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Chronic active Epstein-Barr virus (CAEBV) infection characterized by persistent infectious mononucleosis-like symptoms can lead to cardiovascular diseases. We encountered two pregnant women with CAEBV histories complicated with cardiovascular diseases. A 36-year-old woman with a history of myocardial infarction due to CAEBV and coronary artery bypass grafting became pregnant. Her left ventricular ejection fraction (LVEF) decreased, and cesarean section was performed at 36 weeks of gestation. Her LVEF recovered after delivery. A 32-year-old woman with a history of CAEBV and chronic hypertension was diagnosed with mild pulmonary arterial hypertension (PAH) after conception. She strongly desired to continue the pregnancy. She became complicated with severe superimposed preeclampsia at 31 weeks of gestation, and cesarean section was performed. Her PAH did not deteriorate during pregnancy or the postpartum period. Women treated for CAEBV, even with complete remission, require a preconception evaluation focused on the cardiovascular system and careful management of their pregnancy.

This study aimed to review the obstetric complications during subsequent pregnancies after uterine artery embolization (UAE) for postpartum hemorrhage (PPH) by exploring the relationship between prior UAE and obstetric complications through a meta-analysis. We conducted a systematic literature review through March 31, 2021, using PubMed, Scopus, and the Cochrane Central Register of Controlled Trials in compliance with the PRISMA guidelines and determined the effect of prior UAE for PPH on the rate of placenta accreta spectrum (PAS), PPH, placenta previa, hysterectomy, fetal growth restriction (FGR), and preterm birth (PTB). Twenty-three retrospective studies (2003–2021) met the inclusion criteria. They included 483 pregnancies with prior UAE and 320,703 pregnancies without prior UAE. The cumulative results of all women with prior UAE indicated that the rates of obstetric complications PAS, hysterectomy, and PPH were 16.3% (34/208), 6.5% (28/432), and 24.0% (115/480), respectively. According to the patient background-matched analysis based on the presence of prior PPH, women with prior UAE were associated with higher rates of PAS (odds ratio [OR] 20.82; 95% confidence interval [CI] 3.27–132.41) and PPH (OR 5.32, 95% CI 1.40–20.16) but not with higher rates of hysterectomy (OR 8.93, 95% CI 0.43–187.06), placenta previa (OR 2.31, 95% CI 0.35–15.22), FGR (OR 7.22, 95% CI 0.28–188.69), or PTB (OR 3.00, 95% CI 0.74–12.14), compared with those who did not undergo prior UAE. Prior UAE for PPH may be a significant risk factor for PAS and PPH during subsequent pregnancies. Therefore, at the time of delivery, clinicians should be more attentive to PAS and PPH when women have undergone prior UAE. Since the number of women included in the patient background-matched study was limited, further investigations are warranted to confirm the results of this study.

Background Uterine artery embolization (UAE) is used to treat severe postpartum hemorrhage (PPH). According to a few studies, UAE for PPH was associated with preterm birth, fetal growth restriction (FGR), and placenta accreta spectrum (PAS) in subsequent pregnancies. These previous studies, however, lacked controls, and to the best of our knowledge, no systematic literature reviews have been conducted thus far. We report the results of our retrospective case-control study of pregnancies after UAE at a single center and include a literature review to evaluate the risk of PAS in pregnancies after UAE. Methods We retrospectively reviewed data from deliveries at our hospital between January 2012 and October 2017. We divided the delivery data into cases with previous UAEs performed for PPH (the post-UAE group) and those without UAEs (the non-UAE group, which included women without previous PPH). We defined PAS as cases in which hysterectomy was performed and pathological examination confirmed the diagnosis. Results are presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). Results We used data from 3155 patients in this study, of whom 16 patients had undergone UAE (post-UAE group) and 3139 had not (non-UAE group). We found no differences between the groups in terms of frequency of preterm births (12.5% versus 14.2%, respectively; OR, 0.863; 95% CI, 0.218 to 3.414; P = 0.84) or FGR (6.2% versus 10.0%, respectively; OR, 0.602; 95% CI, 0.104 to 3.584; P = 0.61). However, cases of PAS were significantly more common in the post-UAE group (37.5%) than in the non-UAE group (1.2%; OR, 50.303; 95% CI, 17.38 to 145.592; P < 0.01). Conclusion Our results suggest that previous UAE is a significant risk factor for PAS.

In this study, we aimed to investigate whether there was a significant prognostic difference between single and multiple cervical dilations when inducing second-trimester abortion.We conducted a retrospective review of 238 pregnant women who underwent termination of pregnancy at 12-21 weeks of gestation at Osaka University Hospital in Osaka, Japan, between January 2010 and May 2018. Termination of pregnancy was performed by vaginal administration of 1 mg gemeprost every 3 h for up to five doses per day after uterine cervical dilation using lamicel.The women were categorized into two groups: 191 women had a delivery time of24 h, whereas 47 had delivery times24 h. Contrasting the groups, there were significant differences with regard to numbers of primiparas (88 [46.1%] and 32 [68.1%], respectively) and lamicel exchanges ± SD (1.9 ± 0.67 for24 h and 2.4 ± 0.87 for24 h, respectively). Additionally, we compared the prognosis of primiparas that received just a single lamicel with that of primiparas that had ≥2 exchanged, but no significant differences were noted in the number of patients with a delivery time of24 h and the number of used gemeprost.Primipara is a risk factor for delayed delivery time of induced abortion. However, increasing the number of exchanged lamicel did not significantly reduce the delivery time; therefore, it should be performed as minimally as possible.

Increasing evidence suggests a relationship between in vitro fertilization-embryo transfer (IVF-ET) and placenta accreta spectrum (PAS). Some studies have reported a lower rate of antenatal diagnosis of PAS after IVF-ET compared to PAS with spontaneous conception. This study aimed to review the diagnostic accuracy of PAS after IVF-ET and to explore the relationship between IVF-ET pregnancy and PAS. According to the PRISMA guidelines, a comprehensive systematic review of the literature was conducted through August 31, 2020 to determine the effects of IVF-ET on PAS. In addition, a meta-analysis was conducted to explore the relationship between IVF-ET pregnancy and PAS. Twelve original studies (2011–2020) met the inclusion criteria. Among these, 190,139 IVF-ET pregnancies and 248,534 spontaneous conceptions met the inclusion criteria. In the comparator analysis between PAS after IVF-ET and PAS with spontaneous conception (n = 2), the antenatal diagnosis of PAS after IVF-ET was significantly lower than that of PAS with spontaneous conception (22.2% versus 94.7%, P versus 46.9%, P P P P

OBJECTIVE This study aimed to review the effect of endometriosis on the prevalence of placenta previa and postpartum hemorrhage in pregnant patients and the surgical outcomes of pregnant patients with endometriosis developing placenta previa. DATA SOURCES In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of the literature was conducted on December 31, 2020, using PubMed, Scopus, and the Cochrane Library. STUDY ELIGIBILITY CRITERIA Comparative studies between pregnant women with and without endometriosis and studies that investigated the surgical outcomes of patients with and without endometriosis developing placenta previa were included. METHODS Here, 2 reviewers independently screened the titles and abstracts, completed data extraction, and assessed the reporting quality using the Risk of Bias in Nonrandomized Studies of Interventions tool. RESULTS Overall, 19 studies (from 2010 to 2020) met the inclusion criteria (98,463 pregnancies with endometriosis and 7,184,313 pregnancies without endometriosis). In the adjusted pooled analysis, endometriosis was associated with a higher rate of placenta previa (adjusted odds ratio, 3.17; 95% confidence interval, 2.58–3.89), whereas the incidence of postpartum hemorrhage was similar between pregnant women with and without endometriosis (adjusted odds ratio, 1.15; 95% confidence interval, 0.99–1.34). When the analysis was restricted to histologically confirmed endometriosis cases, the relationship of endometriosis with placenta previa (adjusted odds ratio, 4.23; 95% confidence interval, 1.74–10.30) and postpartum hemorrhage (adjusted odds ratio, 1.29; 95% confidence interval, 0.50–3.34) was consistent with results from the nonrestricted analysis. There was no study that examined the surgical outcomes of patients with endometriosis developing placenta previa patients. However, there are 3 studies that examined the effect of endometriosis on surgical outcomes during cesarean delivery: 1 study showing that endometriosis was associated with increased intraoperative bleeding during emergent cesarean delivery; the other study showing that endometriosis was associated with an increased incidence of postpartum hemorrhage during cesarean delivery (adjusted odds ratio, 1.1; 95% confidence interval, 1.0–1.2), especially in primiparous women with singleton pregnancies (adjusted odds ratio, 1.7; 95% confidence interval, 1.5–2.0); and another study suggesting a significantly higher rate of hysterectomy (7.1%) and bladder injury (7.1%) in patients with endometriosis than in those without endometriosis. CONCLUSION Endometriosis can potentially be associated with adverse surgical outcomes during cesarean delivery. Although there is a correlation between endometriosis and increased rate of placenta previa, the surgical outcomes of patients with endometriosis developing placenta previa remain understudied.

Background A diagnostic sign on magnetic resonance imaging, suggestive of posterior extrauterine adhesion (PEUA), was identified in patients with placenta previa. However, the clinical features or surgical outcomes of patients with placenta previa and PEUA are unclear. Our study aimed to investigate the clinical characteristics of placenta previa with PEUA and determine whether an altered management strategy improved surgical outcomes. Methods This single institution retrospective study examined patients with placenta previa who underwent cesarean delivery between 2014 and 2019. In June 2017, we recognized that PEUA was associated with increased intraoperative bleeding; thus, we altered the management of patients with placenta previa and PEUA. To assess the relationship between changes in practice and surgical outcomes, a quasi-experimental method was used to examine the difference-in-difference before (pre group) and after (post group) the changes. Surgical management was modified as follows: (i) minimization of uterine exteriorization and adhesion detachment during cesarean delivery and (ii) use of Nelaton catheters for guiding cervical passage during Bakri balloon insertion. To account for patient characteristics, propensity score matching and multivariate regression analyses were performed. Results The study cohort (n = 141) comprised of 24 patients with placenta previa and PEUA (PEUA group) and 117 non-PEUA patients (control group). The PEUA patients were further categorized into the pre (n = 12) and post groups (n = 12) based on the changes in surgical management. Total placenta previa and posterior placentas were more likely in the PEUA group than in the control group (66.7% versus 42.7% [P = 0.04] and 95.8% versus 63.2% [P n = 72), intraoperative blood loss was significantly higher in the PEUA group (n = 24) than in the control group (n = 48) (1515 mL versus 870 mL, P t = 2.46, P = 0.02). Intraoperative blood loss in the post group was successfully reduced, as opposed to in the pre group (1180 mL versus 1827 mL, P = 0.04). Conclusions PEUA was associated with total placenta previa, posterior placenta, and increased intraoperative bleeding in patients with placenta previa. Our altered management could reduce the intraoperative blood loss.

The underlying mechanism of preeclampsia by which an angiogenic imbalance results in systemic vascular endothelial dysfunction remains unclear. Complement activation directly induces endothelial dysfunction and is known to be involved in preeclampsia; nevertheless, the association between complement activation and angiogenic imbalance has not been established. This study aimed to evaluate whether angiogenic imbalance affects the expression and secretion of inhibitory complement factor H (CFH) in endothelial cells, resulting in complement activation and systemic vascular endothelial dysfunction. Viability of human umbilical vein endothelial cells (HUVECs) was assessed upon CFH knockdown by targeted-siRNA, and were incubated with complement factors. HUVECs were also treated with placental growth factor (PlGF) and/or soluble fms-like tyrosine kinase 1 (sFlt1), and CFH expression and secretion were measured. These cells were evaluated by cell viability assay and cell surface complement activation was quantified by immunocytochemical assessment of C5b-9 deposition. HUVECs transfected with CFH-siRNA had significantly lower viability than that of control cells. Moreover, the expression and secretion of CFH were significantly increased upon PlGF treatment compared with PlGF + sFlt1 combo. HUVECs treated with PlGF had less C5b-9 deposition and higher viability than HUVECs treated with PlGF + sFlt1. In summary, CFH was found to be essential for endothelial cell survival by inhibiting complement activation. An angiogenic imbalance, including decreased PlGF and increased sFlt1, suppresses CFH expression and secretion, resulting in complement activation on the surface of endothelial cells and systemic vascular endothelial dysfunction.

BackgroundThis study aimed to identify and review associations between the types of sutures used for uterine compression suture (UCS) and its outcomes in postpartum hemorrhage.MethodsAn electronic search using PubMed and Scopus databases was performed. We included the English articles reported from January 1, 1997, to May 31, 2017, using search words or terms regarding the types of suture and needle used for UCSs. We only included studies describing the sutures in the systematic review.ResultsWe found 196 studies and included 76 (38.8%) in our analysis. We collected data on maternal outcomes for 924 patients and categorized them. Of the 76 studies, suture sizes 0, 1, and 2 were used in 6, 44, and 32 articles, respectively (some studies used multiple sutures). Of the 45 studies mentioning the needles, curved and straight needles were used in 35 and 10, respectively. The results of our review revealed that about 80% of previous articles used Catgut and Polyglactin 910 sutures. Because no studies that compared the efficacy of different size of sutures were identified, we investigated the differences using the cases reported in previous studies mentioned above. In the first analysis, we compared the uterine preservation rate between size 1 and size 2 sutures. We found no significant difference in uterine preservation rate (92.8%: size 1 vs. 94.2%: size 2,p > 0.05) but found significant difference in transfusion rate (62.4% vs. 79.1%,p p = 0.033).ConclusionsOur systematic review showed that approximately 80% of cases were treated by Catgut and Polyglactin 910. Due to the heterogeneity of cases included in this review, it is difficult to estimate which suture is better for UCSs. More robust studies are necessary to enable the identification of the superior suture for performing UCSs.

AIM Previous studies have shown adverse obstetric outcomes of the laparoscopic resection of a rudimentary horn. Our study aimed to investigate the obstetric outcome in our institution and to review previous studies. METHODS Using a retrospective analysis, data were reviewed from singleton pregnancies with maternal uterine anomalies at a medical center in Osaka, Japan, between January 2011 and March 2016. The uterine anomaly cases were divided into a 'postlaparoscopic resection of the rudimentary horn' group (study group) and an 'other uterine anomalies' (bicornuate uterus, uterine didelphys and unicornuate uterus) group (control group). Primary outcomes of interest were differences in obstetric outcomes, such as spontaneous preterm birth rate, small for gestational age (SGA) infant rate and hypertensive disorders of pregnancy (HDP) rate between the study and the control group, and the secondary outcome of interest was mode of delivery in the study group. RESULTS Data from 40 deliveries were included in the study (7 deliveries: study group, 33 deliveries: control group). No significant difference was observed between the two groups in terms of either mean gestational weeks at delivery (36.4 weeks vs 37.1 weeks; P = .38), cesarean delivery rate (57.1% vs 57.5%; P = 1.0), SGA infant rate (

Aim The purpose of this study was to report the 3-year experience of a nationwide demonstration project to introduce non-invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the current status of NIPT in Japan. Methods Tests were conducted to detect aneuploidy in high-risk pregnant women, and adequate genetic counseling was provided. The clinical data, test results, and pregnancy outcomes were recorded. We discuss the problems of NIPT on the basis of published reports and meta-analyses. Results From April 2013 to March 2016, 30 613 tests were conducted at 55 medical sites participating in a multicenter clinical study. Among the 30 613 women tested, 554 were positive (1.81%) and 30 021 were negative (98.1%) for aneuploidy. Of the 289, 128, and 44 women who tested positive for trisomies 21, 18, and 13, respectively, and underwent definitive testing, 279 (96.5%), 106 (82.8%), and 28 (63.6%) were determined to have a true-positive result. For the 13 481 women with negative result and whose progress could be traced, two had a false-negative result (0.02%). The tests were performed on the condition that a standard level of genetic counseling be provided at hospitals. Conclusion Here, we report on the 3-year nationwide experience with NIPT in Japan. It is important to establish a genetic counseling system to enable women to make informed decisions regarding prenatal testing. Moreover, a welfare system is warranted to support women who decide to give birth to and raise children with chromosomal diseases.

Background Sheehan’s syndrome occurs because of severe postpartum hemorrhage causing ischemic pituitary necrosis. Sheehan’s syndrome is a well-known condition that is generally diagnosed several years postpartum. However, acute Sheehan’s syndrome is rare, and clinicians have little exposure to it. It can be life-threatening. There have been no reviews of acute Sheehan’s syndrome and no reports of successful pregnancies after acute Sheehan’s syndrome. We present such a case, and to understand this rare condition, we have reviewed and discussed the literature pertaining to it. An electronic search for acute Sheehan’s syndrome in the literature from January 1990 and May 2014 was performed. Case presentation A 27-year-old woman had massive postpartum hemorrhage (approximately 5000 mL) at her first delivery due to atonic bleeding. She was transfused and treated with uterine embolization, which successfully stopped the bleeding. The postpartum period was uncomplicated through day 7 following the hemorrhage. However, on day 8, the patient had sudden onset of seizures and subsequently became comatose. Laboratory results revealed hypothyroidism, hypoglycemia, hypoprolactinemia, and adrenal insufficiency. Thus, the patient was diagnosed with acute Sheehan’s syndrome. Following treatment with thyroxine and hydrocortisone, her condition improved, and she was discharged on day 24. Her next pregnancy was established 2 years after her first delivery. She required induction of ovulation for the next conception. The pregnancy, delivery, and postpartum period were uneventful. An electronic search of the literature yielded 21 cases of acute Sheehan’s syndrome. Presenting signs varied, including adrenal insufficiency (12 cases), diabetes insipidus (4 cases), hypothyroidism (2 cases), and panhypopituitarism (3 cases), with a median time of presentation after delivery for each of those conditions being 7.9, 4, 18, and 9 days, respectively. Serial changes in magnetic resonance imaging were reported in some cases of acute Sheehan’s syndrome. Conclusion Clinicians should be aware of the risk of acute Sheehan’s syndrome after a massive postpartum hemorrhage in order to diagnose it accurately and treat it promptly.

Objective To evaluate sonographic findings and clinical outcomes after induced medical abortions. Study design We reviewed records of women who had induced medical abortions at 12–21 weeks of gestation at the Osaka University Hospital between January 2010 and May 2018. Clinicians evaluated each patient using two-dimensional grayscale transvaginal ultrasonography approximately 1 day, 1 week and 1 month after abortion as a routine care in our hospital. Clinicians employed color Doppler imaging if they detected hyperechoic mass within the endometrial cavity. We evaluated the endometrial vascularity as follows: grade 1, minimal flow; grade 2, moderate flow; and grade 3, highly vascular. We evaluated the incidence of vascularity and assessed the clinical course according to the quantity of vascularity. Clinicians did not provide intervention based on ultrasound findings alone. Results Of 319 patients, 75 (24%) had vascularity at one or more evaluations, including 1% (3/319), 12% (38/319) and 15% (48/319) at 1 day, 1 week and 1 month after abortion, respectively. Of these, 44 had grade 1, 16 had grade 2, and 15 had grade 3. Fifty-four women (72%) with a vascularity had no symptoms. All sonographically-identified vascularity resolved spontaneously regardless of symptoms and quantity of vascularity within 150 days (mean interval 68.6 ± 32.2 days). No patients required transfusion or invasive procedures. Conclusions Vascular endometrial findings were prevalent after induced medical abortions; however, most were asymptomatic, appeared an average of approximately 3 weeks after abortion, and all resolved spontaneously. Implications Although hypervascularity can be found routinely on ultrasonography after induced medical abortions, this finding commonly resolves spontaneously regardless of symptoms and its quantity. Thus, hemodynamically stable patients, even those with sonographic hypervascularity, can be managed expectantly.

Introduction Preeclampsia therapy has not been established, except for the termination of pregnancy. The aim of this study was to identify a potential therapeutic agent from traditional Japanese medicine (Kampo) using the drug repositioning method. Materials and methods We screened a library of 74 Kampo to identify potential drugs for the treatment of preeclampsia. We investigated the angiogenic effects of these drugs using human umbilical vein endothelial cells (HUVECs). Enzyme-linked immunosorbent assays were performed to measure the levels of placental growth factor (PlGF) in conditioned media treated with 100 μg/mL of each drug. We assessed whether the screened drugs affected cell viability. We performed tube formation assays to evaluate the angiogenic effects of PlGF-inducing drugs. PlGF was measured after administering 10, 50, 100, and 200 μg/mL of the candidate drug in the dose correlation experiment, and at 1, 2, 3, 6, 12, and 24 h in the time course experiment. We also performed tube formation assays with the candidate drug and 100 ng/mL of soluble fms-like tyrosine kinase 1 (sFlt1). PlGF production by the candidate drug was measured in trophoblastic cells (BeWo and HTR-8/SVneo). The Mann-Whitney U test or one-way analyses of variance followed by the Newman-Keuls post-hoc test were performed. P–values < 0.05 were considered significant. Results Of the 7 drugs that induced PlGF, Tokishakuyakusan (TS), Shoseiryuto, and Shofusan did not reduce cell viability. TS significantly facilitated tube formation (P = 0.017). TS administration increased PlGF expression in a dose- and time-dependent manner. TS significantly improved tube formation, which was inhibited by sFlt1 (P = 0.033). TS also increased PlGF production in BeWo (P = 0.001) but not HTR-8/SVneo cells (P = 0.33). Conclusions By using the drug repositioning method in the in vitro screening of the Kampo library, we identified that TS may have a therapeutic potential for preeclampsia. Its newly found mechanisms involve the increase in PlGF production, and improvement of the antiangiogenic state.

This study aimed to determine the association between umbilical cord leucine-rich alpha-2 glycoprotein (LRG) and fetal infection and investigate the underlying mechanism of LRG elevation in fetuses. We retrospectively reviewed the medical records of patients who delivered at Osaka University Hospital between 2012 and 2017 and selected those with histologically confirmed chorioamnionitis (CAM), which is a common pregnancy complication that may cause neonatal infection. The participants were divided into two groups: CAM with fetal infection (CAM-f[+] group,n =14) and CAM without fetal infection (CAM-f[−] group,n =31). Fetal infection was defined by the histological evidence of funisitis. We also selected 50 cases without clinical signs of CAM to serve as the control. LRG concentrations in sera obtained from the umbilical cord were unaffected by gestational age at delivery, neonatal birth weight, nor the presence of noninfectious obstetric complications (all,p> 0.05). Meanwhile, the LRG levels (median, Interquartile range [IQR]) were significantly higher in the CAM-f(+) group (10.37 [5.21–13.7] μg/ml) than in the CAM-f(−) (3.61 [2.71–4.65] μg/ml) or control group (3.39 [2.81–3.93] μg/ml;p< 0.01). The area under the receiver operating characteristic (ROC) curve of LRG for recognizing fetal infection was 0.92 (optimal cutoff, 5.08 μg/ml; sensitivity, 86%; specificity, 88%). In a mouse CAM model established by lipopolysaccharide administration, the fetal LRG protein in sera andLRGmRNA in the liver were significantly higher than those in phosphate-buffered saline (PBS)-administered control mice (p< 0.01).In vitroexperiments using a fetal liver-derived cell line (WRL68) showed that the expression ofLRGmRNA was significantly increased after interleukin (IL)-6, IL-1β, and tumor necrosis factor- alpha (TNF-α) stimulation (p< 0.01); the induction was considerably stronger following IL-6 and TNF-α stimulation (p< 0.01). In conclusion, LRG is an effective biomarker of fetal infection, and fetal hepatocytes stimulated with inflammatory cytokines may be the primary source of LRG productionin utero.

OBJECTIVE To evaluate the reasons for nonreportable cell-free DNA (cfDNA) results in noninvasive prenatal testing (NIPT), we retrospectively studied maternal characteristics and other details associated with the results. METHODS A multicenter retrospective cohort study in pregnant women undergoing NIPT by massively parallel sequencing (MPS) with failed cfDNA tests was performed between April 2013 and March 2017. The women's data and MPS results were analyzed in terms of maternal characteristics, test performance, fetal fraction (FF), z scores, anticoagulation therapy, and other details of the nonreportable cases. RESULTS Overall, 110 (0.32%) of 34 626 pregnant women had nonreportable cfDNA test results after an initial blood sampling; 22 (20.0%) cases had a low FF (

Excessive soluble fms-like tyrosine kinase-1 (sFlt-1) has been strongly implicated in preeclampsia. An increase in the serum sFlt-1 level occurs before the onset of preeclampsia, and the sFlt-1 level is already higher in women who are predisposed to preeclampsia than in normotensive pregnant women. This study aimed to investigate the relation between arginase and sFlt-1 in the plasma of preeclamptic women and normotensive pregnant women. We suggested that a regulatory mechanism exists that suppresses the level of sFlt-1. The relationship between arginase, one of the nitric oxide (NO) modulators, and sFlt-1 was examined. First, the pregnant women were divided into 4 groups: group 1, sFlt-16000 pg/ml and arginase activity110 U/L; group 2, sFlt-1 ≥6000 pg/ml and arginase activity110 U/L; group 3, sFlt-1 ≥6000 pg/ml and arginase activity ≥110 U/L; and group 4, sFlt-16000 pg/ml and arginase activity ≥110 U/L. Groups 2 and 3 comprised preeclamptic women. The preeclampsia/normotensive ratio increased from groups 1 to 3. Under the higher sFlt-1 condition, lower arginase activity was associated with lower occurrence of preeclampsia. Next, in human umbilical endothelial vein cells (HUVECs), a slightly higher concentration of sFlt-1, as in group 2, reduced arginase expression and arginase activity, and S-(2-boronoethyl)-l-cysteine (BEC; arginase inhibitor) impaired sFlt-1 secretion. In contrast, a higher level of sFlt-1 increased arginase expression and activity in HUVECs, as in group 3. These results showed that arginase controlled sFlt-1 elevation to some extent. In conclusion, our results suggest the existence of a mechanism to maintain the level of sFlt-1. Soluble Flt-1 negatively regulated itself against increasing serum sFlt-1 in preeclampsia. Moreover, this study revealed that arginase inhibitors are a potential treatment option for preeclampsia.

We sought to investigate obstetric outcomes and acceptance rates for blood products or types of autotransfusion by Jehovah’s Witnesses (JWs) at a single institution in Japan. We retrospectively reviewed cases of 84 pregnant JW patients and 95 deliveries from April 2001 to August 2017. We examined the acceptance rates of blood transfusions, blood products, and autotransfusion types in patients who experienced postpartum hemorrhage (PPH), and investigated estimated hemorrhage volume at delivery and PPH treatments. Of the 84 JW patients, none accepted blood transfusion; however, 75 patients (89.3%) accepted blood products, 57 (67.9%) accepted autotransfusion using intraoperative cell salvage, and four (4.8%) refused all alternatives to blood transfusion. Furthermore, PPH > 1000 mL occurred in 18 of the 95 (18.9%) deliveries. Of these 18 patients, four (22.2%) required blood products and three (16.7%) required supracervical hysterectomy to control PPH. No maternal deaths occurred. Approximately 95% of the patients observed accepted all or some alternatives to blood transfusion. To treat JW patients in a safer manner, understanding their individual acceptance of alternatives to blood transfusion is important for the strategic use of such alternatives.

Objective The purpose of this study is to compare the fetal fractions during non-invasive prenatal testing (NIPT) in singleton pregnancies according to gestational age and maternal characteristics to evaluate the utility of this parameter for the prediction of pregnancy complications including gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP). Study design This study was a multicenter prospective cohort study. The present data were collected from women whose NIPT results were negative. The relationships between the fetal fractions and the gestational age, maternal weight and height, and incidences of miscarriage, preterm delivery, and pregnancy complications including GDM, HDP and placental abruption were assessed. Results A total of 5582 pregnant women with verified NIPT negative results were registered in the study. The demographic characteristics of the study populations were statistically analyzed, and the women with HDP tended to have a low fetal fraction in samples taken during early gestation. The area under the curve (AUC) in a receiver operating characteristic curve (ROC) analysis was 0.608 for women with HDP. Conclusion A low fetal fraction on NIPT might be correlated with future HDP. However, predicting HDP during early pregnancy in women with a low fetal fraction might be difficult.

We screened a library of 528 approved drugs to identify candidate compounds with therapeutic potential as preeclampsia treatments via their proangiogenic properties. Using human umbilical vein endothelial cells (HUVECs), we assessed whether the screened drugs induced placental growth factor (PIGF) and restored damaged endothelial cell function. Enzyme-linked immunosorbent assays (ELISAs) were carried out to measure levels of PlGF in conditioned media treated with each drug (100 µmol/L) in the drug library. Tube formation assays were performed using HUVECs to evaluate the angiogenic effects of drugs that induced PlGF. We also performed ELISA, quantitative reverse transcription polymerase chain reaction, and tube formation assays after treatment with a range of concentrations of the candidate drug. Of the drugs that induced PlGF, vardenafil was the only compound that significantly facilitated tube formation in comparison with the control cells (P < .01). Treatment with vardenafil at concentrations of 50, 100, and 250 µmol/L increased expression of PlGF in a dose-dependent manner. Vardenafil (250 µmol/L) significantly improved tube formation which was inhibited in the presence of soluble fms-like tyrosine kinase 1 (100 ng/mL) and/or soluble endoglin (100 ng/mL). Production of PlGF from HUVECs in the presence of sera derived from patients with preeclampsia was significantly elevated by administration of vardenafil (250 µmol/L). By assessing drug repositioning through screening a library of approved drugs, we identified vardenafil as a potential protective agent against preeclampsia. The therapeutic mechanism of vardenafil may involve inhibition of the systemic maternal antiangiogenic state that leads to preeclampsia, in addition to its vasodilating effect. As concentrations used are high and unlikely to be useful clinically, further work is needed before testing it in humans.

Background Maternal outcomes after conservative management of placenta percreta are poorly understood. Objective To assess the success and complication rates of conservative management of placenta percreta. Search strategy The PubMed, MEDLINE, and Scopus databases were searched for English-language articles published between January 1990 and December 2016, using combinations of search terms related to conservative management of placenta percreta. Selection criteria Only studies describing conservative treatment for placenta percreta (without placental removal) were included in the systematic review. Data collection and analysis There were 44 studies included and maternal outcomes were reviewed and categorized among 72 patients. Main results The uterus was preserved among 42 (58%) patients and severe complications developed among 40 (56%). Prophylactic uterine artery embolization (UAE) did not improve success rates (P=0.807); however, the mean time for complete placental resorption was lower in the UAE group than in the non-UAE group (22.4 weeks vs 35.3 weeks; P=0.014). Hysterectomy was performed at a mean of 44.6 days after cesarean delivery. Among the 23 patients with hysterectomy-related complications, 18 (78%) experienced bladder injury, intraoperative bleeding (>2000 mL), or both. The use of chemotherapy did not improve success rates (P=0.064). Conclusions The present systematic review revealed high maternal morbidity during conservative management of placenta percreta.

The aim of this study was to report the pregnancy outcomes of women who received different doses of corticosteroid supplementation during labor and delivery.We conducted a retrospective review of 102 pregnant women who received oral corticosteroid therapy, delivered at Osaka University Hospital, and were administered intravenous corticosteroid supplementation during labor and delivery. From January 2008 to May 2012, 47 women were administered a high dose of corticosteroids (HD group). From June 2012 to December 2016, 55 women were given a low dose of corticosteroids (LD group).There were no significant differences in the patient characteristics between the two groups. The most frequent disease was systemic lupus erythematosus (30/102; 29.4%). Most women used prednisolone for more than 1 year (91/102; 89.2%) and at a dose of more than 5 mg/day (88/102; 86.3%). The total intravenous dose of hydrocortisone during labor and delivery ± standard deviation was 233.5 ± 129.4 mg (HD group) and 143.4 ± 38.1 mg (LD group), exhibiting a significantly larger dose in the HD group. No patients suffered an adrenal deficiency and there were no significant differences in the hemodynamics. There were three cases of puerperal endometritis, two patients with hyperglycemia, and one wound infection in the HD group, whereas one case of puerperal endometritis in the LD group. There were no significant differences in the neonatal outcomes.Pregnancy outcomes did not differ between the high and low doses of corticosteroid supplementation during labor and delivery.

We report a case of mirror syndrome caused by parvovirus B19, which resolved after intra-uterine transfusion. Mirror syndrome is a rare condition characterised by a triad of foetal hydrops, generalized maternal oedema and placentomegaly. Although the mechanism underlying the onset of this syndrome is unknown, it probably shares a common pathophysiologic origin with pre-eclampsia. Our patient showed increased circulating levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and decreased levels of placental growth factor (PlGF), which have also been reported in pre-eclampsia. The sFlt-1/PlGF ratio decreased immediately after intra-uterine transfusion, followed by resolution of both maternal and foetal symptoms. This suggests that the sFlt-1/PlGF ratio may help to predict the post-treatment course of mirror syndrome.

During pregnancy, and especially during labor, the maternal carbon dioxide level declines considerably. Maternal carbon dioxide levels show a close relation with fetal carbon dioxide levels. The latter affects fetal cerebral oxygenation by regulating cerebral blood flow and shifting the oxyhemoglobin dissociation curve. In addition, maternal hypocapnia appears to impair placental oxygen transfer. Thus, maternal hyperventilation may interfere with optimal fetal cerebral oxygenation. Here, we provide a brief overview of the literature relevant to this issue.

The incidence of pre-eclampsia is significantly higher in trisomy 13 pregnancies than in normal pregnancies. Soluble fms-like tyrosine kinase-1 (sFlt-1), located on chromosome 13, is an anti-angiogenic molecule derived from the placenta and contributes to the pathogenesis of pre-eclampsia. Elevated sFlt-1 and reduced placental growth factor (PlGF) are associated with trisomy 13 pregnancies and may play a pathogenic role in the subsequent development of pre-eclampsia. Here we present a case of a trisomy 13 pregnancy without any signs of pre-eclampsia that showed alterations in circulating angiogenic factors and abnormal placental appearance. The placenta developed edematous changes and contained multiple small cysts. Histology of the placenta confirmed avascular edematous cystic villi and did not show the typical appearance of a partial mole or mesenchymal dysplasia. The sFlt-1/PlGF ratio in maternal serum (134) was much higher than that in gestational age-matched women who were normotensive (2.9–7.2; mean, 5.0). Immunostaining for Flt-1 and endoglin was more intense in our case compared with gestational age-matched controls, and at a similar level to a case of pre-eclampsia. Placental findings that showed avascular edematous cystic villi in our case may be associated with angiogenic imbalance involved in the pathogenesis of pre-eclampsia in trisomy 13 pregnancies.

Interstitial, angular, and cornual pregnancies and intrauterine pregnancies in an anomalous uterus are separate entities, and the impact of each condition on obstetric outcomes is completely different. However, there is considerable confusion in understanding and managing the natural course of each condition due to a lack of uniform terminology. The single most important factor for differentiating these types of pregnancies is to make an early diagnosis. The differences between interstitial, angular, and cornual pregnancies on 2-dimensional (2D) sonography are subtle. Although magnetic resonance imaging can be used to differentiate these conditions, it is not preferred as the initial assessment tool because of its limited availability and cost-effectiveness. Three-dimensional (3D) sonography has the advantage of providing views of the uterus that cannot be obtained with conventional 2D sonography. We describe 3 cases of interstitial, angular, and intrauterine pregnancies in a septate uterus that were clearly differentiated by 3D sonography. We demonstrate the differences in diagnostic imaging findings and emphasize the importance of 3D sonography in differentiating these entities.

The objective of this study was to document early neonatal (7 days) pulmonary outcome in the rabbit model for preterm birth and hyperoxia-induced lung injury. Preterm pups were delivered at 28 days (term = 31 days; early saccular phase of lung development) by cesarean section, housed in an incubator, and gavage fed for 7 days. Pups were divided into the following groups: 1) normoxia (21% O2; normoxia group) and 2) and hyperoxia (>95% O2; hyperoxia group). Controls were pups born at term who were housed in normoxic conditions (control group). Outcome measures were survival, pulmonary function tests using the whole body plethysmograph and forced oscillation technique, and lung morphometry. There was a significant difference in survival of preterm pups whether they were exposed to normoxia (83.3%) or hyperoxia (55.9%). Hyperoxic exposure was associated with increased tissue damping and elasticity and decreased static compliance compared with normoxic controls ( P < 0.01). Morphometry revealed an increased linear intercept and increased mean wall transection length, which translates to larger alveoli with septal thickening in hyperoxia compared with normoxia ( P < 0.01). In conclusion, the current experimental hyperoxic conditions to which preterm pups are exposed induce the typical clinical features of bronchopulmonary dysplasia. This model will be used to study novel preventive or therapeutic interventions.

During pregnancy, and especially during labor, the maternal carbon dioxide level declines considerably. Maternal carbon dioxide levels show a close relation with fetal carbon dioxide levels. The latter affects fetal cerebral oxygenation by regulating cerebral blood flow and shifting the oxyhemoglobin dissociation curve. In addition, maternal hypocapnia appears to impair placental oxygen transfer. Thus, maternal hyperventilation may interfere with optimal fetal cerebral oxygenation. Here, we provide a brief overview of the literature relevant to this issue.

To investigate the relationship between maternal hyperventilation and fetal blood gas values and to estimate its possible association with fetal oxygenation, maternal transcutaneous partial pressure of carbon dioxide (tcP(CO2)) values were analyzed in association with umbilical venous P(CO2) (UVP(CO2)), umbilical venous partial pressure of oxygen (UVP(O2)), and umbilical venous oxyhemoglobin saturation (UVHbo (2)) values. Pregnant women without labor (30.7 ± 3.7 mm Hg, n = 20) showed significantly lower tcP(CO2) values compared with nonpregnant women (37.4 ± 4.0 mm Hg, n = 10). Pregnant women in the second stage of labor showed even lower tcP(CO2) values compared with pregnant women during the first stage of labor (20.8 ± 5.9 mm Hg vs 28.4 ± 5.0 mm Hg, n = 26). Maternal tcP(CO2) values had significant positive correlations with UVP(CO2) (r = .78, P.001), UVP(O2) (r = .62, P.001), and UVHb(O2) values (r = .59, P.001). Maternal hyperventilation had a close relationship with lower UVP(CO2), UVP(O2), and UVHbo(2) values, which might interfere with optimal fetal cerebral oxygenation.