells circulating within blood from women with preeclampsia, and pregnancy-specific &bgr;1 glycoprotein expression is positively correlated with the clinical severity of preeclampsia. LEVEL OF EVIDENCE: II

Evaluation of physiological alterations of the placenta through analysis of cell-free messenger ribonucleic acid concentrations of angiogenic factors

OBJECTIVE Placental messenger ribonucleic acid (mRNA) has been shown to circulate in maternal plasma. We investigated concentrations of vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGFR-1), and endoglin in subjects with preeclampsia, compared with normal pregnancies. STUDY DESIGN Peripheral blood samples were obtained from preeclampsia (n = 43) and control subjects (n = 41). Plasma ribonucleic acid was subjected to analysis by reverse transcription-polymerase chain reaction assay to examine the mRNA distribution among women with preeclampsia and control subjects during weeks 35-41 of gestation. RESULTS Concentrations of VEGF, VEGFR-1, and endoglin mRNA of women with preeclampsia were significantly increased. The mRNA values were observed to correlate directly with the severity of hypertension and proteinuria. VEGFR-1 mRNA was markedly elevated in women with preeclampsia and hemolysis, elevated liver enzymes, and low platelet syndrome. CONCLUSION The mRNA concentrations of VEGF, VEGFR-1, and endoglin were observed to correlate directly with the severity of preeclampsia.

Antioxidant supplementation in pregnant women with low antioxidant status

Aim:  The aim of this study was to investigate the benefit of antioxidant supplementation in a cohort of women with low antioxidant status and determine the changes in cell‐free mRNA.

Expression of angiogenesis-related genes in the cellular component of the blood of preeclamptic women.

The purpose of this study is to assess the changes in the expression of angiogenesis-related genes in the cellular component of the blood from preeclamptic patients. Blood samples were obtained from the preeclampsia (PE) and control participants. Cellular RNA was analyzed by reverse transcription polymerase chain reaction (PCR) to identify any angiogenesis-related genes and thereby assess the mRNA expression among women with PE and controls during weeks 35 to 41 of gestation. Significant differences were observed between PE and controls in all of the angiogenesis-related genes examined. In PE, for the increased expression of transforming growth factor-β1 (TGF-β1), endoglin and fms-like tyrosine kinase-1 (Flt-1); and the reduced expression of vascular endothelial growth factor (VEGF), placental growth factor (PlGF). fms-Like tyrosine kinase-1 and endoglin significantly correlated with the systolic pressure, while VEGF, Flt-1, and endoglin all correlated with proteinuria. An altered expression of angiogenesis-related genes was demonstrated in the cellular component of blood from preeclamptic patients. These findings indicate that this approach may offer an alternative way for evaluating the pathogenesis of PE.

Prediction of pre-eclampsia by an analysis of placenta-derived cellular mRNA in the blood of pregnant women at 15–20 weeks of gestation

Please cite this paper as: Sekizawa A, Purwosunu Y, Farina A, Shimizu H, Nakamura M, Wibowo N, Rizzo N, Okai T. Prediction of pre‐eclampsia by an analysis of placenta‐derived cellular mRNA in the blood of pregnant women at 15–20 weeks of gestation. BJOG 2010;117:557–564.

Vitamin B6 supplementation in pregnant women with nausea and vomiting

To determine whether supplementation with vitamin B6 improves nausea and/or vomiting in pregnancy.

Vitamin B₆ supplementation in pregnant women with nausea and vomiting.

To determine whether supplementation with vitamin B6 improves nausea and/or vomiting in pregnancy.