論文 - 桂木 真司
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Pregnancy-associated hemorrhagic stroke: A nationwide survey in Japan
Enomoto N., Tanaka H., Katsuragi S., Hayata E., Hasegawa J., Nakata M., Takahashi J.C., Sekizawa A., Ishiwata I., Ikeda T.
Journal of Obstetrics and Gynaecology Research 47 ( 6 ) 2066 - 2075 2021年6月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Obstetrics and Gynaecology Research
Aim: The number of maternal deaths due to pregnancy-associated hemorrhagic stroke has not decreased despite a gradual decrease of maternal death in Japan. This study aimed to clarify the risk factors of hypertensive disorders of pregnancy-associated hemorrhagic stroke. Methods: This retrospective study analyzed pregnancy-associated hemorrhagic stroke patients with hypertensive disorders of pregnancy between 2013 and 2017 among 407 Japanese maternal and perinatal centers. Patients were divided into good or poor outcome groups and their maternal backgrounds and neonatal prognoses were compared. Results: We analyzed 61 cases, including 41 survival and 20 death cases, obtained from a secondary survey. Among the 61 hemorrhagic stroke cases, 62% were related to hypertensive disorders. Hypertensive disorders of pregnancy were observed in 75% of death cases. Use of MgSO4 or antihypertensive medication did not differ between the poor and good outcomes groups. In cases with antepartum onset of hypertensive disorders of pregnancy, outcomes were poor in 12 and good in 6 cases. Nine patients with poor outcomes and one with a good outcome had hypertension at the outpatient department without systemic evaluation (p = 0.043). Six poor outcomes patients and one good outcome spent more than 1 day from diagnosis at an outpatient clinic. Neurosurgery was performed in 11 poor outcome patients. Conclusion: Pregnant women who present with a hypertensive disorder at an outpatient clinic probably need to undergo blood tests and careful observation. Delayed systemic evaluation and intensive care for only a few days may result in the development of hemorrhage.
DOI： 10.1111/jog.14786
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Aortic dissection during pregnancy and puerperium: A Japanese nationwide survey
Tanaka H., Kamiya C.A., Horiuchi C., Morisaki H., Tanaka K., Katsuragi S., Hayata E., Hasegawa J., Nakata M., Sekizawa A., Ishiwata I., Ikeda T.
Journal of Obstetrics and Gynaecology Research 47 ( 4 ) 1265 - 1271 2021年4月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Obstetrics and Gynaecology Research
Aim: This study aimed to characterize the incidence and clinical significance of pregnancy-related aortic dissection using a large-scale survey in Japan. Methods: A questionnaire requesting the detailed information included in the clinical charts of pregnancy-related aortic dissection cases (without any personally identifying information) was designed between 2013 and 2017 and administered to 407 perinatal centers in Japan. The response rate was 70.5%. Seventeen cases of pregnancy-related aortic dissection were identified. Results: Maternal death due to aortic dissection was observed in nine patients (56.2%) while seven survived (43.8%). Dissection occurred during the postpartum period in 10 cases (62.5%), the third trimester in 4 (25.0%), labor in 1 (6.2%), and the second trimester in 1 (6.2%). The most common underlying diseases were: Marfan syndrome (25.0%), Loeys-Dietz syndrome (6.2%), hypertension (6.2%), and Takayasu aortitis (6.2%). Stanford type A aortic dissection was associated with maternal death during both pregnancy and the postpartum period. However, deceased patients showed lower rates of pre-diagnosed connective tissue disease than did survivors. Conclusions: The mortality rate of aortic dissection that occurred during pregnancy or postnatal periods was more than 50%. Aortic dissection occurred more frequently in the postnatal period than during pregnancy, and less frequently in women previously diagnosed with connective tissue disease than in women without any medical history of aortic disorders. If symptoms suggestive of aortic dissection, such as severe back pain, are observed, even after the end of pregnancy, exhaustive diagnostic examinations should be carried out.
DOI： 10.1111/jog.14657
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Pulmonary thromboembolism during pregnancy and puerperium: Comparison of survival and death cases
Takakura S., Tanaka H., Tanaka K., Katsuragi S., Hayata E., Nakata M., Hasegawa J., Sekizawa A., Ishiwata I., Ikeda T.
Journal of Obstetrics and Gynaecology Research 47 ( 4 ) 1312 - 1321 2021年4月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Obstetrics and Gynaecology Research
Aim: In Japan, the frequency of maternal deaths due to obstetric hemorrhage has been decreasing in the last decade, while that resulting from other causes such as pulmonary thromboembolism (PTE) was consistent. To help reduce maternal deaths due to PTE, we investigated PTE during pregnancy and puerperium and compared the survival and death cases, and aimed to find out life and death factors. Methods: This study was a retrospective analysis based on a clinical chart review in 407 maternal and perinatal centers. We compared the survival and death cases of PTE during pregnancy and puerperium from 2013 to 2017. Results: In PTE during pregnancy, the survival cases underwent significantly earlier diagnoses than the death cases, and thromboprophylaxis was performed in most of both the survival and death cases of PTE during puerperium according to the existing Japanese guidelines; however, only one fourth of the total cases underwent anticoagulation to prevent venous thromboembolism (VTE). Conclusions: Early diagnosis of PTE in suspected cases was associated with better survival during pregnancy.
DOI： 10.1111/jog.14687
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Reference range for C1-esterase inhibitor (C1 INH) in the third trimester of pregnancy
Tanaka H., Tanaka K., Enomoto N., Takakura S., Magawa S., Maki S., Nii M., Toriyabe K., Katsuragi S., Ikeda T.
Journal of Perinatal Medicine 49 ( 2 ) 166 - 169 2021年2月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Perinatal Medicine
The objectives of this study were to (i) establish the reference range and mean value for normal levels of C1-esterase inhibitor (C1 INH) during pregnancy, and (ii) investigate the association between C1 INH and uterine atony, as measured by blood loss at delivery. We prospectively studied 200 healthy pregnant women who were registered. We studied C1 INH levels in 188 women at 34 and 35 gestational weeks of pregnancy. The reference range for C1 INH during the third trimester of pregnancy was calculated using the value of C1 INH that was determined at registration. The mean value of C1 INH was determined to be 70.3% (95% confidence interval, 68.7-71.9). While the C1 INH levels in four women were determined to be 40% lower than the calculated mean value, amniotic fluid embolism (AFE) did not occur in any of the women studied. This study successfully demonstrated that a reference value for C1 INH activity can be established using the methods described herein. Further research is needed to determine whether C1 INH is involved in obstetric coagulopathy syndrome such as amniotic fluid embolism.
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Katsuragi S., Tanaka H., Hasegawa J., Kanayama N., Nakata M., Murakoshi T., Osato K., Nakamura M., Tanaka K., Sekizawa A., Ishiwata I., Yamamoto Y., Wakasa T., Takeuchi M., Yoshimatsu J., Ikeda T.
Journal of Maternal-Fetal and Neonatal Medicine 34 ( 3 ) 432 - 438 2021年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Maternal-Fetal and Neonatal Medicine
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.
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Stroke during pregnancy and puerperium among Japanese women: a single-center registry
Katsuragi S., Suzuki R., Toyoda K., Neki R., Miyamoto S., Iihara K., Takahashi J., Ikeda T., Yoshimatsu J.
Journal of Maternal-Fetal and Neonatal Medicine 34 ( 18 ) 2957 - 2964 2021年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Maternal-Fetal and Neonatal Medicine
Background: Stroke is one of the major causes of maternal death. This study aimed to analyze the maternal and fetal outcomes of stroke occurred during pregnancy and puerperium. Methods: We conducted a retrospective analysis of patients admitted to our perinatology center between 1982 and 2012 with a diagnosis of acute cerebral stroke during pregnancy or within 6 weeks postpartum. Results: Thirty-four patients were registered and all the patients had never been diagnosed as stroke nor detected cerebrovascular abnormalities before the current pregnancies. They were divided into 8 ischemic strokes (ISs) and 26 intracranial hemorrhage group. In the hemorrhage group, there was a spontaneous abortion and two patients chose artificial abortions to avoid rehemorrhage, and there were another three intrauterine fetal deaths (IUFDs) in the acute stage of maternal stroke. More patients in hemorrhage group delivered in preterm than in IS group for the treatment of stroke, 10/23 (43%) versus 0/8 (0%), p <.05. More patients in hemorrhage group had low Glasgow Coma Scale (GCS) (3–8) than in IS group at the onset of the stroke, 12/26 (46%) versus 0/8 (0%), p <.05. There were three maternal deaths and 6/23 (26%) were neurologically dependent in hemorrhage group in the chronic stage, whereas 87% were independent in IS group, p <.05. Conclusions: Hemorrhagic stroke was more common etiology of stroke related to pregnancy than IS in this study. Intensive and multidisciplinary care was needed especially in hemorrhagic stroke related to pregnancy as in the hemorrhagic stroke the fetal survival rate was lower, and maternal conscious levels at the onset of the stroke and neurological outcomes in the chronic stage were worse than IS.
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Retrospective study of pregnancies in women with Thr331Ala fibrinogen polymorphisms
Okumura A., Tanaka H., Tanaka K., Katsuragi S., Kamimoto Y., Ikeda T.
Journal of Maternal-Fetal and Neonatal Medicine 33 ( 23 ) 3894 - 3899 2020年12月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Maternal-Fetal and Neonatal Medicine
Background: We aimed to retrospectively review data of pregnant women with the α-fibrinogen Thr331Ala polymorphism; evaluate the relationship between this polymorphism and spontaneous abortion (SA), fetal growth restriction (FGR), and intrauterine fetal death (IUFD); and assess the effects of aspirin and/or heparin. Materials and methods: We examined the outcomes of 29 pregnancies (nine women) in women with the α-fibrinogen Thr331Ala polymorphism. Of these, 16 were untreated, whereas 13 were treated with heparin and/or aspirin. Results: The live birth rate was significantly higher in the treated group than in the nontreated group (69.2 versus 6.2%; p =.0004). In addition, the prophylactic use of a low dose of aspirin and/or heparin during early pregnancy in women with Thr331Ala may be an effective method for reducing fetal loss in these patients. Conclusions: This polymorphism interacts with pregnancy to result in poor obstetrical outcomes, but these effects can be mitigated with medical intervention. This study is the first to report outcomes of pregnancies complicated by the Thr331Ala polymorphism, which we believe may cause thrombophilia, SA, and IUFD. This study highlights the need for further research on this polymorphism in pregnancy.
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Tsuchiya K., Tanaka K., Tanaka H., Maki S., Enomoto N., Takakura S., Nii M., Toriyabe K., Katsuragi S., Ikeda T.
Medicina (Lithuania) 56 ( 12 ) 1 - 8 2020年12月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Medicina (Lithuania)
Background and Objectives: Fetal growth restriction (FGR) is associated with fetal mortality and is a risk factor for cerebral palsy and future lifestyle-related diseases. Despite extensive research, no effective treatment strategy is available for FGR. Mammalian target of rapamycin (mTOR) signaling is important for the growth of fetal organs and its dysregulation is associated with miscarriage. Here, we focused on mTOR signaling and investigated how the activities of phospho-ribosomal protein S6 (rps6) and phospho-eukaryotic translation initiation factor 4E (eIF-4E), which act downstream of mTOR signaling in the human placenta, change following treatment of FGR with tadalafil and aimed to elucidate the underlying mechanism of action. Placental hypoxia was investigated by immunostaining for hypoxia-inducible factor (HIF)-2α. Materials and Methods: Phosphor-rps6 and phosphor-eIF4E expression were examined by Western blotting and enzyme-linked immunosorbent assay, respectively. Results: HIF-2α expression significantly increased in FGR placenta compared with that in the control placenta but decreased to control levels after tadalafil treatment. Levels of phospho-rps6 and phospho-eIF-4E were significantly higher in FGR placenta than in control placenta but decreased to control levels after tadalafil treatment. Conclusions: Tadalafil restored the levels of HIF-2α, phospho-rps6, and eIF-4E in FGR placenta to those observed in control placenta, suggesting that it could be a promising treatment strategy for FGR.
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Katsuragi S., Okamura T., Kokubo Y., Watanabe M., Higashiyama A., Ikeda T., Miyamoto Y.
Journal of Obstetrics and Gynaecology Research 46 ( 3 ) 517 - 526 2020年3月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Obstetrics and Gynaecology Research
Aim: We previously reported that female babies born small developed cardiovascular risks in middle age. The present study was conducted using the same cohort to examine the relationship between physique at 6 years and the metabolic disease risk in middle age. Methods: Data collected from 721 women aged 41–69 years who underwent a medical examination at a single institution between 2007 and 2008 were retrospectively examined. We collected data from medical examinations and a questionnaire on physique (thin, normal, and fat) at 6 years. The relationship between birthweight and physique at 6 years was investigated. Results: Among females who were born small (< 2500 g), 80%, 16%, and 4% became thin, normal, or fat, respectively, by 6 years. Physique at 6 years had a negative relationship with future triglyceride, fasting glucose, HbA1C, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) levels and a positive relationship with high-density lipoprotein cholesterol levels. Conclusion: Although our findings may be specific to the study population, physique at 6 years had a negative relationship with the metabolic disease risk in middle-aged Japanese women. Insulin and MOMA-IR levels negatively correlated with physique at 6 years, and development from low birthweight infants to childhood obesity was rare in this cohort.
DOI： 10.1111/jog.14206
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Kikuchi H., Noda S., Katsuragi S., Ikeda T., Horio H.
PLoS ONE 15 ( 2 ) 2020年2月
掲載種別：研究論文（学術雑誌） 出版者・発行元：PLoS ONE
Objective: The relevance between time-series fetal heart rate (FHR) pattern changes during labor and outcomes such as arterial blood gas data at delivery has not been studied. Using 3-tier and 5-tier classification systems, we studied the relationship between time-series FHR pattern changes before delivery and umbilical artery blood gas data at delivery. Methods: The subjects were 1,909 low-risk women with vaginal delivery (age: 29.1 ± 4.4 years, parity: 1.7 ± 0.8). FHR patterns were classified by a skilled obstetrician based on each 10 min-segment of the last 60 min before delivery from continuous CTG records in an obstetric clinic. Results: The relationship between each 10 min-segment FHR pattern classification from 60 minutes before delivery and umbilical artery blood pH and base excess (BE) values at delivery changed with time. In the 3-tier classification, mean pH of Category I group in each 10 min-segment was significantly higher than that of Category II group. For Category I groups in each 10-minute segment, its number decreased and its average pH increased as the delivery time approached. In the 5-tier classification, there was the same tendency. About each level group in 10 min-segment, the higher the level, the lower the blood gas values, and mean pH of higher level groups decreased as the delivery time approached. Conclusions: The relationship between classifications and outcomes was clear at any time from 60 min before delivery in 3- and 5-tier classifications, and the 5-tier classification was more relevant.
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Katsuragi S., Tanaka H., Hasegawa J., Kurasaki A., Nakamura M., Kanayama N., Nakata M., Hayata E., Murakoshi T., Yoshimatsu J., Osato K., Tanaka K., Oda T., Sekizawa A., Shimaoka T., Ishiwata I., Takahashi J., Ikeda T.
Journal of Maternal-Fetal and Neonatal Medicine 1 - 6 2020年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Maternal-Fetal and Neonatal Medicine
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.
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Katsuragi S., Okamura T., Kokubo Y., Watanabe M., Higashiyama A., Ikeda T., Miyamoto Y.
Journal of Atherosclerosis and Thrombosis 27 ( 3 ) 204 - 214 2020年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Atherosclerosis and Thrombosis
Aim: To investigate the relationship between perinatal condition around birth and cardiovascular risk in later life. Methods: Retrospective data were examined from 1241 city dwellers (521 men, 720 women; age 41–69 years) who had undergone medical examination at a single institution including blood tests and physical measurements from 2007 to 2008. The questionnaire was conducted to determine how perinatal factors affect their lives later. We also selected and studied a total of 28 individuals (12 men and 16 women) specifically about the conformity rate of the breastfeeding method between participants’ memories and what was written in the maternal and child health handbooks. Results: The conformity rate of the breastfeeding method between a self-questionnaire and his/her maternal and child health handbook was well correlated (r =0.73; p＜0.025). Among the data in women who were born at home, HbA1C levels (5.36±0.03 vs. 5.25±0.05 mg/dL, p=0.03) and low-density lipoprotein cholesterol (136.0±1.4 vs. 129.3±2.5 mg/dL, p=0.04) were higher than women who were born at the hospital. Women raised by formula showed higher low-density lipoprotein cholesterol levels than women fed breast milk or a mixture of breast milk and formula (150.2±4.8 vs. 138.7±3.7, 142.5±2.6 mg/dL, p =0.04). Fasting blood glucose levels at an adult time in men and women born through breech presentation were higher than those by the cephalic presentation (123.2±7.8 vs. 106.8±1.2 mg/dL, p=0.03). Conclusion: The study proposed that some perinatal conditions around birth such as delivery place, presenting part, and lactation affected especially Japanese women’s cardiovascular risks between ages 41 and 69 years.
DOI： 10.5551/jat.49577
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Risk factors for cardiovascular events among pregnant women with cardiovascular disease
Nii M., Tanaka H., Tanaka K., Katsuragi S., Kamiya C.A., Shiina Y., Niwa K., Ikeda T.
Internal Medicine 59 ( 9 ) 1119 - 1124 2020年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Internal Medicine
Objective: Cardiovascular disease increases the risk of maternal mortality. This study examined the risk factors for cardiovascular events in pregnant women with cardiovascular disease. Methods: This was a case-control study conducted in 2 phases at Japanese maternal and fetal care centers. The primary survey, using an interviewer-administered questionnaire, investigated whether the institutions had managed pregnant women with cardiovascular disease from April 2014 to March 2016. From 424 individual facilities surveyed, 135 facilities were found to have experience in managing pregnant women. In the secondary survey, the 135 institutions were asked to complete a web-based questionnaire, which collected detailed clinical information about cases, including cardiovascular disease, cardiovascular events, maternal background, and the perinatal outcome. Results: Information on 302 pregnant women with cardiovascular disease was collected. None of the 302 patients died. There were 25 women with cardiovascular events (cardiovascular event group) and 277 women without cardiovascular events (non-cardiovascular event group); the two groups were compared. No significant differences were found in the perinatal outcomes. Medication use before pregnancy was identified as a risk factor for cardiovascular events (adjusted odds ratio, 23.28; 95% confidence interval, 8.15-66.47; p< 0.001). In pregnant women with cardiovascular disease, New York Heart Association (NYHA) functional class II or III before pregnancy was associated with a higher risk of cardiovascular events in comparison to NYHA functional class I (p<0.001 for both). Conclusion: Medication use before pregnancy and NYHA functional class >I were risk factors for cardiovascular events in pregnant women with cardiovascular disease.
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Katsuragi S., Parer J.T., Noda S., Onishi J., Kikuchi H., Ikeda T.
Journal of Maternal-Fetal and Neonatal Medicine 28 ( 13 ) 1608 - 1613 2015年9月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Maternal-Fetal and Neonatal Medicine
© 2014 Informa UK Ltd. All rights reserved. Objective: We have reported a 7-fold reduction in newborn umbilical arterial (UA) metabolic acidemia after adoption of a rule-based 5-category color-coded fetal heart rate (FHR) management framework. We sought evidence for the relationship being causal by detailed analysis of FHR characteristics and acid-base status before and after training. Methods: Rates of UA pH and base excess (BE) were determined over a 5-year period in a single Japanese hospital, serving mainly low-risk patients, with 3907 deliveries. We compared results in the 2 years before and after a 6-month training period in the FHR management system. We used a previously published classification schema, which was linked to management guidelines. Results: After the training period, there was an increase in the percentage of normal patterns (23%), and a decrease in variable decelerations (14%), late decelerations (8%) and prolonged decelerations (12%) in the last 60 min of labor compared to the pre-training period. There was also a significant reduction in mean UA pH and BE in the groups with decelerations after introduction of the FHR management framework. Conclusions: The adoption of this FHR management system was associated with a reduction of decelerations and metabolic acidemia, without a change in cesarean or vacuum delivery rates. These results suggest that the obstetrical providers were able to better select for intervention those patients destined to develop more severe acidemia, demonstrating a possible causal relationship between the management system and reduced decelerations and metabolic acidemia.
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Katsuragi S., Ikeda T., Noda S., Onishi J., Ikenoue T., Parer J.T.
Journal of Maternal-Fetal and Neonatal Medicine 26 ( 1 ) 71 - 74 2013年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Maternal-Fetal and Neonatal Medicine
Objective: To determine whether a rule-based system for fetal heart rate interpretation can result in reduced metabolic acidemia without increasing obstetrical intervention. Methods: Rates of vacuum-assisted delivery and Cesarean sections, and umbilical artery pH and base excess values were determined over a 5-year period in a single hospital with 3907 deliveries in Japan. Results were compared for 2 years before and 2 years after a 6-month training period in rule-based fetal heart rate interpretation. Results: The pre- and post-training rates of unscheduled Cesarean deliveries (4.8% vs. 6.0%) and vacuum deliveries (21.2% vs. 18.1%) did not differ significantly. The rates of umbilical arterial pH <7.15 (1.51% vs. 0.18%, p < 0.05) and base excess <-12 mEq/L (1.76% vs. 0.25%, p < 0.05) were significantly lower after training. Conclusion: A standardized fetal heart rate pattern management system was associated with a 7-fold reduction of newborn metabolic acidemia with no change in operative intervention. © 2013 Informa UK, Ltd.
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新生児低酸素性虚血性脳症に対するグリア細胞由来神経栄養因子による治療戦略
桂木 真司, 池田 智明, 池ノ上 克
脳と発達 43 ( 4 ) 265 - 272 2011年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本小児神経学会
 新生仔ラットの脳内におけるグリア細胞由来神経栄養因子 (GDNF) の発現量は発達とともに変化する. 低酸素虚血負荷を与えたラットの脳内では結紮側の受傷部位において特にGDNFが増加する. 外因性のGDNFを脳に直接作用させるため, 細胞にGDNFの遺伝子を導入し, 半透膜製カプセル内に充填し, 大脳実質内に移植する方法を開発した. この方法は長期間, 低用量の薬剤を安全に供給できる特徴を持つ. 同方法を低酸素虚血負荷を与えた新生仔ラットに応用した. 梗塞面積は著明に減少し, 神経保護効果を持つことが示された. また, 同方法は低酸素虚血負荷後の記憶と学習障害に関しても長期にわたり優れた改善効果を示した.
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Katsuragi S., Ikeda T., Ikenoue T.
No To Hattatsu 43 ( 4 ) 265 - 272 2011年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：No To Hattatsu
Hypoxic-ischemic encephalopathy is one of the main causes of neurological disabilities. It has been reported that the infarcted area can be reduced by injection of glial cell line-derived neurotrophic factor (GDNF) into the brain parenchyma after a hypoxic/ischemic insult in neonatal rats. We have shown that GDNF is expressed in neuronal and non-neuronal cells throughout all regions of the developing rat brain. We developed a system for the delivery of a constant supply of glial cell line-derived neurotrophic factor to the brain via implantation of GDNF secreting cells directly into the brain parenchyma. The aim of this study was to examine the neuroprotective effect of GDNF using this delivery system. We implanted a capsule containing GDNF secreting cells in 7 day old Wistar rats, and two days later, they underwent hypoxic-ischemic stress. The capsule provided strong neurological protection, as indicated by a reduction in the infarcted area and the severity of histological damage in the treated group compared with controls. We then investigated whether this new delivery method improved the long time learning and memory disability caused by hypoxic-ischemic stress. We examined the effect of implantation of the cells on three tasks : 1) eight arm radial maze task for short memory ; 2) choice reaction time task for reference memory; and 3) water maze task for long term memory. In all of the three tasks, implantation of the GDNF capsule improved learning and memory disability. Glial cell line-derived neurotrophic factor treatment is effective not only in reducing brain damage but also in preventing learning and memory impairment following hypoxic-ischemic insult in neonatal rats.
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桂木 真司, 鮫島 浩, 池ノ上 克
日本産婦人科・新生児血液学会誌 = The Japanese journal of obstetrical, gynecological & neonatal hematology 16 ( 1 ) "S - 17"-"S-18" 2006年6月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Katsuragi S., Ikeda T., Date I., Shingo T., Yasuhara T., Ikenoue T.
American Journal of Obstetrics and Gynecology 192 ( 4 ) 1137 - 1145 2005年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Obstetrics and Gynecology
Objective: It has been reported that an infarcted area is reduced by the injection of glial cell line-derived neurotrophic factor into brain parenchyma after hypoxic/ischemic insult in neonatal rats. For use of glial cell line-derived neurotrophic factor in humans, we have developed a system for the delivery of a constant supply of glial cell line-derived neurotrophic factor to the brain. The aim of this study was to examine the neuroprotective effect of glial cell line-derived neurotrophic factor with the use of this delivery system. Study design: Baby hamster kidney cells were transfected with human glial cell line-derived neurotrophic factor complementary DNA, encapsulated in semipermeable hollow fibers, and implanted into the left cerebrum of 12-day-old Wistar rats (glial cell line-derived neurotrophic factor group, 11 rats). Nontransfected baby hamster kidney cells served as controls (control group, 9 rats). Two days after implantation, the rats received a hypoxic/ischemic stress, with a modification of Levine's method. Seven days later the rats were killed, and coronal brain slices were cut 2, 4, 6, 8, and 10 mm from the anterior pole. The cortex, hippocampus, striatum, and thalamus were evaluated for damage severity. The serum concentrations of glial cell line-derived neurotrophic factor were also determined. Results: The left brain hemispheric area was significantly larger; the neuronal damage to each brain region was significantly less, and the serum glial cell line-derived neurotrophic factor concentrations were significantly higher in the glial cell line-derived neurotrophic factor group, compared with the control group. Conclusion: Grafting of encapsulated glial cell line-derived neurotrophic factor-secreting cells is a promising way to protect the neonatal brain from hypoxic/ischemic insult. © 2005 Elsevier Inc. All rights reserved.
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Katsuragi S., Ikeda T., Date I., Shingo T., Yasuhara T., Mishima K., Aoo N., Harada K., Egashira N., Iwasaki K., Fujiwara M., Ikenoue T.
American Journal of Obstetrics and Gynecology 192 ( 4 ) 1028 - 1037 2005年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Obstetrics and Gynecology
Objective: Implantation of encapsulated glial cell line-derived neurotrophic factor-secreting cells into brain parenchyma reduces histological brain damage following hypoxic-ischemic stress in neonatal rats. We examined the effect of glial cell line-derived neurotrophic factors on long-term learning and memory impairment and morphological changes up to 18 weeks after hypoxic-ischemic stress in neonatal rats. Study design: Baby hamster kidney cells were transfected with expression vector either including (glial cell line-derived neurotrophic factor-hypoxic-ischemic group; n = 10) or not including (control-hypoxic-ischemic group; n = 8) human glial cell line-derived neurotrophic factor cDNA, encapsulated in semipermeable hollow fibers, and implanted into the left brain parenchyma of 7-day-old Wistar rats. Two days after implantation the rats received hypoxic-ischemic stress, and their behavior was then examined in several learning tasks: the 8-arm radial maze, choice reaction time, and water maze tasks, which examine short-term working memory, attention process, and long-term reference memory, respectively. The rats were killed 18 weeks after the hypoxic-ischemic insult for evaluation of brain damage. Two additional control groups were used: the control group (n = 15), which underwent no treatment, and the glial cell line-derived neurotrophic factor group (n = 6), which underwent implantation of the glial cell line-derived neurotrophic factor capsule but did not undergo hypoxic-ischemic stress. Results: The decrease in the size of the cerebral hemisphere was significantly less in the glial cell line-derived neurotrophic factor-hypoxic-ischemic group, compared with the control-hypoxic-ischemic group, and improved performance was observed in all three tasks for the glial cell line-derived neurotrophic factor-hypoxic-ischemic group: for the control-hypoxic-ischemic group versus the glial cell line-derived neurotrophic factor-hypoxic-ischemic group, respectively, in the 8-arm radial maze test, average number of correct choices was 6.2 ± 0.1 versus 6.9 ± 0.1 (P < .01); in the choice reaction time test, average reaction time for a correct response was 2.35 ± 0.1 seconds versus 1.97 ± 0.09 seconds (P < .01); in the water maze test, average swimming length was 1120.0 ± 95.2 cm versus 841.6 ± 92.1 cm (P < .01). All results for the glial cell line-derived neurotrophic factor group were similar to those for the control group. Conclusion: Glial cell line-derived neurotrophic factor treatment is effective in not only reducing brain damage but also inhibiting learning and memory impairment, following hypoxic-ischemic insult in neonatal rats. No adverse effects in learning and memory tests were observed in the glial cell line-derived neurotrophic factor group. © 2005 Elsevier Inc. All rights reserved.