Details of a Researcher - Kasuga, Yoshifumi

Papers - Kasuga, Yoshifumi

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The Association Between Glucose Variability and Insulin Parameters in Gestational Diabetes Diagnosed After 24 Gestational Weeks

Kasuga Y., Kajikawa K., Ishikawa N., Ogata Y., Takahashi M., Akita K., Tamai J., Fukuma Y., Tanaka Y., Otani T., Fukutake M., Ikenoue S., Tanaka M.

Nutrients 17 ( 3 ) 2025.02

Background/Objectives: Recently, it was reported that glucose variability (GV) calculated using the 75 g oral glucose tolerance test (OGTT) is associated with adverse perinatal outcomes. However, its role in gestational diabetes mellitus (GDM) remains unclear. We investigated the association between GV and insulin parameters in Japanese women diagnosed with GDM after 24 weeks of gestation (late GDM). Methods: A total of 280 mothers with late GDM cared for at Keio University Hospital were included in this study. Using 75 g OGTT, the initial increase and subsequent decrease were calculated as the GV. Results: The initial increase was significantly positively associated with 1 h plasma glucose level (PG) and 2 h PG with 75 g OGTT (p < 0.001), but fasting PG, insulinogenic index (IGI), and homeostasis model assessment—insulin resistance were negatively associated with the initial increase (all p < 0.001). The subsequent decrease was significantly positively correlated with 1 h PG (p < 0.001) but negatively correlated with 2 h PG (p < 0.001), IGI (p = 0.009), and the whole-body insulin sensitivity index derived from the OGTT (p = 0.02). Insulin Secretion-Sensitivity Index-2 was not associated with an initial increase or subsequent decrease. Conclusions: Since the initial increase might reflect insulin secretion and the subsequent decrease might reflect insulin sensitivity in Japanese women with late GDM, GV could alter several insulin parameters. Further studies are required to investigate the usefulness of GV in the management of GDM.

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Should the Definition of Low Birth Weight Be Same in Every Ethnicity Considering the DOHaD Concept?

Kasuga Y, Tanaka M

Pediatric reports 17 ( 1 ) 2025.01

ISSN 2036-749X

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胎児発育不全に右大動脈弓を伴った9番染色体トリソミーモザイクの1例

酒井美晴, 秋田啓介, 春日義史, 福間優花, 玉井順子, 田中雄也, 長谷川慶太, 大谷利光, 池ノ上学, 丸山哲夫, 青木大輔, 田中守

関東連合産科婦人科学会誌 ((一社)関東連合産科婦人科学会) 61 ( 4 ) 392 - 396 2024.11

ISSN 2186-0610

【緒言】9番染色体トリソミーモザイクは心奇形などを合併する周産期死亡率の高い予後不良な染色体異常である.今回我々は当院で周産期管理を行った胎児9番染色体トリソミーモザイクの1例を経験したので報告する.【症例】39歳.G2P1(第1子は妊娠36週で常位胎盤早期剥離による死産分娩).タイミング法で妊娠成立後,妊娠11週の頭殿長より分娩予定日を決定,当院で妊婦健診を行っていた.なお,無侵襲的出生前遺伝学的検査や羊水検査の受検はなかった.妊娠21週の胎児超音波断層法で大動脈縮窄症を疑い,精査を行った.妊娠23週時に胎児発育不全(-2.0SD),単一臍帯動脈,右大動脈弓,左上大静脈遺残と診断した.妊娠31週には推定体重1,071g(-3.0SD)となったことから入院管理とした.妊娠34週6日,胎児機能不全の診断で緊急帝王切開術を施行した.児は女児,1,119g(-4.0SD),Apgar score 7/8点(1/5分値),上記診断の他に眼瞼裂斜上,耳介低位,小顎を認めた.さらに,出生後の染色体検査で9番染色体トリソミーモザイクと診断された.【結語】今回我々は胎児発育不全に右大動脈弓を伴った9番染色体トリソミーモザイクの1例を経験した.本症例のように右大動脈弓を合併する場合もあり,9番染色体トリソミーモザイクは多彩な臨床像を呈することが再認識された.(著者抄録)

Abstracts of the 34th World Congress on Ultrasound in Obstetrics and Gynecology, 15-18 September 2024, Budapest, Hungary

Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 64 2024.09

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Use of the Japanese gestational diabetes mellitus diagnostic strategy during the COVID-19 pandemic in Japan: A questionnaire survey

Kasuga Y., Miyakoshi K., Yokoyama M., Nakanishi S., Iwama N., Ichikawa R., Abiko A., Harashima S., Sugiyama T.

Journal of Obstetrics and Gynaecology Research 50 ( 6 ) 955 - 960 2024.06

ISSN 13418076

Aim: Some concerns exist that diagnosis of gestational diabetes mellitus (GDM) may be missed when the simplified diagnostic criteria of the Japanese Society of Diabetes and Pregnancy (JSDP) for GDM (published during the COVID-19 pandemic) are used. Moreover, limited data is available regarding how widespread these diagnostic criteria are used when managing GDM during the COVID-19 pandemic. Therefore, this study aimed to determine how GDM diagnosis has changed during the COVID-19 pandemic in Japan. Methods: The changes in GDM diagnosis during the COVID-19 pandemic were investigated using an online questionnaire to 2159 obstetric facilities in Japan. The questionnaire collected data on facility type, awareness of Japanese GDM diagnostic strategies, modifications to diagnostic methods for early and late GDM, and opinions on GDM management, with the pandemic divided into seven periods. Results: We received responses from 593 facilities (27%). Approximately 90% of the facilities did not change their diagnostic process for early GDM or late GDM (occurring after 24 weeks gestation). However, during the COVID-19 pandemic, 19 facilities discontinued the use of 75-g oral glucose tolerance tests before 24 weeks of gestation, and 17 facilities discontinued it after 24 weeks of gestation, instead using the aforementioned Japanese GDM diagnostic strategy. Conclusions: Although a limited number of facilities modified their diagnostic method in response to the COVID-19 pandemic, this study demonstrated that those that adjusted their diagnostic method primarily used the Japanese COVID-19 GDM strategy by the JSDP.

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Perinatal Outcomes of Diet Therapy in Gestational Diabetes Mellitus Diagnosed before 24 Gestational Weeks

Kasuga Y., Takahashi M., Kajikawa K., Akita K., Otani T., Ikenoue S., Tanaka M.

Nutrients 16 ( 11 ) 2024.05

To evaluate perinatal outcomes and risk factors for large for gestational age (LGA; birth weight over 90 percentile) in gestational diabetes diagnosed before 24 gestational weeks and treated with diet therapy alone until delivery (Diet Early gestational diabetes mellitus (Diet Early GDM)), we assessed the maternal characteristics and perinatal outcomes of patients with early GDM (n = 309) and normal glucose tolerance (NGT; n = 309) at Keio University Hospital. The gestational weight gain (GWG) expected at 40 weeks was significantly lower in the Diet Early GDM group than in the NGT group. The Diet Early GDM group exhibited a significantly lower incidence of low birth weight (<2500 g) and higher Apgar score at 5 min than the NGT group. Multiple logistic regression analysis revealed that the pre-pregnancy body mass index and GWG expected at 40 weeks were significantly associated with LGA for Diet Early GDM. No differences were observed in random plasma glucose levels in the first trimester, 75 g oral glucose tolerance test values, and initial increase or subsequent decrease between the two groups. Dietary early GDM did not exhibit a worse prognosis than NGT. To prevent LGA, it might be important to control maternal body weight not only during pregnancy but also before conception.

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Association of maternal obesity with growth of fetal fractional limb volume

Ikenoue S., Akiba Y., Ishii R., Otani T., Kasuga Y., Tanaka M.

Early Human Development 191 105990 2024.04

ISSN 03783782

Background: Maternal obesity influences birth weight and newborn adiposity. Fetal fractional limb volume has recently been introduced as a useful parameter for the proxy of fetal adiposity. However, the association between maternal adiposity and the growth of fetal fractional limb volume has not been examined. Aims: To investigate the association of maternal pre-pregnancy BMI with the growth of fetal fractional limb volume. Study design: Prospective cohort study. Subjects: Women with singleton uncomplicated pregnancies enrolled between July 2017 and June 2020. Outcome measures: Fetal fractional limb volume was assessed between 20 and 40 weeks' gestation, measured as cylindrical limb volume based on 50 % of the total diaphysis length. The measured fractional limb volume at each gestational week were converted to z-scores based on a previous report. The association between pre-pregnancy BMI and fetal fractional limb volume was examined. Maternal age, parity, gestational weight gain and fetal sex were considered as potential confounding variables. Results: Ultrasound scans of 455 fractional arm volume and thigh volume were obtained. Fractional limb volume increased linearly until the second trimester of gestation, then increased exponentially in the third trimester. Maternal pre-pregnancy BMI was significantly correlated with z-scores of fractional arm volume and thigh volume across gestation. The post-hoc analysis showed the association between pre-pregnancy BMI and fractional arm volume was significant especially between 34 and 40 weeks. Conclusions: Maternal obesity influences the growth pattern of fetal fractional limb volume. Fractional arm volume may potentially provide a useful surrogate marker of fetal nutritional status in late gestation.

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血清hCG値の推移を観察した妊娠高血圧腎症合併間葉性異形成胎盤の1例

山本大貴, 田中邦生, 高橋まりな, 梶川かおる, 秋田啓介, 福間優花, 大谷利光, 池ノ上学, 春日義史, 山上亘, 田中守

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 73 ( 2 ) 402 - 406 2024.04

ISSN 2186-0599

間葉性異形成胎盤(PMD)は5000妊娠に1例で発生する稀な胎盤形態異常である.今回我々は血清hCG値の推移を観察した妊娠高血圧腎症(PE)合併PMDの1例を経験したので報告する.症例は30歳,1妊0産.体外受精-胚移植で妊娠成立後,妊娠15週の経腹超音波断層法で胎盤に大小不同な嚢胞を多数認めた.血清hCGは417484mIU/mlであり,その後漸減したが妊娠後期も高値であり,PMDと胎児共存奇胎を鑑別に管理した.妊娠34週健診時,高血圧と蛋白尿を認めPEの診断となり,症状の増悪のため妊娠35週に緊急帝王切開術を施行した.児は2245gの女児,Apgar score 7/8点(1/5分値),明らかな外表奇形は認めなかった.胎盤は1237gで,病理組織学的検査でPMDと診断した.本症例では,妊娠初期に血清hCGが高値であるPMDではPE発症に注意し管理することが重要である可能性が示唆された.(著者抄録)

Sonographic changes in uterine vein thrombosis during pregnancy on transvaginal ultrasound

Sato A., Tanaka K., Sakuma M., Ikenoue S., Kasuga Y., Tanaka M.

Journal of Medical Ultrasonics 51 ( 2 ) 369 - 370 2024.04

ISSN 13464523

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広汎子宮頸部摘出術後に生じる月経変化とその妊娠成績に及ぼす影響

松田理沙, 西尾浩, 松井友哉, 椎名美季, 大野あゆみ, 谷本慧子, 横田めぐみ, 春日義史, 岩田卓, 山上亘, 田中守

関東連合産科婦人科学会誌 ((一社)関東連合産科婦人科学会) 61 ( 1 ) 90 - 96 2024.03

ISSN 2186-0610

【目的】広汎子宮頸部摘出術(radical trachelectomy:RT)後の月経変化は一定の割合で発生するが,その妊娠成績への影響に関しての報告は限定的である.今回,当科でRTを施行した症例について月経変化が妊娠成績に及ぼす影響について検討した.【方法】2002年9月から2021年3月に当院で腹式RTを施行した289例を対象とし,手術前後での月経変化(月経量,持続日数,月経周期,月経痛の変化および無月経)の有無を診療録より調査した.さらに月経変化と妊娠成績の関連について統計学的に解析を行った.【成績】RTを施行した289例中102例(35.3%)が手術後に月経変化を認めていた.その内訳は月経痛が38例(13.1%),月経量減少もしくは持続日数の短縮が35例(12.1%),月経不順が29例(10.0%),持続日数延長が15例(5.2%)であった(重複あり).また無月経が14例(4.8%)に生じ,うち6例が子宮性無月経と診断された.月経変化のあった群では,月経変化のない群と比較し頸管狭窄の頻度が有意に高かった(56例54.9% vs 21例11.2%,p<0.001).さらに月経変化のあった群では妊娠率は有意に低く(24例23.5% vs 72例38.5%,p=0.013),不妊治療を必要とした症例の割合が高かった(46例75.4% vs 73例57.9%,p=0.023).最後に,月経変化のあった群での流産率は有意に高く(11例45.8% vs 15例22.1%,p=0.036),周産期合併症(切迫流早産,早産期前期破水,絨毛膜羊膜炎,胎盤位置異常など)の頻度が高い傾向を認めた(18例85.7% vs 40例61.5%,p=0.059).【結論】RT施行後の月経変化は妊娠成立およびその維持に影響を及ぼすことが示唆された.(著者抄録)

Obstetric outcomes of transabdominal cerclage: A retrospective observational study in Japan

Kasuga Y., Tanigaki S., Seo K., Harada A., Kuwabara Y., Ishioka S., Tanaka M.

Journal of Obstetrics and Gynaecology Research 50 ( 10 ) 1835 - 1840 2024

ISSN 13418076

Objective: This study aimed to investigate the obstetric outcomes of transabdominal cerclage (TAC) in Japan. Methods: Questionnaires on TAC were sent to 183 institutions performing high-quality perinatal management in Japan. As a first-step questionnaire, we asked whether TAC was performed between January 1, 2011, and December 31, 2022. In the second step of the questionnaire, the characteristics of all cases were asked from all institutions in which TAC was performed. Results: The response rate for the first survey was 59% (108/183). Of the 108 institutions, 27 performed TAC (25%) in 133 pregnancies. Of these 27 institutions, 19 responded to the second survey. One hundred twenty-five pregnancies were included in this study, five of which were aborted (gestational weeks <22 weeks), and 69 babies were born after 37 gestational weeks (55%). Eighty-two open abdominal cerclages were performed at 17 institutions and 43 laparoscopic TACs at three institutions. There were no differences in the age at TAC, gestational weeks at TAC, operative time of TAC, gestational weeks at delivery, incidence rate of second-trimester loss, or preterm delivery (before 37 gestational weeks) rate between the two groups. However, blood loss during open TAC was greater than that during laparoscopic TAC. Conclusion: TAC is a rare surgery for cervical insufficiency in Japan. TAC may be a safe and useful method for preventing second-trimester loss and preterm delivery in high-risk patients. TAC may also be a key option in Japan to improve perinatal outcomes in patients with cervical insufficiency.

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Origins of obesity in the womb: Fetal adiposity and its determinants

Ikenoue S., Tamai J., Akita K., Otani T., Kasuga Y., Tanaka M.

Journal of Obstetrics and Gynaecology Research 50 ( 12 ) 2178 - 2182 2024

ISSN 13418076

Birth weight is an important predictor of perinatal complications and long-term health outcomes of offspring. Fetal programming influenced by maternal obesity, overnutrition, and hyperglycemia has been proposed as the fuel overload hypothesis. Recent investigations related with fetal body composition have revealed that neonatal adiposity can be predicted by fetal fat mass, and that maternal insulin resistance and serum leptin level are indicators of fetal adiposity. Based on the current evidence, the origins of obesity can partly be traced back into the fetal life. Further clarification of the determinants of fetal fat mass may lead to the clinical interventions and treatment strategies for fetal growth and development. This effort potentially leads to the elucidation of pathological conditions related with long-term health outcomes and the primary prevention of childhood obesity and early onset metabolic syndrome.

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Multiple positive points during the 75 g oral glucose tolerance test are good predictors for early insulin therapy in gestational diabetes mellitus diagnosed before 24 gestational weeks

Kasuga Y., Takahashi M., Kajikawa K., Akita K., Tamai J., Fukuma Y., Tanaka Y., Hasegawa K., Otani T., Ikenoue S., Tanaka M.

Journal of Diabetes Investigation 15 ( 12 ) 1803 - 1808 2024

ISSN 20401116

Aims/Introduction: This study evaluated the risk factors for insulin therapy before 24 gestational weeks (early insulin therapy) in pregnant women with gestational diabetes diagnosed before 24 gestational weeks (E-GDM). Materials and Methods: This study included 530 singleton mothers with E-GDM who underwent a 75 g oral glucose tolerance test (OGTT) in the first trimester at Keio University Hospital between January 2013 and December 2021. E-GDM can be classified according to its management into only diet therapy until delivery (Diet E-GDM), insulin therapy started before 24 gestational weeks (EarlyIns E-GDM), and insulin therapy started after 24 gestational weeks (LateIns E-GDM). We analyzed the risk factors for EarlyIns E-GDM. Results: Patients with EarlyIns E-GDM had a significantly higher maternal age at delivery, pre-pregnancy BMI, first trimester hemoglobin A1c, 1 h plasma glucose levels (1 h-PG), and 2 h-PG, as well as a more pronounced initial increase and subsequent decrease, compared with those in the Diet E-GDM group. However, the Apgar scores at both 1 and 5 min were significantly lower in patients with EarlyIns E-GDM than in those with Diet E-GDM. The number of abnormal values in the OGTT showed the largest area under the receiver operating characteristic curve (AUC) for predicting EarlyIns E-GDM (0.83, 95% confidence interval [CI]: 0.79–0.86), followed by the 1 h-PG value (AUC: 0.81, 95% CI: 0.77–0.85). The initial increase showed the third largest AUC (0.78, 95% CI: 0.74–0.82). Conclusions: Although further research is needed, our data suggest the importance of early insulin therapy in cases of E-GDM with multiple abnormal OGTT values, especially with high 1 h-PG levels and initial increase.

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Efficacy of controlled-release dinoprostone vaginal insert for elective induction of labor before due date

Tamai J., Ikenoue S., Akita K., Fukuma Y., Tanaka Y., Hasegawa K., Otani T., Kasuga Y., Tanaka M.

Journal of Obstetrics and Gynaecology Research 50 ( 12 ) 2226 - 2230 2024

ISSN 13418076

Aim: The induction of labor before due date has recently been proved to reduce the rate of cesarean sections and is not associated with increased risk of adverse perinatal outcomes as compared to expectant management. Controlled-release dinoprostone (PGE2) vaginal insert has recently been approved for use in Japan. However, evidence regarding its efficacy in cervical ripening and labor induction before due date remains limited. We aimed to compare the efficacy of PGE2 vaginal inserts and mechanical dilation for labor induction before due date. Methods: This retrospective cohort study included 206 mothers at 37, 38, and 39 weeks' gestation delivered at our institution between January 2021 and October 2022. Perinatal outcomes, including the success rate of vaginal delivery, were compared between the PGE2 (n = 46) and metreurynter/laminaria tent (non-PGE2) (n = 160) groups. The success rate of vaginal delivery was defined as the proportion of women who delivered vaginally within 48 h of initiating oxytocin augmentation. Results: The success rate of vaginal delivery was significantly higher in the PGE2 group (37/49, 80.4%) than in the non-PGE2 group (106/177, 66.2%). Emergency cesarean section related to non-reassuring fetal status was performed with none in the PGE2 group and with eight (5.0%) in the non-PGE2 group. Conclusions: The rate of vaginal delivery was significantly higher in the PGE2 group for elective labor induction between 37 and 39 weeks. The PGE2 vaginal insert could increase the success rate of vaginal delivery for elective induction of labor at 39 weeks.

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Pregnancy complicated by fetal goiter following lung transplantation for idiopathic pulmonary arterial hypertension: A case study

Hamuro A., Kasuga Y., Saito S., Uchida H., Hiraide T., Yamada Y., Arimitsu T., Date H., Fukushima H., Tanaka M.

Taiwanese Journal of Obstetrics and Gynecology 64 ( 1 ) 131 - 133 2024

ISSN 10284559

Objective: We report a case of pregnancy following lung transplantation (LT) for idiopathic pulmonary arterial hypertension (IPAH) in Japan. Case Report: A female developed IPAH at 14 years of age and underwent a successful bilateral living-donor lobar LT from her parents at 19 years of age (gravida 2, para 0). At the age of 40 years, the patient became pregnant via artificial insemination. At 28 weeks of gestation, polyhydramnios and a fetal goiter were detected on transabdominal ultrasound. The patient was diagnosed with deep vein thrombosis and pulmonary embolism. The patient underwent emergency cesarean section to deliver a male neonate weighing 1340 g (−0.41SD) at 30 weeks of gestation, with an Apgar score of 5/5 (1/5 min). Conclusion: To our knowledge, this is the first reported case of a successful pregnancy following LT in Japan. Specialists should work together to manage pregnancies following LT.

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A capture methyl-seq protocol with improved efficiency and cost-effectiveness using pre-pooling and enzymatic conversion

Hasegawa K., Nakabayashi K., Ishiwata K., Kasuga Y., Hata K., Tanaka M.

BMC Research Notes (BMC Research Notes) 16 ( 1 ) 141 2023.12

Objective: The opportunities for sequencing-based methylome analysis of clinical samples are increasing. To reduce its cost and the amount of genomic DNA required for library preparation, we aimed to establish a capture methyl-seq protocol, which adopts pre-pooling of multiple libraries before hybridization capture and TET2/APOBEC-mediated conversion of unmethylated cytosine to thymine. Results: We compared a publicly available dataset generated by the standard Agilent protocol of SureSelect XT Human Methyl-Seq Kit and our dataset obtained by our modified protocol, EMCap, that adopted sample pre-pooling and enzymatic conversion. We confirmed that the quality of DNA methylation data was comparable between the two datasets. As our protocol, EMCap, is more cost-effective and reduces the amount of input genomic DNA, it would serve as a better choice for clinical methylome sequencing.

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Efficacy and safety of a telemedicine system in subjects with gestational diabetes mellitus (TELEGLAM): Study protocol for a randomized controlled trial

Aoyama K., Nakajima Y., Meguro S., Sato Y., Goto R., Hida M., Arimitsu T., Kasuga Y., Tanaka M., Itoh H.

Heliyon 9 ( 11 ) e22504 2023.11

ISSN 24058440

Background: Strict glycemic control is important to prevent perinatal complications in patients with gestational diabetes mellitus (GDM). Patients often require insulin injection, and frequent hospital visits are necessary to adjust the dose of insulin, which is considered burdensome for pregnant patients. Telemedicine may reduce the burden of hospital visits, and previous studies have reported its safety in GDM patients. This study aimed to evaluate the efficacy of telemedicine in GDM patients, focusing on patient satisfaction and health economic indicators. Methods: This is a single-center, two-arm, randomized, open-label parallel-group study. Subjects will be selected from the patient population attending the Department of Endocrinology, Metabolism, and Nephrology, Keio University School of Medicine, Japan. Patients diagnosed with GDM by an oral glucose tolerance test (OGTT) by 29 weeks and 6 days of gestation who have undergone self-monitoring of blood glucose (SMBG) and insulin injection are eligible for inclusion. In the intervention group, telemedicine will be administered using the MeDaCa telemedicine system developed by the Medical Data Card, Inc., Tokyo, Japan. Subjects in the control group will be examined face-to-face every 2–3 weeks, as usual. We set health economic indicators and patient satisfaction as the primary endpoints, and will perform a cost-consequence analysis. Glycemic control indicators and perinatal outcomes will be evaluated as secondary endpoints. Conclusions: Eligible patients are currently being recruited. Recruitment will be completed when the expected number of patients are enrolled.

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自然妊娠成立後,経腟分娩に至ったOHVIRA症候群合併妊娠の一例

林宥希, 福間優花, 春日義史, 玉井順子, 葉室明香, 田中雄也, 長谷川慶太, 池ノ上学, 小林佑介, 青木大輔, 田中守

関東連合産科婦人科学会誌 ((一社)関東連合産科婦人科学会) 60 ( 4 ) 683 - 688 2023.11

ISSN 2186-0610

【緒言】Obstructed hemivagina and ipsilateral renal anomaly(OHVIRA)症候群はMueller管の癒合不全により,子宮形態異常,腟血腫,患側の腎形成不全を呈する稀な疾患である.今回OHVIRA症候群と診断した後,自然妊娠が成立し,36週で経腟分娩に至った症例を経験したので報告する.【症例】23歳,1妊0産.妊娠前に撮影した骨盤部MRI検査で重複子宮を認め,患側の右子宮は腟との連続性を認めず留血腫も見られなかった.さらに右腎欠損を伴うことよりOHVIRA症候群と診断した.妊娠10週5日に当科にて左子宮に自然妊娠を確認した.妊娠31週5日に子宮頸管長は15.0mmと短縮し,妊娠33週5日で切迫早産管理目的に緊急入院とした.妊娠36週0日に一時退院としたが,妊娠36週5日に前期破水し,妊娠36週6日に経腟分娩に至った.【結語】我々はOHVIRA症候群と診断した後,自然妊娠が成立し,妊娠36週に経腟分娩に至った症例を経験した.OHVIRA症候群合併妊娠では本症例のように経腟分娩可能な症例もあり,形態異常の程度が多岐にわたるため,個々の症例に合わせた検討が必要である.(著者抄録)

Factors associated with low birthweight among late preterm singletons in Japan using pregnancy birth registry data

Kasuga Y., Tanaka K., Akita K., Tamai J., Hamuro A., Fukuma Y., Hasegawa K., Ikenoue S., Tanaka M.

Journal of Developmental Origins of Health and Disease 14 ( 5 ) 584 - 590 2023.10

ISSN 20401744

Late preterm (LP, born between 34 0/7 and 36 6/7 weeks of gestation) infants may experience several adverse outcomes, similar to those experienced by low birthweight (LBW, birthweight <2500 g) infants. However, while LP infants are often born with LBW, the association between LP and LBW remains unknown. This study aimed to investigate LBW rate and independent risk factors for LBW in LP singleton neonates. We retrospectively analyzed data of LP singleton neonates, born between 2013 and 2017, from the Japan Society of Obstetrics and Gynecology Successive Pregnancy Birth Registry System. The exclusion criteria included stillbirths and infants with missing data. Logistic regression analyses were performed to investigate maternal and perinatal factors associated with LBW in LP singletons. LBW was observed in 62.5% (n = 35,113) of 56,160 LP singleton births. In the multiple logistic regression analysis, LBW in LP neonates was independently associated with modifiable maternal factors, including pre-pregnancy underweight, inadequate gestational weight gain, and smoking during pregnancy, as well as non-modifiable factors, including younger maternal age, nulliparity, hypertensive disorder of pregnancy, preeclampsia, cesarean section delivery, and female offspring. According to the Japanese pregnancy birth registry data, more than half of LP neonates were LBW. We previously discussed the issue of LBW regarding infants with different backgrounds, as there are many different causes of LBW. Several risk factors should be subdivided and considered for the risk of LP and LBW.

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非常時妊娠糖尿病診断に関する調査研究報告

春日義史, 宮越敬, 横山真紀, 中西沙由理, 岩間憲之, 市川雷師, 安孫子亜津子, 原島伸一, 杉山隆, 日本糖尿病・妊娠学会非常時GDM診断に関するワーキンググループ

糖尿病と妊娠 ((一社)日本糖尿病・妊娠学会) 23 ( 2 ) S - 50 2023.08

ISSN 1347-9172

目的:コロナ禍で妊娠糖尿病(gestational diabetes mellitus:GDM)診断がどのように変化したかを明らかにする。方法:全国の分娩取り扱い施設(2159施設)に対し、コロナ禍でのGDM診断方法の変化について調査した(回答率27%)。結果:妊娠24週未満/以降GDMともに90%前後の施設が診断方法を変更しなかった。一方、妊娠24週未満では19施設、24週以降では17施設が75g経口糖負荷試験を中止し、日本糖尿病・妊娠学会による「妊娠中の糖代謝異常のスクリーニング～COVID-19パンデミック対応～」を使用した。結論:今後のさらなる非常時に備え、有用な簡易型診断基準を作成するため、リスク因子抽出などの検討が必要であると考えられた。(著者抄録)

Pregnancy outcomes following radical trachelectomy for early-stage cervical cancer: A retrospective observational study in the Kanto area, Japan.

Kasuga Y, Hasegawa K, Hamuro A, Fukuma Y, Tamai J, Tanaka Y, Ikenoue S, Tanaka M

International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics (International Journal of Gynecology and Obstetrics) 164 ( 1 ) 108 - 114 2023.06

ISSN 0020-7292

Objective: The authors aimed to investigate the prevalence of pregnancy and obstetric outcomes in patients who underwent radical trachelectomy (RT) for early-stage cervical cancer in the Kanto area, Japan. Method: A survey among 113 perinatal centers affiliated with the Kanto Society of Obstetrics and Gynecology was conducted to investigate their experience in managing pregnancies following RT, between 2010 and 2020. The association between preterm delivery (before 34 gestational weeks) and a midtrimester short cervix (<13 mm) was evaluated. Results: The authors retrospectively collected maternal and perinatal data from 13 hospitals. There were 135 pregnancies among 115 women following RT. Of the 135 pregnancies, 32 were miscarriages (<12 gestational weeks: n = 22; >12 gestational weeks: n = 10), and 103 were delivered after 22 gestational weeks. The incidences of preterm delivery before 28 and 34 gestational weeks were 8.7% and 30.1%, respectively. A midtrimester short residual cervix was associated with preterm delivery (P = 0.046). Conclusion: Since more than 100 pregnancies were recorded after RT in the Kanto area, many physicians had more opportunities to manage pregnancy after RT. Pregnancy following RT is associated with increased risk of preterm delivery, and midtrimester short residual cervix is a good predictor of preterm delivery.

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Genome-wide association study of preterm birth and gestational age in a Japanese population.

Hasegawa K, Kumasaka N, Nakabayashi K, Kamura H, Maehara K, Kasuga Y, Hata K, Tanaka M

Human genome variation (Human Genome Variation) 10 ( 1 ) 19 2023.06

ISSN 2054-345X

Preterm birth (PTB), defined as the birth of a baby at <37 weeks of gestation, is known to be the main cause of neonatal morbidity and mortality. Here, we report genetic associations between preterm birth and gestational age in a Japanese population. We conducted a genome-wide association study (GWAS) of 384 cases who delivered prematurely and 644 controls and considered gestational age as a quantitative trait in 1028 Japanese women. Unfortunately, we were unable to identify any significant variants associated with PTB or gestational age using the current sample. We also examined genetic associations previously reported in European populations and identified no associations, even with the genome-wide subthreshold (p value < 10–6). This data report aims to provide summary statistics of current GWASs on PTB in a Japanese population for future meta-analyses of genetics and PTB with larger sample sizes.

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Obstetric outcomes after medroxyprogesterone acetate treatment for early stage endometrial cancer or atypical endometrial hyperplasia: a single hospital-based study

Oishi M., Kasuga Y., Fukuma Y., Hamuro A., Tamai J., Tanaka Y., Hasegawa K., Yoshimura T., Ikenoue S., Ochiai D., Yamagami W., Tanaka M.

International Journal of Clinical Oncology (International Journal of Clinical Oncology) 28 ( 4 ) 587 - 591 2023.04

ISSN 13419625

Background: To investigate perinatal outcomes in pregnancy after high-dose medroxyprogesterone acetate (MPA) therapy for early stage endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) and to determine whether pregnancy after MPA therapy is at a higher risk of placenta accreta. Methods: Data of 51 pregnancies in 46 women who received MPA therapy for EC or AEH and delivered after 22 weeks of gestation at Keio University Hospital were reviewed. A retrospective matched case–control study was performed to determine the risk of placenta accreta in pregnancy after MPA therapy compared with singleton pregnancies without any history of maternal malignancy treatments. Results: The incidence of placenta accreta was higher in the MPA group than in the control group (15.7 vs. 0%, p = 0.0058). However, no differences in other perinatal outcomes were observed between groups. While gestational weeks at delivery in the MPA group were later than those in the control group (p = 0.0058), no difference in the incidence of preterm delivery was recorded between groups. In the MPA therapy group, the number of patients who underwent ≥ 6 dilation and curettage (D&C) was higher in the placenta accreta group than in the non-placenta accreta group (50.0 vs. 14.0%, p = 0.018). Patients with ≥ 6 D&Cs demonstrated a 6.0-fold increased risk of placenta accreta (p = 0.043, 95% CI 1.05–34.1) than those receiving ≤ 3 D&Cs. Conclusion: Pregnancy after MPA therapy is associated with a high risk of placenta accreta. In cases in which the frequency of D&C is high, placenta accreta should be considered.

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染色体異常を伴わない胎児臍帯ヘルニアの2例

木村由実子, 玉井順子, 春日義史, 秋田啓介, 田中邦生, 葉室明香, 福間優花, 長谷川慶太, 大谷利光, 池ノ上学, 青木大輔, 田中守

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 72 ( 2 ) 327 - 331 2023.04

ISSN 2186-0599

緒言:今回我々は染色体異常を伴わない胎児臍帯ヘルニアの2例の周産期管理を行ったので報告する.症例1は41歳,1妊0産.体外受精-胚移植により妊娠成立し,妊娠13週に臍帯ヘルニアを指摘された.症例2は40歳,1妊0産.自然妊娠にて妊娠成立し,妊娠12週に胎児腹部腫瘤を指摘された.いずれも妊娠16週の羊水検査で正常核型であり,超音波断層法では肝脱出型臍帯ヘルニアと単一臍帯動脈以外の形態異常は指摘されなかった.出生後の精査にて症例1は食道閉鎖,鎖肛,軟口蓋裂,左多合指症等を認めたためVATER連合,症例2は耳介の形態や高インスリン血症からBeckwith-Wiedemann症候群が疑われた.結論:染色体異常を伴っていない臍帯ヘルニアでは,他の症候群の1症候であり出生後に判明する場合があることを念頭に胎児の慎重な観察と家族への十分な説明を行うことが望ましいと考えられた.(著者抄録)

コロナ禍における周産期合併症の変化

春日義史, 田中雄也, 田中守

DOHaD研究 ((一社)日本DOHaD学会) 11 ( 2 ) 152 - 157 2023.03

ISSN 2187-2562

Ultrasonographic Prediction of Placental Invasion in Placenta Previa by Placenta Accreta Index

Hasegawa K., Ikenoue S., Tanaka Y., Oishi M., Endo T., Sato Y., Ishii R., Kasuga Y., Ochiai D., Tanaka M.

Journal of Clinical Medicine (Journal of Clinical Medicine) 12 ( 3 ) 2023.02

ISSN 2077-0383

This study aimed to investigate the diagnostic accuracy of the placenta accreta index (PAI) for predicting placenta accreta spectrum (PAS) in women with placenta previa. We analyzed 33 pregnancies with placenta previa at Keio University Hospital. The PAI was assessed in the early third trimester, and PAS was diagnosed histologically or clinically defined as retained placenta after manual removal attempts. The PAI and incidence of PAS were analyzed. Ten women (30%) were diagnosed with PAS and had higher volumes of perioperative bleeding (p = 0.016), higher rate of requiring uterine artery embolization (p = 0.005), and peripartum hysterectomy (p = 0.0002) than women without PAS. A PAI > 2 was the most useful cut-off point for predicting PAS and was more sensitive than prediction values using traditional evaluation (history of cesarean section and placental location). Post-hoc analysis revealed a higher rate of previous history of cesarean delivery (30% vs. 4.4%, p = 0.038), severe placental lacunae (≥grade2) (70% vs. 8.7%, p = 0.0003), thin myometrial thickness (90% vs. 22%, p = 0.0003), anterior placenta (100% vs. 30%, p = 0.0002), and presence of bridging vessels (30% vs. 0%, p = 0.0059) in PAS women. PAI could help predict the outcomes of women with placenta previa with and without a history of cesarean delivery to reduce PAS-induced perinatal complications.

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Risk factors of neonatal hypoglycemia in neonates born to mothers with gestational diabetes

Arimitsu T., Kasuga Y., Ikenoue S., Saisho Y., Hida M., Yoshino J., Itoh H., Tanaka M., Ochiai D.

Endocrine Journal (Endocrine Journal) 70 ( 5 ) 511 - 517 2023

ISSN 09188959

Hypoglycemia is one of the most significant problems in neonates born to mothers with gestational diabetes (GDM). This study aimed to identify novel predictors of hypoglycemia in neonates born to mothers with GDM. A total of 443 term singleton infants from mothers diagnosed with GDM and cared for at Keio University Hospital between January 2013 and December 2019 were included in this study. Neonatal hypoglycemia was defined as hypoglycemia of less than 47 mg/dL at 1 or 2 or 4 h after birth, according to previous studies. Among 443 full-term singleton neonates born to mothers with GDM, 200 developed hypoglycemia (45%). Gestational weight gain (GWG), HbA1c at 1st trimester, HbA1c at GDM diagnosis, and the incidence of insulin therapy in the neonatal hypoglycemia group were significantly higher than those in the non-neonatal hypoglycemia group (p = 0.016, p = 0.032, p = 0.011, and p = 0.017, respectively). Regarding the multiple regression analysis adjusted for nulliparity, GWG, and gestational weeks at delivery, the odds ratio for maternal HbA1c ≥5.2% at 1st trimester was 1.63 (p = 0.034), and maternal insulin therapy during pregnancy was 1.72 (p = 0.015). In conclusion, HbA1c in the 1st trimester and insulin therapy during pregnancy were good predictors of hypoglycemia in neonates born to GDM mothers, especially when their HbA1c was 5.2% or more. Further research will be necessary to improve the perinatal management of hypoglycemia.

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Fetal growth restriction and a single umbilical artery are independent predictors of hypospadias during pregnancy

Endo T., Iida M., Ichihashi Y., Oishi M., Ikenoue S., Kasuga Y., Sato T., Hida M., Ishii T., Asanuma H., Hasegawa T., Tanaka M., Ochiai D.

Placenta (Placenta) 130 53 - 59 2022.12

ISSN 01434004

Introduction: Little is known about the association between hypospadias and small fetuses, as well as the pathological implications of fetal growth restriction (FGR). Thus, we aimed to investigate the association between hypospadias and small fetuses using a database of fetal ultrasound and obstetric events. Methods: A cohort of male singleton infants delivered after 22 weeks of gestation at Keio University Hospital between 2013 and 2019 was retrospectively reviewed. FGR was defined according to the Delphi criteria. Logistic regression analysis was performed to identify the significant predictors of hypospadias. Placental pathology was reviewed in cases with hypospadias. Results: Of the 2,040 male infants included in the present study, 23 had hypospadias. The prevalences of a single umbilical artery (SUA), small for gestational age, maternal hypertensive disorders of pregnancy, and a small placenta, were significantly higher in infants with hypospadias. Multiple logistic regression analysis revealed that FGR (odds ratio [OR] = 9.39; 95% confidence interval [CI], 2.50–35.3) and the presence of a SUA (OR = 33.4; 95% CI, 8.00–139.5) were independently and significantly associated with hypospadias. When FGR was stratified by the time of onset, its association with hypospadias was significant regardless of the time of onset. Moreover, placental histological findings suggested that fetal vascular malperfusion might play a role in hypospadias. Discussion: FGR and SUAs are independent prenatal predictors of the development of hypospadias, and fetal vascular malperfusion of the placenta may be involved in the etiology of hypospadias.

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Human Amniotic Fluid Stem Cells Ameliorate Thioglycollate-Induced Peritonitis by Increasing Tregs in Mice

Abe Y., Ochiai D., Taguchi M., Kanzaki S., Ikenoue S., Kasuga Y., Tanaka M.

International Journal of Molecular Sciences (International Journal of Molecular Sciences) 23 ( 12 ) 2022.06

ISSN 16616596

Mesenchymal stem cells (MSCs) affect immune cells and exert anti-inflammatory effects. Human amniotic fluid stem cells (hAFSCs), a type of MSCs, have a high therapeutic effect in animal models of inflammation-related diseases. hAFSCs can be easily isolated and cultured from amniotic fluid, which is considered a medical waste. Hence, amniotic fluid can be a source of cells for MSC therapy of inflammatory diseases. However, the effect of hAFSCs on acquired immunity in vivo, especially on regulatory T cells, has not yet been fully elucidated. Therefore, in this study, we aimed to understand the effects of hAFSCs on acquired immunity, particularly on regulatory T cells. We showed that hAFSCs ameliorated the thioglycollate-induced inflammation by forming aggregates with host immune cells, such as macrophages, T cells, and B cells in the peritoneal cavity. Further, the regulatory T cells increased in the peritoneal cavity. These results indicated that, in addition to helping the innate immunity, hAFSCs could also aid the acquired immune system in vivo against inflammation-related diseases by increasing regulatory T cells.

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The associated factors of low birthweight among term singletons in Japan: a pregnancy birth registry analysis.

Kasuga Y, Iida M, Tanaka Y, Tamagawa M, Hasegawa K, Ikenoue S, Sato Y, Tanaka M, Ochiai D

Journal of epidemiology 33 ( 9 ) 450 - 455 2022.04

ISSN 0917-5040

Background: Progress in reducing the global low birthweight (LBW) has been insufficient. Although the focus has been on preventing preterm birth, evidence regarding LBW in term births is limited. Despite its low preterm birth prevalence, Japan has a higher LBW proportion than other developed countries. This study aimed to examine the prevalence of LBW in term singleton births and its associated factors using a national database. Methods: We retrospectively analyzed the data of neonates registered in the Japan Society of Obstetrics and Gynecology Successive Pregnancy Birth Registry System who were born 2013–2017. Exclusion criteria included stillbirths, delivery after 42 gestational weeks, and missing data. Logistic regression analyses were performed to investigate the maternal and perinatal factors associated with LBW in term singletons using the data of 715,414 singleton neonates. Results: The overall prevalence of LBW was 18.3%, and 35.7% of LBWs originated from singleton term pregnancies. Multiple logistic regression analyses indicated that both modifiable and non-modifiable factors were independently associated with LBW in term neonates. The modifiable maternal factors included pre-pregnancy underweight, inadequate gestational weight gain, and smoking during pregnancy, while the non-modifiable factors included younger maternal age, nulliparity, hypertensive disorders of pregnancy, cesarean section delivery, female offspring, and congenital anomalies. Conclusion: Using the Japanese pregnancy birth registry data, more than one-third of LBWs were found to originate from singleton term pregnancies. Both modifiable and non-modifiable factors were independently associated with LBW in term neonates. Prevention strategies on modifiable risk factor control will be effective in reducing LBW worldwide.

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切迫早産管理中に肺血栓塞栓症を発症した1例

緒形恵, 田中雄也, 春日義史, 内田志穂, 明石一浩, 池ノ上学, 西尾浩, 落合大吾, 青木大輔, 田中守

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 71 ( 2 ) 349 - 354 2022.04

ISSN 2186-0599

緒言:肺血栓塞栓症(Pulmonary Thromboembolism:PTE)は母体死亡の7%に認める予後不良な疾患である。今回我々は切迫早産管理中にPTEを発症した1例を経験したので報告する。症例:42歳、2妊0産、妊娠29週4日に切迫早産の診断で入院した。安静度は病棟内フリーとした。妊娠33週3日、ベッドより離床した際に呼吸苦、動悸、脱力感を自覚し、胸部造影CTで両側肺動脈本幹および末梢に多数の造影欠損を認めたことから急性PTEと診断した。発症当日に緊急帝王切開術を施行し、児は2010gの女児、Apgar scoreは9/10点(1/5分値)であった。術後1日目より抗凝固療法を開始し、経過良好にて術後23日目に退院した。結論:安静臥床としていない切迫早産でもPTEを発症する可能性が示唆され、入院期間が長期になる場合はPTE発症に留意する必要があると考えられた。(著者抄録)

COVID-19流行期における妊娠糖尿病診断を考える

春日義史

糖尿病と妊娠 ((一社)日本糖尿病・妊娠学会) 22 ( 1 ) S - 30 2022.02

ISSN 1347-9172

緒言:本研究の目的は「妊娠中の糖代謝異常のスクリーニング〜COVID-19パンデミック対応〜」を検証することである。方法:妊娠24週未満診断妊娠糖尿病(E-GDM:304例)、妊娠24週以降診断GDM(L-GDM:264例)をおのおのCOVID-19流行期GDM診断基準にしたがって再分類した。結果:E-GDMのうち、41例は糖代謝異常、263例は非糖代謝異常に再分類された。また、L-GDMのうち、104例はGDMと再分類されたが、160例はGDMと再分類されなかった。結論:E-GDM、L-GDMともにCOVID-19流行期GDM診断基準では多くの症例が非糖代謝異常と診断された。(著者抄録)

DNA methylation analysis of cord blood samples in neonates born to gestational diabetes mothers diagnosed before 24 gestational weeks

Kasuga Y., Kawai T., Miyakoshi K., Hori A., Tamagawa M., Hasegawa K., Ikenoue S., Ochiai D., Saisho Y., Hida M., Tanaka M., Hata K.

BMJ Open Diabetes Research and Care (BMJ Open Diabetes Research and Care) 10 ( 1 ) 2022.01

Accepted

Introduction Genome-wide methylation analyses of gestational diabetes mellitus (GDM) diagnosed after 24 gestational weeks (late GDM (L-GDM)) using cord blood have been reported. However, epigenetic changes in neonates born to mothers with GDM diagnosed before 24 gestational weeks (early GDM (E-GDM)) have not been reported. We investigated DNA methylation in neonates born to mothers with E-GDM using cord blood samples. Research design and methods Genome-wide DNA methylation analysis was performed using an Illumina EPIC array to compare methylation rates of 754 255 autosomal sites in cord blood samples from term neonates born to 162 mothers with GDM (E-GDM: n=84, L-GDM: n=78) and 60 normal glucose tolerance (normal OGTT) pregnancies. GDM was diagnosed based on Japan Society of Obstetrics and Gynecology criteria modified with International Association of Diabetes in Pregnancy Study Group criteria. In this study, all GDM mothers underwent dietary management, while self-monitoring of blood glucose and insulin administration was initiated when dietary modification did not achieve glycemic control. Results There were no significant differences in genome-wide DNA methylation of cord blood samples between the GDM (E-GDM and L-GDM) groups and normal OGTT group or between the E-GDM and normal OGTT groups, L-GDM and normal OGTT groups, and E-GDM and L-GDM groups. Conclusions This is the first report to determine the DNA methylation patterns in neonates born to mothers with E-GDM. Neonates born to mothers with GDM, who were diagnosed based on Japan Society of Obstetrics and Gynecology criteria, may not differ in DNA methylation compared with those born to normal OGTT mothers.

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Adenocarcinoma in situ or early-stage cervical cancer is a risk factor for preterm delivery after cervical conization: a multicenter observational study

Kasuga Y., Ikenoue S., Nishio H., Yamagami W., Ochiai D., Tanabe K., Tashima Y., Hirao N., Miyakoshi K., Kasai K., Suda Y., Nemoto T., Shiraishi S., Yoshida H., Kurahashi T., Takamatsu K., Iwasaki S., Yamashita H., Akiba Y., Arase T., Hara S., Nakada S., Tanaka M., Aoki D.

Journal of Maternal-Fetal and Neonatal Medicine (Journal of Maternal-Fetal and Neonatal Medicine) 35 ( 25 ) 1 - 6 2022

ISSN 14767058

Objective: Pregnancy after conization is associated with a high risk of preterm delivery. However, because risk factors for preterm delivery after conization remain unknown, we conducted a multicenter observational study to investigate risk factors associated with preterm delivery. Methods: We selected patients who had previously undergone conization and reviewed medical records from 18 hospitals in cooperation with Keio University School of Medicine between January 2013 and December 2019. Women were classified as nulliparous and primiparous, and a multiple logistic regression analysis was performed to evaluate the relative contributions of the various maternal risk factors for preterm delivery (i.e. delivery before 37 gestational weeks). Results: Among 409 pregnant women after conization, 68 women delivered preterm (17%). The incidence of nulliparity (p =.014) was higher and a history of preterm delivery (p =.0010) was more common in the preterm delivery group than in the term delivery group. Furthermore, the proportion of women diagnosed with adenocarcinoma in situ (AIS) and cervical cancer in the preterm delivery group was higher than that in the term delivery group (p =.0099 and.0004, respectively). In multiple regression models in nulliparous women, cervical cancer or AIS (Odds ratio [OR]: 4.16, 95% CI: 1.26–13.68, p =.019) and a short cervix in the second trimester (OR: 13.41, 95% CI: 3.88–46.42, p <.0001) increased the risk of preterm delivery. Furthermore, a history of preterm delivery (OR: 7.35, 95% CI: 1.55–34.86, p =.012), cervical cancer or AIS (OR: 5.07, 95% CI: 1.24–20.73, p =.024), and a short cervix in the second trimester (OR: 4.29, 95% CI: 1.11–16.62, p =.035) increased the risk of preterm delivery in the multiple regression models in primiparous women. Conclusion: Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGES Prior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization. The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group.

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Prophylactic administration of human amniotic fluid stem cells suppresses inflammation-induced preterm birth via macrophage polarization

Abe Y., Ochiai D., Kanzaki S., Sato Y., Otani T., Ikenoue S., Kasuga Y., Tanaka M.

Molecular and Cellular Biochemistry (Molecular and Cellular Biochemistry) 478 ( 2 ) 363 - 374 2022

ISSN 03008177

Ascending inflammation from the vagina is a major cause of preterm birth. Currently, this condition—especially when uncontrolled—has no effective treatment. Human amniotic fluid stem cells (hAFSCs) are mesenchymal stem cells known to exert potent anti-inflammatory effects in animal models of perinatal diseases, such as periventricular leukomalacia, myelomeningocele, and neonatal sepsis. However, hAFSC therapy for inflammation-induced preterm birth has not been tested. In order to determine the therapeutic effect of hAFSC transplantation, we employed a preterm mouse model of ascending infection; this model was constructed by administering lipopolysaccharide to pregnant mice. We investigated the preterm birth rate and evaluated the inflammation of tissues, which is related to progressive infections, such as those involving the cervix, placenta, and lavage cells, using real-time qPCR. Further, we tracked the fluorescence of fluorescently labeled hAFSCs using an in vivo imaging system, and hAFSC aggregation was evaluated using immunohistochemistry analysis. We also investigated the presence of multiple types of peritoneal macrophages via flow cytometry analysis. Finally, we performed sphere culturing and co-culturing to determine the therapeutic effects of hAFSCs, such as their anti-inflammatory effects and their potential to alter macrophage polarization. We found that hAFSC administration to the peritoneal cavity significantly reduced inflammation-induced preterm birth in the mouse model. The treatment also significantly suppressed inflammation of the placenta and cervix. Transplanted hAFSCs may have aggregated with peritoneal macrophages, switching them from an inflammatory to an anti-inflammatory type. This property has been reported in vivo previously, but here, we examined the effect in vitro. Our findings support the hypothesis that hAFSCs suppress inflammation and reduce preterm birth by switching macrophage polarity. This study is the first to demonstrate that hAFSCs are effective in the treatment and prevention of inflammation-induced preterm birth.

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Deep neural network-based classification of cardiotocograms outperformed conventional algorithms

Ogasawara J., Ikenoue S., Yamamoto H., Sato M., Kasuga Y., Mitsukura Y., Ikegaya Y., Yasui M., Tanaka M., Ochiai D.

Scientific Reports (Scientific Reports) 11 ( 1 ) 13367 2021.12

Accepted

Cardiotocography records fetal heart rates and their temporal relationship to uterine contractions. To identify high risk fetuses, obstetricians inspect cardiotocograms (CTGs) by eye. Therefore, CTG traces are often interpreted differently among obstetricians, resulting in inappropriate interventions. However, few studies have focused on quantitative and nonbiased algorithms for CTG evaluation. In this study, we propose a newly constructed deep neural network model (CTG-net) to detect compromised fetal status. CTG-net consists of three convolutional layers that extract temporal patterns and interrelationships between fetal heart rate and uterine contraction signals. We aimed to classify the abnormal group (umbilical artery pH < 7.20 or Apgar score at 1 min < 7) and the normal group from CTG data. We evaluated the performance of the CTG-net with the F1 score and compared it with conventional algorithms, namely, support vector machine and k-means clustering, and another deep neural network model, long short-term memory. CTG-net showed the area under the receiver operating characteristic curve of 0.73 ± 0.04, which was significantly higher than that of long short-term memory. CTG-net, a quantitative and automated diagnostic aid system, enables early intervention for putatively abnormal fetuses, resulting in a reduction in the number of cases of hypoxic injury.

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【DOHaDとCOVID-19】コロナ禍におけるDOHaD研究の状況と学会支援の必要性

濱田裕貴, 春日義史, 久保佳範

DOHaD研究 ((一社)日本DOHaD学会) 10 ( 1 ) 1 - 5 2021.12

ISSN 2187-2562

Prepregnancy assessment of liver function to predict perinatal and postpregnancy outcomes in biliary atresia patients with native liver

Takahashi N., Ochiai D., Yamada Y., Tamagawa M., Kanamori H., Kato M., Ikenoue S., Kasuga Y., Kuroda T., Tanaka M.

Journal of Clinical Medicine (Journal of Clinical Medicine) 10 ( 17 ) 2021.09

Accepted, ISSN 2077-0383

Considering that some biliary atresia (BA) survivors with native liver have reached reproductive age and face long‐lasting complications, specific attention needs to be paid to pregnant cases. This study aimed to investigate the relationship between liver function, perinatal outcomes, and prognosis. A database review was conducted to identify pregnant BA cases with native liver and perinatal data, and clinical information on BA‐related complications was analyzed. Perinatal serum cholinesterase (ChE) levels, model for end‐stage liver‐disease (MELD) score, and platelet trends were analyzed, and the association between these indicators and perinatal outcomes was investigated. Patients were categorized into three groups according to the perinatal clinical outcomes: favorable (term babies with or without several episodes of cholangitis; n = 3), borderline (term baby and following liver dysfunction; n = 1), and unfavorable (premature delivery with subsequent liver failure; n = 1). Lower serum ChE levels, lower platelet counts, and higher MELD scores were observed in the unfavorable category. Borderline and unfavorable patients displayed a continuous increase in MELD score, with one eventually needing a liver transplantation. Pregnancy in patients with BA requires special attention. Serum ChE levels, platelet counts, and MELD scores are all important markers for predicting perinatal prognosis.

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Clinical results of a massive blood transfusion protocol for postpartum hemorrhage in a university hospital in japan: A retrospective study

Ochiai D., Abe Y., Yamazaki R., Uemura T., Toriumi A., Matsuhashi H., Tanaka Y., Ikenoue S., Kasuga Y., Tanosaki R., Tanaka M.

Medicina (Lithuania) (Medicina (Lithuania)) 57 ( 9 ) 2021.09

Accepted, ISSN 1010660X

Background and objectives: Massive postpartum hemorrhage (PPH) is the most common cause of maternal death worldwide. A massive transfusion protocol (MTP) may be used to provide significant benefits in the management of PPH; however, only a limited number of hospitals use MTP protocol to manage massive obstetric hemorrhages, especially in Japan. This study aimed to assess the clinical outcomes in patients in whom MTP was activated in our hospital. Materials and Methods: We retrospectively reviewed the etiology of PPH, transfusion outcomes, and laboratory findings among the patients treated with MTP after delivery in our hospital. Results: MTP was applied in 24 cases (0.7% of deliveries). Among them, MTP was activated within 2 h of delivery in 15 patients (62.5%). The median estimated blood loss was 5017 mL. Additional procedures to control bleeding were performed in 19 cases, including transarterial embolization (18 cases, 75%) and hysterectomy (1 case, 4.2%). The mean number of units of red blood cells, fresh frozen plasma, and platelets were 17.9, 20.2, and 20.4 units, respectively. The correlation coefficients of any two items among red blood cells, fresh frozen plasma, platelets, blood loss, and obstetrical disseminated intravascular coagulation score ranged from 0.757 to 0.892, indicating high levels of correlation coefficients. Although prothrombin time and activated partial thromboplastin time levels were significantly higher in the <150 mg/dL fibrinogen group than in the ≥150 mg/dL fibrinogen group at the onset of PPH, the amount of blood loss and blood transfusion were comparable between the two groups. Conclusions: Our MTP provides early access to blood products for patients experiencing severe PPH and could contribute to improving maternal outcomes after resuscitation in our hospital. Our study suggests the implementation of a hospital-specific MTP protocol to improve the supply and utilization of blood products to physicians managing major obstetric hemorrhage.

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The efficacy of transarterial embolization for postpartum hemorrhage complicated with disseminated intravascular coagulation: A single‐center experience

Ochiai D., Nakatsuka S., Abe Y., Ikenoue S., Kasuga Y., Inoue M., Jinzaki M., Tanaka M.

Journal of Clinical Medicine (Journal of Clinical Medicine) 10 ( 18 ) 2021.09

Accepted, ISSN 2077-0383

Indications for the use of transarterial embolization (TAE) for postpartum hemorrhage (PPH) have been established. However, the efficacy of TAE for PPH complicated by disseminated intravascular coagulation (DIC) remains controversial. In this study, we investigated the efficacy of TAE for PPH complicated by DIC. A database review was conducted to identify patients who were treated with TAE for PPH at our hospital. TAE was performed in 41 patients during the study period. Effective hemostasis was achieved in all cases, but additional procedures, such as reembolization or hysterectomy, were required in five patients (12.2%). The typical causes of PPH included uterine atony (18 cases), placenta previa (15 cases), amniotic fluid embolism (DIC‐type) (11 cases), and placenta accreta spectrum (10 cases). The mean blood loss was 3836 mL. The mean obstetrical DIC and the International Society on Thrombosis and Hemostasis DIC scores were 7.9 and 2.6, respectively. The efficacy of hemostasis was comparable between patients with and without DIC. However, the complete success rate of TAE was lower in patients with DIC as the condition worsened than that in non‐DIC patients. Overall, TAE is effective as a minimally invasive treatment for PPH complicated by DIC.

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Newer Insights Into Fetal Growth and Body Composition

Ikenoue S., Kasuga Y., Endo T., Tanaka M., Ochiai D.

Frontiers in Endocrinology (Frontiers in Endocrinology) 12 708767 2021.07

Accepted, ISSN 1664-2392

Based on epidemiological and experimental evidence, the origins of childhood obesity and early onset metabolic syndrome can be extended back to developmental processes during intrauterine life. It is necessary to actively investigate antecedent conditions that affect fetal growth by developing reliable measures to identify variations in fetal fat deposition and body composition. Recently, the resolution of ultrasonography has remarkably improved, which enables better tissue characterization and quantification of fetal fat accumulation. In addition, fetal fractional limb volume has been introduced as a novel measure to quantify fetal soft tissue volume, including fat mass and lean mass. Detecting extreme variations in fetal fat deposition may provide further insights into the origins of altered fetal body composition in pathophysiological conditions (i.e., fetal growth restriction or fetal macrosomia), which are predisposed to the metabolic syndrome in later life. Further studies are warranted to determine the maternal or placental factors that affect fetal fat deposition and body composition. Elucidating these factors may help develop clinical interventions for altered fetal growth and body composition, which could potentially lead to primary prevention of the future risk of metabolic dysfunction.

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Epigenetic Changes in Neonates Born to Mothers With Gestational Diabetes Mellitus May Be Associated With Neonatal Hypoglycaemia

Kasuga Y., Kawai T., Miyakoshi K., Saisho Y., Tamagawa M., Hasegawa K., Ikenoue S., Ochiai D., Hida M., Tanaka M., Hata K.

Frontiers in Endocrinology (Frontiers in Endocrinology) 12 690648 2021.06

Accepted, ISSN 1664-2392

The detection of epigenetic changes associated with neonatal hypoglycaemia may reveal the pathophysiology and predict the onset of future diseases in offspring. We hypothesized that neonatal hypoglycaemia reflects the in utero environment associated with maternal gestational diabetes mellitus. The aim of this study was to identify epigenetic changes associated with neonatal hypoglycaemia. The association between DNA methylation using Infinium HumanMethylation EPIC BeadChip and neonatal plasma glucose (PG) level at 1 h after birth in 128 offspring born at term to mothers with well-controlled gestational diabetes mellitus was investigated by robust linear regression analysis. Cord blood DNA methylation at 12 CpG sites was significantly associated with PG at 1 h after birth after adding infant sex, delivery method, gestational day, and blood cell compositions as covariates to the regression model. DNA methylation at two CpG sites near an alternative transcription start site of ZNF696 was significantly associated with the PG level at 1 h following birth (false discovery rate-adjusted P < 0.05). Methylation levels at these sites increased as neonatal PG levels at 1 h after birth decreased. In conclusion, gestational diabetes mellitus is associated with DNA methylation changes at the alternative transcription start site of ZNF696 in cord blood cells. This is the first report of DNA methylation changes associated with neonatal PG at 1 h after birth.

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Predictors of later insulin therapy for gestational diabetes diagnosed in early pregnancy.

Tamagawa M, Kasuga Y, Saisho Y, Tanaka Y, Hasegawa K, Oishi M, Endo T, Sato Y, Ikenoue S, Tanaka M, Ochiai D

Endocrine journal (Endocrine Journal) 68 ( 11 ) 1321 - 1328 2021.06

Accepted, ISSN 0918-8959

Interventions for gestational diabetes mellitus (GDM), diagnosed in early pregnancy, have been a topic of controversy. This study aimed to elucidate factors that predict patients with GDM diagnosed before 24 gestational weeks (early GDM: E-GDM) who require insulin therapy later during pregnancy. Furthermore, we identified patients whose impaired glucose tolerance should be strictly controlled from early gestation onward. Women diagnosed with GDM were categorized based on the gestational age at diagnosis into E-GDM (n = 388) or late GDM (L-GDM, diagnosed after 24 weeks, n = 340) groups. Clinical features were compared between the groups, and the predictors for insulin therapy was evaluated in the E-GDM group. There were no significant between-group differences in terms of perinatal outcomes (e.g., gestational weeks at delivery, fetal growth, hypertensive disorder of pregnancy), with the exception of the Apgar score at 5 min. Moreover, there was no significant difference in the frequency of insulin therapy during pregnancy between the two groups. Using multiple logistic regression analysis, pre-pregnancy body mass index (BMI) ≥25 kg/m2, a family history of diabetes, and higher fasting plasma glucose (FPG), 1 h-plasma glucose (PG), and 2 h-PG values increased insulin therapy risk during pregnancy in the E-GDM group. Furthermore, since E-GDM patients with abnormal levels of FPG, as well as 1 h-PG or 2 h-PG, and those with pre-pregnancy BMI ≥25 kg/m2 and a family history of diabetes had a higher risk of later insulin therapy during pregnancy, they may require more careful follow-up in the perinatal period.

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What are the causes for low birthweight in Japan? A single hospital-based study

Kasuga Y., Ikenoue S., Tamagawa M., Oishi M., Endo T., Sato Y., Iida M., Sato Y., Tanaka M., Ochiai D.

PLoS ONE (PLoS ONE) 16 ( 6 June ) e0253719 2021.06

Accepted

Low-birthweight (LBW; <2,500 g) babies are at a higher risk of poor educational achievement, disability, and metabolic diseases than normal-birthweight babies in the future. However, reliable data on factors that contribute to LBW have not been considered previously. Therefore, we aimed to examine the distribution of the causes for LBW. A retrospective review of cases involving 4,224 babies whose mothers underwent perinatal care at Keio University Hospital between 2013 and 2019 was conducted. The LBW incidence was 24% (1,028 babies). Of the 1,028 LBW babies, 231 babies were from multiple pregnancies. Of the 797 singleton LBW babies, 518 (65%) were born preterm. Obstetric complications in women with preterm LBW babies included premature rupture of membrane or labor onset (31%), hypertensive disorders of pregnancy (HDP, 64%), fetal growth restriction (24%), non-reassuring fetal status (14%), and placental previa/vasa previa (8%). Of the 279 term LBW babies, 109 (39%) were small for gestational age. Multiple logistic regression analyses revealed the following factors as LBW risk factors in term neonates: low pre-pregnancy maternal weight, inadequate gestational weight gain, birth at 37 gestational weeks, HDP, anemia during pregnancy, female sex, and neonatal congenital anomalies. HDP was an LBW risk factor not only in preterm births but also in term births. Our results suggest that both modifiable and non-modifiable factors are causes for LBW. It may be appropriate to consider a heterogeneous rather than a simple classification of LBW and to evaluate future health risks based on contributing factors.

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Management of pregnancy after radical trachelectomy.

Kasuga Y, Ikenoue S, Tanaka M, Ochiai D

Gynecologic oncology (Gynecologic Oncology) 162 ( 1 ) 220 - 225 2021.04

Accepted, ISSN 0090-8258

Radical trachelectomy (RT) is a surgery for early-stage cervical cancer treatment that preserves the childbearing ability, and its use has become increasingly common worldwide. Thus, the rate of conception in women who have undergone RT is increasing. However, pregnancy after RT is associated with a higher risk of several obstetric complications such as preterm delivery, preterm premature membrane rupture, and abnormal bleeding from varices at the site of uterovaginal anastomosis. Furthermore, since RT have a residual prophylactic cerclage, it is difficult to manage first- and second-trimester miscarriages. There is little previous data on the management of pregnancy after RT. In this review article, we summarize various management methods and experiences to provide a guide to clinicians for perinatal management after RT.

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帝王切開術後の腹腔内出血に対し、腹部コンパートメント症候群に準じて治療介入した1例

大石真希, 落合大吾, 春日義史, 田中雄也, 玉川真澄, 遠藤豊英, 佐藤佑, 池ノ上学, 田中守, 青木大輔

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 70 ( 2 ) 231 - 236 2021.04

Accepted, ISSN 2186-0599

産科領域における腹部コンパートメント症候群(abdominal compartment syndrome:ACS)の報告は稀である。今回我々は、帝王切開術後に腹腔内出血を認め、ACSに準じて加療した症例を経験した。症例は43歳、妊娠39週0日に分娩中に児の持続徐脈を認め、超緊急帝王切開術を施行し常位胎盤早期剥離と診断した。帰室1時間後、出血性ショック状態のため産科危機的出血を宣言し子宮動脈塞栓術を施行した。術後1日目、著明な腹部膨隆を認め、ACSを疑い腹部造影CT検査を行ったが臓器血流障害は認めなかった。また、膀胱内圧は14mmHgと上昇しており、約4Lの血性腹水を経腹的にドレナージしたところ呼吸状態が劇的に改善した。そして、その後の経過は順調で術後7日目に退院した。ACS疑いの症例では、腹腔内圧の推定には膀胱内圧が有用であり、早期の治療介入が病態改善に寄与する可能性が示唆された。(著者抄録)

Cell sheets using human amniotic fluid stem cells reduce tissue fibrosis in murine full-thickness skin wounds

Ochiai D., Abe Y., Fukutake M., Sato Y., Ikenoue S., Kasuga Y., Masuda H., Tanaka M.

Tissue and Cell (Tissue and Cell) 68 101472 2021.02

Accepted, ISSN 00408166

The use of mesenchymal stem cell sheets is a promising strategy for skin regeneration. The injection of dissociated human amniotic fluid stem cells (hAFSCs) was recently found to accelerate cutaneous wound healing with reduced fibrotic scarring, similar to fetal wound healing. However, the use of hAFSCs in applications of cell sheet technology remains limited. The aim of this study was to determine the in vivo efficacy of in vitro-cultured hAFSC sheets in wound healing. The cell sheets were characterized by immunohistochemistry and RT-qPCR and grafted onto full-thickness wounds in BALB/c mice. The wound size was measured, and re-epithelialization, granulation tissue area, and collagen content of the regenerated wound were analyzed histologically. Although the hAFSC sheet contained abundant extracellular matrix molecules and expressed high levels of anti-fibrotic mediators, its grafting did not affect wound closure or the size of the granulation tissue area. In contrast, the organization of type I collagen bundles in the regenerated wound was markedly reduced, while the levels of type III collagen were increased after implantation of the hAFSC sheet. These results suggest that hAFSC sheets can exert anti-fibrotic properties without delaying wound closure.

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Defining the Normal Growth Curve of Fetal Fractional Limb Volume in a Japanese Population.

Ikenoue S, Akiba Y, Endo T, Kasuga Y, Yakubo K, Ishii R, Tanaka M, Ochiai D

Journal of clinical medicine (Journal of Clinical Medicine) 10 ( 3 ) 1 - 9 2021.01

Accepted, ISSN 2077-0383

Fetal fractional limb volume is a useful measure for predicting birth weight and newborn adiposity; however, a normal growth curve has been reported solely in the United States. As the birth weight of neonates in Japan is significantly lower than that in the US, fetal fractional limb volume is likely to be smaller in the Japanese population. This study aimed to define the normal growth curve of fractional arm volume (AVol) and thigh volume (TVol) in the Japanese population. Ultrasound scans of 453 AVol and TVol pairs were obtained; each AVol and TVol percentile at each gestational age was calculated. The measured AVol and TVol at each gestational week were also converted to z-scores based on a previous report. The growth curves increased linearly until the second trimester and exponentially in the third trimester. Linear regression showed a significant negative correlation between gestational age and AVol and TVol z-scores. The growth pattern of fetal fractional limb volume in the Japanese population is consistent with, but smaller than, that reported in the US; this difference becomes greater as the gestational age progresses.

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Amniotic fluid stem cells as a novel strategy for the treatment of fetal and neonatal neurological diseases

Abe Y., Ochiai D., Sato Y., Otani T., Fukutake M., Ikenoue S., Kasuga Y., Tanaka M.

Placenta (Placenta) 104 247 - 252 2021.01

Accepted, ISSN 01434004

Even in the context of modern medicine, infants with fetal and neonatal neurological diseases such as cerebral palsy and myelomeningocele suffer serious long-lasting impairment due to the irreversible neuronal damage. The promotion of neurologically intact survival in patients with perinatal intractable neurological diseases requires the development of novel strategies. One promising strategy involves the use of human amniotic fluid stem cells (hAFSCs), which have attracted much attention in recent years and are known to exert anti-inflammatory and neuroprotective effects. In recent years, the therapeutic effects of hAFSCs on fetal-neonatal neurological diseases have become evident as per intense research efforts by our group and others. Specifically, hAFSCs administered into the nasal cavity migrated to the brain and controlled local inflammation in a rodent model of neonatal hypoxic-ischemic encephalopathy. In contrast, hAFSCs administered intraperitoneally did not migrate to the brain; they rather formed spheroids in the abdominal cavity, resulting in the suppression of systemic inflammation (including in the brain) via the secretion of anti-inflammatory cytokines in concert with peritoneal macrophages in a rodent model of periventricular leukomalacia. Moreover, studies in a rat model of myelomeningocele suggested that hAFSCs administered in utero secreted hepatocyte growth factor and protected the exposed spinal cord during pregnancy. Importantly, autologous hAFSCs, whose use for fetal-neonatal treatment does not raise ethical issues, can be collected during pregnancy and prepared in sufficient numbers for therapeutic use. This article outlines the results of preclinical research on fetal stem cell therapy, mainly involving hAFSCs, in the context of perinatal neurological diseases.

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A safe delivery system to prevent COVID-19 transmission without negative-pressure isolation delivery rooms: Experience from a hospital with nosocomial outbreak

Kasuga Y., Ochiai D., Tamagawa M., Oishi M., Endo T., Sato Y., Iida M., Ikenoue S., Tanaka M.

Taiwanese Journal of Obstetrics and Gynecology (Taiwanese Journal of Obstetrics and Gynecology) 60 ( 1 ) 183 - 184 2021.01

Accepted, ISSN 10284559

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A case of abdominal compartment syndrome caused by amniotic fluid embolism treated with ABTHERA™ therapy: World's first report in the obstetric field

Hirata M., Hasegawa K., Kasuga Y., Haiden A., Ikenoue S., Yamamoto R., Tanaka M., Sasaki J., Ochiai D.

Taiwanese Journal of Obstetrics and Gynecology (Taiwanese Journal of Obstetrics and Gynecology) 60 ( 3 ) 579 - 580 2021

Accepted, ISSN 10284559

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Expectant management for early pregnancy miscarriage after radical trachelectomy: A single hospital-based study

Kasuga Y., Ikenoue S., Tanaka Y., Tamagawa M., Hasegawa K., Oishi M., Endo T., Sato Y., Tanaka M., Ochiai D.

Acta Obstetricia et Gynecologica Scandinavica (Acta Obstetricia et Gynecologica Scandinavica) 100 ( 7 ) 1322 - 1325 2021

Accepted, ISSN 00016349

Introduction: Women who have undergone radical trachelectomy as a fertility-sparing treatment for early-stage cervical cancer may be at higher risk for retained tissues after early-term miscarriage due to cervical cerclage or cervical necrosis. Dilatation and curettage or aspiration may present additional risks in these women. The aim of this study was to assess the efficacy of expectant management for early pregnancy miscarriage after radical trachelectomy. Material and methods: Keio University Hospital records were reviewed for women who conceived after abdominal radical trachelectomy and received perinatal care between 1 April 2012 and 31 March 2020. A total of 62 women (76 pregnancies) were identified, and 13 of these women experienced miscarriage before 12 gestational weeks. The management and outcome of these cases were reviewed in detail. Results: The median maternal age at miscarriage was 39 years (range 31–42 years) and the median duration from abdominal radical trachelectomy to conception was 2.60 years (range 0.49–7.30 years). Cervical necrosis before conception occurred in one case (8%). One patient requested treatment with aspiration and the remaining 12 cases were managed with observation for a median of 23 days (range 7–50 days). There were no cases of endometritis or cases requiring dilatation and curettage for residue tissue. Further, no cases developed laceration of the residual cervix and no loss of cerclage sutures after discharge was noted. Conclusions: Expectant management seems to be safe and appropriate for first trimester miscarriage after abdominal radical trachelectomy.

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Clinical utility of 1-month postpartum random plasma glucose and glycated hemoglobin combined with pre-pregnancy body mass index for detecting postpartum glucose intolerance in Japanese women with gestational diabetes

Sugiyama K., Saisho Y., Kasuga Y., Ochiai D., Itoh H.

Journal of Diabetes Investigation (Journal of Diabetes Investigation) 12 ( 12 ) 2242 - 2246 2021

Accepted, ISSN 20401116

During the coronavirus disease 2019 pandemic, the Japanese Society of Diabetes and Pregnancy proposed the use of random plasma glucose and glycated hemoglobin measured 1 month after delivery combined with pre-pregnancy body mass index to detect postpartum glucose intolerance instead of carrying out the oral glucose tolerance test in women with gestational diabetes. We retrospectively evaluated the clinical utility of this strategy to detect postpartum glucose intolerance evaluated by the oral glucose tolerance test after delivery. A total of 275 Japanese women with gestational diabetes were included in the present study. The specificity of 1-month postpartum random plasma glucose and glycated hemoglobin combined with pre-pregnancy body mass index to predict postpartum glucose intolerance was 98.0%, with a negative predictive value of 72.6%. However, sensitivity was 6.4%, with a positive predictive value of 55.6%. In conclusion, this Japanese Society of Diabetes and Pregnancy strategy showed high specificity, but low sensitivity, for detecting glucose intolerance postpartum.

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Prophylactic therapy with human amniotic fluid stem cells improves long-term cognitive impairment in rat neonatal sepsis survivors

Abe Y., Ochiai D., Sato Y., Kanzaki S., Ikenoue S., Kasuga Y., Tanaka M.

International Journal of Molecular Sciences (International Journal of Molecular Sciences) 21 ( 24 ) 1 - 12 2020.12

Accepted, ISSN 16616596

A systemic inflammatory response induces multiple organ dysfunction and results in poor long-term neurological outcomes in neonatal sepsis. However, there is no effective therapy for treating or preventing neonatal sepsis besides antibiotics and supportive care. Therefore, a novel strategy to improve neonatal sepsis-related morbidity and mortality is desirable. Recently, we reported that prophylactic therapy with human amniotic stem cells (hAFSCs) improved survival in a rat model of lipopolysaccharide (LPS)-induced neonatal sepsis through immunomodulation. Besides improving the mortality, increasing survival without major morbidities is an important goal of neonatal intensive care for neonatal sepsis. This study investigated long-term neurological outcomes in neonatal sepsis survivors treated with hAFSCs using the LPS-induced neonatal sepsis model in rats. We found that prophylactic therapy with hAFSCs improved spatial awareness and memory-based behavior in neonatal sepsis survivors at adolescence in rats. The treatment suppressed acute reactive gliosis and subsequently reduced astrogliosis in the hippocampal region over a long period of assessment. To the best of our knowledge, this is the first report that proves the concept that hAFSC treatment improves cognitive impairment in neonatal sepsis survivors. We demonstrate the efficacy of hAFSC therapy in improving the mortality and morbidity associated with neonatal sepsis.

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特定妊婦への選定状況からみた当院における精神疾患合併妊娠の実態

桑名温子, 清河駿樹, 大橋千恵, 今村裕子, 石垣順子, 鈴木毅, 金善惠, 樋口隆幸, 林保良, 染谷健一, 中田さくら, 春日義史

関東連合産科婦人科学会誌 ((一社)関東連合産科婦人科学会) 57 ( 4 ) 431 - 436 2020.11

Accepted, ISSN 2186-0610

分娩後の養育について妊娠中からの公的支援が必要と考えられる妊婦を特定妊婦に選定し,多職種が連携して支援している.精神疾患合併妊娠は特定妊婦選定の理由の1つとなりうるが,家庭環境などを考慮し非選定例も多い.本研究の目的は,精神疾患合併妊娠を特定妊婦選定の有無で分類し検討することでその背景を明らかにすることとした.対象は2018年1月から2019年8月に当院で対応した精神疾患の既往または合併のある妊婦118例(特定妊婦28例,非特定妊婦90例)であり,当院倫理委員会承認のもと母体背景,精神疾患診断名と治療状況,周産期予後について検討した.特定妊婦群では若年妊娠(p<0.05),未婚,生活保護受給者,妊娠中の内服継続,通院継続,治療の自己中断歴(各々p<0.01)が有意に多かった.特定妊婦群ではうつ病以外にパーソナリティー障害や精神発達遅滞が多く,覚醒剤使用後遺症が3例あった.周産期予後について有意差はなかった.7例が児童相談所に保護となり,いずれも特定妊婦群であった.周産期予後に差はないものの,児童相談所保護が多いことから,妊娠中から地域との連携をスムーズにするという点で特定妊婦選定の意義が再認識された.医療機関においては一般診療以外の労力が大きいことから,選定対象と具体的な対応については今後も検討が必要であると考えられた.(著者抄録)

Preterm delivery and hypertensive disorder of pregnancy were reduced during the COVID-19 pandemic: A single hospital-based study.

Kasuga Y, Tanaka M, Ochiai D

The journal of obstetrics and gynaecology research 46 ( 12 ) 2703 - 4 2020.10

ISSN 1341-8076

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Sonographic findings of cervical laceration caused by vaginal delivery in pregnancy after radical trachelectomy.

Kasuga Y, Miyakoshi K, Endo T, Takeda T, Nakamura M, Ochiai D, Tanaka M

Journal of medical ultrasonics (2001) 47 ( 4 ) 655 - 657 2020.10

ISSN 1346-4523

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Prophylactic therapy with human amniotic fluid stem cells improved survival in a rat model of lipopolysaccharide-induced neonatal sepsis through immunomodulation via aggregates with peritoneal macrophages.

Sato Y, Ochiai D, Abe Y, Masuda H, Fukutake M, Ikenoue S, Kasuga Y, Shimoda M, Kanai Y, Tanaka M

Stem cell research & therapy (Stem Cell Research and Therapy) 11 ( 1 ) 300 2020.07

Accepted

Background: Despite recent advances in neonatal care, sepsis remains a leading cause of mortality in neonates. Mesenchymal stem cells derived from various tissues, such as bone marrow, umbilical cord, and adipose tissue, have beneficial effects on adult sepsis. Although human amniotic fluid stem cells (hAFSCs) have mesenchymal stem cell properties, the efficacy of hAFSCs on neonatal sepsis is yet to be elucidated. This study aimed to investigate the therapeutic potential of hAFSCs on neonatal sepsis using a rat model of lipopolysaccharide (LPS)-induced sepsis. Methods: hAFSCs were isolated as CD117-positive cells from human amniotic fluid. Three-day-old rat pups were intraperitoneally treated with LPS to mimic neonatal sepsis. hAFSCs were administered either 3 h before or at 0, 3, or 24 h after LPS exposure. Serum inflammatory cytokine levels, gene expression profiles from spleens, and multiple organ damage were analyzed. hAFSC localization was determined in vivo. In vitro LPS stimulation tests were performed using neonatal rat peritoneal macrophages co-cultured with hAFSCs in a cell-cell contact-dependent/independent manner. Immunoregulation in the spleen was determined using a DNA microarray analysis. Results: Prophylactic therapy with hAFSCs improved survival in the LPS-treated rats while the hAFSCs transplantation after LPS exposure did not elicit a therapeutic response. Therefore, hAFSC pretreatment was used for all subsequent studies. Inflammatory cytokine levels were elevated after LPS injection, which was attenuated by hAFSC pretreatment. Subsequently, inflammation-induced damages in the brain, lungs, and liver were ameliorated. hAFSCs aggregated with peritoneal macrophages and/or transiently accumulated in the liver, mesentery, and peritoneum. Paracrine factors released by hAFSCs induced M1-M2 macrophage polarization in a cell-cell contact-independent manner. Direct contact between hAFSCs and peritoneal macrophages further enhanced the polarization. Microarray analysis of the spleen showed that hAFSC pretreatment reduced the expression of genes involved in apoptosis and inflammation and subsequently suppressed toll-like receptor 4 signaling pathways. Conclusions: Prophylactic therapy with hAFSCs improved survival in a rat model of LPS-induced neonatal sepsis. These effects might be mediated by a phenotypic switch from M1 to M2 in peritoneal macrophages, triggered by hAFSCs in a cell-cell contact-dependent/independent manner and the subsequent immunomodulation of the spleen.

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Universal screening for SARS-CoV-2 in asymptomatic obstetric patients in Tokyo, Japan.

Ochiai D, Kasuga Y, Iida M, Ikenoue S, Tanaka M

Accepted, ISSN 0020-7292

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A new diagnostic strategy for gestational diabetes during the COVID-19 pandemic for the Japanese population.

Kasuga Y, Saisho Y, Ikenoue S, Ochiai D, Tanaka M

Diabetes/metabolism research and reviews 36 ( 8 ) e3351 2020.05

Accepted, ISSN 1520-7552

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The association between placenta implantation at prior myomectomy locations and perinatal outcomes in pregnant women who previously underwent one-step hysteroscopic myomectomy

Kasuga Y., Lin B.L., Kim S.H., Higuchi T., Iwata S., Nakada S.

Gynecology and Minimally Invasive Therapy (Gynecology and Minimally Invasive Therapy) 9 ( 2 ) 54 - 58 2020.04

Accepted, ISSN 22133070

© 2020 Gynecology and Minimally Invasive Therapy. Objectives: There are no data describing the correlation between placenta implantation at prior myomectomy locations and perinatal outcomes in pregnant women after transcervical resection myomectomy (TCR-M). The aim of the study is to investigate the correlations between placenta implantation at prior myomectomy locations and perinatal outcomes in pregnant women who had previously undergone TCR-M. Materials and Methods: This was a retrospective, single-center study. We reviewed the records of 34 pregnant women who had previously undergone TCR-M for submucosal myoma and perinatal care in our hospital between January 2012 and January 2019. We examined surgical and pregnancy outcomes and evaluated correlations between placenta implantation at prior myomectomy locations and perinatal outcomes in women who delivered after 22 gestational weeks (n = 24). Results: Median maternal age at conception was 38 years (range, 28-44) and median duration between TCR-M and conception was 1.4 years (range, 0.3-5.8). There were 24 deliveries after 22 gestational weeks and 10 pregnancy losses. Among these 24 deliveries, the median gestational age at delivery was 39 weeks (range, 34-41); median birthweight, 3025 g (range, 2092-4012); and median blood loss at delivery, 573 g (range, 100-3000). There were no cases of placenta accreta and uterine rupture. Placenta implantation at a prior myomectomy location was detected in 14/24 women using transabdominal ultrasonography. Median blood loss was significantly higher in the implantation than in the nonimplantation group (P < 0.01). Conclusion: Our one-step TCR-M is useful for women with submucosal myoma. However, we suggest that clinicians should review and check the association between prior myomectomy locations and placenta implantation.

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頭痛および視野欠損を契機に診断に至った脳動脈解離による脳梗塞合併妊娠の1例

秋田啓介, 春日義史, 玉川真澄, 上條慎太郎, 大石真希, 遠藤豊英, 大谷利光, 池ノ上学, 落合大吾, 宮越敬, 田中守, 青木大輔

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 69 ( 2 ) 212 - 217 2020.04

Accepted, ISSN 2186-0599

緒言:脳動脈解離は若年発症脳梗塞の原因となり、リスク因子としては片頭痛や高血圧が挙げられるが、妊婦における初発例は稀である。今回我々は妊娠中に発症した脳動脈解離による脳梗塞の1例を経験したので報告する。症例:31歳、3妊1産。既往歴として片頭痛を認めた。妊娠26週0日に激しい頭痛が出現し、その1週間後に右側半盲を認めた。頭部MRI/MRA検査で左後大脳動脈の狭小化と左後頭葉の虚血性変化が認められ、脳動脈解離による脳梗塞の診断となった。神経学的症状の増悪や血圧の変動なく経過し、妊娠37週5日に経腟分娩に至った。児は2926gの女児でApgar score 8/10点(1/5分値)であった。分娩中や分娩後に血圧の変動や新規の神経学的異常所見の出現は認めなかった。結論:神経学的異常所見を伴う頭痛を認める際には脳動脈解離を含めた脳血管障害を念頭に頭蓋内病変精査を行う必要があると考えられた。(著者抄録)

妊娠中期に卵巣癌と診断し、手術療法と化学療法治療後に生児を得られた1例

田中邦生, 長谷川慶太, 吉村拓馬, 大石真希, 大谷利光, 池ノ上学, 春日義史, 落合大吾, 岩田卓, 宮越敬, 田中守, 青木大輔

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 69 ( 2 ) 387 - 391 2020.04

Accepted, ISSN 2186-0599

緒言:卵巣癌合併妊娠は1万から5万例に1例と頻度が低く、対応に一定の見解はない。今回我々は妊娠中期に卵巣癌を診断され、手術療法と化学療法を行い生児を得られた症例を経験した。症例:44歳、1妊0産。妊娠16週時に卵巣癌を疑われ、妊娠18週時に右付属器摘出術、左卵巣腫瘍摘出術、大網生検を施行した。右卵巣原発の高異型度漿液性癌IIIC期の診断にて術後パクリタキセルとカルボプラチン(TC)併用療法を4サイクル施行し、妊娠35週5日時に選択的帝王切開術とinterval debulking surgeryを同時に施行した。2118gの女児を娩出し、術後TC療法を2サイクル施行した。術後母体は再発を認めず、児の発育も良好である。結論:卵巣癌合併妊娠に対して、予め分娩時期を想定した管理・治療を行ったことで母児ともに合併症なく手術療法と化学療法を行うことができた。(著者抄録)

Transvaginal ultrasound features of the residual cervix in pregnancy after radical trachelectomy

Kasuga Y., Miyakoshi K., Tanaka M.

Journal of Medical Ultrasonics (Journal of Medical Ultrasonics) 47 ( 2 ) 335 - 337 2020

ISSN 13464523

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Differences in fetal fractional limb volume changes in normal and gestational diabetic pregnancies: an exploratory observational study

Akiba Y., Ikenoue S., Endo T., Kasuga Y., Ochiai D., Miyakoshi K., Ishii R., Yakubo K., Tanaka M.

BJOG: An International Journal of Obstetrics and Gynaecology (BJOG: An International Journal of Obstetrics and Gynaecology) 128 ( 2 ) 329 - 335 2020

Accepted, ISSN 14700328

© 2020 Royal College of Obstetricians and Gynaecologists Objective: Fetal fractional limb volume has been proposed as a useful measure for quantifying fetal soft tissue development. The aim of this study was to investigate the growth of fractional arm volume (AVol) and fractional thigh volume (TVol) of fetuses with maternal gestational diabetes (GDM) compared with those of fetuses with normal glucose tolerance (NGT). We hypothesised fetal fractional limb volume would be larger in the GDM group than in the NGT group in late gestation. Design: Exploratory observational study. Setting: Saitama Municipal Hospital. Sample: A total of 165 (125 NGT and 40 GDM) singleton Japanese pregnant women. Methods: AVol and TVol were assessed between 20 and 37 weeks’ gestation as cylindrical limb volumes based on 50% of the fetal humeral or femoral diaphysis length. Women were diagnosed as GDM based on the criteria of the Japan Society of Obstetrics and Gynecology. Main outcome measures: AVol and TVol were compared between women with NGT and those with GDM at each gestational age period (2-week intervals from 20 to 37 weeks’ gestation). Results: Overall, 287 ultrasound scans were performed (NGT group, 205 scans; GDM group, 82 scans). There was no significant difference of AVol between the groups before 32 weeks’ gestation. AVol was significantly larger in the GDM group than in the NGT group after 32 weeks’ gestation (P < 0.05). TVol was not statistically different between the groups across gestation. Conclusions: Detection of variations in fetal AVol may provide greater insight into understanding the origins of altered fetal body proportion in GDM. Tweetable abstract: AVol, but not TVol, is significantly larger in fetuses with GDM than in those with NGT after 32 weeks’ gestation.

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Impaired early phase insulin secretion associated with gestational diabetes mellitus in underweight women

Kasuga Y., Miyakoshi K., Saisho Y., Ikenoue S., Ochiai D., Tanaka M.

Journal of Maternal-Fetal and Neonatal Medicine (Journal of Maternal-Fetal and Neonatal Medicine) 35 ( 12 ) 1 - 3 2020

Accepted, ISSN 14767058

© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group. Background: No reports have focused on the clinical and metabolic characteristics of gestational diabetes (GDM) in underweight women. The aim of this study is to investigate the clinical and metabolic features of underweight GDM (pregravid BMI, <18.5 kg/m2: U-GDM). Materials and methods: Women diagnosed with GDM were categorized based on their pre-pregnancy BMI as either underweight (n = 49) or normal weight (pregravid BMI, 18.5–25.0 kg/m2: n = 271: N-GDM). During the study period, GDM was diagnosed using the International Association of Diabetes in Pregnancy Study Group criteria. Women with multi-fetal pregnancies, fetal congenital anomalies, overt diabetes in pregnancy, and pre-gestational diabetes mellitus were excluded. Results: There were no notable differences in maternal age at delivery and the rate of nulliparous between the U-GDM and N-GDM groups. Regarding antepartum oral glucose tolerance test profiles, women with U-GDM exhibited significantly lower fasting plasma glucose (FPG) levels than those with N-GDM (p <.01). The Insulinogenic Index of women with U-GDM was significantly lower than that of women with N-GDM (p <.05). Conclusion: Impaired early phase insulin secretion was associated with GDM onset in underweight women.

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Changes in bone metabolic profile associated with pregnancy or lactation

Miyamoto T., Miyakoshi K., Sato Y., Kasuga Y., Ikenoue S., Miyamoto K., Nishiwaki Y., Tanaka M., Nakamura M., Matsumoto M.

Scientific Reports (Scientific Reports) 9 ( 1 ) 6787 2019.12

Accepted

© 2019, The Author(s). Calcium and nutrients are transferred from mothers to fetuses or infants during pregnancy or lactation, respectively, promoting metabolic changes in the mother, many uncharacterized. To evaluate these changes, we undertook two parallel studies. In one we analyzed fourteen clinical cases of vertebral fragility fractures, at or before three months after partum, in mothers who breastfed their infants. In the other, we enrolled 79 additional pregnant subjects, some who chose to breastfeed and others who did not, and analyzed changes in bone metabolic status starting between 34 and 36 weeks of gestation and ending one month after partum. In the larger group, bone-resorbing and bone-forming parameters such as serum TRACP5b and osteocalcin, respectively, significantly increased after partum. Among parameters that changed after partum, serum PTH and the bone-resorbing markers serum TRACP5b and urine NTX were significantly higher in mothers who only breastfed infants compared to mothers who fed infants formula or a mix of both. However, bone-forming parameters were comparable between breastfeeding and non-breast-feeding groups after partum, suggesting that elevated bone-resorption occurs only in the breastfeeding group. Radiographic analysis after partum demonstrated that no subject among the 79 analyzed showed vertebral fractures, even those who breastfed exclusively. Among fracture cases analyzed, subjects exhibited significantly lower bone mineral density than did non-fracture cases in breastfeeding-only subjects. We conclude that bone metabolic status significantly changes over the period between pregnancy and post-partum lactation, and that low bone mineral density seen in a small subset of breastfeeding-only cases likely causes post-partum vertebral fragility fractures.

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再癒着に留意した子宮鏡下癒着剥離術施行後に良好な周産期経過をたどった重度アッシャーマン症候群の1例

王洪欣, 春日義史, 吉村拓馬, 大橋千恵, 石垣順子, 鈴木毅, 金善惠, 樋口隆幸, 染谷健一, 林保良, 中田さくら

神奈川産科婦人科学会誌 (神奈川産科婦人科学会) 56 ( 1 ) 29 - 32 2019.10

Accepted, ISSN 0910-2485

緒言:アッシャーマン症候群は子宮内膜損傷により子宮内腔が癒着した状態であり、子宮性不妊の原因となる。今回我々は再癒着に留意した子宮鏡下癒着剥離術(trans-cervical resection of Asherman syndrome:(TCR-A)施行後に良好な周産期経過をたどった重度アッシャーマン症候群の1例を経験した。症例:29歳、3妊0産(人工妊娠中絶1回、稽留流産2回)、いずれも子宮内容除去術を施行されている。過少月経ならびに既往よりアッシャーマン症候群を疑われ、精査加療目的に当院を紹介受診した。子宮鏡検査では子宮内腔の2/3以上が結合織性癒着し、重度アッシャーマン症候群と診断し、TCR-Aの方針とした。子宮内腔の白色で内膜が存在しない癒着部分をはさみ鉗子で鋭的に切断解放し、術後癒着予防のために子宮内避妊器具を挿入した。術後1ヵ月の子宮鏡検査では子宮内腔の再癒着を認めなかった。術後5ヵ月で自然妊娠成立し、癒着胎盤の発生に留意して管理したが、妊娠経過に異常は認めなかった。妊娠37週3日に経腟分娩に至り、児は2265gの女児、Apgar score8/9点(1/5分値)であった。分娩時出血量は200g、胎盤剥離はスムーズであり、癒着胎盤を認めなかった。結語:再癒着に留意したTCR-Aを行ったことで自然妊娠成立し、良好な妊娠分娩予後をたどった可能性が示唆された。(著者抄録)

腰背部痛を主訴に来院した結核性胸膜炎合併妊娠の1例

松井友哉, 春日義史, 石垣順子, 鈴木毅, 金善惠, 樋口隆幸, 染谷健一, 中田さくら

神奈川産科婦人科学会誌 (神奈川産科婦人科学会) 56 ( 1 ) 46 - 49 2019.10

Accepted, ISSN 0910-2485

目的:本邦における結核発生数は減少傾向にあるものの、他の先進国と比較して多く、特に発展途上国出身者に多い。今回我々は腰背部痛を主訴に来院した結核性胸膜炎合併妊娠の1例を経験したので報告する。症例:42歳、8妊5産、フィリピン国籍。妊娠20週に約2週間継続した咳を認めたが、鎮咳薬で軽快していた。妊娠23週2日、左腰背部痛と呼吸苦を主訴に外来を受診したところ、左季肋部圧痛と左肋骨脊柱角叩打痛を認めた。腎盂腎炎の診断で入院管理とし、抗菌薬投与を開始したところ、第6病日に吸気時に増悪する背部痛が顕在化した。画像検査や採血検査上、結核が疑われたが、喀痰培養検査などは陰性であったために経皮的胸膜生検を行った。臨床経過ならびに病理組織学的検査結果より結核性胸膜炎及び肺結核と診断したため、多剤併用療法を開始した。その後の経過は順調であり、既往帝王切開術後妊娠のために妊娠37週5日に選択的帝王切開術を施行した。児は男児で3380g、Apgar score8/9点(1/5分値)であった。児に先天性結核は認めず、母児ともに術後7日目に退院した。結論:今回我々は腰背部痛を主訴に来院した結核性胸膜炎合併妊娠の1例を経験した。結核性胸膜炎発症時には腰背部痛を主訴に来院する可能性があり、特に発展途上国出身者では腰背部痛の鑑別疾患として結核性胸膜炎を念頭に入れることも必要であると考えられた。(著者抄録)

日本人妊娠糖尿病既往女性における産後糖代謝異常発症予測因子に関する後方視的検討

春日義史, 宮越敬, 税所芳史, 池ノ上学, 荒田尚子, 田中守

糖尿病と妊娠 ((一社)日本糖尿病・妊娠学会) 19 ( 2 ) S - 67 2019.08

Accepted, ISSN 1347-9172

日本人妊娠糖尿病(Gestational Diabetes Mellitus:GDM)既往女性における産後糖代謝異常(Postpartum Abnormal Glucose Tolerance:pAGT)発症予測因子を検討した。対象は日本人GDM合併単胎妊婦のうち、分娩後1年以内に75gOGTTを受けた女性である(pAGT[n=59]、正常耐糖能型[n=154])。GDM診断時OGTT血糖値ならびに遺伝因子とpAGTとの関連解析を行ったところ、OGTT2時間値のpAGT発症予測能が高かった(AUC=0.72)。遺伝因子では4遺伝子がpAGT群においてリスクアレルを多く持つ傾向にあり、検出された4遺伝子中、3遺伝子はインスリン分泌関連遺伝子であった。日本人GDM既往女性において、GDM診断時OGTT 2時間値がpAGT発症予測に有用であり、遺伝学的にインスリン分泌不全の関与が示唆された。(著者抄録)

Ultrasound Findings of Varices at the Site of Uterovaginal Anastomosis in a Pregnant Woman After Radical Trachelectomy.

Kasuga Y, Miyakoshi K, Tanaka M

Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine (Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine) 38 ( 12 ) 3363 - 3364 2019.05

Accepted, ISSN 0278-4297

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Twelve-year experience of office-setting removal of lost intrauterine devices in place for more than 10 years

Kasuga Y., Lin B., Maki J., Wang H., Yoshimura T., Nagai Y., Nakada S.

European Journal of Contraception and Reproductive Health Care (European Journal of Contraception and Reproductive Health Care) 24 ( 3 ) 206 - 208 2019.05

Accepted, ISSN 13625187

© 2019, © 2019 The European Society of Contraception and Reproductive Health. Objective: We investigated the effectiveness of removing lost intrauterine devices (IUDs) that had been in place for over 10 years, using Lin's biopsy grasper in an office setting. Methods:This single-centre, retrospective study conducted between March 2006 and June 2018 included 49 women who had had an IUD in place for contraception for more than 10 years and who underwent removal of the lost IUD using Lin's biopsy grasper under transabdominal sonography without use of a tenaculum, anaesthesia and analgesia, after dilation of the cervical os and hysteroscopy. Results: The women's median age was 52 years (range 34–80 years) and the median duration of insertion was 17 years (range 10–43 years). Forty-eight (98%) women had their lost IUD removed using Lin's biopsy grasper. Among the removed IUDs, there were eight FD-1 IUDs with a string, 13 FD-1 IUDs without a string, 13 Chinese IUDs, seven Ota ring IUDs, three KS ring IUDs, two Saf-T-Coil IUDs, two Lippe loop IUDs and one Wing IUD. All women tolerated the procedure and there were no major operative complications. Conclusions: Lin's biopsy grasper was effective in removing IUDs that had been in place for a long time.

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Clinical and genetic characteristics of abnormal glucose tolerance in Japanese women in the first year after gestational diabetes mellitus

Kasuga Y., Miyakoshi K., Tajima A., Saisho Y., Ikenoue S., Ochiai D., Matsumoto T., Arata N., Hata K., Tanaka M.

Journal of Diabetes Investigation (Journal of Diabetes Investigation) 10 ( 3 ) 817 - 826 2019.05

Accepted, ISSN 20401116

© 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd Aims/Introduction: Risk factors of type 2 diabetes mellitus in Japanese women with recent gestational diabetes mellitus are unknown. The objective of the present study was to investigate the clinical and genetic characteristics associated with postpartum abnormal glucose tolerance in Japanese women with gestational diabetes mellitus. Materials and Methods: A total of 213 Japanese women with recent gestational diabetes mellitus who underwent a postpartum 2-h oral glucose tolerance test were investigated. The association between antepartum clinical characteristics and postpartum abnormal glucose tolerance (diabetes or prediabetes based on the Japan Diabetes Society criteria) was examined. Frequencies of 45 known type 2 diabetes mellitus-associated genetic variants were also compared between women with and without postpartum abnormal glucose tolerance. Results: A total of 59 women showed postpartum abnormal glucose tolerance (prediabetes, n = 51; diabetes, n = 8). Plasma glucose levels at 1 or 2 h, the insulinogenic index and the insulin secretion-sensitivity index-2 of the antepartum oral glucose tolerance test were independent of postpartum abnormal glucose tolerance risk factors (P = 0.006, P = 0.00002, P = 0.01 and P = 0.006, respectively). Four genetic variants (rs266729 [ADIPOQ], rs6017317 [HNF4A], rs5215 [KCNJ11] and rs7177055 [HMG20A]) showed a nominally significant association with postpartum abnormal glucose tolerance (P < 0.05, respectively). Among these, three were related to insulin secretion. Postpartum abnormal glucose tolerance risk significantly increased with increasing risk-allele number (P = 0.0005; odds ratio 1.91). Conclusions: Clinical features and genetic variants related to impaired insulin secretion are risk factors of postpartum abnormal glucose tolerance in Japanese women with recent gestational diabetes mellitus.

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Glycemic and metabolic features in gestational diabetes: singleton versus twin pregnancies.

Akiba Y, Miyakoshi K, Ikenoue S, Saisho Y, Kasuga Y, Ochiai D, Matsumoto T, Tanaka M

Endocrine journal 66 ( 7 ) 647 - 651 2019.04

ISSN 0918-8959

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筋腫分娩様に腟内に突出した巨大子宮頸部筋腫合併妊娠の1例

田中邦生, 春日義史, 王洪欣, 吉村拓馬, 大橋千恵, 眞木順子, 鈴木毅, 金善惠, 樋口隆幸, 染谷健一, 林保良, 中田さくら

関東連合産科婦人科学会誌 ((一社)関東連合産科婦人科学会) 56 ( 1 ) 73 - 77 2019.03

Accepted, ISSN 2186-0610

【緒言】子宮筋腫は妊娠適齢期女性において頻度の高い疾患であり,筋腫合併妊娠は比較的よく遭遇する病態である.今回我々は筋腫分娩様に腟内に突出した巨大子宮頸部筋腫合併妊娠の1例を経験したので報告する.【症例】32歳,3妊1産(経腟分娩1回,自然流産1回).自然妊娠成立後,無月経11週に当院を受診した.初診時には腟内を占拠する7cm大の子宮筋腫を認め筋腫分娩が疑われた.MRI検査(妊娠15週)にて,子宮頸管後壁との境界が不明瞭な9cm×6cm×9cmの腫瘤が腟内に突出しており,筋腫は子宮頸部後壁発生の頸部筋腫であると診断した.妊娠中は経過観察の方針とし,特に有害事象の発症はなかった.筋腫が腟内を占拠していたため,経腟分娩は困難と判断し,帝王切開術の方針とした.妊娠36週4日に選択的帝王切開術を施行し,出血リスクを考慮して筋腫切除は行わなかった.児は1,915gの女児で,Apgar score 8/9点(1/5分値)であり,構造異常は認めなかった.また,術中出血量は818gで診察でも有茎性筋腫ではなく,子宮頸部後壁発生の頸部筋腫であることを確認し,悪露流出可能を確認後に手術を終了とした.術後経過良好にて術後7日目に退院した.【結語】頸部筋腫と有茎性筋腫分娩との鑑別にMRI検査は有用であり,頸部筋腫と筋腫分娩の鑑別を行えたことで経過観察を行い,良好な予後を得られた.(著者抄録)

子宮鏡手術を契機にKaufmann療法を中止したところ自然妊娠し生児を得た早発卵巣不全の1例

眞木順子, 林保良, 王洪欣, 吉村拓馬, 大橋千恵, 鈴木毅, 春日義史, 金善惠, 樋口隆幸, 染谷健一, 中田さくら

神奈川産科婦人科学会誌 (神奈川産科婦人科学会) 55 ( 2 ) 145 - 147 2019.02

Accepted, ISSN 0910-2485

今回我々は、急性骨髄性白血病治療後の早発卵巣不全に対して長年Kaufmann治療を行い、子宮粘膜下筋腫に対する子宮鏡手術を契機にKaufmann療法を中止したところ自然妊娠に至った一例を経験したので報告する。症例は30歳 0妊0産であり、9歳で急性骨髄性白血病を発症し、12歳の再発時に骨髄移植、放射線治療の既往がある。自然周期での月経はなく、16歳から14年間Kaufmann療法にて消退出血を起こしてきた。不正出血の症状を認めたため、外来にて精査したところ14.8×13.0×13.5mmの突出率70〜80%程度の粘膜下筋腫を認め、Kaufmann療法中止の上、子宮鏡下子宮筋腫核出術の方針となった。手術当日経腹超音波にて子宮内に胎嚢及び胎児心拍を認め、妊娠7週相当であったため、手術は中止とし、周産期管理を行い、生児を得た。Kaufmann療法は以前リバウンド作用による排卵誘発法として用いられており、数周期施行後にKaufmann療法を中止すると、卵巣機能が活性化され、排卵が回復する可能性があるとされている。原発性無月経であってもKaufmann療法を中止し、月経周期や排卵が自然回復する可能性があることを念頭に置く必要がある。(著者抄録)

腹腔鏡下子宮筋腫核出術中の内膜穿破時に摘出した内膜腫瘤から診断し得た、子宮内膜異型増殖症の1例

染谷健一, 竹田貴, 吉村拓馬, 王洪欣, 大橋千恵, 眞木順子, 鈴木毅, 春日義史, 金善惠, 樋口隆幸, 林保良, 中田さくら

神奈川産科婦人科学会誌 (神奈川産科婦人科学会) 55 ( 2 ) 159 - 163 2019.02

Accepted, ISSN 0910-2485

子宮や付属器の良性疾患に対する手術の前に、一般的に悪性疾患の除外のために子宮頸部細胞診や子宮内膜細胞診などを行うことが多いが、特に内膜細胞診はその精度に留意が必要である。今回我々は、術前の画像診断、細胞診ともに悪性所見を認めなかった症例において、子宮筋腫に対して腹腔鏡下子宮筋腫核出術を行い、術中の内膜破綻を機に内膜のポリープ状病変を発見し、子宮内膜異型増殖症の診断に至った症例を経験したので、報告する。症例は37歳女性、0妊0産、過多月経を主訴に、粘膜下筋腫を含む多発筋腫を指摘され、紹介受診。画像上、40mm大の粘膜下筋腫及び左内膜症性嚢胞を認め、スクリーニングの子宮頸部及び内膜細胞診に異常なきことを確認し、腹腔鏡下子宮筋腫核出術、左卵巣嚢腫摘出術を施行した。術中の筋腫核出の際に内膜が破綻し、内腔にポリープ状病変があることを偶発的に発見し、切除した。病理診断にて、同病変は子宮内膜異型増殖症であった。術後に再度、子宮内膜細胞診、組織診、子宮鏡観察にて内腔病変の残存や癌の併存を疑う所見のなきことを確認し、全腹腔鏡下腟式子宮全摘出術を行った。本症例のように、子宮筋腫による内腔変形がある場合、子宮内膜細胞診によるスクリーニングには限界があることを十分に理解し、筋腫核出などの妊孕性温存手術を行う際は、術前に子宮鏡による内腔観察を考慮することが重要であると考えられた。(著者抄録)

Size for gestational age at birth according to offspring sex and gestational weight gain in underweight women

Kasuga Y., Shigemi D., Tamagawa M., Suzuki T., Kim S., Higuchi T., Yasunaga H., Nakada S.

Journal of Developmental Origins of Health and Disease (Journal of Developmental Origins of Health and Disease) 10 ( 5 ) 536 - 541 2019

Accepted, ISSN 20401744

© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2019. Although maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are related to fetal growth, there is a paucity of data regarding how offspring sex affects the relationship between maternal BMI in underweight mothers (pre-pregnancy BMI <18.5 kg/m 2 ) and size for gestational age at birth. The aim of this study was to investigate the effect of offspring sex on the relationships among maternal pre-pregnancy BMI, GWG and size for gestational age at birth in Japanese underweight mothers. Records of women with full-term pregnancies who underwent perinatal care at Kawasaki Municipal Hospital (Kawasaki, Japan) between January 2013 and December 2017 were retrospectively reviewed. The study cohort included underweight (n=566) and normal-weight women (18.5 kg/m 2 1/2pre-pregnancy BMI<25 kg/m 2 ; n=2671). The incidence of small for gestational age (SGA) births in the underweight group was significantly higher than that in the normal-weight group (P<0.01). Additionally, SGA incidence in the underweight group was significantly higher than that in the normal-weight group (P<0.01) in female, but not male (P=0.30) neonates. In the women with female neonates, pre-pregnancy underweight was associated with a significantly increased probability of SGA (odds ratio [OR]: 1.80; P<0.01), but inadequate GWG was not (OR: 1.38; P=0.11). In contrast, in women with male neonates, inadequate GWG was associated with a significantly increased probability of SGA (OR: 1.53; P=0.03), but not with pre-pregnancy underweight (OR: 1.30; P=0.10). In conclusion, the present results suggest that pre-pregnancy underweight is associated with SGA in female offspring but not in male offspring.

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Intrauterine Protrusion of Metal Coils: A Rare Complication of Uterine Artery Embolization

Yoshimura T., Kasuga Y., Higuchi T., Lin B.

Journal of Minimally Invasive Gynecology (Journal of Minimally Invasive Gynecology) 26 ( 7 ) 1215 - 1216 2019

ISSN 15534650

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Impaired fetal growth in mothers with inadequate gestational weight gain: a retrospective study in Japanese uncomplicated pregnancy.

Ikenoue S, Miyakoshi K, Kasuga Y, Ochiai D, Matsumoto T, Tanaka M

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians (Journal of Maternal-Fetal and Neonatal Medicine) 33 ( 13 ) 1 - 5 2018.12

Accepted, ISSN 1476-7058

Introduction: The average birth weight in Japan has gradually decreased and the number of low birth weight infant has increased over the last 30 years. Japanese pregnant women are characterized with lower prevalence of obesity than those in other developed countries, and maternal underweight before pregnancy is independently associated with low birth weight. However, the association between maternal inadequate gestational weight gain (GWG) and the risk of small for gestational age (SGA) in Japanese uncomplicated pregnant women has not been fully understood. This study aimed to examine the effect of maternal inadequate GWG on the risk of SGA in Japanese uncomplicated pregnancies. Methods: We retrospectively analyzed uncomplicated Japanese singleton pregnancies that delivered at term gestation in our institution from 2006 to 2016. The association between GWG and birth weight was analyzed by multiple linear regression. Potential confounding factors included maternal age, parity, prepregnancy BMI, and neonatal sex. The association between inadequate GWG and SGA was also examined by logistic regression. Results: A total of 3837 mother–neonate dyads were analyzed. Maternal GWG was 10.1 ± 3.7 kg (mean ± SD), and 2529 (66%) had inadequate GWG. After adjusting for confounding factors, GWG significantly correlated with birth weight (standardized β = 0.199, p <.001). Inadequate GWG increased the risk of delivering SGA neonate (adjusted odds ratio (aOR) = 1.97 [1.45–2.68], p <.001). This association was particularly pronounced in underweight (aOR = 2.95 [1.38–6.29], p =.005) and normal weight mothers (aOR = 1.79 [1.27–2.52], p =.001), and not in overweight/obese mothers (p =.115). Conclusion: Maternal GWG is associated with birth weight in Japanese women with uncomplicated singleton pregnancies. Inadequate GWG is an important risk factor of SGA, particularly in non-obese women. The present finding would potentially provide further evidence that promoting adequate gestational weight gain in Japanese underweight and normal weight mothers would reduce SGA, as well as metabolic dysfunction in later life.

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当院で対応した特定妊婦の実態

春日義史, 玉川真澄, 鈴木毅, 金善惠, 樋口隆幸, 上野和典

日本周産期・新生児医学会雑誌 ((一社)日本周産期・新生児医学会) 54 ( 4 ) 965 - 968 2018.12

Accepted, ISSN 1348-964X

2017年1月〜12月に周産期管理を行った特定妊婦47例の母体背景を検討した。分娩時年齢の中央値は28歳、若年妊娠は2例で、未婚者31例中11例はパートナー不在であった。特定妊婦への選定理由(重複あり)は、経済的理由37例、精神疾患合併妊娠21例、要保護児童もしくは要支援児童を養育している妊娠17例、児童虐待既往あり7例、家庭内暴力被害者7例、違法薬物使用歴あり3例、精神発達遅延1例、性的暴力による妊娠1例であった。児は自宅引き取り44例であったが、2例は乳児院、1例は里親に預けられた。1ヵ月検診未受診は5例、出生届未提出は1例であり、2例は現在まで入院費未払いである。

難治性骨盤内炎症性疾患を呈した好酸球性胃腸炎の1例

玉川真澄, 仙波宏史, 山上亘, 高柳裕子, 春日義史, 小林佑介, 冨永英一郎, 田中守, 青木大輔

関東連合産科婦人科学会誌 ((一社)関東連合産科婦人科学会) 55 ( 4 ) 453 - 458 2018.11

Accepted, ISSN 2186-0610

好酸球性胃腸炎(Eosinophilic Gastroenteritis:EGE)は,消化管に著明な好酸球浸潤を来たす希少な消化器疾患である.嚥下障害,腹痛,下痢など多彩な消化器症状を生じ,有病率は10万人に数名とされる.難治性の骨盤内炎症性疾患(Pelvic Inflammatory Disease:PID)を呈したEGEの1例を報告する.症例は45歳,2妊2産,アレルギーなし.39℃の発熱および下腹痛を主訴に来院した.子宮及び左付属器に著明な圧痛があり,また成熟嚢胞性奇形腫を疑う左卵巣腫瘍を認めた.PIDを疑い抗菌薬投与を開始したものの発熱と炎症所見は改善しなかったため,左付属器および右卵管を摘出したが,術後経過は軽快と再燃を繰り返した.病理所見を再評価したところ,洗浄腹水および付属器漿膜への好酸球浸潤が著明であることからEGEの診断に至った.副腎皮質ステロイド投与を開始し,炎症所見は軽快し退院となった.EGEの診断は消化管粘膜または腹水への好酸球浸潤の病理診断に基づくが,必ずしも容易ではない.本症例においては,病理所見の再評価が診断に重要な役割を果たした.難治性の骨盤腹膜炎に遭遇した際は,試験腹腔鏡による骨盤内検索および腹水を含めた病理学的検索が診断の一助となりうることが示唆された.(著者抄録)

Is the risk of small for gestational age influenced by maternal body composition in young Japanese women?

Kasuga Y, Kim SH, Suzuki T, Higuchi T, Nakada S

Accepted, ISSN 1476-7058

© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. Background: We aimed to investigate whether there was a high incidence of young Japanese mothers being underweight (pregravid body mass index [BMI] < 18.5 kg/m2) and if they delivered infants who were small for gestational age (SGA). Materials and methods: Our study was carried out from 2013 to 2017 and included adolescent women (maternal age at delivery: <20 years old; n = 94), women in their early twenties (maternal age at delivery: 20–24 years; n = 479), and controls (maternal age at delivery: 25–34 years; n = 2061). Results: In both the adolescent and early twenties groups, the incidence of being underweight, based on prepregnancy BMI, was significantly higher than controls (p <.0001 and p <.05, respectively). In both groups, gestational weight gain (GWG) was significantly higher than controls (p <.0001). There were no notable group differences in the incidences of SGA. Conclusion: The incidence of being underweight was higher in younger mothers than in controls. However, the risk of SGA did not increase in younger mothers, possibly because their GWG overcame the influence of their pre-pregnancy body composition.

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当院で周産期管理を施行した肥満妊婦における非妊時BMI別妊娠中体重増加量と出生体重の関連に関する検討

春日義史, 玉川真澄, 鈴木毅, 金善惠, 樋口隆幸, 上野和典

日本周産期・新生児医学会雑誌 ((一社)日本周産期・新生児医学会) 54 ( 3 ) 784 - 788 2018.09

Accepted, ISSN 1348-964X

当院で周産期管理を行った肥満妊婦を過体重群(Ov群)と肥満群(Ob群)に分類し、妊娠中体重増加量(GWG)が出生体重に与える影響について検討した。2013〜2016年に当院で周産期管理を行った単胎妊婦3402例のうち、Ov群374例、Ob群130例を対象とした。Ov群と比較してOb群の方がGWGは有意に少なかった。GWG適正群はOv群に有意に多く、Ob群ではGWG不足群がOv群に比して有意に多かった。また、両群の適正群におけるlarge-for gestational-age(LGA)発症率はOv群で12.7%、Ob群で23.3%であり、両群の過剰群では21.3%、47.6%とさらにLGA発症率が上昇した。GWGが出生体重に与える影響について検討するため、両群においてGWGと出生体重との相関分析を行ったところ、両群で有意な相関関係を示した。特にOb群の方がOv群よりもGWGと出生体重は高い相関を示した。

腹膜炎を繰り返した長期間留置子宮内避妊器具に対してLin式ポリープ鉗子で抜去した1例

春日義史, 林保良, 王洪欣, 吉村拓馬, 大橋千恵, 眞木順子, 鈴木毅, 金善惠, 樋口隆幸, 染谷健一, 中田さくら

神奈川産科婦人科学会誌 (神奈川産科婦人科学会) 55 ( 1 ) 58 - 60 2018.09

Accepted, ISSN 0910-2485

【目的】長期間留置された子宮内避妊器具(intrauterine device:IUD)は種々の細菌感染の原因となり、摘出不能例については子宮全摘術も含めた外科的加療を要することがある。今回我々は腹膜炎を繰り返した長期間留置子宮内避妊器具に対してLin式ポリープ鉗子で抜去した1例を経験したので報告する。【症例】57歳、3妊2産(人工妊娠中絶1回、経腟分娩2回)。30年前にIUDを挿入されたが、牽引糸が切れてしまい、抜去困難となっていた。当院来院2ヵ月前に下腹部痛と帯下異常を主訴に前医を受診し、急性骨盤腹膜炎の診断で入院にて抗菌薬加療された。また、それ以前にも同様の症状で入院加療された既往があった。前医では子宮全摘術が検討されたものの、複数回の骨盤内感染治療後であり強度腹腔内癒着の可能性が危惧され、経腟的IUD摘出目的に当院紹介受診した。当院子宮鏡外来にて、経腟超音波検査及び子宮鏡にてFD-1を確認した。経腹超音波検査下にヘガール頸管拡張器3号まで使用して子宮頸管を拡張後、Lin式ポリープ鉗子を挿入しFD-1を摘出した。なお、一連の操作は無麻酔下に施行し、患者は軽度疼痛のみで、出血もなく処置は終了した。【結論】腹膜炎を繰り返し、経腟的摘出は困難と考えられた長期間IUD挿入症例であっても、我々の方法では摘出可能であった。(著者抄録)

妊娠中の母体体重増加不良と出生体重に関する後方視的検討

池ノ上学, 宮越敬, 佐藤佑, 秋葉洋平, 大谷利光, 福武麻里絵, 春日義史, 落合大吾, 松本直, 田中守

糖尿病と妊娠 ((一社)日本糖尿病・妊娠学会) 18 ( 2 ) S - 86 2018.08

Accepted, ISSN 1347-9172

本邦では近年、やせ妊婦の増加と妊娠中の体重増加不良が指摘されている。今回、当院で単胎正期産分娩に至った3837例について、米国Institute of Medicine基準による母体体重増加不良と、在胎期間別出生時体格標準値(日本小児科学会)によるlight-for-date(LFD:出生体重<10パーセンタイル)との関連を年齢、経産数、非妊時BMI、児の性別を交絡因子として解析した。体重増加不良群では、LFDが有意に高率であり(adjusted odds ratio:1.94)、とくにやせ群(BMI < 18.5)と標準群(18.5 ≦ BMI< 25)でのみ有意差を認めた。やせ群と標準群では母体体重増加不良がLFDのリスク因子であることが示された。(著者抄録)

当院における妊娠合併卵巣嚢腫に対する全腹腔鏡下卵巣嚢腫切除術と腹腔鏡補助下卵巣嚢腫切除術の比較検討

玉川真澄, 樋口隆幸, 鈴木毅, 春日義史, 金善惠, 上野和典, 林保良, 中田さくら, 染谷健一

神奈川産科婦人科学会誌 (神奈川産科婦人科学会) 54 ( 2 ) 143 - 147 2018.02

Accepted, ISSN 0910-2485

近年妊娠合併卵巣嚢腫に対して腹腔鏡下手術を行う施設が増えているが、妊娠中の腹腔鏡下手術については未だ議論があり、術式や母体・胎児の予後に関して一定した見解はない。今回我々は妊娠合併卵巣嚢腫の腹腔鏡下手術において、術式が手術成績と周産期予後に及ぼす影響について後方視的に検討した。当院で施行された妊娠中の腹腔鏡下卵巣嚢腫切除術20例を体内法群9例、体外法群11例に分け、年齢、BMI、緊急手術、腫瘍径、手術・気腹時間、出血量、術後投薬・CRP・入院期間、分娩の転帰と週数、児の出生体重・奇形・合併症について比較検討した。術中子宮損傷の合併症はなかった。組織型では成熟嚢胞性奇形腫が最多であった。2群間の比較において、手術成績では体外法群で有意に気腹時間が短く、術後のCRPが高値であり、入院期間が長かった。周産期予後では、両群ともに流早産や胎児発育不全、児の奇形や合併症は認められなかった。成熟嚢胞性奇形腫切除の際、その手技は体外法群では容易であったが、体内法群では非妊時よりも難しく、腹腔内への嚢腫内容物漏出が全例で発生した。体外法は術後に下腹部小切開の侵襲による影響を伴っていたが、周産期予後では体内法と同様の良好な結果を得た。さらに体外法は体内法と比べ、子宮を圧迫して胎児循環に影響する気腹の時間を短縮する、術後化学性腹膜炎の原因となる嚢腫内容物漏出を防ぐなどの利点を有する可能性が示唆された。(著者抄録)

Cover Image, Volume 176A, Number 1, January 2018

Ikenoue S., Miyakoshi K., Ishii T., Sato Y., Otani T., Akiba Y., Kasuga Y., Ochiai D., Matsumoto T., Ichihashi Y., Matsuzaki Y., Tachikawa K., Michigami T., Nishimura G., Ikeda K., Hasegawa T., Tanaka M.

American journal of medical genetics. Part A (American journal of medical genetics. Part A) 176 ( 1 ) i 2018.01

Accepted, ISSN 1552-4825

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Discordant fetal phenotype of hypophosphatasia in two siblings

American Journal of Medical Genetics, Part A (American Journal of Medical Genetics, Part A) 176 ( 1 ) 171 - 174 2018.01

Accepted, ISSN 15524825

© 2017 Wiley Periodicals, Inc. Hypophosphatasia (HPP) is an autosomal recessive metabolic disorder with impaired bone mineralization due to mutations in the ALPL gene. The genotype-phenotype correlation of this disorder has been widely described. Here, we present two affected siblings, whose fetal phenotypes were discordant. A 31-year-old Japanese woman, G0P0, was referred to our institution because of fetal micromelia. After obstetric counseling, the pregnancy was terminated at 21 weeks’ gestation. Post-mortem radiographs demonstrated severely defective mineralization of the skeleton. The calvarial, spinal, and tubular bones were mostly missing. Only the occipital bones, mandible, clavicles, ribs, one thoracic vertebra, ilia, and tibia were relatively well ossified. The radiological findings suggested lethal HPP. Genetic testing for genomic DNA extracted from the umbilical cord identified compound heterozygous mutations in the ALPL gene (c.532T>C, p.Y178H; c.1559delT, p.Leu520Argfs*86). c.532T>C was a novel variant showing no residual activity of the protein by the functional analysis. The parents were heterozygous carriers. In the next pregnancy, biometric values on fetal ultrasonography at 20 and 26 weeks’ gestation were normal. At 34 weeks, however, a small chest and shortening of distal long bones came to attention. The neonate delivered at 41 weeks showed serum ALP of <5U/L. Radiological examination showed only mild thoracic hypoplasia and metaphyseal mineralization defects of the long bones. ALP replacement therapy was introduced shortly after birth, and the neonate was discharged at day 22 without respiratory distress. Awareness of discordant fetal phenotypes in siblings with HPP precludes a diagnostic error, and enables early medical intervention to mildly affected neonates.

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子宮動脈塞栓術が奏効した帝王切開瘢痕部妊娠の1例

荘慎太郎, 松本直, 佐藤佑, 大谷利光, 秋葉洋平, 春日義史, 池ノ上学, 落合大吾, 宮越敬, 田中守, 青木大輔

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 66 ( 4 ) 647 - 651 2017.10

Accepted, ISSN 2186-0599

近年、帝王切開率の上昇に伴い、帝王切開瘢痕部妊娠(Cesarean Scar Pregnancy、以下CSP)も増加傾向にあるとされる。CSPでは危機的産科出血や妊娠中の子宮全摘のリスクが高く、早期診断と慎重な周産期管理が求められる。今回我々は子宮動脈塞栓術が奏効したCSPの1例を経験したので報告する。症例は36歳、初回妊娠時に回旋異常による帝王切開の既往があり、妊娠6週2日に異所性妊娠疑いで当院受診となった。超音波検査にて胎嚢は子宮頸部に認められ、着床部位の筋層の菲薄化や胎嚢に流入する豊富な血流などの所見よりCSPの診断に至った。CSPの妊娠転帰について説明した結果、早期の妊娠中断を希望され妊娠6週6日に子宮動脈塞栓術および子宮内容除去術を実施した。術中の出血量は少量であり、経過良好にて術後4日目に退院となった。CSPの管理において子宮動脈塞栓術が有用であることが示唆された。(著者抄録)

Mid-trimester residual cervical length and the risk of preterm birth in pregnancies after abdominal radical trachelectomy: a retrospective analysis.

Kasuga Y, Miyakoshi K, Nishio H, Akiba Y, Otani T, Fukutake M, Ikenoue S, Ochiai D, Matsumoto T, Tanaka K, Minegishi K, Kuji N, Roberts R, Aoki D, Tanaka M

BJOG : an international journal of obstetrics and gynaecology 124 ( 11 ) 1729 - 1735 2017.10

ISSN 1470-0328

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妊娠糖尿病における血糖自己測定保険適用に関する後方視的検討

佐藤佑, 春日義史, 宮越敬, 秋葉洋平, 大谷利光, 福武麻里絵, 池ノ上学, 落合大吾, 松本直, 税所芳史, 田中守

糖尿病と妊娠 ((一社)日本糖尿病・妊娠学会) 17 ( 2 ) S - 47 2017.08

Accepted, ISSN 1347-9172

妊娠糖尿病(gestational diabetes mellitus;GDM)診療において、2016年度よりハイリスクGDMのみならず、75g経口ブドウ糖負荷試験(oral glucose tolerance test;OGTT)2点・3点陽性例および非妊時BMI(body massindex(BMI))≧25のOGTT1点陽性例に対しても血糖自己測定(self monitoring of blood glucose;SMBG)が保険適用となった。今回われわれは2011〜2015年に当院で周産期管理を行ったGDM合併妊娠387例に改定された保険算定基準を適用し、その臨床像を検討した。なお、当該期間において当院ではGDM全例にSMBGを導入した。第一に、算定基準改定前に11例(2.8%)であったSMBG保険適用症例は、新基準を用いた場合には148例(38%)であった。また、非該当例に比べ、改定基準該当例のインスリン導入率および分娩直前インスリン投与量は有意に高値であった(p<0.01)。今回の解析結果よりSMBG保険適用改定基準は実臨床における糖代謝異常重症度を反映するものと考えられた。(著者抄録)

当院における妊娠糖尿病例の胎児発育に関する後方視的検討

宮越敬, 税所芳史, 秋葉洋平, 大谷利光, 福武麻里絵, 春日義史, 池ノ上学, 落合大吾, 松本直, 田中守

糖尿病と妊娠 ((一社)日本糖尿病・妊娠学会) 17 ( 2 ) S - 57 2017.08

Accepted, ISSN 1347-9172

今回われわれは、血糖自己測定(self monitoringof blood glucose;SMBG)による厳重な管理を行った妊娠糖尿病(gestational diabetes mellitus;GDM)例の胎児発育を後方視的に検討した。対象は2011〜2015年に当院にて周産期管理を行った単胎正期産例(正常耐糖能[NGT]1668例、GDM 303例)である。NGTおよびGDMにおける出生体重、light-for-dates(LFD)、heavy-fordates(HFD)には有意差を認めず、非妊娠時の母体体格による層別化後も同様の結果であった。自験例の解析結果からは、GDMにおける胎児発育はNGTと同等であり、SMBGに基づく厳重なGDM管理はLFDを増加させることなくHFD発症予防に有効と考えられた。(著者抄録)

Association of common polymorphisms with gestational diabetes mellitus in Japanese women: A case-control study.

Kasuga Y, Hata K, Tajima A, Ochiai D, Saisho Y, Matsumoto T, Arata N, Miyakoshi K, Tanaka M

Endocrine journal 64 ( 4 ) 463 - 475 2017.04

Accepted, ISSN 0918-8959

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良好な周産期予後が得られた胎児鏡下胎盤吻合血管レーザー凝固術に伴う羊膜穿破例

神野雄一, 松本直, 大谷利光, 秋葉洋平, 福武麻里絵, 春日義史, 落合大吾, 宮越敬, 田中守, 青木大輔

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 65 ( 4 ) 640 - 643 2016.10

Accepted, ISSN 2186-0599

双胎間輸血症候群(TTTS)に対する胎児鏡下胎盤吻合血管レーザー凝固術(FLP)において羊膜穿破例の周産期予後は非穿破例と比較し不良とされる。今回我々はFLPに伴い羊膜穿破が生じたが、良好な周産期予後が得られた1例を経験したので報告する。症例は妊娠24週時にTTTSを発症し、他院にてFLPが実施された。術中に羊膜穿破が認められたものの、術後経過は良好であった。妊娠29週より自院にて周産期管理を再開し、早産兆候が出現したことや羊膜穿破に伴う合併症が発症する可能性などを考慮し、妊娠32週6日に選択的帝王切開術を施行した。術中所見において臍帯相互巻絡は認められず、母児ともに経過は良好であった。本症例においては羊膜穿破を早期に認識していたことで慎重な周産期管理を行い、臍帯の相互巻絡等の重篤な続発症を発症する前に妊娠終了時期を決定することが可能であった。(著者抄録)

妊娠初期に診断された妊娠糖尿病例の臨床像に関する検討

秋葉洋平, 宮越敬, 税所芳史, 大谷利光, 福武麻里絵, 春日義史, 落合大吾, 松本直, 田中守

糖尿病と妊娠 ((一社)日本糖尿病・妊娠学会) 16 ( 2 ) 137 - 139 2016.08

Accepted, ISSN 1347-9172

International Association of Diabetes and Pregnancy Study Group(IADPSG)と本邦の妊娠初期における妊娠糖尿病(GDM)診断基準は異なる。本研究の目的はIADPSG基準では正常耐糖能と判定される妊娠初期GDM臨床像の解析である。自施設で周産期管理を行った妊娠初期GDM(n=151)をGDM診断時75g経口ブドウ糖負荷試験の空腹時血糖高値群(血糖値≧92mg/dL:n=106)と低値群(血糖値<92mg/dL:n=45)に分け、両群の糖代謝異常重症度を比較検討した。まず、両群の母体背景(分娩時母体年齢、非妊時BMI、GDM既往、糖尿病家族歴)は同等であった。またインスリン療法導入率および分娩直前インスリン使用量について両群間に有意差を認めなかった。したがって、IADPSG基準では正常耐糖能と判定される妊娠初期GDMに対しても適切な血糖管理が必要であることが示された。(著者抄録)

Prenatal diagnosis of thrombosed dural sinus malformation with periorbital hemangioma: a case report.

Ochiai D, Miyakoshi K, Miwa T, Fukutake M, Kasuga Y, Matsumoto T, Tanaka M

European journal of obstetrics, gynecology, and reproductive biology 198 157 - 159 2016.03

Accepted, ISSN 0301-2115

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妊娠を契機に発見された浸潤子宮頸癌症例の検討

菅裕佳子, 西尾浩, 宮内安澄, 春日義史, 仲村勝, 森定徹, 岩田卓, 田中京子, 宮越敬, 田中守, 青木大輔

関東連合産科婦人科学会誌 ((一社)関東連合産科婦人科学会) 53 ( 1 ) 139 - 145 2016.03

Accepted, ISSN 2186-0610

妊娠を契機に発見される子宮頸癌は子宮頸癌全体の2〜3%とされる.しかし,これらについての臨床的な取り扱いは明確でない.本研究では当院で治療を行った妊娠を契機に発見された浸潤子宮頸癌症例15例について診療録をもとに後方視的に検討を行った.全症例の内訳は,臨床進行期IB1期14例,IIB期1例,組織型は,扁平上皮癌10例,腺癌5例であった.診断の契機となった子宮頸部細胞診で細胞診異常が確認された時期は13例(87%)が1st trimesterであった.これに続き子宮頸部組織診または円錐切除術によって確定診断された時期は8例(53.3%)が1st trimester,7例(46.7%)が2nd trimesterであった.妊娠転帰は11例が妊娠を継続せず,速やかに広汎子宮全摘出術を行い,4例は本人希望により妊娠継続し,予定帝王切開術と広汎子宮全摘出術を同時に行った.この妊娠非継続例,継続例の2群間において妊娠初期子宮頸部細胞診,確定診断,広汎子宮全摘出術の各施行時期について解析を行った.その結果,それぞれの中央値は,非継続例では妊娠6週,12週,17週で,継続例では妊娠10週,18週,32週となり,細胞診施行時期は2群間で有意な差は認めず,確定診断については妊娠継続例で遅い傾向を認めた.妊娠初期スクリーニング検査で細胞診異常を認めた際には速やかな対応が重要であると考えられた.(著者抄録)

Pregnancy Outcomes After Abdominal Radical Trachelectomy for Early-Stage Cervical Cancer: A 13-Year Experience in a Single Tertiary-Care Center.

Kasuga Y, Nishio H, Miyakoshi K, Sato S, Sugiyama J, Matsumoto T, Tanaka K, Ochiai D, Minegishi K, Hamatani T, Iwata T, Morisada T, Nakamura M, Fujii T, Kuji N, Aoki D, Tanaka M

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 26 ( 1 ) 163 - 8 2016.01

Accepted, ISSN 1048-891X

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Time-dependent changes in insulin requirement for maternal glycemic control during antenatal corticosteroid therapy in women with gestational diabetes: a retrospective study.

Itoh A, Saisho Y, Miyakoshi K, Fukutake M, Kasuga Y, Ochiai D, Matsumoto T, Tanaka M, Itoh H

Endocrine journal 63 ( 1 ) 101 - 4 2016

Accepted, ISSN 0918-8959

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妊娠初期における脳瘤の検出を契機にMeckel-Gruber症候群と胎内診断した1例

樋口敦彦, 中村加奈子, 宮越敬, 春日義史, 松本直, 福武麻里絵, 落合大吾, 田中守, 青木大輔

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 64 ( 4 ) 591 - 595 2015.10

Accepted, ISSN 2186-0599

Meckel-Gruber syndrome(MGS)は、後頭部脳瘤・嚢胞性腎疾患・軸後性多趾症を主徴とする常染色体劣性遺伝性疾患である。今回我々は妊娠初期の超音波検査による脳瘤の検出を契機にMGSと胎内診断した1例を経験した。症例は31歳、4経妊2経産。当院での妊婦健診中、妊娠13週時に経腟超音波にて脳瘤を検出し、妊娠15週時に両側多嚢胞性腎を認め、MGSと胎内診断した。超音波所見をもとに児の病態および予後を本人・家族へ説明したところ、妊娠継続および分娩が身体的・経済的に患者の健康を害するおそれがあると判断し、妊娠17週6日に人工妊娠中絶に至った。病理解剖検査にて死産児に脳瘤、両側多嚢胞性腎、軸後性多趾症、耳介低位、片側口唇口蓋裂、内反足を認めMGSと診断し、現在遺伝子検査中である。超音波スクリーニングにて脳瘤を認めた場合には、MGSも念頭においた詳細な超音波検査が必要である。(著者抄録)

妊娠糖尿病の血糖管理と血糖自己測定法(SMBG)　妊娠糖尿病におけるインスリン療法導入リスク因子に関する検討　当院における血糖自己測定に基づく妊娠管理例の解析

宮越敬, 税所芳史, 正木繭, 福武麻里絵, 春日義史, 落合大吾, 松本直, 峰岸一宏, 伊藤裕, 田中守

糖尿病と妊娠 ((一社)日本糖尿病・妊娠学会) 15 ( 1 ) 77 - 81 2015.08

Accepted, ISSN 1347-9172

基準改定後の妊娠糖尿病(GDM)の臨床像に関する検討は散見されるが、インスリン療法予測因子に関する知見は少ない。今回われわれはGDMにおけるインスリン療法導入リスク因子の抽出を目的とし本研究を行った。対象は2011〜2013年に当院でGDMスクリーニングを受け、分娩に至った単胎妊娠1386例である。GDM全例に6分割の食事療法および血糖自己測定(SMBG)を施行し、血糖管理が不良の場合には積極的にインスリン療法を導入した。1386例中GDMは214例(15.4%)であり、75g経口ブドウ糖負荷試験(OGTT)の陽性ポイントの内訳は、1点陽性(1p_GDM)151例、2点もしくは3点陽性(2/3p_GDM)63例であった。まず、周産期予後を検討したところ、GDMおよび正常耐糖能例における児発育は同等であった。また1p_GDMおよび2/3p_GDMにおけるインスリン療法導入例はおのおの23例(15%)および45例(71%)であり、1p_GDMでは糖尿病(DM)家族歴が、2/3p_GDMでは診断時HbA1cがインスリン療法導入リスク因子として抽出された(感度:DM家族歴36%、診断時HbA1c 72%)。なお、1p_GDMおよび2/3p_GDM例において、インスリン療法導入リスク因子陽性例と陰性例の分娩前インスリン投与量は同等であった。1p_GDMにおけるDM家族歴のインスリン療法導入予測感度が低いこと、リスク因子陰性例と陽性例におけるインスリン投与量が同等であったことから、リスク因子のみを用いてインスリン療法を要する症例を選別することは困難と考えられた。(著者抄録)

胎児肺成熟を目的としたベタメタゾン投与後の母体血糖管理に要したインスリン必要量に関する後方視的検討

伊藤新, 税所芳史, 宮越敬, 福武麻里絵, 春日義史, 落合大吾, 松本直, 峰岸一宏, 田中守, 伊藤裕

糖尿病と妊娠 ((一社)日本糖尿病・妊娠学会) 15 ( 1 ) 103 - 105 2015.08

Accepted, ISSN 1347-9172

耐糖能異常合併妊婦への胎児肺成熟を目的としたベタメタゾン投与時には母体高血糖に注意する必要がある。これまで当院では耐糖能異常合併例へのベタメタゾン投与時にはインスリン療法による血糖管理を行ってきた。今回われわれはベタメタゾン療法中の母体血糖管理に要したインスリン投与量について後方視的に検討した。対象は当院にて2007〜2013年にベタメタゾン療法(12mg筋肉内投与、24時間毎、計2回)を受けた妊娠糖尿病合併単胎妊婦13名(年齢36.1±7.6歳、妊娠週数28.9±3.5週)である。全例においてベタメタゾン療法中は禁食とし、インスリン持続静脈注射により血糖値を70-120mg/dlに管理した。ベタメタゾン療法中のインスリン投与量とその経時的変化を解析したところ、インスリン投与量はベタメタゾン投与3時間後より漸増し、8時間後に最大となった後、16時間後より漸減し24時間後には最大値の半量となった。またベタメタゾン再投与後も同様の推移を示した(平均インスリン投与量:1日目99.2±45.2U/日、2日目96.2±29.1U/日)。なお、塩酸リトドリン非投与群に比べ投与群では有意に多量のインスリンを要した(118.4±41.0 vs. 75.7±25.6U/日、p<0.05)。本検討によりベタメタゾン療法中の血糖管理には約100U/日のインスリン静注を要し、2日間の単位時間あたりの投与量は二峰性の推移を示すことが明らかとなった。(著者抄録)

自然羊膜破綻による臍帯相互巻絡を認めた一絨毛膜二羊膜性双胎の1例

中川亮, 落合大吾, 真壁健, 福武麻里絵, 春日義史, 松本直, 峰岸一宏, 宮越敬, 田中守, 青木大輔

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 64 ( 2 ) 205 - 210 2015.04

Accepted, ISSN 2186-0599

一絨毛膜二羊膜性双胎では、稀に自然羊膜破綻をきたし、一絨毛膜一羊膜性双胎と同様の病態となることがある。この場合には、臍帯相互巻絡による胎児死亡をきたす可能性がある。今回我々は、一絨毛膜二羊膜性双胎の妊娠管理中、自然羊膜破綻に臍帯相互巻絡を合併した症例を経験した。我々は、自然羊膜破綻と臍帯相互巻絡を胎内診断した後、待機的な妊娠管理を行い、妊娠32週に帝王切開施行し2児の生児を得た。自然羊膜破綻をきたした一絨毛膜二羊膜性双胎は、妊娠経過中に臍帯相互巻絡を起こすことがあり、その胎内診断を行うことは可能である。しかし、臍帯相互巻絡を胎内診断したとしても即時の娩出は要さない。自然羊膜破綻をきたした一絨毛膜二羊膜性双胎では、一絨毛膜一羊膜性双胎に準じた入院管理を行い、至適分娩時期まで妊娠継続することが望ましい。(著者抄録)

当院で周産期管理を行った卵子提供後妊娠の周産期事象に関する検討

澤野佳子, 松本直, 春日義史, 福武麻里絵, 正木繭, 池ノ上学, 門平育子, 峰岸一宏, 宮越敬, 吉村泰典

日本周産期・新生児医学会雑誌 ((一社)日本周産期・新生児医学会) 50 ( 3 ) 940 - 944 2014.09

Accepted, ISSN 1348-964X

周産期管理を行った卵子提供(OD)後妊娠症例24例25妊娠の治療背景と周産期事象について検討した。その結果、母体年齢の中央値は48歳で、初産が22例(88%)であった。周産期事象発症率は、前置胎盤12%、妊娠高血圧症候群20%、産後弛緩出血8%、妊娠糖尿病20%、切迫早産28%であった。自己胚IVF妊娠例と比較しOD後妊娠では、前置胎盤、妊娠高血圧症候群、癒着胎盤の発症率が有意に高率であった。新生児予後では、SGA児を3例認めたが、児の予後は概ね良好であった。OD後妊娠のうち双胎妊娠は8例(32%)であり、単胎群と比べ双胎群では有意に妊娠期間の短縮や出生体重の減少、アプガースコア5分値の低下を認めた。

ESBL産生E.coliにより妊娠中期に敗血症を発症した絨毛膜羊膜炎の1例

佐伯直彦, 福武麻里絵, 春日義史, 宮越敬, 正木繭, 池ノ上学, 門平育子, 松本直, 峰岸一宏, 進伸幸, 吉村泰典, 青木大輔

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 63 ( 2 ) 314 - 317 2014.04

Accepted, ISSN 2186-0599

症例は36歳、0経妊0経産。腹式広汎性子宮頸部摘出術(頸管縫縮術同時施行)を受け体外受精-胚移植にて妊娠成立に至った。妊娠20週0日より子宮収縮の増強および高熱を呈し、絨毛膜羊膜炎(CAM)疑いにてSulbactam/ampicillin投与を開始した。血液培養検査にてextended-spectrum β-lactamase(ESBL)産生Escherichia coli(E.coli)を認め抗菌薬をmeropenemに変更したが、全身状態悪化し妊娠20週4日に妊娠中断に至った。膿性羊水からもESBL産生E.coliが検出され病理組織検査にて組織学的CAMと診断された。Meropenem投与継続にて産後経過は良好であった。本症例では妊娠継続は困難であったが早期の起因菌同定により母体の敗血症増悪の回避が可能であった。また頸管縫縮術施行後であったことがCAM増悪に関与したものと推測された。(著者抄録)

当院で経験した前置血管症例の周産期臨床像の検討　超音波検査および胎盤所見を中心に

祝井麻希, 春日義史, 宮越敬, 福武麻里絵, 正木繭, 池ノ上学, 門平育子, 松本直, 峰岸一宏, 吉村泰典, 青木大輔

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 63 ( 1 ) 30 - 35 2014.01

Accepted, ISSN 2186-0599

前置血管は胎児血管が卵膜上を走行し、内子宮口付近に存在する病態である。未診断例では児の予後は不良であるが、早期診断することで良好な予後が期待できる。今回我々は当院で経験した前置血管症例の周産期臨床像について、文献的考察を含めて後方視的に検討した。対象は2009年1月以降に当院で周産期管理を行った前置血管6例である。全例単胎(自然妊娠5例、体外受精/胚移植1例)で、診断週数は妊娠27週(中央値)であった。分娩週数は妊娠35週(中央値)で全例帝王切開術を行い、母児ともに予後良好であった。術中に超音波検査を用いて胎児血管の走行を確認し、胎児血管の破綻を回避した。6例中4例に低置胎盤を認め、全例が臍帯卵膜付着であった。既報のごとく、前置血管症例には付属物異常の合併が高率であったことから、胎盤位置異常や臍帯付着部異常症例に関しては前置血管の発症を念頭に置いた超音波検査や管理が重要であると考えられた。(著者抄録)

Clinical impact of women with gestational diabetes mellitus by the new consensus criteria: two year experience in a single institution in Japan.

Ikenoue S, Miyakoshi K, Saisho Y, Sakai K, Kasuga Y, Fukutake M, Izumi Y, Matsumoto T, Minegishi K, Yoshimura Y

Endocrine journal 61 ( 4 ) 353 - 8 2014

Accepted, ISSN 0918-8959

Access to Document (DOI)

妊娠初期の人工妊娠中絶術後に大量性器出血をきたした胎盤ポリープの1例

秋葉洋平, 春日義史, 宮越敬, 冨永英一郎, 古谷正敬, 池ノ上学, 野上侑哉, 松本直, 升田博隆, 峰岸一宏, 吉村泰典, 青木大輔

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 62 ( 4 ) 562 - 567 2013.10

Accepted, ISSN 2186-0599

今回我々は、妊娠初期の人工妊娠中絶術後に大量性器出血をきたした胎盤ポリープの1例を経験したので報告する。症例は37歳、4経妊2経産。前医における妊娠7週時の人工妊娠中絶術ののち、術後43日日に大量性器出血を生じ当院に救急搬送となった。経腟超音波検査およびDynamic CTにて動脈性血流を伴う子宮内腫瘤を認め、胎盤ポリープ疑いと診断した。子宮動脈塞栓術後も小量の性器出血が持続し、MRIでは腫瘤への血流残存を認めた。患者本人が妊孕性温存を希望しなかったため、腹腔鏡下腟式子宮全摘出術を施行した。摘出子宮には内腔に突出する有茎性腫瘤(長径7cm)を認め、病理組織検査にて胎盤ポリープと確定診断された。胎盤ポリープは妊娠初期の流産後でも発症しうる疾患であり、妊娠終了後の大量性器出血時の鑑別診断において常に念頭におく必要がある。(著者抄録)

Complete chorion-amnion separation presenting as a stuck fetus.

Kasuga Y, Miyakoshi K, Ikenoue S, Kadohira I, Matsumoto T, Minegishi K, Yoshimura Y

Acta obstetricia et gynecologica Scandinavica 92 ( 8 ) 990 - 1 2013.08

Accepted, ISSN 0001-6349

Access to Document (DOI)

当院における新診断基準導入後の妊娠糖尿病の臨床像に関する検討

池ノ上学, 宮越敬, 税所芳史, 春日義史, 門平育子, 松本直, 峰岸一宏, 吉村泰典

糖尿病と妊娠 ((一社)日本糖尿病・妊娠学会) 13 ( 1 ) 80 - 83 2013.08

Accepted, ISSN 1347-9172

既報の新基準妊娠糖尿病(GDM)の臨床像は、旧基準でのデータベース解析をもとに推測されたものが多く、基準改定後の実際の臨床像に関して十分な知見は得られていない。そこでわれわれは、基準改定後に当院にて妊娠初期から周産期管理を行った単胎妊婦853例を対象に、GDMの臨床像について後方視的検討を行った。853例中GDM例は101例(11.8%)、overt diabetesは3例(0.3%)であった。さらに経口糖負荷試験(OGTT)陽性ポイント数に関して、OGTT 1点陽性例は69例(68%)、2点/3点陽性例は32例(2点陽性例:24例、3点陽性例:8例)であった。また101例中55例は妊娠初期スクリーニングにて検出された。分娩までの血糖コントロールに関して、OGTT 1点陽性例に比べてOGTT 2点/3点陽性例のインスリン導入率は有意に高値であった(20%vs.84%、p<0.05)。なお、OGTT 1点陽性例のなかでは、糖尿病家族歴を有する場合にインスリン療法を要する頻度が高率であった。本検討により、OGTT 1点陽性例はGDMの過半数を占めることが示され、糖尿病家族歴を有するOGTT 1点陽性例では、インスリン療法を要する可能性を念頭においた周産期管理が必要と考えられた。(著者抄録)

妊娠糖尿病既往女性における産後早期糖代謝異常の発症に関する検討

宮越敬, 税所芳史, 池ノ上学, 春日義史, 門平育子, 松本直, 峰岸一宏, 吉村泰典

糖尿病と妊娠 ((一社)日本糖尿病・妊娠学会) 13 ( 1 ) 88 - 92 2013.08

Accepted, ISSN 1347-9172

妊娠糖尿病(GDM)の新診断基準は周産期合併症のリスクをもとに作成されたものであり、産後早期糖代謝異常の発症リスクに関する知見は少ない。そこで本研究では基準改定後の当院における周産期データをもとに、GDM既往女性の産後早期糖代謝異常の発症頻度およびその予測指標を検討した。対象は2011年以降に当院で周産期管理を行った新基準GDMのうち産後4〜6ヵ月に75g経口ブドウ糖負荷試験(OGTT)を受けた女性47名(GDM診断時OGTT 1点陽性33例;2点陽性11例;3点陽性3例)である。日本糖尿病学会診断基準をもとに産後早期糖代謝異常の有無を判定したところ、糖代謝正常型29名、糖代謝異常型18名(境界型14名;糖尿病型4名)であった。GDM診断時OGTT陽性ポイント数別に検討すると、OGTT 1点、2点および3点陽性例のおのおの33%、45%、67%において産後早期に糖代謝異常型を認めた。またreceiver-operating characteristic(ROC)解析を用いてGDM診断時の血糖・metabolic phenotypeによる産後早期糖代謝異常の発症予測能を検討した。OGTT 1時間値、2時間値およびoral disposition index(DI)による予測では、ROC曲線下面積はそれぞれ0.74、0.70および0.74であった。ROC解析に基づきOGTT 1時間値、2時間値およびOral DIのカットオフ値をそれぞれ160mg/dl、143mg/dl、1.72とした場合、産後早期糖代謝異常の発症予測に関する感度は94%、89%および72%、特異度は48%、51%および71%となった。以上より、OGTT1時間値および2時間値およびOral DIが産後早期糖代謝異常発症予測に有用である可能性が示唆された。(著者抄録)

Antenatal management of recurrent fetal goitrous hyperthyroidism associated with fetal cardiac failure in a pregnant woman with persistent high levels of thyroid-stimulating hormone receptor antibody after ablative therapy.

Matsumoto T, Miyakoshi K, Saisho Y, Ishii T, Ikenoue S, Kasuga Y, Kadohira I, Sato S, Momotani N, Minegishi K, Yoshimura Y

Endocrine journal 60 ( 12 ) 1281 - 7 2013

Accepted, ISSN 0918-8959

Access to Document (DOI)

Marked decline in beta cell function during pregnancy leads to the development of glucose intolerance in Japanese women.

Saisho Y, Miyakoshi K, Ikenoue S, Kasuga Y, Matsumoto T, Minegishi K, Yoshimura Y, Itoh H

Endocrine journal 60 ( 4 ) 533 - 9 2013

Accepted, ISSN 0918-8959

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