The risk factors for both preeclampsia (PE) and gestational hypertension (GH) are limited. Recent... more The risk factors for both preeclampsia (PE) and gestational hypertension (GH) are limited. Recent data suggested that decreased circulating galectin-1 ( Gal-1), which binds to neuropirin-1, may have a pathologic role. Our aim was to evaluate whether serum level of Gal-1 in the second trimester could predict not only PE but also GH. We prospectively recruited 1413 women at 19-25weeks, and serum levels of soluble endoglin (sEng) and Gal-1 were measured in consecutive 72 normal pregnant women, and all women with PE (n=36) and GH (n=21). Gal-1 in women with subsequent onset of PE and GH was significantly lower than in controls, respectively (median [interquartile range]: 8.21 [6.05-10.11], 7.73 [6.41-10.56] vs. 9.84 [8.39-10.56]). High blood pressure (BP) (⩾120/80mmHg), abnormal uterine artery Doppler, sEng ⩾2.5th percentile, and Gal-1 < first quartile value were independent risk factors for predicting PE (adjusted odds ratio [aOR] and 95% confidence interval [95%CI]: 5.6 [1.6-19.8], 7.4 [1.8-30.6], 12.9 [3.8-43.6] and 5.6 [1.6-19.4], respectively), and combined use of them yielded a sensitivity, specificity, and positive likelihood ratio (LR+) (95% CI) of 78%, 93%, 10.7 (4.5-24.5), respectively. In addition, high BP, high sEng and low Gal-1 were independent risk factors for GH (aOR and 95% CI: 5.7 [1.5-21.9], 5.7 [1.5-21.3] and 4.2 [1.2-15.1], respectively), and combined use of them yielded a sensitivity, specificity, and LR+ of 60%, 89%, 5.3 [2.5-11.2], respectively. Decreased levels of Gal-1 in the second trimester predict the subsequent onset of not only PE but also GH. A. Ohkuchi: None. C. Hirashima: None. S. Nagayama: None. H. Suzuki: None. K. Takahashi: None. S. Matsubara: None. M. Suzuki: None.
INTRODUCTION Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. S... more INTRODUCTION Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. Several studies have demonstrated the beneficial effects of antithrombin replacement in patients with preeclampsia. Here, we describe the study protocol of KOUNO-TORI (KW-3357 randOmized, mUlti-center, double-bliNd, placebO-controlled phase 3 sTudy in patients with early Onset pReeclampsIa) to evaluate recombinant human antithrombin gamma (rhAT-gamma) for the treatment of early-onset severe de novo preeclampsia. MATERIAL AND METHODS Patients with early-onset severe de novo preeclampsia who are ≥24 to <32 weeks pregnant at the time of registration and have an antithrombin activity of ≤100% at screening are included. The target population is selected based on a reanalysis of the data of a previous plasma-derived antithrombin phase 3 study. Primary endpoint is the prolongation of pregnancy from the initiation of rhAT-gamma treatment to the pregnancy termination. Secondary endpoints include gestational age in terms of achievement of 32- and 34-weeks'gestation, and gestational age in terms of achievement of 28 weeks' gestation for patients enrolled at <28 weeks' gestation. Maternal, fetal, and neonatal outcomes will be assessed. DISCUSSION As we have selected a specifically defined target population based on reanalysis of data of a previous plasma-derived antithrombin phase 3 study, the results of our study are expected to provide efficacy and safety data concerning rhAT-gamma treatment in Japanese patients. This study could help identify an effective novel treatment for such patients with early-onset severe preeclampsia for whom appropriate treatment is unavailable.
Background Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Ea... more Background Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management. Objectives To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers. Design This was an individual participant data meta-analysis of cohort studies. Setting Source data from secondary and tertiary care. Predictors We identified predictors from systematic reviews, and prioritised for importance in an international survey. Primary outcomes Early-onset (delivery at < 34 weeks’ gestation), late-onset (delivery at ≥ 34 weeks’ gestation) and any-onset pre-eclampsia. Analysis We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models ...
The risk factors for both preeclampsia (PE) and gestational hypertension (GH) are limited. Recent... more The risk factors for both preeclampsia (PE) and gestational hypertension (GH) are limited. Recent data suggested that decreased circulating galectin-1 ( Gal-1), which binds to neuropirin-1, may have a pathologic role. Our aim was to evaluate whether serum level of Gal-1 in the second trimester could predict not only PE but also GH. We prospectively recruited 1413 women at 19-25weeks, and serum levels of soluble endoglin (sEng) and Gal-1 were measured in consecutive 72 normal pregnant women, and all women with PE (n=36) and GH (n=21). Gal-1 in women with subsequent onset of PE and GH was significantly lower than in controls, respectively (median [interquartile range]: 8.21 [6.05-10.11], 7.73 [6.41-10.56] vs. 9.84 [8.39-10.56]). High blood pressure (BP) (⩾120/80mmHg), abnormal uterine artery Doppler, sEng ⩾2.5th percentile, and Gal-1 &amp;amp;lt; first quartile value were independent risk factors for predicting PE (adjusted odds ratio [aOR] and 95% confidence interval [95%CI]: 5.6 [1.6-19.8], 7.4 [1.8-30.6], 12.9 [3.8-43.6] and 5.6 [1.6-19.4], respectively), and combined use of them yielded a sensitivity, specificity, and positive likelihood ratio (LR+) (95% CI) of 78%, 93%, 10.7 (4.5-24.5), respectively. In addition, high BP, high sEng and low Gal-1 were independent risk factors for GH (aOR and 95% CI: 5.7 [1.5-21.9], 5.7 [1.5-21.3] and 4.2 [1.2-15.1], respectively), and combined use of them yielded a sensitivity, specificity, and LR+ of 60%, 89%, 5.3 [2.5-11.2], respectively. Decreased levels of Gal-1 in the second trimester predict the subsequent onset of not only PE but also GH. A. Ohkuchi: None. C. Hirashima: None. S. Nagayama: None. H. Suzuki: None. K. Takahashi: None. S. Matsubara: None. M. Suzuki: None.
INTRODUCTION Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. S... more INTRODUCTION Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. Several studies have demonstrated the beneficial effects of antithrombin replacement in patients with preeclampsia. Here, we describe the study protocol of KOUNO-TORI (KW-3357 randOmized, mUlti-center, double-bliNd, placebO-controlled phase 3 sTudy in patients with early Onset pReeclampsIa) to evaluate recombinant human antithrombin gamma (rhAT-gamma) for the treatment of early-onset severe de novo preeclampsia. MATERIAL AND METHODS Patients with early-onset severe de novo preeclampsia who are ≥24 to <32 weeks pregnant at the time of registration and have an antithrombin activity of ≤100% at screening are included. The target population is selected based on a reanalysis of the data of a previous plasma-derived antithrombin phase 3 study. Primary endpoint is the prolongation of pregnancy from the initiation of rhAT-gamma treatment to the pregnancy termination. Secondary endpoints include gestational age in terms of achievement of 32- and 34-weeks'gestation, and gestational age in terms of achievement of 28 weeks' gestation for patients enrolled at <28 weeks' gestation. Maternal, fetal, and neonatal outcomes will be assessed. DISCUSSION As we have selected a specifically defined target population based on reanalysis of data of a previous plasma-derived antithrombin phase 3 study, the results of our study are expected to provide efficacy and safety data concerning rhAT-gamma treatment in Japanese patients. This study could help identify an effective novel treatment for such patients with early-onset severe preeclampsia for whom appropriate treatment is unavailable.
Background Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Ea... more Background Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management. Objectives To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers. Design This was an individual participant data meta-analysis of cohort studies. Setting Source data from secondary and tertiary care. Predictors We identified predictors from systematic reviews, and prioritised for importance in an international survey. Primary outcomes Early-onset (delivery at < 34 weeks’ gestation), late-onset (delivery at ≥ 34 weeks’ gestation) and any-onset pre-eclampsia. Analysis We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models ...
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Papers by Akihide Ohkuchi