Local vaginal bioelectrical impedance can predict preterm delivery in mice.

Preterm birth is a serious pregnancy complication that affects neonatal mortality, morbidity, and long-term neurological prognosis. Predicting spontaneous preterm delivery (PTD) is important for its management. While excluding the risk of PTD is important, identifying women at high risk of PTD is imperative for medical intervention. Currently used PTD prediction parameters in clinical practice have shown high negative predictive values, but low positive predictive values. We focused on sulfated and sialylated glycocalyx changes in the uterus and vagina prior to the onset of parturition and explored the potential of electrophysiological detection of these changes as a PTD prediction parameter with a high positive predictive value. In vivo local vaginal bioelectrical impedance (VZ) was measured using two different mouse PTD models. PTD was induced in ICR mice through the subcutaneous injection of mifepristone or local intrauterine injection of lipopolysaccharide (LPS). The PTD rates were 100% and 60% post-administration of mifepristone (16-20 h, n = 4) and LPS (12-24 h, n = 20), respectively. The local VZ values (15 and 10 h after mifepristone or LPS treatment, respectively) were significantly lower in the PTD group than in the non-PTD group. Receiver operator characteristic (ROC) curve analysis of VZ at 125 kHz as a predictor of PTD showed an area under the ROC curve of 1.00 and 0.77 and positive predictive values of 1.00 and 0.86, for the mifepristone and LPS models, respectively, suggesting that local VZ value can predict PTD. Histological examination of the LPS-treated model 6 h post-treatment revealed increased expression of sulfomucins and/or sulfated proteoglycans and sialomucins in the cervical epithelium, cervical stroma and vaginal stroma. In conclusion, local VZ values can determine sulfated and sialylated glycocalyx alterations within the uterus and vagina and might be a useful PTD prediction parameter.

Severe hemolysis, elevated liver enzymes, and low platelet syndrome requiring differentiation of thrombotic microangiopathy: Four cases from a nationwide survey in Japan.

Severe cases of hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome requiring plasma exchange or dialysis should be differentiated from other thrombotic microangiopathy (TMA) and treated appropriately. To evaluate the prevalence and clinical characteristics of such cases in Japan, a questionnaire-based survey was conducted among obstetricians who are members of the Perinatal Research Network Group in Japan. There were a total of 335 cases of HELLP syndrome over a 3-year period in the 48 facilities that responded to the survey. Four patients required plasma exchange or dialysis, of which two were diagnosed with atypical hemolytic uremic syndrome and two with TMA secondary to systemic lupus erythematosus. Although such severe HELLP syndrome is rare, identifying the clinical features and making accurate differential diagnosis are critical for optimal clinical outcomes for mothers and neonates.

Systemic inflammation enhances metastatic growth in a syngeneic neuroblastoma mouse model.

BACKGROUND: We previously showed that total tumor resection enhances metastatic growth in a syngeneic metastatic mouse model of neuroblastoma. In this study, we further investigated which surgical factors contributed most to metastatic growth. METHODS: Tumor cells derived from MYCN transgenic mice were subcutaneously injected into wild-type mice. Mice were randomly assigned to receive partial resection (PR group), subcutaneous implantation of a sponge (Sp group), or observation (Obs group). The lymph node metastasis volume and the frequency of lung metastasis were compared 14 days after assignment by measuring C-reactive protein (CRP) and interleukin-6 (IL-6) levels. RESULTS: The lymph node metastasis volume in the Sp group was larger than in the Obs group (148.4 [standard deviation {SD}: 209.5] vs. 10.2 [SD 12.8] mm3). The frequency of lung metastasis was greater in the Sp group than in the PR group (11.9 [SD 12.2] vs. 6.6 [SD 4.0] counts/slide). The CRP level in the Sp group was higher than in the PR group (2.3 [SD 0.5] vs. 1.5 [SD 0.4] µg/mL), and the IL-6 level in the Sp group was higher than in the PR or Obs groups (28.4 [SD 34.5] vs. 12.4 [SD 19.0] vs. 5.4 [SD 8.1] pg/mL). CONCLUSION: Metastatic growth may be enhanced by systemic inflammation.

Neonatal outcomes of congenital diaphragmatic hernia in full term versus early term deliveries: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to review the optimal timing of delivery at term for neonates with prenatally diagnosed congenital diaphragmatic hernia (CDH). We reviewed the literature up to December 19, 2022 using MEDLINE and the Cochrane Library databases. The inclusion criteria were original articles, comparative studies of CDH neonates delivered at an early term (37-38 weeks of gestation) and at full term (39 weeks of gestation or later), and comparative studies investigating outcomes of CDH neonates. Six studies met the inclusion criteria, including 985 neonates delivered at an early term and 629 delivered at full term. The cumulative rate of survival to discharge showed no significant difference between CDH neonates delivered at an early term (395/515; 76.7%) or at full term (345/467; 73.9%) (risk ratio [RR] 1.01; 95% confidence interval [CI], 0.89-1.16; p = 0.85). Furthermore, the number of neonates requiring oxygen therapy at discharge was not significantly different between CDH neonates delivered at an early term (32/370; 8.6%) and at full term (14/154; 9.1%) (RR, 0.99; 95% CI, 0.36-2.70; p = 0.99). Therefore, the optimal timing of delivery at term for neonates with CDH remains unclear.

Obstetrical outcomes of labor with and without analgesia in Robson classification groups 1 and 2a: a single-center retrospective study.

PURPOSE: This study aimed to elucidate the effects of neuraxial analgesia on labor in women classified based on the Robson classification system. METHODS: We retrospectively reviewed the clinical data of singleton cephalic nulliparous deliveries in labor at term between January 2018 and December 2021 and compared obstetrical outcomes between deliveries with and without neuraxial analgesia in women of Robson group 1 (spontaneous labor) and group 2a (induced labor). Statistical analyses were performed using the Wilcoxon ranked-sum test, Fisher's exact test, and logistic regression model. Statistical significance was set at p < 0.05. RESULTS: We identified 2726 deliveries during the period, of which 387 deliveries (215 with analgesia and 172 without analgesia) were in Robson group 1 and 502 deliveries (258 with analgesia and 244 without analgesia) in Robson 2a. In Robson group 1 pregnancies, the cesarean section (CS) rate was higher in those who received analgesia (15%) than in those who did not (3%) (p = 0.0001). Multivariate analysis revealed that labor with analgesia was a significant risk factor for CS (p < 0.0001). Similarly, in Robson group 2a pregnancies, we observed a higher CS rate in those with analgesia than in those without analgesia (18 vs. 11%, p = 0.042). CONCLUSION: A higher CS rate was observed in deliveries with analgesia than in those without analgesia both in the Robson group 1 and group 2a pregnancies.

The accuracy of contrast-enhanced computed tomography scans to detect postpartum haemorrhage: an observational study.

INTRODUCTION: Postpartum haemorrhage is a major cause of maternal mortality. Although contrast-enhanced computed tomography (CE-CT) is useful to reveal arterial bleeding, its accuracy in postpartum haemorrhage is unclear. The aim of this study was to evaluate the accuracy of CE-CT scanning in detecting postpartum haemorrhage. METHODS: This was a retrospective observational study. We included patients with postpartum haemorrhage treated by emergency physicians in collaboration with obstetricians. We calculated the sensitivity, specificity, and positive and negative predictive values for CE-CT scanning to detect arterial bleeding. RESULTS: CE-CT scanning was performed in 52 patients, and 31 patients had extravasation. The sensitivity of CE-CT scanning to detect arterial extravasation was 100% (15/15), specificity was 28.6% (2/7), positive predictive value was 75% (15/20), and negative predictive value was 100% (2/2). CONCLUSION: We showed the sensitivity of CE-CT scanning to detect arterial extravasation in patients with postpartum haemorrhage to be 100%.

Atypical preeclampsia without underlying disease and elevated sFlt-1/PlGF ratio.

Atypical preeclampsia before 20 weeks of gestation without an underlying disease is very rare; however, the soluble Fms-like tyrosine kinase 1/placental growth factor (sFlt-1/PlGF) ratios remain unknown. Four pregnant women with no underlying disease, except for a history of childhood IgA vasculitis, developed preeclampsia at 13, 14, 17, and 18 weeks of gestation with sFlt-1/PlGF ratios of 1589, 1183, 500, and 1460 pg/mL, respectively. Their pregnancies were terminated, and they delivered within 2 weeks. All previously abnormal clinical findings normalized within 3 months. The sFlt-1/PlGF ratios were elevated in the four patients with atypical preeclampsia without underlying disease before 20 weeks of gestation. A high sFlt-1/PlGF ratio may be indicative of preeclampsia when no underlying disease is present in pregnancies of less than 20 weeks of gestation.

Successful management of a pregnant woman of lower-limb arteriovenous malformation with chronic cardiac failure.

The clinical features of extracranial arteriovenous malformations (AVM) vary from stages I (quiescence) with few symptoms to IV (decompensation) with overt symptoms of cardiac failure. Although the maternal outcomes of pregnant women with extracranial AVM is understudied due to its rarity, previous studies suggested the difficulty in the management of recurrent hemorrhage due to AVM progression during perinatal period; thus, pregnant case of extracranial AVM complicated with cardiac failure were considered challenging. We have reported a woman of stage IV extracranial AVM in the right lower limb with a history of below-the-knee amputation, in which two pregnancies and vaginal deliveries under epidural anesthesia were managed successfully. Cardiac failure did not exacerbate throughout the gestational or postpartum periods. Ulceration gradually worsened, with no massive hemorrhage. It is ideal to assess abnormal vascularity, especially in the lower abdomen, vagina, and epidural and subdural spaces, through magnetic resonance imaging to ensure safe delivery.

Outcome of Inducing Labor in Pregnancies with Suspected Fetal Growth Restriction: Oxytocin Discontinuation during the Active Phase of Labor versus Conventional Management.

OBJECTIVE: Although fetal growth restriction (FGR) is associated with an increased risk of cesarean delivery during induced labor, there is limited evidence to guide labor management. This study aimed to investigate the prognosis of induced labor in pregnancies with suspected FGR and whether oxytocin discontinuation during the active phase of labor affects maternal and neonatal outcomes. STUDY DESIGN: This retrospective cohort study investigated singleton pregnancies with vertex presentation and indications for labor induction owing to FGR after 34.0 weeks of gestation at Osaka University Hospital. From January 2010 to December 2013, women were conventionally managed, and oxytocin was continued until delivery unless there was an indication for discontinuation (conventional management group). From January 2013 to December 2020, oxytocin was routinely discontinued, or the dose was reduced at the beginning of the active phase of labor (oxytocin discontinuation group). RESULTS: A total of 161 women (conventional management group, n = 74; oxytocin discontinuation group, n = 87) were included. After the active phase of induced labor, the total incidence of cesarean delivery was very low (3.1%), and the duration was short (173 ± 145 minutes). Oxytocin discontinuation was associated with lower cesarean delivery (1.1 vs. 5.4%; p = 0.12) and uterine tachysystole (9.8 vs. 23.0%; p = 0.08) rates and longer duration of the second stage of labor (mean: 56.5 ± 90 vs. 34.2 ± 45 minutes; p = 0.08) than conventional management; however, the difference was not significant. The other maternal and neonatal outcomes, including postpartum hemorrhage, did not also significantly differ between them. CONCLUSION: After the active phase of induced labor for suspected FGR, the risk of cesarean delivery is low, and the high incidence of uterine tachysystole and rapid labor progression should be considered cautiously. Oxytocin can be safely discontinued during the active phase of labor in women undergoing labor induction for FGR without an increased risk of cesarean delivery or other unfavorable outcomes. KEY POINTS: · The cesarean delivery rate was low after the active phase.. · The labor progress after the active phase was rapid.. · Oxytocin can be safely discontinued during the active phase..

The RPOC long axis is a simple indicator for predicting the need of invasive strategies for secondary postpartum hemorrhage in either post-abortion or post-partum women: a retrospective case control study.

BACKGROUND: The retained products of conception (RPOC) and related conditions (RPOC-ARC) are the main cause of secondary postpartum hemorrhage (sPPH), but there is no clear consensus for their management. The purpose of this study was to characterize those RPOC-ARC that require invasive treatment and those that could be managed more conservatively. METHODS: We retrospectively analyzed 96 cases of RPOC-ARC that occurred after miscarriage, abortion, or delivery at a gestational age between 12 and 42 completed weeks, that were managed within our institution from May 2015 to August 2020. We reviewed the associations between the occurrence of sPPH requiring invasive treatment with clinical factors such as the maternal background and the characteristics of the lesions. RESULTS: The range of gestational age at delivery in our study was 12-21 weeks in 61 cases, 22-36 in 5, and 37 or later in 30. Among them, nine cases required invasive procedures for treatment. The onset of sPPH was within one month of delivery in all but two cases, with a median of 24 days (range 9-47). We found significant differences between requirements for invasive versus non-invasive strategies according to gestational age at delivery, assisted reproductive technology (ART) pregnancy, amount of blood loss at delivery, and the long axis of the RPOC-ARC lesion (p = 0.028, p = 0.009, p = 0.004, and p = 0.002, respectively). Multivariate analysis showed that only the long axis of the lesion showed a significant difference (p = 0.029). The Receiver Operating Characteristic (ROC) curve for predicting the need for invasive strategies using the long axis of the lesion showed that with a cutoff of 4.4 cm, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) was 87.5, 90.0, 43.8, and 98.7%, respectively. CONCLUSION: The long axis of the RPOC-ARC is a simple indicator for predicting which sPPH will require invasive procedures, which use is rare in cases with lesions less than 4.4 cm or those occurring after the first postpartum month. Conservative management should be considered in such cases.

Atypical preeclampsia with systemic lupus erythematosus and elevated soluble fms-like tyrosine kinase 1/placental growth factor ratio.

While systemic lupus erythematosus is often complicated by preeclampsia, it is difficult to differentiate between its exacerbation and preeclampsia. The soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio is unknown in systemic lupus erythematosus with preeclampsia before 20 weeks of gestation. Three nulliparous women with systemic lupus erythematosus developed preeclampsia at 13, 13, and 17 weeks of gestation with sFlt-1/PlGF ratios of 427, 865, and 525, respectively. Two patients terminated their pregnancies and delivered within 2 weeks, while one experienced intrauterine fetal death 4 weeks after the measurements. Their symptoms gradually improved, and all patients were discharged within 3 months. The sFlt-1/PlGF ratio may be used in the differential diagnosis of preeclampsia and systemic lupus erythematosus exacerbation before 20 weeks of gestation.

Placenta previa with posterior extrauterine adhesion: clinical features and management practice.

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 < 0.01], respectively). After propensity score matching (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 < 0.01). Multivariate regression analysis revealed that PEUA was a significant risk factor for intraoperative bleeding before changes were implemented in practice (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.

[A Case of Spontaneous Spinal Epidural Hematoma during Chemotherapy with Paclitaxel and Ramucirumab for Advanced Gastric Cancer].

Spontaneous spinal epidural hematomas(SSEH)are rare. The causes of SSEH include hematologic disorders, anticoagulation and antiplatelet therapy, vascular malformations, neoplasms, trauma, or medical interventions, such as epidural catheterization or spinal surgery. However, the cause is usually unclear in most cases. We report a case of SSEH during chemotherapy with paclitaxel and ramucirumab for advanced gastric cancer. A 68-year-old woman was referred to our hospital with a diagnosis of advanced gastric cancer. After 4 courses of neoadjuvant chemotherapy containing S-1 plus oxaliplatin, distal gastrectomy with D2 lymphadenectomy was performed. Postoperative chemotherapy with paclitaxel and ramucirumab was initiated, with a diagnosis of ypStage Ⅲc(T4aN3bM0). She was later transported by ambulance to our hospital with symptoms of sudden onset posterior neck pain and weakness of the extremities. Magnetic resonance imaging(MRI)of her cervical spine showed an epidural hematoma from C2 to C5. The symptoms improved gradually after admission, and the epidural hematoma decreased in size on MRI. Hemorrhagic events such as SSEH should be considered during treatment with angiogenesis inhibitors.

Endometrial carcinoma in a gravid uterus: a case report and literature review.

BACKGROUND: Endometrial carcinoma (EC) is rarely diagnosed during pregnancy. Therefore, the histopathological findings, clinical course, and gross appearance of the resected uterus during pregnancy are not well known. We present a case of EC diagnosed during pregnancy. In addition, we reviewed the literature dating from January 1995 to March 2019 for cases of EC diagnosed during pregnancy and within 15 months after pregnancy, and we discussed this topic to improve the understanding of this rare condition. CASE PRESENTATION: A 35-year-old woman underwent an urgent cesarean delivery in gestational week 35 due to antepartum bleeding caused by placenta previa. Hysterectomy was performed with the diagnosis of placenta accreta spectrum (PAS). Remarkably, the postoperative gross and histopathological examinations revealed an endometrioid adenocarcinoma (grade 1). The histopathological findings revealed a pattern similar to that of EC not related with pregnancy. Immunohistochemistry revealed an overexpression of the estrogen and progesterone receptors; however, the p53 expression was negative. We performed laparoscopic bilateral salpingo-oophorectomy and pelvic lymphadenectomy 102 days after the cesarean hysterectomy, and confirmed surgical stage IA without metastases. Our patient has had no recurrence in 4 years after the cesarean delivery. An electronic search of the literature revealed 25 cases of EC (including our case) diagnosed during or after pregnancy. Sixteen of the 25 patients were diagnosed after abortions in the first trimester, 9 were diagnosed within 14 months of childbirth, and our case was the first with diagnosis from a surgical specimen of peripartum hysterectomy due to the PAS. In 23 of the 25 cases endometrioid adenocarcinoma grade 1 to 2 was found, and it seemed to have a good prognosis. CONCLUSION: The present findings suggest that careful examination of a resected uterus is essential, even when surgery is performed for an obstetric indication. Our case is an extremely rare case of EC during pregnancy; the histopathological pattern was similar to that of typical EC, and no recurrence was noted. The high levels of estrogen and progesterone during pregnancy did not seem to promote tumor progression in our case.

Single versus multiple cervical dilation by osmotic dilator before induction of labor for second-trimester abortion.

AIM: 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. METHODS: 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. RESULTS: The women were categorized into two groups: 191 women had a delivery time of <24 h, whereas 47 had delivery times >24 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 for <24 h and 2.4 ± 0.87 for >24 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 of >24 h and the number of used gemeprost. CONCLUSION: 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.

Impact of maternal methylenetetrahydrofolate reductase C677T polymorphism on intervillous and decidual pathology with pregnancy loss.

AIM: The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and intervillous and decidual pathology in patients with pregnancy loss was investigated. METHODS: We performed a cross-sectional study on 243 patients presenting with pregnancy loss for the degree of intervillous fibrin and thrombosis (IT), and decidual fibrin and thrombosis (DT) and determined their MTHFR C677T genotypes. Overall differences in age, body mass index (BMI), gravidity, parity, number of pregnancy losses and gestational period when the pathologic samples were obtained, also were determined. RESULTS: There were no significant differences in age, BMI, gravidity, parity, number of pregnancy losses and gestational period, relative to MTHFR C677T genotype (TT vs CT vs CC). There were significantly more T allele carriers and TT genotype patients among patients with severe IT (odds ratio [OR] 1.653, P = 0.033 and OR 2.246, P = 0.032, respectively) and those with severe IT and decidual thrombosis (OR 2.602, P = 0.012 and OR 3.375, P = 0.035, respectively). The CC genotype was protective against the four studied pathologic grades. CONCLUSION: To our knowledge, this is the first study showing that the MTHFR C677T TT genotype and T allele are associated with severe intervillous and decidual pathologies in patients with pregnancy loss. Differences in pathologic grades of MTHFR C677T TT genotype could support the hypothesis that further periconceptional treatment for pregnancy loss could be customized depending on single nucleotide polymorphisms.

New dedicated blunt straight needles and sutures for uterine compression sutures: a retrospective study and literature review.

BACKGROUND: We developed a dedicated blunt straight needle with No. 2 polydioxanone sutures (2-Monodiox®) for uterine compression sutures (UCSs) and aimed to assess the outcomes and complication rates of UCSs for postpartum hemorrhage by comparing with commercially available needle and suture types. METHODS: A retrospective analysis was performed between January 2010 and February 2018. During the study period, two types of commercially available sutures and 2-Monodiox® were used. PubMed, MEDLINE, and Scopus databases were searched for English articles published between January 1997 and May 2017 using search terms related to the suture and needle types for UCSs to discuss the dedicated needles and sutures for UCS. RESULTS: The analysis included 47 cases of UCSs for the uterine body with three suture types (No. 0 polydioxanone, 7 cases; No. 1 poliglecaprone 25, 21 cases; and No. 2 polydioxanone, 19 cases). B-Lynch suture using No. 0 sutures was associated with a significantly lower uterine preservation rate than those with Nos. 1 and 2 sutures (42.9% vs. 95.2 and 89.5%, respectively; p < 0.01). A modified Hayman suture technique was performed using 2-Monodiox® sutures, which achieved a similar uterine preservation rate compared with B-Lynch suture using No. 1 poliglecaprone 25 sutures. No patients developed severe complications. The literature review showed that no dedicated sutures have developed for UCSs. Three dedicated needles for UCSs have been developed, and 2-Monodiox® is the first dedicated blunt straight needle for UCSs. CONCLUSION: Our data showed that No. 0 sutures should not be used for B-Lynch suture. The uterine preservation rate is similar for 2-Monodiox® with modified Hayman suture and No. 1 poliglecaprone 25 sutures with B-Lynch suture, without the occurrence of severe complications.

Clinical Characteristics of Jra Alloimmunization in Pregnancy: A Case Series.

Only few studies have reported on Jra alloimmunization in pregnancy, and its clinical course remains unclear. We reviewed our cases to clarify the change in the peak systolic velocity of the middle cerebral artery (MCA-PSV) during pregnancy and the critical anti-Jra antibody titer to predict fetal anemia. We collected the data of pregnant women with anti-Jra antibody from two hospitals between 2010 and 2017. We extracted data on maternal information, number of intrauterine blood transfusions (IUT), trend of anti-Jra antibody titer, changes of MCA-PSV, and neonatal outcome. We had 16 cases. IUTs were performed in 6 fetuses with severe anemia between 27 and 32 weeks' gestation. The MCA-PSV did not increase more than 1.5 multiples of the median (MoM) after 32 weeks' gestation. No significant difference was found in the maximum titer between cases with IUT and those without IUT. All pregnancies but one delivered at term. No neonates developed severe anemia or jaundice. MCA-PSV did not increase higher than 1.5 MoM later during the pregnancy. A critical titer to predict fetal anemia did not exist. Spontaneous term delivery could be expected even in fetuses who underwent IUT before 32 weeks' gestation.

Preeclampsia: Maternal Systemic Vascular Disorder Caused by Generalized Endothelial Dysfunction Due to Placental Antiangiogenic Factors.

Preeclampsia, a systemic vascular disorder characterized by new-onset hypertension and proteinuria after 20 weeks of gestation, is the leading cause of maternal and perinatal morbidity and mortality. Maternal endothelial dysfunction caused by placental factors has long been accepted with respect to the pathophysiology of preeclampsia. Over the past decade, increased production of placental antiangiogenic factors has been identified as a placental factor leading to maternal endothelial dysfunction and systemic vascular dysfunction. This review summarizes the recent advances in understanding the molecular mechanisms of endothelial dysfunction caused by placental antiangiogenic factors, and the novel clinical strategies based on these discoveries.

Arginase controls soluble vascular endothelial growth factor receptor 1 (sFlt1) to maintain pregnancy homeostasis.

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-1 <6000 pg/ml and arginase activity <110 U/L; group 2, sFlt-1 ≥6000 pg/ml and arginase activity <110 U/L; group 3, sFlt-1 ≥6000 pg/ml and arginase activity ≥110 U/L; and group 4, sFlt-1 <6000 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.