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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

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

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. [ABSTRACT FROM AUTHOR]

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

Thrombocytopenia during pregnancy has many different causes, but Mycoplasma pneumoniae is not usually considered one of the several pathogens that induce thrombocytopenia. Herein, we present a case of severe thrombocytopenia that was associated with M. pneumoniae during pregnancy. The patient experienced fever, cough, and cytopenia with M. pneumoniae-specific IgM antibody increasing from 40-fold to 160-fold during the 2 weeks of illness. A diagnosis was made after excluding other diseases that cause thrombocytopenia. The patient was successfully treated with azithromycin hydrate, and she delivered a healthy newborn without any complications. Pregnant women who are infected with M. pneumoniae during pregnancy may develop severe and fatal thrombocytopenia. Prompt diagnosis and initiation of treatment lead to early recovery. [ABSTRACT FROM AUTHOR]

Rectal perforation is uncommon in ovarian cancer, even in advanced stages. Pure primary ovarian squamous cell carcinoma is a very rare subtype of ovarian cancer and has not been reported to cause rectal perforation. A 50-year-old woman presented with rectal bleeding. Rectosigmoidoscopy suggested perforation of a pelvic tumor into the rectum. Abdominopelvic magnetic resonance imaging revealed a 9 cm heterogeneous mass in the pouch of Douglas. We performed complete cytoreduction, including an en-bloc resection of the tumor and rectosigmoid colon. Histopathology showed squamous cell carcinoma of the left ovary penetrating the rectal wall. A common symptom of rectal bleeding was caused by a very rare entity of ovarian cancer penetrating the rectal wall, but thorough evaluation led to its accurate diagnosis and appropriate treatment. [ABSTRACT FROM AUTHOR]

We report a case of mirror syndrome caused by parvovirus B19, which resolved after intra-uterine transfusion. Mirror syndrome is a rare condition characterised by a triad of foetal hydrops, generalized maternal oedema and placentomegaly. Although the mechanism underlying the onset of this syndrome is unknown, it probably shares a common pathophysiologic origin with pre-eclampsia. Our patient showed increased circulating levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and decreased levels of placental growth factor (PlGF), which have also been reported in pre-eclampsia. The sFlt-1/PlGF ratio decreased immediately after intra-uterine transfusion, followed by resolution of both maternal and foetal symptoms. This suggests that the sFlt-1/PlGF ratio may help to predict the post-treatment course of mirror syndrome. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: This study investigated the hypothesis that ceftriaxone preconditioning ameliorates brain damage in neonatal animals through glutamate transporter 1 (GLT-1) upregulation. Study design: Sprague Dawley rats were pretreated with ceftriaxone, erythromycin, minocycline, or saline for 5 consecutive days starting from postnatal day 2 (P2), and GLT-1/glutamate-aspartate transporter (GLAST) messenger RNA (mRNA) and protein levels were examined in the P7 brains. After ceftriaxone or saline preconditioning, the P7 rats underwent hypoxic-ischemic (H-I) procedure or sham operation. One week after the procedure (P14), hematoxylin-eosin staining, microtubule-associated protein 2 (MAP-2) immunostaining, and transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay were used to examine neuronal damage and possible neurotoxicity. Results: Repeated ceftriaxone injections significantly increased GLT-1 mRNA and protein levels but not GLAST. Following such treatment and H-I procedure, the MAP-2-positive area increased and TUNEL-positive cells decreased. Conclusion: Antenatal ceftriaxone may help to provide neuroprotection in the immature brain and become a new prophylactic strategy to reduce neonatal encephalopathy in clinical perinatal medicine. [ABSTRACT FROM PUBLISHER]

Background: Fetal ovarian cysts are the most frequently diagnosed intra-abdominal cysts; however, the evidence for perinatal management remains controversial. Methods: We retrospectively reviewed cases of fetal ovarian cysts diagnosed by prenatal ultrasonography at our institution between January 2010 and January 2020. The following were investigated: gestational age at diagnosis, cyst size, appearance, prenatal ultrasound findings, and postnatal outcomes. Prior to 2018, expectant management was applied in all cases; after 2018, in utero aspiration (IUA) of simple cysts ≥40 mm was performed. Results: We diagnosed 29 and seven simple and complex cysts, respectively. Fourteen patients had simple cysts with a maximum diameter <40 mm, and two of them progressed to complex cysts during follow-up; however, when the diameter was limited to <35 mm, no cases showed progression to complex cyst. Fifteen of the simple cysts were ≥40 mm; three progressed to complex cysts, and two of them were confirmed to be ovarian necrosis. In four patients who underwent IUA, the ovaries could be preserved. Conclusions: IUA is a promising therapy for preserving ovaries with simple cysts ≥40 mm in diameter; however, the indications for fetal surgery and the appropriate timing of intervention require further study. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To assess the association between use of uterine compression sutures (UCSs) and postoperative complications.Methods: In a retrospective analysis, data were reviewed from cesarean deliveries at a medical center in Osaka, Japan, between January 2011 and March 2016. The deliveries were divided into elective and emergency cesarean groups. For each group, data on postoperative complications were compared between patients with UCSs and those without UCSs but at least 1500 mL of blood loss.Results: Data from 158 patients were included in the study. No severe complications were observed. Among the patients who underwent elective cesarean, no differences were observed between the UCS and non-UCS groups in the frequency of postoperative endometritis (3/28 [10.7%] vs 6/54 [11.1%]; P=0.957) or ileus (2/28 [7.1%] vs 3/54 [5.6%]; P=0.776). After emergency cesarean, postoperative endometritis was significantly more common in the UCS than in the non-UCS group (8/39 [20.5%] vs 4/37 [10.8%]; P=0.021), but the frequency of ileus did not differ (1/39 [2.6%] vs 2/37 [5.4%]; P=0.61).Conclusion: Use of UCSs during emergency cesarean delivery might increase the risk of postoperative endometritis. [ABSTRACT FROM AUTHOR]

Placenta percreta is a rare condition that presents a risk of massive intraoperative hemorrhage. To decrease maternal morbidity in such cases, conservative management was recently adopted as an option. Nevertheless, severe morbidity occurs in 42% of cases. In addition, the clinical course of conservative management remains unclear. We encountered a case of placenta percreta that was successfully treated by conservative management without complications or other clinical interventions. Serial magnetic resonance imaging (MRI) was performed to investigate the natural course of conservative management of placenta percreta. MRI on postoperative day (POD) 99 showed a decrease in placental size without gadolinium enhancement. MRI on POD 162 showed that the residual placenta was approximately 4 cm in size without gadolinium enhancement. On POD 265, the placenta had almost disappeared. This is the first series of MRI of conservative management of placenta percreta without clinical interventions. We present our case and a literature review. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

Abstract: Ureaplasma spp. are members of the family Mycoplasmataceae and have been considered to be associated with chorioamnionitis and preterm delivery. However, it is unclear whether Ureaplasma spp. have virulence factors related to these manifestations. The purpose of the present study was to determine whether the immunogenic protein multiple-banded antigen (MBA) from Ureaplasma parvum is a virulence factor for preterm delivery. We partially purified MBA from a type strain and clinical isolates of U. parvum, and also synthesized a diacylated lipopeptide derived from U. parvum, UPM-1. Using luciferase assays, both MBA-rich fraction MRF and UPM-1 activated the NF-κB pathway via TLR2. UPM-1 upregulated IL-1β, IL-6, IL-12p35, TNF-α, MIP2, LIX, and iNOS in mouse peritoneal macrophage. MRF or UPM-1 was injected into uteri on day 15 of gestation on pregnant C3H/HeN mice. The intrauterine MRF injection group had a significantly higher incidence of intrauterine fetal death (IUFD; 38.5%) than the control group (14.0%). Interestingly, intrauterine injection of UPM-1 caused preterm deliveries at high concentration (80.0%). In contrast, a low concentration of UPM-1 induced a significantly higher rate of fetal deaths (55.2%) than the control group (14.0%). The placentas of the UPM-1 injection group showed neutrophil infiltration and increased iNOS protein expression. Our data indicate that MBA from the clinical isolate of U. parvum is a potential virulence factor for IUFD and preterm delivery in mice and that the N-terminal diacylated lipopeptide is essential for the initiation of inflammation. [Copyright &y& Elsevier]

Abstract: Neonatal hypoxic–ischemic encephalopathy (HIE) is one of the major causes of neurodegeneration and mortality in the neonatal period. Although hypoxic preconditioning (HPC) provided strong neuroprotection against HIE in an animal model, the mechanism underlying this effect is not fully understood especially in the immature brain. Here, we investigated whether thyroid hormones (THs), especially triiodothyronine (T3), which are essential during normal brain development, contribute to the neuroprotective mechanisms of HPC by using an established model of HPC in neonatal rats. HPC treatment (8% O2 for 2.5h at 37°C) was performed in immature rats at postnatal day 6 (P6). Subsequently, we investigated the levels of THs, TH receptors (TRs) and type 2 and 3 deiodinase (D2 and D3) mRNA, and glutamate transporter 1 (GLT1) at 24h after HPC treatment, and myelin basic protein (MBP) at 6, 12 and 24h after HPC treatment. The HIE procedure was performed at 24h after HPC, and the neuroprotective effect of HPC was assessed via microtubule-associated protein 2 (MAP2) and MBP immunohistochemical staining at 14 days after HIE (P21). HPC treatment afforded marked neuroprotection at 14 days after HIE. The local level of T3 was upregulated 24h after HPC treatment in the developing rat brain, probably via the upregulation of D2. In addition, the expression of MBP and GLT1, which are the downstream protein of T3, were significantly increased 24h after HPC treatment. The present study indicates that thyroid hormones and their associated molecules may be involved in neuroprotective mechanisms of HPC during the developmental period. [Copyright &y& Elsevier]

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

To investigate the relationship between maternal hyperventilation and fetal blood gas values and to estimate its possible association with fetal oxygenation, maternal transcutaneous partial pressure of carbon dioxide (tcPCO2) values were analyzed in association with umbilical venous PCO2 (UVPCO2), umbilical venous partial pressure of oxygen (UVPO2), and umbilical venous oxyhemoglobin saturation (UVHbo2) values. Pregnant women without labor (30.7 ± 3.7 mm Hg, n = 20) showed significantly lower tcPCO2 values compared with nonpregnant women (37.4 ± 4.0 mm Hg, n = 10). Pregnant women in the second stage of labor showed even lower tcPCO2 values compared with pregnant women during the first stage of labor (20.8 ± 5.9 mm Hg vs 28.4 ± 5.0 mm Hg, n = 26). Maternal tcPCO2 values had significant positive correlations with UVPCO2 (r = .78, P < .001), UVPO2 (r = .62, P < .001), and UVHbO2 values (r = .59, P < .001). Maternal hyperventilation had a close relationship with lower UVPCO2, UVPO2, and UVHbo2 values, which might interfere with optimal fetal cerebral oxygenation. [ABSTRACT FROM AUTHOR]

Normal pregnancy is the controlled state of inflammation and this systemic inflammatory response is reported to be more intense in preeclampsia. The current study tested the hypothesis that maternal serum stimulates interleukin 6 (IL-6) production from endothelial cells and that nicotine inhibits these effects. Human umbilical vein endothelial cells (HUVECs) were incubated with or without 0.5% serum from healthy pregnant women at term (n = 5) and treated with or without nicotine (10-9 to 10-6 mol/L) in the presence of 0.5% serum. Cell survival was determined by colorimetric assay. Interleukin 6 concentration and nuclear transcription factor kappa B (NF-κB) activities were determined by enzyme-linked immunosorbent assay (ELISA)-based method. Interleukin 6 production by endothelial cells was significantly stimulated in the presence of maternal serum. Nicotine significantly preserved cell survival and suppressed IL-6 production from endothelial cells. Nicotine also significantly inhibited NF-κB activation in endothelial cells. Nicotine inhibited inflammatory reaction through NF-κB suppression in vitro model of maternal vascular endothelium, and this effect may be one of the explanations for the reduced risk of preeclampsia in smokers. [ABSTRACT FROM AUTHOR]

In utero exposure to infection or inflammation is a strong and independent predictor of cerebral palsy. Using a rat model of neonatal hypoxic--ischemic (HI) encephalopathy, we investigated the hypothesis that C-reactive protein (CRP), which is not specific for infection, aggravates vulnerability of the immature brain to HI. Seven-day-old rats were divided into human CRP treated and control groups. After injection of each solution, they underwent left common carotid artery ligation and exposure to 8% hypoxia for 40 minutes. Human CRP, rat CRP, and interleukin 6 (IL-6) concentrations in serum were measured by enzyme-linked immunosorbent assay 30 to 60 minutes after injection of each solution. Four days later, microtubule-associated protein 2 (MAP-2) immunostaining was used to examine the brains for neuronal damage. Human CRP treatment significantly reduced the MAP-2 positive area ratio, compared with control group ( P < .05), suggesting that human CRP-enhanced susceptibility to HI-induced brain damage. Mean serum human CRP concentration in the human CRP group was 1823 ± 520 ng/mL (range: 365-3964 ng/mL). Interleukin 6 concentrations in serum were moderately elevated in both groups, without significant differences, and rat CRP concentrations were within normal range. C-reactive protein makes the immature brain susceptible to HI insult, even if the insult causes little or no injury by itself. [ABSTRACT FROM AUTHOR]

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%. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

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

Key Clinical Message: Vasa previa has been represented in many reports only by images of the placenta with velamentous cord insertion after delivery. Our image of the restored membranous vessels with an intact membrane of the uterine lower segment is educational and should help readers to visualize vasa previa. Vasa previa has been represented in many reports only by images of the placenta with velamentous cord insertion after delivery. Our image of the restored membranous vessels with an intact membrane of the uterine lower segment is educational and should help readers to visualize vasa previa. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests a relationship between in vitro fertilization-embryo transfer (IVF-ET) and placenta accreta spectrum (PAS). Some studies have reported a lower rate of antenatal diagnosis of PAS after IVF-ET compared to PAS with spontaneous conception. This study aimed to review the diagnostic accuracy of PAS after IVF-ET and to explore the relationship between IVF-ET pregnancy and PAS. According to the PRISMA guidelines, a comprehensive systematic review of the literature was conducted through August 31, 2020 to determine the effects of IVF-ET on PAS. In addition, a meta-analysis was conducted to explore the relationship between IVF-ET pregnancy and PAS. Twelve original studies (2011–2020) met the inclusion criteria. Among these, 190,139 IVF-ET pregnancies and 248,534 spontaneous conceptions met the inclusion criteria. In the comparator analysis between PAS after IVF-ET and PAS with spontaneous conception (n = 2), the antenatal diagnosis of PAS after IVF-ET was significantly lower than that of PAS with spontaneous conception (22.2% versus 94.7%, P < 0.01; < 12.9% versus 46.9%, P < 0.01). The risk of PAS was significantly higher in women who conceived with IVF-ET than in those with spontaneous conception (odds ratio [OR]: 5.03, 95% confidence interval [CI]: 3.34–7.56, P < 0.01). In the sensitivity analysis accounting for the type of IVF-ET, frozen ET was associated with an increased risk of PAS (OR: 4.60, 95%CI: 3.42–6.18, P < 0.01) compared to fresh ET. Notably, frozen ET with hormone replacement cycle was significantly associated with the prevalence of PAS compared to frozen ET with normal ovulatory cycle (OR: 5.76, 95%CI 3.12–10.64, P < 0.01). IVF-ET is associated with PAS, and PAS after IVF-ET was associated with a lower rate of antenatal diagnosis. Therefore, clinicians can pay more attention to the presence of PAS during antenatal evaluation in women with IVF-ET, especially in frozen ET with hormone replacement cycle. [ABSTRACT FROM AUTHOR]

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

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

The cover image is based on the Clinical Image Gross image of vasa previa restored in the postpartum period by Shinya Matsuzaki et al., DOI: 10.1002/ccr3.2067. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Previous studies have shown adverse obstetric outcomes of the laparoscopic resection of a rudimentary horn. Our study aimed to investigate the obstetric outcome in our institution and to review previous studies. Methods: Using a retrospective analysis, data were reviewed from singleton pregnancies with maternal uterine anomalies at a medical center in Osaka, Japan, between January 2011 and March 2016. The uterine anomaly cases were divided into a ‘postlaparoscopic resection of the rudimentary horn’ group (study group) and an ‘other uterine anomalies’ (bicornuate uterus, uterine didelphys and unicornuate uterus) group (control group). Primary outcomes of interest were differences in obstetric outcomes, such as spontaneous preterm birth rate, small for gestational age (SGA) infant rate and hypertensive disorders of pregnancy (HDP) rate between the study and the control group, and the secondary outcome of interest was mode of delivery in the study group. Results: Data from 40 deliveries were included in the study (7 deliveries: study group, 33 deliveries: control group). No significant difference was observed between the two groups in terms of either mean gestational weeks at delivery (36.4 weeks vs 37.1 weeks; P = .38), cesarean delivery rate (57.1% vs 57.5%; P = 1.0), SGA infant rate (<10th percentile) (0% vs 24.2%; P = .31) and HDP rate (0.0% vs 3.0%; P = 1.0). Three of seven cases with postlaparoscopic resection of the rudimentary horn were able to deliver vaginally without complications. Conclusion: Our study shows that the obstetric outcome observed in the study group was similar to that observed in the control group. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Placenta percreta is a rare obstetric condition associated with the risk of massive intraoperative hemorrhage. Recently, conservative management of placenta percreta has been performed to reduce maternal morbidity. However, various complications have been reported during such management. Only a few cases of asymptomatic disseminated intravascular coagulation (DIC) or fever without infection have been reported. Here, we discuss such a case and review the related literature to understand this rare condition better. For this, we performed an electronic literature review.Case Presentation: We present the clinical course, results of blood tests, and serial magnetic resonance images of a 35-year-old female (gravida 5, para 2) with placenta percreta complicated by placenta previa that was managed conservatively. The patient successfully delivered a healthy baby by a cesarean delivery via a transverse uterine fundal incision at 36 weeks of gestation. We did not observe intraoperative complications during cesarean delivery, and the postoperative course remained uncomplicated until 47 days after the delivery. However, asymptomatic DIC developed after 47 days, and her serum fibrinogen level declined to 42 mg/dL, which was successfully treated with anticoagulant therapy by a therapeutic dose of intravenous heparin for 22 days (postoperative days 48-69). Although DIC resolved, subsequent fever persisted for approximately 1 month (postoperative days 67-103). Infection was ruled out, and conservative management was successfully continued. Literature review revealed that successful conservative management of a patient with asymptomatic DIC and subsequent fever without infection is extremely rare.Conclusions: Some patients with DIC and fever can continue conservative management of placenta percreta, although careful examination and monitoring are needed. [ABSTRACT FROM AUTHOR]

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

Background: The Jr(a) antigen of JR blood group systems is located on ABCG2 and Jr(a-) subjects whose red blood cells (RBCs) lack ABCG2 have been identified mostly among the Japanese. Although anti-Jr(a) can cause fetal anemia, little is known regarding its mechanism.Study Design and Methods: We reviewed clinical courses of all reported cases with fetal anemia due to anti-Jr(a) . We analyzed the ABCG2 expressions of cord RBCs at various gestational ages. We examined the effects of sera containing anti-Jr(a) from three pregnancies with fetal anemia or monoclonal anti-Jr(a) on erythropoiesis and phagocytosis. We also examined epitopes of anti-Jr(a) .Results: Case series suggested that the majority of fetal anemia with anti-Jr(a) may not be progressive in the later gestational ages. ABCG2 expression levels of cord RBCs were significantly higher than those of adults and neonates with high individual variation and gradually decreased with advancing gestational ages. Anti-Jr(a) did not significantly impact erythroid colony formation, although we detected a tendency toward the suppression of erythroid burst-forming unit formation by anti-Jr(a) using feline marrow cells. Anti-Jr(a) did not induce phagocytosis of sensitized RBCs by monocytes. While many anti-Jr(a) recognized the same regions as a monoclonal anti-ABCG2, 5D3, epitopes of anti-Jr(a) did not correlate with the incidence of fetal anemia.Conclusion: ABCG2 expression levels in cord RBCs are higher than those of adults, and the change of ABCG2 expression in erythroid lineage cells may influence the clinical course of fetal anemia with anti-Jr(a) , although we could not detect significant effects of anti-Jr(a) on erythroid colony formation or phagocytosis. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to assess the incidence and risk factors for recurrent spontaneous preterm birth (PTB) in Japan. Material and Methods A retrospective cohort study was conducted at five tertiary perinatal centers in Osaka, Japan from 2008 through 2012. Perinatal data were collected from medical records of women with a singleton gestation and a previous spontaneous PTB. Exclusion criteria were first-trimester spontaneous abortion, first antenatal visit beyond 14 weeks of gestation, and previous PTB with medical indications, placenta previa, abruptio placenta, multiple pregnancy, fetal anomaly, and antepartum fetal demise. The associations between recurrent spontaneous PTB and perinatal factors were evaluated by logistic regression analysis. Results Of 547 women with a previous spontaneous PTB, 89 (16.3%) suffered a recurrent spontaneous PTB. The risk factors for recurrence included multiple previous spontaneous PTB (adjusted odds ratio [aOR]: 2.26; 95% confidence interval [CI]: 1.19-4.30; P = 0.013), no previous term birth (aOR: 2.08; 95%CI: 1.24-3.49; P = 0.005), and interpregnancy interval < 12 months (aOR: 2.13; 95%CI: 1.17-3.85; P = 0.013). Conclusion Approximately one in six women with a previous spontaneous PTB suffered a recurrent spontaneous PTB. Multiple previous spontaneous PTB, no previous term birth, and short interpregnancy interval were independent risk factors for recurrence. [ABSTRACT FROM AUTHOR]

We describe an extremely rare case of a pregnant woman who had a successful delivery despite developing bypass graft occlusion after right external iliac bypass surgery. External and common iliac artery bypass surgery is often performed when arteriosclerosis obliterans or thromboangiitis obliterans result in iliac artery occlusion or when revascularization is required because of iliac artery injury. Because arteriosclerosis obliterans and thromboangiitis obliterans rarely develop in young women or girls, most physicians have little experience with graft occlusion after iliac artery bypass surgery. Here we describe and discuss the published work pertaining to this extremely rare case. [ABSTRACT FROM AUTHOR]

Key Clinical Message Placenta percreta (with bladder invasion) is a rare obstetric condition with the risk of massive intraoperative hemorrhage. In these cases, the combination of a transverse uterine fundal incision and retrograde cesarean hysterectomy could be useful to minimize maternal hemorrhage and avoid severe bladder injury. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to determine whether amniotic fluid levels of annexin A2, a phospholipid-binding protein that is abundant in amnion and regulates fibrin homeostasis, are associated with histological chorioamnionitis, preterm premature rupture of the membranes, and subsequent preterm delivery. Materials and Methods: Amniotic fluid was obtained from 55 pregnant women with preterm labor and/or preterm premature rupture of the membranes before 32 weeks of gestation, and amniotic fluid levels of annexin A2 were measured with a sandwich enzyme-linked immunosorbent assay. Results: Amniotic fluid levels of annexin A2 in patients with histological chorioamnionitis was higher than that in the remainder ( P = 0.053), whereas amniotic fluid levels of annexin A2 in patients with preterm premature rupture of the membranes was significantly higher than that in the remainder ( P = 0.002). Amniotic levels of annexin A2 was a fair test (area under receiver-operator characteristic curve = 0.679), and amniotic fluid levels of annexin A2 > 878.2 ng/mL had a sensitivity of 68.8%, a specificity of 65.2%, a positive predictive value of 73.3%, and a negative predictive value of 60.0% for predicting delivery within 2 weeks after amniotic fluid sampling. Furthermore, the combined use of amniotic fluid cut-off levels of 878.2 ng/mL for annexin A2 and 13.3 ng/mL for interleukin-8 improved the specificity (91.3%) and the positive predictive value (89.5%). Conclusions: We identified amniotic fluid levels of annexin A2, especially in combination with amniotic fluid levels of interleukin-8, as a novel predictive marker for preterm delivery. [ABSTRACT FROM AUTHOR]

The increasing use of nanomaterials has raised concerns about their potential risks to human health. Recent studies have shown that nanoparticles can cross the placenta barrier in pregnant mice and cause neurotoxicity in their offspring, but a more detailed understanding of the effects of nanoparticles on pregnant animals remains elusive. Here, we show that silica and titanium dioxide nanoparticles with diameters of 70 nm and 35 nm, respectively, can cause pregnancy complications when injected intravenously into pregnant mice. The silica and titanium dioxide nanoparticles were found in the placenta, fetal liver and fetal brain. Mice treated with these nanoparticles had smaller uteri and smaller fetuses than untreated controls. Fullerene molecules and larger (300 and 1,000 nm) silica particles did not induce these complications. These detrimental effects are linked to structural and functional abnormalities in the placenta on the maternal side, and are abolished when the surfaces of the silica nanoparticles are modified with carboxyl and amine groups. [ABSTRACT FROM AUTHOR]

Problem The human tumor-associated receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is considered to play a role in the inhibition of the maternal immune response during pregnancy. The aim of our study was to investigate the expression of RCAS1 protein in the placenta and to compare its concentration in maternal and cord blood sera between normal pregnancies and pregnancies complicated by gestational diabetes mellitus (GDM). Method of study Samples were obtained from women with GDM ( n = 8), women with type 1 DM ( n = 5), and healthy term controls ( n = 27) after delivery. Placentas were studied by immunohistochemistry, and real-time polymerase chain reaction. For assessment of RCAS1 concentrations in maternal and cord blood sera, enzyme-linked immunosorbent assay was performed. Results The RCAS1 protein mRNA expression in the placentas of patients with GDM was significantly lower than that in the controls ( P = 0.005). The maternal blood RCAS1 protein concentration of the GDM cases was also significantly lower than that in the controls ( P = 0.0411), whereas the cord blood RCAS1 protein concentration was significantly higher in the GDM and type 1 DM groups than in the controls ( P = 0.0311 and P = 0.0192, respectively). Conclusion The present results suggest that RCAS1 protein might have an important role in the development of GDM. [ABSTRACT FROM AUTHOR]

Background. S100B protein is a unique calcium-binding protein. Its biological role within the cell populations is not completely defined. Some pathological conditions that develop during pregnancy could affect S100B concentrations in the amniotic fluid, cord blood, and maternal serum. The aim of our study was to assess the correlation between S100B protein expression in the amnion, amniotic fluid and gestational age in the third trimester of uncomplicated pregnancies. Methods. Amnion, amniotic fluid, maternal peripheral and umbilical cord blood samples were collected from healthy women who delivered at 31-36 weeks (n=17), 37-40 weeks (n=22), and 41-42 weeks (n=21). The expression of S100B in the amnion was assessed by immunohistochemistry and real-time (RT)-PCR, and its concentrations in amniotic fluid, maternal and cord blood sera were determined by ELISA. Results. The S100B protein expression in the amnion and its concentrations in amniotic fluid, maternal and cord blood sera of patients in the third trimester were not significantly different at various gestational ages. Conclusions. The S100B protein expression in the amnion and the S100B protein concentrations in amniotic fluid, maternal and cord blood do not vary significantly in the third trimester of uncomplicated pregnancies. [ABSTRACT FROM AUTHOR]

Vasa previa is associated with high fetal morbidity and mortality rates. Although early diagnosis is important, rare types (non‐type I and II) of vasa previa are diagnostically challenging. Our reconstructed images of the rare type of vasa previa are educational and could help clinicians to clinically diagnose this condition. [ABSTRACT FROM AUTHOR]

We aimed to identify a magnetic resonance imaging (MRI) feature that can predict posterior extrauterine adhesion (posterior adhesion) antenatally, in patients with placenta previa. We retrospectively reviewed patients with placenta previa who underwent a preoperative MRI examination of placenta accreta spectrum. We categorized the patients into two groups based on whether the cervix was anterior or posterior to a line perpendicular to the anatomical conjugate on the MRI. We projected the perpendicular line toward a straight line through the broad of the back on T2-weighted sagittal MRI images and measured the angle between this line and the line passing through the cervical canal. We analyzed the correlation of the cervical canal angle with the presence of posterior adhesions. Of the 96 patients analyzed, 71 patients had an anteverted cervix and 25 patients had a retroverted cervix. There were 21 posterior adhesions. The adhesion rate was significantly higher in patients with a retroverted cervix than those with an anteverted cervix (8.5% vs. 60%; p = 0.00). The cervical canal angle was ≤10° in 25 patients; of these 17 had adhesions (sensitivity, 81.0%; specificity, 89.3%; area under the curve, 0.887; 95% confidence interval, 0.792–0.981). This finding, labeled "positive horizontal cervix sign," may be a promising indicator of posterior adhesions in patients with placenta previa. [ABSTRACT FROM AUTHOR]