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  • ISSN: 2333-6439
    Special Issue entitled: Prediction of preeclampsia
    Akihide Ohkuchi
    Department of Obstetrics and Gynecology
    Jichi Medical University School of Medicine
    Japan
    Special Issue on Prediction of Preeclampsia
    Research Article
    Kayo Takahashi, Akihide Ohkuchi*, Mami Kobayashi, Shigeki Matsubara, and Mitsuaki Suzuki
    Abstract:
    Aims: To summarize the occurrence risk of hypertensive disease in pregnancy (HDP) in women with a past history of HDP.
    Methods: Relevant references were quoted from previous review articles, and recent articles from 2005 to 2013 were systemically searched using PubMed. Average occurrence rate was calculated.
    Results: We found 25 articles on the occurrence rate of HDP in women with a past history of all preeclampsia (PE), 15 articles on women with a past history of severe HDP including early-onset PE (EO-PE), HELLP syndrome and/or eclampsia, 3 articles on women with a past history of gestational hypertension (GH), and 4 articles on women with a past history of either PE or GH (PE/GH). In women with a past history of PE, the occurrence rate of PE, EO-PE, GH, and PE/GH was 14%, 5.1%, 20%, and 34%, respectively. In women with a past history of severe HDP, the occurrence rate of PE, EO-PE, GH, and PE/GHwas 28%, 11%, 33%, and 53%, respectively. In women with a past history of GH, the occurrence rate of PE, GH, and PE/GH was 6.6%, 39%, and 45%, respectively. PE/GH recurred in 32% of women with a past history of PE/GH.
    Conclusions: PE recurred in almost one-seventh of women with a past history of PE, and GH recurred in almost one-third of women with a past history of GH. The occurrence risk of PE and EO-PE in women with a past history of severe HDP was almost twice as high as in those with a past history of PE.
    Chikako Hirashima, Akihide Ohkuchi*, Kayo Takahashi, Rie Usui, Shigeki Matsubara and Mitsuaki Suzuki
    Abstract:
    Aim: To perform a systematic review of screening for early-onset preeclampsia (EO-PE) by angiogenesis-related factors alone, such as soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF) and soluble endoglin (sEng), or the combination use of angiogenesis-related factors and other risk factors.
    Methods: We searched for eligible articles in PubMed from 2007 to 2014, and previously published review articles. A positive likelihood ratio (LR+) ≥10 was considered clinically useful for screening.
    Results: Twenty-one articles with sensitivity and s false-positive rate (FPR) were used. For angiogenesis-related factors alone at the cut-off level of 5% FPR in unselected or low-risk women, PlGF in the 1st trimester, PlGF in the 2nd trimester, and the sFlt-1/PlGF ratio in the 2nd trimester, yielded an average LR+ of 6.8, 14.6 and, 12.7, respectively. For the combination use of angiogenesis-related factors at the cut-off level of 5% FPR in unselected or low-risk women, the average LR+ in the 1st, 2nd, and early 3rd trimesters was 13.2, 14.6 and 25.4, respectively.
    Conclusion: The prediction of EO-PE using PlGF or the sFlt-1/PlGF ratio in the 2nd trimester women appears to be clinically useful. The prediction of EO-PE using the combination use of angiogenesis-related factors and other risk factors in the 1st and 2nd trimesters also appears to be clinically useful. The prediction of EO-PE using the combination of angiogenesis-related factors and other risk factors in the early 3rd trimester yielded the best LR+.
    Akihide Ohkuchi*, Kayo Takahashi, Chikako Hirashima, RieUsui, Shigeki Matsubara and Mitsuaki Suzuki
    Abstract:
    Aim: To perform a systematic review of screening for early-onset preeclampsia (EO-PE) by uterine artery Doppler (UAD) alone or combination use of UAD and other risk factors.
    Methods: We searched for eligible articles in PubMed from 2000–2012, and previously published review articles. The positive likelihood ratio (LR+) ≥10 was considered clinically useful for screening.
    Results: Forty articles with sensitivity and a false-positive rate (FPR) were used for calculating LR+ and post-test probability for predicting EO-PE. In unselected or low-risk women, the average LR+ at the cut-off level of 5% FPR, using UAD alone in the 1stand 2nd trimesters, and the combination use of UAD in the 1stand 2nd trimesters,was11.2, 11.0, 14.3, and 15.9, respectively. In three studies of high-risk women, the combination of UAD and other risk factors in the 2nd trimester yielded a post-test probability of >0.20.
    Conclusion: The prediction of EO-PE using UAD indices at a cut-off level of 5% FPR in unselected or low-risk women appears to be clinically useful. In addition, the prediction of EO-PE using the combination of UAD and other risk factors in the 2nd trimester in high-risk women is promising.
    Noriko Hirose, Akihide Ohkuchi*, RieUsui, Shigeki Matsubara, and Mitsuaki Suzuki
    Abstract:
    Aim: In women with chronic kidney disease (CKD), dialysis, and kidney transplantation, the occurrence rate of preeclampsia is increased. We collected articles on pregnant women with CKD, dialysis, and kidney transplantation, and summarized the occurrence rates of preeclampsia.
    Methods: We searched for articles on pregnant women with CKD, dialysis, and kidney transplantation in PubMed and in review articles.
    Results: We found 6 articles on pregnant women with CKD which reported the incidence rate of preeclampsia; preeclampsia occurred in >20%.We found 4 articles on pregnancy with dialysis which reported the incidence rate of preeclampsia; preeclampsia occurredin >19%. One meta-analysis reported in 2011summarized the overall pooled incidence rate of preeclampsia in women with kidney transplantation; preeclampsia occurred in an average of 27%.
    Conclusion: Preeclampsia risk in pregnant women with CKD, dialysis, and kidney transplantation appears to be very high, >19%.
    Shiho Nagayama, Akihide Ohkuchi*, RieUsui, Shigeki Matsubara, and Mitsuaki Suzuki
    Abstract:
    Aims: Our aim was to evaluate the role of the father in the occurrence of preeclampsia in the second pregnancy.
    Methods: We searched for articles evaluating the effect of a change of paternity on the occurrence of preeclampsia in PubMed and in review articles.
    Results: We found 5 articles evaluating the effect of a change of paternity in the second pregnancy on the occurrence of preeclampsia. In 4 articles, we could calculate the average incidence rate of preeclampsia; 629,962 women were included in these articles. In women with a normal first pregnancy, preeclampsia in the second pregnancy occurred in 1.5% (8,601/566,727) with the same father, and 2.0% (722/34,638) with a different father (p<0.001). In women with preeclampsia in the first pregnancy, preeclampsia in the second pregnancy occurred in 13.9% (3,729/26,797) with the same father, and 12.8% (231/1,800) with a different father (p= 0.198).
    Conclusions: When women had a normal first pregnancy, preeclampsia in the second pregnancy occurred more frequently in women when there was a different father than the same husband. However, when women had preeclampsia in the first pregnancy, the change of paternity was not significantly related to the occurrence of preeclampsia in the second pregnancy. Although the effect of the change of paternity on the occurrence of preeclampsia might be small, the results of our systematic review support the hypothesis of a ‘dangerous father.'
    Hirotada Suzuki1, Akihide Ohkuchi1*, Koumei Shirasuna2,3, Hironori Takahashi1, Rie Usui1, Shigeki Matsubara1 and Mitsuaki Suzuki1
    Abstract:
    Aim: Animal models of preeclampsia (PE) have been extensively developed. Angiogenic/angiostatic balance theory bysoluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF) and soluble endoglin (sEng) for the genesis of PE is one of the most successful models of translational research from bench to bed. However, the balance theory of angiogenic/angiostatic factors does not explain the genesis of PE entirely. We attempted to list articles on animal models of PE and to gain insight into possible biomarker candidates for predicting PE.
    Methods: We collected 64 articles animal models of PE, consisting of 25 different methods. For angiotensinogen/renin, complement component C1q, 2-methoxyoestradiol (2-ME)/catechol-O-methyltransferase (COMT), galectin-1 (Gal-1), heme oxygenase-1 (HO-1), interleukin (IL)-10, and asymmetric dimethylarginine (ADMA)/L-arginine, we searched for articles on the prediction of PE in PubMed.
    Results: Angiotensinogen in the first trimester, prorenin at 8 weeks of gestation in women with type 1 diabetes, and plasma prorenin receptor in early pregnancy might predict the occurrence of PE. Low Gal-1 levels during the first trimester might predict the occurrence of PE during the second trimester. IL-10 levels did not change before the onset of PE. Maternal plasma ADMA in the second and third trimesters was higher in women with PE. We could not find any cohort or nested case-control studies on complement component C1q, 2-ME/COMT, and HO-1.
    Conclusion: Clinically useful biomarkers other than angiogenesis-related factors were not found. Basic research using animal models will gain insight into possible biomarker candidates for predicting PE.
    Review Article
    Hiroaki Itoh* and NaohiroKanayama
    Abstract:
    The incidence of obesity in women of childbearing age has consistently increased in the last half-century. Maternal obesity is a strong risk factor that a deteriorates the perinatal outcome of both mothers and neonates, and this has raised specific issues related to the management of pregnancy in obese women. Maternal obesity is a well-known risk factor for the development of preeclampsia. Several large population studies have shown that obese women are two to three times more likely to develop preeclampsia than their leaner counterparts. This association between maternal obesity and an increased incidence of preeclampsia is an important factor that deteriorates perinatal mortality and morbidity in obese mothers. In this review, we described the epidemiology, possible mechanistic background, transgenerational effect, and lifestyle interventions concerning the association between maternal obesity and risk of preeclampsia.
    Kazuo Eguchi*
    Abstract:
    Among the several risk factors of preeclampsia (PE), blood pressure (BP) elevation could be one of the earliest and most reliable signs of the disease. Various BP parameters, such as mean arterial pressure, ambulatory BP, and home BP, could be useful for the prediction of PE in pregnant women. When a pregnant woman before 20th gestational week has high BP, three possibilities can be considered: white-coat hypertension, sustained hypertension, and hypertension with chronic kidney disease. White-coat hypertension can be diagnosed by home BP monitoring or ambulatory BP monitoring (ABPM), and not at high risk for PE. So antihypertensive drugs are usually not necessary. In the case of sustained hypertension, early treatment is usually needed, but in some patients with sustained hypertension, BP can be normalized early in the course of pregnancy because of the physiological fall of BP. On the other hand, caution is needed for mild hypertension with CKD. Although most of the components of maternal outcomes depend on baseline levels of renal function, high BP can exacerbate renal functions of these patients, even during pregnancy. In this situation, the BP target is set as <140/90mmH. In case of essential hypertension during pregnancy, the risk of ‘pre-existing hypertension plus superimposed gestational hypertension with proteinuria' would be a previous history of preeclampsia and mild BP elevation such as SBP 130 - 139 mm Hg, and DBP 80 - 89 mm Hg. Appropriate BP control using antihypertensive medication other than renin angiotensin aldosterone system blockers is needed.
    Hironori Takahashi1,2*, Akihide Ohkuchi1, Rie Usui1, Toshihiro Takizawa2, Shigeki Matsubara1 and Mitsuaki Suzuki1
    Abstract:
    microRNA (miRNA) has been focused on placental biology and pathogenesis. Chromosome 19 miRNA cluster (C19MC) miRNAs are known for placenta- and primate-specific miRNAs. C19MC miRNAs are detected in maternal plasma even as early as the first trimester. To date, there are no miRNAs to be used as biomarkers of some disease in routine practice, although a few studies suggested C19MC miRNAs as biomarkers of obstetrical diseases. C19MC miRNAs have been also reported as onco-miRs and C19MC miRNAs target multiple genes in several kinds of malignancies. Two new insights into C19MC miRNAs in obstetrics have been recently reported. First, C19MC miRNAs induced viral resistance in non-trophoblast cells by autophagy. Second, fetal oncogenesis is associated with C19MC miRNAs. To clarify the pathogenesis of an obstetrical disease, roles of C19MC miRNAs need to be further investigated.
    Mini Review
    Akihide Ohkuchi*
    Abstract:
    Aim: To summarize recent articles on the risk factors of preeclampsia in twin pregnancies from 2002 to 2014.
    Methods: Recent articles from 2002 to 2014 were searched using PubMed.
    Results: We found 8 articles analyzing the risk factors of preeclampsia in twin pregnancies and focused on the following three risk factors: i) egg (oocyte) donation, ii) chorionicity (dichorionic (DC) twins vs. monochorionic (MC) twins), iii) assisted reproductive technology (ART) (in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) vs. no-IVF/ICSI). Two articles evaluated the risk of egg (oocyte) donation for developing preeclampsia in twin pregnancies, and both reported that egg (oocyte) donation was a significant risk factor for the occurrence of PE in twin pregnancies. However, the effects of chorionicity and ART on the occurrence of PE in twins are still controversial.
    Conclusions: We attempted a mini-review on the risk factors of preeclampsia in women with twin pregnancies. Egg (oocyte) donation was a risk factor of preeclampsia in twin pregnancies. Since women with twin pregnancies have an almost three-fold increased risk of PE compared with those with singleton pregnancy, egg (oocyte) donor recipients with multiple pregnancies might face a very high risk of preeclampsia.
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