TheTADAlafil treatment for Fetuses with early-onset growth Restriction: multicentrer, randomizsed, phase II trial (TADAFER II) study showed the possibility of prolonging the pregnancy period in cases of early-onset fetal growth restriction; however, it was an open-label study. To establish further evidence for the efficacy of tadalafil in this setting, we planned a multicentre, randomised, placebo-controlled, double-blind trial.This trial will be conducted in 180 fetuses with fetal growth restriction enrolled from medical centres in Japan; their mothers will be randomised into three groups: arm A, receiving two times per day placebo; arm B, receiving one time per day 20 mg tadalafil and one time per day placebo and arm C, receiving 20 mg two times per day tadalafil. The primary endpoint is the prolongation of gestational age at birth, defined as days from the first day of the protocol-defined treatment to birth. To minimise bias in terms of fetal baseline conditions and timing of delivery, a fetal indication for delivery as in TADAFER II will be established in this trial. The investigator will evaluate fetal baseline conditions at enrolment and decide the timing of delivery based on this indication.This study has been approved by Mie University Hospital Clinical Research Review Board on 22 July 2019 (S2018-007). Written informed consent will be obtained from all mothers before recruitment. Our findings will be widely disseminated through peer-reviewed publications.jRCTs041190065.
This study aimed to compare the efficacy and safety of a controlled-release dinoprostone vaginal delivery system (PROPESS) and a metreurynter for labor induction.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.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.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.
Objective: 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). Design: Prospective, controlled study. Setting: Single tertiary center. Population or Sample: Fourteen pregnant women with FGR aged 20–44 years and at ≥20 weeks’ gestation were recruited between May 2019 and July 2020. Methods: They underwent 2D PC-MRI for UtA blood flow measurement 3 days after diagnosis. They were compared with 14 gestational age (GA)-matched healthy pregnant women (control group). Six patients in the FGR group received tadalafil at 20 mg twice daily after the first MRI until delivery. They underwent a second MRI 1 week later and were compared with 6 of the 14 GA-matched healthy pregnant women. Main Outcome Measures: Total UtA blood/body surface area Results: The median total UtA blood/body surface area was 420 mL/min/m (290–494) in the FGR group and 547 mL/min/m (433–681) in the control group (p=0.01). Percent increases of blood flow in the FGR and control groups were significantly different at 68.8% (51–75) and 18.8% (16–57), respectively (p<0.01). Both intraobserver reproducibility (r=0.997, p<0.01; intraclass correlation coefficients (ICC), 0.997) and interobserver reproducibility (r=0.997, p<0.01; ICC, 0.998) were high. Conclusions: UtA blood flow in pregnant women with FGR was significantly lower than that in healthy pregnant women. Tadalafil may improve UtA blood flow, thereby improving placental function in pregnant patients with FGR.
Introduction Muscle invasive bladder cancer during pregnancy is scarcely reported. Case presentation A 41‐year‐old ex‐smoker Asian female, managed with clean intermittent catheterization for 3 years due to neurogenic bladder caused by spinal cord disease, presented with gross hematuria at 10 weeks of gestation. The patient was diagnosed with muscle invasive bladder cancer, cT3aN0M0. Maternal treatment was prioritized and gemcitabine plus cisplatin as neoadjuvant chemotherapy was started at 17 weeks of gestation. Cesarean section was performed at 32 weeks of gestation, followed by robot‐assisted radical cystectomy 3 weeks later. Histopathological examination revealed urothelial carcinoma, G3, ypT3b. Postoperative adjuvant nivolumab followed by enfortumab vedotin was not successful and the patient died 8 months after robot‐assisted radical cystectomy. Unfortunately, the premature infant with congenital heart disease died of necrotizing enterocolitis at 1‐month‐old. Conclusion Gemcitabine plus cisplatin chemotherapy in the patient with muscle invasive bladder cancer during pregnancy was safe but ultimately resulted in unfavorable outcomes in this case.
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;
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.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.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.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.
Here, we tested the correlation between maternal placental growth factor (PlGF) and fetal heart rate (FHR) monitoring findings.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.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. There 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.PlGF was correlated with FHR monitoring findings and might be a promising biomarker of intrapartum fetal function.
Abstract 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.
Abstract Although evaluation by digital examination of the cervix is the standard method used worldwide for evaluating the progress of delivery, it has a problem because it is subjective. Transperineal ultrasound (TPU) is used as an adjunct to digital evaluation for accurate assessment of the fetal descent and rotation of the advanced part of the fetus. This study aimed to clarify the impact of the introduction of TPU on perinatal outcomes at Mie university hospital. This retrospective study analyzed single pregnant women who underwent delivery management at our hospital between April 2020 and March 2021. Perinatal outcomes were compared between patients who were used TPU (TPU+ group) and those who were not used TPU (TPU- group). The angle of progression and head direction were measured. The rate of vaginal delivery was significantly increased, and the second stage of labor was significantly prolonged in the TPU+ group. There was a significant difference between termination in the latent phase occurred in 3/8 (38%) cases in the TPU+ group and 20/25 (80%) cases in the TPU- group. The rate of vaginal delivery may be increased by accurate evaluation of the progress of delivery with TPU.
