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OBJECTIVE: To evaluate the usefulness of novel diffusion-weighted imaging (DWI) findings for diagnosing placenta accreta spectrum (PAS). MATERIALS AND METHODS: This retrospective study included 49 pregnant women with suspected PAS who underwent 1.5 T placental MRI. Diffusion lacunae were defined as intraplacental areas showing hypointensity on DWI and hyperintensity on the apparent diffusion coefficient map. Two radiologists evaluated the number and size of placental lacunae on DWI, and flow void in the diffusion lacunae on T2-weighted imaging. The radiologists also evaluated established MRI features of PAS described in the SAR-ESUR consensus statement. Pearson's chi-square test or Mann-Whitney U test was used to compare findings between patients with and without PAS. Interobserver reliability for DWI and established MRI features was also assessed. Optimal thresholds for the number and maximum size of diffusion lacunae for differentiating PAS from the no-PAS group were determined using receiver operating characteristic curve analyses. RESULTS: Eighteen patients were diagnosed with PAS, and 31 patients with placental previa without PAS. The number and maximum size of diffusion lacunae were significantly larger in patients with than in patients without PAS (p < 0.0001). Combining assessment of the number of diffusion lacunae with assessment of their maximum size yielded a diagnostic performance with sensitivity, specificity and accuracy of 83%, 94% and 90%, respectively. Flow voids within the diffusion lacunae had sensitivity, specificity and accuracy of 88%, 84% and 86%, respectively. CONCLUSION: The number and size of diffusion lacunae, and T2 flow void in diffusion lacunae may be useful findings for diagnosing PAS.

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Expectant management is not recommended for cesarean scar pregnancies because they are often associated with placenta accreta, cesarean hysterectomy, and massive life-threatening hemorrhages during delivery. Herein, we report a case of placenta accreta spectrum with ureteral invasion due to the progression of a cesarean scar pregnancy. Case. A 41-year-old woman, with a history of three cesarean sections and two miscarriages, was referred to our hospital at 25 weeks of gestation with a diagnosis of placenta accreta spectrum and bladder invasion. Although the gestational sac was located anterior to the lower uterine segment, a cesarean-scar pregnancy was not diagnosed. A cesarean hysterectomy was performed at 31 weeks of gestation with the placement of an aortic balloon. The placenta was found to adhere to the ureter with more than the expected parenchymal tissue displacement (FIGO Classification 3b). The ureter was not obstructed and was preserved by leaving the placenta slightly on the ureteral side. Postoperatively, a ureteral stent was placed because of the ureteral stricture in the area where the placenta had adhered. Two months after surgery, the ureteral stent was removed after observing an improvement in stenosis. An adherent placenta due to continued cesarean scar pregnancy should be managed by assuming placental invasion beyond the parenchyma into the ureter.

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Background: One of the major risks of preterm birth is a history of conization. However, the risk of infection due to this procedure is still not well known. Using next-generation sequencing, we aimed to reveal the influence of conization on vaginal microbiota in the following pregnancy, and their relationship between spontaneous preterm birth (sPTB). Methods: We conducted a prospective cohort study including 133 pregnant patients, of whom 25 had conization histories and 108 did not. Vaginal microbiome samples were collected using swabs by an obstetrician upon inclusion in the first trimester and during delivery. V1-V2 of the 16S rRNA gene were amplified and analyzed to identify the bacteria. Results: The conization group had a significantly lower delivery week (34 weeks vs. 36 weeks, p = 0.003) and higher sPTB rate (64% vs. 8.3%, p ≤ 0.001) than the control group. In the conization group, alpha (Chao 1, p = 0.02; phylogenetic diversity whole tree, p = 0.04) and beta diversity (permutational multivariate analysis of variance test, p = 0.04) of the vaginal microbiota was significantly higher during delivery in patients who delivered preterm than in those who delivered term. Community-state type IV in the first trimester was significantly associated with sPTB (overall odds ratio 3.80, 95% confidence interval 1.33-10.8, p = 0.01). Conclusions: Conization is a risk factor for sPTB. Increased risk of sPTB in patients after conization may belong to the vulnerable defense mechanism, due to the shortened cervix and decreased cervical mucus.

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OBJECTIVES: A high rate of preterm birth has been reported in Okinawa Prefecture, the southernmost island prefecture of Japan. Hence, this study aimed to identify the risk factors for preterm birth in this prefecture. METHODS: This retrospective study included data from January 2013 to December 2019 from three facilities in Okinawa Prefecture. Of 13,468 cases of preterm birth at ≥ 22 weeks of gestation, 11,868 were included in this study. Stillbirth and multiparity cases were excluded. First, we compared the overall preterm and full-term birth groups by categorizing the patient background, obstetric, and fetal risk factors. Further, we categorized preterm births into three groups (22-27, 28-33, and 34-36 weeks of gestation) and examined patient background factors to identify potential risk factors for the occurrence of preterm birth in each group. RESULTS: Preterm births accounted for 21.2% (2,521 cases) of all cases, with the rates of 2.6% (317 cases), 6.7% (800 cases), and 11.8% (1,404 cases) at 22-27, 28-33, and 34-36 weeks of gestation, respectively. To prevent preterm birth in Okinawa Prefecture, the present study specifically focused on patient background characteristics. In the multinomial logistic regression, the risk factors for preterm birth at 22-27 weeks of gestation were previous preterm birth (P < 0.0001) and lower age (P = 0.026); at 28-33 weeks of gestation, the risk factors were previous preterm birth (P < 0.0001) and history of cervical conization (P = 0.009); and at 34-36 weeks of gestation, only previous preterm birth (P < 0.0001) was a risk factor. CONCLUSIONS FOR PRACTICE: Previous preterm birth, younger age, and history of cervical conization were risk factors for Preterm birth in Okinawa. To reduce premature births in Okinawa Prefecture, it is important to pick up women with these risk factors and provide them with appropriate guidance and education on an ongoing basis.

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Bladder pseudoexstrophy is a rare form of bladder exstrophy. Bladder exstrophy occurs in 1 in every 30,000 to 50,000 live births. Because bladder pseudoexstrophy is asymptomatic, it may be undiagnosed even in adulthood. A 31-year-old woman with uterus bicornis unicollis and a low-set umbilicus underwent emergency cesarean delivery during the 37th week of pregnancy for chorioamnionitis. Perioperatively, asymptomatic anatomical abnormalities were identified, which included separated rectus abdominis muscles and diastasis of the symphysis pubis. The urinary tract was normal. The patient was diagnosed with bladder pseudoexstrophy. A low-set umbilicus may be a potential marker for the diagnosis of bladder pseudoextrophy.

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Ovarian cysts develop rarely in fetuses during pregnancy and usually disappear after birth. However, during pregnancy, torsion and rupture of the cyst can occur and it is necessary to manage such cases. At present, there is no standardized prenatal or neonatal treatment. However, the preservation of ovarian function is an important consideration. Here, we present a case involving a 35-year-old woman who gave birth to an infant with a complicated ovarian cyst, which was resolved through laparoscopic surgery on the third day after birth. The prenatal diagnosis of the fetal ovarian cyst was performed prenatally using ultrasound and magnetic resonance imaging (MRI). However, torsion of the ovarian pedicle was suspected because of dorsal thickening of the cyst wall and fluid formation indicated by high intensity on T1- and T2-weighted MRI. Surgery was complicated due to involvement in the torqued pedicle of the left fallopian tubal fimbria, which was released. The cyst was drained and partially resected, and then the pedicle torsion was released. By four years and five months of follow-up, there had been no ovarian cyst findings on ultrasound or MRI. Larger cysts are more likely to involve torsion of the ovarian pedicle and potential bleeding. Considering that, in this case, the cyst was large and proved to be ischemic-hemorrhagic, the decision to operate seemed justified.

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INTRODUCTION: 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. METHODS AND ANALYSIS: 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. ETHICS AND DISSEMINATION: 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. TRIAL REGISTRATION: jRCTs041190065.

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A complete hydatidiform mole coexisting with a fetus (CHMCF) is a rare form of twin pregnancy. High-risk gestational trophoblastic neoplasia (GTN) can occur after a CHMCF pregnancy, although the frequency is low. In cases of GTN, the clinical diagnosis and that based on the International Federation of Gynecology and Obstetrics (FIGO) scoring system can differ. This case report concerns a patient with a choriocarcinoma that was initially diagnosed and treated as a low-risk stage III GTN following a live birth from a CHMCF pregnancy. We used short tandem repeat (STR) analysis to identify the causative pregnancy as the patient's earlier complete hydatidiform mole. Clinicians should anticipate a high-risk GTN when treating persistent trophoblastic disease (PTD) in patients with a non-typical course.

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Radical trachelectomy (RT) is a method of fertility preservation for patients with early invasive uterine cervical cancer stage IA2 or IB1 with a tumor diameter of ≤2 cm. However, women who have undergone RT have high risks of abortion and premature birth. To prevent premature birth, cervical cerclage is performed in patients with an ultra-short cervix, but the portio vaginalis is not visible in these patients, and transvaginal uterine cervical cerclage is almost impossible. In such cases, transabdominal cerclage (TAC) is considered. The patient reported here was a 39-year-old Japanese woman, gravida 2, para 0. At 37 years, she was diagnosed with cervical cancer, stage IB1 (according to the International Federation of Gynecology and Obstetrics [FIGO] classification), so abdominal modified RT was performed. One year after the operation, she became pregnant through in vitro fertilization and embryo transfer. The cervical length was 17 mm at 13 weeks of gestation but was shortened to 5 mm at 16 weeks of gestation, so TAC was performed. An emergency cesarean section was performed because of increased genital bleeding at 34 weeks of gestation and a live baby was delivered.

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Sigmoid volvulus requires urgent treatment, and it is particularly rare among pregnant women without a history of laparotomy. A delay in diagnosis may lead to serious consequences for the mother and fetus, and a rapid diagnosis and treatment in this setting is essential. The patient was a 19-year-old primiparous woman. She complained of repeated exacerbations and remissions of abrupt lower abdominal pain for the past 2 days and was transported to our hospital at 33 weeks of gestation. Ultrasonography revealed no placental thickening, and maternal bowel dilation was difficult to identify. Plain abdominal X-ray showed a dilated colon on the left side of the abdomen. Contrast-enhanced CT scan of the abdomen revealed a volvulus on the dorsal side of the uterus. The proximal end of the transverse to sigmoid colon was markedly dilated, and the distal end was collapsed. The elevated lactate level on blood gas analysis suggested intestinal ischemia. She was suspected of having a sigmoid volvulus at 33 weeks and 3 days of gestation. We decided to perform a cesarean section to secure the operative field for an intestinal resection following delivery. A male weighing 1840 g with Apgar scores 8/8 was delivered. The sigmoid colon was approximately 80 cm in length. A 360-degree clockwise rotation of was observed with a very distended but viable sigmoid loop. Following reduction of the volvulus, the sigmoid colon was fixed to the left side of the peritoneum. The mother had an uneventful postoperative course, and the infant was discharged without any sequelae. This case demonstrates two important lessons. First, sigmoid volvulus can occur in pregnant women even if they never had a laparotomy. Second, abdominal contrast-enhanced CT is useful for rapid diagnostic and treatment decisions relative to this pathology.

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The case is presented of a 29-year-old primiparous woman who was COVID-19-positive at 34 weeks of gestation and who developed severe acute respiratory distress syndrome. After a four-day history of fever and mild dyspnea, she was referred to hospital. Ciclesonide, dexamethasone, heparin sodium, and sulbactam/ampicillin were initiated, followed by remdesivir and tocilizumab. On the fourth day after admission (at 34 weeks 5 days of gestation), respiratory failure required ventilator management. An emergency cesarean section was performed and a 2565-g male infant was delivered with an Apgar score of 8/8 and negative COVID-19 status. However, on the following day the patient's respiratory condition deteriorated and mechanical ventilation was initiated. Subsequently, her respiratory condition quickly improved and mechanical ventilation was terminated 4 days after intubation. She was discharged 12 days after cesarean delivery. Our case provides additional evidence that raises concerns regarding the unfavorable maternal consequences of COVID-19 infection during pregnancy.

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OBJECTIVES: Neonates delivered by women who were taking psychotropic or anticonvulsant drugs during pregnancy are at increased risk of developing neonatal withdrawal syndrome. We investigated the incidence of neonatal withdrawal symptoms and the effects of multiple maternal medications and breastfeeding on neonatal withdrawal symptoms. STUDY DESIGN: This study examined the overall incidence of neonatal withdrawal symptoms in neonates delivered from 2004 to 2016 by women who were taking oral antipsychotics, antidepressants, anxiolytics, sedatives, or anticonvulsant drugs during pregnancy. Moreover, we compared the incidence of neonatal symptoms between mothers taking single drugs and multiple drugs, and between breastfed and formula-fed neonates. We scored the neonates according to the neonatal withdrawal syndrome checklist created by Isobe et al., which is widely used in Japan. RESULTS: We examined 131 mothers and their 134 neonates. Withdrawal symptoms were found in 54.5 % of neonates. Symptoms were found in 32.4 % of neonates delivered by mothers taking single drugs and 62.9 % of neonates delivered by mothers taking two or more drugs (p = 0.0019). One or more withdrawal symptoms developed in 46.4 % of breastfed neonates and 66.1 % of formula-fed neonates (p = 0.034). Five infants had a score of 8 or more points on the withdrawal checklist, which is an indication to consider treatment with pharmacotherapy. All five of these neonates were mainly formula-fed, and their mothers were taking two or more drugs. CONCLUSIONS: The incidence of withdrawal symptoms was high in neonates delivered by women taking psychotropic or anticonvulsant drugs; however, there were few serious cases. The risk increased when a mother was taking multiple drugs. Breastfeeding appeared to protect against withdrawal symptoms.

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Pseudoaneurysms generally develop when an arterial puncture site is inadequately sealed. We encountered a case of vaginal pseudoaneurysm that developed 3 years after cesarean section in a 35-year-old gravida 7 para 4 woman who was prescribed with anticoagulant and antiplatelet drugs after surgeries for ventricular septal defect and aortic valve replacement. Pelvic computed tomography scan revealed a large mass, which showed a dappled contrast filling on the arterial phase, located in the posterior vaginal wall. The vaginal pseudoaneurysm was completely occluded by embolization of the left vaginal artery. Anticoagulation and antiplatelet therapies can be potential causes of spontaneous pseudoaneurysm rupture. Extrauterine pseudoaneurysm has a long period of time between cesarean section and pseudoaneurysm discovery. Considering that pseudoaneurysm shows different clinical features for each patient, we should always consider pseudoaneurysm when we assess a patient with postpartum hemorrhage.

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We previously identified suppressyn (SUPYN), a placental protein that negatively regulates the cell fusion essential for trophoblast syncytialization via binding to the trophoblast receptor for syncytin-1, ASCT2, and hypothesized that SUPYN may thereby regulate cell-cell fusion in the placenta. Here, we redefine in vivo SUPYN localization using specific monoclonal antibodies in a rare early placental sample, showing SUPYN localization in villous and extravillous trophoblast subtypes, the decidua and even in placental debris in the maternal vasculature. In human trophoblast cell lines, we show SUPYN alters ASCT2 glycosylation within the secretory pathway and that this binding is associated with inhibition of cell fusion. Using newly-optimized trophoblast isolation protocols that allow tracking of ex vivo cell fusion, we present transcription and translation dynamics of fusion-related proteins over 96 hours in culture and the effects of changes in ambient oxygen levels on these processes. We report converse syncytin-1 and SUPYN transcriptional and translational responses to surrounding oxygen concentrations that suggest both are important in the effects of hypoxia and hyperoxia on placental syncytialization. Our results suggest that SUPYN's anti-fusogenic properties may be exerted at several sites in the maternal body and its dysregulation may be associated with diseases of abnormal placentation.

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Massive subchorionic thrombohematoma (MST), termed Breus' mole, is a rare condition in which a large maternal blood clot separates the chorionic plate from the villous chorion. Common complications of MST include fetal growth restriction, preeclampsia, and intrauterine fetal death. Here, we present a case of a 17-year-old Japanese woman referred to our institution at 21 weeks of gestation. Ultrasound examination revealed a large placental mass with mixed high and low echogenicity measuring approximately 7.6 cm in thickness. Doppler examination showed absence of end-diastolic velocity of the umbilical artery. At 22 weeks of gestation, the patient had a stillbirth weighing 138g. The placenta weighed 502 g and was 8 cm thick, and the total blood loss was 270 g. Macroscopic examination revealed that a subchorionic blood clot measuring 12 cm × 5 cm covered a large portion of the placenta with well-defined margins on the fetal surface. Microscopic examination revealed an intervillous hematoma and fibrinous deposits directly beneath the chorionic plate with adjacent compressive effects. Based on these findings, MST was diagnosed. Because MST is rare, it must be considered in the differential diagnosis of parental conditions. Magnetic resonance imaging can be optimal for diagnosing MST when ultrasound diagnosis is difficult.

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We report a case of Cornelia de Lange syndrome (CdLS) where prenatal diagnosis was not made even with major anomaly. A 33-year-old Japanese woman was referred to our institution at 23 weeks of gestation because of fetal forearm defect. Ultrasound examination revealed short forearms and short humeri and femurs (-2.1 SD). The fetal estimated body weight was 450 g (-1.3 SD). Fetal MRI at 26 weeks of gestation revealed short forearms and hypoplasty of hand fingers. Fetal growth restriction became evident thereafter, leading to intrauterine fetal death occurring at 29 weeks of gestation. A stillbirth baby was of 798 g in body weight and 33.0 cm in length. External examination showed a low hairline, synophrys, low-set ear, hypertrichosis, and smooth long philtrum with thin lips. The neck appeared short and broad. Finally, CdLS was diagnosed. The prenatal diagnosis might be possible as the arm findings were totally characteristic in a small fetus, regardless of whether an overhanging upper lip was identified. Because CdLS is a rare condition, it is important to consider its possibility as a part of differential diagnosis.

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A 37-year-old (G4P3) woman was referred to our hospital at 32 weeks of gestation for the evaluation of a fetus with an intrathoracic cystic lesion. Ultrasonography and magnetic resonance imaging revealed that a fetal cystic lesion without a mucosal layer was located in the posterior mediastinum. These findings were consistent with a bronchogenic cyst. At 38 3/7 weeks of gestation, an elective cesarean section was performed because of her previous cesarean section. A female neonate without any external anomalies, weighing 2,442 g, with Apgar scores of 8 and 9, and requiring no resuscitation was born. Four weeks after delivery, the neonate was admitted because of respiratory distress due to mass effect. At right lateral thoracotomy, a 105 × 65 mm of solitary smooth-walled cyst containing serosanguineous fluid was found in the posterior mediastinum, which was excised completely. Histologic examination revealed the diagnosis of the mediastinal gastric duplication cyst. The neonate made an uneventful recovery. Accurate diagnosis is not necessary, but detection and continuous observation are logical. Although gastric duplication, particularly intrathoracic, is a rare pathology, it should be considered in the differential diagnosis of any intrathoracic cyst.

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Two types of congenital bronchial atresia (proximal and peripheral) have been classified. We report two cases of peripheral bronchial atresia diagnosed by prenatal ultrasonography (US) and magnetic resonance imaging (MRI). Evaluating an enlarged lung mass that is homogeneously hyperechoic on US and hyperintense on T2-weighted MRI can help in determining whether bronchial atresia is present. Proximal type is suggested when a dilated main bronchus is observed as a tubule structure of an involved lung hilum. In our cases, T2-weighted MRI revealed homogeneously hyperintense lung lesion with decreased signal intensity of adjacent lobe, flattening diaphragm, and mediastinal shift. Dilatation of the main bronchus was not observed and the opposite lung was normal in appearance. These findings were explained by secondary compression due to enlargement of the involved lung. The preservation of vascular structure and the retained normal shape, though enlarged, in the affected lobe were observed, which demonstrated undisrupted pulmonary architecture of the lobe. Thus, congenital cystic adenomatoid malformation was excluded because pulmonary architecture was relatively preserved. Finally, presumed diagnoses of the peripheral bronchial atresia were made and confirmed by postnatal chest computed tomography.

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A 40-year-old pregnant woman presented with a fetal abdominal cyst and oligohydramnios. Color Doppler scan revealed a single blood vessel from the fetal aorta into a single umbilical artery. Severe oligohydramnios limited ultrasonographic evaluation of the fetal lower limbs, kidneys, or bladder. The pregnancy was terminated; the fetus showed fused lower limbs, bulging abdomen, and absent external genitalia and was diagnosed with type III sirenomelia. On autopsy, no normal bladder was observed, but duodenal atresia, anorectal atresia, and right renal agenesis were found. An intra-abdominal cyst, diagnosed histologically as a saccular cloaca, occupied the abdominal cavity. Ultrasonographic diagnosis of fetal sirenomelia is difficult due to poor depiction of the lower limbs. A vitelline artery leading to a single umbilical artery and a fetal abdominal cyst occupying most of the abdominal cavity are considered fetal sirenomelia associated with large defects of the gastrointestinal and genitourinary tracts.

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Secondary postpartum hemorrhage (PPH) and postabortion hemorrhage are rare complications. Retained products of conception (RPOC) is among the most common causes of both secondary PPH and postabortion hemorrhage. Other less common causes of secondary PPH are uterine vascular abnormalities such as arteriovenous malformations and pseudoaneurysms. These are usually related to a history of a procedure such as dilation and curettage or cesarean delivery. Subinvolution of the placental site is an idiopathic cause of secondary PPH; this condition may be underrecognized and therefore could have a higher incidence than currently reported. Gestational trophoblastic disease is rare but commonly presents as secondary PPH and resembles RPOC in radiologic appearance. The first-line imaging modality for secondary PPH is ultrasound, but computed tomography and magnetic resonance imaging may be used if the ultrasound findings are indeterminate. Angiography is an important tool for the definitive diagnosis of uterine vascular abnormalities. Appropriate management requires radiologists to be familiar with the multimodality imaging features of secondary PPH or postabortion hemorrhage.

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