Predictive Indicators and Outcomes of Pregnancies Affected by Stage I Twin-Twin Transfusion Syndrome Treated With Fetoscopic Laser Photocoagulation.

OBJECTIVE: The significance of fetoscopic laser photocoagulation (FLP) in stage I twin-twin transfusion syndrome (TTTS) remains controversial. This study aimed to clarify the outcomes and prognostic factors of stage I TTTS after FLP. METHOD: We conducted a retrospective cohort study on patients with stage I TTTS who underwent FLP in Japan. The primary outcome was neonatal survival at 28 days. The adjusted odds ratios (aOR) of pre- and intraoperative factors for mortality in recipient and donor twins were calculated. RESULTS: This study included 272 twin pairs. The survival rate of at least one twin and both twins was 98% (267 pairs) and 85% (232 pairs), respectively. Survival of the recipient twin was observed in 253 cases (93%). No factor was associated with the mortality of the recipients. Among the donor twins, 246 (90%) survived. Preoperative twin anemia-polycythemia sequence (aOR, 17.45; 95% CI, 3.16-96.31) and arterio-arterial vascular anastomosis (AAA) identified at FLP (aOR, 2.78; 95% CI, 1.10-7.06) were independently associated with mortality of the donors. CONCLUSION: The neonatal survival rate for both recipient and donor twins was > 90% among patients with stage I TTTS who underwent FLP. AAA is a risk factor for mortality in donors following FLP, though the pathophysiology of AAA remains to be clarified.

Sensitive detection of hemodynamic changes after fetoscopic laser photocoagulation by assessing intraventricular pressure difference in fetuses with twin-to-twin transfusion syndrome.

OBJECTIVES: To assess the hemodynamics of twin-to-twin transfusion syndrome (TTTS), we measured the intraventricular pressure difference (IVPD), a sensitive marker of myocardial diastolic function, using fetal echocardiography. METHODS: We included 28 monochorionic diamniotic (MD) twins diagnosed with TTTS who underwent fetoscopic laser photocoagulation (FLP) between 2018 and 2022. Color M-mode Doppler images of both cardiac ventricles were obtained before and after FLP. According to this evaluation, the IVPDs were divided into three groups; those with total, basal, and mid-apical IVPD. RESULTS: Of the 28 twins, 21 were available for analysis (including eight, eight, three, and two cases in stages Quintero Ⅰ, Ⅱ, Ⅲd, and Ⅲr, respectively). Comparing the pre and postFLP results, significant increases in total and mid-apical IVPD in the left ventricle (LV) of recipient twins were noted (total and mid-apical IVPD: p=0.026 and 0.013, respectively). In the LV of the donor twins, all IVPDs were significantly increased after FLP (total, basal, and mid-apical IVPD: p=0.003, 0.001, and 0.022, respectively). In addition, comparisons between the donor and recipient groups did not show significant differences in either ventricle before FLP. CONCLUSIONS: IVPD detected subtle hemodynamics changes, such as volume overload and diastolic dysfunction in TTTS before and after FLP. Therefore, IVPD may be a useful marker for monitoring myocardial diastolic function in TTTS.

Intertwin discordance of aldosterone levels in amniotic fluid with placental anastomoses in monochorionic twins: Insight into the pathophysiology of twin-to-twin transfusion syndrome.

INTRODUCTION: Our objective was to investigate the association between the presence of placental anastomoses and intertwin differences in renin-angiotensin-aldosterone activation in monochorionic twins using amniotic fluid aldosterone (AF-ALD) levels. In addition, this study also examined the association between AF-ALD and the ALD levels in the umbilical cord blood (UCB-ALD) in monochorionic twins. MATERIAL AND METHODS: This prospective study included monochorionic diamniotic (MD) twin pregnancies that were not complicated by twin-to-twin transfusion syndrome (TTTS) at delivery. Amniotic fluid and umbilical cord vein blood samples were collected from each twin at delivery, and the ALD levels were measured subsequently. The MD twins were divided into two groups: those with placental anastomoses and those without anastomoses owing to fetoscopic laser surgery. The differences in the AF-ALD levels between the larger and smaller twins were analyzed. RESULTS: The AF-ALD levels showed a strong and significant positive correlation with UCB-ALD levels in 131 MD twins (r = 0.804, p < 0.001). Intertwin differences were examined in 41 and 28 pairs of MD twins with and without placental anastomoses, respectively. The AF-ALD levels in the smaller twins were significantly higher than those in the larger twins among the pairs of MD twins with placental anastomoses (p = 0.003); however, no statistically significant intertwin differences were observed among the twins without placental anastomoses (p > 0.05). CONCLUSIONS: The AF-ALD levels reflect the UCB-ALD levels in MD twins. The presence of placental anastomoses led to intertwin discordance in the ALD levels in MD twins even uncomplicated with TTTS. It was considered that monochorionic twins have this clinical background, and it leads to the development of TTTS.

Endometrial congestion is the only hysteroscopic finding indicative of chronic endometritis.

Chronic endometritis (CE), an inflammatory condition characterized by plasma cell infiltration within the endometrial stroma, is prevalent among women experiencing unexplained infertility or recurrent miscarriages. CE is traditionally diagnosed by endometrial biopsy using CD138 immunohistochemistry staining. Despite some studies suggesting hysteroscopy as an alternative diagnostic tool, its reliability compared with biopsy remains controversial. This study evaluated the diagnostic accuracy of hysteroscopy for CE by examining endometrial features, such as congestion, micropolyps, edema, and polyps, and comparing these with biopsy-confirmed cases of CE. This retrospective observational study was conducted at Toho University Omori Medical Center between June 2017 and November 2019 and included patients undergoing both hysteroscopy and histopathological examination. Endometrial congestion was identified as the only hysteroscopic finding significantly associated with CE, showing a moderate diagnostic agreement with biopsy results. These findings highlight the importance of further investigating hysteroscopic features of CE and their diagnostic implications and identify endometrial congestion as a potential predictive marker for CE.

Infection route associated with invasive group A streptococcal toxic shock syndrome in maternal deaths: Nationwide analysis of maternal mortalities in Japan.

OBJECTIVES: To clarify the infection route in maternal death due to invasive group A streptococcal (GAS) infection and toxic shock syndrome (TSS). METHODS: A retrospective study was conducted on maternal deaths due to GAS-TSS in Japan between January 2010 and March 2024. The final causal diagnosis of maternal death and the infection routes of GAS were analysed using medical records, laboratory data and autopsy findings. RESULTS: Among the 616 maternal deaths during the study period, 48 (8%) involved infectious diseases. The most common infection was invasive GAS (56%, n = 27), 21 (78%) and six cases occurred during the antepartum and puerperium periods, respectively. In the GAS-TSS group, 71% (15/21) infections were originated the upper respiratory tract. However, in the puerperium cases, 67% (4/6) were infected from the genital tract. In addition, no maternal deaths due to GAS-TSS were reported during the COVID-19 pandemic period in Japan from 2020 to 2023. CONCLUSION: Most antepartum GAS infections were from the upper respiratory tract. They may be reduced by preventive measures, including frequent disinfection, wearing masks and isolation from persons at high risk of carrying GAS, such as symptomatic children. On the other hand, GAS-TSS during puerperium infection via the genital tract.

The iPREFACE score is useful for predicting fetal acidemia: A retrospective cohort study of 113 patients who underwent emergency cesarean section for non-reassuring fetal status during labor.

BACKGROUND: The iPREFACE score may aid in predicting fetal acidemia and neonatal asphyxia in emergency cesarean and vaginal deliveries, which may improve labor management precision in the future. OBJECTIVE: This study aimed to assess the score use of the iPREFACE as an objective indicator of the need for rapid delivery in cases of repeated abnormal waveforms without concurrent indications for immediate medical intervention during labor. STUDY DESIGN: This retrospective cohort study was conducted among term (37+ 0 days to 41+6 days) singleton pregnant women who underwent emergency cesarean delivery owing to a nonreassuring fetal status. The integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring-decision of emergency cesarean delivery score, calculated from a 30-minute cardiotocography waveform before the decision to perform emergency cesarean delivery, and the integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring-removal of cardiotocography transducer score, calculated from a 30-minute cardiotocography waveform before cardiotocography transducer removal, were employed. The primary outcome was the assessment of the predictive ability of these scores for fetal acidemia, whereas the secondary outcomes were differences in umbilical artery blood gas findings and postnatal outcomes between the 2 groups, divided by the cutoff values of the integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring-removal of cardiotocography score. RESULTS: The integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring-decision of emergency cesarean delivery and integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring-removal of cardiotocography transducer scores demonstrated the capability to predict an umbilical artery blood pH of <7.2. The integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring-decision of emergency cesarean delivery and -removal of cardiotocography transducer score, with cutoff values of 37 and 46 points, respectively, exhibited an area under the receiver operating characteristic curve of 0.82 and 0.87, respectively. The integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring-removal of cardiotocography transducer group with ≥46 points had higher incidence rates of an umbilical cord artery blood pH of <7.2, <7.1, and <7.0 and neonatal intensive care unit admissions for neonatal asphyxia. CONCLUSION: The integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring, derived from cardiotocography during an emergency cesarean delivery, may enable clinicians to predict fetal acidemia in cases of nonreassuring fetal status. Improved prediction of fetal acidemia and facilitation of timely intervention hold promise for enhancing the outcomes of mothers and newborns during childbirth. Prospective studies are warranted to establish precise cutoff values and to validate the clinical application of these scores.

Relationship between maternal mortality and ritodrine hydrochloride as a tocolytic agent in Japan.

AIM: In Japan, unlike Western countries, tocolytic agents are administered in long-term protocols to treat threatened preterm labor. Evaluating the side effects of this practice is crucial. We examined whether ritodrine hydrochloride had been administered in cases of maternal death, aiming to investigate any relationship between ritodrine administration and maternal death. METHODS: This retrospective cohort study used reports of maternal deaths from multiple institutions in Japan between 2010 and 2020. Data on the reported cases were retrospectively analyzed, and data on the route of administration, administered dose, and clinical findings, including causes of maternal death, were extracted. The amount of tocolytic agents was compared between maternal deaths with ritodrine administration and those without. RESULTS: A total of 390 maternal deaths were reported to the Maternal Death Exploratory Committee in Japan during the study period. Ritodrine hydrochloride was administered in 32 of these cases. The frequencies (n) and median doses (range) of oral or intravenous ritodrine hydrochloride were 34.4% (11) and 945 (5-2100) mg and 84.4% (27) and 4032 (50-18 680) mg, respectively. Frequencies of perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema as causes of maternal death were significantly higher with ritodrine administration than without it. CONCLUSIONS: Our results suggest a relationship between long-term administration of ritodrine hydrochloride and an increased risk of maternal death due to perinatal cardiomyopathy, cerebral hemorrhage, diabetic ketoacidosis, and pulmonary edema. In cases where ritodrine should be administered to prevent preterm labor, careful management and monitoring of maternal symptoms are required.

Swim-up method is superior to density gradient centrifugation for preserving sperm DNA integrity during sperm processing.

Purpose: This study aimed to evaluate the effects of swim-up and density gradient centrifugation methods on sperm DNA fragmentation. Methods: Nineteen normozoospermic patient samples with ≥100 × 106 motile sperms were included in this study. Sperm DNA fragmentation, progressive motility, and progressive motile sperm number were measured before and after the swim-up method or density gradient centrifugation. Results: Sperm DNA fragmentation was not statistically different between swim-up-(14.4 ± 2.1%, p = 0.32) and density gradient centrifugation-processed (25.0 ± 3.0%, p = 0.20) and unprocessed semen samples (19.2 ± 1.9%). Sperm DNA fragmentation was significantly lower in swim-up-than in density gradient centrifugation-processed samples (p < 0.05). Sperm progressive motility was significantly higher (p < 0.05) in swim-up-(92.9 ± 1.0%) and density gradient centrifugation-processed (81.3 ± 2.0%) samples, with the former being higher, than in unprocessed semen samples (53.1 ± 3.7%). The recovery rate of progressive motile sperms was significantly lower in swim-up-(9.7 ± 1.4%) than in density gradient centrifugation-processed samples (17.2 ± 1.8%, p < 0.05). Conclusions: The swim-up method is superior to density gradient centrifugation, evidenced by less sperm DNA fragmentation and higher sperm progressive motility. The recovery rate of progressive motile sperms was better after density gradient centrifugation than after swim-up.

Effect of blastocyst shrinkage on assisted reproductive outcomes: a retrospective cohort study describing a new morphological evaluation of blastocyst pre-vitrification and post-warming.

BACKGROUND: The failure of frozen-thawed blastocysts to re-expand adequately within a few hours after warming has been reported to have a negative impact on assisted reproductive technology (ART) outcomes. However, the extent to which this failure truly affects ART outcomes has not yet been presented in a manner that is easily understandable to medical practitioners and patients. This study aimed to assess the effects of blastocyst shrinkage on ART outcomes and determine a more effective morphological evaluation approach for use in clinical settings. METHODS: This retrospective observational cohort study of frozen-thawed blastocyst transfer cycles was conducted from April 2017 to March 2022. Overall, 1,331 cycles were eligible for inclusion, of which 999 were good-quality blastocysts (GQB) and 332 were non-good-quality blastocysts (non-GQB). All frozen-thawed blastocyst transfer cycles performed during the specified study period were included in the study. Exclusion criteria were established to mitigate potential sources of bias as these cycles could impact implantations. We calculated rates and age-adjusted odds ratios of implantation, clinical pregnancy, ongoing pregnancy, and live birth of the re-expansion group, which showed sufficient expansion, and shrinkage group, which showed insufficient expansion. We also calculated the implantation, clinical pregnancy, ongoing pregnancy, and live birth rates of the re-expansion and shrinkage groups for each morphological scoring system parameter. RESULTS: A reduced ART outcome was observed with use of blastocysts with shrinkage after vitrification/warming. The age-adjusted odds ratios for implantation, clinical pregnancy, ongoing pregnancy, and live birth were lower in the shrinkage group than in the re-expansion group. CONCLUSIONS: This study examined the adverse effect of blastocyst shrinkage after warming and recovery culturing on reproductive outcomes in a clinically useful manner by retrospectively examining a substantial number of frozen-thawed embryo transfer cycles. The study findings can possibly reduce concerns regarding over- or under-estimation of blastocyst implantation by allowing providers and patients to refer to the data.

High maternal mortality rate associated with advanced maternal age in Japan.

This study aimed to clarify the relationship between maternal mortality and advanced maternal age in Japan and to provide useful information for future perinatal management. Maternal death rates by age group were investigated for all maternal deaths in Japan for an 11-year period, from 2010 to 2021. Maternal deaths among those aged ≥ 40 years were examined in detail to determine the cause, and the number of deaths by cause was calculated. The causes of onset of the most common causes of death were also investigated. The maternal mortality rates were 0.8 (95% confidence interval [CI] 0.3-4.7) for < 20 years, 2.6 (95% CI 1.7-3.8) for 20-24 years, 2.9 (95% CI 2.3-3.6) for 25-29 years, 3.9 (95% CI 3.3-4.5) for 30-34 years, 6.8 (95% CI 5.9-7.9) for 35-39 years, and 11.2 (95% CI 8.8-14.3) for ≥ 40 years of age. Patients who were ≥ 40 years of age had a significantly higher mortality rate compared to that in other age groups. Hemorrhagic stroke was the most common cause of death in patients aged ≥ 40 years (15/65 [23%]), and preeclampsia (8/15 [54%]) was the most common cause of hemorrhagic stroke. Maternal mortality is significantly higher in older than in younger pregnant women in Japan, with hemorrhagic stroke being the most common cause of maternal death among women > 40 years of age. More than half of hemorrhagic strokes are associated with hypertension disorder of pregnancy. These facts should be considered by women who become pregnant at an advanced age and by healthcare providers involved in their perinatal care.

Optimal timing to retrieve oocytes for fertility preservation in patients with acute myeloid leukemia: two cases of controlled ovarian stimulation using DuoStim with a literature review.

Fertility preservation (FP) for hematological malignancies is difficult because immediate chemotherapy is needed after diagnosis. We report two cases of acute myeloid leukemia (AML) treated with controlled ovarian stimulation (COS) and oocyte cryopreservation using DuoStim after first-line chemotherapy. In Cases 1 and 2, COS and oocyte retrieval (OR) were performed using DuoStim 116 and 51 days after first-line chemotherapy, respectively, and 14 and 6 unfertilized oocytes, respectively, were cryopreserved. Another round of COS and OR was performed using the random-start method 82 days after first-line chemotherapy, and 22 unfertilized oocytes were cryopreserved. DuoStim is useful to maximize OR for patients with a short interval for FP. Many oocytes can be retrieved depending on the timing of recruitment from primary to secondary follicles, although ovarian reserve capacity declines immediately after first-line chemotherapy. Aggressive FP should be performed before allogeneic hematopoietic stem cell transplantation becomes necessary.

COVID-19 mRNA vaccination status and concerns among pregnant women in Japan: a multicenter questionnaire survey.

BACKGROUND: mRNA vaccination is an effective, safe, and widespread strategy for protecting pregnant women against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, information on factors such as perinatal outcomes, safety, and coverage of mRNA vaccinations among pregnant women is limited in Japan. Therefore, this study aimed to investigate the perinatal outcomes, coverage, adverse effects, and short-term safety of mRNA vaccination as well as vaccine hesitancy among pregnant women. METHODS: We conducted a multicenter online survey of postpartum women who delivered their offspring at 15 institutions around Tokyo from October 2021 to March 2022. Postpartum women were divided into vaccinated and unvaccinated groups. Perinatal outcomes, COVID-19 prevalence, and disease severity were compared between the two groups. Adverse reactions in the vaccinated group and the reasons for being unvaccinated were also investigated retrospectively. RESULTS: A total of 1,051 eligible postpartum women were included. Of these, 834 (79.4%) had received an mRNA vaccine, while 217 (20.6%) had not, mainly due to concerns about the effect of vaccination on the fetus. Vaccination did not increase the incidence of adverse perinatal outcomes, including fetal morphological abnormalities. The vaccinated group demonstrated low COVID-19 morbidity and severity. In the vaccinated group, the preterm birth rate, cesarean section rate, and COVID-19 incidence were 7.2%, 33.2%, and 3.3%, respectively, compared with the 13.7%, 42.2%, and 7.8% in the unvaccinated group, respectively. Almost no serious adverse reactions were associated with vaccination. CONCLUSIONS: mRNA vaccines did not demonstrate any adverse effects pertaining to short-term perinatal outcomes and might have prevented SARS-CoV-2 infection or reduced COVID-19 severity. Concerns regarding the safety of the vaccine in relation to the fetus and the mother were the main reasons that prevented pregnant women from being vaccinated. To resolve concerns, it is necessary to conduct further research to confirm not only the short-term safety but also the long-term safety of mRNA vaccines.

Are There Maternal Deaths Related to Hemorrhagic Stroke Due to Hypertensive Disorder of Pregnancy That Could Be Potentially Preventable by Tight Hypertension Management in Antepartum? A Retrospective Study from the Maternal Death Exploratory Committee in Japan.

BACKGROUND: Unlike Europe and the United States, Japan has seen numerous maternal deaths from hemorrhagic strokes related to hypertensive disorders of pregnancy (HDP). This study retrospectively analyzed deaths associated with HDP-related hemorrhagic stroke in Japan to determine the number of deaths that may have been prevented with blood pressure control during pregnancy. METHODS: This study included maternal deaths related to hemorrhagic stroke cases. The proportion of patients without proteinuria whose blood pressure exceeded 140/90 mmHg between 14+0 and 33+6 weeks of gestation were determined. Lastly, the application of tight antihypertensive management was evaluated. RESULTS: Among 34 HDP-related maternal deaths, 4 cases involved patients without proteinuria whose blood pressures exceeded 140/90 mmHg between 14+0 and 33+6 weeks of gestation. These included two chronic hypertension and two gestational hypertension cases. None of the patients received antihypertensive agents, and their blood pressures were managed leniently. CONCLUSION: Among HDP-related hemorrhagic stroke deaths in Japan, only a few cases of maternal death could have been prevented with tight blood pressure management, as described in the CHIPS randomized controlled trial. Therefore, to prevent HDP-related hemorrhagic stroke in Japan, new preventive strategies during pregnancy should be established.

Pregnancy-related maternal deaths due to cardiovascular diseases in Japan from 2010 to 2019: an analysis of maternal death exploratory committee data.

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of maternal deaths in high-income countries. This study aimed to assess the characteristics of maternal deaths due to CVDs and the quality of care provided to patients, and to identify elements to improve maternal care in Japan. METHODS: This descriptive study used the maternal death registration data of the Maternal Deaths Exploratory Committee of Japan between 2010 and 2019. RESULTS: Of 445 eligible pregnancy-related maternal deaths, 44 (9.9%) were attributed to CVD. The most frequent cause was aortic dissection (18 patients, 40.9%), followed by peripartum cardiomyopathy (8 patients, 18.2%), and pulmonary hypertension (5 patients, 11.4%). In 31.8% of cases, cardiopulmonary arrest occurred within 30 min after initial symptoms. Frequent symptoms included pain (27.3%) and respiratory symptoms (27.3%), with 61.4% having initial symptoms during the prenatal period. 63.6% of the patients had known risk factors, with age ≥35 years (38.6％), hypertensive disorder (15.9%), and obesity (15.9%) being the most common. Quality of care was assessed as suboptimal in 16 (36.4%) patients. Cardiac risk assessment was insufficient in three patients with preexisting cardiac disease, while 13 patients had symptoms and risk factors warranting intensive monitoring and evaluation. CONCLUSION: Aortic dissection was the leading cause of maternal death due to CVDs. Obstetrics care providers need to be familiar with cardiac risk factors and clinical warning signs that may lead to impending fatal cardiac events. Timely risk assessment, patient awareness, and a multidisciplinary team approach are key to improving maternal care in Japan.

Different expressions of cardiac biomarkers between different types of acquired right ventricular outflow tract abnormality in monochorionic twins.

OBJECTIVE: To investigate the differences in amniotic fluid cardiac biomarkers and clinical features among types of right ventricular outflow tract (RVOT) abnormality in monochorionic (MC) twins. METHOD: This prospective study included MC twins that underwent laser surgery. Recipient or larger twins (group A) and donor or smaller twins (group B) were assessed and divided into those with a normal right ventricular outflow tract (normal RVOT), functional pulmonary atresia (fPA), or pulmonary stenosis (PS). Amniotic fluid levels of NT-proBNP (afNT-proBNP) and cardiac troponin T (afTnT) were examined during surgery. RESULTS: Of 190 fetuses in group A, there were 14 RVOT abnormality cases (including 7 fPA and 7 PS). No group B fetuses showed RVOT abnormality findings. In group A, later and earlier gestational age at surgery were observed in fPA (25.1 ± 2.8 weeks) and PS groups (17.8 ± 0.9 weeks). All survived PS cases demonstrated progressive pulmonary valve obstruction, not observed in fPA groups. AfNT-proBNP were significantly higher in fPA and PS than in the normal RVOT group (p < 0.05). AfTnT was significantly higher in group A with PS than fPA and normal RVOT groups (p < 0.05). CONCLUSION: Among RVOT abnormality types in group A, amniotic fluid cardiac biomarkers were differently expressed, and clinical features were also differentiated. These findings provide insight into the pathophysiological influence on RVOT in MC twins. CLINICAL TRIAL REGISTRATION: This study was registered with the Japanese Clinical Trial Registry "UMIN-CTR" (http://www.umin.ac.jp/ctr/index-j.htm; trial ID numbers UMIN000024486 and 000037702).

Association of amniotic fluid natriuretic peptide levels with ductus venosus Doppler flow in recipient twins with twin-to-twin transfusion syndrome : DV flow and NT-proBNP in TTTS recipient twins.

PURPOSE: This study examined the relationships between fetal quantitative Doppler parameters and amniotic fluid N-terminal prohormone brain natriuretic peptide (afNT-proBNP) levels as a biomarker of the increased cardiac load in recipient twins with twin-to-twin transfusion syndrome (TTTS). METHODS: This single-center, prospective study included all monochorionic diamniotic (MD) twin pregnancies that were diagnosed with TTTS and underwent fetoscopic laser surgery. Doppler flow was used to measure the pulsatility index (PI) of the umbilical artery (UA), ductus venosus (DV), and middle cerebral artery (MCA) of each recipient and donor twins. The afNT-proBNP levels of recipient twins were examined at the time of surgery. The Spearman or Pearson correlation coefficients were used to assess the relationships between afNT-proBNP levels and Doppler parameters. RESULTS: A total of 150 MD twin pregnancies were included. The afNT-proBNP levels of the recipient twins showed a stronger correlation with the DV-PI (r = 0.637; P < 0.001) of recipient twins than with the UA-PI and MCA-PI of recipient twins. The Doppler parameters of donor twins were scarcely correlated with the afNT-proBNP levels of the recipient twins. CONCLUSION: A positive correlation between the DV-PI and afNT-proBNP levels of recipient twins with TTTS was observed. The recipient twin with an increased DV-PI is expected to be under a high cardiac load; therefore, DV-PI is a useful parameter for assessing increased NT-proBNP levels consecutively and noninvasively. CLINICAL TRIAL REGISTRATION: This study was registered with Japanese Clinical Trial Registry "UMIN-CTR" ( http://www.umin.ac.jp/ctr/index-j.htm ; trial ID numbers UMIN000024486 and 000037702).

Optimal duration of cardiotocography assessment using the iPREFACE score to predict fetal acidemia.

Cardiotocography (CTG) applicability to improve fetal outcomes remains controversial. This study aimed to determine the clinically optimal CTG assessment duration using the integrated score index to predict fetal acidemia by intrapartum fetal heart rate monitoring (iPREFACE score). This single-center, retrospective observational study included 325 normal full-term singleton vaginal deliveries at the Toho University Omori Medical Center, from September 2018 to March 2019. The iPREFACE(10), iPREFACE(30), and iPREFACE(60) scores were calculated at 10, 30, and 60 min immediately before delivery. The primary outcome was fetal acidemia (umbilical artery blood pH < 7.2). The secondary outcome was the correlation between all iPREFACE scores and the umbilical artery blood pH, base excess (BE), and lactate values. Patients without accurate CTG findings or with failure of umbilical artery blood sampling immediately after birth were excluded, leaving 145 patients in the final analysis. Of these, 16, three, and two had umbilical artery blood pH of < 7.2, < 7.1, and < 7.0, respectively. All iPREFACE scores significantly correlated with umbilical artery blood pH, BE, and lactate values. iPREFACE(30) had the highest predictive capacity for fetal acidemia, suggesting that 30 min immediately before delivery may be a useful scoring time in clinical practice.

Time trend analysis of perinatal mortality, stillbirth, and early neonatal mortality of multiple pregnancies for each gestational week from the year 2000 to 2019: A population-based study in Japan.

Multiple pregnancies pose a high risk of morbidity and mortality in both mothers and infants; thus, obtaining reliable information based on a large population is essential to improve management. We used the maternal and child health statistics, which are published annually, from the database of the Ministry of Health, Labor, and Welfare. The data obtained were aggregated in 5-year intervals, and we used them to analyze the proportion of the number of births for each week of pregnancy to the total of each singleton and multiple pregnancy. For perinatal health indicators (perinatal mortality, stillbirth, and neonatal mortality), the obtained data were calculated and plotted on graphs for each week of pregnancy. Moreover, these indicators were calculated by dividing them into first twin and second twin fetuses. Stillbirth weights were aggregated in several groups, and a histogram was displayed. Between 2000 and 2019, there were 21,068,275 live births, 67,666 stillbirths, and 16,443 early neonatal deaths, excluding 7,148 (7,104 singletons, 44 multiple births) cases, in which the exact gestational weeks at birth were unknown. More than 95% of multiple pregnancies were twin births. Perinatal mortality, stillbirth, and early neonatal mortality rates in multiple pregnancies were the lowest at approximately 37 weeks of gestation and lower than those of single pregnancies at approximately 36 weeks of gestation. Perinatal mortality and stillbirth rates were higher during the delivery of the second twins than the first-born twins, but the early neonatal mortality rate remained approximately the same during the delivery of both twins. As the data in the government database are accumulated and published continuously, indicators can be calculated in the future using the method presented in this study. Further, our findings may be useful for policymaking related to managing multiple pregnancies.

Tadalafil treatment for fetuses with early-onset growth restriction: a protocol for a multicentre, randomised, placebo-controlled, double-blind phase II trial (TADAFER IIb).

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.