Hypertension Research in Pregnancy
Online ISSN : 2187-9931
Print ISSN : 2187-5987
ISSN-L : 2187-5987
Volume 1, Issue 2
Displaying 1-10 of 10 articles from this issue
Review
  • Keizo Kanasaki, Megumi Kanasaki
    Article type: REVIEW ARTICLE
    2013 Volume 1 Issue 2 Pages 57-65
    Published: October 24, 2013
    Released on J-STAGE: January 29, 2014
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    Preeclampsia is a devastating pregnancy-associated hypertensive syndrome. Although it is quite common, the pathophysiology of preeclampsia is not yet clear and remains “a disease of theory”. Angiogenic defect hypotheses have been intensively investigated, and some biomarkers have been independently analyzed as pathogenic clinical target molecules without direct proof of their roles in preeclampsia. In this review, we assessed an up-to-date list of proposed angiogenic defects for their relevance to preeclampsia. In addition, we introduce our working hypothesis of preeclampsia pathophysiology, which involves interactions between metabolic and angiogenic defects.
  • Tatsuo Yamamoto, Fumihisa Chishima, Masahiko Matsuura
    Article type: REVIEW
    2013 Volume 1 Issue 2 Pages 66-70
    Published: October 24, 2013
    Released on J-STAGE: January 29, 2014
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    Angiogenic factors play important roles in the regulation of placental vasculogenesis, and placental vascular development may be regulated by a local balance between angiogenic and antiangiogenic factors. Vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) are potent angiogenic growth factors capable of inducing proliferation, migration, and activation of endothelial cells. Soluble vascular endothelial growth factor receptor 1 (sVEGFR1) functions as an antagonist of both VEGF and PlGF. In this review, we survey literature on the use of peripheral blood PlGF levels or the sFlt-1/PlGF ratio to predict preeclampsia. While peripheral blood PlGF levels may not be clinically useful for predicting preeclampsia, the sFlt-1/PlGF ratio is a promising tool for assessing the risk of early-onset preeclampsia, although the sFlt-1/PlGF ratio does not perform well as a screening test for preeclampsia.
Original Articles
  • Shintaro Makino, Atsushi Iwata, Hiroyuki Seki, Satoru Takeda
    Article type: ORIGINAL ARTICLE
    2013 Volume 1 Issue 2 Pages 71-74
    Published: October 24, 2013
    Released on J-STAGE: January 29, 2014
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    Aim: We investigated incidences of pregnancy induced hypertension (PIH) and prolonged symptoms (hypertension and/or proteinuria) during the puerperal period, focusing on blood pressure in the early second trimester.
    Methods: Initial blood pressure data at 16 to 20 weeks of gestation were available from 1,398 women for analysis. Data were classified into the following groups: normal, mild pre-hypertension (preHT), severe preHT, and hypertension, according to JNC-7 criteria. Both the incidence and duration of symptoms were investigated in each group.
    Results: PIH incidences significantly increased as initial blood pressure increased. Also, significantly prolonged puerperal periods were observed in cases of severe preHT.
    Conclusions: Our data confirmed that initial blood pressure may be a useful predictor of subsequent PIH. Remaining symptoms in the puerperal period may be caused by latent endothelial cell dysfunction seen in preHT before or in early pregnancy.
  • Mamoru Morikawa, Takashi Yamada, Takahiro Yamada, Shoji Sato, Kazutosh ...
    Article type: ORIGINAL ARTICLE
    2013 Volume 1 Issue 2 Pages 75-80
    Published: October 24, 2013
    Released on J-STAGE: January 29, 2014
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    Aims: We aimed to determine the effects of nulliparity, maternal age, and pre-pregnancy body mass index (BMI, kg/m2) on the development of pregnancy induced hypertension (PIH) in Japanese women, including gestational hypertension (GH) and preeclampsia (PE).
    Methods: Data on 138,530 women with singleton pregnancies who were registered with the Japan Society of Obstetrics and Gynecology and gave birth at ≥22 weeks of gestation during the three years from 2007 and 2009 were analyzed.
    Results: PIH was diagnosed in 6,578 (4.7%) women, including 3,326 (2.4%) with GH and 3,252 (2.3%) with PE. PIH was more frequent in nulliparous than multiparous women (relative risk [95% confidence interval], 1.30 [1.24 to 1.37]) and increased linearly with advancing maternal age after 35 years and also with increasing pre-pregnancy BMI. PIH also varied greatly among 24 groups stratified according to 4 maternal age categories and 6 pre-pregnancy BMI categories, with the lowest frequency (2.7%) among lean (BMI<18.5) women 20–34 years of age and the highest frequency (21.7%) among obese (BMI≥30) women ≥40 years of age.
    Conclusions: Our findings provide useful information for counseling Japanese women about the risk of PIH at the beginning of pregnancy.
  • Katsuhiko Naruse, Taihei Tsunemi, Akira Onogi, Natsuki Koike, Juria Ak ...
    Article type: ORIGINAL ARTICLE
    2013 Volume 1 Issue 2 Pages 81-87
    Published: October 24, 2013
    Released on J-STAGE: January 29, 2014
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    Aim: In the placenta, hypoxia followed by reoxygenation (ischemia and reperfusion) is regarded as a trigger for the pathological onset of preeclampsia. In this study, we isolated primary trophoblasts from human term placenta, exposed them to hypoxic stress, and measured subsequent levels of cytokines, proteases, protease inhibitors, and ligands of receptor for advanced glycation endproducts (RAGE) to identify the trigger molecule released from hypoxic placenta into maternal circulation.
    Methods: Ten placental samples were taken from healthy elective caesarean section patients. Trophoblasts were isolated using a Percoll-based method and cultured under 20% oxygen with or without 3 rounds of 0.1% hypoxic stimulation for 1 h.
    Results: Cell viability did not differ between normal and hypoxic cultures (MTT assay), but cell injury was attenuated in hypoxic culture (LDH assay). In cell culture supernatants, concentrations of MMP-2, TIMP-2, IL-6, and IL-10 decreased in hypoxia compared to normal culture, while the RAGE ligand HMGB1 increased significantly in hypoxic culture. There were no significant differences in concentrations of MMP-9, TIMP-1, IL-8, or S100A12.
    Conclusions: These results suggest that human term placenta under hypoxia and reperfusion releases the RAGE ligand HMGB1, a “danger signal”, that can trigger systemic inflammation and lead to preeclampsia or placenta-based complications in pregnancy.
  • Kazuko Uematsu, Eiko Kobayashi, Emi Katsumoto, Mitsuhiro Sugimoto, Tad ...
    Article type: ORIGINAL ARTICLE
    2013 Volume 1 Issue 2 Pages 88-92
    Published: October 24, 2013
    Released on J-STAGE: January 29, 2014
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    Aim: We measured umbilical cord blood and maternal plasma concentrations of labetalol hydrochloride (labetalol) at delivery in women with pregnancy induced hypertension (PIH) who received labetalol treatment, and also investigated the influence of labetalol on neonatal findings.
    Methods: We surveyed background, neonatal findings, and health checkups after birth among PIH patients who received labetalol. Umbilical cord blood was collected within 15 min after delivery and venous blood within 2 h. Umbilical cord blood and maternal plasma concentrations of labetalol were measured using liquid chromatography-tandem mass spectrometry.
    Results: PIH was evaluated as severe hypertension in 20 patients and mild hypertension in 9 according to the Guidelines for the Management of PIH. Umbilical cord blood concentrations of labetalol were 17.2±11.4 ng/ml in the 150 mg/day group (n=22) and 32.8±11.6 ng/ml in the 300 mg/day group (n=7). Mean maternal plasma concentrations of labetalol in the 150 mg/day and 300 mg/day groups were 29.2±21.0 ng/ml and 49.3±12.6 ng/ml, respectively. The 300 mg/day group also included 2 low-birthweight neonates, whose Apgar scores were 5 after 1 min but returned to normal values after 5 min. There were no abnormalities in Apgar score or umbilical cord blood pH in any other neonates and no abnormal findings at neonatal checkups. Patients who continued drug therapy after delivery even performed breast feeding.
    Conclusions: There was some correlation between labetalol concentrations in umbilical cord blood and in maternal plasma (r=0.688), with the former corresponding to 60% to 70% of the latter.
  • Keiichi Matsubara, Miki Mori, Yuko Matsubara, Yuka Uchikura, Akihiro N ...
    Article type: ORIGINAL ARTICLE
    2013 Volume 1 Issue 2 Pages 93-97
    Published: October 24, 2013
    Released on J-STAGE: January 29, 2014
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    Aim: Preeclampsia (PE) is a disorder characterized by hypertensive symptoms and proteinuria in pregnant women. Previous studies have demonstrated that endothelial cell (EC) dysfunction is involved in the pathogenesis of PE. Intracellular free calcium ions are thought to function as secondary messengers in the EC signaling pathway. The aim of this study is to evaluate factors found in sera of PE patients by measuring their effects on intracellular calcium ion concentration ([Ca2+]i) in ECs.
    Methods: ECs obtained from umbilical cords of normal pregnant women were cultured and incubated with Fura-2/acetoxymethyl ester (Fura-2AM). [Ca2+]i values were measured in ECs treated with sera from 29 normal pregnant women, 7 PE patients, and 10 non-pregnant women by monitoring fluorescence using a CAM 220 fluorometer.
    Results: [Ca2+]i values were significantly higher in ECs treated with sera from normal pregnant women compared to those from non-pregnant women, and the effects were even stronger when ECs were treated with sera from pregnant women who were in later stages of pregnancy. Furthermore, sera from PE patients significantly increased EC [Ca2+]i compared to those from normal pregnant women in the 3rd trimester.
    Conclusions: It is possible that serum factors play important roles in the maintenance of normal pregnancy. Furthermore, EC activation could be associated with the pathogenesis of PE through increases in EC [Ca2+]i.
  • Kazushi Watanabe, Ai Iwasaki, Toshitaka Mori, Chiharu Kimura, Hiroshi ...
    Article type: ORIGINAL ARTICLE
    2013 Volume 1 Issue 2 Pages 98-102
    Published: October 24, 2013
    Released on J-STAGE: January 29, 2014
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    Aim: The aim of this study was to determine whether oxidative stress occurring in the maternal body also affects the fetus in preeclamptic women with fetal growth restriction (FGR).
    Methods: We recruited 14 preeclamptic women with FGR, 13 preeclamptic women without FGR, and 10 uncomplicated pregnant women. We measured concentrations of derivatives of reactive oxygen metabolites (d-ROMs) as a marker of oxygen free radicals and biological antioxidant potential (BAP) in a umbilical artery and vein.
    Results: Umbilical artery and vein d-ROM levels were elevated in preeclamptic women with FGR compared to the control group. Umbilical artery d-ROM levels were significantly higher than in the vein in preeclamptic women with FGR, but not in those without FGR. Umbilical artery BAP levels did not change significantly in all three groups. Umbilical arterial blood pH was significantly lower and the partial pressure of carbon dioxide (PaCO2) was significantly higher in preeclamptic women with FGR. Umbilical arterial blood partial pressure of oxygen (PaO2) tended to be lower in preeclamptic women with FGR.
    Conclusions: These results indicate that oxidative stress occurring in the maternal body also affects the fetus in preeclamptic women with FGR.
  • Kei Takahashi, Kazuya Mimura, Takeshi Kanagawa, Yukiko Kinugasa-Tanigu ...
    Article type: ORIGINAL ARTICLE
    2013 Volume 1 Issue 2 Pages 103-107
    Published: October 24, 2013
    Released on J-STAGE: January 29, 2014
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    Aim: The purpose of this study was to review the maternal and fetal outcomes in pregnant women with systemic lupus erythematosus (SLE), and to evaluate the prognostic risk factors that may contribute to obstetric outcomes or SLE flare-ups.
    Methods: We evaluated 100 births in 97 SLE patients who were seen at Osaka University from 1995 to 2013. Main outcome measures included obstetric outcomes and SLE flare-ups.
    Results: The mean patient age was 30.7±4.6 years, and the nulliparity rate was 62.8%. Corticosteroids were taken by 75.3% of the patients, and 48.5% were on a dosage of ≥7.5 mg/day. Disease flare-up and preeclampsia occurred in 17.5% and 11.3% of the patients, respectively. Seven SLE flare-ups (41.2%) occurred after delivery. Fourteen of the patients with a flare-up were taking high dose corticosteroids (≥7.5 mg/day) and showed significantly poorer obstetric outcomes compared to patients taking low dose corticosteroids (<7.5 mg/day) (P=0.0021).
    Conclusions: A multidisciplinary approach in the care of pregnant women with SLE is important for good maternal and fetal outcomes. Furthermore, a high daily dosage of corticosteroids may be a prognostic risk factor for adverse SLE flare-ups.
  • Tamao Yamamoto, Ayano Matsuura, Yoshikatsu Suzuki
    Article type: ORIGINAL ARTICLE
    2013 Volume 1 Issue 2 Pages 108-112
    Published: October 24, 2013
    Released on J-STAGE: January 29, 2014
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    Aim: Calcium intake is relatively low in Japanese women. The present study was to investigate longitudinal calcium metabolism during pregnancy and its characteristic changes in women with pregnancy induced hypertension (PIH) in Japan.
    Methods: A total of 435 pregnant Japanese women participated in this study. Fifty nine developed PIH, including 24 with preeclampsia and 35 with gestational hypertension. The urinary calcium to creatinine (Ca/Cr) ratio and serum calcium concentrations were measured at the 1st, 2nd, and 3rd trimesters and postpartum. In preeclampsia, they were classified on focusing onset time, severity and intrauterine fetal growth.
    Results: The urinary Ca/Cr ratio at the 3rd trimester was reduced, while serum calcium concentrations were reduced at the 2nd trimester in three groups. In preeclamptic women, urinary Ca/Cr ratios at 3rd trimester and after onset of disease were significantly reduced, while the serum calcium concentration at the 2nd trimester was markedly reduced. Changes in urinary calcium and serum calcium were similar in all groups of preeclampsia.
    Conclusions: The characteristic changes in calcium metabolism seen in preeclampsia might be present in Japanese women, who were known to have low calcium intake.
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