Kazuhiro Osato

Current status of pregnancy-related maternal mortality in Japan: a report from the Maternal Death Exploratory Committee 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.

Increase in Maternal Death-Related Venous Thromboembolism During Pregnancy in Japan (2010–2013)

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.

Retrospective Review of Thoracoamniotic Shunting Using a Double-Basket Catheter for Fetal Chylothorax

Objective: From a single-center retrospective cohort with fetal chylothorax, we evaluated the factors related to the decision to use shunting, poor prognostic factors, and reported shunting outcomes with a new double basket-catheter device. Methods: A retrospective single-center study was performed in 35 cases of fetal chylothorax. Results: There were 35 cases of chylothorax: 23 with hydrops and 12 without hydrops. Twenty-one procedures were performed on 15 fetuses (11 with hydrops) with a single shunt in 11, two shunts in 3 and four shunts in 1. All 12 nonhydropic cases survived. In 23 hydropic cases, overall survival rates with and without thoracoamniotic shunting were 46 and 33%, respectively. The mortality rates of fetal hydropic cases with and without ascites were 93 and 11%, respectively. Fetal ascites, progression of fetal hydrops, and premature delivery at <33 weeks were significant risk factors for a poor prognosis. Progression of polyhydramnios after shunting was also associated with a poor prognosis. Obstruction of the catheter was observed in 38%. There were no direct fetal deaths associated with shunting. Conclusion: Thoracoamniotic shunting should be considered for pleural effusion before development of fetal hydrops, or at least before the appearance of fetal ascites. A double-basket catheter tends to be obstructive, but may be less invasive for fetuses.

Spontaneous uterine rupture in the 35th week of gestation after laparoscopic adenomyomectomy

Uterine rupture rarely occurs during pregnancy, but it is a critical situation if so. It is already known that a history of uterine surgeries, such as cesarean section or myomectomy, is a risk factor for uterine rupture. Currently, the laparoscopic adenomyomectomy is a widely performed procedure, but associated risks have not been defined. We observed a case of spontaneous uterine rupture in a patient during the 35th week of gestation, after a laparoscopic adenomyomectomy. A 42-year-old, gravida 2, para 0 woman became pregnant after a laparoscopic adenomyomectomy and her pregnancy was conventional. At a scheduled date in the 35th week of gestation, after combined spinal epidural anesthesia and frequent uterine contractions, a weak pain suddenly ensued. After 13 minutes of uterine contractions, vaginal bleeding was evident. A cesarean section was performed, and the uterine rupture was found in the scar. After a laparoscopic adenomyomectomy, a pregnant uterus can easily rupture by rather weak and short uterine contractions, and is characterized by vaginal bleeding. When uterine bleeding is observed in pregnant women that have a history of adenomyomectomy, one should consider uterine rupture.

Maternal Death Due to Stroke Associated With Pregnancy-Induced Hypertension.

BACKGROUND The aim of this study was to clarify the clinical features of maternal death due to stroke associated with pregnancy-induced hypertension (PIH) in Japan. METHODS AND RESULTS Reported maternal deaths occurring between 2010 and 2012 throughout Japan were analyzed by the Maternal Death Exploratory Committee. Among a total of 154 reports of maternal death, those due to stroke with (n=12) or without (n=13) PIH were compared. Cerebral stroke occurred more frequently in the third trimester and during the second stage of labor in deaths with PIH, whereas it occurred at any time point in deaths not involving PIH. Although 83% of patients with PIH who died had experienced initial symptoms in a hospital, more than half of them required maternal transport due to lack of medical resources. Among the patients without PIH, some vascular abnormalities were identified, but no evidence was found among the patients with PIH. In addition, 58% of PIH cases resulting in stroke were complicated by hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome. CONCLUSIONS Appropriate management of PIH during pregnancy and labor, including anti-hypertensive therapy and early maternal transport to tertiary hospital, may reduce the maternal death rate.

The increase in the rate of maternal deaths related to cardiovascular disease in Japan from 1991-1992 to 2010-2012

BACKGROUND Cardiovascular diseases (CVD), both genetic and acquired, increase the risk of maternal death (MD) unless proper genetic/clinical counseling is provided and a multidisciplinary approach is adopted during pregnancy. In recent decades, there has been a significant increase in the number of women with CVD of child-bearing age and in the incidence of pregnancy among relatively older women. However, the impact of this phenomenon on MD has not been carefully investigated. METHODS This retrospective study compares the incidence and etiology of maternal deaths related to cardiovascular disease (MD-CVD) in Japan in 2010-2012 to that seen in 1991-1992. RESULTS Seven cases of MD-CVD were reported in 1991-1992, compared to 15 in 2010-2012. In 2010-2012, the causes included aortic dissection (n=5), peripartum cardiomyopathy (n=3), sudden adult/arrhythmic death syndrome (n=2), acute cardiomyopathy (n=2), pulmonary hypertension (n=2), and myocardial infarction (n=1), and four of these causes were not encountered in 1991-1992. The incidence of MD over the total number of pregnancies decreased from 9.4 per 100,000 cases in 1990-1992 to 4.6 per 100,000 cases in 2010-2012 (p<0.05). However, the incidence of MD-CVD over the number of cases of MD increased from 2.9% in 1991-1992 to 9.7% in 2010-2012 (p<0.05). CONCLUSIONS The present study demonstrates that the rate of MD-CVD among the cases of MD has increased 3-fold in Japan over the past 20 years. Thus, it is of critical importance to better understand the etiologies and early signs of MD-CVD and to devise an effective management program for pregnancies complicated by CVD.

Retrospective study of tadalafil for fetal growth restriction: Impact on maternal and perinatal outcomes

The aim of this retrospective study was to assess tadalafil treatment in pregnant women with fetal growth restriction (FGR) in terms of maternal and perinatal outcomes.

High frequency of decreased antithrombin level in pregnant women with thrombosis

Venous thromboembolism (VTE) occurs frequently in pregnant women and is a significant cause of maternal death. Hemostatic abnormalities were examined in 18 pregnant women with thrombosis. We studied five families with congenital antithrombin (AT) deficiency, and two families with congenital protein C (PC) deficiency. One woman with PC deficiency showed protein S (PS) Tokushima. The AT activity levels were significantly lower at the onset of thrombosis in the pregnant women than during the stable state. The PS activity and antigen levels were also significantly lower at the onset of thrombosis. In the patients with congenital AT deficiency, AT activity was significantly low in the stable state and decreased further at the onset of thrombosis. Although AT levels were normal before pregnancy, they subsequently decreased and in two cases the patients required the administration of AT after pregnancy. Gene analysis revealed one family with AT Budapest, one family with AT Toyama, and three families with AT Glasgow. Additionally, there were one family with PC Tochigi and one family with combined heterozygous of PC deficiency and PS Tokushima. In conclusion, the deficiency of natural anticoagulants, especially AT, is an important cause of pregnancy-related VTE.

Cases of death due to serious group A streptococcal toxic shock syndrome in pregnant females in Japan

Serious group A streptococcal (GAS) infections and its toxic shock syndrome (TSS) are associated with early onset and rapid progression, often resulting in death [1, 2]. The initial symptoms of a high fever and abdominal or chest pain are characteristics and are attributable to a common cold syndrome or viral infection [1]. The incidence rate is extremely low, with rates largely between 2 and 4 per 1,00,000 [3]. However, GAS-TSS is still one of the causes of maternal death. The perinatal and infant mortality rates in Japan are lowest worldwide (3:1,000). On the other hand, the maternal mortality rate is relatively high (4:1,00,000) [4]. Therefore, the Japan Association of Obstetricians and Gynecologists (JAOG) established a registration system for maternal death in 2010. If maternal death occurs, detailed reports are to be submitted to the JAOG. The individual data are analyzed by the Maternal Death Exploratory Committee (Chairman: Ikeda, T.). This committee consists of 15 obstetricians, four anesthesiologists, two pathologists, an emergency physician and some specialists who attend review sessions every month, in order to make recommendations for reducing the maternal mortality every year. The present study was performed as part of a series which analyzed maternal deaths in Japan by this committee. Report forms regarding the maternal death cases where a female patient died during pregnancy or within a year after delivery are submitted to this registration system. The 12 pages of the report form contain approximately 100 questions, and elicit detailed information about the clinical history of each death, the facility characteristics and which personnel participated in the patient’s care. All of the anonymized reports were analyzed for factors associated with the maternal mortality and the circumstances of death. A total of 155 reports of maternal death were completely analyzed by the Maternal Death Exploratory Committee between 2010 and 2012, while 128 cases of maternal death that occurred during pregnancy or within 42 days after delivery were reported by the Ministry of Health, Labour and Welfare, Japan [4]. Because GAS-TSS is still one of the causes of maternal death, though number of maternal death is decreasing in Japan, we thought it was necessary to clarify the clinical course and features of maternal death due to serious GAS infection in order to reduce the maternal mortality rate. In the analyzed reports of maternal deaths between 2010 and 2013, the clinical features in the pregnant patients who died due to serious GAS-TSS were reviewed in the present study. Cases were enrolled when the diagnosis of GASTSS based upon the previously published criteria [5] was made, and when culture findings were positive or the GAS toxin was detected. J. Hasegawa (&) A. Sekizawa Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo 142-8666, Japan e-mail: hasejun@oak.dti.ne.jp

Safety and dose-finding trial of tadalafil administered for fetal growth restriction: A phase-1 clinical study

We designed a safety and dose‐finding trial of tadalafil administered for fetal growth restriction (FGR).