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Aim: Although several studies reported the measurement of fetal oxygen saturation using fetal pulse oximetry (FPO) for evaluation of the fetal intrapartum condition, a systematic review of the seven randomized controlled trials (RCTs) provided no evidence to support FPO for intrapartum fetal monitoring. In the present review, we re‐evaluate an overview for the use of FPO and seven RCTs of FPO. Methods: We reviewed numerous previous reports on FPO and seven RCTs of intrapartum FPO. RCTs were conducted with the main outcome measure being a reduction in the cesarean section rate. Results: The largest trial with 5341 entries failed to show any reduction. The negative result from this RCT may be explained by the use of a different cutoff value for fetal oxygen saturation compared to the other RCT; in addition, there were differences in the indications for cesarean section due to dystocia and in the definition of non‐reassuring fetal status (NRFS). An abnormal FPO value, defined as the fetal oxygen saturation value <30% for at least 10 min, is useful for making a diagnosis of fetal acidosis. A newly developed device, an examiner's finger‐mounted tissue oximetry, accurately measures tissue oxygen saturation while overcoming the drawbacks of FPO, such as infection risk and slipping off of the sensor during descent of the fetal head. Conclusion: FPO (including the new device) with fetal heart rate monitoring in selected cases of NRFS may reduce the cesarean section rate. [ABSTRACT FROM AUTHOR]

The article presents study to describe preliminary experience with a finger-mounted fetal tissue oximetry probe during the 2nd stage of labor. It mentions measurement of fetal tissue oxygen saturation by using a finger-mounted fetal tissue oximetry during cervical examinations. It reveals tissue oxygen saturation of the fetal head was obtained by finger-mounted fetal tissue oximetry.

The registry program of amniotic fluid embolism ( AFE) in Japan started in 2003. More than 400 hundred clinical diagnosed amniotic fluid embolism has been accumulated. Those data showed that there were two etiologies of AFE: the fetal materials create physical obstructions in the maternal microvessels in various organs, such as the lung; and (ii) the liquids cause an anaphylactoid reaction that leads to pulmonary vasospasm and activation of platelets, white blood cells and/or complements. The clinical findings showed that AFE was characterized mainly by cardiopulmonary collapse, the other involves the presence of disseminated intravascular coagulation ( DIC) and atonic bleeding. Zinc coproporphyrin-1, sialyl Tn antigen ( STN), complement C3, C4 and interleukin-8 have been used as serum markers of AFE. The levels of zinc coproporphyrin-1 and STN were increased in cardiopulmonary collapse type AFE, and a marked reduction of C3 and C4 was observed in DIC type AFE. At the primary medical institution, initial treatments for shock airway management, vascular management, fluid replacement, administration of anti- DIC therapy such as antithrombin, and administration of fresh frozen plasma should be provided. C1 esterase inhibitor activity in AFE cases was significantly lower than those of normal pregnant women. C1 esterase inhibitor may be a promising candidate of treatment of AFE. [ABSTRACT FROM AUTHOR]

Rapid growth in infancy considerably increases the risk of obesity and metabolic disorders in adulthood especially among neonates born small. To investigate the mechanism involved, we developed an animal model of undernourishment in utero by maternal caloric restriction, in which the Z scores of body weight at weaning (19.5 days) positively correlated with parameters of obesity, metabolic disorders, and remodeling of subcutaneous adipose tissue, such as numbers of macrophages in adipose tissue, the ratio of inflammatory M1 to anti-inflammatory M2 macrophages, estimated by gene expression of specific antigens, and the relative ratio of small adipocytes less than 30 μm in diameter, on a high-fat diet at 17 weeks of age. To our knowledge, this is the first report of a possible connection between infantile body weight and adipose tissue remodeling in obesity after undernourishment in utero. [ABSTRACT FROM AUTHOR]

To clarify the cause of maternal deaths, an autopsy is essential. However, there has been no systemic analysis of maternal death in Japan based on autopsy cases. Maternal death reports were retrieved from a large amount of registered autopsy data on maternal death in the series of 'Annual of pathological autopsy cases in Japan'. These files contain 468 015 autopsy records from 1989 to 2004. We collected 193 cases of maternal death due to direct obstetric causes. We recorded all the data into Excel files. Then we analyzed the causes of death and classified them into 11 categories. The causes of maternal death were as follows: amniotic fluid embolism (AFE), 24.3%; disseminated intravascular coagulation (DIC) related to pregnancy-induced hypertension, 21.2%; pulmonary thromboembolism, 13.0%; injury to the birth canal, 11.4%; medical and surgical complications, 9.8%; and atonic bleeding or DIC of unknown cause, 8.3%. A discrepancy between the clinical diagnosis and pathological diagnosis was frequently observed in cases of AFE, septic DIC and injury to the birth canal. AFE diagnosed by autopsy was often clinically diagnosed as atonic bleeding or DIC of unknown cause before death. Half of the cases of AFE diagnosed by autopsy were associated with DIC. We found that AFE, DIC related to pregnancy-induced hypertension, pulmonary thromboembolism and injury to the birth canal were the major causes of maternal death in Japan. AFE had various clinical features such as uterine atony and DIC in addition to pulmonary cardiac collapse. [ABSTRACT FROM AUTHOR]

Examines the effect of anti-macrophage inhibitory factor (MIF) on pregnant mare serum gonadotropin growth and ovulation. Proliferation of the granulosa and theca cells; Reduction in the number of follicles; Inhibition of anti-MIF on follicular growth.

Aim Methods Results Conclusions In Japan, unlike Western countries, tocolytic agents are administered in long‐term protocols to treat threatened preterm labor. Evaluating the side effects of this practice is crucial. We examined whether ritodrine hydrochloride had been administered in cases of maternal death, aiming to investigate any relationship between ritodrine administration and maternal death.This retrospective cohort study used reports of maternal deaths from multiple institutions in Japan between 2010 and 2020. Data on the reported cases were retrospectively analyzed, and data on the route of administration, administered dose, and clinical findings, including causes of maternal death, were extracted. The amount of tocolytic agents was compared between maternal deaths with ritodrine administration and those without.A total of 390 maternal deaths were reported to the Maternal Death Exploratory Committee in Japan during the study period. Ritodrine hydrochloride was administered in 32 of these cases. The frequencies (n) and median doses (range) of oral or intravenous ritodrine hydrochloride were 34.4% (11) and 945 (5–2100) mg and 84.4% (27) and 4032 (50–18 680) mg, respectively. Frequencies of perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema as causes of maternal death were significantly higher with ritodrine administration than without it.Our results suggest a relationship between long‐term administration of ritodrine hydrochloride and an increased risk of maternal death due to perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema. In cases where ritodrine should be administered to prevent preterm labor, careful management and monitoring of maternal symptoms are required. [ABSTRACT FROM AUTHOR]

We experienced three cases and four successful deliveries with congenital afibrinogenaemia and propose the following guidelines for the prenatal and peripartum management: (i) genital bleeding usually begins at 5 weeks' gestation and spontaneous abortion always occurs at 6–8 weeks' gestation without fibrinogen infusion; (ii) the fibrinogen level must be at least 0·60 g/l and, if possible, higher than 1·0 g/l during the pregnancy; (iii) the necessary amounts of fibrinogen increase as the pregnancy progresses and the preterm labour occurs; (iv) the fibrinogen level under the continuous infusion of fibrinogen during labour must be at least 1·5 g/l and, if possible, higher than 2·0 g/l to prevent placental abruption; (v) the puerperium is usually uneventful with a reduced dose of fibrinogen infusion. [ABSTRACT FROM AUTHOR]

Amniotic fluid embolism (AFE) and placental abruption (PA) are typical obstetric diseases associated with disseminated intravascular coagulation (DIC). AFE is more likely to be complicated with enhanced fibrinolysis than PA. AFE may have an additional mechanism activating fibrinolytic cascade. We aimed to compare the coagulation/fibrinolysis factors among AFE, PA, and peripartum controls. We assessed AFE cases registered in the Japanese AFE Registry, and PA cases complicated with DIC (severe PA) and peripartum controls recruited at our hospital. The following factors in plasma were compared: prothrombin fragment 1 + 2 (PF1 + 2), plasmin α2-plasmin inhibitor complex (PIC), tissue factor (TF), tissue plasminogen activator (tPA), annexin A2 (AnnA2), total thrombin activatable fibrinolysis inhibitor (TAFI) including its activated form (TAFIa), and plasminogen activator inhibitor-type 1 (PAI-1). PF1 + 2 and PIC were markedly increased in both AFE (n = 27) and severe PA (n = 12) compared to controls (n = 23), without significant difference between those disease groups; however, PIC in AFE showed a tendency to elevate relative to PF1 + 2, compared with severe PA. AFE had significantly increased tPA and decreased total TAFI levels compared with severe PA and controls, which might be associated with further plasmin production in AFE and underlie its specific fibrinolytic activation pathway. [ABSTRACT FROM AUTHOR]

Introduction: With category II fetal heart rate tracings, the preferred timing of interventions to prevent fetal hypoxic brain damage while limiting operative interventions remains unclear. We aimed to estimate fetal extracellular base deficit (BDecf) during labor with category II tracings to quantify the timing of potential interventions to prevent severe fetal metabolic acidemia. Material and methods: A longitudinal study was conducted using the database of the Recurrence Prevention Committee, Japan Obstetric Compensation System for Cerebral Palsy, including infants with severe cerebral palsy born at ≥34 weeks' gestation between 2009 and 2014. Cases included those presumed to have an intrapartum onset of hypoxic–ischemic insult based on the fetal heart rate pattern evolution from reassuring to an abnormal pattern during delivery, in association with category II tracings marked by recurrent decelerations and an umbilical arterial BDecf ≥ 12 mEq/L. BDecf changes during labor were estimated based on stages of labor and the frequency/severity of fetal heart rate decelerations using the algorithm of Ross and Gala. The times from the onset of recurrent decelerations to BDecf 8 and 12 mEq/L (Decels‐to‐BD8, Decels‐to‐BD12) and to delivery were determined. Cases were divided into two groups (rapid and slow progression) based upon the rate of progression of acidosis from onset of decelerations to BDecf 12 mEq/L, determined by a finite‐mixture model. Results: The median Decels‐to‐BD8 (28 vs. 144 min, p < 0.01) and Decels‐to‐BD12 (46 vs. 177 min, p < 0.01) times were significantly shorter in the rapid vs slow progression. In rapid progression cases, physicians' decisions to deliver the fetus occurred at ~BDecf 8 mEq/L, whereas the "decisions" did not occur until BDecf reached 12 mEq/L in slow progression cases. Conclusions: Fetal BDecf reached 12 mEq/L within 1 h of recurrent fetal heart rate decelerations in the rapid progression group and within 3 h in the slow progression group. These findings suggest that cases with category II tracings marked by recurrent decelerations (i.e., slow progression) may benefit from operative intervention if persisting for longer than 2 h. In contrast, cases with sudden bradycardia (i.e., rapid progression) represent a challenge to prevent severe acidosis and hypoxic brain injury due to the limited time opportunity for emergent delivery. [ABSTRACT FROM AUTHOR]

The sex of the conceived child is a significant concern for parents. To verify whether there women have pregnancy bias toward boys or girls, we investigated whether the history of continuous same-sex pregnancy was associated with the subsequent child's sex. We prospectively analyzed data from the Japan Environment and Children's Study, a birth cohort study. We included all cases of singleton live births (n = 98 412). Women with pregnancy due to infertility treatment were excluded (n = 6255); Similarly, women with a history of miscarriage, artificial abortion, stillbirth, and multiple pregnancies, and those with missing data on the sex of the previous child were excluded. Altogether, 62 718 women were included. For the first live birth, a male-biased sex ratio of 1.055 was observed. Further, no significant difference was found in the sex ratio of the conceived child between women with one boy and those with one girl previously. However, when there were more than two children previously, the subsequently conceived child's male/female sex ratio was significantly higher among boy-only mothers than among girl-only mothers. The results indicated that several pregnant women are biased toward conceiving either boys or girls. [ABSTRACT FROM AUTHOR]

Aim: This nationwide study aimed to investigate the practical management of term premature rupture of membrane (PROM) and its relationship with maternal and neonatal outcomes. Methods: We conducted a questionnaire survey of 415 facilities participating in the Japan Perinatal Registry Network of the Japan Society of Obstetrics and Gynecology in 2016. The patients were women expecting vaginal birth after PROM at term without clinical chorioamnionitis. We classified the facilities into three groups based on duration of the expectant management after PROM (within 24, 24, and 48 h). Furthermore, we analyzed the association between perinatal outcomes and management protocol using the Japan Perinatal Registry Network Database 2016. Results: Of 415 facilities, 346 (83.4%) completed and returned the survey. Among 231 facilities with management protocols, an interval of 3 days from PROM to delivery was acceptable in 167 facilities (72.3%). One hundred forty‐nine facilities (64.5%) responded that they did not perform mechanical cervical dilation, and 90 (39.0%) used oxytocin as a uterotonic irrespective of cervical maturation. The number of hospitals that had a policy to administer antibiotics to Group B streptococcus‐positive patients was 211 (91.3%). Neonatal outcomes at birth and the frequency of cesarean section and postpartum fever did not differ among the three groups. Conclusions: Most facilities in the Japan Perinatal Registry Network managed women at term to delivery within 3 days after PROM with attention to bacterial infection. Expectant management up to 48 h after PROM did not increase the risk of postpartum fever, compared to labor induction immediately after PROM. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between hypoxic‐ischaemic insult timing and brain injury type in infants with severe cerebral palsy (CP). Design Longitudinal study. Setting: Database of the Recurrence Prevention Committee, Japan Obstetric Compensation System for Cerebral Palsy. Sample Infants with severe CP born at ≥34 weeks of gestation. Methods: The intrapartum fetal heart rate (FHR) strips were categorised as continuous bradycardia; persistently non‐reassuring (NR‐NR); reassuring‐prolonged deceleration (R‐PD); Hon's pattern (R‐Hon); persistently reassuring (R‐R); and unclassified. The brain magnetic resonance imaging (MRI) scans were categorised based on the predominant site involved: basal ganglia‐thalamus (BGT); white matter (WM); watershed (WS); stroke; normal; and unclassified. Main outcome measures: Manifestations of the brain MRI types and the association between FHR evolution pattern and MRI type were analysed. Results: Among 672 eligible infants, 76% had BGT‐dominant injury, 5.4% WM, 1.2% WS, 1.6% stroke, 1.9% normal, and 14% unclassified. Placental abruption and small‐for‐gestational age were associated with an increased (adjusted odds ratio [aOR] 8.02) and decreased (aOR 0.38) risk of BGT injury, respectively. The majority of infants had BGT injury in most FHR groups (bradycardia, 97%; NR‐NR, 75%; R‐PD, 90%; R‐Hon, 76%; and R‐R, 45%). The risk profiles in case of BGT in the NR‐NR group were similar to those in the R‐PD and R‐Hon groups. Conclusion: BGT‐dominant brain damage accounted for three‐fourths of the cases of CP in term or near‐term infants, even in prenatal onset cases. Hypoxic‐ischaemic insult has a major impact on CP development during the antenatal period. Basal ganglia‐thalamus injury constitutes 76% of severe cerebral palsy cases, predominant even in antenatal‐onset cases. Basal ganglia‐thalamus injury constitutes 76% of severe cerebral palsy cases, predominant even in antenatal‐onset cases. This article includes Author Insights, a video abstract available at https://vimeo.com/bjogabstracts/authorinsights17089. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study is to find clues to improve perinatal outcomes in the case of cerebrovascular acute disorders during pregnancy.Study Design: We analyzed 35 cases of cerebrovascular diseases related to maternal deaths in Japan those that occurred during pregnancy and reported to the Committee of the Ministry of Health, Labor, and Welfare from 2010 to 2018.Results: Cerebrovascular acute disorders occurred at 34.6 ± 6.6 gestational weeks. There were seven intrauterine fetal deaths (IUFD), and eight cases showed neonatal asphyxia with umbilical arterial pH between 6.7 and 7.0 (asphyxia cases, n = 15). In two of eight newborns, brain hypothermia therapy was given, and all survived without neurological sequelae. Maternal dyspnea was significantly related to severe prolonged decelerations of the fetus (p < .05), and asphyxia cases (p < .005). Median time from maternal onset to delivery (OD time) was significantly longer in asphyxia cases than in the non-asphyxia cases (84 vs 29 min, p < .05). OD time over 30 min was significantly related to the antepartum occurrence, cervical dilatation <5 cm (p < .05), onset outside of the hospital (p < .001), and maternal transfer before delivery (p < .001).Conclusion: More than 40% of cases experienced fetal asphyxia, and 20% ended in IUFD in maternal deaths related to cerebrovascular acute disorders. Maternal respiratory support and rapid delivery would be the keys to improve perinatal outcomes in case of cerebrovascular acute disorders during pregnancy. [ABSTRACT FROM AUTHOR]

Study Question: Does fibrin promote trophoblast growth in human and mouse blastocysts during early embryo implantation?Summary Answer: Mouse blastocysts were unaffected by fibrin; however, human blastocysts were significantly suppressed by fibrin in trophoblast growth and then switched to growth promotion through increased fibrinolysis with urokinase-type plasminogen activator (uPA) activity.What Is Known Already: Fibrin(ogen) plays an important role in various physiological processes and is also critical for maintaining feto-maternal attachment during pregnancy. The addition of fibrin to embryo transfer media has been used to increase implantation rates in human ART; however, its mechanism of action' in vitro has not yet been characterized.Study Design, Size, Duration: Vitrified mouse and human blastocysts were warmed and individually cultured in vitro for up to 120 and 168 h, respectively, on a fibrin substrate. Blastocysts were cultured at 37°C in 6% CO2, 5% O2 and 89% N2. Blastocyst development and related fibrinolytic factors were analyzed.Participants/materials, Setting, Methods: ICR strain mouse embryos were purchased from a commercial supplier. Human blastocysts were donated with informed consent from two fertility centers. Mouse and human blastocysts cultured on fibrin-coated plates were compared to those on non-coated and collagen-coated plates in vitro. Trophoblast growth and fibrin degradation were assessed based on the cell area and fibrin-free area, respectively. Fibrinolytic factors were detected in supernatants using plasminogen-casein zymography. The fibrinolytic activity of blastocysts was investigated using a selective uPA inhibitor, exogenous uPA, plasminogen activator inhibitor-1 (PAI-1) inhibitor and fibrin degradation products (FDPs). Fibrinolysis-related mRNA expression level was detected using quantitative real-time PCR.Main Results and the Role Of Chance: Fibrin did not affect the developmental speed or morphology of mouse blastocysts, and a large fibrin-degrading region was observed in the attachment stage. In contrast, fibrin significantly suppressed the outgrowth of trophoblasts in human blastocysts, and trophoblasts grew after the appearance of small fibrin-degrading regions. uPA was identified as a fibrinolytic factor in the conditioned medium, and uPA activity was significantly weaker in human blastocysts than in mouse blastocysts. The inhibition of uPA significantly reduced the outgrowth of trophoblasts in mouse and human blastocysts. Human blastocysts expressed PLAU (uPA), PLAUR (uPA receptor), SERPINE1 (PAI-1) and SERPINB2 (PAI-2), whereas mouse blastocysts were limited to Plau, Plaur and Serpine1. In a subsequent experiment on human blastocysts, the addition of exogenous uPA and the PAI-1 inhibitor promoted trophoblast growth in the presence of fibrin, as did the addition of FDPs.Limitations, Reasons For Caution: This model excludes maternal factors and may not be fully reproduced in vivo. Donated human embryos are surplus embryos that may inherently exhibit reduced embryonic development. In addition, donated ART-derived embryos may exhibit weak uPA activity, because women with sufficient uPA-active embryos may not originally require ART. The present study used orthodox culture methods, and results may change with the application of recently developed protocols for culture blastocysts beyond the implantation stage.Wider Implications Of the Findings: The present results suggest that the distinct features of trophoblast outgrowth in human blastocysts observed in the presence of fibrin are regulated by a phenotypic conversion induced by contact with fibrin and FDPs. Mouse embryos did not exhibit the human phenomenon, indicating that the present results may be limited to humans.Study Funding/competing Interest(s): The present study was supported by the Department of Obstetrics and Gynecology at the Hamamatsu University School of Medicine and Kishokai Medical Corporation. None of the authors have any conflicts of interest to declare.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Urokinase-type plasminogen activator (uPA) degrades the extracellular matrix and plays critical roles in tumor invasion and metastasis. Matriptase, a membrane-bound serine protease, was shown to activate uPA in a uPA receptor-free, solution-based study. We now investigate whether matriptase affects activation of receptor-bound uPA and contributes to the invasiveness of HRA human ovarian cancer cells in vitro and tumor behavior in nude mice. Here we show the followlng. 1) uPA expression was effectively stimulated by TGF-β1 in HRA cells. 2) Antisense (AS)-matriptase transfection achieved a marked inhibition of receptor-bound pro-uPA activation without altering expression of uPA and uPA receptor mRNA and proteins, irrespective of whether cells were stimulated with TGF-β1. 3) Tumor cell receptor-bound pro-uPA could be efficiently cleaved by matriptase to generate enzymatically active twochain uPA. Thus, matriptase can substitute for plasmin in the proteolytic activation of pro-uPA to enzymatically active uPA. 4) The AS-matriptase-treated cells had a decreased ability to invade an extracellular matrix layer, as compared with control cells. 5) When the ASmatriptase-treated cells were injected intraperitoneally into nude mice, the mice developed smaller tumors. Our data identify a novel role for matriptase for activation of receptor-bound uPA. [ABSTRACT FROM AUTHOR]

Using a cDNA microarray analysis, we previously found that exposure of a highly invasive ovarian cancer cell line HRA with bikunin, a Kunitz-type protease inhibitor, or bikunin gene overexpression markedly reduced phosphoinositide kinase (PI3K) p85 gene expression, demonstrating that PI3K may be a candidate bikunin target gene. To clarify how reduced levels of PI3K may confer repressed invasiveness, we transfected HRA cells with PI3K p85 antisense-oligodeoxynucleotide (AS-ODN) and compared the properties of the transfected cells with those of parental cells and sense (S)-ODN cells. We have also demonstrated previously that transforming growth factor-β1 (TGF-β1) stimulates urokinase-type plasminogen activator (uPA)-dependent invasion and metastasis of HRA cells. Here, we show that 1) TGF-β1 induced a rapid increase of the PI3K activity that was accompanied by increased expression (5-fold) of the uPA mRNA; 2) pharmacological inhibition of PI3K or AS-PI3K ODN transfection inhibited TGF-β1-stimulated Akt phosphorylation; 3) both PI3K pharmacological inhibitors and forced expression of AS-PI3K ODN reduced TGF-β1-stimulated uPA mRNA and protein expression by ∼70% compared with controls; 4) concentrations of PI3K inhibitors, sufficient to inhibit uPA up-regulation, inhibited TGF-β1-dependent HRA cell invasion; 5) the AS-PI3K ODN cells had a decreased ability to invade the extracellular matrix layer as compared with controls; and 6) when the AS-PI3K ODN cells were injected intraperitoneally into nude mice, the mice developed smaller intraperitoneal tumors and showed longer survival. We conclude that PI3K plays an essential role in promoting uPA-mediated invasive phenotype in HRA cells. Our data identify a novel role for PI3K as a bikunin target gene on uPA up-regulation and invasion. [ABSTRACT FROM AUTHOR]

Background: Amniotic fluid contains a significant level of urinary trypsin inhibitor (UTI). Previously, we reported that UTI inhibits calcium influx of myometrium and it is effective in preventing uterine contraction. This study examined the effects of UTI upon potassium channels, which is important for membrane excitability.Methods: Whole-cell patch-clamp recordings were performed in fibroblasts derived from human fetal skin. Potassium currents were recorded and the effects of exogenous UTI and/or cadmium determined.Results: Tetraethylammonium sensitive potassium currents were elicited by step or ramp stimulations at depolarized membrane potentials (over +30 mV). Administration of 1 micro M UTI significantly increased these potassium currents by 16.9%. When calcium channels were blocked by the administration of cadmium, UTI increased the rest of the potassium currents by 4.8%. This indicates that UTI increased calcium-dependent potassium currents by 94.8% but only increased voltage-dependent potassium currents by 4.8%.Conclusions: Urinary trypsin inhibitor is a physiological substance of fetal origin that modulates calcium-dependent and voltage-dependent potassium channels. These data suggest that UTI is capable of regulating the membrane properties of the fetal and myometrial cells in contact with amniotic fluid. [ABSTRACT FROM AUTHOR]

Venous thrombosis is a serious disorder that may be fatal if complicated by pulmonary embolism. Venous thrombosis is usually related to one of three factors: reduced blood flow, changes in vessel wall integrity, or changes in the blood composition. Factors leading to thrombosis are classified as either genetic or acquired. Puerperium and oral contraceptives are examples of the acquired factors. The risk of thrombosis during pregnancy is high compared to that in the overall population,. however, this increases by three to five times in puerperium. Deep vein thrombosis (DVT) complicated by pulmonary thromboembolism (PE) is considered the leading cause of maternal death in the United States and Europe [Am. J. Obstet. Gynecol. 164 (1991) 603; Obstet. Gynecol. 84 (1994) 240] and the third cause in Japan [M Ishikawa, Maternal mortality and pulmonary thromboembolism. Study on maternal mortality in Japan. Report from the Ministry of Health of Japan in Maternal and Child Health Research, 1996. p. 123–128]. Patients without history of familial thrombophilia have 14-fold higher risk of DVT during puerperium [Thromb. Haemost. 25 (1999) 610]. Little is known about the underlying mechanism of thrombotic disorders in puerperium. It is recognized that oral contraceptive estrogen enhances the risk of DVT [Am. J. Epidemiol. 133 (1991) 32]. However, there is little research regarding the relation between estrogen and blood coagulation, although it is known that plasma estrogen reaches extremely high levels near term. We assume that high-level plasma estrogen plays an important role in the blood coagulation activity that results in the occurrence of DVT. To assess this likely association, we studied the effects of high estrogen levels on coagulation in rat plasma. [Copyright &y& Elsevier]

Summary Plasma cells play a pivotal role in the immune system and areresponsible for the synthesis and release of immunoglobulins. Numerous invitro culture experiments on the yolk sac demonstrated the generationof mature cells of the myeloid and lymphoid lineages under appropriateculture conditions. However, there are no reports describing thedevelopment of mature lymphoid cells in the yolk sac so far. Forthis reason, we undertook this study to investigate the developmentof antibody-containing plasma cells during early yolk sac haematopoiesis. Immunohistochemistryand immunoelectron microscopy were employed in the study. Resultsof this work demonstrated very weak immune staining for the intracytoplasmicIgA, IgG, and IgM at days 10 and 11 of embryonic life, while darkstaining was obtained at 12 days. Positive staining was localizedto the endodermal cell layer. Electron microscopic examinationsrevealed the existence of cells with the typical characteristicsof plasma cells inside the endodermal cell layer, which may suggesttheir endodermal origin. To further verify the nature of these cells,intracytoplasmic immunoglobulins were demonstrated by immunoelectronmicroscopy. The present study demonstrated emergence of mature functioningplasma cells in early rat yolk sac. In a previous work we hypothesizedthe possibility of endodermal origin of yolk sac macrophages. Thisstudy adds additional evidence to support that hypothesis. The possiblerole of plasma cells in the yolk sac is discussed. [ABSTRACT FROM AUTHOR]

Hepatocyte growth factor/scatter factor (HGF/SF) can induce proliferation and motility and promote invasion of tumor cells. Since HGF/SF receptor, c-Met, is expressed by tumor cells, and since stimulation of CD44, a transmembrane glycoprotein known to bind hyaluronic acid (HA) in its extracellular domain, is involved in activation of c-Met, we have studied the effects of CD44 stimulation by ligation with HA upon the expression and tyrosine phosphorylation of c-Met on human chondrosarcoma cell line HCS-2/8. The current study indicates that (a) CD44 stimulation by fragmented HA upregulates expression of c-Met proteins; (b) fragmented HA also induces tyrosine phosphorylation of c-Met protein within 30 min, an early event in this pathway as shown by the early time course of stimulation; (c) the effects of HA fragments are critically HA size-dependent. High molecular weight HA is inactive, but lower molecular weight fragments (Mr 3.5 kDa) are active with maximal effect in the μg/ml range; (d) the standard form of CD44 (CD44s) is critical for the response because the effect on c-Met, both in terms of upregulation and phosphorylation, is inhibited by preincubation with an anti-CD44 monoclonal antibody; and (e) phosphorylation of c-Met induced by CD44 stimulation is inhibited by protein tyrosine kinase inhibitor, tyrphostin. Therefore, our study represents the first report that CD44 stimulation induced by fragmented HA enhances c-Met expression and tyrosine phosphorylation in human chondrosarcoma cells. Taken together, these studies establish a signal transduction cascade or cross-talk emanating from CD44 to c-Met. [Copyright &y& Elsevier]

Our laboratory showed that bikunin, a Kunitz-type protease inhibitor, suppresses 4β-phorbol 12-myristate 13-acetate (PMA)- or tumor necrosis factor-alpha (TNFα)-induced urokinase-type plasminogen activator (uPA) expression in different cell types. In addition to its effects on protease inhibition, bikunin could be modulating other cellular events associated with the metastatic cascade. To test this hypothesis, we examined whether bikunin was able to suppress the expression of uPA receptor (uPAR) mRNA and protein in a human chondrosarcoma cell line, HCS-2/8, and two human ovarian cancer cell lines, HOC-I and HRA. The present study showed that (a) bikunin suppresses the expression of constitutive and PMA-induced uPAR mRNA and protein in a variety of cell types; (b) an extracellular signal-regulated kinase (ERK) activation system is necessary for the PMA-induced increase in uPAR expression, as PD098059 and U0126, which prevent the activation of MEK1, reduce the uPAR expression; (c) bikunin markedly suppresses PMA-induced phosphorylation of ERK1/2 at the concentration that prevents uPAR expression, but does not reduce total ERK1/2 antigen level; (d) bikunin has no ability to inhibit overexpression of uPAR in cells treated with sodium vanadate; and (e) we further studied the inhibition of uPAR expression by stable transfection of HRA cells with bikunin gene, demonstrating that bikunin secretion is necessary for inhibition of uPAR expression. We conclude that bikunin downregulates constitutive and PMA-stimulated uPAR mRNA and protein possibly through suppression of upstream targets of the ERK-dependent cascade, independent of whether cells were treated with exogenous bikunin or transfected with bikunin gene. [ABSTRACT FROM AUTHOR]

This study aimed to determine whether blood loss and fibrinogen can differentiate amniotic fluid embolism (AFE) from postpartum haemorrhage (PPH). This retrospective case–control study included nine patients with clinical AFE ("AFE group") and 78 patients with PPH managed at our tertiary care perinatal centre between January 2014 and March 2016. Patients meeting the Japanese diagnostic criteria for AFE were stratified into cardiopulmonary collapse-type AFE and disseminated intravascular coagulation (DIC)-type AFE groups. The relationship between blood loss and fibrinogen at onset was examined to compare DIC severity. Vital signs at onset were not significantly different. The AFE group had significantly less blood loss at onset (1506 mL vs 1843 mL, P = 0.0163), significantly more blood loss 2 h post-onset (3304 mL vs 1996 mL, P < 0.0001) and more severe coagulopathy and fibrinolysis. The blood loss/fibrinogen (B/F) ratio at onset was significantly higher in the DIC-type AFE group (23.15 ± 8.07 vs 6.28 ± 3.35 mL dL/mg, P < 0.0001). AFE was complicated by catastrophic DIC irrespective of blood loss at onset. Fibrinogen exhibited the strongest correlation among test findings at onset. The B/F ratio may help differentiate PPH from DIC-type AFE and diagnose clinical AFE, facilitating optimal replacement of coagulation factors during the early stages. [ABSTRACT FROM AUTHOR]

There is a paucity of data on the risk of preterm birth subcategorized by gestational age in pregnancies after the pre-pregnancy excisional treatment for cervical lesions. In addition, little is known about the effect of prophylactic cerclage on the risk of preterm birth. The aim of this study was to investigate the risk of preterm birth stratified by gestational period and its reduction by the prophylactic cerclage in women with prior excisional surgery. We retrospectively analyzed a cohort of singleton pregnancies in the Japan Perinatal Registry Network Database (2013–2014, n = 307,001). Cases included pregnancies after the surgery (i.e. conization and loop electrosurgical excision procedure). Controls comprised the propensity-score matched pregnancies without pre-pregnancy surgery. The main outcome was the occurrence of preterm birth. The effect of prophylactic cervical cerclage on the risk of preterm birth after the excisional surgery was also examined using cases. In the propensity-score matched population (cases, n = 1389; controls, n = 1389), cases exhibited a higher risk of preterm birth and preterm prelabor rupture of membranes (PROM), compared with controls (preterm birth: 25.3 versus 10.6%; preterm PROM: 14.0 versus 3.5%: both p <.0001). Odds ratios (OR; 95% confidence interval [CI]) for preterm birth at 22–27 weeks, 28–31 weeks, 32–33 weeks, and 34–36 weeks were 3.4 [1.8–6.5], 4.6 [2.7–7.7], 2.2 [1.4–3.5], and 2.1 [1.6–2.7], respectively. The association was stronger for preterm PROM at earlier gestational age (22–27 weeks, 28–31 weeks, 32–33 weeks, and 34–36 weeks: 5.2 [2.3–11.8], 7.1 [3.4–15.0], 3.8 [1.7–8.3], and 3.9 [1.8–4.6], respectively). In cases, 171 underwent the prophylactic cervical cerclage. The occurrence of preterm birth and preterm PROM was comparable between those with and without the cerclage (28.7 versus 24.2, and 12.9 versus 13.3%, respectively). Pre-pregnancy excisional cervical surgery was associated with the increased risk of preterm birth, especially before 32 weeks of gestation. The prophylactic cerclage did not reduce the risk of preterm birth. [ABSTRACT FROM AUTHOR]

Objective: We reviewed malignancy related maternal deaths in Japan to ascertain if there were avoidable factors.Methods: Malignancy-related maternal death in Japan reported to the Maternal Death Exploratory Committee, from 2010 to 2016 inclusive.Results: There were 12 cases of maternal death caused by malignancy. There were four gastric cancers (two poorly differentiated adenocarcinoma, one signet ring cell carcinoma with adenocarcinoma, one histology not available), 3 leukemia (two acute myeloid leukemia, one aggressive NK cell leukemia), two ureteral cancers (histology not available), one malignant lymphoma (diffuse large B-cell lymphoma with translocation), one brain tumor (gliomatosis cerebri), and one cervical cancer (glassy cell carcinoma). Two gastric cancer patients had chronic gastric pain before conception. In two cases the physicians commented that they had avoided computed tomography and the brain biopsy needed for diagnosis because the patient was pregnant. At diagnosis, the clinical stages were II-IV in 9, and the performance status was 3-5 in 8. Indication for delivery was exacerbated maternal condition in 5, for treatment in 3, spontaneous labor in 3, and one patient declined elective delivery. Median [interquartile rage] (range) gestational weeks of delivery was 29 [24-30] (19-40). One cervical cancer patient had a radical hysterectomy and chemotherapy for 10 months. However, three leukemia and one gastric cancer patients had chemotherapy within 10 d because they deteriorated rapidly. Another seven cases did not have any treatment because of poor general condition or because they remained undiagnosed. In all cases, the Committee considered that there was no evidence of substandard care.Conclusion: In these cases, both the clinical stages and biological degree of malignancy were high. In two-thirds of cases, early termination of the pregnancy was indicated because of deteriorating maternal condition. Chemotherapy was not effective because of short available time for therapy and the advanced stage of the cancers when diagnosed. Encouraging women to have a thorough medical assessment before conception, and early diagnosis and treatment before pregnancy, appears to be the only practical way to reduce deaths from malignancy while a woman is pregnant. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to identify risk factors for the onset of cerebral palsy (CP) in neonates due to placental abruption and investigate their characteristics. Methods: A retrospective case–control study was conducted using a nationwide registry from Japan. The study population included pregnant women (n = 122) who delivered an infant with CP between 2009 and 2015, where placental abruption was identified as the single cause of CP. The control group consisted of pregnant women with placental abruption, who delivered an infant without CP and were managed from 2013 to 2014. They were randomly identified from the prenatal database of the Japan Society of Obstetrics and Gynecology (JSOG‐DB; n = 1214). Risk factors were investigated using multivariate analysis. Results: Alcohol consumption (3.38, 2.01–5.68) (odds ratio, 95% confidence interval), smoking during pregnancy (3.50, 1.32–9.25), number of deliveries (1.28, 1.05–1.56), polyhydramnios (5.60, 1.37–22.6), oral administration of ritodrine hydrochloride (2.09, 1.22–3.57) and hypertensive disorders in pregnancy (2.25, 1.27–4.07) were significant risk factors. In contrast, intravenous administration of oxytocin (odds ratio, 95% confidence interval: 0.22, 0.09–0.58) and magnesium sulfate (0.122, 0.02–0.89) attenuated risk. Conclusion: Alcohol consumption, smoking during pregnancy, number of deliveries, polyhydramnios, oral administration of ritodrine hydrochloride and hypertensive disorders in pregnancy were identified as risk factors for CP following placental abruption. Regarding alcohol consumption and smoking during pregnancy, the results suggest the importance of educational activities targeting pregnant women to increase their awareness of placental abruption. [ABSTRACT FROM AUTHOR]

An opaque fetal membrane based on gross appearance is traditionally indicative of histological chorioamnionitis; however, to the best of our knowledge, there is currently no supportive evidence, and its diagnostic efficiency has not yet been scientifically demonstrated. The present study aimed to provide scientific insights into the traditional concept of an opaque fetal membrane based on gross appearance being an indicator of histological chorioamnionitis. We examined the placental pathology after screening of the placental gross appearance and perinatal complications and did not examine uncomplicated deliveries. We investigated the relationship between the presence of an opaque fetal membrane and histological chorioamnionitis (Cohort 1, 571 placentas) or the outcomes of neonates delivered at term (Cohort 2, 409 placentas) at Hamamatsu University School of Medicine between 2010 and 2017. The judgment of a positive opaque fetal membrane based on gross appearance correlated with histological chorioamnionitis (Cohort 1). Its sensitivity and specificity were 66.7 and 89.9%, respectively, while positive and negative predictive values were 86.8 and 73.0%, respectively. The judgment of a positive opaque fetal membrane based on gross appearance significantly correlated with chorioamnionitis-related complications in term newborns after adjustments for confounding factors (OR;1.82 [1.07–3.11], P<0.05) (Cohort 2). A correlation was observed even after adjustments for confounding factors. The present study is the first to demonstrate that the judgment of a positive opaque fetal membrane based on gross appearance correlated with histological chorioamnionitis as well as chorioamnionitis-related complications in newborns delivered at term. The present results provide support for the traditionally-described importance of gross inspections for an opaque fetal membrane soon after birth. [ABSTRACT FROM AUTHOR]

This small-scale randomized controlled study aimed to examine the effect of l- arginine supplementation on the human chorionic gonadotropin (hCG)–positive rate and clinical pregnancy rate (CPR) in women undergoing assisted reproductive technology (ART) treatment for 3 months. From November 2017 to March 2018, 120 patients aged less than 40 years and planning for egg retrieval for embryo transfer were enrolled. The patients were divided into the AS2000 group (n = 36; l- arginine, 2 g; folate, 400 μg; and vitamin E, 10 mg), AS1000 group (n = 37; l- arginine, 1 g; and folate, 200 μg), and control group (n = 36). The main outcome was the hCG-positive rate or CPR in 3 months. The cumulative hCG-positive rates during the administration period were 44.2%, 54.2%, and 52.1%, and the CPRs were 39.5%, 41.7%, and 47.9% in the control, AS1000, and AS2000 groups, respectively. Odds ratios of the hCG-positive rate and CPR in the global l- arginine group (AS1000 and AS2000) versus those in the control group were 1.33 (95% confidence interval [CI], 0.62-2.90) and 1.11 (95% CI, 0.51-2.46), respectively. In the subgroup of women receiving ART because of male infertility, the hCG-positive rate and CPR were significantly increased in the l- arginine groups compared to those in the control group (13.42 [95% CI, 1.42-366.9] and 13.62 (95% CI, 1.42-367.6), respectively). Thus, arginine supplementation may be an option for women who desire pregnancy, especially those undergoing an ART program because of male infertility. [ABSTRACT FROM AUTHOR]

Aim: The difference of placental weight (PW) and fetal/placental weight ratio (F/P) Z scores by mode of delivery is unclear. To investigate such differences and the actual conditions underlying the imbalance between fetal and placental growth. Methods: The data from Japanese database 2013 were assessed. Light‐for‐dates (LFD, n = 12 884), appropriate‐for‐dates (n = 114 464) and heavy‐for‐dates (n = 13 164) from 140 512 placentas/infants of mothers delivered a singleton infant. Using Z scores of PW and F/P based on the standard curves of a sex‐, parity‐ and gestational‐age‐specific PW and F/P, the rate of inappropriately heavy placenta according to the mode of delivery (vaginal [VD] vs cesarean [CS]) was investigated. Results: (i) The PW and F/P were heavier and bigger in VD than in CS, in each subgroup. In the LFD groups, the PW Z score in VD was higher than that in CS, whereas the F/P Z score was lower than in VD than that in CS. (ii) Data of single regression analyses between the PW Z score and F/P Z score in VD groups were different from those in CS, especially in LFD infants. (iii) In the LFD subgroups, the rates of inappropriately heavy placenta in VD (n = 7781) and CS (n = 5103) were 0.54% and 0.86%, respectively. Conclusion: Difference in the mode of delivery influenced the PW and F/P, and the rate of inappropriately heavy placenta is associated with mode of delivery among LFD infants. This methodology might give us a clue to search a useful way for identifying the high‐risk groups requiring postnatal counseling. [ABSTRACT FROM AUTHOR]

Objective: Hypertensive disorder of pregnancy (HDP) is a major cause of maternal death. The goal of this study was to investigate factors associated with maternal death due to HDP. Study design: HDP-related maternal deaths in Japan reported to the Committee of the Ministry of Health, Labor and Welfare from 2010 to 2015 were examined. Results: Out of 47 cases of HDP, 30 were identified as the major cause of maternal death. The median maternal age was 34 years (range 24-45) and the mortality in women aged ≥40 years was seven times higher that than in women aged <34 years. The etiologies were intracerebral hemorrhage (n = 22), subarachnoid hemorrhage (n = 3), subcapsular hematoma of the liver (n = 2), peripartum cardiomyopathy (n = 2), and eclampsia (n = 1), and 19 cases were deemed preventable. The most frequent antepartum problems were delays in hospitalization, maternal transfer, and termination of pregnancy. In four cases, diagnosis of HELLP syndrome was too late because laboratory data were not checked, despite the patient reporting epigastric pain or showing elevation of blood pressure (BP). Treatment for lowering of BP was improper in 2/3 intrapartum cases, even though BP was elevated during pregnancy (144 versus 188 mmHg, p < .001). There was inadequate lowering of BP and lack of use of magnesium sulfate in 7/11 postpartum cases (64%), despite aspartate aminotransferase (AST) (p < .005), alanine aminotransferase (ALT) (p < .01), lactate dehydrogenase (LDH) (p < .005), and platelet count (PLT) (p < .01) all significantly worsening after delivery. Conclusion: HDP accounts for 11% of maternal deaths in Japan. Mothers aged ≥40 years are most at risk for HDP-related maternal death. Major concerns for preventabilities were late hospitalization, maternal transportation, and termination of pregnancy for term or near-term HDP. Regular vital checks and prompt lowering of BP were lacked during labor in most cases. HELLP syndrome should be managed at a general hospital with sufficient medical resources. [ABSTRACT FROM AUTHOR]

Aim: Uterine atony is a major cause of postpartum hemorrhage. We recently proposed a new concept for the histopathophysiology of refractory uterine atony, postpartum acute myometritis (PAM), characterized by acute inflammatory changes with massive stromal edema, increased numbers of complement C5a receptors and diffuse mast cell activation in the myometrium. We herein focused on the possible involvement of the kinin‐kallikrein system in the rapid development of interstitial edema in PAM, particularly bradykinin receptor type 1 (B1R), which is up‐regulated under inflammatory conditions. The present study investigated B1R expression with uterine interstitial edema in PAM. Methods: Our institution plays an important role in a Japanese amniotic fluid embolism registry project. We selected PAM cases from uterine samples delivered to us for further analyses between 2012 and 2017. Control tissues were collected during cesarean section and planned hysterectomy. B1R expression was semi‐quantitatively measured by immunohistochemistry, while uterine interstitial edema was estimated by semi‐quantitative measurements of the alpha smooth muscle actin‐negative area using immunohistochemistry. Results: There were 36 and 8 cases in the PAM and control groups, respectively. The alpha smooth muscle actin‐negative area was increased in the PAM group, concomitant with the significant up‐regulation of B1R expression in uterine smooth muscle cells, vascular endothelial cells, and neutrophils. A positive correlation was observed between these two factors. Conclusion: We demonstrated the up‐regulated expression of B1R in the myometrium and its positive correlation with histologically estimated interstitial edema, suggesting the contribution of the kinin‐kallikrein‐B1R system to the development of interstitial edema in PAM cases. [ABSTRACT FROM AUTHOR]

Introduction: There is a paucity of data on the risk of preterm birth subcategorized by gestational age in pregnancies after the pre-pregnancy excisional treatment for cervical lesions. In addition, little is known about the effect of prophylactic cerclage on the risk of preterm birth. The aim of this study was to investigate the risk of preterm birth stratified by gestational period and its reduction by the prophylactic cerclage in women with prior excisional surgery.Materials and Methods: We retrospectively analyzed a cohort of singleton pregnancies in the Japan Perinatal Registry Network Database (2013-2014, n = 307,001). Cases included pregnancies after the surgery (i.e. conization and loop electrosurgical excision procedure). Controls comprised the propensity-score matched pregnancies without pre-pregnancy surgery. The main outcome was the occurrence of preterm birth. The effect of prophylactic cervical cerclage on the risk of preterm birth after the excisional surgery was also examined using cases.Results: In the propensity-score matched population (cases, n = 1389; controls, n = 1389), cases exhibited a higher risk of preterm birth and preterm prelabor rupture of membranes (PROM), compared with controls (preterm birth: 25.3 versus 10.6%; preterm PROM: 14.0 versus 3.5%: both p < .0001). Odds ratios (OR; 95% confidence interval [CI]) for preterm birth at 22-27 weeks, 28-31 weeks, 32-33 weeks, and 34-36 weeks were 3.4 [1.8-6.5], 4.6 [2.7-7.7], 2.2 [1.4-3.5], and 2.1 [1.6-2.7], respectively. The association was stronger for preterm PROM at earlier gestational age (22-27 weeks, 28-31 weeks, 32-33 weeks, and 34-36 weeks: 5.2 [2.3-11.8], 7.1 [3.4-15.0], 3.8 [1.7-8.3], and 3.9 [1.8-4.6], respectively). In cases, 171 underwent the prophylactic cervical cerclage. The occurrence of preterm birth and preterm PROM was comparable between those with and without the cerclage (28.7 versus 24.2, and 12.9 versus 13.3%, respectively).Conclusions: Pre-pregnancy excisional cervical surgery was associated with the increased risk of preterm birth, especially before 32 weeks of gestation. The prophylactic cerclage did not reduce the risk of preterm birth. [ABSTRACT FROM AUTHOR]

Short-chain fatty acids (SCFAs) produced by fermentation from prebiotics not only provide energy but also activate cell membrane receptors, thereby contributing to the maintenance of homeostasis in the human body. Recently, free fatty acid receptor 2 (FFAR2), which uses SCFAs as ligands, was found to exert oncoprotective effects on several types of neoplasia. This study examined whether SCFAs have oncoprotective effects on uterine cervical neoplasia. Immunohistochemical analysis revealed that FFAR2 was expressed in atypical cells and cancer cells of cervical neoplasia. Moreover, reverse transcription polymerase chain reaction showed that FFAR2 was expressed in a human cervical cancer cell line, HeLa. We also found that SCFAs inhibited the proliferation of HeLa cells, and a FFAR2 antagonist, GLPG0974, used to suppress the binding of SCFAs significantly restored the cell viability of HeLa cells blocked by acetic acid treatment. These results suggest that ingestion of prebiotics and the resulting production of SCFAs may play an oncoprotective role against uterine cervical neoplasia via FFAR2 expression. [ABSTRACT FROM AUTHOR]

Aim: To investigate the influence of reproductive medicine in maternal death cases in Japan. Methods: This retrospective study investigated the incidence of maternal deaths related to reproductive medicine in Japan from 2013 to 2015, and the relationship between fertility treatment and maternal death. Results: Fifteen out of 134 women (11.2%) involved in this study who underwent treatment for infertility died. Four experienced pregnancy with severe maternal complications (26.6%). The complications were active systemic lupus erythematosus, exacerbated depression, uncontrolled arrhythmia and uncontrolled type 2 diabetes mellitus. At least three of these four died due to these complications. Conclusion: The maternal death rate of women who have undergone fertility treatment is similar to the birth rate due to assisted reproductive technology in Japan. Some maternal death cases involve severe uncontrolled complications. Therefore, medical histories should be evaluated before fertility treatment. [ABSTRACT FROM AUTHOR]

Abstract The present retrospective study provides an in-depth analysis of the maternal sepsis-related deaths reported in Japan, and aims to guide future care regarding maternal sepsis. This is a nationwide, retrospective, descriptive cohort study. Data were retrospectively analyzed on all maternal death cases related to sepsis reported in Japan from 2010 through 2016. A total of 7,347,727 births and 317 maternal deaths were reported during the study period. The cause of maternal death was sepsis in 24 women (7.5%). Causative bacteria were Streptococcus pyogenes (54.2%), Chlamydia psittaci (8.3%), Mycobacterium tuberculosis (8.3%), Escherichia coli (4.2%), Neisseria meningitidis (4.2%), Epstein-Barr virus (4.2%), and unknown (16.6%). In maternal death due to S. pyogenes (13 women), onset periods ware antepartum in 10 women (76.9%) and postpartum in 3 (23.1%); death within 24 h after hospital admission occurred in 7 women (53.8%); and the median time from hospital admission to death was 12 h (6–744 h). The most common causative bacteria in to maternal sepsis-related death were GAS. When encountering severe sepsis during the peripartum period, we recommend considering severe GAS infection and early intervention. [ABSTRACT FROM AUTHOR]

Abstract Introduction Pulmonary thromboembolism (PTE) is a leading cause of maternal death and frequently occurs during early puerperium. Amniotic fluid components are frequently observed in the maternal circulation in parturition; however, it currently remains unclear whether amniotic fluid contamination in maternal blood is related to the high incidence of PTE in early postpartum. Objectives To examine the influence of amniotic fluid on blood coagulation and fibrinolysis systems with thromboelastometry. Materials and methods Twenty-one pregnant women were recruited. We used whole citrated blood in ROTEM® (Tem Innovations GmbH, Munich, Germany), including the non-activated assay (NATEM), assessments for extrinsic (EXTEM) and intrinsic pathways (INTEM), fibrin polymerization (FIBTEM), and hyperfibrinolysis (APTEM), with amniotic fluid contamination, and measured the clotting time (CT), clot formation time (CFT), alpha, amplitude at 10 min (A10), maximum clot firmness (MCF), and lysis indices at 30 min (LI30) and 60 min (LI60). Results Short CT in all assays as well as short CFT, high alpha, and increased A10 and MCF in NATEM were observed with amniotic fluid contamination. A10 and MCF as well as LI30 and LI60 decreased in EXTEM. Decreased LI60 with the mixture of amniotic fluid was not improved by tranexamic acid in APTEM. Conclusions Amniotic fluid accelerated thrombin production and activated platelet aggregation without inducing hyperfibrinolysis in whole blood. The activated tissue factor pathway with amniotic fluid produced soft and fragile clots due to its influence on platelets, which may be associated with, at least partly, the high incidence of PTE in early puerperium, particularly after cesarean section. Highlights • Amniotic fluid activated blood coagulation and platelet aggregation. • Amniotic fluid increased clot firmness by augmenting platelet function. • Hyperfibrinolysis was not induced by amniotic fluid contact with maternal blood. • Amniotic fluid made clots fragile via an extrinsic pathway in thromboelastometry. • These results suggest a relationship with PTE in early postpartum. [ABSTRACT FROM AUTHOR]

Objective: The number of stroke-related maternal deaths is increasing in Japan. We investigated methods to reduce maternal death from stroke.Methods: We analyzed stroke-related maternal deaths in Japan reported to the Committee of the Ministry of Health, Labor, and Welfare from 2010 to 2014 inclusive.Results: A total of 35 cases were identified. The median maternal age was 35 years (range 22-45) and the incidence of stoke in women ≥40 was seven-fold higher than in <34. Etiologies were pregnancy induced hypertension in 16, subarachnoid hemorrhage in seven, cerebral infarction in three, arteriovenous malformation in two, Moyamoya disease in one, and origin unknown cerebral hemorrhage in six. These cases occurred in antepartum 43%, in postpartum 31%, and in intrapartum 26%. 23 cases were deemed non-preventable and 12 cases preventable. Possible preventable factors occurred antepartum in 23, postpartum in seven, and intrapartum in six. Preventable features included inadequate hypertension control (33%), presenting too late for termination of pregnancy (14%), delayed hospitalization (11%), and delayed maternal transfer (11%).Conclusions: A total of 90% of strokes were hemorrhagic, and older mothers (≥ 40) were most at risk. Most possible preventable factors occurred antepartum, and improved control of hypertension and earlier termination would help to reduce maternal death from stroke. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the relationship between placental pathological findings and physiological development during the neonate and infantile periods. Study participants were 258 infants from singleton pregnancies enrolled in the Hamamatsu Birth Cohort for Mothers and Children (HBC Study) whose placentas were stored in our pathological division. They were followed up from birth to 18 months of age. Physiological development (body weight and the ponderal index [PI]) was assessed at 0, 1, 4, 6, 10, 14, and 18 months. Placental blocks were prepared by random sampling and eleven pathological findings were assessed, as follows: ‘Accelerated villous maturation’, ‘Decidual vasculopathy’, ‘Thrombosis or Intramural fibrin deposition’, ‘Avascular villi’, ‘Delayed villous maturation’, ‘Maternal inflammatory response’, ‘Fetal inflammatory response’, ‘Villitis of unknown etiology (VUE)’, ‘Deciduitis’, ‘Maternal vascular malperfusion’, and ‘Fetal vascular malperfusion’. Mixed model analysis with the use of the xtmixed command by the generic statistical software, Stata version 13.1., identified ‘Accelerated villous maturation’ and ‘Maternal vascular malperfusion’ as significant predictors of a lower body weight and ‘Deciduitis’ as a significant predictor of a small PI, throughout the first 18 months of life. In conclusion, the present study is the first to demonstrate that some pathological findings of the placenta are associated with changes in infantile physical development during the initial 18 months of life in the Japanese population. [ABSTRACT FROM AUTHOR]

Objective: To clarify the necessity for and problems related to autopsy for determining the cause of maternal death in Japan.Methods: Women who died during pregnancy or within a year after delivery were analyzed by the Maternal Death Exploratory Committee between 2012 and 2015 in Japan. Maternal deaths were analyzed to verify the requirement of autopsy in cases in which autopsy was performed and the need for autopsy in cases in which it was not performed.Results: Among the 49 cases performed autopsy, the final diagnosis was compatible with the clinical course in 24 cases, while the autopsy diagnosis was incompatible with the clinical course in 13 cases. In two cases, the final diagnosis was based on the clinical course, but an autopsy could exclude other possible causes. In three cases, no exact cause of maternal death was identified after autopsy. On the other hand, in cases without an autopsy, the final diagnosis was made using ante-mortem operating findings and surgical specimens in twenty-one cases. Though, thirty-one cases were estimated diagnosis based on post-mortem imaging or ante-mortem examinations, the exact original cause of death was not determined in 25 cases, and the cause of death could not be identified in eight cases without autopsy.Conclusion: Because in most cases the autopsy provides an exact cause of death, the necessity of autopsies should be more widely accepted in Japan. [ABSTRACT FROM AUTHOR]

Abstract: We conducted a questionnaire survey on the current obstetric management of preterm labor (PL) and preterm premature rupture of the membranes (pPROM). The questionnaire covered approximately a third of all preterm deliveries and nearly half of the preterm deliveries before 32 gestational weeks. The diagnostic criterion for PL was either painful uterine contractions or cervical dilatation. Tocolytic agents were primarily used as long‐term maintenance therapy. Intrauterine infection was clinically diagnosed at most responding institutions. Amniocentesis was performed for PL or pPROM at only a small number (10%) of institutions. Prenatal steroids were administered for PL or pPROM, if indicated, at approximately 40–60% of responding institutions. Prophylactic antibiotics to maintain pregnancy were administered for pPROM at approximately 90% and for PL at approximately 20% of institutions. Maintenance therapy with a tocolytic agent was used for pPROM at approximately 90% of institutions. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the rate of coagulopathy progression in amniotic fluid embolism (AFE), using the level of fibrinogen.Methods: We examined all cases of maternal death (46 cases) related to AFE between 2010 and 2013 in Japan (total number of deliveries: 4,291,459). Fibrinogen, blood loss from AFE onset to fibrinogen measurement, and time from onset to fibrinogen measurement were investigated. The correlations of fibrinogen with time from onset to fibrinogen measurement and blood loss at fibrinogen measurement were analyzed.Results: Fibrinogen was undetectable (less than 50 mg/dL) in 14 cases (93%) and 65 mg/dL in one case (7%). All the cases involving not less than 1000 mL of blood loss or within 60 min from onset to fibrinogen measurement demonstrated low levels of fibrinogen.Conclusions: Coagulopathy in AFE was not directly proportional to bleeding. Furthermore, coagulopathy in AFE developed in a remarkably short length of time. If AFE is suspected, fibrinogen level should be measured rapidly for favoring a more AFE to decrease the risk of death from AFE. And, rapid treatment of coagulopathy can help reduce mortality from AFE. [ABSTRACT FROM AUTHOR]

Aim We aimed to evaluate the clinical usefulness of serum squamous cell carcinoma (SCC) antigen for the diagnosis of amniotic fluid embolism (AFE). Methods Sera and information of 20 patients with AFE (autopsy-proven AFE, four cases; clinical AFE, 16 cases) were obtained from the Japan Amniotic Fluid Embolism Registration Center at Hamamatsu University School of Medicine. As controls, we included 74 gestational-age-matched healthy women who gave birth to healthy newborns during the period from December 2012 to January 2014. Receiver-operator curves (ROC) were used to evaluate the diagnostic performance of SCC levels for prediction of AFE. Results Serum SCC antigen levels in women with autopsy-proven AFE (112.0 ± 169.4 ng/mL, P = 0.001) and clinical AFE (9.5 ± 10.3 ng/mL, P = 0.004) were significantly higher than those in healthy controls with normal delivery (4.4 ± 2.2 ng/mL). On ROC analysis, the optimal cut-off value for SCC antigen levels was 7.15 ng/mL, for which the sensitivity and specificity for AFE prediction was 60.0% and 89.2%, respectively (area under the ROC, 0.785; 95% confidence interval, 0.663-0.908; P < 0.001). Conclusion Serum SCC antigen may be a promising predictor of the entry of amniotic fluid into the maternal circulation, potentially serving as a candidate marker for noninvasive diagnosis of AFE. [ABSTRACT FROM AUTHOR]

Hysterosalpingography (HSG) using iodinated contrast medium is X-ray diagnostic test that examines the inside of the uterus and fallopian tubes in infertile women. In this study, we compared thyroid function (thyroid stimulating hormone: TSH and free-T4: FT4 levels) after HSG with an oil-soluble contrast medium (OSCM) and a water-soluble contrast medium (WSCM). One hundred and sixty-four and 94 patients with normal thyroid function received HSG with OSCM and WSCM, respectively. Approximately 25% of the women in the OSCM group developed subclinical hypothyroidism (SCH), whereas only less than 10% of the patients in the WSCM group developed SCH. Our data clearly indicate that WSCM is safe for thyroid function in women who plan to get pregnant. [ABSTRACT FROM PUBLISHER]

Background and Aim Liver dysfunction with decreased antithrombin (AT) activity and/or thrombocytopenia is life threatening in pregnant women. Whether AT is clinically useful for prediction of liver dysfunction remains unclear. Methods A total of 541 women were registered prospectively at gestational week 34.7 (20.0-41.4) with available data on antenatal AT and platelet count (PLC). Results Liver dysfunction defined as serum aspartate aminotransferase > 45 IU/L concomitant with lactate dehydrogenase > 400 IU/L occurred in five women antenatally (≤ 2 weeks before delivery) and in 17 women post-partum (within 1 week post-partum). Median (5th-95th) antenatal value was 85 (62-110)% for AT and 202 (118-315) × 109/L for PLC in the 541 women and was significantly lower in women with than without perinatal liver dysfunction; 75 (51-108) versus 86 (62-110)% and 179 (56-244) versus 203 (121-316) × 109/L, respectively. Nineteen (86%) women with liver dysfunction showed AT ≤ 62% or thrombocytopenia (PLC ≤ 118 × 109/L) perinatally, but five lacked thrombocytopenia throughout the perinatal period. The best cut-off (AT, 77%; PLC, 139 × 109/L) suggested by receiver operating characteristic curve gave antenatal AT and PLC sensitivity of 59% and 41% with positive predictive value of 8.6% and 14%, respectively, and combined use of AT and PLC improved sensitivity to 73% (16/22) with positive predictive value of 9.2% for prediction of perinatal liver dysfunction. Conclusions Reduced AT not accompanied by thrombocytopenia can precede liver dysfunction. Clinical introduction of AT may enhance the safety of pregnant women. [ABSTRACT FROM AUTHOR]

Aim Oxygen saturation during the term of delivery to the first cry, when fetal circulation dynamically changes, has not yet been examined. The aim of this study was therefore to determine whether the continuous measurement of regional tissue oxygen saturation (rSO2) from crowning until 5 min after delivery is possible using fetal tissue oximetry with a sensor attached to the examiner's finger. Methods Oxygen saturation levels in fetal cranial tissue between the second stage of delivery to crowning and up to 5 min after delivery were measured using fetal tissue oximetry with a sensor attached to the examiner's finger. Thirty-five deliveries were examined, and oxygen saturation was measured in seven infants from delivery of the head until 5 min after birth. Umbilical cord blood gas was measured in all cases. This clinical test was performed under the permission of the Ethics Committee of Hamamatsu University School of Medicine. Results Average tissue oxygen saturation in the second stage of delivery and at 5 min after delivery were 50.3 ± 16.3% and 56.8 ± 8.46%, respectively. In cases of continuous measurement, average rSO2 for crowning, immediately after delivery, and the first cry was 32.7 ± 9.5%, 30.0 ± 6.6%, and 31.6 ± 5.5%, respectively. Conclusion We herein successfully measured oxygen saturation levels in fetal cranial tissue during crowning, delivery of the head, the first cry, and 5 min after delivery using fetal tissue oximetry with a sensor attached to the examiner's finger. [ABSTRACT FROM AUTHOR]

Amniotic fluid embolism (AFE) is recognized as a type of syndrome characterized by the abrupt onset of hypoxia, hypotension, seizures, or disseminated intravascular coagulopathy (DIC), occurring during labor, delivery, or immediately postpartum, caused by the inflow of amniotic components into the maternal circulation. AFE is a rare condition but one of the most serious obstetrical complications, resulting in a high mortality rate among pregnant women. Despite earlier recognition and intensive critical management, we often encounter patients who unfortunately do not recover from the exacerbation of AFE-related conditions. A major concern is that there are no effective evidence-based therapies for AFE, because its pathophysiology is still not well understood. This article reviewed AFE, focusing on the pathology and currently proposed pathophysiology. [ABSTRACT FROM AUTHOR]

We investigated the potential relationship between maternal depressive symptoms during the postpartum period and non-verbal communication skills of infants at 14 months of age in a birth cohort study of 951 infants and assessed what factors may influence this association. Maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale, and non-verbal communication skills were measured using the MacArthur-Bates Communicative Development Inventories, which include Early Gestures and Later Gestures domains. Infants whose mothers had a high level of depressive symptoms (13+ points) during both the first month postpartum and at 10 weeks were approximately 0.5 standard deviations below normal in Early Gestures scores and 0.5-0.7 standard deviations below normal in Later Gestures scores. These associations were independent of potential explanations, such as maternal depression/anxiety prior to birth, breastfeeding practices, and recent depressive symptoms among mothers. These findings indicate that infants whose mothers have postpartum depressive symptoms may be at increased risk of experiencing delay in non-verbal development. [ABSTRACT FROM AUTHOR]

Background: The Japan Association of Obstetricians and Gynecologists (JAOG) recommends transfusion with a fresh-frozen plasma (FFP):red blood cell (RBC) ratio of 1 or more in postpartum hemorrhage. However, no global consensus exists concerning this, and little is known regarding the impact of FFP:RBC ratio on maternal mortality. This study evaluates the efficacy of transfusion with FFP:RBC ratio of 1 or more for amniotic fluid embolism (AFE) with coagulopathy.Study Design and Methods: The Maternal Death Exploratory Committee, established by the JAOG, conducted this retrospective nationwide case-control study in Japan. Women with AFE and coagulopathy were included in the study and were stratified into survival and death groups. Obstetric variables and therapy methods (hysterectomy, uterine artery embolism, and transfusion with FFP:RBC ratio ≥ 1) were compared between the survival and death groups.Results: A total of 54 women had AFE and coagulopathy (death group, n = 22; survival group, n = 32). Only nine (40.9%) women in the death group were transfused with FFP:RBC ratio of 1 or more, whereas 29 (90.6%) women in the survival group were transfused with FFP:RBC ratio of 1 or more. FFP:RBC ratio of 1 or more was found to be associated with better survival rate (adjusted odds ratio, 28.32; 95% confidence interval, 4.26-188.37). No difference was found in obstetric variables, hysterectomy, and uterine artery embolism between survival and death groups.Conclusion: Transfusion with FFP:RBC ratio of 1 or more is associated with higher survival rate in women with AFE with coagulopathy. [ABSTRACT FROM AUTHOR]

Aim: To clarify the frequency of occurrence of uterine rupture and its prognosis, a nationwide survey was performed. Methods: Cases of uterine rupture recorded for a period of 5 years were included. Results: There were 152 cases of uterine rupture with an incidence rate of 0.015%. The scarred uterine rupture cases were found to have a significantly earlier occurrence of uterine ruptures in comparison to the unscarred cases: unscarred 39.0 weeks, cesarean section 37.0 weeks, myomectomy 32 weeks and adenomyomectomy 30–32 weeks. And it became apparent that the frequency of hysterectomy, cerebral palsy and neonatal death were higher in the cases of uterine rupture during labor than before delivery. Among the cases of scarred uterine rupture, neonatal prognosis was poorer in cases of pregnancy after myomectomy or adenomyomectomy in comparison with postcesarean section cases. Conclusion: This survey revealed the current incidence of uterine rupture in Japan. [ABSTRACT FROM AUTHOR]