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 during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. Methods IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model pre...
European Journal of Clinical Microbiology & Infectious Diseases, 2018
Our aim was to investigate the association between vaginal Ureaplasma species (spp.) and the subs... more Our aim was to investigate the association between vaginal Ureaplasma species (spp.) and the subsequent occurrence of chorioamnionitis (CAM), perinatal death, neonatal morbidity, and long-term neurodevelopmental impairments (NDIs) at 3 years of age. We analyzed 55 pregnant women with singleton pregnancy who had preterm premature rupture of the membranes (pPROM) at < 28 +0 weeks of gestation, and delivered between 22 +0 and 31 +6 weeks at our tertiary hospital in 2007-2016. NDIs were defined as either cerebral palsy or developmental delay evaluated at 1.5 and/or 3 years old. The presence of Ureaplasma spp. and Mycoplasma hominis were evaluated using urea-arginine broth and Mycoplasma PPLO Agar. The presence of Ureaplasma spp. in the vagina was positive in 41%. Vaginal Ureaplasma spp. was a significant risk factor for CAM; however, it was not significantly associated with the occurrence of perinatal death, pulmonary hypoplasia, respiratory distress syndrome, transient tachypnea of the newborn, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia defined as oxygen required and occasional ventilatory assistance required at week 36 as modified (BPD 36), or NDIs. The crude odds ratio (95% confidence interval) of Ureaplasma spp. for the occurrence of CAM was 9.5 (1.10-82) (p = 0.041). In very preterm birth infants with pPROM, CAM, BPD 36 , and NDIs occurred in 78, 60, and 36%, respectively. Vaginal Ureaplasma spp. was a significant risk factor for CAM in very preterm birth infants with pPROM. The incidences of BPD 36 and NDIs in such infants were very high, nearing 3/5 and 1/3, respectively.
Clinical and Experimental Obstetrics & Gynecology, 2017
Purpose of investigation: Cesarean scar pregnancy (CSP) is a life-threatening condition that requ... more Purpose of investigation: Cesarean scar pregnancy (CSP) is a life-threatening condition that requires early pregnancy termination. Its early ultrasound diagnosis is clinically important; however, previous studies focused on the CSP site itself. The present study was conducted to investigate the authors' clinical impression that a uterine-fundal hypoechoic mass is more frequently observed in CSP. Such a finding, if confirmed, may contribute to ultrasound diagnosis of CSP. The authors also determined the relationship between the treatment strategy and outcome, with special emphasis on conditions eventually requiring uterine artery embolization (UAE). Materials and Methods: This was a case-control study of CSP, and the authors analyzed all 14 women that were treated in this single tertiary institute over a period of ten years. Control subjects consisted of all pregnant women with prior cesarean section (CS) but no CSP. Results: Patients with CSP were significantly more likely to have a hypoechoic mass than controls (42.9 vs. 15.4%, respectively; p = 0.028). On confining results to a "fundal" hypoechoic mass, only CSP(+) patients showed it (CSP vs. control: 28.6 vs. 0%, respectively; p < 0.001). Six (43%: 6/14) received UAE: four following vaginal evacuation (artificial or spontaneous), and two for bleeding after methotrexate (MTX) treatment. Conclusion: Patients with CSP more frequently had a uterine-fundal hypoechoic mass, whose detection may trigger a detailed observation of the CSP site, possibly leading to CSP diagnosis.
To characterise congenital mesoblastic nephroma (CMN), with special emphasis on polyhydramnios an... more To characterise congenital mesoblastic nephroma (CMN), with special emphasis on polyhydramnios and the neonatal prognosis, we summarise 31 CMN patients (30 reported patients and the present patient). CMN was detected at a median of 30 weeks’ gestation, and infants were delivered at a median of 34 weeks’ gestation. Of 27 patients with available data, 19 (70%) had polyhydramnios, of which 8 required amnio- drainage. Women with amnio-drainage gave birth significantly earlier (30.4 weeks’ gestation) than those without polyhydramnios (36.7 weeks’ gestation). Thus, CMN was frequently associated with polyhydramnios and this polyhydramnios was associated with a significant increase in the risk of preterm birth. Of 20 patients with available data, the affected-side kidney was ‘compressed’ in 16 and ‘replaced’ in 4: polyhydramnios was present in a half vs 100%, respectively, suggesting that a ‘replaced’ kidney may suggest a more aggressive tumour and may be associated with a poorer prognosis. Univariate analysis showed that early gestational week at diagnosis was the only feature significantly associated with poor prognosis. Thus, polyhydramnios, ‘replaced’ kidney and early gestational week at diagnosis, may indicate poor prognosis, to which obstetricians should pay attention.
In 2003, pregnant rats administered soluble fmslike tyrosine kinase 1 (sFlt-1) manifested protein... more In 2003, pregnant rats administered soluble fmslike tyrosine kinase 1 (sFlt-1) manifested proteinuria and hypertension, strongly indicating that increases in sFlt-1 and decreases in vascular endothelial growth factor/placental growth factor (VEGF/PlGF) in the maternal circulation may cause the occurrence of PE. Thereafter, we started investigations on angiogenesis-related factors in women with PE and/or gestational hypertension (GH). Methods: After gaining informed consents from pregnant cohort and women with PE/GH, we collected serum/plasma, stored them, later measured the levels of sFlt-1, PlGF, soluble endoglin (sEng), HSD17B1, galectin-1. Results: (1) In normal pregnant women, serum levels of sFlt-1 decreased from the 1st trimester (tri.) to the 2nd tri., then increased toward the 3rd tri.; in contrast, serum levels of PlGF increased from the 1st tri. to the early 3rd tri., then decreased toward the 3rd tri. (2) In women with PE, serum levels of sFlt-1 and sEng after the onset of PE were increased, and serum level of PlGF were decreased. (3) Onset threshold of the sFlt-1/PlGF ratio (measured by ELISA), which was different from abnormal threshold defined by normal reference range of sFlt-1/PlGF ratio, existed; the onset threshold at 26-31 weeks of gestation for predicting PE with onset at <36 weeks of gestation yielded sensitivity (SE) of 36%, specificity (SP) of 99.0%, and positive likelihood ratio (95% confidence interval) (LR+ [95% CI]) of 38 (11-132).
Oral communication abstracts Conclusions: On ultrasound GCT is characterized by a large multilocu... more Oral communication abstracts Conclusions: On ultrasound GCT is characterized by a large multilocular or solid mass with a large number of locules and increased vascularization; it rarely has papillarities.
Journal of Obstetrics and Gynaecology Research, 2014
In placenta previa (PP), anterior placentation, compared with posterior placentation, is reported... more In placenta previa (PP), anterior placentation, compared with posterior placentation, is reported to more frequently cause massive hemorrhage during cesarean section (CS). Whether this is due to the high incidence of placenta accreta, previous CS, or a transplacental approach in anterior placenta is unclear. We attempted to clarify this issue. We retrospectively analyzed the relation between the bleeding amount during CS for PP and various factors that may cause massive hemorrhage (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;2400 mL) (n = 205) in a tertiary center. If the preoperatively ultrasound-measured distance from the internal cervical ostium to the placental edge was longer in the uterine anterior wall than in the posterior wall, we defined it as anterior previa, and vice versa. Patients with accreta, previous CS, total previa, and anterior placentation bled significantly more than their counterparts. Multivariate logistic regression analysis showed that accreta (odds ratio [OR] 12.6), previous CS (OR 4.7), total previa (OR 4.1), and anterior placentation (OR 3.5) were independent risk factors of massive hemorrhage. Anterior placentation, namely, the placenta with a longer os-placental edge distance in the anterior wall than in the posterior wall, was a risk of massive hemorrhage during CS for PP.
Mean blood pressure (MBP), bilateral notching (BN) in the uterine artery and increased circulatin... more Mean blood pressure (MBP), bilateral notching (BN) in the uterine artery and increased circulating levels of soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio are predictors of preeclampsia (PE). Recently, we disclosed that reducing the plasma level of hydroxysteroid (17-b) dehydrogenase 1 (HSD17B1), which is a steroidogenetic enzyme catalyzing the conversion of estrone to 17b-estradiol, is a potential prognostic factor for PE. Our aim was to evaluate whether HSD17B1 is an independent risk factor for predicting PE after adjusting for the effects of MBP, BN and the plasma level of the sFlt-1/PlGF ratio in the second trimester. One hundred and twenty-eight consecutive normal pregnant women without gestational hypertension (GH) or PE and 30 women with PE were selected from 1724 pregnant women. Multivariate logistic regression with a forward stepwise procedure was used to construct a prediction model. A past history of GH/PE, a family history of hypertension, pre-pregnancy body mass index, MBP, BN, plasma levels of sFlt-1/PlGF ratio and plasma levels of HSD17B1 were significantly associated with the occurrence of PE; however, only MBP (OR (95% confidence interval), 1.08 (1.03-1.14)), BN (7.5 (1.9-30)), sFlt-1/PlGF (21 (2.7-163)) and HSD17B1 (0.43 (0.22-0.85)) were independent risk factors for PE. The area under the receiver-operating-characteristic curve for the combination model was 0.89, yielding a sensitivity of 0.84, a specificity of 0.88 and a positive likelihood ratio of 7.2 (4.0-13). In conclusion, HSD17B1 is an independent risk factor for PE, and the combination of several risk factors including HSD17B1 in the second trimester may improve the prediction of PE.
Background: Japan experienced two rubella outbreaks in the past decade (2004 and 2012-2013), resu... more Background: Japan experienced two rubella outbreaks in the past decade (2004 and 2012-2013), resulting in 10 and 20 infants with congenital rubella syndrome (CRS), respectively. This study was performed to determine whether the seronegative rate was lower in multiparous women than in primiparous women in Japan. Methods: Hemagglutination inhibition (HI) test results during pregnancy were analyzed retrospectively in 11048 primiparous and 9315 multiparous women who gave birth at six hospitals in northern Japan in the 5-year study period (January 2008 through December 2012). Women with HI titer < 1:8 were defined as susceptible to rubella. Results: The seronegative rate was significantly lower in multiparous than primiparous women aged 30-31 years (2.3% [22/967] vs. 4.
In this study, we performed small RNA library sequencing using human placental tissues to identif... more In this study, we performed small RNA library sequencing using human placental tissues to identify placenta-specific miRNAs. We also tested the hypothesis that human chorionic villi could secrete miRNAs extracellularly via exosomes, which in turn enter into maternal circulation. By small RNA library sequencing, most placenta-specific miRNAs (e.g., MIR517A) were linked to a miRNA cluster on chromosome 19. The miRNA cluster genes were differentially expressed in placental development. Subsequent validation by real-time PCR and in situ hybridization revealed that villous trophoblasts express placenta-specific miRNAs. The analysis of small RNA libraries from the blood plasma showed that the placenta-specific miRNAs are abundant in the plasma of pregnant women. By real-time PCR, we confirmed the rapid clearance of the placenta-specific miRNAs from the plasma after delivery, indicating that such miRNAs enter into maternal circulation. By using the trophoblast cell line BeWo in culture, we demonstrated that miRNAs are indeed extracellularly released via exosomes. Taken together, our findings suggest that miRNAs are exported from the human placental syncytiotrophoblast into maternal circulation, where they could target maternal tissues. Finally, to address the biological functions of placenta-specific miRNAs, we performed a proteome analysis of BeWo cells transfected with MIR517A. Bioinformatic analysis suggests that this miRNA is possibly involved in tumor necrosis factor-mediated signaling. Our data provide important insights into miRNA biology of the human placenta.
While activated/phagocytosing phagocytes infiltrating to the chorioamnion are considered to be on... more While activated/phagocytosing phagocytes infiltrating to the chorioamnion are considered to be one of the causal agents of preterm labor onset, whether placental villous macrophages (Hofbauer cells) are activated/phagocytosing in this condition is not known. We concomitantly localized two important phagocytosis-related enzymes, acid phosphatase (ACP) and glucose-6-phosphate dehydrogenase (G6PD), in Hofbauer cells in second trimester placental villi, and compared them with those from infection-related second trimester-spontaneous abortion (miscarriage) placentas. There were two types of Hofbauer cells. The first cells exhibited ACP stainings confined to the lysosomes, suggesting that they are dormant/non-activated cells. Approximately two-thirds of these cells showed weak G6PD labeling on the cytosolic side of endoplasmic reticula, and G6PD labeling was hardly recognizable in the remaining one-third. The second cells, possessing large phagosomes, showed marked ACP labeling in the phagosomes, suggesting that they are activated/phagocytosing cells. All these cells exhibited G6PD labeling, and in &#39;bursting cells&#39; (possibly hyperactivated cells) G6PD deposits were marked. The percentage of activated cells in miscarriage placentas was significantly higher (44.8 +/- 6.0%) than that in gestational age-matched controls (17.4 +/- 5.3%). These observations indicated that (1) G6PD activity increased in activated/phagocytosing Hofbauer cells, and (2) the percentage of phagocytosing cells increased in infection-related miscarriage placentas. Hofbauer activation and G6PD may play an role in the pathogenesis/pathophysiology of preterm labor onset.
Acta Obstetricia et Gynecologica Scandinavica, 2000
Background. Chorioamnionitis (CAM) may accelerate lung maturation in fetuses. It is possible that... more Background. Chorioamnionitis (CAM) may accelerate lung maturation in fetuses. It is possible that CAM prevents infant death after live birth. Methods. A retrospective study of live-born singletons at ∞32 weeks of gestation between 1993 and 1997. Perinatal risk factors for adverse outcomes were analyzed using a logistic regression model, with special reference to the presence of histologically confirmed CAM. Adverse outcomes included infant death before 1 year of age, and survival with cerebral palsy and/or mental retardation. Results. A total of 81 infants, weighing 1181∫426 g, were born at 28.1∫2.3 weeks of gestation. Of those, 15 (19%) died before 1 year of age, while 16 (20%) infants developed major handicaps by 1.5 years of age (six with cerebral palsy, eight with mental retardation, and two with both cerebral palsy and mental retardation). CAM, present in 44 women, was significantly associated with a reduced risk of death after live birth, with an odds ratio of 0.11 (pΩ0.01). Only the presence of such intracranial lesions as periventricular leukomalacia and intraventricular hemorrhage were significantly associated with an increased risk of major handicaps (odds ratio of 11.0, pΩ0.04). Adverse outcomes occurred in a similar proportion of infants in groups without CAM (14/37) and with CAM (17/44). However, among infants with adverse outcomes, the number of deaths was significantly higher in the group without CAM (10/14) vs. with CAM (5/12) (p∞0.05). Conclusions. The presence of CAM may somehow prevent infant death after live birth. Larger studies are required to confirm this phenomenon.
Acta Obstetricia et Gynecologica Scandinavica, 2000
The number and percentage of viable vaginal polymorphonuclear leukocytes (vPMNs) are known to be ... more The number and percentage of viable vaginal polymorphonuclear leukocytes (vPMNs) are known to be increased in women who experience preterm labor. Whether those parameters may be associated with the presence of histologic chorioamnionitis (CAM) is not known. We investigated prospectively 39 women at 26.3 +/- 6.2 weeks of gestation. The following were determined in vaginal washings: total number of vPMNs and the percent that were viable, the pH, and the concentrations of granulocyte elastase and interleukin-8 (IL-8). In addition, the white blood cell count and the serum level of C-reactive protein were determined in peripheral blood. The placenta and the umbilical cord were examined histologically with special reference to the presence of CAM. The optimal cutoff value for prediction of histologic CAM was obtained for each variable using receiver operating characteristic curves. A multivariate logistic-regression model was used to determine the independent risk factors for this disorder. Histologic CAM was present in ten women (37.1 +/- 3.8 weeks) and absent in 29 women (38.2 +/- 1.5 weeks). The total number of vPMNs, the percent of viable vPMNs, and the IL-8 level were all significantly increased in the women with CAM, in contrast to those without CAM. When the optimal cutoff value for each of seven covariates was entered into the model, only the percent of viable vPMNs, &gt; or = 11%, demonstrated a significant relationship with histologic CAM (odds ratio 26.9; 95% confidence interval 1.3 to 545; p &lt; 0.05). Women with a % viability of vPMNs of &gt; or = 11% were at a significantly higher risk for histologic CAM. Data suggest that an influx of PMNs into the vagina occurs continuously in patients with histologic CAM.
In this study, to search for novel preeclampsia (PE) biomarkers, we focused on microRNA expressio... more In this study, to search for novel preeclampsia (PE) biomarkers, we focused on microRNA expression and function in the human placenta complicated with PE. By comprehensive analyses of microRNA expression, we identified 22 microRNAs significantly upregulated in preeclamptic placentas, 5 of which were predicted in silico to commonly target the mRNA encoding hydroxysteroid (17-β) dehydrogenase 1 (HSD17B1), a steroidogenetic enzyme expressed predominantly in the placenta. In vivo HSD17B1 expression, at both the mRNA and protein levels, was significantly decreased in preeclamptic placentas. Of these microRNAs, miR-210 and miR-518c were experimentally validated to target HSD17B1 by luciferase assay, real-time PCR, and ELISA. Furthermore, we found that plasma HSD17B1 protein levels in preeclamptic pregnant women reflected the decrease of its placental expression. Moreover, a prospective cohort study of plasma HSD17B1 revealed a significant reduction of plasma HSD17B1 levels in pregnant wom...
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 during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. Methods IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model pre...
European Journal of Clinical Microbiology & Infectious Diseases, 2018
Our aim was to investigate the association between vaginal Ureaplasma species (spp.) and the subs... more Our aim was to investigate the association between vaginal Ureaplasma species (spp.) and the subsequent occurrence of chorioamnionitis (CAM), perinatal death, neonatal morbidity, and long-term neurodevelopmental impairments (NDIs) at 3 years of age. We analyzed 55 pregnant women with singleton pregnancy who had preterm premature rupture of the membranes (pPROM) at < 28 +0 weeks of gestation, and delivered between 22 +0 and 31 +6 weeks at our tertiary hospital in 2007-2016. NDIs were defined as either cerebral palsy or developmental delay evaluated at 1.5 and/or 3 years old. The presence of Ureaplasma spp. and Mycoplasma hominis were evaluated using urea-arginine broth and Mycoplasma PPLO Agar. The presence of Ureaplasma spp. in the vagina was positive in 41%. Vaginal Ureaplasma spp. was a significant risk factor for CAM; however, it was not significantly associated with the occurrence of perinatal death, pulmonary hypoplasia, respiratory distress syndrome, transient tachypnea of the newborn, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia defined as oxygen required and occasional ventilatory assistance required at week 36 as modified (BPD 36), or NDIs. The crude odds ratio (95% confidence interval) of Ureaplasma spp. for the occurrence of CAM was 9.5 (1.10-82) (p = 0.041). In very preterm birth infants with pPROM, CAM, BPD 36 , and NDIs occurred in 78, 60, and 36%, respectively. Vaginal Ureaplasma spp. was a significant risk factor for CAM in very preterm birth infants with pPROM. The incidences of BPD 36 and NDIs in such infants were very high, nearing 3/5 and 1/3, respectively.
Clinical and Experimental Obstetrics & Gynecology, 2017
Purpose of investigation: Cesarean scar pregnancy (CSP) is a life-threatening condition that requ... more Purpose of investigation: Cesarean scar pregnancy (CSP) is a life-threatening condition that requires early pregnancy termination. Its early ultrasound diagnosis is clinically important; however, previous studies focused on the CSP site itself. The present study was conducted to investigate the authors' clinical impression that a uterine-fundal hypoechoic mass is more frequently observed in CSP. Such a finding, if confirmed, may contribute to ultrasound diagnosis of CSP. The authors also determined the relationship between the treatment strategy and outcome, with special emphasis on conditions eventually requiring uterine artery embolization (UAE). Materials and Methods: This was a case-control study of CSP, and the authors analyzed all 14 women that were treated in this single tertiary institute over a period of ten years. Control subjects consisted of all pregnant women with prior cesarean section (CS) but no CSP. Results: Patients with CSP were significantly more likely to have a hypoechoic mass than controls (42.9 vs. 15.4%, respectively; p = 0.028). On confining results to a "fundal" hypoechoic mass, only CSP(+) patients showed it (CSP vs. control: 28.6 vs. 0%, respectively; p < 0.001). Six (43%: 6/14) received UAE: four following vaginal evacuation (artificial or spontaneous), and two for bleeding after methotrexate (MTX) treatment. Conclusion: Patients with CSP more frequently had a uterine-fundal hypoechoic mass, whose detection may trigger a detailed observation of the CSP site, possibly leading to CSP diagnosis.
To characterise congenital mesoblastic nephroma (CMN), with special emphasis on polyhydramnios an... more To characterise congenital mesoblastic nephroma (CMN), with special emphasis on polyhydramnios and the neonatal prognosis, we summarise 31 CMN patients (30 reported patients and the present patient). CMN was detected at a median of 30 weeks’ gestation, and infants were delivered at a median of 34 weeks’ gestation. Of 27 patients with available data, 19 (70%) had polyhydramnios, of which 8 required amnio- drainage. Women with amnio-drainage gave birth significantly earlier (30.4 weeks’ gestation) than those without polyhydramnios (36.7 weeks’ gestation). Thus, CMN was frequently associated with polyhydramnios and this polyhydramnios was associated with a significant increase in the risk of preterm birth. Of 20 patients with available data, the affected-side kidney was ‘compressed’ in 16 and ‘replaced’ in 4: polyhydramnios was present in a half vs 100%, respectively, suggesting that a ‘replaced’ kidney may suggest a more aggressive tumour and may be associated with a poorer prognosis. Univariate analysis showed that early gestational week at diagnosis was the only feature significantly associated with poor prognosis. Thus, polyhydramnios, ‘replaced’ kidney and early gestational week at diagnosis, may indicate poor prognosis, to which obstetricians should pay attention.
In 2003, pregnant rats administered soluble fmslike tyrosine kinase 1 (sFlt-1) manifested protein... more In 2003, pregnant rats administered soluble fmslike tyrosine kinase 1 (sFlt-1) manifested proteinuria and hypertension, strongly indicating that increases in sFlt-1 and decreases in vascular endothelial growth factor/placental growth factor (VEGF/PlGF) in the maternal circulation may cause the occurrence of PE. Thereafter, we started investigations on angiogenesis-related factors in women with PE and/or gestational hypertension (GH). Methods: After gaining informed consents from pregnant cohort and women with PE/GH, we collected serum/plasma, stored them, later measured the levels of sFlt-1, PlGF, soluble endoglin (sEng), HSD17B1, galectin-1. Results: (1) In normal pregnant women, serum levels of sFlt-1 decreased from the 1st trimester (tri.) to the 2nd tri., then increased toward the 3rd tri.; in contrast, serum levels of PlGF increased from the 1st tri. to the early 3rd tri., then decreased toward the 3rd tri. (2) In women with PE, serum levels of sFlt-1 and sEng after the onset of PE were increased, and serum level of PlGF were decreased. (3) Onset threshold of the sFlt-1/PlGF ratio (measured by ELISA), which was different from abnormal threshold defined by normal reference range of sFlt-1/PlGF ratio, existed; the onset threshold at 26-31 weeks of gestation for predicting PE with onset at <36 weeks of gestation yielded sensitivity (SE) of 36%, specificity (SP) of 99.0%, and positive likelihood ratio (95% confidence interval) (LR+ [95% CI]) of 38 (11-132).
Oral communication abstracts Conclusions: On ultrasound GCT is characterized by a large multilocu... more Oral communication abstracts Conclusions: On ultrasound GCT is characterized by a large multilocular or solid mass with a large number of locules and increased vascularization; it rarely has papillarities.
Journal of Obstetrics and Gynaecology Research, 2014
In placenta previa (PP), anterior placentation, compared with posterior placentation, is reported... more In placenta previa (PP), anterior placentation, compared with posterior placentation, is reported to more frequently cause massive hemorrhage during cesarean section (CS). Whether this is due to the high incidence of placenta accreta, previous CS, or a transplacental approach in anterior placenta is unclear. We attempted to clarify this issue. We retrospectively analyzed the relation between the bleeding amount during CS for PP and various factors that may cause massive hemorrhage (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;2400 mL) (n = 205) in a tertiary center. If the preoperatively ultrasound-measured distance from the internal cervical ostium to the placental edge was longer in the uterine anterior wall than in the posterior wall, we defined it as anterior previa, and vice versa. Patients with accreta, previous CS, total previa, and anterior placentation bled significantly more than their counterparts. Multivariate logistic regression analysis showed that accreta (odds ratio [OR] 12.6), previous CS (OR 4.7), total previa (OR 4.1), and anterior placentation (OR 3.5) were independent risk factors of massive hemorrhage. Anterior placentation, namely, the placenta with a longer os-placental edge distance in the anterior wall than in the posterior wall, was a risk of massive hemorrhage during CS for PP.
Mean blood pressure (MBP), bilateral notching (BN) in the uterine artery and increased circulatin... more Mean blood pressure (MBP), bilateral notching (BN) in the uterine artery and increased circulating levels of soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio are predictors of preeclampsia (PE). Recently, we disclosed that reducing the plasma level of hydroxysteroid (17-b) dehydrogenase 1 (HSD17B1), which is a steroidogenetic enzyme catalyzing the conversion of estrone to 17b-estradiol, is a potential prognostic factor for PE. Our aim was to evaluate whether HSD17B1 is an independent risk factor for predicting PE after adjusting for the effects of MBP, BN and the plasma level of the sFlt-1/PlGF ratio in the second trimester. One hundred and twenty-eight consecutive normal pregnant women without gestational hypertension (GH) or PE and 30 women with PE were selected from 1724 pregnant women. Multivariate logistic regression with a forward stepwise procedure was used to construct a prediction model. A past history of GH/PE, a family history of hypertension, pre-pregnancy body mass index, MBP, BN, plasma levels of sFlt-1/PlGF ratio and plasma levels of HSD17B1 were significantly associated with the occurrence of PE; however, only MBP (OR (95% confidence interval), 1.08 (1.03-1.14)), BN (7.5 (1.9-30)), sFlt-1/PlGF (21 (2.7-163)) and HSD17B1 (0.43 (0.22-0.85)) were independent risk factors for PE. The area under the receiver-operating-characteristic curve for the combination model was 0.89, yielding a sensitivity of 0.84, a specificity of 0.88 and a positive likelihood ratio of 7.2 (4.0-13). In conclusion, HSD17B1 is an independent risk factor for PE, and the combination of several risk factors including HSD17B1 in the second trimester may improve the prediction of PE.
Background: Japan experienced two rubella outbreaks in the past decade (2004 and 2012-2013), resu... more Background: Japan experienced two rubella outbreaks in the past decade (2004 and 2012-2013), resulting in 10 and 20 infants with congenital rubella syndrome (CRS), respectively. This study was performed to determine whether the seronegative rate was lower in multiparous women than in primiparous women in Japan. Methods: Hemagglutination inhibition (HI) test results during pregnancy were analyzed retrospectively in 11048 primiparous and 9315 multiparous women who gave birth at six hospitals in northern Japan in the 5-year study period (January 2008 through December 2012). Women with HI titer < 1:8 were defined as susceptible to rubella. Results: The seronegative rate was significantly lower in multiparous than primiparous women aged 30-31 years (2.3% [22/967] vs. 4.
In this study, we performed small RNA library sequencing using human placental tissues to identif... more In this study, we performed small RNA library sequencing using human placental tissues to identify placenta-specific miRNAs. We also tested the hypothesis that human chorionic villi could secrete miRNAs extracellularly via exosomes, which in turn enter into maternal circulation. By small RNA library sequencing, most placenta-specific miRNAs (e.g., MIR517A) were linked to a miRNA cluster on chromosome 19. The miRNA cluster genes were differentially expressed in placental development. Subsequent validation by real-time PCR and in situ hybridization revealed that villous trophoblasts express placenta-specific miRNAs. The analysis of small RNA libraries from the blood plasma showed that the placenta-specific miRNAs are abundant in the plasma of pregnant women. By real-time PCR, we confirmed the rapid clearance of the placenta-specific miRNAs from the plasma after delivery, indicating that such miRNAs enter into maternal circulation. By using the trophoblast cell line BeWo in culture, we demonstrated that miRNAs are indeed extracellularly released via exosomes. Taken together, our findings suggest that miRNAs are exported from the human placental syncytiotrophoblast into maternal circulation, where they could target maternal tissues. Finally, to address the biological functions of placenta-specific miRNAs, we performed a proteome analysis of BeWo cells transfected with MIR517A. Bioinformatic analysis suggests that this miRNA is possibly involved in tumor necrosis factor-mediated signaling. Our data provide important insights into miRNA biology of the human placenta.
While activated/phagocytosing phagocytes infiltrating to the chorioamnion are considered to be on... more While activated/phagocytosing phagocytes infiltrating to the chorioamnion are considered to be one of the causal agents of preterm labor onset, whether placental villous macrophages (Hofbauer cells) are activated/phagocytosing in this condition is not known. We concomitantly localized two important phagocytosis-related enzymes, acid phosphatase (ACP) and glucose-6-phosphate dehydrogenase (G6PD), in Hofbauer cells in second trimester placental villi, and compared them with those from infection-related second trimester-spontaneous abortion (miscarriage) placentas. There were two types of Hofbauer cells. The first cells exhibited ACP stainings confined to the lysosomes, suggesting that they are dormant/non-activated cells. Approximately two-thirds of these cells showed weak G6PD labeling on the cytosolic side of endoplasmic reticula, and G6PD labeling was hardly recognizable in the remaining one-third. The second cells, possessing large phagosomes, showed marked ACP labeling in the phagosomes, suggesting that they are activated/phagocytosing cells. All these cells exhibited G6PD labeling, and in &#39;bursting cells&#39; (possibly hyperactivated cells) G6PD deposits were marked. The percentage of activated cells in miscarriage placentas was significantly higher (44.8 +/- 6.0%) than that in gestational age-matched controls (17.4 +/- 5.3%). These observations indicated that (1) G6PD activity increased in activated/phagocytosing Hofbauer cells, and (2) the percentage of phagocytosing cells increased in infection-related miscarriage placentas. Hofbauer activation and G6PD may play an role in the pathogenesis/pathophysiology of preterm labor onset.
Acta Obstetricia et Gynecologica Scandinavica, 2000
Background. Chorioamnionitis (CAM) may accelerate lung maturation in fetuses. It is possible that... more Background. Chorioamnionitis (CAM) may accelerate lung maturation in fetuses. It is possible that CAM prevents infant death after live birth. Methods. A retrospective study of live-born singletons at ∞32 weeks of gestation between 1993 and 1997. Perinatal risk factors for adverse outcomes were analyzed using a logistic regression model, with special reference to the presence of histologically confirmed CAM. Adverse outcomes included infant death before 1 year of age, and survival with cerebral palsy and/or mental retardation. Results. A total of 81 infants, weighing 1181∫426 g, were born at 28.1∫2.3 weeks of gestation. Of those, 15 (19%) died before 1 year of age, while 16 (20%) infants developed major handicaps by 1.5 years of age (six with cerebral palsy, eight with mental retardation, and two with both cerebral palsy and mental retardation). CAM, present in 44 women, was significantly associated with a reduced risk of death after live birth, with an odds ratio of 0.11 (pΩ0.01). Only the presence of such intracranial lesions as periventricular leukomalacia and intraventricular hemorrhage were significantly associated with an increased risk of major handicaps (odds ratio of 11.0, pΩ0.04). Adverse outcomes occurred in a similar proportion of infants in groups without CAM (14/37) and with CAM (17/44). However, among infants with adverse outcomes, the number of deaths was significantly higher in the group without CAM (10/14) vs. with CAM (5/12) (p∞0.05). Conclusions. The presence of CAM may somehow prevent infant death after live birth. Larger studies are required to confirm this phenomenon.
Acta Obstetricia et Gynecologica Scandinavica, 2000
The number and percentage of viable vaginal polymorphonuclear leukocytes (vPMNs) are known to be ... more The number and percentage of viable vaginal polymorphonuclear leukocytes (vPMNs) are known to be increased in women who experience preterm labor. Whether those parameters may be associated with the presence of histologic chorioamnionitis (CAM) is not known. We investigated prospectively 39 women at 26.3 +/- 6.2 weeks of gestation. The following were determined in vaginal washings: total number of vPMNs and the percent that were viable, the pH, and the concentrations of granulocyte elastase and interleukin-8 (IL-8). In addition, the white blood cell count and the serum level of C-reactive protein were determined in peripheral blood. The placenta and the umbilical cord were examined histologically with special reference to the presence of CAM. The optimal cutoff value for prediction of histologic CAM was obtained for each variable using receiver operating characteristic curves. A multivariate logistic-regression model was used to determine the independent risk factors for this disorder. Histologic CAM was present in ten women (37.1 +/- 3.8 weeks) and absent in 29 women (38.2 +/- 1.5 weeks). The total number of vPMNs, the percent of viable vPMNs, and the IL-8 level were all significantly increased in the women with CAM, in contrast to those without CAM. When the optimal cutoff value for each of seven covariates was entered into the model, only the percent of viable vPMNs, &gt; or = 11%, demonstrated a significant relationship with histologic CAM (odds ratio 26.9; 95% confidence interval 1.3 to 545; p &lt; 0.05). Women with a % viability of vPMNs of &gt; or = 11% were at a significantly higher risk for histologic CAM. Data suggest that an influx of PMNs into the vagina occurs continuously in patients with histologic CAM.
In this study, to search for novel preeclampsia (PE) biomarkers, we focused on microRNA expressio... more In this study, to search for novel preeclampsia (PE) biomarkers, we focused on microRNA expression and function in the human placenta complicated with PE. By comprehensive analyses of microRNA expression, we identified 22 microRNAs significantly upregulated in preeclamptic placentas, 5 of which were predicted in silico to commonly target the mRNA encoding hydroxysteroid (17-β) dehydrogenase 1 (HSD17B1), a steroidogenetic enzyme expressed predominantly in the placenta. In vivo HSD17B1 expression, at both the mRNA and protein levels, was significantly decreased in preeclamptic placentas. Of these microRNAs, miR-210 and miR-518c were experimentally validated to target HSD17B1 by luciferase assay, real-time PCR, and ELISA. Furthermore, we found that plasma HSD17B1 protein levels in preeclamptic pregnant women reflected the decrease of its placental expression. Moreover, a prospective cohort study of plasma HSD17B1 revealed a significant reduction of plasma HSD17B1 levels in pregnant wom...
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Papers by A. Ohkuchi