論文 - 池ノ上　学

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年09月

ISSN  2077-0383

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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年09月

ISSN  1010660X

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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年09月

ISSN  2077-0383

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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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Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study

Papageorghiou A.T., Deruelle P., Gunier R.B., Rauch S., García-May P.K., Mhatre M., Usman M.A., Abd-Elsalam S., Etuk S., Simmons L.E., Napolitano R., Deantoni S., Liu B., Prefumo F., Savasi V., do Vale M.S., Baafi E., Zainab G., Nieto R., Maiz N., Aminu M.B., Cardona-Perez J.A., Craik R., Winsey A., Tavchioska G., Bako B., Oros D., Rego A., Benski A.C., Hassan-Hanga F., Savorani M., Giuliani F., Sentilhes L., Risso M., Takahashi K., Vecchiarelli C., Ikenoue S., Thiruvengadam R., Soto Conti C.P., Ferrazzi E., Cetin I., Nachinab V.B., Ernawati E., Duro E.A., Kholin A., Firlit M.L., Easter S.R., Sichitiu J., Bowale A., Casale R., Cerbo R.M., Cavoretto P.I., Eskenazi B., Thornton J.G., Bhutta Z.A., Kennedy S.H., Villar J.

American Journal of Obstetrics and Gynecology （American Journal of Obstetrics and Gynecology）  225 （ 3 ） 289.e1 - 289.e17 2021年09月

ISSN  00029378

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Background: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. Objective: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. Study Design: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. Results: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32–2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25–2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17–3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99–2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99–5.49) and 6.26 (95% confidence interval, 4.35–9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63–2.86; risk ratio, 2.53; 95% confidence interval, 1.44–4.45; and risk ratio, 2.84; 95% confidence interval, 1.67–4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32–2.35), 2.07 (95% confidence interval, 1.20–3.57), and 2.77 (95% confidence interval, 1.66–4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. Conclusion: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19.

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Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study.

Villar J, Ariff S, Gunier RB, Thiruvengadam R, Rauch S, Kholin A, Roggero P, Prefumo F, do Vale MS, Cardona-Perez JA, Maiz N, Cetin I, Savasi V, Deruelle P, Easter SR, Sichitiu J, Soto Conti CP, Ernawati E, Mhatre M, Teji JS, Liu B, Capelli C, Oberto M, Salazar L, Gravett MG, Cavoretto PI, Nachinab VB, Galadanci H, Oros D, Ayede AI, Sentilhes L, Bako B, Savorani M, Cena H, García-May PK, Etuk S, Casale R, Abd-Elsalam S, Ikenoue S, Aminu MB, Vecciarelli C, Duro EA, Usman MA, John-Akinola Y, Nieto R, Ferrazi E, Bhutta ZA, Langer A, Kennedy SH, Papageorghiou AT

JAMA pediatrics 175 （ 8 ） 817 - 826 2021年08月

ISSN  2168-6203

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Maternal and Neonatal Morbidity and Mortality among Pregnant Women with and without COVID-19 Infection: The INTERCOVID Multinational Cohort Study

Villar J., Ariff S., Gunier R.B., Thiruvengadam R., Rauch S., Kholin A., Roggero P., Prefumo F., Do Vale M.S., Cardona-Perez J.A., Maiz N., Cetin I., Savasi V., Deruelle P., Easter S.R., Sichitiu J., Soto Conti C.P., Ernawati E., Mhatre M., Teji J.S., Liu B., Capelli C., Oberto M., Salazar L., Gravett M.G., Cavoretto P.I., Nachinab V.B., Galadanci H., Oros D., Ayede A.I., Sentilhes L., Bako B., Savorani M., Cena H., García-May P.K., Etuk S., Casale R., Abd-Elsalam S., Ikenoue S., Aminu M.B., Vecciarelli C., Duro E.A., Usman M.A., John-Akinola Y., Nieto R., Ferrazi E., Bhutta Z.A., Langer A., Kennedy S.H., Papageorghiou A.T.

JAMA Pediatrics （JAMA Pediatrics）  175 （ 8 ） 817 - 826 2021年08月

ISSN  21686203

　概要を見る

Importance: Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. Objective: To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. Design, Setting, and Participants: In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. Exposures: COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. Main Outcomes and Measures: The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity. Results: A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity. Conclusions and Relevance: In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.

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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 - 708767 2021年07月

ISSN  1664-2392

　概要を見る

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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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年07月

ISSN  00016349

　概要を見る

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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Management of pregnancy after radical trachelectomy

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

Gynecologic Oncology （Gynecologic Oncology）  162 （ 1 ） 220 - 225 2021年07月

ISSN  00908258

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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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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 - 690648 2021年06月

ISSN  1664-2392

　概要を見る

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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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年06月

　概要を見る

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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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年05月

ISSN  10284559

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胎児心循環機能のモニタリングによる周産期管理を実施した高拍出性心不全を呈した胎児巨大肝血管腫の1例

林 彩世, 小澤 克典, 室本 仁, 杉林 里佳, 小杉 洋平, 柴田 優花, 池ノ上 学, 和田 誠司, 伊藤 裕司, 左合 治彦

超音波医学 （(公社)日本超音波医学会）  48 （ 3 ） 133 - 137 2021年05月

ISSN  1346-1176

　概要を見る

胎児巨大肝血管腫は動静脈シャントによって高拍出性心不全を呈し,胎盤循環も悪化する.そのため胎盤循環を含めた胎児循環の評価を行い適切な娩出時期を決定する必要があるが,いまだ確立した評価方法がない.臍静脈血流量(UVFV)の総心拍出量(CCO)における割合(UVFV/CCO)は胎盤循環の指標となることが報告されており,この指標を含めた心循環機能評価を行うことで早期に病状の変化をとらえた胎児巨大肝血管腫の症例を報告する.妊娠27週に心胸郭断面積比(CTAR)48.5%の心拡大と軽度の僧帽弁・三尖弁逆流を認めた.CCO 1,214ml/min,UVFV 350ml/minと増加を認めたが,UVFV/CCOは28.9%と保たれ,羊水量は正常で胎児水腫を認めなかった.しかし,妊娠30週1日にCTAR 62.9%と増悪,CCO 1,620ml/min,UVFV 236ml/minとなり,UVFV/CCOは14.6%に低下した.胎児水腫は認めなかったが羊水過少となり,Biophysical profiling score 2/10点と低値であった.妊娠30週4日に胎児心拍数陣痛図において基線細変動の減少が出現し,胎児機能不全と診断,緊急帝王切開術を施行した.児は2,340g,Apgar score 1点(1分値),5点(5分値),臍帯動脈血pH 7.254で出生した.日齢1.5に肝血管腫に対してコイル塞栓術を行ったが原病のコントロールがつかず,グラム陽性球菌による敗血症で日齢70に永眠した.UVFV/CCOの減少が巨大肝血管腫による胎児胎盤循環の悪化を反映すると思われた.(著者抄録)

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年04月

ISSN  2186-0599

　概要を見る

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)

Placental Corticotrophin-Releasing Hormone is a Modulator of Fetal Liver Blood Perfusion

Ikenoue S., Waffarn F., Ohashi M., Tanaka M., Gillen D.L., Buss C., Entringer S., Wadhwa P.D.

Journal of Clinical Endocrinology and Metabolism （Journal of Clinical Endocrinology and Metabolism）  106 （ 3 ） 646 - 653 2021年03月

ISSN  0021972X

　概要を見る

Context: Variation in fetal liver blood flow influences fetal growth and postnatal body composition. Placental corticotrophin-releasing hormone has been implicated as a key mediator of placental-fetal perfusion. Objective: To determine whether circulating levels of placental corticotrophin-releasing hormone across gestation are associated with variations in fetal liver blood flow. Design: Prospective cohort study. Methods: Fetal ultrasonography was performed at 30 weeks' gestation to characterize fetal liver blood flow (quantified by subtracting ductus venosus flow from umbilical vein flow). Placental corticotrophin-releasing hormone was measured in maternal circulation at approximately 12, 20, and 30 weeks' gestation. Multiple regression analysis was used to determine the proportion of variation in fetal liver blood flow explained by placental corticotrophin-releasing hormone. Covariates included maternal age, parity, pre-pregnancy body mass index, gestational weight gain, and fetal sex. Results: A total of 79 uncomplicated singleton pregnancies were analyzed. Fetal liver blood flow was 68.4 ± 36.0 mL/min (mean ± SD). Placental corticotrophin-releasing hormone concentrations at 12, 20, and 30 weeks were 12.5 ± 8.1, 35.7 ± 24.5, and 247.9 ± 167.8 pg/mL, respectively. Placental corticotrophin-releasing hormone at 30 weeks, but not at 12 and 20 weeks, was significantly and positively associated with fetal liver blood flow at 30 weeks (r = 0.319; P = 0.004) and explained 10.4% of the variance in fetal liver blood flow. Conclusions: Placental corticotrophin-releasing hormone in late gestation is a possible modulator of fetal liver blood flow and may constitute a biochemical marker in clinical investigations of fetal growth and body composition.

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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年02月

ISSN  2077-0383

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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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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 - 101472 2021年02月

ISSN  00408166

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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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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年01月

ISSN  01434004

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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年01月

ISSN  10284559

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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 2021年01月

査読有り,  ISSN  14700328

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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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