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Background Few reports have presented an overall view of pregnant women with coronavirus disease 2019 (COVID-19) across an entire country and throughout the entire gestation period. Furthermore, no such reports are available for Japan. We examined the clinical characteristics and outcomes of pregnant women with COVID‑19 on a national scale in Japan. Methods A nationwide questionnaire-based survey for all 2,185 maternity services in Japan was conducted between July and August 2020. Information regarding maternal characteristics and epidemiological, clinical, treatment, and perinatal outcomes of pregnant women diagnosed with COVID-19 between 16 January and 30 June 2020 were collected. Main outcome measures were incidence of pregnant women with COVID-19 and infant infection, positive rate of the universal screening test for asymptomatic pregnant women, identification of infection route and rates of maternal death, and severe cases. Results Responses from 1,418 institutions were assessed (65% of all delivery institutions in Japan). Seventy-two pregnant women were reported to have been diagnosed with COVID-19. The positive rate of the universal screening test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among asymptomatic pregnant women was 0.03% (2/7428). The most common route of infection was familial (57%). Fifty-eight pregnant women with COVID-19 were symptomatic, of whom five (8.6%) had a severe infection and one died (a tourist). Severe respiratory symptoms, oxygen administration, and pneumonia were frequently reported in the third trimester and postpartum period compared with in early pregnancy (22.2% vs 2.5% [P = 0.03], 38.9% vs 7.5% [P = 0.01], and 50.0% vs 7.5% [P Conclusions In Japan, the number of cases of COVID-19 infection in pregnant women is very low. Compared with early pregnancy, late pregnancy may be a risk factor for exacerbation of symptoms and familial transmission is the most common route of infection. The importance of infection prevention should be emphasised, especially in women in late pregnancy, their families, and any cohabitants.

Aim Extended-field concurrent chemoradiation therapy (Ex-CCRT) has been widely used for para-aortic lymph node (PAN) metastases confirmed by radiographic assessment without surgical exploration. The objective of this prospective study was to evaluate the clinical value of laparoscopic retroperitoneal PAN biopsy in locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastases. Methods From May 2017 to March 2020, stage IIB-IIIB cervical cancer patients who were diagnosed with PLN metastasis using positron emission tomography-computed tomography (PET-CT) with maximum standardized uptake value (SUVmax) ≥2.0 underwent laparoscopic retroperitoneal PAN biopsy. The radiation fields were extended to PAN areas with pathological metastases. Results Fourteen patients were diagnosed with cervical squamous cell carcinoma of the International Federation of Gynecology and Obstetrics (FIGO) stage IIB (n = 7) and IIIB (n = 7). The median operating time was 138 min (range, 104-184 min). The median number of harvested PANs was 19 (range, 6-36). Three patients were positive for PAN metastasis on histological analysis. In this study, the sensitivity and specificity of PET-CT were 66.7% and 90.9%, respectively. Conclusion Our study is characterized by the use of more appropriate eligibility criteria for LACC with PLN metastases. Our results revealed that laparoscopic retroperitoneal PAN biopsy may be a useful approach to determine the radiation field for PANs during standard radiotherapy planning.

Objective This study assessed maternal cytomegalovirus antibodies, and the occurrence of primary and congenital cytomegalovirus infections, and risk factors of congenital infection after a maternal primary infection. Study design We included 19,435 pregnant women in Japan, who were tested for serum cytomegalovirus antibodies before 20 gestational weeks. Immunoglobulin (Ig) G avidity was evaluated in women with both IgG and IgM antibodies; tests were repeated at ≥28 gestational weeks among women without IgG and IgM antibodies. Result Primary and congenital infections were 162 and 23 cases, respectively. The risk ratios for congenital infection were 8.18 (95% confidence interval: 2.44–27.40) in teenage versus older women, and 2.25 (95% confidence interval: 1.28–3.94) in parity ≥ 2 versus parity ≤ 1. Of 22 live birth congenital infection cases, three had abnormal neurological findings. Conclusion We demonstrated teenage and parity ≥ 2 pregnant women as risk factors of post-primary congenital infection.

Background/aim To compare the surgical outcomes of robotic and laparoscopic hysterectomy with or without pelvic lymphadenectomy among obese patients [body mass index (BMI) >30 kg/m2] with early-stage endometrial cancer. Patients and methods We examined 42 obese patients with early-stage endometrial cancer who underwent laparoscopic (LH) or robotic hysterectomy (RH) between April 2014 and April 2020 in our institution. We analysed intraoperative and postoperative data for both procedures. Results Of the 42 women, 22 and 20 patients underwent RH and LH, respectively, with or without pelvic lymphadenectomy. The operation times, harvested lymph nodes, and BMI did not differ between the groups. In the subset of patients who underwent pelvic lymphadenectomy, those in the RH group had shorter hospital stays (p=0.001) and less intraoperative bleeding (p=0.006). Conclusion Obese patients with endometrial cancer who underwent robotic surgery had less blood loss and shorter hospital stays than those who underwent laparoscopic surgery.

Obturator nerve injury is an uncommon complication frequently associated with pelvic gynecologic or urologic cancer surgery. It can lead to disability or adversely affect quality of life. Large segmental defects are particularly difficult to manage as the limited mobility of the nerve prevents tension-free direct end-to-end anastomosis. A 36-year-old woman with cervical cancer underwent sentinel lymph node biopsy, laparoscopic radical hysterectomy, and bilateral adnexectomy. During the procedure, the sentinel lymph node (right obturator node) adherent to the obturator nerve was resected together with the nerve segment leaving a 3 cm defect. Immediate laparoscopic obturator nerve repair was performed using an artificial nerve conduit leading to successful recovery. We report this unique case due to rarity of large segmental obturator nerve defects and present laparoscopic nerve repair with artificial nerve conduits as a useful treatment alternative of these important injuries, without nerve donor site morbidity.

Aim To evaluate psychological stress among pregnant and puerperal women in Japan during the coronavirus disease 2019 (COVID‐19) pandemic. Methods In this cross‐sectional study, we recruited pregnant women and puerperal women who delivered between January and September 2020 in Japan, using an online questionnaire. Participants were divided into low, middle, and high groups according to the degree of the epidemic in their region of residence. Related factors were analyzed using the chi‐squared test. The relationship between COVID‐19 epidemic regions and depression risks and anxiety using the Edinburgh Postnatal Depression Scale (EPDS) and Kessler 6 scale (K6) was evaluated using a univariate and multivariable logistic regression model. Results Overall, 7775 cases, including 4798 pregnant and 2977 puerperal women, were analyzed. The prevalence of high EPDS and K6 scores was significantly increased in pregnant women in the high than those in the low epidemic regions (EPDS: adjusted odds ratio [aOR] 1.453, 95% confidence interval [CI] 1.205–1.753; K6: aOR 1.601, 95% CI 1.338–1.918). There was no difference in EPDS score, but the prevalence of high K6 scores was significantly increased in puerperal women in the high than those in the low epidemic regions (aOR 1.342, 95% CI 1.066–1.690). Further, restriction on going to their hometown for delivery increased the prevalence of high EPDS scores among pregnant (aOR 1.663, 95% CI 1.296–2.133) and puerperal women (aOR 1.604, 95% CI 1.006–2.557). Conclusions Decreased support due to the COVID‐19 pandemic affected the psychological status of pregnant and puerperal women; hence, investing medical resources in their healthcare essential.

AIM The purpose of this study was to evaluate the current state and clinical characteristics of spontaneous hemoperitoneum in pregnancy (SHiP) in Japan by performing a comprehensive survey. METHODS We reviewed data on pregnant women who developed SHiP during 2013-2017 (for 5 years), and were admitted to any of the perinatal centers in Japan. The survey assessed maternal background and maternal and neonatal prognosis. We divided the cases into two groups, favorable and poor prognosis groups, and made comparisons between the two groups. RESULTS Of the 407 facilities in Japan, 267 (66%) facilities responded to our survey. Overall, 31 cases of SHiP were registered. Maternal death occurred in one case (3%) due to liver bleeding with an unknown cause. Of 23 cases with a SHiP onset during pregnancy, 12 (53%) had been misdiagnosed as placental abruption. The prognosis for the fetuses included miscarriage or stillbirth in three cases (10%) and asphyxia in 12 cases (42%). There was no significant correlation between the amount of intra-abdominal blood loss and neonatal prognosis based on umbilical artery pH. Incidences of preterm birth

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.

Background Streptococcal toxic shock syndrome is associated with the highest rates of infection-related maternal mortality. We conducted a comparative analysis of background factors and treatment course between patients who survived and those who did not to improve our understanding of the optimal initial treatment approach for this fulminant disease. Methods: A retrospective observational study was conducted based on clinical data collected from two national organizations. Clinical data of patients who died and of those who survived, including background information, clinical course, and treatment administered, were collated. Results: No statistical differences were found between groups for age, parity, season, gestational age, or the patient’s location at the onset of symptoms. After the onset of initial symptoms, survivors were administered antibiotics systematically during their first visit to a clinic (p = 0.006). More survivors had received treatment within 1 hour of onset of fulminant disease (p = 0.069). The number of fetal deaths was significantly higher in the mortality group (p = 0.003), while that of fetal survival was higher in the group of maternal survivors (p = 0.055). Maternal survivors with non-specific initial symptoms received early intervention if there was a family history of group A streptococcal infection or a positive rapid antigen test result. Conclusions Intensive care, including systemic administration of antibiotics, may contribute to maternal survival when administered immediately (within 1 hour) after the onset of fulminant streptococcal toxic shock syndrome. Eliciting a family history of streptococcal infection and conducting a rapid antigen test can identify patients needing early intervention.

Antenatal glucocorticoids improve outcomes among premature infants but are associated with hyperglycemia, which can exacerbate hypoxic-ischemic injury. It is still unclear how antenatal glucocorticoids or hyperglycemia modulate fetal cardiovascular adaptations to severe asphyxia. In this study, preterm fetal sheep received either saline or 12 mg im maternal dexamethasone, followed 4 h later by complete umbilical cord occlusion (UCO) for 25 min. An additional cohort of fetuses received titrated glucose infusions followed 4 h later by UCO to control for the possibility that hyperglycemia contributed to the cardiovascular effects of dexamethasone. Fetuses were studied for 7 days after UCO. Maternal dexamethasone was associated with fetal hyperglycemia ( P < 0.001), increased arterial pressure ( P < 0.001), and reduced femoral ( P < 0.005) and carotid ( P < 0.05) vascular conductance before UCO. UCO was associated with bradycardia, femoral vasoconstriction, and transient hypertension. For the first 5 min of UCO, fetal blood pressure in the dexamethasone-asphyxia group was greater than saline-asphyxia ( P < 0.001). However, the relative increase in arterial pressure was not different from saline-asphyxia. Fetal heart rate and femoral vascular conductance fell to similar nadirs in both saline and dexamethasone-asphyxia groups. Dexamethasone did not affect the progressive decline in femoral vascular tone or arterial pressure during continuing UCO. By contrast, there were no effects of glucose infusions on the response to UCO. In summary, maternal dexamethasone but not fetal hyperglycemia increased fetal arterial pressure before and for the first 5 min of prolonged UCO but did not augment the cardiovascular adaptations to acute asphyxia.

BackgroundAlthough spinal schwannomas generally grow very slowly, it has been reported that these clinical growths and their associated neurological symptoms accelerate during pregnancy. Because these cases are rare, surgical intervention for this tumor during pregnancy poses a significant challenge. The change of pregnancy-related hormones, such as estrogen and progesterone, is considered to have an effect on the clinical symptoms of spinal tumors. Expressions of the receptors for estrogen and progesterone in orbital and vestibular schwannomas have been reported; however, those expressions in spinal schwannomas have not been examined.Case presentationA 36-year-old woman at 8 weeks' gestation suffered from developing neck pain and neurological symptoms in the right upper extremity. Magnetic resonance imaging (MRI) confirmed the presence of a cervical intradural extramedullary tumor. Under general anesthesia, using intraoperative neurophysiological monitoring of motor-evoked potentials (MEPs), spinal tumor resection following a hemi-laminoplasty was performed in a prone position at 12 weeks gestation. The pathological diagnosis following surgery was spinal schwannoma. Her neurological symptoms were significantly improved after surgery and she delivered a healthy baby in her 40th week of pregnancy. At a 12-month follow-up, no abnormalities were observed during medical examinations of both mother and child. An immunohistochemical study identified the expression of estrogen receptors, but not progesterone receptors, in the spinal schwannoma.ConclusionsA cervical spinal schwannoma was successfully removed under general anesthesia at 12 weeks gestation by coordination between orthopaedic, obstetric and anesthesia teams. For the first time, an immunohistochemical analysis showed that the expression of estrogen receptors was identified in spinal schwannoma cells, suggesting the possibility that these hormone receptors in spinal schwannoma might contribute to the worsening of neurological symptoms during pregnancy.

The goal of this study is to find clues to improve perinatal outcomes in the case of cerebrovascular acute disorders during pregnancy.We analyzed 35 cases of cerebrovascular diseases related to maternal deaths in Japan those that occurred during pregnancy and reported to the Committee of the Ministry of Health, Labor, and Welfare from 2010 to 2018.Cerebrovascular acute disorders occurred at 34.6 ± 6.6 gestational weeks. There were seven intrauterine fetal deaths (IUFD), and eight cases showed neonatal asphyxia with umbilical arterial pH between 6.7 and 7.0 (asphyxia cases,More than 40% of cases experienced fetal asphyxia, and 20% ended in IUFD in maternal deaths related to cerebrovascular acute disorders. Maternal respiratory support and rapid delivery would be the keys to improve perinatal outcomes in case of cerebrovascular acute disorders during pregnancy.

Aim To clarify whether the incidence of umbilical cord prolapse (UCP) at delivery is related to the cervical ripening balloon (CRB). Methods A postal questionnaire study was conducted in 2018 in institutions providing maternity services across Japan. Questions on the number of deliveries, labor inductions, used CRB and cases of UCP in 2017 were included. Because a similar questionnaire survey was conducted in 2012, the incidence of UCP and frequency of the use of CRB were compared. Results A total of 1354 answers were assessed (57% of all delivery institutions). The total number of deliveries was 490 279. Of these, 78% were transvaginal; 74 cases of UCP were reported (0.015%), while 13 cases were reported from obstetric facilities never using CRB (0.008%). The incidence of UCP (odds ratio [95% confidence interval]) was 0.036% in the intracervical type (4.3 [1.6-11.3]), 0.091% in the disk-type (11.0 [4.2-29.0]) and 0.067% in the ball-type (8.1 [2.8-22.8]). Frequencies of the use of CRB were 7.3% and 6.6% in the 2012 and 2018 surveys, respectively. The use of the intracervical type increased from 2.8% in the 2012 survey to 3.5% in the 2018 survey, while that of the disk-type and ball-type declined. However, the incidence of UCP was not different between the two surveys regardless of the use of cervical ripening balloons (0.014% vs 0.015% with CRB, 0.005% vs 0.008% without CRB). Conclusion Although the frequency of CRB use significantly declined, the incidence of UCP did not significantly reduce in the last 5 years.

This study aimed to evaluate whether the Edinburgh Postnatal Depression Scale (EPDS) score predicts the occurrence of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) after delivery.The women in this study were registered at 35-36 weeks of pregnancy at Mie University Hospital from 2013 to 2015. We prospectively divided the puerperants into those with an EPDS score ≥9 (the high-EPDS group) and those with an EPDS score9 (the low-EPDS group) at 1 month postpartum. We compared the incidence rate of severe PMS and PMDD between both groups at 1 year after delivery.Of 200 registered cases, 178 (89.0%) did not experience severe PMS or PMDD before pregnancy. Among them, 21 were in the high-EPDS group, and 89 in the low-EPDS group. Four of the 21 women (19.0%) in the high-EPDS group and five of the 89 (5.6%) in the low-EPDS group had severe PMS or PMDD at 1 year after delivery. The incidence rate of severe PMS or PMDD in the high-EPDS group was higher than that in the low-EPDS group (p = 0.07).The novel finding of this study is that the EPDS may predict the occurrence of severe PMS/PMDD after delivery. The EPDS will contribute to the early detection of these diseases and to improving the quality of life of the patients by allowing treatment initiation at an early stage.

Background: The maternal circulatory system and hormone balance both change dynamically during pregnancy, delivery, and the postpartum period. Although atrial natriuretic peptides and brain natriuretic peptides produced in the heart control circulatory homeostasis through their common receptor, NPR1, the physiologic and pathophysiologic roles of endogenous atrial natriuretic peptide/brain natriuretic peptide in the perinatal period are not fully understood. Methods: To clarify the physiologic and pathophysiologic roles of the endogenous atrial natriuretic peptide/brain natriuretic peptide–NPR1 system during the perinatal period, the phenotype of female wild-type and conventional or tissue-specific Npr1-knockout mice during the perinatal period was examined, especially focusing on maternal heart weight, blood pressure, and cardiac function. Results: In wild-type mice, lactation but not pregnancy induced reversible cardiac hypertrophy accompanied by increases in fetal cardiac gene mRNAs and ERK1/2 (extracellular signaling-regulated kinase) phosphorylation. Npr1-knockout mice exhibited significantly higher plasma aldosterone level than did wild-type mice, severe cardiac hypertrophy accompanied by fibrosis, and left ventricular dysfunction in the lactation period. Npr1-knockout mice showed a high mortality rate over consecutive pregnancy–lactation cycles. In the hearts of Npr1-knockout mice during or after the lactation period, an increase in interleukin-6 mRNA expression, phosphorylation of signal transducer and activator of transcription 3, and activation of the calcineurin–nuclear factor of the activated T cells pathway were observed. Pharmacologic inhibition of the mineralocorticoid receptor or neuron-specific deletion of the mineralocorticoid receptor gene significantly ameliorated cardiac hypertrophy in lactating Npr1-knockout mice. Anti–interleukin-6 receptor antibody administration tended to reduce cardiac hypertrophy in lactating Npr1-knockout mice. Conclusions: These results suggest that the characteristics of lactation-induced cardiac hypertrophy in wild-type mice are different from exercise-induced cardiac hypertrophy, and that the endogenous atrial natriuretic peptide/brain natriuretic peptide–NPR1 system plays an important role in protecting the maternal heart from interleukin-6–induced inflammation and remodeling in the lactation period, a condition mimicking peripartum cardiomyopathy.

OBJECTIVE. To propose an ideal patient candidate with early-stage cervical cancer for undergoing fertility-sparing trachelectomy. METHODS. This nationwide, multicenter, retrospective study was conducted by the Japan Society of Obstetrics and Gynecology involving women aged

Background It is crucial to interpret fetal heart rate patterns with a focus on the pattern evolution during labor to estimate the relationship between cerebral palsy and delivery. However, nationwide data are not available. Objective The aim of our study was to demonstrate the features of fetal heart rate pattern evolution and estimate the timing of fetal brain injury during labor in cerebral palsy cases. Study Design In this longitudinal study, 1069 consecutive intrapartum fetal heart rate strips from infants with severe cerebral palsy at or beyond 34 weeks of gestation, were analyzed. They were categorized as follows: (1) continuous bradycardia (Bradycardia), (2) persistently nonreassuring, (3) reassuring-prolonged deceleration, (4) Hon’s pattern, and (5) persistently reassuring. The clinical factors underlying cerebral palsy in each group were assessed. Results Hypoxic brain injury during labor (those in the reassuring-prolonged deceleration and Hon’s pattern groups) accounted for 31.5% of severe cerebral palsy cases and at least 30% of those developed during the antenatal period. Of the 1069 cases, 7.86% were classified as continuous bradycardia (n=84), 21.7% as persistently nonreassuring (n=232), 15.6% as reassuring-prolonged deceleration (n=167), 15.9% as Hon’s pattern (n=170), 19.8% as persistently reassuring (n=212), and 19.1% were unclassified (n=204). The overall interobserver agreement was moderate (kappa 0.59). Placental abruption was the most common cause (31.9%) of cerebral palsy, accounting for almost 90% of cases in the continuous bradycardia group (64 of 73). Among the cases in the Hon’s pattern group (n=67), umbilical cord abnormalities were the most common clinical factor for cerebral palsy development (29.9%), followed by placental abruption (20.9%), and inappropriate operative vaginal delivery (13.4%). Conclusion Intrapartum hypoxic brain injury accounted for approximately 30% of severe cerebral palsy cases, whereas a substantial proportion of the cases were suspected to have either a prenatal or postnatal onset. Up to 16% of cerebral palsy cases may be preventable by placing a greater focus on the earlier changes seen in the Hon’s fetal heart rate progression.

Advances in perinatal care have improved the prognoses of both mothers and neonates; however, cerebral palsy continues to occur. In this study, we examined methods for the intragestational evaluation of the health of infants who later developed cerebral palsy. A retrospective review was conducted on light-for-dates cases among the 2113 cause analysis reports issued by the Japan Obstetric Compensation System between January 2009 and September 2018. In our examination, we determined that non-stress tests and ultrasonic Doppler tests were used to evaluate fetal well-being. Moreover, we observed cases in which additional testing was not performed even when fetal growth restriction (FGR) was identified. Appropriate management of FGR may help reduce the incidence of cerebral palsy.

AIM We previously reported that female babies born small developed cardiovascular risks in middle age. The present study was conducted using the same cohort to examine the relationship between physique at 6 years and the metabolic disease risk in middle age. METHODS Data collected from 721 women aged 41-69 years who underwent a medical examination at a single institution between 2007 and 2008 were retrospectively examined. We collected data from medical examinations and a questionnaire on physique (thin, normal, and fat) at 6 years. The relationship between birthweight and physique at 6 years was investigated. RESULTS Among females who were born small (

To evaluate the effectiveness and safety of tadalafil treatment for hypertensive disorder of pregnancy (HDP).In an open-label, randomized clinical trial, singleton pregnancies with HDP between 20 and 33 weeks of gestation were randomized to take 20 mg oral tadalafil every day (tadalafil treatment group) or no drug (conventional treatment group). The primary outcome was prolongation of pregnancy from randomization to delivery. However, this article primarily focuses on the safety assessments performed in the tadalafil treatment for HDP population, because the safety of using PDE5 inhibitors as therapeutic agents for fetal growth restriction (FGR) has been a problem worldwide.From October 2016 to March 2018, 28 patients were randomized to each group and two cases were excluded (tadalafil treatment group: 12 cases; conventional treatment group: 14 cases). The significant adverse events related to tadalafil did not occur in the tadalafil treatment group. Among maternal adverse events, specifically with regard to headaches, there were significant differences between the two groups (0% in tadalafil group versus 43% in conventional treatment group;Tadalafil treatment is safe for pregnant women with HDP. Moreover, tadalafil did not prolong the gestational period in pregnant women with HDP.

OBJECTIVES Outborn (born outside tertiary centers) infants, especially extremely preterm infants, are at an increased risk of mortality and morbidity in comparison to inborn (born in tertiary centers) infants. Extremely preterm infants require not only skilled neonatal healthcare providers but also highly specialized equipment and environment surroundings. Maternal transport at an appropriate timing must be done to avoid the delivery of extremely preterm infants in a facility without the necessary capabilities. Cases of unexpected deliveries at birth centers or level I maternity hospitals need to be attended emergently. We compared the differences in short- and long-term outcomes between outborn and inborn infants to improve our regional perinatal system. DESIGN Retrospective cohort study. SETTING Neonatal Research Network of Japan database. PATIENTS Extremely preterm infants (gestational age between 22 + 0 and 27 + 6 wk) in the Neonatal Research Network of Japan database between 2003 and 2011. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS A total of 12,164 extremely preterm infants, who were divided into outborn (n = 785, 6.5%) and inborn (n = 11,379, 93.5%) groups, were analyzed. Significant differences were observed in demographic and clinical factors between the two groups. Outborn infants had higher short-term odds of severe intraventricular hemorrhage (adjusted odds ratio, 1.49; 95% CI, 1.11-2.00; p < 0.01), necrotizing enterocolitis (adjusted odds ratio, 1.49; 95% CI, 1.11-2.00; p < 0.01), and focal intestinal perforation (adjusted odds ratio, 1.58; 95% CI, 1.09-2.30; p = 0.02). There were no significant differences in long-term outcomes between the two groups, except in the rate of cognitive impairment (adjusted odds ratio, 1.49; 95% CI, 1.01-2.20; p = 0.04). CONCLUSIONS The frequency of severe intraventricular hemorrhage, necrotizing enterocolitis or focal intestinal perforation, and cognitive impairment was significantly higher in outborn infants. Thus, outborn/inborn birth status may play a role in short- and long-term outcomes of extremely preterm infants. However, more data and evaluation of improvement in the current perinatal environment are needed.

Background Standardized treatment of fetal tachyarrhythmia has not been established. Objectives This study sought to evaluate the safety and efficacy of protocol-defined transplacental treatment for fetal supraventricular tachycardia (SVT) and atrial flutter (AFL). Methods In this multicenter, single-arm trial, protocol-defined transplacental treatment using digoxin, sotalol, and flecainide was performed for singleton pregnancies from 22 to Results A total of 50 patients were enrolled at 15 institutions in Japan from 2010 to 2017; short ventriculoatrial (VA) SVT (n = 17), long VA SVT (n = 4), and AFL (n = 29). One patient with AFL was excluded because of withdrawal of consent. Fetal tachyarrhythmia resolved in 89.8% (44 of 49) of cases overall and in 75.0% (3 of 4) of cases of fetal hydrops. Pre-term births occurred in 20.4% (10 of 49) of patients. Maternal AEs were observed in 78.0% (39 of 50) of patients. Serious AEs occurred in 1 mother and 4 fetuses, thus resulting in discontinuation of protocol treatment in 4 patients. Two fetal deaths occurred, mainly caused by heart failure. Neonatal tachyarrhythmia was observed in 31.9% (15 of 47) of neonates within 2 weeks after birth. Conclusions Protocol-defined transplacental treatment for fetal SVT and AFL was effective and tolerable in 90% of patients. However, it should be kept in mind that serious AEs may take place in fetuses and that tachyarrhythmias may recur within the first 2 weeks after birth.

The severity of the hemolytic disease of the fetus and newborn (HDFN) due to Jra mismatch ranges from no symptoms to severe anemia that requires intrauterine and exchange transfusions. We encountered a newborn, born to a healthy mother having anti-Jra at 38 weeks of pregnancy, who had moderate anemia, a positive direct antiglobulin test (DAT) result, no increased erythropoiesis, and no jaundice at birth. Flow cytometry revealed that the Jra antigen of red cells in the infant was nearly negative at birth, biphasic at 5 weeks, and lowly expressed at 7 months of life. We searched online for previous case reports on HDFN due to Jra incompatibility. Among 63 reported cases, excluding 25 cases, 38 were included with the present case for analysis. Of 39 newborns, 10 developed clear anemia (hemoglobin

To predict the prognosis of infants with congenital heart disease, accurate prenatal diagnosis of structural abnormality and heart failure are both necessary. The aim of this study was to investigate whether cardiovascular profile (CVP) and biophysical profile (BP) scores are useful for predicting prognosis in infants with congenital heart defect (CHD).A retrospective review of singletons prenatally diagnosed with CHD at a tertiary pediatric cardiac center between 2011 and 2015 was undertaken.A total of 202 patients with CHD were analyzed. Perinatal and infant deaths occurred in 16 (7.9%) and 10 cases (5.0%), respectively. Infants with the last CVP score ≤ 5 had 18.7-fold higher perinatal mortality than those with a last CVP score 5 (P 0.01). Infants with a last BP score ≤ 6 had 18.7-fold higher perinatal mortality than those with a last BP score 6 (P 0.01). Infants with a CVP score decrease in utero had 4.5-fold higher infant mortality than those with an increase or no change (P 0.01). Multivariate analysis showed that single-ventricle physiology, pre-term birth at37 weeks of gestation, last CVP score ≤ 5, and last BP score ≤ 6 were independent predictors of perinatal mortality. Single-ventricle physiology and a CVP score decrease were independent predictors of infant mortality.CVP and BP scores are useful for predicting perinatal prognosis in infants with CHD. A CVP score decrease in utero is associated with infant mortality, suggesting that serial CVP score assessment may be useful for management planning.

Objective: The goal of the study was to clarify the risk factors for pregnancy complicated with Eisenmenger syndrome (ES). Materials and methods: A retrospective study was performed in 15 patients with ES who were managed throughout pregnancy at one institution from 1982 to 2013. Cases associated with congenital heart diseases other than atrial septal defect (ASD), ventricular septal defect (VSD), and patent ductus arteriosus (PDA) were excluded. Results: The congenital heart diseases in ES included ASD (n = 3), VSD (n = 9), and PDA (n = 3). Ten women chose termination and 5 continued with their pregnancies. In the 5 continuation cases (PDA 1, VSD 4), worsening of cyanosis, exertional fatigue and dyspnea appeared between 25 and 30 weeks gestation and cesarean section was performed at 30 (28–33) weeks. LVEF, PaO2, and SpO2 decreased and heart rate increased significantly from before pregnancy to 25–30 weeks gestation. From before to during the pregnancy, there were no significant changes in mean PABP or pulmonary vascular resistance (PVR) in four cases with data (582–592, 885 to 868, 1280 to 1291, 1476–1522 dyn × s/cm2). PVR at conception had a negative relationship with delivery weeks. NYHA classes before, during and 1 year after pregnancy were II, III and II. In one recent case, epoprostenol and tadalafil were administered during pregnancy. Conclusions: Pregnancy with ES has a high risk due to hypooxygenation, cyanosis, and cardiac failure, which can appear as common complications as early as the 2nd trimester. Early interventions with meticulous care are required for these complications during pregnancy and delivery. Keywords: Cardiac failure, Cyanosis, Eisenmenger syndrome, Pregnancy

Arterial switch operation (ASO) for dextro-transposition of the great arteries (d-TGA) has gradually replaced the atrial switch operation and has become the standard operation. To date, the outcomes of pregnant women with d-TGA after this new operation have not been investigated. In this study, we investigated the impact of ASO on pregnant outcomes and mid-term prognosis in women with d-TGA and compared with the atrial switch operation through the literature review.There were 20 pregnancies in 10 women with d-TGA after ASO and 6 resulted in abortion. Among 14 successful pregnancies in 10 women, 11 pregnancies achieved the term delivery and 3 pregnancies, including 1 twin pregnancy, resulted in preterm labor. Maternal cardiovascular events occurred in 4 (heart failure and arrhythmias in 3 and arrhythmia in 1), and all were controllable with medications. Risk factors for the peripartum cardiac events were older age at ASO and delivery, and higher concentration of brain natriuretic peptide (BNP) at first trimester (p0.05). In 7-60 month-follow-up after delivery, no case showed deterioration of functional class and systemic ventricular function. According to the literature review, women after ASO demonstrated a better prognosis than those after the atrial switch operation.The majority of women with d-TGA after ASO tolerated pregnancy and delivery well. The older age at ASO, an elderly pregnancy, and higher BNP levels at the first trimester were possibly risk factors of peripartum cardiovascular events among the group. The literature reviews and this study may indicate the advantage of systemic left ventricle compared with systemic right ventricle in long-term outcomes after delivery.

Myotonic dystrophy is an autosomal-dominant disorder. Its congenital type is the most severe form, with respiratory failure that can be a life-threatening event after birth. There are no antenatal treatments that can improve neonatal outcomes of myotonic dystrophy. We treated a fetus with congenital myotonic dystrophy by administering indomethacin to the 31-year-old Japanese mother affected by myotonic dystrophy and polyhydramnios. We observed increased fetal breathing movement and a reduction of the amniotic fluid volume. The baby was born at 37 weeks and discharged from the neonatal intensive care unit with a favorable outcome. Indomethacin treatment is likely to improve fetal lung function and to control the amniotic fluid volume. This report emphasizes the importance of further investigations regarding the optimal management of congenital myotonic dystrophy.

Purpose: We conducted a questionnaire survey in 15 pediatric oncology hospitals in Japan to better understand the current status of fertility preservation in childhood and adolescents. Methods: The survey period was from September 2020 to December 2020. We mailed questionnaires to 64 departments involved in pediatric cancer treatments at the 15 hospitals. The primary outcomes were the timing of providing explanations on fertility preservation, presence of health care provider while providing explanations, cooperation between medical staff, and cooperation between hospitals. Results: The response rate was 100% (64/64). Regarding the time at which this information was provided, 79.6% of patients (43/54) received it before cancer treatment; 5.6% (3/54), after remission; and 14.8% (8/54), both time points. Nurses were mostly in attendance (70%) when oncologists provided information to patients. Nine (60%) hospitals did not have a reproductive department. Among these, 28.6% of the respondents referred patients to a reproductive facility that performed fertility preservation. Providing information about fertility preservation was challenging owing to the shortage of specific explanatory materials (35.1%) and the lack of cooperation between pediatric oncologists and reproductive endocrinologists (24.6%). Conclusion: Based on this survey, educational activities regarding fertility preservation centered on pediatric oncologists and nurses are needed. Furthermore, a system for providing explanatory materials for fertility preservation and encouraging cooperation at the physician and hospital levels is also needed (IRB No. H2020-111).

Sudden unexpected death in epilepsy (SUDEP) is defined as the sudden death of a patient with epilepsy in the absence of an anatomic or toxicologic cause. Whether pregnancy is a risk factor for SUDEP is unclear. Using data submitted to the Japan Association of Obstetricians and Gynecologists (JAOG), which has been collating information regarding all maternal deaths in Japan since 2000, this study evaluated maternal mortality data from 2010 to 2019 to evaluate the current circumstances of maternal death related to SUDEP in Japan. Six women died due to SUDEP during this period, the maternal mortality rate related to SUDEP was 0.066/100,000 individuals. Two women each died during the second trimester, third trimester, and postpartum period. Four and two women were receiving monotherapy and no therapy with anti-epileptic drugs, respectively. The duration of epilepsy was ≤15 years in three women, &gt, 15 years in one woman, and unknown in two women. This study furthers our understanding of the prevalence of maternal deaths due to SUDEP in Japan. Further studies are needed to confirm whether pregnancy is a risk factor for SUDEP.

Background The aim of the present study was to clarify the evolution of the fetal heart rate (FHR) patterns in infants with cerebral palsy (CP) according to each type of umbilical cord trouble. Methods A case-control study was attempted in the subjects born from 2009 to 2014 and those with a birth weight of > 2000 g, gestational age of > 33 weeks, and disability due to CP, CP associated with (126 cases) and without (594 controls) umbilical cord troubles were compared. Results Therty-two were umbilical cord prolapse and 94 were other umbilical cord troubles coexisting antenatally. Abnormal FHR patterns had already been identified on admission in 13% of cases with umbilical cord prolapse and 40% of cases with cord trouble coexisting antenatally. A persistent non-reassuring pattern was significantly frequent in cases with cord trouble coexisting antenatally (p = 0.012) and less frequent in cases with umbilical cord prolapse (p = 0.003). Reactive-PD was significantly identified in 69% of the cases with umbilical cord prolapse and 35% of the cases with cord trouble coexisting antenatally, especially in the first stage of labor (p

BACKGROUND/AIM A higher number of neoadjuvant chemotherapy (NACT) cycles translate to a lower risk of morbidity and mortality, but few studies have analyzed the prognostic impact of >4 cycles of NACT. PATIENTS AND METHODS Overall, 52 patients [31 patients, NACT plus interval debulking surgery (IDS); 21 patients, NACT alone owing to progressive disease] who underwent NACT between January 2008 and December 2014 were evaluated. RESULTS In total, 6, 7-10, and 11-18 cycles of NACT were performed in 52.3%, 27.3%, and 20.5% of the patients, respectively. The median overall survival was 76.0 months (range=36.0-94.0 months), and the median progression-free survival was 26.0 months (range=18.0-54.0 months) in the NACT plus IDS group. CONCLUSION At least six cycles of NACT plus IDS are associated with a lower rate of multi-organ resection and a high rate of complete resection or optimal (

Background/aim This study aimed to compare laparoscopy with laparotomy and evaluate the effectiveness of a laparoscopic combined retroperitoneal and transperitoneal approach for para-aortic lymphadenectomy in patients with endometrial cancer. Patients and methods In this single-center retrospective study, patients with endometrial cancer who underwent para-aortic lymphadenectomy between December 2016 and November 2019 were analyzed. The patient's clinical and pathologic data were procured from medical records. Statistical analyses were performed using Fisher's exact and the Mann-Whitney U-tests. Results A total of 37 and 28 patients were included in the laparoscopic and laparotomy groups, respectively. The laparoscopic group had similar operative time, similar number of resected para-aortic and pelvic lymph nodes, less intraoperative blood loss and complications, lower rate of blood transfusion, and shorter postoperative stay than the laparotomy group. Conclusion Laparoscopic combined retroperitoneal and transperitoneal approach for endometrial cancer is safe and effective compared to laparotomy.

Fetal heart rate variability (FHRV) is a key index of antenatal and intrapartum fetal well-being. FHRV is well established to be mediated by both arms of the autonomic nervous system, but it remains unknown whether higher centers in the forebrain contribute to FHRV. We tested the hypothesis that selective forebrain ischemia would impair the generation of FHRV. Sixteen chronically instrumented near-term fetal sheep were subjected to either forebrain ischemia induced by bilateral carotid occlusion or sham-ischemia for 30 min. Time, frequency, and nonlinear measures of FHRV were assessed during and for seven days after ischemia. Ischemia was associated with profound suppression of electroencephalographic (EEG) power, which remained suppressed throughout the recovery period ( P < 0.001). During the first 5 min of ischemia, multiple time and frequency domain measures were increased (all P < 0.05) before returning back to sham levels. A delayed increase in sample entropy was observed during ischemia ( P < 0.05). For the first 3 h after ischemia, there was moderate suppression of two measures of FHRV (very-low frequency power and the standard deviation of RR-intervals, both P < 0.05) and increased sample entropy ( P < 0.05). Thereafter, all measures of FHRV returned to control levels. In conclusion, profound forebrain ischemia sufficient to lead to severe neural injury had only transient effect on multiple measures of FHRV. These findings suggest that the forebrain makes a limited contribution to FHRV. FHRV therefore primarily originates in the hindbrain and is unlikely to provide meaningful information on forebrain neurodevelopment or metabolism.

Aim The number of maternal deaths due to pregnancy-associated hemorrhagic stroke has not decreased despite a gradual decrease of maternal death in Japan. This study aimed to clarify the risk factors of hypertensive disorders of pregnancy-associated hemorrhagic stroke. Methods This retrospective study analyzed pregnancy-associated hemorrhagic stroke patients with hypertensive disorders of pregnancy between 2013 and 2017 among 407 Japanese maternal and perinatal centers. Patients were divided into good or poor outcome groups and their maternal backgrounds and neonatal prognoses were compared. Results We analyzed 61 cases, including 41 survival and 20 death cases, obtained from a secondary survey. Among the 61 hemorrhagic stroke cases, 62% were related to hypertensive disorders. Hypertensive disorders of pregnancy were observed in 75% of death cases. Use of MgSO4 or antihypertensive medication did not differ between the poor and good outcomes groups. In cases with antepartum onset of hypertensive disorders of pregnancy, outcomes were poor in 12 and good in 6 cases. Nine patients with poor outcomes and one with a good outcome had hypertension at the outpatient department without systemic evaluation (p = 0.043). Six poor outcomes patients and one good outcome spent more than 1 day from diagnosis at an outpatient clinic. Neurosurgery was performed in 11 poor outcome patients. Conclusion Pregnant women who present with a hypertensive disorder at an outpatient clinic probably need to undergo blood tests and careful observation. Delayed systemic evaluation and intensive care for only a few days may result in the development of hemorrhage.

Objective: Investigate the characteristics and serology of pregnant women with cytomegalovirus (CMV) immunoglobulin (Ig)G seroconversion during pregnancy to understand the risk factors associated with primary CMV infection and the occurrence of fetal congenital CMV infection. Materials and methods: We retrospectively studied 3202 pregnant women who were CMV IgG-negative in early pregnancy and were retested for IgG in late pregnancy. Characteristics were compared between participants with and without IgG seroconversion, and serological parameters were compared between participants with and without fetal congenital CMV infection. Results: Twenty-six participants showed CMV IgG seroconversion and fifteen showed fetal congenital CMV infection. Seroconversion rates were significantly higher in teens (5.0%) than in older women (20s: 0.8%; 30s and over: 0.6%) (p

Aim This study aimed to characterize the incidence and clinical significance of pregnancy-related aortic dissection using a large-scale survey in Japan. Methods A questionnaire requesting the detailed information included in the clinical charts of pregnancy-related aortic dissection cases (without any personally identifying information) was designed between 2013 and 2017 and administered to 407 perinatal centers in Japan. The response rate was 70.5%. Seventeen cases of pregnancy-related aortic dissection were identified. Results Maternal death due to aortic dissection was observed in nine patients (56.2%) while seven survived (43.8%). Dissection occurred during the postpartum period in 10 cases (62.5%), the third trimester in 4 (25.0%), labor in 1 (6.2%), and the second trimester in 1 (6.2%). The most common underlying diseases were: Marfan syndrome (25.0%), Loeys-Dietz syndrome (6.2%), hypertension (6.2%), and Takayasu aortitis (6.2%). Stanford type A aortic dissection was associated with maternal death during both pregnancy and the postpartum period. However, deceased patients showed lower rates of pre-diagnosed connective tissue disease than did survivors. Conclusions The mortality rate of aortic dissection that occurred during pregnancy or postnatal periods was more than 50%. Aortic dissection occurred more frequently in the postnatal period than during pregnancy, and less frequently in women previously diagnosed with connective tissue disease than in women without any medical history of aortic disorders. If symptoms suggestive of aortic dissection, such as severe back pain, are observed, even after the end of pregnancy, exhaustive diagnostic examinations should be carried out.

The aim of this study is to analyze whether soluble fms-like tyrosine kinase-1 (sFlt-1) can be correlated with the severity of PE.This study was conducted in a single hospital and is a prospective, observational study. sFlt-1 was measured at the diagnosis of preeclampsia. The period from diagnosis to pregnancy termination (pregnancy prolongation periods) was defined as the barometer for the severity of PE. The correlations between sFlt-1 level with pregnancy prolongation periods were then analyzed.Eighteen pregnant women diagnosed with early-onset preeclampsia were recruited. sFlit-1 value significantly negatively correlated with the pregnancy prolongation period from diagnosis (sFlt-1 was correlated with the pregnancy prolongation periods after onset of PE. sFlt-1 in early-onset PE may reflect the severity of PE in pregnant women.

A nationwide questionnaire survey about community-acquired infection of coronavirus disease 2019 (COVID-19) was conducted in July 2020 to identify the characteristics of and measures taken by Japanese medical facilities providing maternity services. A case-control study was conducted by including medical facilities with (Cases) and without (Control) community-acquired infection of COVID-19. Responses from 711 hospitals and 707 private clinics were assessed (72% of all hospital and 59% all private clinics provided maternity service in Japan). Seventy-five COVID-19-positive pregnant women were treated in 52 facilities. Community-acquired infection was reported in 4.1% of the facilities. Of these, 95% occurred in the hospital. Nine patients developed a community-acquired infection in the maternity ward or obstetric department. Variables that associated with community-acquired infection of COVID-19 (adjusted odds ratio [95% confidence interval]) were found to be state of emergency prefecture (4.93 [2.17–11.16]), PCR test for SARS-CoV-2 on admission (2.88 [1.59–5.24]), and facility that cannot treat COVID-19 positive patients (0.34 [0.14–0.82]). In conclusion, community-acquired infection is likely to occur in large hospitals that treat a higher number of patients than private clinics do, regardless of the preventive measures used.

The medical comorbidities including skin diseases are associated with male infertility. The most common cause of male infertility is the inability of testes to produce sperm, however, the influence of persistent dermatitis on testicular function has not been elucidated so far. We investigated the relationship between skin inflammation and impaired sperm production using a spontaneous dermatitis mouse model. We examined the breeding records of dermatitis mice and their wild-type littermates. Sperm count, motility, and viability were analyzed by direct microscopic observation and flow cytometry. In addition, testis and epididymis were histologically examined. Finally, sperm viability was evaluated in another dermatitis mouse model and in wild-type mice in which inflammatory cytokines were intraperitoneally administered. Compared to wild-type littermate mice, the number of children born was lower in mice with dermatitis. The body weight and testis size were decreased age-dependently. In the skin disease group, the sperm count and movement ratio were clearly decreased, and reduced sperm viability was observed. Histological examination revealed the detachment of Sertoli cells and reduced spermatogenesis. The fibrosis of epididymal stroma was severe, and it might affect defective sperm maturation in the epididymis. In addition, this phenomena was reproduced by a hapten applied dermatitis mouse model and the intraperitoneal administration of inflammatory cytokines. Once the skin is inflamed, inflammatory cytokines are produced and released, which may affect testicular and sperm function. Additional studies are needed to determine the relationship between male infertility and severe dermatitis in human.

Our study aimed to evaluate a prognostic value of early changes in apparent diffusion coefficients (ADC) and tumor volume during treatment in patients with cervical cancer treated with chemoradiotherapy or radiotherapy, and to assess whether the early changes provided an incremental value to pre-treatment ADC and tumor volume in predicting disease recurrences.A total of 103 patients with stage IB-IVA cervical cancer including 76 (74%) patients with stage ≥IIIA who underwent magnetic resonance imaging before and during (25 ± 4.6 days after start) the treatment were enrolled. Eighty-one patients received chemoradiotherapy and the remaining 22 had radiotherapy. Both a volumetric ADC and volume of a tumor before and during treatment were measured. %ADC increase and %Volume reduction were defined as changes in the ADCs and tumor volume before and during treatment, respectively.During a median follow-up of 2.7 years, 42 (41%) patients had disease recurrences. Univariate Cox regression analysis revealed that pre-treatment ADC (Hazard ratio [HR] = 2.8; p = 0.002), %ADC increase (HR = 6.8; p 0.001), and %Volume reduction (HR = 2.7; p = 0.003) were significant predictors for disease recurrences. On multivariate analysis, %ADC increase was the only independent predictor (adjusted HR = 5.2; p 0.001) for disease recurrences when adjusted for %Volume reduction and pre-treatment ADC. Global chi-square analysis demonstrated that %ADC increase and %Volume reduction had an additional prognostic value over pre-treatment ADC and tumor volume (p 0.05). Kaplan-Meier curve analysis showed that both smaller %ADC increase and %Volume reduction were associated with worse prognosis in disease-free survival (log-rank, p 0.001 and p = 0.002, respectively).Among patients with cervical cancer treated with chemoradiotherapy or radiotherapy, early changes in tumor ADCs and tumor volume during treatment are associated with better prognosis. %ADC increase and %Volume reduction during the treatment have an additional prognostic value for predicting tumor recurrence to pre-treatment ADC and tumor volume.

Severe neonatal gastrointestinal diseases such as necrotizing enterocolitis or spontaneous intestinal perforation are potentially lethal conditions which predominantly occur in preterm infants. Cytomegalovirus (CMV), which is known to cause congenital and acquired infections in the newborns, has also been implicated in such severe gastrointestinal diseases in premature infants. However, the pathogenic role of CMV and effect of antiviral therapy in severe gastrointestinal disease in premature neonates is currently unclear. We present an infant, born at 26-weeks' gestation, presented with progressive dyspepsia and abdominal distention after the closure of the symptomatic patent ductus arteriosus at the day of life (DOL) 4, requiring the emergent surgery for ileal perforation at the DOL8. After the surgery, abdominal symptoms persisted and the second emergent surgery was performed for the recurrent ileal perforation at DOL17. Even then the abdominal symptoms prolonged and pathological examination in the affected intestine at the second surgery showed CMV inclusion body. Immunoreactivity for CMV antigen was detected in the specimen at the first surgery on DOL8. Blood and urinary CMV-DNA were detected at DOL28. CMV-DNA was also detected in the dried umbilical cord which was obtained within a week from birth. A 6-week course of intravenous ganciclovir (12 mg/kg/day) was started at DOL34 and then symptoms resolved along with decreasing blood CMV-DNA. Pathological findings characteristic of CMV were not detected in the resection specimen at the ileostomy closure at DOL94. These observations indicate that anti-CMV therapy may be beneficial for some premature infants with severe CMV-associated gastrointestinal diseases and warrants further studies focusing on pathogenic role, diagnosis, treatment and prevention of this underrecognized etiology of severe gastrointestinal diseases particularly in premature neonates.

Objective To evaluate timing and a prediction model for pregnancy in early-stage cervical cancer patients who underwent fertility-sparing trachelectomy. Design Retrospective cohort. Setting Academic multicenter. Patient(s) Women ages Intervention(s) Planned fertility-sparing trachelectomy. Main Outcome Measure(s) Cumulative incidences and clinicopathological characteristics of those who developed subsequent pregnancy were examined. Result(s) There were 77 (21.6%) women who had subsequent pregnancies after fertility-sparing trachelectomy with 1-, 2-, and 5-year cumulative pregnancy rates of 2.8%, 6.2%, and 17.4%, respectively. The median time to develop subsequent pregnancy was 3.2 years. In a competing risk analysis, women had a higher risk of recurrent cancer than conception during the first 11 months postsurgery. On multivariable analysis, younger age, being married, and postoperative reproductive treatment were independently associated with an increased chance of developing a subsequent pregnancy. The subsequent pregnancy index (SPI) score to predict the likelihood of having pregnancy was proposed, and it was calculated based on age, marital status, and reproductive treatment (2, 2, and 4 points, respectively). Women with a higher SPI score had significantly higher subsequent pregnancy rates (5-year pregnancy rate; the score was 3 in 4.7% of cases; 4 to 5 in 11.3%; 6 to 7 in 27.4%; and 8 in 50.8%), but they had similar recurrence rates (5.0%). Conclusion(s) The SPI score proposed in our study is useful in predicting subsequent pregnancy in women with early-stage cervical cancer undergoing fertility-sparing trachelectomy.

Objective Cardiovascular disease increases the risk of maternal mortality. This study examined the risk factors for cardiovascular events in pregnant women with cardiovascular disease. Methods This was a case-control study conducted in 2 phases at Japanese maternal and fetal care centers. The primary survey, using an interviewer-administered questionnaire, investigated whether the institutions had managed pregnant women with cardiovascular disease from April 2014 to March 2016. From 424 individual facilities surveyed, 135 facilities were found to have experience in managing pregnant women. In the secondary survey, the 135 institutions were asked to complete a web-based questionnaire, which collected detailed clinical information about cases, including cardiovascular disease, cardiovascular events, maternal background, and the perinatal outcome. Results Information on 302 pregnant women with cardiovascular disease was collected. None of the 302 patients died. There were 25 women with cardiovascular events (cardiovascular event group) and 277 women without cardiovascular events (non-cardiovascular event group); the two groups were compared. No significant differences were found in the perinatal outcomes. Medication use before pregnancy was identified as a risk factor for cardiovascular events (adjusted odds ratio, 23.28; 95% confidence interval, 8.15-66.47; pI were risk factors for cardiovascular events in pregnant women with cardiovascular disease.

To assess the long-term effects of tadalafil, a therapeutic agent for fetal growth restriction (FGR), we evaluated the developmental progress of 1.5-year-old infants whose mothers had taken tadalafil during pregnancy. Twenty-four infants were assessed. We evaluated infant body weight, height, and head circumference, and performed the Kyoto Scale of Psychological Development (KSPD) test, a standardized developmental assessment covering Postural&ndash, Motor (P&ndash, M), Cognitive&ndash, Adaptive (C&ndash, A), and Language-Social (L&ndash, S) functions. The sum score was converted to a developmental quotient (DQ). The mean gestational week of the included cases was 36.1 (29&ndash, 39) weeks, and the mean birth weight was 1841 (874&ndash, 2646) g. Twenty-one and 20 out of the 24 cases, respectively, attained body weight and height similar to those of age-matched normal infants (within the 3rd percentile), all cases caught up in head circumference. KSPD was performed for 18 cases at 1.5 years of corrected age. The mean DQ scores were 87 (in total): 82 in P&ndash, M, 90 in C&ndash, A, and 88 in L&ndash, S. The total DQ score in one case (5.6%) was less than 70, and ranged from 70 to 85 in five cases (27.7%), and was more than 85 in 11 cases (61.1%). The growth and development of infants born of tadalafil-treated mothers seem to show good progress at a corrected age of 1.5 years.

We have demonstrated that tadalafil facilitates fetal growth in mice with L-NG-nitroarginine methyl ester (L-NAME)-induced preeclampsia (PE) with fetal growth restriction (FGR). Tadalafil is a selective phosphodiesterase 5 inhibitor that dilates the maternal blood sinuses in the placenta, thereby facilitating the growth of the fetus. The purpose of this study was to investigate the effects of tadalafil treatment for PE and FGR on the developing brain in FGR offspring using an L-NAME-induced mouse model of PE with FGR. A control group of dams received carboxymethylcellulose (CMC). L-NAME-treated groups received L-NAME dissolved in CMC from 11 days post coitum (d.p.c.). The L-NAME-treated dams were divided into two subgroups 14 d.p.c. One subgroup continued to receive L-NAME. The other subgroup received L-NAME with tadalafil suspended in CMC. Tadalafil treatment for PE with FGR reduced the expression of hypoxia-inducible factor-2α in the placenta and in the brain of the FGR fetus. Moreover, tadalafil treatment in utero shows improved synaptogenesis and myelination in FGR offspring on postnatal day 15 (P15) and P30. These results suggest that tadalafil treatment for PE with FGR not only facilitates fetal growth, but also has neuroprotective effects on the developing brain of FGR offspring through modulating prenatal hypoxic conditions.

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

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.