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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., (© 2024 Japan Society of Obstetrics and Gynecology.)

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., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: To clarify the necessity for and problems related to autopsy for determining the cause of maternal death in Japan., Methods: Women who died during pregnancy or within a year after delivery were analyzed by the Maternal Death Exploratory Committee between 2012 and 2015 in Japan. Maternal deaths were analyzed to verify the requirement of autopsy in cases in which autopsy was performed and the need for autopsy in cases in which it was not performed., Results: Among the 49 cases performed autopsy, the final diagnosis was compatible with the clinical course in 24 cases, while the autopsy diagnosis was incompatible with the clinical course in 13 cases. In two cases, the final diagnosis was based on the clinical course, but an autopsy could exclude other possible causes. In three cases, no exact cause of maternal death was identified after autopsy. On the other hand, in cases without an autopsy, the final diagnosis was made using ante-mortem operating findings and surgical specimens in twenty-one cases. Though, thirty-one cases were estimated diagnosis based on post-mortem imaging or ante-mortem examinations, the exact original cause of death was not determined in 25 cases, and the cause of death could not be identified in eight cases without autopsy., Conclusion: Because in most cases the autopsy provides an exact cause of death, the necessity of autopsies should be more widely accepted in Japan.

Objective: To clarify the problems related to maternal deaths in Japan, including the diseases themselves, causes, treatments and the hospital or regional systems., Design: Descriptive study., Setting: Maternal death registration system established by the Japan Association of Obstetricians and Gynecologists (JAOG)., Participants: Women who died during pregnancy or within a year after delivery, from 2010 to 2014, throughout Japan (N=213)., Main Outcome Measures: The preventability and problems in each maternal death., Results: Maternal deaths were frequently caused by obstetric haemorrhage (23%), brain disease (16%), amniotic fluid embolism (12%), cardiovascular disease (8%) and pulmonary disease (8%). The Committee considered that it was impossible to prevent death in 51% of the cases, whereas they considered prevention in 26%, 15% and 7% of the cases to be slightly, moderately and highly possible, respectively. It was difficult to prevent maternal deaths due to amniotic fluid embolism and brain disease. In contrast, half of the deaths due to obstetric haemorrhage were considered preventable, because the peak duration between the initial symptoms and initial cardiopulmonary arrest was 1-3 h., Conclusions: A range of measures, including individual education and the construction of good relationships among regional hospitals, should be established in the near future, to improve primary care for patients with maternal haemorrhage and to save the lives of mothers in Japan., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: The aim of the present work was to understand the current circumstances of maternal-death-related venous thromboembolism (MD-VTE) in Japan. We retrospectively investigated the characteristics of cases of MD-VTE, and compared past and present rates of occurrence., Methods and Results: We examined the Japanese data for MD-VTE in 2010-2013, and compared it with that from 1991-1992. MD-VTE occurred in 17 women in 1991-1992, and in 13 women in 2010-2013. The maternal mortality ratio of MD-VTE was 0.7 per 100,000 in 1991-1992 and 0.4 per 100,000 in 2010-2013. Both the maternal mortality ratio and rate of MD-VTE in 2010-2013 deceased significantly compared with 1991-1992 (P<0.05). However, the number of cases of MD-VTE during pregnancy was 6 among 13 women (41%) in 2010-2013, but 1 in 17 women (6%) in 1991-1992, showing an increase (P<0.05). In the present study, cesarean delivery was more frequently associated with MD-VTE., Conclusions: MD-VTE overall has decreased within the past 20 years in Japan. But, MD-VTE during pregnancy in 2010-2013 increased relative to 1991-1992. Future guidelines for prevention of VTE may need to extend beyond the perioperative period to decrease the incidence of MD-VTE.

Aim: To clarify the cause of maternal deaths, an autopsy is essential. However, there has been no systemic analysis of maternal death in Japan based on autopsy cases., Material & Methods: Maternal death reports were retrieved from a large amount of registered autopsy data on maternal death in the series of 'Annual of pathological autopsy cases in Japan'. These files contain 468,015 autopsy records from 1989 to 2004. We collected 193 cases of maternal death due to direct obstetric causes. We recorded all the data into Excel files. Then we analyzed the causes of death and classified them into 11 categories., Results: The causes of maternal death were as follows: amniotic fluid embolism (AFE), 24.3%; disseminated intravascular coagulation (DIC) related to pregnancy-induced hypertension, 21.2%; pulmonary thromboembolism, 13.0%; injury to the birth canal, 11.4%; medical and surgical complications, 9.8%; and atonic bleeding or DIC of unknown cause, 8.3%. A discrepancy between the clinical diagnosis and pathological diagnosis was frequently observed in cases of AFE, septic DIC and injury to the birth canal. AFE diagnosed by autopsy was often clinically diagnosed as atonic bleeding or DIC of unknown cause before death. Half of the cases of AFE diagnosed by autopsy were associated with DIC., Conclusion: We found that AFE, DIC related to pregnancy-induced hypertension, pulmonary thromboembolism and injury to the birth canal were the major causes of maternal death in Japan. AFE had various clinical features such as uterine atony and DIC in addition to pulmonary cardiac collapse., (© 2010 The Authors. Journal of Obstetrics and Gynaecology Research © 2010 Japan Society of Obstetrics and Gynecology.)

Objective: The goal of this study is to find clues to improve perinatal outcomes in the case of cerebrovascular acute disorders during pregnancy.Study Design: 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.Results: 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, n = 15). In two of eight newborns, brain hypothermia therapy was given, and all survived without neurological sequelae. Maternal dyspnea was significantly related to severe prolonged decelerations of the fetus (p < .05), and asphyxia cases (p < .005). Median time from maternal onset to delivery (OD time) was significantly longer in asphyxia cases than in the non-asphyxia cases (84 vs 29 min, p < .05). OD time over 30 min was significantly related to the antepartum occurrence, cervical dilatation <5 cm (p < .05), onset outside of the hospital (p < .001), and maternal transfer before delivery (p < .001).Conclusion: 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. [ABSTRACT FROM AUTHOR]

Objective: We reviewed malignancy related maternal deaths in Japan to ascertain if there were avoidable factors.Methods: Malignancy-related maternal death in Japan reported to the Maternal Death Exploratory Committee, from 2010 to 2016 inclusive.Results: There were 12 cases of maternal death caused by malignancy. There were four gastric cancers (two poorly differentiated adenocarcinoma, one signet ring cell carcinoma with adenocarcinoma, one histology not available), 3 leukemia (two acute myeloid leukemia, one aggressive NK cell leukemia), two ureteral cancers (histology not available), one malignant lymphoma (diffuse large B-cell lymphoma with translocation), one brain tumor (gliomatosis cerebri), and one cervical cancer (glassy cell carcinoma). Two gastric cancer patients had chronic gastric pain before conception. In two cases the physicians commented that they had avoided computed tomography and the brain biopsy needed for diagnosis because the patient was pregnant. At diagnosis, the clinical stages were II-IV in 9, and the performance status was 3-5 in 8. Indication for delivery was exacerbated maternal condition in 5, for treatment in 3, spontaneous labor in 3, and one patient declined elective delivery. Median [interquartile rage] (range) gestational weeks of delivery was 29 [24-30] (19-40). One cervical cancer patient had a radical hysterectomy and chemotherapy for 10 months. However, three leukemia and one gastric cancer patients had chemotherapy within 10 d because they deteriorated rapidly. Another seven cases did not have any treatment because of poor general condition or because they remained undiagnosed. In all cases, the Committee considered that there was no evidence of substandard care.Conclusion: In these cases, both the clinical stages and biological degree of malignancy were high. In two-thirds of cases, early termination of the pregnancy was indicated because of deteriorating maternal condition. Chemotherapy was not effective because of short available time for therapy and the advanced stage of the cancers when diagnosed. Encouraging women to have a thorough medical assessment before conception, and early diagnosis and treatment before pregnancy, appears to be the only practical way to reduce deaths from malignancy while a woman is pregnant. [ABSTRACT FROM AUTHOR]

Aim: To investigate the influence of reproductive medicine in maternal death cases in Japan. Methods: This retrospective study investigated the incidence of maternal deaths related to reproductive medicine in Japan from 2013 to 2015, and the relationship between fertility treatment and maternal death. Results: Fifteen out of 134 women (11.2%) involved in this study who underwent treatment for infertility died. Four experienced pregnancy with severe maternal complications (26.6%). The complications were active systemic lupus erythematosus, exacerbated depression, uncontrolled arrhythmia and uncontrolled type 2 diabetes mellitus. At least three of these four died due to these complications. Conclusion: The maternal death rate of women who have undergone fertility treatment is similar to the birth rate due to assisted reproductive technology in Japan. Some maternal death cases involve severe uncontrolled complications. Therefore, medical histories should be evaluated before fertility treatment. [ABSTRACT FROM AUTHOR]

Objective: The number of stroke-related maternal deaths is increasing in Japan. We investigated methods to reduce maternal death from stroke.Methods: We analyzed stroke-related maternal deaths in Japan reported to the Committee of the Ministry of Health, Labor, and Welfare from 2010 to 2014 inclusive.Results: A total of 35 cases were identified. The median maternal age was 35 years (range 22-45) and the incidence of stoke in women ≥40 was seven-fold higher than in <34. Etiologies were pregnancy induced hypertension in 16, subarachnoid hemorrhage in seven, cerebral infarction in three, arteriovenous malformation in two, Moyamoya disease in one, and origin unknown cerebral hemorrhage in six. These cases occurred in antepartum 43%, in postpartum 31%, and in intrapartum 26%. 23 cases were deemed non-preventable and 12 cases preventable. Possible preventable factors occurred antepartum in 23, postpartum in seven, and intrapartum in six. Preventable features included inadequate hypertension control (33%), presenting too late for termination of pregnancy (14%), delayed hospitalization (11%), and delayed maternal transfer (11%).Conclusions: A total of 90% of strokes were hemorrhagic, and older mothers (≥ 40) were most at risk. Most possible preventable factors occurred antepartum, and improved control of hypertension and earlier termination would help to reduce maternal death from stroke. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the rate of coagulopathy progression in amniotic fluid embolism (AFE), using the level of fibrinogen.Methods: We examined all cases of maternal death (46 cases) related to AFE between 2010 and 2013 in Japan (total number of deliveries: 4,291,459). Fibrinogen, blood loss from AFE onset to fibrinogen measurement, and time from onset to fibrinogen measurement were investigated. The correlations of fibrinogen with time from onset to fibrinogen measurement and blood loss at fibrinogen measurement were analyzed.Results: Fibrinogen was undetectable (less than 50 mg/dL) in 14 cases (93%) and 65 mg/dL in one case (7%). All the cases involving not less than 1000 mL of blood loss or within 60 min from onset to fibrinogen measurement demonstrated low levels of fibrinogen.Conclusions: Coagulopathy in AFE was not directly proportional to bleeding. Furthermore, coagulopathy in AFE developed in a remarkably short length of time. If AFE is suspected, fibrinogen level should be measured rapidly for favoring a more AFE to decrease the risk of death from AFE. And, rapid treatment of coagulopathy can help reduce mortality from AFE. [ABSTRACT FROM AUTHOR]

Background and Aim Liver dysfunction with decreased antithrombin (AT) activity and/or thrombocytopenia is life threatening in pregnant women. Whether AT is clinically useful for prediction of liver dysfunction remains unclear. Methods A total of 541 women were registered prospectively at gestational week 34.7 (20.0-41.4) with available data on antenatal AT and platelet count (PLC). Results Liver dysfunction defined as serum aspartate aminotransferase > 45 IU/L concomitant with lactate dehydrogenase > 400 IU/L occurred in five women antenatally (≤ 2 weeks before delivery) and in 17 women post-partum (within 1 week post-partum). Median (5th-95th) antenatal value was 85 (62-110)% for AT and 202 (118-315) × 109/L for PLC in the 541 women and was significantly lower in women with than without perinatal liver dysfunction; 75 (51-108) versus 86 (62-110)% and 179 (56-244) versus 203 (121-316) × 109/L, respectively. Nineteen (86%) women with liver dysfunction showed AT ≤ 62% or thrombocytopenia (PLC ≤ 118 × 109/L) perinatally, but five lacked thrombocytopenia throughout the perinatal period. The best cut-off (AT, 77%; PLC, 139 × 109/L) suggested by receiver operating characteristic curve gave antenatal AT and PLC sensitivity of 59% and 41% with positive predictive value of 8.6% and 14%, respectively, and combined use of AT and PLC improved sensitivity to 73% (16/22) with positive predictive value of 9.2% for prediction of perinatal liver dysfunction. Conclusions Reduced AT not accompanied by thrombocytopenia can precede liver dysfunction. Clinical introduction of AT may enhance the safety of pregnant women. [ABSTRACT FROM AUTHOR]

Amniotic fluid embolism (AFE) is recognized as a type of syndrome characterized by the abrupt onset of hypoxia, hypotension, seizures, or disseminated intravascular coagulopathy (DIC), occurring during labor, delivery, or immediately postpartum, caused by the inflow of amniotic components into the maternal circulation. AFE is a rare condition but one of the most serious obstetrical complications, resulting in a high mortality rate among pregnant women. Despite earlier recognition and intensive critical management, we often encounter patients who unfortunately do not recover from the exacerbation of AFE-related conditions. A major concern is that there are no effective evidence-based therapies for AFE, because its pathophysiology is still not well understood. This article reviewed AFE, focusing on the pathology and currently proposed pathophysiology. [ABSTRACT FROM AUTHOR]

Aim The purpose of this study was to evaluate the possibility of establishing predictors of mortality in women with amniotic fluid embolism. Methods Our previous report identified eight factors associated with amniotic fluid embolism ( AFE) fatality: dyspnea, cardiac arrest, loss of consciousness, serum sialyl Tn greater than 47 U/mL, serum interleukin-8 greater than 100 pg/mL, vaginal delivery, multiparity and term delivery. The ratio of the number of positive fatal factors to the number of possible fatal factors in the same case was calculated as the abundance ratio, which was used because information regarding all eight factors was not retrievable for all the patients at the time of registration. The patient group was divided into four quartiles based on this abundance ratio, and the mortality rate in each quartile was compared with the overall mortality rate among the 130 patients with AFE enrolled between 1992 and 2006. The validity of this approach was confirmed in another dataset from a cohort of 38 patients with AFE in 2007. Results A statistically significant positive correlation was observed between the abundance ratio and the mortality in each quartile ( P < 0.01) for the patients with AFE enrolled between 1992 and 2006. This result was also found in the AFE patients enrolled in 2007 ( P < 0.05). Thus, an increased in the abundance ratio of the eight fatal factors resulted in an increased case fatality rate. Conclusion These data suggested that the abundance ratio of fatal factors may be a useful predictor of mortality and therefore may be expected to improve prognostic accuracy in the future. [ABSTRACT FROM AUTHOR]

The article discusses the result of studies which examined the causes of maternal death. It analyzes the pathology of atonic bleeding and amniotic fluid embolism to determine ways to prevent maternal death. The findings reveal that fibrinogen level decreases earlier than antithrombin and platelet during atonic bleeding.

Despite the decrease in maternal mortality rate, amniotic fluid embolism (AFE) is still one of the most feared complications of pregnancy due to the high rate of mortality in Japan. The authors present a fatal case of a healthy 39-year-old woman who died during delivery after a normal 40-week second pregnancy. Shortly after the arrival at hospital, an abrupt drop of foetal heart rate was observed, followed by deterioration of consciousness and cardiac arrest of the patient. Prompt cardiopulmonary resuscitation (CPR) was performed but the patient died about an hour and a half after her arrival at hospital. Forensic autopsy confirmed the pathohistological diagnosis of amniotic fluid embolism supported by histochemical analysis results and excluded other possible causes of death. This paper stresses the fundamental importance of autopsy in an unexpected maternal death in conjunction with the significance of data accumulation on maternal death. [ABSTRACT FROM AUTHOR]