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AIM: This study aimed to investigate the safety and efficacy of tadalafil in protecting the fetus from hypoxic stress caused by repeated labor pains during delivery and preventing fetal hypoxic-ischemic encephalopathy. METHODS: The study used a three-case cohort approach. Three patients were administered 10 mg tadalafil and monitored for serious adverse events. In the absence of serious tadalafil-associated adverse events as assessed by the Safety Evaluation Committee, three new patients were added to the study and treated with 20 mg/dose. The blood levels of tadalafil were recorded before and after 2, 4, 8, and 12 h of administration and 2 h after delivery. RESULTS: A total of seven patients were enrolled, and after excluding one patient who delivered before 37 weeks, tadalafil was administered to six patients. Maternal adverse events were considered acceptable from the maternal perspective, with grade 1 headache, anorexia, and myalgia and no obstetrical complications after delivery at both doses. No serious neonatal adverse events were associated with tadalafil. Tadalafil blood levels remained stable at both doses. In addition, the level of soluble fms-like tyrosine kinase-1 did not alter, while that of the placental growth factor differed significantly before and after tadalafil administration. CONCLUSIONS: The study confirmed the safety of tadalafil administration during delivery for both mothers and newborns. The stable tadalafil blood levels confirmed the efficacy of the tested administration regime at 12 h interval. These findings would assist in conducting phase II trials to further verify the optimal dose and safety of tadalafil.
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Feto , Trabalho de Parto , Recém-Nascido , Gravidez , Humanos , Feminino , Tadalafila/efeitos adversos , Fator de Crescimento Placentário , Cuidado Pré-NatalRESUMO
BACKGROUND: During the coronavirus disease (COVID-19) pandemic, caesarean section (CS) has been the preferred deliver method for pregnant women with COVID-19 in order to limit the use of hospital beds and prevent morbidity among healthcare workers. METHODS: To evaluate delivery methods used during the COVID-19 pandemic as well as the rates of adverse events and healthcare worker morbidity associated with caesarean deliveries. METHODS: We investigated maternal and neonatal backgrounds, delivery methods, indications and complication rates among pregnant women with COVID-19 from December 2020 to August 2022 in Mie Prefecture, Japan. The predominant mutation period was classified as the pre-Delta, Delta and Omicron epoch. RESULTS: Of the 1291 pregnant women with COVID-19, 59 delivered; 23 had a vaginal delivery and 36 underwent CS. Thirteen underwent CS with no medical indications other than mild COVID-19, all during the Omicron epoch. Neonatal complications occurred significantly more often in CS than in vaginal delivery. COVID-19 in healthcare workers was not attributable to the delivery process. CONCLUSION: The number of CS with no medical indications and neonatal complications related to CS increased during the COVID-19 pandemic. Although this study included centres that performed vaginal deliveries during COVID-19, there were no cases of COVID-19 in healthcare workers. It is possible that the number of CS and neonatal complications could have been reduced by establishing a system for vaginal delivery in pregnant women with recent-onset COVID-19, given that there were no cases of COVID-19 among the healthcare workers included in the study.
We evaluated the incidence of adverse events associated with caesarean section (CS) deliveries and the morbidity of health care workers, which increased during the coronavirus infection pandemic. Maternal and neonatal background, delivery methods, indications and complication rates of pregnant women with COVID-19 from December 2020 to August 2022 in Mie Prefecture were investigated by time of onset. Of the 1291 pregnant women with COVID-19, 59 delivered while affected; 23 underwent vaginal delivery and 36 CS. Of these, 13 who underwent CS in the omicron epoch had no medical indication other than mild COVID-19. Neonatal complications were significantly more common with CS than with vaginal delivery, and there was no occurrence of COVID-19 in healthcare workers. In this study, there were no cases of COVID-19 among health care workers; establishing a system to perform vaginal delivery for pregnant women with COVID-19 could have reduced the number of CS and neonatal complications.
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COVID-19 , Cesárea , Parto Obstétrico , Complicações Infecciosas na Gravidez , SARS-CoV-2 , Humanos , Feminino , Gravidez , COVID-19/epidemiologia , Japão/epidemiologia , Adulto , Complicações Infecciosas na Gravidez/epidemiologia , Cesárea/estatística & dados numéricos , Parto Obstétrico/estatística & dados numéricos , Parto Obstétrico/métodos , Recém-NascidoRESUMO
Herein, oxide quasicrystal-related (OQC-R) structure and Ce-Ti-O-(3 × 3) superstructure ultrathin films were prepared on Pt(111) and characterized using scanning tunneling microscopy (STM) and low-energy electron diffraction. The OQC-R structure with dodecagonal clusters consisting of triangles, squares, and rhombuses was observed in STM images. The first discovery of the OQC-R structure with a magnetic rare earth metal expands the possibility of discovering new oxide quasicrystals with novel magnetism or superconductivity. By depositing Ti on an OQC-R ultrathin film and post-annealing, a honeycomb lattice of the Ce-Ti-O-(3 × 3) superstructure was prepared. From X-ray photoelectron spectroscopy (XPS) and resonant-photoelectron spectroscopy, the chemical states of the Ce and Ti atoms in the OQC-R structure corresponded to the Ce3+ and Ti2+ states, while those for the Ce-Ti-O-(3 × 3) superstructure corresponded to the Ce3+, Ti3+, and Ti2+ states. The phase transformation from the OQC-R structure to the Ce-Ti-O-(3 × 3) honeycomb superstructure likely occurred when the amount of Ti increased and was more oxidized. The elemental atomic density was also calibrated using XPS and Rutherford backscattering spectroscopy. These results propose tentative structural models of the OQC-R structure as Ce18Ti14O41 and the Ce-Ti-O-(3 × 3) superstructure as CeTi6O9.
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The placenta accreta spectrum without previa is difficult to diagnose before delivery and sometimes requires hysterectomy. A fertility preservation procedure is useful when placenta accreta spectrum is unexpectedly encountered. A 38-year-old woman, conceived by in vitro fertilization (IVF), was not diagnosed of placenta accreta spectrum until delivery. A cesarean section was performed for fetal breech presentation. The placenta could not be detached from the uterine fundus and marked bleeding started. We conducted the "TURIP" procedure: ensured hemostasis with tourniquet of uterine isthmus, uterus inversion to expose the adhesion site with intra-venous nitroglycerin administration, placental detachment by sharp dissection under direct visualization. The detached areas were sutured for hemostasis. The patient recovered uneventfully and achieved the second pregnancy by IVF 1 year later. The TURIP procedure is useful to preserve fertility in unpredicted placenta accreta spectrum without previa, even in undiagnosed cases before delivery.
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Preservação da Fertilidade , Placenta Acreta , Placenta Prévia , Inversão Uterina , Gravidez , Feminino , Humanos , Adulto , Cesárea/métodos , Placenta Acreta/cirurgia , Torniquetes , Placenta , Placenta Prévia/cirurgia , Estudos RetrospectivosRESUMO
Background and Objectives: Tadalafil is expected to treat fetal growth restriction (FGR), a risk factor for stillbirth and neonatal morbidity. This study aimed to evaluate the fetal biometric growth pattern of fetuses with FGR treated with tadalafil by ultrasonographic assessment. Materials and Methods: This was a retrospective study. Fifty fetuses diagnosed with FGR and treated by maternal administration of tadalafil and ten controls who received conventional treatment at Mie University Hospital from 2015 to 2019 were assessed. Fetal biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW) at the start of treatment and at two weeks and four weeks of treatment were mainly assessed by ultrasound examination. The Wilcoxon signed-rank test was used to assess the measures. The Kyoto Scale of Psychological Development (KSPD) was used to assess the developmental prognosis on tadalafil-treated children at 1.5 years of corrected age (CA) and 3 years old. Results: The median gestational age at the start of treatment was 30 and 31 weeks in the tadalafil and control groups, respectively, and the median gestational age at delivery was 37 weeks in both groups. The Z-score of HC was significantly increased at 4 weeks of treatment (p = 0.005), and the umbilical artery resistance index was significantly decreased (p = 0.049), while no significant difference was observed in the control group. The number of cases with an abnormal score of less than 70 on the KSPD test was 19% for P-M, 8% for C-A, 19% for L-S, and 11% for total area at 1.5 years CA. At 3 years old, the respective scores were 16%, 21%, 16%, and 16%. Conclusions: Tadalafil treatment for FGR may maintain fetal HC growth and infants' neuro-developmental prognosis.
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Biometria , Retardo do Crescimento Fetal , Gravidez , Recém-Nascido , Feminino , Criança , Lactente , Humanos , Tadalafila/uso terapêutico , Retardo do Crescimento Fetal/tratamento farmacológico , Estudos Retrospectivos , Prognóstico , Ultrassonografia Pré-NatalRESUMO
OBJECTIVE: Here, we tested the correlation between maternal placental growth factor (PlGF) and fetal heart rate (FHR) monitoring findings. METHODS: We included 35 women with single pregnancies from 35 to 42 weeks of gestation who were hospitalized owing to onset of labor. Blood samples were collected at the start of labor. Intrapartum FHR monitoring parameters included total deceleration area, average deceleration area (mean deceleration area per 10 min), and five-tier classification level. RESULTS: Of the 35 women, 26 (74%) had vaginal delivery and 9 (26%) had cesarean section. After excluding 2 women who had cesarean section for arrest of labor, we analyzed 26 women who had vaginal delivery (VD group) and 7 who had cesarean section for fetal indications (CSF group). PlGF level was significantly higher in the VD group (157 ± 106 pg/ml) than in the CSF group (74 ± 62 pg/ml) (P = 0.03). There were no significant correlations between PlGF and total (r = -0.07) or average (r = -0.08) deceleration area.ãThere was a significant negative correlation (r = -0.42, P = 0.01) between PlGF and the percentage of level 3 or higher in the five-level classification. CONCLUSION: PlGF was correlated with FHR monitoring findings and might be a promising biomarker of intrapartum fetal function.
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Monitorização Fetal/métodos , Frequência Cardíaca Fetal , Fator de Crescimento Placentário/sangue , Desaceleração , Parto Obstétrico/métodos , Feminino , Monitorização Fetal/classificação , Humanos , Trabalho de Parto , GravidezRESUMO
AIM: To evaluate the tolerability of casirivimab and imdevimab (CAS/IMB) therapy in pregnant women with COVID-19 in Japan and its impact on the neonate and process of delivery. METHODS: Eight cases of pregnancy complicated by COVID-19 and requiring hospitalization during the delta variant epidemic were included. Gestational age, initial symptoms, pregnancy complications and outcome, severity of illness, blood test findings at the time of treatment initiation and on days 3-5 after administration, body temperature at administration, and 8, 24, and 48 h post-administration, delivery outcome, and neonatal findings were recorded. Ten pregnant women who required hospitalization at the same time and did not receive CAS/IMB were used as controls. RESULTS: Of the eight cases, seven were mild, and one case was of moderate severity. Body temperature in the CAS/IMB group was significantly higher at 8 h post-administration than that at the time of administration. However, body temperature significantly reduced at 24 and 48 h post-administration in the CAS/IMB group compared with that in the control group. There were no apparent adverse events after CAS/IMB administration. CONCLUSIONS: Maternal administration of CAS/IMB was safe. Although it was difficult to evaluate the improvement in disease by blood test findings, the fever improved within 24 h, which suggests rapid improvement in patient condition.
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Tratamento Farmacológico da COVID-19 , Complicações Infecciosas na Gravidez , Anticorpos Monoclonais , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , SARS-CoV-2RESUMO
AIM: To evaluate the utility of the risk score in assessing the current status and prognosis of COVID-19 in pregnancy. METHODS: Seventy-seven cases affected before the Omicron variant epidemic and 50 pregnant cases affected by the Omicron variant were included. The risk score consists of maternal background, current condition, and examination findings. We determined the risk score in the early stages of disease onset. RESULTS: There were no significant differences in the maternal or gestational ages between the groups. The risk score was significantly lower in the After-Group patients (those affected during the Omicron epoch), while 14.3% of the Before-Group patients (those affected during the pre-Delta and Delta epochs), experienced a worsening of disease after the visit to the center, whereas none of the After-Group patients did. The Before Group's frequency of risk score items was higher among the two groups for "fever for ≥48 h," "mild pneumonia image," and "blood tests," whereas "disease onset 14 days after the second vaccination" was increased in After Group. The blood test parameters for platelet count, C-reactive protein, and D-dimer levels were not significantly different between the groups. CONCLUSIONS: The risk score system appeared superior in detecting deteriorating cases. There were no cases of post-illness deterioration in the After-Group, suggesting that cases of the Omicron variant in pregnancy may have had a less severe course compared to that of previous variants. However, there was no significant difference between the groups in terms of a specific blood test evaluation, suggesting the need for a combined evaluation of cases affected during pregnancy.
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COVID-19 , Complicações Infecciosas na Gravidez , Gravidez , Feminino , Humanos , SARS-CoV-2 , Fatores de Risco , Medição de RiscoRESUMO
Fetal growth restriction (FGR) is a major cause of poor perinatal outcomes. Although several studies have been conducted to improve the prognosis of FGR in infants, no effective intrauterine treatment method has been established. This study aimed to use tadalafil, a phosphodiesterase 5 inhibitor (PDE5) inhibitor, as a novel intrauterine treatment and conducted several basic and clinical studies. The study investigated the effects of tadalafil on placental mTOR signaling. Tadalafil was administered to mice with L-NG-nitroarginine methyl ester (L-NAME)-induced FGR and associated preeclampsia (PE). Placental phosphorylated mTOR (p-mTOR) signaling was assessed by fluorescent immunohistochemical staining and Western blotting. The expression of p-mTOR was significantly decreased in mice with FGR on 13 days post coitum (d.p.c.) but recovered to the same level as that of the control on 17 d.p.c. following tadalafil treatment. The results were similar for 4E-binding protein 1 (4E-BP1) and S6 ribosomal (S6R) protein, which act downstream in the mTOR signaling pathway. We demonstrate that the tadalafil treatment of FGR in mice improved placental mTOR signaling to facilitate fetal growth. Our study provides the key mechanistic detail about the mode of action of tadalafil and thus would be helpful for future clinical studies on FGR.
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Retardo do Crescimento Fetal , Pré-Eclâmpsia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Tadalafila/farmacologia , Animais , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Retardo do Crescimento Fetal/tratamento farmacológico , Retardo do Crescimento Fetal/metabolismo , Camundongos , NG-Nitroarginina Metil Éster/efeitos adversos , NG-Nitroarginina Metil Éster/farmacologia , Placenta , Pré-Eclâmpsia/induzido quimicamente , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/metabolismo , GravidezRESUMO
Background and Objectives: Vasopressors are used for treating maternal hypotension. However, the appropriate administration method and effects on newborns have not been reported. We evaluated maternal blood pressure fluctuation and neonatal findings in patients who received continuous vasopressor administration during elective cesarean sections and those who received bolus vasopressor administration upon onset of hypotension. Materials and Methods: We retrospectively analyzed the data of 220 patients scheduled for elective cesarean delivery under spinal anesthesia at Mie University Hospital between April 2017 and March 2021. The patients were classified according to the method of vasopressor administration. Maternal information, intraoperative maternal blood pressure fluctuation, and neonatal findings were examined. A multiple regression analysis was performed for the administration of postpartum neonatal respiratory support using maternal background information and other variables related to blood pressure changes as independent variables. Results: The Continuous group and the Bolus group were composed of 98 and 122 patients, respectively. No difference was observed in maternal background information between the groups. Significant changes were noted in several blood pressure parameters between both groups. As for neonatal parameters, newborns of Bolus group patients had lower pO2, 1 min and 5 min Apgar scores, and required more respiratory support than those of Continuous group patients. In the multiple regression analysis, the groups and maternal post-anesthesia diastolic blood pressure variability were considered explanatory variables. Conclusions: Maternal hypotension and the need for neonatal respiratory support associated with anesthesia administration in elective cesarean section may be improved by continuous vasopressor administration upon induction of combined spinal-epidural anesthesia.
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Anestesia Epidural , Anestesia Obstétrica , Raquianestesia , Hipotensão , Anestesia Epidural/efeitos adversos , Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Cesárea/efeitos adversos , Feminino , Humanos , Hipotensão/tratamento farmacológico , Hipotensão/etiologia , Recém-Nascido , Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVES: The objectives of this study were to (i) establish the reference range and mean value for normal levels of C1-esterase inhibitor (C1 INH) during pregnancy, and (ii) investigate the association between C1 INH and uterine atony, as measured by blood loss at delivery. METHODS: We prospectively studied 200 healthy pregnant women who were registered. We studied C1 INH levels in 188 women at 34 and 35 gestational weeks of pregnancy. The reference range for C1 INH during the third trimester of pregnancy was calculated using the value of C1 INH that was determined at registration. RESULTS: The mean value of C1 INH was determined to be 70.3% (95% confidence interval, 68.7-71.9). While the C1 INH levels in four women were determined to be 40% lower than the calculated mean value, amniotic fluid embolism (AFE) did not occur in any of the women studied. CONCLUSIONS: This study successfully demonstrated that a reference value for C1 INH activity can be established using the methods described herein. Further research is needed to determine whether C1 INH is involved in obstetric coagulopathy syndrome such as amniotic fluid embolism.
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Proteína Inibidora do Complemento C1/metabolismo , Terceiro Trimestre da Gravidez/sangue , Adulto , Feminino , Humanos , Gravidez , Estudos Prospectivos , Valores de ReferênciaRESUMO
AIM: This study aimed to compare the efficacy and safety of a controlled-release dinoprostone vaginal delivery system (PROPESS) and a metreurynter for labor induction. METHODS: This retrospective case-controlled study included 117 pregnant women (51 and 66 in the PROPESS and metreurynter groups, respectively) who required labor induction after >37 weeks' gestation at Mie University Hospital between January 2018 and September 2020. The primary outcome was the success rate of vaginal delivery. The secondary outcomes were changes in the Bishop score from the first insertion of PROPESS or the metreurynter to removal, uterine hyperstimulation and non-reassuring fetal status during the first insertion, proportion of pregnant women who needed pre-delivery oxytocin after removal, time to vaginal delivery after the first insertion, proportion of pregnant women who delivered vaginally within 12 or 24 h after the first insertion, and neonatal outcomes. RESULTS: The proportion of pregnant women, especially primiparas, who delivered vaginally was significantly higher in the PROPESS group (26/34 [76.5%]) than in the metreurynter group (25/52 [48.1%]; p = 0.01). Moreover, among multiparas in the PROPESS group who delivered vaginally, nine (56.3%) out of 16 women delivered vaginally within 3 h of labor onset. CONCLUSIONS: PROPESS for cervical ripening may reduce the risk of undergoing cesarean section in pregnant women requiring labor induction, especially primiparas. It is important to consider the possibility of precipitate labor when using the PROPESS in multiparas.
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Maturidade Cervical , Ocitócicos , Administração Intravaginal , Cesárea , Preparações de Ação Retardada , Parto Obstétrico , Dinoprostona , Feminino , Humanos , Recém-Nascido , Japão , Trabalho de Parto Induzido , Gravidez , Estudos RetrospectivosRESUMO
AIM: In Japan, the frequency of maternal deaths due to obstetric hemorrhage has been decreasing in the last decade, while that resulting from other causes such as pulmonary thromboembolism (PTE) was consistent. To help reduce maternal deaths due to PTE, we investigated PTE during pregnancy and puerperium and compared the survival and death cases, and aimed to find out life and death factors. METHODS: This study was a retrospective analysis based on a clinical chart review in 407 maternal and perinatal centers. We compared the survival and death cases of PTE during pregnancy and puerperium from 2013 to 2017. RESULTS: In PTE during pregnancy, the survival cases underwent significantly earlier diagnoses than the death cases, and thromboprophylaxis was performed in most of both the survival and death cases of PTE during puerperium according to the existing Japanese guidelines; however, only one fourth of the total cases underwent anticoagulation to prevent venous thromboembolism (VTE). CONCLUSIONS: Early diagnosis of PTE in suspected cases was associated with better survival during pregnancy.
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Complicações na Gravidez , Embolia Pulmonar , Tromboembolia Venosa , Anticoagulantes , Feminino , Humanos , Japão/epidemiologia , Período Pós-Parto , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/mortalidade , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidade , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/mortalidadeRESUMO
The PROPESS, a controlled-release dinoprostone vaginal delivery system, is a pharmacological cervical ripening intervention and promotes cervical change causing uterine contraction. During insertion of the PROPESS, uterine hyperstimulation could occur and result in fetal heart rate (FHR) abnormality. We report a case of uterine hyperstimulation accompanied with FHR abnormality caused by the PROPESS in a pregnant woman. Postural change, oxygenation, fluid infusion, and the immediate PROPESS removal were ineffective to address the adverse event, so we administered nitroglycerin for acute uterine relaxation. The nitroglycerin resulted in uterine relaxation, and the FHR abnormality was resolved immediately, thereby preventing an emergency cesarean section. Therefore, nitroglycerin could be considered an effective option for uterine hyperstimulation accompanied with FHR abnormality caused by the PROPESS.
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Dinoprostona , Ocitócicos , Cesárea , Preparações de Ação Retardada , Feminino , Frequência Cardíaca Fetal , Humanos , Trabalho de Parto Induzido , Nitroglicerina/uso terapêutico , Ocitócicos/uso terapêutico , GravidezRESUMO
AIM: To investigate the effects of Mycoplasma/Ureaplasma cultured in amniotic fluid on perinatal characteristics in preterm delivery between 22 and 33 weeks of gestation. METHODS: The study was conducted in a tertiary perinatal center and involved 38 pregnant women who had undergone amniocentesis to evaluate intrauterine infection due to preterm labor or premature rupture of membranes. The subjects were divided into three groups based on the culture results: negative (Negative Group, n = 24), positive for Mycoplasma/Ureaplasma (M/U Group, n = 6), and positive for other pathogens (Other Pathogens Group, n = 8). One-way analysis of variance was used to compare the three groups. RESULTS: The incidence of histological chorioamnionitis and neonatal sepsis was significantly different among the three groups (the Negative Group and the Other Pathogens Group, P < 0.01; the M/U Group and the Other Pathogens Group, P = 0.03). In the M/U Group, no infants had sepsis, severe intraventricular hemorrhage, cystic periventricular leukomalacia, or poor neurological outcomes, but one infant developed bronchopulmonary dysplasia and needed home oxygen treatment. Although one died of gastrorrhexis, the remaining five patients had normal brain magnetic resonance imaging findings and developed normally. CONCLUSION: The presence of Mycoplasma/Ureaplasma isolated from amniotic fluid did not cause neonatal sepsis or poor prognosis. In some infants, there was no histological chorioamnionitis in the placenta. These pathogens thus seem to be less invasive than any other microbes with respect to perinatal outcomes.
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Líquido Amniótico/microbiologia , Ruptura Prematura de Membranas Fetais/microbiologia , Mycoplasma/isolamento & purificação , Resultado da Gravidez , Ureaplasma/isolamento & purificação , Adulto , Amniocentese , Feminino , Humanos , Infecções por Mycoplasma/diagnóstico , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Infecções por Ureaplasma/diagnósticoRESUMO
Background and Objectives: Fetal growth restriction (FGR) is associated with fetal mortality and is a risk factor for cerebral palsy and future lifestyle-related diseases. Despite extensive research, no effective treatment strategy is available for FGR. Mammalian target of rapamycin (mTOR) signaling is important for the growth of fetal organs and its dysregulation is associated with miscarriage. Here, we focused on mTOR signaling and investigated how the activities of phospho-ribosomal protein S6 (rps6) and phospho-eukaryotic translation initiation factor 4E (eIF-4E), which act downstream of mTOR signaling in the human placenta, change following treatment of FGR with tadalafil and aimed to elucidate the underlying mechanism of action. Placental hypoxia was investigated by immunostaining for hypoxia-inducible factor (HIF)-2α. Materials and Methods: Phosphor-rps6 and phosphor-eIF4E expression were examined by Western blotting and enzyme-linked immunosorbent assay, respectively. Results: HIF-2α expression significantly increased in FGR placenta compared with that in the control placenta but decreased to control levels after tadalafil treatment. Levels of phospho-rps6 and phospho-eIF-4E were significantly higher in FGR placenta than in control placenta but decreased to control levels after tadalafil treatment. Conclusions: Tadalafil restored the levels of HIF-2α, phospho-rps6, and eIF-4E in FGR placenta to those observed in control placenta, suggesting that it could be a promising treatment strategy for FGR.
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Retardo do Crescimento Fetal , Sirolimo , Feminino , Retardo do Crescimento Fetal/tratamento farmacológico , Humanos , Hipóxia , Gravidez , Serina-Treonina Quinases TOR , Tadalafila/uso terapêuticoRESUMO
INTRODUCTION: We aimed to examine the effect of uterine arterial (UtA) blood flow changes after tadalafil treatment for fetal growth restriction (FGR) using two-dimensional (2D) phase-contrast magnetic resonance imaging (PC-MRI). METHODS: We recruited 14 pregnant women with FGR aged 20-44 years, at ≥20 weeks' gestation, between May 2019 and July 2020. They underwent 2D PC-MRI for UtA blood flow measurement 3 days (interquartile range: 2-4) after diagnosis. This group (FGR group) was compared with 14 gestational age (GA)-matched healthy pregnant women (control group). Six patients in the FGR group received treatment with tadalafil administered at 20 mg twice daily after the first MRI until delivery. They underwent a second MRI a week later. RESULTS: The median total UtA blood/body surface area was 420 mL/min/m2 (290-494) in the FGR group and 547 mL/min/m2 (433-681) in the control group (p = 0.01). Percent increase in blood flow were significantly different between the FGR cases treated with tadalafil and control at 15.8 % (14.3-21.3) and 4.2 % (3.6-8.7), respectively (p = 0.03). DISCUSSION: UtA blood flow in pregnant women with FGR was significantly lower than that in healthy pregnant women. Tadalafil is expected to improve UtA blood flow, thereby improving placental function in pregnant patients with FGR.
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Retardo do Crescimento Fetal , Gestantes , Feminino , Gravidez , Humanos , Tadalafila/farmacologia , Tadalafila/uso terapêutico , Retardo do Crescimento Fetal/diagnóstico por imagem , Retardo do Crescimento Fetal/tratamento farmacológico , Placenta , Artérias , Ultrassonografia Pré-NatalRESUMO
Fetal growth restriction (FGR) is a major concern in perinatal care. Various medications have been proposed as potential treatments for this serious condition. Nonetheless, there is still no definitive treatment. We studied tadalafil, a phosphodiesterase-5 inhibitor, as a therapeutic agent for FGR in clinical studies and animal experiments. In this review, we summarize our preclinical and clinical data on the use of tadalafil for FGR. Our studies in mouse models indicated that tadalafil improved FGR and hypertensive disorders of pregnancy. A phase II trial we conducted provided evidence supporting the efficacy of tadalafil in prolonging pregnancy (52.4 vs. 36.8 days; p = 0.03) and indicated a good safety profile for fetuses and neonates. Fetal, neonatal, and infant mortality was significantly lower in mothers receiving tadalafil treatment than that in controls (total number: 1 vs. 7, respectively; p = 0.03), and no severe adverse maternal events associated with tadalafil were observed. Although further studies are needed to establish the usefulness of tadalafil in FGR treatment, our research indicates that the use of tadalafil in FGR treatment may be a paradigm shift in perinatal care.
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OBJECTIVE: COVID-19 is an ongoing pandemic and has been extensively studied. However, the effects of COVID-19 during pregnancy, particularly on placental function, have not been verified. In this study, we used blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) to evaluate whether COVID-19 incidence during pregnancy has any lasting effects with respect to placental oxygenation. METHODS: This is a case-control study, in which eight cases of singleton pregnancies before 30 weeks gestation with COVID-19 mothers were included. Placental oxygenation was evaluated using BOLD-MRI after 32 weeks of gestation. BOLD-MRI was consecutively performed under normoxia (21% O2), hyperoxia (100% O2), and normoxia for 4 min each. Individual placental time-activity curves were evaluated to calculate the peak score (peakΔR2*) and the time from the start of maternal oxygen administration to the time of peakΔR2* (time to peakΔR2*). Eighteen COVID-19-free normal pregnancies from a previous study were used as the control group. RESULTS: No significant differences were found between the two groups regarding maternal background, number of days of delivery, birth weight, and placental weight. The parameter peakΔR2* was significantly decreased in the COVID-19 group (8 ± 3 vs. 5 ± 1, p < .001); however, there was no significant difference in time to peakΔR2* (458 ± 74 s vs. 471 ± 33 s, p = .644). CONCLUSIONS: In this study, BOLD-MRI was used to evaluate placental oxygenation during pregnancy in COVID-19-affected patients. COVID-19 during pregnancy decreased placental oxygenation even post-illness, but had no effect on fetal growth; further investigation of the possible effects of COVID-19 on the fetus and mother is warranted.
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COVID-19 , Hiperóxia , Gravidez , Humanos , Feminino , Placenta , Oxigênio , Estudos de Casos e Controles , Imageamento por Ressonância Magnética/métodosRESUMO
The association between prepartum time-series fetal heart rate pattern changes and cord blood gas data at delivery was examined using the conventional 5-tier classification and the Rainbow system for 229 female patients who delivered vaginally. They were classified into three groups based on the results of umbilical cord blood gas analysis at delivery. The fetal heart rate pattern classifications were based on analysis of measurement taken at 10-min intervals, beginning at 120 min pre-delivery. The relationship between fetal heart rate pattern classification and cord blood pH at delivery changed over time. The 5-tier classification at each interval increased before delivery in the Mild and Severe groups compared with the Normal group. No significant differences were observed between acidemia groups. The Rainbow classification showed a significant differences between the acidemia groups at each interval, particularly during the prepartum period. A relationship between classification and outcome was evident before delivery for both the 5-tier classification and Rainbow system.