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Amniotic fluid embolism (AFE) is a rare but fatal obstetric complication, characterized by sudden cardiovascular collapse, respiratory failure, and disseminated intravascular coagulation. Maternal mortality associated with AFE is high, making early recognition and prompt treatment important. In AFE with cardiac arrest, survival following acute cardiopulmonary dysfunction is crucial. In recent years, venoarterial extracorporeal membrane oxygenation (VA-ECMO) has attracted attention as an aggressive treatment for AFE with cardiac arrest. A 40-year-old woman experienced sudden cardiac arrest due to AFE during cesarean section. Cardiopulmonary resuscitation and VA-ECMO (also called percutaneous cardiopulmonary support) were initiated early. Finally, she recovered without any complications. VA-ECMO can provide temporary respiratory and hemodynamic support until cardiopulmonary function improves after a few days in intensive care. VA-ECMO should be considered as an early treatment for AFE with cardiac arrest.

Twin-twin transfusion syndrome (TTTS) complicates approximately 10% of monochorionic twin pregnancies and is associated with almost 90% mortality if left untreated. Fetoscopic laser photocoagulation (FLP) is the first-line therapy for TTTS, and an overall twin survival rate of 75% and at least one survival rate of 90% have been established. We report a case of TTTS complicated with bleeding from the uterine wall by inserting the procedure after FLP. The patient consequently underwent emergency caesarean section. The bleeding was uncontrollable due to atonic bleeding and emergency hysterectomy was performed. To detect the possibility of amniotic fluid embolism (AFE), biochemical blood samples demonstrated that there was no inflow of fetal ingredients in blood vessels of uterine tissue. There was no evidence of damage to any specific vessels by histopathological staining. These findings indicated that the cause of massive bleeding was unlikely to have been AFE. It was concluded that atonic bleeding was likely caused by uncontrollable hemorrhage from an injury lesion where an endoscope had been inserted.

Objective To assess the contribution of maternal blood detection of IGFBP-1 for the diagnosis of amniotic-fluid embolism in clinical daily practice. Design A retrospective multicentre cohort study. Setting Three tertiary care obstetric units in France. Sample Data of 86 women for whom amniotic-fluid embolism had been suspected and maternal serum detection of IGFBP-1 had been performed between 2011 and 2019 were analysed. Methods The criteria defined by the United Kingdom Obstetric Surveillance System (UKOSS) were used for the retrospective diagnosis of amniotic-fluid embolism. The more structured definition proposed by the Society for Maternal-Fetal Medicine and the Amniotic Fluid Embolism Foundation (SMFM) was also used as secondary endpoint. Main outcome measures Agreements between biological and clinical assessments were tested. The performance of blood detection of IGFBP-1 for the diagnosis of amniotic-fluid embolism according to the UKOSS criteria, and to the SMFM definition, was also assessed. Results There was only slight agreement between clinical and laboratory diagnosis of amniotic-fluid embolism (Cohen's Kappa coefficient: 0.04). Blood detection of IGFBP-1 had a sensitivity of 16%, a specificity of 88%, a positive and a negative likelihood ratio of 1.3 and 0.95, respectively, and a positive and a negative predictive value of 58 and 50%, respectively, for the diagnosis of amniotic-fluid embolism based on the UKOSS criteria. The use of the more structured SMFM definition of amniotic-fluid embolism did not substantially change the results. Conclusion These results question the usefulness of blood detection of IGFBP-1 for the early diagnosis of amniotic-fluid embolism in daily clinical practice. Tweetable abstract This retrospective multicentre study questions the contribution of IGFBP-1 detection for the diagnosis of AFE.

Aim Intraoperative cell salvage and autotransfusion (ICSA) is a useful technique for women undergoing cesarean sections who are predicted to experience significant bleeding. This method can reduce allogeneic transfusions as well as its associated risks and costs. Amniotic fluid embolism (AFE) is an abnormal maternal response to ICSA similar to the classic systemic inflammatory response syndrome, but its mechanism is not well understood. This study was conducted to investigate the biochemical aspects of AFE. Methods A prospective case-controlled pilot study was conducted in a general perinatal hospital in Japan. ICSA was performed using a two-step retransfusion process. Blood samples were collected presurgery, immediately postsurgery, and 24 h after surgery. Changes in sialyl Tn antigen (STN), complement C3 and C4, fibrinogen, and fibrin degradation product and D-dimer, C1 esterase inhibitor, and interleukin-8 (all considered AFE-related markers) activities were compared between patients who underwent cesarean sections with ICSA (ICSA group) versus without ICSA (control group). Results Fibrinogen levels were significantly lower in the ICSA group than in the control group before surgery but not immediately after or 24 h after surgery. D-dimer was significantly higher immediately after surgery but not 24 h later. STN was significantly lower only before surgery. None of the AFE-related markers showed significant differences between the groups after 24 h. No adverse events were observed in the ICSA group. Conclusions There is no clinical evidence that ICSA alters the biochemical statuses of AFE-related markers in a manner that could lead to adverse maternal responses.

High index of suspicion of amniotic fluid embolism should be considered in any intrapartum or postpartum collapse where the obvious cause of collapse is not identified.

Aim Uterine atony is a major cause of postpartum hemorrhage. We recently proposed a new concept for the histopathophysiology of refractory uterine atony, postpartum acute myometritis (PAM), characterized by acute inflammatory changes with massive stromal edema, increased numbers of complement C5a receptors and diffuse mast cell activation in the myometrium. We herein focused on the possible involvement of the kinin-kallikrein system in the rapid development of interstitial edema in PAM, particularly bradykinin receptor type 1 (B1R), which is up-regulated under inflammatory conditions. The present study investigated B1R expression with uterine interstitial edema in PAM. Methods Our institution plays an important role in a Japanese amniotic fluid embolism registry project. We selected PAM cases from uterine samples delivered to us for further analyses between 2012 and 2017. Control tissues were collected during cesarean section and planned hysterectomy. B1R expression was semi-quantitatively measured by immunohistochemistry, while uterine interstitial edema was estimated by semi-quantitative measurements of the alpha smooth muscle actin-negative area using immunohistochemistry. Results There were 36 and 8 cases in the PAM and control groups, respectively. The alpha smooth muscle actin-negative area was increased in the PAM group, concomitant with the significant up-regulation of B1R expression in uterine smooth muscle cells, vascular endothelial cells, and neutrophils. A positive correlation was observed between these two factors. Conclusion We demonstrated the up-regulated expression of B1R in the myometrium and its positive correlation with histologically estimated interstitial edema, suggesting the contribution of the kinin-kallikrein-B1R system to the development of interstitial edema in PAM cases.

The use of cell salvage during caesarean section has been increasing steadily, although there are concerns relating to cost, a perceived risk of amniotic fluid embolism, and fetal red cell sensitisation. We present observational data from almost a decade of use of intra-operative cell salvage in obstetrics. By the end of this period, we set up cell salvage collection for > 98% of all caesarean sections. From 2008 to 2017, 1170 women have had a re-infusion of cell salvaged blood with no clinical safety concerns; the median (IQR [range]) volume was 231 (154-306 [80-1690]) ml. During this time there has been a marked reduction in the number of women who were transfused allogeneic blood, as well as the amount of blood transfused. In total, 647 (55%) women have had alloimmunisation testing, with two positive cases. Quality control data indicate that the quality of blood processed from partial first bowls is no worse than that from full bowls. We discuss the costs of providing this service with regard to: staffing costs; single suction; leucodepletion filters; selectivity in the processing of collected blood; and the use of partial first bowls.

A pregnant female rhesus macaque died spontaneously during stage two labor. Gross and histopathologic findings included severe pulmonary edema, with low numbers of blood vessels containing pale basophilic mucinous material (Alcian Blue positive and PTAH negative), consistent with intravascular amniotic fluid-derived mucin resulting in pulmonary amniotic fluid embolism.

AIM: We aimed to evaluate the clinical usefulness of serum squamous cell carcinoma (SCC) antigen for the diagnosis of amniotic fluid embolism (AFE). METHODS: Sera and information of 20 patients with AFE (autopsy-proven AFE, four cases; clinical AFE, 16 cases) were obtained from the Japan Amniotic Fluid Embolism Registration Center at Hamamatsu University School of Medicine. As controls, we included 74 gestational-age-matched healthy women who gave birth to healthy newborns during the period from December 2012 to January 2014. Receiver-operator curves (ROC) were used to evaluate the diagnostic performance of SCC levels for prediction of AFE. RESULTS: Serum SCC antigen levels in women with autopsy-proven AFE (112.0 ± 169.4 ng/mL, P = 0.001) and clinical AFE (9.5 ± 10.3 ng/mL, P = 0.004) were significantly higher than those in healthy controls with normal delivery (4.4 ± 2.2 ng/mL). On ROC analysis, the optimal cut-off value for SCC antigen levels was 7.15 ng/mL, for which the sensitivity and specificity for AFE prediction was 60.0% and 89.2%, respectively (area under the ROC, 0.785; 95% confidence interval, 0.663-0.908; P < 0.001). CONCLUSION: Serum SCC antigen may be a promising predictor of the entry of amniotic fluid into the maternal circulation, potentially serving as a candidate marker for noninvasive diagnosis of AFE., 博士（医学）・乙第1436号・令和元年9月27日, © 2017 Japan Society of Obstetrics and Gynecology, This is the peer reviewed version of the following article: [https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/jog.13453], which has been published in final form at [https://doi.org/10.1111/jog.13453]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

Aim We aimed to evaluate the clinical usefulness of serum squamous cell carcinoma (SCC) antigen for the diagnosis of amniotic fluid embolism (AFE). Methods Sera and information of 20 patients with AFE (autopsy-proven AFE, four cases; clinical AFE, 16 cases) were obtained from the Japan Amniotic Fluid Embolism Registration Center at Hamamatsu University School of Medicine. As controls, we included 74 gestational-age-matched healthy women who gave birth to healthy newborns during the period from December 2012 to January 2014. Receiver–operator curves (ROC) were used to evaluate the diagnostic performance of SCC levels for prediction of AFE. Results Serum SCC antigen levels in women with autopsy-proven AFE (112.0 ± 169.4 ng/mL, P = 0.001) and clinical AFE (9.5 ± 10.3 ng/mL, P = 0.004) were significantly higher than those in healthy controls with normal delivery (4.4 ± 2.2 ng/mL). On ROC analysis, the optimal cut-off value for SCC antigen levels was 7.15 ng/mL, for which the sensitivity and specificity for AFE prediction was 60.0% and 89.2%, respectively (area under the ROC, 0.785; 95% confidence interval, 0.663–0.908; P < 0.001). Conclusion Serum SCC antigen may be a promising predictor of the entry of amniotic fluid into the maternal circulation, potentially serving as a candidate marker for noninvasive diagnosis of AFE.

Aim The objective of this study was to determine the mortality rate of amniotic fluid embolism (AFE) using population-based studies and case series. Methods A literature search was conducted using the two key words: ‘amniotic fluid embolism (AFE)’ AND ‘mortality rate’. Thirteen population-based studies were evaluated, as well as 36 case series including at least two patients. Results The mortality rate from population-based studies varied from 11% to 44%. When nine population-based studies with over 17 000 000 live births were aggregated, the maternal mortality rate was 20.4%. In contrast, the mortality rate of AFE in case series varies from 0% to 100% with numerous rates in between. Conclusion The AFE mortality rate in population-based studies varied from 11% to 44% with the best available evidence supporting an overall mortality rate of 20.4%. Data from case series should no longer be used as a basis for describing the lethality of AFE.

Extracorporeal membrane oxygenation (ECMO) is commonly used in patients who experience circulatory arrest or significant cardiac dysfunction and is associated with improved clinical outcomes. We conducted a retrospective observational study on ECMO application at a single tertiary center over a five-year period. Five patients who suffered post-partum hemorrhage resulting from uterine atony were treated with ECMO. The mean age was 36.8 ± 3.9 years; the mean gestational age was 37.8 ± 2.2 weeks; the initial mean maternal hemoglobin level was 5.0 ± 2.4 mg/dL; and the mean estimated blood loss was 3260 ± 1545 mL before treatment. All patients were treated with venoarterial ECMO and one was treated with both venoarterial and venovenous ECMO. The mean ECMO usage duration was 32.6 ± 18.8 h (range 10-54). Four (80%) patients survived until discharge without experiencing neurological sequela. ECMO should not be a contraindication for treatment of post-partum hemorrhage and such patients should be weaned as soon as possible to ensure the early recovery of cardiac function.

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.

BACKGROUND The Japan Association of Obstetricians and Gynecologists (JAOG) recommends transfusion with a fresh-frozen plasma (FFP):red blood cell (RBC) ratio of 1 or more in postpartum hemorrhage. However, no global consensus exists concerning this, and little is known regarding the impact of FFP:RBC ratio on maternal mortality. This study evaluates the efficacy of transfusion with FFP:RBC ratio of 1 or more for amniotic fluid embolism (AFE) with coagulopathy. STUDY DESIGN AND METHODS The Maternal Death Exploratory Committee, established by the JAOG, conducted this retrospective nationwide case–control study in Japan. Women with AFE and coagulopathy were included in the study and were stratified into survival and death groups. Obstetric variables and therapy methods (hysterectomy, uterine artery embolism, and transfusion with FFP:RBC ratio ≥ 1) were compared between the survival and death groups. RESULTS A total of 54 women had AFE and coagulopathy (death group, n = 22; survival group, n = 32). Only nine (40.9%) women in the death group were transfused with FFP:RBC ratio of 1 or more, whereas 29 (90.6%) women in the survival group were transfused with FFP:RBC ratio of 1 or more. FFP:RBC ratio of 1 or more was found to be associated with better survival rate (adjusted odds ratio, 28.32; 95% confidence interval, 4.26-188.37). No difference was found in obstetric variables, hysterectomy, and uterine artery embolism between survival and death groups. CONCLUSION Transfusion with FFP:RBC ratio of 1 or more is associated with higher survival rate in women with AFE with coagulopathy.

Amniotic fluid embolism (AFE) is a rare complication of pregnancy and its mortality rate is high. There have been few reports of AFE with presence of severe coagulopathy and incoagulable bleeding, and absence of cardiopulmonary symptoms or limited cardiopulmonary symptoms, followed by massive blood loss during delivery. Such cases have been referred to as disseminated intravascular coagulopathy-type AFE, and the characteristics of this condition have been presented previously. Here we report three cases that fulfilled the diagnostic characteristics of disseminated intravascular coagulopathy-type AFE.

Amniotic fluid embolism (AFE) causes consumption coagulopathy, which requires a massive transfusion to save the mother's life. The preparation of such a massive transfusion is too time-consuming in extremely emergent clinical settings and occasionally leads to devastating side effects such as transfusion-associated acute lung injury. C1 esterase inhibitor (C1INH) is a protein with the ability to inhibit complement, coagulation and kinin pathways. The C1INH concentration in AFE patients is low, and it has been speculated that the administration of C1INH concentrate could have a striking and beneficial effect on AFE patients in critical condition by ameliorating their perturbed coagulation system. We report the case of a 32-year-old Japanese AFE patient in whom deteriorated vital signs and coagulopathy recovered within minutes after an injection of C1INH concentrate. C1INH concentrate can quickly revive the deteriorated vital signs and the atonic uterus that stem from AFE and may reduce the total amount of transfusion.

Aim The aim of this study was to provide basic documents applicable to studying the usefulness of administering fibrinogen concentrate to patients with massive post-partum hemorrhage. We investigated the usage of fibrinogen concentrate at training institutions for specialist physicians of the Japan Society of Obstetrics and Gynecology. Material and Methods The subjects were women who required fibrinogen concentrate for hemostasis of post-partum hemorrhage during the period between April 2008 and March 2013. The underlying diseases, obstetric disseminated intravascular coagulation scores, blood loss, amount of blood transfusion, dose of fibrinogen concentrate administered, and plasma fibrinogen levels before and after the administration of fibrinogen concentrate were retrospectively investigated. Results Ninety-nine (98.0%) patients survived and two died after taking fibrinogen concentrate. Of the surviving 99 cases, the average amount of blood loss at the time of initial fibrinogen administration and total blood loss was 3559 ± 2103 mL and 4562 ± 3198 mL, respectively. The dose per administration was 3 g, and the plasma fibrinogen level before the initial administration of fibrinogen concentrate was 70.5 mg/dL, thereafter increasing to 187.0 mg/dL. The increase in the fibrinogen level was 32.9 mg/dL/g of fibrinogen concentrate. It was less than 150 mg/dL after the first administration of fibrinogen concentrate only in patients with amniotic fluid embolism and patients with atonic bleeding showed the smallest increase in fibrinogen per gram of fibrinogen concentrate. No adverse events, including thromboembolism, were reported. Conclusion The results indicated the increase in blood fibrinogen levels to, on occasion, be insufficient even with fibrinogen concentrate use; however, this survey may support the safety and usefulness of fibrinogen concentrate for PPH.

Aim To investigate the utility of recombinant activated Factor VII (rFVIIa) for severe post-partum hemorrhage (PPH) in Japan. Methods We studied 69 patients treated with rFVIIa for severe PPH; 44 patients were from the registry of Japan Society of Obstetrical, Gynecological and Neonatal Hematology, and 25 were identified by a survey of the Japan Society of Obstetrics and Gynecology. Results Overall, the mean and median blood loss were 11 835 mL and 8639 mL, respectively. Treatment before rFVIIa included transarterial embolization in 23 patients and hysterectomy in 38. Forty-two patients had a single dose, 17 had two doses, and four had three doses. The mean (± SD) single dose was 81.60 ± 16.25 µg/kg. Sixty-five patients survived, and four died. The cause of PPH in patients who died was uterine rupture plus amniotic fluid embolism in two patients, uterine cervical laceration in one, and placental abruption in one. The amount of blood loss in cases of death was 6428–43 810 mL. This suggested that whether a patient survives or not was more dependent on her general condition before and after rFVIIa treatment than on the amount of blood loss. Four patients had thromboembolic events after rFVIIa treatment (deep vein thrombosis; deep vein thrombosis plus pulmonary embolism; acute myocardial infarction; and pulmonary embolism); all of these patients recovered. Conclusion The present promising results may support the utility of rFVIIa for severe PPH in Japan.

Key Clinical Message: Hypofibrinogenemia is rare in pulmonary thromboembolism. A pregnant woman with dyspnea, abdominal pain, restlessness, agitation and protein S deficiency exhibited normal blood oxygenation and high D-dimer (370 mu g/mL) and undetectable fibrinogen levels in the blood. The pathogenesis responsible for present findings may have some features similar to amniotic fluid embolism.

Aim To evaluate whether the presence of amniotic components in the maternal uterine vasculature could be a specific pathological indicator for amniotic fluid embolism (AFE). Methods Medical records of patients treated between January 2006 and March 2013 were retrospectively examined to identify patients who underwent post-partum hysterectomy or autopsy due to maternal death. Three subjects with AFE with disseminated intravascular coagulation (DIC)-type post-partum hemorrhage (PPH), and 13 non-AFE subjects were included in analysis. Histochemical staining using hematoxylin–eosin (HE) and alcian blue, and immunohistochemical staining for sialyl-Tn were conducted to detect amniotic components in the maternal uterine vasculature. Results Alcian blue was positive for amniotic components in the uterine vasculature of all subjects with AFE and of several subjects without AFE. Similarly, HE and sialyl-Tn were negative in some AFE subjects and positive in some non-AFE subjects. Conclusions The presence of maternal intravascular fetal material is not a specific indicator for AFE with DIC-type PPH. Therefore, the presence of fetal components in the uterine vasculature is unlikely to be a definitive indicator for AFE.

Aim The aim of this study was to elucidate the clinical characteristics and risk factors for amniotic fluid embolism (AFE). Methods We performed a retrospective case study analysis of patients using medical records and autopsy records. The diagnosis of AFE was based on the presence of clinical symptoms using Clark's criteria and autopsy results. We analyzed patient records from a 29-year period in three hospitals affiliated with the Nippon Medical School in Japan. Results Ten diagnoses of AFE were found in the records. First, we classified AFE patients into two types based on the initial presenting symptoms: post-partum hemorrhage and cardiopulmonary collapse. Fifty percent of the patients initially presented with post-partum hemorrhage and disseminated intravascular coagulation. Most were diagnosed with post-partum hemorrhage or uterine atony at AFE onset. Similarly, 50% presented with cardiopulmonary arrest or pulmonary arrest as initial symptoms, and most were diagnosed with eclampsia. Second, risk factors for AFE included advanced maternal age, multiparity, increased intrauterine pressure and disruptions of the uterine vasculature. Third, the case fatality rate was 70%. Fourth, squamous cells were observed in maternal central venous blood of five patients. Conclusion AFE patients were classified into two types based on presenting signs and symptoms. Knowledge of the various initial symptoms of AFE enables a correct diagnosis.

The registry program of amniotic fluid embolism (AFE) in Japan started in 2003. More than 400 hundred clinical diagnosed amniotic fluid embolism has been accumulated. Those data showed that there were two etiologies of AFE: the fetal materials create physical obstructions in the maternal microvessels in various organs, such as the lung; and (ii) the liquids cause an anaphylactoid reaction that leads to pulmonary vasospasm and activation of platelets, white blood cells and/or complements. The clinical findings showed that AFE was characterized mainly by cardiopulmonary collapse, the other involves the presence of disseminated intravascular coagulation (DIC) and atonic bleeding. Zinc coproporphyrin-1, sialyl Tn antigen (STN), complement C3, C4 and interleukin-8 have been used as serum markers of AFE. The levels of zinc coproporphyrin-1 and STN were increased in cardiopulmonary collapse type AFE, and a marked reduction of C3 and C4 was observed in DIC type AFE. At the primary medical institution, initial treatments for shock airway management, vascular management, fluid replacement, administration of anti-DIC therapy such as antithrombin, and administration of fresh frozen plasma should be provided. C1 esterase inhibitor activity in AFE cases was significantly lower than those of normal pregnant women. C1 esterase inhibitor may be a promising candidate of treatment of AFE.

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

We report a case of significant reduction in bispectral index (BIS) associated with suspected amniotic fluid embolism (AFE) that occurred prior to change in haemodynamic variables. The patient was a 29-year-old nulliparous, who was admitted for Caesarean section under general anaesthesia in the 33rd week of pregnancy. After the baby was born, the BIS value suddenly decreased to 0, with suppression ratio of 100. One minute later, saturation decreased abruptly to 85%, end-tidal carbon dioxide (EtCO2) decreased to 5 mmHg, peak inspiratory pressure increased to 35 cm H2O, and non-invasive blood pressure (BP) failed to obtain a reading. After administration of vasoactive drugs, the systolic BP was maintained at 100 mmHg or higher, the BIS value rose to 10-20, and the EtCO2 increased to 24-33 mmHg. In this case, the BIS monitoring may provide an earlier warning of impending cardiovascular collapse in the case of AFE.

Background Amniotic fluid embolism (AFE) is a rare but serious cause of maternal mortality whose aetiology remains obscure. Previous population-based studies have reported associations with labour induction and caesarean delivery. Methods We updated a previous analysis based on the US Nationwide Inpatient Sample from 1999 to 2008. We adapted a diagnostic validation algorithm to minimise false-positive diagnoses, along with statistical methods that account for the stratified random sampling design. Results Of the 8 571 209 deliveries recorded in the database, 276 met our case definition of AFE, of which 62 (22.9% of the 274 with known vital status) were fatal. Significant associations with AFE were observed for medical induction {adjusted odds ratio [aOR] = 1.7 [95% confidence interval (CI) 1.2, 2.5]}, caesarean delivery [aOR = 15.0; 95% CI 9.4, 23.9], instrumental vaginal delivery [aOR = 6.6; 95% CI 4.0, 11.1], and cervical/uterine trauma [aOR = 7.4; 95% CI 3.6, 14.9]. AFE was associated with increases in risk of stillbirth, hysterectomy, maternal death, and prolonged maternal length of delivery hospital stay. Conclusions AFE remains an extremely serious obstetric complication with high risks of maternal and fetal mortality. The increased risks of AFE associated with labour induction and caesarean delivery have implications for elective use of these interventions.

Please cite this paper as: Fransen A, van de Ven J, Merien A, de Wit-Zuurendonk L, Houterman S, Mol B, Oei S. Effect of obstetric team training on team performance and medical technical skills: a randomised controlled trial. BJOG 2012;119:1387–1393. Objective To determine whether obstetric team training in a medical simulation centre improves the team performance and utilisation of appropriate medical technical skills of healthcare professionals. Design Cluster randomised controlled trial. Setting The Netherlands. Sample The obstetric departments of 24 Dutch hospitals. Methods The obstetric departments were randomly assigned to a 1-day session of multiprofessional team training in a medical simulation centre or to no such training. Team training was given with high-fidelity mannequins by an obstetrician and a communication expert. More than 6 months following training, two unannounced simulated scenarios were carried out in the delivery rooms of all 24 obstetric departments. The scenarios, comprising a case of shoulder dystocia and a case of amniotic fluid embolism, were videotaped. The team performance and utilisation of appropriate medical skills were evaluated by two independent experts. Main outcome measures Team performance evaluated with the validated Clinical Teamwork Scale (CTS) and the employment of two specific obstetric procedures for the two clinical scenarios in the simulation (delivery of the baby with shoulder dystocia in the maternal all-fours position and conducting a perimortem caesarean section within 5 minutes for the scenario of amniotic fluid embolism). Results Seventy-four obstetric teams from 12 hospitals in the intervention group underwent teamwork training between November 2009 and July 2010. The teamwork performance in the training group was significantly better in comparison to the nontraining group (median CTS score: 7.5 versus 6.0, respectively; P = 0.014). The use of the predefined obstetric procedures for the two clinical scenarios was also significantly more frequent in the training group compared with the nontraining group (83 versus 46%, respectively; P = 0.009). Conclusions Team performance and medical technical skills may be significantly improved after multiprofessional obstetric team training in a medical simulation centre.

We have assessed the incidence, symptoms and risk factors of amniotic fluid embolism in the Netherlands. Data were retrieved from two nationwide registration systems. From 1983 to 2005 the maternal mortality ratio of amniotic fluid embolism increased from 0.11 to 0.63 (odds ratio (OR) 5.8, 95% confidence interval (CI) 1.3-25.3). The most common signs and symptoms of amniotic fluid embolism were dyspnea and massive obstetric hemorrhage. In the majority of women, onset of symptoms was intrapartum or immediately postpartum. Potential risk factors of developing amniotic fluid embolism were maternal age >30, multiparity (OR 3.3, 95% CI 1.02-10.5), cesarean section (OR 1.3, 95% CI 0.3-5.2) and induction of labor (OR 2.1, 95% CI 2.1-6.1). Perinatal mortality was increased to 38.1% compared with 0.98% in the general pregnant population (p < 0.001) High maternal age and multiparity are the most important risk factors for developing amniotic fluid embolism.

Please cite this paper as: Kramer M, Rouleau J, Liu S, Bartholomew S, Joseph K for the Maternal Health Study Group of the Canadian Perinatal Surveillance System. Amniotic fluid embolism: incidence, risk factors, and impact on perinatal outcome. BJOG 2012;119:874–879. Objective To extend our previous work on AFE in Canada by including stricter criteria for case identification and by examining risks for stillbirth, neonatal mortality and serious maternal and neonatal morbidity. Design Population-based cohort study. Setting Canada. Population or sample In all, 4 508 462 hospital deliveries from fiscal year 1991/92 to 2008/09. Methods To reduce false-positive diagnoses, we restricted our analysis to AFE cases with cardiac arrest, shock or severe hypertension, respiratory distress, mechanical ventilation, coma, seizure, or coagulation disorder. Linkage of maternal and neonatal records, available since 2001/02, enabled us to examine the effects of AFE on neonatal outcomes. Detailed demographic and clinical data facilitated control for a broad array of potential confounding variables. Main outcome measures Amniotic fluid embolism, in-hospital neonatal death, asphyxia, mechanical ventilation, bacterial sepsis, seizure, nonimmune haemolytic or traumatic jaundice and length of hospital stay. Results A total of 292 AFE cases were identified, of which only 120 (40%) were confirmed after applying our additional diagnostic criteria, yielding an AFE incidence of 2.5 per 100 000 deliveries. Of the 120 confirmed cases, 33 (27%) were fatal. Significant modifiable risk factors included medical induction, caesarean delivery, instrumental vaginal delivery, and uterine or cervical trauma. Amniotic fluid embolism was associated with significantly increased risks of stillbirth and neonatal asphyxia, mechanical ventilation, sepsis, seizures and prolonged length of hospital stay. Conclusions Amniotic fluid embolism remains a rare but serious obstetric outcome, with several important modifiable risk factors and major implications for maternal, fetal and neonatal health.

Amniotic fluid embolism (AFE) continues to be one of the most feared complications of pregnancy. A healthy 32-year-old woman died during delivery after a normal 39-week third pregnancy. The family filed a complaint with a criminal court as the causes of death appeared unclear. No risk factor associated with AFE was identified. Clinical presentation was typical, including sudden onset of cardiovascular and respiratory symptoms. Autopsy confirmed the histological diagnosis of amniotic embolism and excluded an iatrogenic cause of death or anesthetic malpractice. This article highlights the value of both antemortem records and histological features in establishing the diagnosis of AFE and demonstrates the fundamental importance of autopsy in an unexpected death related directly or indirectly to a medical procedure. Maternal death during delivery is rare, but traumatic for the medical teams. When a patient dies during anesthesia or immedi- ately following a surgical procedure, the liability of the anesthetic and gynecological teams may be sought. This attitude is generally explained by the fact that it is impossible for the medical team to establish the immediate cause of death with any certainty. The death of the mother is experienced as a tragedy, especially as the women giving birth are young and healthy (1). In the volatile situa- tion that follows unexpected death, the risk of legal proceedings is high, and autopsy may be indicated to investigate the causes of death and the possibility of medical liability. When death occurs during anesthesia and surgery, it has been observed that the rela- tives and ⁄ or their counsel frequently tend to consider the medical chart data as inadequate or untrustworthy (2,3).

SUMMARY The acceptance of cell salvage in obstetrics has been hampered by concerns about amniotic fluid embolism and maternal alloimmunization. The removal of amniotic fluid debris by cell salvage has been proven, but controversy remains as to whether using one or two separate suction devices for removal of amniotic fluid and blood is necessary. There have been recent reports of hypotensive episodes occurring during re-infusion of the salvaged blood with leukodepletion filters. Bradykinin release may be the responsible agent. Maternal alloimmunization can potentially occur as the cell saver cannot differentiate between maternal and fetal red cells. However, the fetal cell transference rate in salvaged blood is of the same magnitude as during a feto-maternal hemorrhage and can be treated by appropriate administration of anti-D. Salvaged blood does not contain any coagulation factors and in massive hemorrhage these factors must be replaced in addition to the red cells. Coagulopathy in bleeding patients that have cell salvage should not be viewed as an adverse event associated with this technique, but rather as inadequate replacement of coagulation products. There is currently no evidence base that cell salvage in obstetrics reduces allogeneic transfusion or is cost-effective. A randomized controlled trial is urgently needed.

Amniotic fluid embolisms (AFE) are one of the most fatal complications of pregnancy. We describe a case of AFE that occurred 2 h after vaginal delivery at 41 weeks of gestation. The diagnosis of AFE was made by symptoms of dyspnea, coagulopathy, and severe hypotension. ZnCP-1, the characteristic component of meconium, was elevated in the serum. Cardiac compressions after repeated cardiac arrests were required during the initial 2 h of resuscitation. Primary resuscitation was performed with airway management and aggressive fluid management, including infusion of 33 units of red cell concentrates and 57 units of fresh frozen plasma. The patient recovered without any aftereffects. This case report warrants that AFE should be considered when coagulopathy and dyspnea are observed during the postpartum period.

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.

Amniotic fluid embolism (AFE) is a sporadic, unpredictable, and usual fatal obstetric complication. The paper deals with two cases of maternal deaths because of AFE verified by medicolegal autopsy. In both the cases, several known risk factors associated with AFE, such as increased maternal age (41 and 35 years), diabetes, augmented labor, and cesarean delivery, were identified. Clinical features were typical, including sudden onset of cardiovascular and respiratory symptoms. In the patient who survived longer, both clinical and autopsy signs of disseminated intravascular coagulopathy were present, while they were absent in the case where death occurred rapidly. This paper describes briefly the particular features to look for at autopsy and stresses the importance of histology examination and staining techniques.

Please cite this paper as: Roberts C, Algert C, Knight M, Morris J. Amniotic fluid embolism in an Australian population-based cohort. BJOG 2010;117:1417–1421. We utilised linked birth, hospital and death data for the entire population to determine the incidence of amniotic fluid embolism (AFE) and its mortality and morbidity. AFE diagnoses were identified from International Classification of Diseases, 10th Revision (ICD10)-coded hospital and/or death records with additional case definition criteria imposed. The AFE incidence was 3.3 per 100 000 (95% CI, 1.9–4.7), maternal fatality rate 35% (95% CI, 15–59) and perinatal mortality rate 32% (95% CI, 12–56). Newly identified risk factors included induction with vaginal prostaglandin and manual removal of the placenta, and survivors were at increased risk of cerebral infarction. Although two-thirds of women and infants survived, AFE also caused severe morbidity.

A 30-year-old woman at 37 weeks of gestation died during labor induction with oxytocin shortly after an episode of abrupt drop of fetal heart rate. Autopsy showed extensive microvascular plugging of the pulmonary capillaries by massive platelet aggregations. Aside from platelet aggregations, the keratinized substances and granulocytes were also shown in the capillary of pulmonary arterioles. These findings were not observed in other systemic organs (heart, liver, spleen, kidney, adrenal, alimentary canal and pancreas). In general, the postmortem histological diagnosis of amniotic fluid embolism consisted of demonstrating mucus, leukocytes, squamous, amorphous, and fatty cells in the arteries of the lung. To our knowledge, there have not been any reports regarding massive platelet aggregations shown at pulmonary capillaries in case of acute amniotic fluid embolism except for an experimental model. This is a rare case of amniotic fluid embolism in which massive platelet aggregations were confirmed in pulmonary capillaries by autopsy.

Objective To assess causes, trends and substandard care factors in maternal mortality in the Netherlands. Design Confidential enquiry into the causes of maternal mortality. Setting Nationwide in the Netherlands. Population 2,557,208 live births. Methods Data analysis of all maternal deaths in the period 1993-2005. Main outcome measures Maternal mortality. Results The overall maternal mortality ratio was 12.1 per 100 000 live births, which was a statistically significant rise compared with the maternal mortality ratio of 9.7 in the period 1983-1992 (OR 1.2, 95% CI 1.0-1.5). The most frequent direct causes were (pre-)eclampsia, thromboembolism, sudden death in pregnancy, sepsis, obstetric haemorrhage and amniotic fluid embolism. The number of indirect deaths also increased, mainly caused by an increase in cardiovascular disorders (OR 2.5, 95% CI 1.4-4.6). Women younger than 20 years and older than 45 years, those with high parity or from nonwestern immigrant populations were at higher risk. Most substandard care was found in women with pre-eclampsia (91%) and in immigrant populations (62%). Conclusions Maternal mortality in the Netherlands has increased since 1983-1992. Pre-eclampsia remains the number one cause. Groups at higher risk for complications during pregnancy should be better identified early in pregnancy or before conception, in order to receive preconception advice and more frequent antenatal visits. There is an urgent need for the better education of women and professionals concerning the danger signs, and for the training of professionals in order to improve maternal health care.

A 32-year-old primigravida underwent a cesarean section at 39 weeks and a male infant was born. Two hours later profuse vaginal bleeding was noted. After bilateral uterine artery embolization, the vaginal bleeding seemed to have been controlled. However, five hours and twenty minutes later she developed profuse vaginal bleeding again and fell into shock regardless of fluid resuscitation. An emergent subtotal hysterectomy was performed and she was diagnosed with disseminated intravascular coagulation (DIC) following surgery. Treatment for hemorrhagic shock and DIC was attempted with massive transfusion in association with continuous dopamine infusion. The total blood loss was estimated to be about 10,000 ml. On the third postoperative day DIC and hemorrhagic shock improved and ventilator weaning was accomplished, however she developed acute renal failure. Hemodialysis treatment for the following 16 days resulted in the improvement of renal function. She was discharged 41 day after delivery. Afterwards, it was realized that the plasma concentration of zinc coproporphyrin-I, a component of amniotic fluid, had considerably increased. Since there was no other cause for the severe bleeding, she should be diagnosed with amniotic fluid embolism (AFE). This case illustrates that AFE may develop an isolated DIC without antecedent hemodynamic or respiratory instability.