Changes in use and outcomes after fibrinogen concentrate insurance coverage for critical obstetrical hemorrhage: a nationwide questionnaire survey in Japan.

Fibrinogen concentrate (FC) for acquired hypofibrinogenemia associated with critical obstetrical hemorrhage (COH) was covered by public medical insurance in September 2021 in Japan. We aimed to investigate changes in the policy of FC use and its effect on COH after insurance coverage. A primary survey covering September 2020 to August 2021 and a secondary survey covering September 2021 to August 2022 were conducted at 428 higher-level medical facilities. We investigated the policy of FC use in transfusion strategy and the maternal outcomes in COH. Among the hospitals that responded to both surveys, the number of facilities that use FC increased from 51.5 (101/196) to 78.6% (154/196) (P < 0.0001). The number of COH cases treated using FC increased from 14.3 to 24.3% (P < 0.0001) and that transfused with ≥ 10 units of red blood cells (RBCs) decreased from 36.8 to 29.8% (P = 0.001). The incidence of pulmonary edema reduced by 3.7-2.0% (P = 0.021), and transfusion-induced allergy by 1.9-0.7% (P = 0.008). No changes were observed in the incidence of thromboembolism, arterial embolization, or hysterectomy. The increased use of FC after insurance coverage led to changes in the transfusion strategy, which may be associated with decreases in transfusions of RBCs, pulmonary edema, and transfusion-induced allergies.

Differences in the prevention and incidence of maternal venous thromboembolism according to the type of institution in Japan in 2018: A sub-analysis of national questionnaire surveillance.

AIM: To clarify the relation between institutions capacity to manage venous thromboembolism (VTE) and its incidence in pregnant women throughout Japan. METHODS: Among the 2299 institutions that received the surveillance questionnaire, 666 (29.0%) responded, after which data from 295 961 women who gave birth at those institutions in 2018 were analyzed. Incidences and characteristics of antepartum and postpartum VTE in perinatal medical centers (PMCs), general hospital with obstetric facilities (GHs), and maternal clinic with beds (MCs) were then determined. RESULTS: The frequencies at which routine antepartum and postpartum thromboprophylaxis for high-risk women and routine transport to the more advanced medical institutions upon antepartum and postpartum pulmonary thromboembolism (PE) onset were performed differed significantly according to types of institution (PMCs: 92.4%, 96.2%, 23.8%, and 21.2%; GHs: 76.5%, 80.6%, 58.8%, and 54.1%; MCs: 29.2%, 41.7%, 96.5%, and 96.2%, respectively). Among the 295 961 women analyzed, 243 (0.082%) developed VTE. Incidences of antepartum VTE differed significantly according to institution types (PMCs: 106.4, GHs: 51.6, and MCs: 11.6 per 100 000 women). PMCs and GHs had significantly higher incidences of postpartum VTE compared to MCs (43.3 and 26.6 vs. 10.7 per 100 000 women, respectively), although PMCs and GHs had similar incidences. Among the four women (1.4%) who died due to VTE, three and one developed a PE in a PMC and MC, respectively. CONCLUSIONS: PMCs had higher incidences of VTE despite their more frequent performance of thromboprophylaxis. Several pregnant women with higher risk of VTE transported to PMCs.

A retrospective cohort study using a national surveillance questionnaire to investigate the characteristics of maternal venous thromboembolism in Japan in 2018.

BACKGROUND: In Japan, the numbers of deliveries by women of older maternal age and women with overweight or obesity have recently increased. Since 2008, the guidelines and practices to prevent the maternal venous thromboembolism (VTE) have been recommended antepartum and postpartum thromboprophylaxis for each risk level of VTE. This study aimed to clarify the incidence and characteristics (type of VTE and thromboprophylaxis) of VTE in pregnant women in Japan to reduce the rate of mortality from VTE METHODS: Of 2299 institutions sent the surveillance questionnaire, 666 (29.0%) responded, and data from 295,961 women who gave birth in those institutions in 2018 were analyzed. We calculated the incidence and characteristics of VTE before and after the deliveries. RESULTS: At the responding institutions, 243 women (0.082%) had VTE in 2018. In 2018, deep vein thrombosis was significantly more common (0.0053%) than pulmonary thromboembolism (0.0019%; p < 0.0001). The incidence of antepartum VTE (0.0055%) was significantly higher than that of postpartum VTE (0.0026%; p < 0.0001). The incidence of VTE after cesarean Sect. (0.0074%) was significantly higher than that after vaginal delivery (0.0012%; p < 0.0001). Of the women with VTE, 4 (1.6%) died. CONCLUSIONS: Among the women thought to have a low risk of VTE during the antepartum period, and especially women who had a vaginal delivery, the actual incidence of VTE might have increased in Japan.

Capacity of Japanese institutions to manage obstetrical disseminated intravascular coagulation in 2018: A national surveillance questionnaire and retrospective cohort study.

AIM: To investigate the management of obstetrical disseminated intravascular coagulation (DIC) in Japan. METHODS: We sent a surveillance questionnaire to 2299 institutions to collect details about the deliveries they performed in 2018. We investigated differences in the management of obstetrical DIC among three types of institutions: perinatal medical centers (PMCs), general hospitals with obstetrical facilities (GHs), and maternal clinics with beds (MCs). RESULTS: We received responses from 703 institutions (30.6% of the total mailed) with results of 306 799 women who gave birth in 2018. In Japan, the potential to treat postpartum hemorrhage and obstetrical DIC was high in the PMC group, moderate in the GH group, and low in the MC group. The incidence of obstetrical DIC in the PMC group (0.44%) was significantly higher than that in the GH (0.21%) and MC (0.06%) groups. The mortality of women with obstetrical DIC in PMCs (1.3%) was similar to that in GHs (0.6%) and MCs (0.0%). The percentages of PMCs that always or sometimes transfused fresh frozen plasma or fibrinogen concentrates (100% and 42.2%, respectively) were significantly higher than those in the GH (88.2% and 29.5%, respectively) and MC groups (29.4% and 5.3%, respectively). Furthermore, institutions whose internal protocols mandated that replacement therapy be always administered in women with obstetrical DIC scores of ≥8 had similar protocols to those for women with fibrinogen levels of ≤1.5 g/L. CONCLUSIONS: The capacity to provide therapy for postpartum hemorrhage and obstetrical DIC varied widely among the three groups of institutions.

Importance of Serum Amino Acid Profile for Induction of Hepatic Steatosis under Protein Malnutrition.

We previously reported that a low-protein diet caused animals to develop fatty liver containing a high level of triglycerides (TG), similar to the human nutritional disorder "kwashiorkor". To investigate the underlying mechanisms, we cultured hepatocytes in amino acid-sufficient or deficient medium. Surprisingly, the intracellular TG level was increased by amino acid deficiency without addition of any lipids or hormones, accompanied by enhanced lipid synthesis, indicating that hepatocytes themselves monitored the extracellular amino acid concentrations to induce lipid accumulation in a cell-autonomous manner. We then confirmed that a low-amino acid diet also resulted in the development of fatty liver, and supplementation of the low-amino acid diet with glutamic acid to compensate the loss of nitrogen source did not completely suppress the hepatic TG accumulation. Only a dietary arginine or threonine deficiency was sufficient to induce hepatic TG accumulation. However, supplementation of a low-amino acid diet with arginine or threonine failed to reverse it. In silico analysis succeeded in predicting liver TG level from the serum amino acid profile. Based on these results, we conclude that dietary amino acid composition dynamically affects the serum amino acid profile, which is sensed by hepatocytes and lipid synthesis was activated cell-autonomously, leading to hepatic steatosis.

A new era in reproductive medicine: consequences of third-party oocyte donation for maternal and fetal health.

The fetus is a semi-allograft for the maternal host in natural pregnancy, but the fetus is a complete allograft after oocyte donation (OD), and there is greater antigenic dissimilarity with the mother. Thus, OD pregnancy is a good model for understanding how the fetus is protected by the maternal immune system. Recent clinical data have revealed a higher risk of miscarriage, gestational hypertension, preterm birth, and low birth weight with OD pregnancy. There is also a higher incidence of chorionic deciduitis, dense fibrinoid deposits in the chorionic basal plate, inflammatory lesions in the chorionic plate, and C4d deposition on syncytiotrophoblasts in OD pregnancy. Impaired accumulation of T cells, regulatory T (Treg) cells, natural killer (NK) cells, and monocytes in the decidua basalis and poor remodeling of spiral arteries are observed in OD pregnancy irrespective of whether preeclampsia occurs. These findings may partly explain why OD pregnancy is associated with a high risk of gestational hypertension and preeclampsia. We need to clarify the immunological and pathological differences between uncomplicated and complicated OD pregnancy. In uncomplicated OD pregnancy, the level of HLA match between mother and baby is significantly higher than would be expected by chance, suggesting that miscarriage may be frequent with marked HLA mismatch. This review discusses the relationship between various aspects of the immune system and complications of OD pregnancy.

Impairment of the accumulation of decidual T cells, NK cells, and monocytes, and the poor vascular remodeling of spiral arteries, were observed in oocyte donation cases, regardless of the presence or absence of preeclampsia.

In oocyte donation (OD) pregnancies, a fetus is a complete allograft to the maternal host and OD pregnancies are an independent risk factor for preeclampsia. Immunocompetent cells contribute to spiral artery remodeling and the failure of this process could contribute to the pathophysiology of preeclampsia. Recent data have shown that impaired autophagy of extravillous trophoblasts (EVT) may induce poor vascular remodeling in preeclampsia. We have studied the distribution of T cells, NK cells and macrophages in the decidua basalis of 14 normotensive OD pregnancies, 5 preeclamptic OD cases, 16 normotensive pregnancy cases, and 13 preeclamptic cases in natural pregnancy or autologous oocyte IVF-ET (NP/IVF). The populations of decidual CD3(+)T cells, CD8(+)T cells, CD4(+)T cells, Foxp3(+)Treg cells, CD56(+)NK cells, and CD68(+) macrophages in preeclampsia were significantly smaller than those in normal pregnancy in NP/IVF. Those frequencies in normotensive OD pregnancies or preeclamptic cases in OD pregnancies were similar to those in preeclamptic cases in NP/IVF. Impaired vascular remodeling was observed in OD pregnancies, regardless of the presence or absence of preeclampsia. The expression of p62, an impaired autophagy marker in EVT of normotensive or preeclamptic OD pregnancies, was significantly higher than that in normal pregnancies in NP/IVF. Immunological change in the decidua basalis and impairment of autophagy in EVT may induce impairment of spiral artery remodeling in OD pregnancies.

Management of the occiput posterior presentation: a single institute experience.

AIM: We have examined the risk factors and management processes of the persistent occiput posterior (pOP) position by analyzing medical records from our hospital. MATERIAL AND METHODS: Medical records and delivery notes from January 2007 to December 2009 were reviewed and 103 patients were identified as having the pOP position during active labor. A total of 1054 patients who had occiput anterior (OA) deliveries were used as control. RESULTS: There was no significant difference in population background between the pOP and control groups. Fifty-eight (56%) cases of pOP were identified before the birth of the fetal head whereas 45 were found to be in pOP at the birth. Among these cases identified as pOP before the birth, 30 (52%) patients underwent an attempt to rotate pOP to OA manually. A total of 14 (47%) attempts were successful and delivered OA vaginally. Of 16 cases whose attempts failed, five (31%) had cesarean delivery and 11 had vaginal OP delivery. The overall cesarean rate in this group was 16.7%. Twenty-eight patients who did not have any corrective intervention had a significantly higher rate of cesarean section (60.7%, P<0.001 by χ(2) analysis). The advanced head station and the wider dilatation resulted in a successful manual rotation. CONCLUSIONS: Attempts to correct pOP by manual rotation have better results when the head is in the mid-pelvis. Also, posture change reduces cesarean section rate. The current data suggest attempts to correct pOP to OA reduce cesarean section rate.

Clinical management and outcome of pregnancies complicated by previous abruption.

OBJECTIVES: We studied the clinical management and prognosis of pregnant women with a history of abruption, as well as the associated risk factors. METHODS: We reviewed the cases of 23 patients with a history of abruption and 66 patients with abruption. RESULTS: The recurrence rate of abruption was 4.3%. Intentional care prolonged gestational age in most patients. Although the incidence of abruption was low (0.44%), the consequences could be perinatal death and maternal disseminated vascular coagulation (DIC). CONCLUSION: To prevent abruption recurrence, careful monitoring during hospitalization is important. Both clinical findings and transabdominal echography are useful in diagnosing abruption.