谷村 憲司 | ![]() |
タニムラ ケンジ | |
医学部附属病院 総合周産期母子医療センター | |
准教授 | |
医学 |
2021年04月 第12回ロート女性健康科学研究賞, HLA クラスⅡ分子の新しい抗原提示機能を応用した不育症・ 産 科異常症の病態解明ならびに治療法開発を目指した基礎ならびに臨床研究』、ロート製薬株式会社
2017年10月 神戸大学医学部, 平成28年度神戸大学医学部優秀学術論文賞, Prediction of congenital cytomegalovirus infection in high-risk pregnant women
その他の賞
2017年07月 兵庫県産科婦人科学会, 平成29年度兵庫県産科婦人科学会賞, Prediction of congenital cytomegalovirus infection in high-risk pregnant women
国内学会・会議・シンポジウム等の賞
2016年10月 International Workshop on Autoantibodies and Autoimmunity, Award for Exceptional Abstract and Presentation, beta2-glycoprotein I / HLA class II complexes are novel autoantigens in antiphospholipid syndrome
国際学会・会議・シンポジウム等の賞
2015年11月 日本生殖免疫学会, 第30回日本生殖免疫学会賞, β2グリコプロテインI/MHCクラスII複合体が抗リン脂質抗体症候群の病態に関連する
国内学会・会議・シンポジウム等の賞
2014年01月 大阪大学微生物病研究所, 平成25年度大阪大学微生物病研究所業績発表会 優秀学術賞, Cellular misfolded proteins transported to the cell surface by MHC class II molecules are targets for autoantibodies in autoimmune diseases
その他の賞
Placental mesenchymal dysplasia (PMD) is a rare placental abnormality that is closely related to severe pregnancy complications. A 27-year-old woman with fetal growth restriction and placenta previa was referred to a university hospital at 22 gestational weeks (GW). She was suspected of having a twin pregnancy with a complete or partial hydatidiform mole and coexisting normal live fetus, because two separate placentas, an enlarged one with multiple cystic lesions and a normal one, were shown on ultrasound examinations. At 27 GW, she experienced a sudden intrauterine fetal death (IUFD) after bleeding due to placenta previa, despite confirmation of fetal well-being at 2 h before bleeding. After delivery, histopathological examination confirmed the diagnosis of PMD. This is the first documented case of a woman with PMD and placenta previa who had a sudden IUFD after bleeding. Patients with both PMD and placenta previa should be considered at extremely high risk for IUFD.
2021年11月, The journal of obstetrics and gynaecology research, 47 (11), 4087 - 4092, 英語, 国際誌[査読有り]
Severe small-for-gestational-age (sSGA) infants exhibit increased mortality and morbidity. Oxidative stress is suggested to be involved in intrauterine growth restriction. This retrospective study aimed to evaluate the oxidative stress level at birth in an sSGA population. Sera of 28 sSGA (sSGA group) and 31 non-sSGA (control group) infants, born at our hospital between March 2017 and March 2020, were evaluated. Oxidative stress (derivative of reactive oxidative metabolites: d-ROM level), biological antioxidant potential (BAP) level, and the ratio of d-ROM/BAP level (oxidative stress index: OSI) were measured. The sSGA group had a significantly lower birth weight (BW), BW z-score, head circumference, and height than the control group (all p < 0.05). No significant difference was noted in the BAP level; sSGA infants exhibited a significantly higher d-ROM level than control infants. sSGA infants showed a significantly increased OSI compared with control infants, and the BW z-score was inversely correlated with d-ROM levels and OSI in sSGA infants (R2 = 0.300; p < 0.01 and R2 = 0.319; p = 0.02, respectively) but not in controls. In conclusion, sSGA infants, including preterm infants, exhibited higher oxidative stress at birth. The severity of fetal growth restriction was significantly correlated with oxidative stress levels at birth in sSGA infants.
2021年10月13日, International journal of environmental research and public health, 18 (20), 英語, 国際誌[査読有り]
研究論文(学術雑誌)
INTRODUCTION: Placenta accreta spectrum (PAS) is a life-threating obstetric complication, and prenatal prediction of PAS can decrease maternal morbidity and mortality. The aim of this prospective cohort study was to determine the clinical factors associated with PAS. METHODS: Pregnant women who delivered at a university hospital were enrolled. Clinical data were collected from medical records, and logistic regression analyses were performed to determine which clinical factors were associated with PAS. RESULTS: Eighty-seven (2.1%) of the 4146 pregnant women experienced PAS. Multivariable analyses revealed that a prior history of cesarean section (CS) (OR 3.3; 95% CI 1.9-5.7; p < 0.01), dilation and curettage (D&C) (OR 2.8; 95% CI 1.7-4.6; p < 0.01), hysteroscopic surgery (OR 5.7; 95% CI 2.3-14.4; p < 0.01), uterine artery embolization (UAE) (OR 44.1; 95% CI 13.8-141.0; p < 0.01), current pregnancy via assisted reproductive technology (ART) (OR 4.1; 95% CI 2.4-7.1; p < 0.01), and the presence of placenta previa in the current pregnancy (OR 13.1; 95% CI 7.9-21.8; p < 0.01) were independently associated with the occurrence of PAS. CONCLUSION: Pregnant women who have a prior history of CS, D&C, hysteroscopic surgery, UAE, current pregnancy via ART, and the presence of placenta previa in the current pregnancy are high risk for PAS.
2021年09月01日, Placenta, 112, 180 - 184, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
A 40-year-old primigravida woman with a monochorionic-triamniotic (MT) triplet pregnancy was hospitalized due to threatened abortion at 16 gestational weeks. Polyhydramnios in two fetuses and oligohydramnios in the third supported a diagnosis of feto-fetal transfusion syndrome (FFTS) at 23 weeks and 3 days of gestation. Severe dyspnea and liver dysfunction required intensive care unit admission and mechanical ventilation support, and abdominal compartment syndrome (ACS) caused by polyhydramnios was clinically diagnosed. When her general condition was not improved regardless of intensive care, the patient delivered the three fetuses by cesarean section at 23 weeks and 5 days gestation. Abdominal decompression was achieved with delivery, and the patient was discharged 13 days after operation without morbidity. This is the first case report of ACS caused by FFTS in a MT triplet pregnancy resulting in extremely preterm birth.
2021年09月, The journal of obstetrics and gynaecology research, 47 (9), 3370 - 3373, 英語, 国際誌[査読有り]
PURPOSE: To evaluate the efficacy of superselective transcatheter arterial embolization (TAE) for intractable postpartum hemorrhage (PPH) due to genital tract trauma (GTT) after vaginal delivery. METHODS: We evaluated 27 patients who underwent TAE for intractable PPH due to GTT after vaginal delivery at our institution between January 2008 and December 2020. Patients were divided into two groups according to TAE procedure; TAE performed as close as possible to the bleeding point, at least more peripherally than the second branch of the anterior division of the internal iliac artery, was defined as superselective TAE (S-TAE). TAE performed from the proximal segment of the internal iliac artery was defined as proximal TAE (P-TAE). Patient characteristics, pre-procedural contrast-enhanced computed tomography (CE-CT), procedure details, technical/clinical success, and complications were evaluated separately for the S-TAE and P-TAE groups. RESULTS: The combined technical/clinical success rate was 92%. No major procedure-related complications were seen (mean follow-up: 6.12 ± 3.93 days). The combined technical/clinical success rate of S-TAE was 100% and of P-TAE was 67% (p = 0.04). S-TAE was performed more frequently in patients with pre-procedural CE-CT (p = 0.01) and use of permanent embolic materials (p = 0.003). CONCLUSION: S-TAE is safe and effective for intractable PPH due to GTT. Pre-procedural CE-CT may be useful for detecting the culprit artery and be helpful in performing S-TAE.
2021年07月24日, Emergency radiology, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
The incidence of syphilis infection among pregnant women is persistently high in Japan and in several developed countries. Here, we report the utility of intravenous benzylpenicillin in 13 infants born to mothers with syphilis infection. Because the recommended treatment (intramuscular benzathine benzylpenicillin) is not available in Japan, we intravenously administered benzylpenicillin for 10 days, which is used for treatment in high-risk cases. The administration of benzylpenicillin in low-risk infants resulted in an extended duration of parent-to-infant separation and increased the infants' exposure to invasive procedures. Thus, establishing evidence of the adequacy of no-treatment follow-up in low-risk groups and introducing intramuscular injections of benzathine benzylpenicillin may improve the management of infants suspected with congenital syphilis in Japan.
2021年07月07日, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
We have found that a novel autoantibody against β2-glycoprotein I (β2GPI)/human leukocyte antigen (HLA) class II complexes (anti-β2GPI/HLA-DR) is involved in the pathogenesis of antiphospholipid syndrome (APS). It was also found that many APS patients who were negative for conventional antiphospholipid antibodies (aPLs) possessed anti-β2GPI/HLA-DR. These results suggested that anti-β2GPI/HLA-DR measurements may be more sensitive for diagnosing APS than conventional aPLs tests. Recurrent pregnancy loss (RPL) is one of the clinical manifestations of APS. Therefore, a prospective, multicenter, cross-sectional study were conducted to assess whether anti-β2GPI/HLA-DR is also associated with RPL. This study of 227 couples with RPL revealed that 22.9% (52/227) of RPL women tested positive for anti-β2GPI/HLA-DR, and 24 (19.8%) of the 121 couples with unexplained RPL tested positive for anti-β2GPI/HLA-DR. Interestingly, thirty-five of the 52 (67.3%) RPL patients who were positive for anti-β2GPI/HLA-DR possessed no conventional aPLs of criteria. This novel autoantibody against β2GPI/HLA class II complexes may be a major risk factor for RPL, and it may be a promising biomarker for diagnosing APS.
IntechOpen, 2021年04月23日, Antiphospholipid Syndrome - Recent Advances in Basic and Clinical Aspects [Working Title][査読有り][招待有り]
論文集(書籍)内論文
Heme oxygenase (HO) is the rate-limiting enzyme in the heme catabolic pathway, which degrades heme into equimolar amounts of carbon monoxide, free iron, and biliverdin. Its inducible isoform, HO-1, has multiple protective functions, including immune modulation and pregnancy maintenance, showing dynamic alteration during perinatal periods. As its contribution to the development of perinatal complications is speculated, two functional polymorphisms of the HMOX1 gene, (GT)n repeat polymorphism (rs3074372) and A(-413)T single nucleotide polymorphism (SNP) (rs2071746), were studied for their association with perinatal diseases. We systematically reviewed published evidence on HMOX1 polymorphisms in perinatal diseases and clarified their possible significant contribution to neonatal jaundice development, presumably due to their direct effect of inducing HO enzymatic activity in the bilirubin-producing pathway. However, the role of these polymorphisms seems limited for other perinatal complications such as bronchopulmonary dysplasia. We speculate that this is because the antioxidant or anti-inflammatory effect is not directly mediated by HO but by its byproducts, resulting in a milder effect. For better understanding, subtyping each morbidity by the level of exposure to causative environmental factors, simultaneous analysis of both polymorphisms, and the unified definition of short and long alleles in (GT)n repeats based on transcriptional capacity should be further investigated.
2021年03月29日, International journal of environmental research and public health, 18 (7), 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Triiodothyronine (T3)-predominant Graves' disease is characterized by increased serum free T3 (FT3) levels after free thyroxine (FT4) levels become normal or even low during antithyroid drug treatment. We encountered a 34-year-old pregnant woman, gravida 5 para 4, who was complicated by T3-predominant Graves' disease. She was diagnosed with Graves' disease at 20 years old, and had received methimazole. Methimazole was changed to potassium iodide to reduce the risk of congenital anomalies during the first trimester. The dose of antithyroid drugs was adjusted based on maternal FT4 levels, so that maternal Graves' disease deteriorated and fetal goitrous hyperthyroidism appeared during the second trimester. Since the fetus presented goiter and tachycardia at 27-28 gestational weeks, doses of methimazole and potassium iodide were increased. A male newborn weighing 2604 g was delivered by a cesarean section at 35 gestational weeks. The newborn was diagnosed with neonatal hyperthyroidism, and received methimazole for six months. He developed normally with normal thyroid function at 1 year old. In pregnancies complicated by T3-predominant Graves' disease, the kinds and doses of antithyroid drugs have to be carefully selected to maintain maternal levels of FT4 as well as FT3 within the normal range, considering trimesters of pregnancy, teratogenicity of medication, and maternal levels of thyroid-stimulating hormone receptor antibody.
2021年02月08日, The Kobe journal of medical sciences, 66 (4), E153-E158, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
To date, the difference in neurodevelopmental outcomes between late preterm infants (LPI) born at 34 and 35 gestational weeks (LPI-34 and LPI-35, respectively) has not been elucidated. This retrospective study aimed to evaluate neurodevelopmental outcomes at 18 months of corrected age for LPI-34 and LPI-35, and to elucidate factors predicting neurodevelopmental impairment (NDI). Records of all LPI-34 (n = 93) and LPI-35 (n = 121) admitted to our facility from 2013 to 2017 were reviewed. Patients with congenital or chromosomal anomalies, severe neonatal asphyxia, and without developmental quotient (DQ) data were excluded. Psychomotor development was assessed as a DQ using the Kyoto Scale of Psychological Development at 18 months of corrected age. NDI was defined as DQ <80 or when severe neurodevelopmental problems made neurodevelopmental assessment impossible. We compared the clinical characteristics and DQ values between LPI-34 (n = 62) and LPI-35 (n = 73). To elucidate the factors predicting NDI at 18 months of corrected age, we compared clinical factors between the NDI (n = 17) and non-NDI (n = 118) groups. No significant difference was observed in DQ values at 18 months of corrected age between the groups in each area and overall. Among clinical factors, male sex, intraventricular hemorrhage (IVH), hyperbilirubinemia, and severe hyperbilirubinemia had a higher prevalence in the NDI group than in the non-NDI group, and IVH and/or severe hyperbilirubinemia showed the highest Youden Index values for predicting NDI. Based on the results of this study, we can conclude that no significant difference in neurodevelopmental outcomes at 18 months of corrected age was observed between LPI-34 and LPI-35. Patients with severe hyperbilirubinemia and/or IVH should be considered to be at high risk for developing NDI.
2021年01月13日, International journal of environmental research and public health, 18 (2), 英語, 国際誌[査読有り]
研究論文(学術雑誌)
This study aimed to investigate the long-term changes in awareness of and knowledge about mother-to-child infections across 6 years in Japan. A questionnaire survey was conducted at our facility from October 2012 to January 2018, and the study periods were divided into 4 phases comprising 16 months each. A multiple-choice questionnaire assessed participants' awareness of the following 13 pathogens of mother-to-child infections: cytomegalovirus (CMV), Toxoplasma gondii (T. gondii), hepatitis B virus, rubella virus, herpes simplex virus, parvovirus B19, hepatitis C virus, human immunodeficiency virus, human T cell leukemia virus type-1, measles virus, varicella-zoster virus, Chlamydia trachomatis, and Treponema pallidum. For the selected four pathogens (i.e., CMV, rubella virus, T. gondii, and parvovirus B19), the questionnaire also evaluated participants' knowledge of transmission routes, the most susceptible time of infection that could yield severe fetal disease during pregnancy, the maximum frequency of fetal infection in cases of maternal infection, and methods to prevent maternal infection. In total, 1433 pregnant Japanese women were included in this study. There was no secular change in awareness of the pathogens concerning mother-to-child infections over time, and we also clarified that the detailed knowledge of the four pathogens of typical mother-to-child infections did not improve. Since knowledge about methods to prevent maternal infection is still insufficient for all pathogens, further advocacy is required to prevent mother-to-child infections.
2021年, PloS one, 16 (1), e0244945, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Infants with symptomatic congenital cytomegalovirus infection (cCMV) suffer from long-term sequelae. This study aimed at evaluating the efficacy of combining immunoglobulin (Ig) fetal therapy (FT) and neonatal therapy (NT) with antiviral drugs to improve neurological outcomes of affected infants. Women whose fetuses had symptomatic cCMV received Ig injection into the fetal peritoneal cavity and/or maternal blood as FT, while affected newborns received oral valganciclovir or intravenous ganciclovir as NT. We compared the neurological outcomes at ≥18 months old between infants receiving FT with or without NT (FT group) and those receiving NT only (NT group). From 2009-2019, 15 women whose fetuses had symptomatic cCMV received FT, while 19 newborns received NT only. In FT group, two newborns died, and two were <18 months old. Neurological outcomes of the remaining 11 infants in FT group were as follows: normal 45.5 %, mild impairments 36.4 %, and severe impairments 18.2 %. In NT group, one newborn died, one's parents refused the follow-up, one was <18 months old, and two had only chorioretinitis as symptoms. Neurological outcomes of the remaining 14 infants in NT group were as follows: normal 21.4 %, mild impairments 14.3 %, and severe impairments 64.3 %. The proportion of infants with severe impairments in FT group was significantly lower than that in NT group (18.2 % vs 64.3 %, p < 0.05). This is the first trial demonstrating that the combination of Ig FT and NT with antiviral drugs may be more effective in improving neurological outcomes of newborns with symptomatic cCMV as compared to NT only.
2020年12月16日, Journal of reproductive immunology, 143, 103263 - 103263, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
<文献概要>血栓性素因のうち抗リン脂質抗体症候群のみ,不育症の明らかな原因といえる。そのほかの血栓性素因としては,わが国ではプロテインS低下,凝固第XII因子低下が代表的である。これらの(抗)凝固因子低下と不育症には弱い関連があるものの,治療が妊娠予後を改善するエビデンスは乏しい。不妊症と血栓性素因との関連についてはさらにエビデンスに乏しく,血栓性素因のある不妊・不育症患者の全例に抗凝固療法を行うべきではない。抗リン脂質抗体症候群については確立された治療法(低用量アスピリンとヘパリンの併用)があり,不育症(生化学的妊娠の反復を含む)や妊娠34週未満早産,胎児発育不全,妊娠高血圧症候群,常位胎盤早期剥離,HELLP症候群などの妊娠合併症があれば,不妊治療施設でもプレコンセプションケアとして積極的に診断検査基準に含まれる抗リン脂質抗体(aPL)を測定する。一方,血栓症の既往からみつかった血栓性素因についてはまったく対応が異なり,不妊治療に伴う卵巣過剰刺激症候群(OHSS)の徴候がみられた場合や妊娠が明らかとなった場合は,積極的にヘパリンを含む抗凝固療法を行う必用がある。また,凝固検査の評価においては,本検査が非常に繊細な検査であり,採血・検体処理手技により検査値が大きく変動する可能性があることに留意し,より正確な凝固検査を実施する体制を整備していくことが重要である。
金原出版(株), 2020年12月, 産婦人科の実際, 69 (13), 1605 - 1614, 日本語This prospective cohort study aimed to determine clinical factors associated with congenital cytomegalovirus (CMV) infection in pregnancy. Newborns born at a perinatal medical center received PCR analyses for CMV-DNA in their urine with informed consent. Clinical data, including age, maternal fever or flu-like symptoms, complications, ultrasound fetal abnormality, gestational weeks at delivery, and birth weight, were collected. Logistic regression analyses determined clinical findings associated with congenital CMV infection (cCMV). cCMV was diagnosed in 32 of 4380 pregnancies. Univariate and multivariable analyses revealed that age < 25 years old (OR 2.7, 95% CI 1.1-6.6; p < 0.05), the presence of maternal fever or flu-like symptoms (5.4, 2.6-11.2; p < 0.01), ultrasound fetal abnormalities (12.7, 5.8-27.7; p < 0.01), and preterm delivery at less than 34 gestational weeks (2.6, 1.1-6.0; p < 0.05) were independent clinical findings associated with cCMV. A combination of maternal fever/flu-like symptoms, ultrasound fetal abnormalities, or preterm delivery at less than 34 gestational weeks as optimal predictive factors showed 90.6% sensitivity, 66.4% specificity, and a maximum Youden index of 0.57. CMV-DNA tests in the urine of newborns born to mothers with these clinical manifestations may be an effective method in detecting cCMV as a targeted screening with a high sensitivity.
2020年11月12日, Scientific reports, 10 (1), 19706 - 19706, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
OBJECTIVE: The clinical manifestations of antiphospholipid syndrome (APS) include vascular thrombosis and pregnancy morbidity as well as recurrent pregnancy loss (RPL). However, in more than half of patients with RPL, the cause is never determined. Recently, β2 -glycoprotein I (β2 GPI) complexed with HLA class II molecules (β2 GPI/HLA-DR) was found to be a major autoantibody target in APS. The present study was undertaken to assess the serum levels of autoantibodies against the β2 GPI/HLA II complex as a potential risk factor for RPL in women. METHODS: Serum levels of antiphospholipid antibodies (aPLs), including IgG/IgM anticardiolipin antibodies, IgG/IgM anti-β2 GPI antibodies, and lupus anticoagulant as well as anti-β2 GPI/HLA-DR antibodies, were measured in 227 women with RPL. In this prospective, multicenter, cross-sectional study, women with RPL and their partners underwent HLA-DR immunotyping and analysis to identify potential causes and risk factors associated with RPL. The normal range for anti-β2 GPI/HLA-DR antibody levels was determined using serum samples obtained from a control population of female subjects (208 women of childbearing potential). RESULTS: Of the 227 women with RPL, aPL antibodies were detected in 19.8%, and 52 (22.9%) tested positive for anti-β2 GPI/HLA-DR antibodies. Among the 227 women, 121 (53.3%) had no risk factors for RPL, and among these women with unexplained RPL, 24 (19.8%) were positive for anti-β2 GPI/HLA-DR antibodies. Of the 112 women who had clinical symptoms of APS but did not have levels of aPLs that met the diagnostic criteria for APS, 21 (18.8%) were positive for anti-β2 GPI/HLA-DR antibodies. CONCLUSION: The anti-β2 GPI/HLA-DR antibody is frequently associated with RPL. Detection of these autoantibodies is useful in understanding the pathogenesis of RPL. Our findings may provide potential new therapeutic strategies for addressing RPL in patients with obstetric APS.
2020年11月, Arthritis & rheumatology (Hoboken, N.J.), 72 (11), 1882 - 1891, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
OBJECTIVES: The aim of this study was to evaluate whether vaginal microbiota is associated with threatened premature labor and preterm delivery. METHODS: This prospective study enrolled 64 pregnant women who underwent vaginal microbiome analyses using 16S ribosomal RNA sequence method with informed consent. The 64 pregnant women consisted of 47 women with threatened premature labor and 17 women with other diseases (non-threatened premature labor) in a case-control study. In a cohort study of threatened premature labor group, 23 pregnancies ended in preterm delivery, and the remaining 24 ended in full-term deliveries. The differences in vaginal microbiota between threatened and non-threatened premature labor groups, and between preterm and full-term delivery groups were evaluated. RESULTS: There were no differences in vaginal microbiota between threatened and non-threatened premature labor groups. There were significant differences between preterm and full-term delivery groups in Nugent score [median 3 (range 0-7) vs. 0 (0-4), p < 0.05], percentage of Lactobacillus species [88% (0-100) vs. 99.8% (55.4-100), p < 0.01], the number of bacterial species [3 (1-13) vs. 2 (1-5), p < 0.05], and positivity of Ureaplasma species (61% vs. 17%, p < 0.01). Univariate and multivariable analyses revealed that positivity of Ureaplasma species was a predictive factor of preterm delivery in women with threatened premature labor (OR, 6.5; 95% CI, 1.3-33.0; p < 0.05). CONCLUSION: Increased positivity of Ureaplasma species in vaginal microbiota was a risk factor for preterm delivery among women with threatened premature labor. Vaginal microbiome analysis may identify high risk pregnancies for preterm delivery.
2020年11月, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 26 (11), 1134 - 1138, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
2005〜2017年に切迫早産のため当院で入院管理を行い妊娠29週未満に分娩となった出生児55例を対象とし、予後不良群と良好群に分け、諸データの比較検討を行った。予後不良の定義は、脳室内出血3度以上、嚢胞性脳室周囲白質軟化症、癲癇、脳性麻痺、在宅酸素療法を要する失明、精神発達遅滞のいずれかを認めたものとし、それ以外の症例を予後良好群とした。比較項目は「破水の有無」「分娩週数」「母体血CRPの最高値」「母体血白血球の最高値」「分娩前母体体温の最高値」「胎児肺成熟を目的とした母体ステロイド投与」「児の性別」「出生体重」「絨毛膜羊膜炎のBlanc分類(度)」とした。検討の結果、予後不良群は良好群に比べて「分娩週数」が有意に早く、他の項目に有意な群間差は認めなかった。予後不良に関連する因子を決定するため単変量ロジスティック回帰分析を行った結果、「分娩週数」と「母体血CRPの最高値」が選択され、これらについて多変量ロジスティック回帰分析を行ったところ「分娩週数」のみが予後不良に関わる独立因子として選択された。
「産婦人科の進歩」編集室, 2020年10月, 産婦人科の進歩, 72 (4), 392 - 394, 日本語INTRODUCTION: Congenital cytomegalovirus infection (CCMVI) may result in neurodevelopmental impairments (NDIs) such as hearing loss, developmental delay, epilepsy, and cerebral palsy. We aimed to investigate the potential for brain magnetic resonance imaging (MRI) to predict NDI in patients with CCMVI. METHODS: We studied infants with CCMVI who were referred to our hospital from April 2010 to October 2018 and underwent a brain MRI within 3 months since birth. We screened for 6 classic presentations of CCMVI including ventriculomegaly, periventricular cysts, hippocampal dysplasia, cerebellar hypoplasia, migration disorders, and white matter abnormalities. Images were interpreted by a blinded pediatric radiologist. NDI was defined as having a developmental quotient <80, hearing dysfunction, blindness, or epilepsy requiring anti-epileptic drugs at approximately 18 months of corrected age. RESULTS: The study involved 42 infants with CCMVI (median gestational age 38 weeks, birthweight 2,516 g). At least one abnormal finding was detected in 28 (67%) infants. Abnormal findings consisted of 3 cerebellar hypoplasia (7%), 7 migration disorders (17%), 26 white matter abnormalities (62%), 12 periventricular cysts (28%), 1 hippocampal dysplasia (2%), and 20 ventriculomegaly (48%). Abnormal findings were significantly more prevalent in infants with clinical symptoms (21/24, 91%) than in those without (7/19, 37%, p < 0.01). For NDI prediction, having ≥2 of ventriculomegaly, periventricular cysts, and white matter abnormality produced the highest Youden index values (0.78). CONCLUSION: Infants with CCMVI with at least 2 of the abovementioned specific brain image abnormalities may be at high risk of developing NDI.
2020年06月03日, Neonatology, 117 (4), 1 - 7, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
OBJECTIVES: This prospective cohort study aimed to evaluate the efficacy of the universal neonatal urine screening, followed by diagnosis, workup and antiviral therapy for symptomatic congenital cytomegalovirus (CMV) infection to reduce neurological impairments and sequelae. METHODS: Neonates born in three facilities underwent the universal urine screening of PCR analyses for CMV-DNA. Neonates with symptomatic congenital CMV infection (cCMV) received oral valganciclovir (VGCV) of 32 mg/kg/day for six weeks or six months, and were evaluated for neurological outcomes including developmental quotient (DQ) and hearing function at around 18 months of corrected age. RESULTS: cCMV was diagnosed in 56 (0.48%) of 11,736 neonates, consisting of 23 neonates with symptomatic and 33 with asymptomatic cCMV. The incidence of cCMV in the general perinatal medical center (0.69%) was higher than that in the primary maternity hospital (0.23%, p<0.01%). Twenty of the 23 infants with symptomatic cCMV received VGCV therapy, and 19 underwent neurological assessment. Eight neonates (42%) had severe sequelae of DQ < 70, bilateral hearing dysfunction, and/or epilepsy. Four neonates (21%) had mild sequelae of DQ 70-79 or unilateral hearing dysfunction only, and seven (37%) showed normal development without any impairment. CONCLUSIONS: This study on a large scale demonstrated that a series of universal neonatal urine screening, diagnosis, workup, and VGCV therapy for neonates with symptomatic cCMV may decrease neurological impairments, because 58% of the treated infants had normal development or mild sequelae. The universal urine screening likely identifies subclinical symptomatic cCMV. Mothers with fetuses of cCMV seem to be selectively transferred to perinatal medical centers before deliveries.
2020年04月06日, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 26 (8), 790 - 794, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
AIM: To evaluate pregnancy outcome and complications in subsequent pregnancies after severe post-partum hemorrhage (PPH) between women with and without a history of uterine artery embolization (UAE). METHODS: Women who had a history of severe PPH, and delivered newborns at ≥22 gestational weeks in subsequent pregnancies were enrolled. Severe PPH was defined as blood loss volume of more than 2000 mL. RESULTS: The blood loss volume (median 1581 mL) in women with UAE (n = 14) was significantly more than that in women without UAE (median 1021 mL, n = 32, P < 0.01), and the recurrence rate of severe PPH in women with UAE (n = 5, 35.7%) was significantly higher than that in women without UAE (n = 3, 9.4%, P < 0.05). There were no significant differences in frequencies of premature delivery, hypertensive disorders of pregnancy, fetal growth restriction, or placenta previa/low lying placenta. Of 14 women with UAE, 7 (50.0%) had abnormally invasive placenta, whereas of 32 women without UAE, none had abnormally invasive placenta. CONCLUSION: Subsequent pregnancies after UAE for severe PPH had high risks for recurrence of severe PPH.
2020年01月, The journal of obstetrics and gynaecology research, 46 (1), 119 - 123, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
BACKGROUND: The aim of this prospective cohort study was to determine clinical factors associated with the occurrence of congenital cytomegalovirus infection (cCMV) in pregnant women. METHODS: Between March 2009 and November 2017, newborns born at a primary maternity hospital received polymerase chain reaction (PCR) analyses for CMV-DNA in their urine with informed consent of the mothers at a low risk. Clinical data, including age, gravidity, parity, body mass index, occupations, maternal fever/flu-like symptoms, pregnancy complications, gestational weeks at delivery, birth weight, and automated auditory brainstem response (AABR), were collected. Logistic regression analyses were performed to determine clinical factors associated with cCMV. RESULTS: cCMV was diagnosed by positive PCR results of neonatal urine in 9 of 4,125 pregnancies. Univariate and multivariable analyses revealed that the presence of fever/flu-like symptoms (odds ratio [OR], 17.9; 95% confidence interval [CI], 3.7-86.7; p<0.001) and threatened miscarriage/premature labor in the second trimester (OR, 6.0; 95%CI 1.6-22.8; p<0.01) were independent clinical factors associated with cCMV. Maternal fever/flu-like symptoms or threatened miscarriage/premature labor in the second trimester had 100% sensitivity, 53.2% specificity, and a maximum Youden index of 0.85. CONCLUSIONS: This cohort study for the first time demonstrated that these clinical factors of pregnant women and newborns were associated with the occurrence of cCMV. This is useful information for targeted screening to assess risks of cCMV in low-risk mothers, irrespective of primary or non-primary CMV infection.
2019年12月02日, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 71 (11), 2833 - 2839, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
[査読有り]
OBJECTIVE: This study aimed to evaluate the neurodevelopmental outcomes of infants with symptomatic congenital cytomegalovirus (SCCMV) disease after antiviral treatment and investigate the symptoms at birth associated with a developmental quotient (DQ) < 70. METHODS: In this prospective study conducted from 2009 to 2018, infants with SCCMV disease who received oral valganciclovir (VGCV; 32 mg/kg/day) for 6 weeks (November 2009 to June 2015) or 6 months (July 2015 to March 2018) were evaluated for their neurodevelopmental outcomes at around 18 months of corrected age. Sequelae were categorized as follows: no impairment with a DQ ≥ 80 and no hearing dysfunction; mild sequelae including unilateral hearing dysfunction or a DQ of 70-79; and severe sequelae with a DQ < 70, bilateral hearing dysfunction requiring hearing aids, blindness or epilepsy requiring anti-epileptic drugs. DQ was assessed using the Kyoto Scale of Psychological Development. Symptoms at birth associated with a DQ < 70 were determined using univariate and receiver operating characteristic curve analyses. RESULTS: Of the 24 treated infants, 21 reached > 18 months of corrected age. Six (29%) were no impairment, 4 (19%) had mild sequelae, and 11 (52%) developed severe sequelae. The symptoms at birth associated with a DQ < 70 were microcephaly and/or small for gestational age. CONCLUSION: In our cohort of infants with SCCMV disease after VGCV treatment, the incidence of severe sequelae at 18 months of corrected age was around 50%. When microcephaly and/or small for gestational age are seen at birth, a low DQ may appear even after oral VGCV treatment.
2019年10月, Brain & development, 41 (9), 743 - 750, 英語, 国際誌[査読有り]
[査読有り]
Although cytomegalovirus (CMV) DNA detection in urine is the standard method for diagnosing congenital cytomegalovirus infection (CCMVI), polymerase chain reaction (PCR) is not comprehensively available. Currently, the efficacy of CMV-specific IgM (CMV-IgM) and CMV-specific IgG (CMV-IgG) detection remains unclear. To determine the sensitivity and specificity of CMV-specific antibodies at birth, we investigated CMV-IgM and CMV-IgG titers in CCMVI cases and non-CCMVI controls, with confirmed diagnoses by urine quantitative real-time PCR within 3 weeks after birth. We included 174 infants with suspected CCMVI in whom serological testing was performed within the first 2 weeks after birth during 2012-2018. We classified the participants into a CCMVI group (n = 32) and non-CCMVI group (n = 142) based on their urine PCR results. The CMV-IgM-positive rate was 27/32 (84.4%) in the CCMVI group, compared with 1/142 (0.7%) in the non-CCMVI group (p < 0.0001). The positive CMV-IgG rates were 32/32 (100%) in the CCMVI group and 141/142 (99.3%) in the non-CCMVI group. The positive predictive value for CMV-IgM was high at 96.4% (27/28). This value may be sufficient for clinical use, especially in settings with limited resources where PCR is unavailable. However, CCMVI screening by CMV-IgM alone appears insufficient because of the considerable number of false-negative cases.
2019年07月01日, International journal of molecular sciences, 20 (13), 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Although cytomegalovirus (CMV) DNA detection in urine is the standard method for diagnosing congenital cytomegalovirus infection (CCMVI), polymerase chain reaction (PCR) is not comprehensively available. Currently, the efficacy of CMV-specific IgM (CMV-IgM) and CMV-specific IgG (CMV-IgG) detection remains unclear. To determine the sensitivity and specificity of CMV-specific antibodies at birth, we investigated CMV-IgM and CMV-IgG titers in CCMVI cases and non-CCMVI controls, with confirmed diagnoses by urine quantitative real-time PCR within 3 weeks after birth. We included 174 infants with suspected CCMVI in whom serological testing was performed within the first 2 weeks after birth during 2012-2018. We classified the participants into a CCMVI group (n = 32) and non-CCMVI group (n = 142) based on their urine PCR results. The CMV-IgM-positive rate was 27/32 (84.4%) in the CCMVI group, compared with 1/142 (0.7%) in the non-CCMVI group (p < 0.0001). The positive CMV-IgG rates were 32/32 (100%) in the CCMVI group and 141/142 (99.3%) in the non-CCMVI group. The positive predictive value for CMV-IgM was high at 96.4% (27/28). This value may be sufficient for clinical use, especially in settings with limited resources where PCR is unavailable. However, CCMVI screening by CMV-IgM alone appears insufficient because of the considerable number of false-negative cases.
2019年07月, International journal of molecular sciences, 20 (13), 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Primary infection with Toxoplasma gondii (T. gondii) during pregnancy may cause congenital infection of the infant. This study evaluated whether screening using IgG avidity and multiplex-nested polymerase chain reaction (PCR) methods was effective for detecting a high-risk pregnancy for congenital T. gondii infection. In a prospective cohort study serum T. gondii IgG avidity was measured in 469 pregnant women who had a positive test for T. gondii antibody plus a positive or equivocal test for IgM. Multiplex-nested PCR for T. gondii DNA on amniotic fluid, maternal blood, and neonatal blood was performed with informed consent. Low (<30%), borderline (30-35%), and high (>35%) IgG avidity indices were found in 104 (22.2%), 30 (6.4%), and 305 (71.4%), respectively. A total of 12 cases had a positive PCR test for amniotic fluids of the prenatal amniocentesis or at birth, or neonatal blood. Seven of the 12 cases were diagnosed as having congenital T. gondii infection, and they had low IgG avidity indices. Congenital T. gondii infection screening using of IgG avidity and multiplex-nested PCR methods for pregnant women with a positive test for T. gondii antibody plus a positive or equivocal test for T. gondii IgM was useful for detecting a high-risk pregnancy and diagnosing congenital T. gondii infection.
2019年06月, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 25 (6), 427 - 430, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
The aim of this prospective cohort study was to evaluate clinical factors associated with pregnancy outcomes in women with recurrent pregnancy loss (RPL). Women with a history of two or more pregnancy losses underwent workups for clinical factors of RPL and their pregnancies were followed-up with informed consent. Two hundred eleven (81.5%) of 259 women with RPL became pregnant. The multivariable analyses demonstrated that age (p < .01, OR 0.9, 95%CI 0.97-0.83), uterine abnormality (p < .05, OR 0.3, 95%CI 0.11-0.8), and protein C (PC) deficiency (p < .01, OR 0.14, 95%CI 0.03-0.6) were independent factors for becoming pregnancy in women with RPL. The number of previous pregnancy loss (p < .01, OR 0.57, 95%CI 0.43-0.75) and natural killer (NK) cell activity ≥33% (p < .01, OR 0.31, 95%CI 0.13-0.73) were independent factors for live birth in the subsequent pregnancy. Advanced age, the presence of uterine abnormality, and PC deficiency were risk factors for reduced pregnancy rate in women with RPL. Increased number of previous pregnancy loss and high NK cell activity were risk factors for miscarriage in the subsequent pregnancy. These results involve important information and are helpful for clinical practitioners.
2019年04月23日, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 35 (10), 1 - 6, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Although earlier studies have shown that antiviral treatment regimens using valganciclovir (VGCV) improved hearing function in some infants with congenital cytomegalovirus (CMV) infection; its efficacy on the severity of hearing dysfunction is unclear. We conducted a prospective study among 26 infants with congenital CMV infections from 2009 to 2018. Oral VGCV (32 mg/kg/day) was administered for 6 weeks (November 2009 to June 2015; n = 20) or 6 months (July 2015 to March 2018, n = 6). Hearing function was evaluated by measuring the auditory brainstem response before VGCV treatment and at 6 months. Hearing dysfunction, defined as a V-wave threshold >40 dB, was categorized into: most severe, ≥91 dB; severe, 61⁻90 dB; and moderate, 41⁻60 dB. Hearing improvement was defined as a decrease of ≥20 dB from the pretreatment V-wave threshold. Of 52 ears in 26 infants with congenital CMV infection, 29 (56%) had hearing dysfunction, and of 29 ears, 16 (55%) improved after VGCV treatment. Although, 16 (84%) of 19 ears with moderate or severe hearing dysfunction improved after treatment (p < 0.001), 10 ears with the most severe form did not. In conclusion, VGCV treatment is effective in improving moderate and severe hearing dysfunction in infants with congenital CMV infection.
2019年03月19日, International journal of molecular sciences, 20 (6), 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Antibodies against fetal platelet alloantigens in maternal blood cause neonatal alloimmune thrombocytopenia (NAIT). We encountered four newborns with NAIT from three women. A woman carried anti-human platelet antigen (HPA)-1a antibody, and vaginally delivered a newborn who had subarachnoid hemorrhage and platelet transfusions. She delivered the second newborn by a cesarean section who had no symptom. The second woman carried anti-human leukocyte antigen-A2 antibody and vaginally delivered a newborn who had no symptom. The third woman with a history of recurrent pregnancy losses carried anti-HPA-4b antibody, and delivered a newborn by a cesarean section who received platelet transfusions and immunoglobulin infusions. Antiplatelet antibody screening may be helpful in women who have a history of blood transfusion, or previous neonates with thrombocytopenia or intracranial hemorrhage.
2019年03月, The Kobe journal of medical sciences, 64 (6), E197 - E199, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
Human cytomegalovirus (CMV) is a common cause of congenital infection that may lead to severe long-term sequelae. Because there are no established vaccines, fetal interventions or neonatal treatments, neither maternal nor neonatal screening is recommended. However, recent studies have indicated that early antiviral treatment may improve neurological outcomes in symptomatic infants with congenital infection. Therefore, prenatal detection may be important in newborns at high risk of such infection. Polymerase chain reaction for CMV DNA in the amniotic fluid is considered the gold standard for diagnosis of intrauterine infection, but its use is limited because amniocentesis is an invasive procedure. In a prospective cohort study, we have reported that the presence of CMV DNA in secretions of the maternal uterine cervix were predictive of congenital infection in groups at high risk. However, we also recently demonstrated that maternal serological screening for primary CMV infection using specific immunoglobulin G, the immunoglobulin G avidity index or specific immunoglobulin M can overlook many cases. Previous research has indicated that the combination of early detection by universal neonatal screening of urinary CMV DNA combined with early antiviral therapy can improve outcomes in infants with symptomatic congenital infection. In this article, we review the current state of maternal and neonatal screening for congenital CMV infection.
2019年03月, The journal of obstetrics and gynaecology research, 45 (3), 514 - 521, 英語, 国際誌[査読有り][招待有り]
研究論文(学術雑誌)
抗リン脂質抗体(aPL)は1980年代中頃に発見され、不育症や妊娠合併症、血栓塞栓症との関連が解析されてきた。抗リン脂質抗体症候群(APS)は1986年に誕生した疾患群で、aPLを有し、かつ臨床症状として血栓症や妊娠高血圧腎症、子癇、胎盤機能不全、胎児発育不全(FGR)による早産、および不育症といった妊娠合併症をきたす疾患である。APS合併妊娠は治療が可能であり、妊娠合併症の原因検索の一つとしてaPLの検索は重要である。(著者抄録)
(株)診断と治療社, 2019年02月, 産科と婦人科, 86 (2号), 223 - 229, 日本語[招待有り]
研究論文(学術雑誌)
Fetal intestinal volvulus is a rare condition, and fetal diagnosis of this disease is still challenging, especially in primary cases not accompanied by other comorbidities, such as intestinal malformations. Herein, we report a case of fetal primary small bowel volvulus associated with acute gastric dilatation detected by ultrasonography. We speculate that the mechanism of acute gastric dilatation in our case was peristatic malfunction of the whole intestine caused by a strangulated ileus resulting from fetal intestinal volvulus. In conclusion, acute gastric dilatation detected by fetal ultrasound can indicate the fetal intestinal volvulus.
2019年01月11日, The Kobe journal of medical sciences, 64 (4), E157-E159 - E159, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
INTRODUCTION: Cytomegalovirus (CMV) infection is the most common cause of congenital viral infections in humans. The unusual structure of the placenta plays a pivotal role in CMV transmission from mothers to fetuses. The aim of this study was to evaluate the histopathological findings of placentas with congenital CMV infections. METHODS: We obtained placental specimens from 35 women who had newborns with congenital CMV infections. Placental specimens, extraplacental membranes, and umbilical cords were stained with hematoxylin and eosin, and subjected to immunohistochemical analysis. We evaluated the localization of CMV-infected cells and other histological parameters. RESULTS: Thirty (86%) of the 35 placentas tested positive for CMV-infected cell proteins by immunohistochemistry. A majority of CMV-positive cells were present in fibroblasts and endothelial cells in the villi. The number of CMV-infected cells was inversely correlated to gestational age at delivery. The frequency of chronic villitis (65% vs. 11%; p < 0.01) and changes of the villi (38% vs. 0%; p < 0.05) in the placentas from mothers with symptomatic congenital CMV infections was higher than those observed in samples from mothers with asymptomatic congenital infections. The frequency of changes of the decidua (43% vs. 5%; p < 0.01) in the placentas from mothers with non-primary CMV infections was higher than those from mothers with primary infections. DISCUSSION: Chronic villitis and changes of the villi were associated with symptomatic congenital CMV infections. The changes of the decidua were associated with congenital CMV infections, in mothers with non-primary CMV infections.
2019年01月, Placenta, 75, 62 - 67, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[招待有り]
研究論文(研究会,シンポジウム資料等)
Early diagnosis and treatment of infants with symptomatic congenital cytomegalovirus (CMV) infection may improve neurological outcomes. For this reason, prenatal detection of newborns at high risk for congenital CMV infection is important. A polymerase chain reaction (PCR) assay for CMV DNA in the amniotic fluid is the gold standard for the diagnosis of intrauterine CMV infection; however, amniocentesis is an invasive procedure. Recently, we have found that the presence of CMV DNA in the maternal uterine cervical secretion is predictive of the occurrence of congenital CMV infection in CMV immunoglobulin M (IgM)-positive pregnant women. In contrast, we have suggested that maternal serological screening for primary CMV infection using CMV-specific immunoglobulin G (IgG), the IgG avidity index, or CMV-specific IgM overlooks a number of newborns with congenital CMV infection. We will review current knowledge of the potential biomarkers for predicting congenital CMV infection.
2018年11月27日, International journal of molecular sciences, 19 (12), 英語, 国際誌[査読有り][招待有り]
研究論文(学術雑誌)
The aim of this nested case-control study was to evaluate clinical factors associated with the occurrence of congenital cytomegalovirus (CMV) infection in pregnant women with non-primary CMV infection. In a cohort study of CMV screening for 2193 pregnant women and their newborns, seven newborns with congenital CMV infection were identified among 1287 pregnant women with non-primary CMV infection that was defined as negative IgM and positive IgG with IgG avidity index >45%. In the 1287 women with non-primary CMV infection, clinical findings and complications were compared between pregnancies with and without congenital CMV infection. Clinical factors associated with the occurrence of congenital CMV infection were evaluated. The birth weight of newborns with congenital CMV infection was less than that of newborns without congenital infection (p < 0.05). Univariate logistic regression analyses demonstrated that threatened premature delivery (OR 10.6, 95%CI 2.0-55.0; p < 0.01) and multiple pregnancy (OR 7.1, 95%CI 1.4-37.4; p < 0.05) were associated with congenital infection. Multivariable logistic regression analyses demonstrated that threatened premature delivery (OR 8.4, 95%CI 1.5-48.1; p < 0.05) was a single risk factor for congenital CMV infection in pregnant women with non-primary CMV infection. This study revealed for the first time that threatened premature delivery was associated with the occurrence of congenital CMV infection in pregnant women with non-primary CMV infection, the pathophysiology of which may be closely associated with CMV reactivation during pregnancy.
2018年09月, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 24 (9), 702 - 706, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
妊娠30週未満で分娩となった胎児発育不全児(FGR)16例を対象に、予後不良に関連する因子について検討した。その結果、後遺症なし生存中の予後良好群は8例、後遺症あり生存または、子宮内胎児死亡、新生児死亡の予後不良群は8例であった。予後良好群に比べ予後不良群では、妊娠回数が少なく、FGR診断時胎児推定体重のSD値が小さく、高度の胎児血流異常ありの割合が高かった。FGRの原因やリスク因子としては妊娠高血圧症候群が62.4%を占めていた。また、FGR診断後にHDP(妊娠高血圧症候群)を発症した症例もみられた。
「産婦人科の進歩」編集室, 2018年08月, 産婦人科の進歩, 70 (3), 270 - 277, 日本語[査読有り]
研究論文(学術雑誌)
PURPOSE: To justify a classification system for angiographic images of uterine artery embolization (UAE) for postpartum hemorrhage (PPH) and identify new risk factors associated with failed embolization. MATERIALS AND METHODS: A retrospective analysis of 63 consecutive patients who underwent UAE for severe PPH was performed. Uterine artery angiography (UA) before embolization was classified into two types: type 1 was defined as complete staining and type 2 was defined as partial staining of the uterine arteries. The clinical outcome, UA classification, and other possible factors previously reported were evaluated. Univariate and multivariate analyses were performed to determine the factors related to clinical outcomes. RESULTS: Sixty-three patients were enrolled (type 1, 22; type 2, 41). The clinical success rates of the primary UAE session were 90.9% (20/22) for type 1 and 61.0% (25/41) for type 2 (p = 0.018). Univariate and multivariate analyses demonstrated that the only UA classification was significantly associated with primary UAE failure (p = 0.033). CONCLUSIONS: The UA classification is an independent predictive factor of the clinical success rate of the primary UAE session for PPH; thus, it is an intuitive and optimal predictor for interventional radiologists to decide whether additional therapy is necessary.
2018年06月, Japanese journal of radiology, 36 (6), 394 - 400, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
Purpose: This study aimed to assess the efficacy of high-dose i.v. immunoglobulin (HIVIg) therapy in pregnant women with antiphospholipid syndrome (APS) secondary to systemic lupus erythematosus with a history of pregnancy failure, despite receiving low-dose aspirin plus unfractionated heparin therapy, of which condition being designated as "aspirin-heparin-resistant APS" (AHRAPS). Methods: The HIVIg therapy (20 g/d, 5 days) was performed for the pregnancies of five women with AHRAPS. Results: Five of the eight pregnancies ended in live births. The gestational ages of delivery in four of the five pregnancies were extended, compared with previous pregnancies. The HIVIg therapy was considered to be successful for these four pregnancies. Excluding one pregnancy that ended in miscarriage with an abnormal chromosome karyotype of the villi, the HIVIg therapy was considered to be successful in four (57.1%) of the seven pregnancies of the women with AHRAPS. Although all the live newborns were prematurely delivered, no adverse effect of the HIVIg therapy was observed. Conclusions: The HIVIg therapy might be beneficial as an immune modifier for pregnant women with AHRAPS. However, the precise indication of which women with AHRAPS who should receive HIVIg therapy remains unknown.
2018年04月, Reproductive medicine and biology, 17 (2), 149 - 154, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
INTRODUCTION: Placenta previa (PP) is one of the most significant risk factors for adherent placenta (AP). The aim of this study was to evaluate the diagnostic efficacy of a novel scoring system for predicting AP in pregnant women with PP. METHODS: This prospective cohort study enrolled 175 women with PP. The placenta previa with adherent placenta score (PPAP score) is composed of 2 categories: (1) past history of cesarean section (CS), surgical abortion, and/or uterine surgery; and (2) ultrasonography and magnetic resonance imaging findings. Each category is graded as 0, 1, 2, or 4 points, yielding a total score between 0 and 24. When women with PP had PPAP score ≥8, they were considered to be at a high risk for AP and received placement of preoperative internal iliac artery occlusion balloon catheters. If they were found to have AP during CS, they underwent hysterectomy or placenta removal using advanced bipolar with balloon catheter occlusion. The predictive accuracy of PPAP score was evaluated. RESULTS: In total, 23 of the 175 women with PP were diagnosed as having AP, histopathologically or clinically. Twenty-one of 24 women with PPAP score ≥8 had AP, whereas two of 151 women with PPAP score <8 had AP. The scoring system yielded 91.3% sensitivity, 98.0% specificity, 87.5% positive predictive value, and 98.7% negative predictive value for predicting AP in women with PP. DISCUSSION: This prospective study demonstrated that PPAP scoring system may be useful for predicting AP in women with PP.
2018年04月, Placenta, 64, 27 - 33, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Congenital complete atrioventricular block (CCAVB) is a condition in which the atria and ventricles beat independently of each other. CCAVB cases require permanent pacemaker implantation until adulthood. Nevertheless, consensus regarding postnatal medical therapy for bradycardia has not been reached. Here we report the case of a newborn with CCAVB, whose intractable bradycardia was successfully treated with transdermal tulobuterol. Tulobuterol is a selective β2-adrenoceptor agonist, widely used safely as bronchodilator in children. It also has positive inotropic and chronotropic effect via β1-adrenoceptors. We believe the tulobuterol patch can be used as an optional therapy for CCAVB where pacemaker implantation is not available.
2018年04月, Kobe J Med Sci, 63 (4), E109 - E112, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
The aim of this prospective study was to determine clinical factors associated with adverse pregnancy outcomes in women with systematic lupus erythematosus (SLE). Fifty-six pregnancies from 46 women with SLE were enrolled. Risk factors for pregnancy loss, premature delivery, hypertensive disorders of pregnancy (HDP), and light-for-date neonate (LFD), were evaluated. Univariate and multivariate logistic regression analyses revealed a history of two or more pregnancy losses before 10 gestational weeks (GW) (OR 11.5, 95%CI 1.72-76.8) as a risk factor for pregnancy loss; low levels of blood complements (OR 7.55, 95%CI 1.10-51.9) and antiphospholipid syndrome (OR 26.5, 95%CI 3.17-219) as risk factors for premature delivery before 37 GW; SLEDAI score at conception (OR 1.68, 95%CI 1.05-2.68) and positive tests for two or more antiphospholipid antibodies (OR 6.89, 95%CI 1.13-41.9) as risk factors for premature delivery before 34 GW; prednisolone therapy >14mg/day (OR 7.55, 95%CI 1.10-51.9) as a risk factor for HDP; and low dose aspirin therapy (OR 0.21, 95%CI 0.05-0.97) decreased the risk for LFD neonate. These results have important implications for clinicians managing SLE complicated pregnancy.
2018年02月, Journal of reproductive immunology, 125, 39 - 44, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り][招待有り]
論文集(書籍)内論文
We report two cases of pulmonary hypoplasia due to fetal ascites in symptomatic congenital cytomegalovirus (CMV) infections despite fetal therapy. The patients died soon after birth. The pathogenesis of pulmonary hypoplasia in our cases might be thoracic compression due to massive fetal ascites as a result of liver insufficiency. Despite aggressive fetal treatment, including multiple immunoglobulin administration, which was supposed to diminish the pathogenic effects of CMV either by neutralization or immunomodulatory effects, the fetal ascites was uncontrollable. To prevent development of pulmonary hypoplasia in symptomatic congenital CMV infections, further fetal intervention to reduce ascites should be considered.
FRONTIERS MEDIA SA, 2017年11月, FRONTIERS IN PEDIATRICS, 5, 241, 英語[査読有り]
研究論文(学術雑誌)
Background: The aim of this prospective cohort study was to evaluate the efficacy of maternal screening for congenital cytomegalovirus infection (CCI) using cytomegalovirus (CMV) immunoglobulin G (IgG) and the IgG avidity index (AI). Methods: Pregnant women underwent screening of CMV IgG and AI measurements. IgG-negative women underwent remeasurement of IgG after educational intervention. Women with an AI ≤45% received further examinations, including measurement of CMV IgM. All newborns received polymerase chain reaction analyses of the urine, and CCI was diagnosed by the detection of CMV-DNA in the urine. Primary infection was defined as an AI <35% and/or positive IgM (>1.20 index). Serum samples from women with an AI >45% were stored, and the IgM levels were measured after delivery. The efficacy of AI and IgM for CCI screening was compared. Results: A total of 1562 (71.2%) women tested positive for IgG. In this study, 10 newborns with CCI were detected. The presence of infection in 3 newborns from mothers with primary infection was predicted by screening of IgG and AI <35%. However, infection in 7 newborns from women with nonprimary infection could not be predicted by screening of CMV IgG, AI <35%, or IgM. The application of an AI <35% for CCI screening yielded 22.2% sensitivity, 95.0% specificity, 2.5% positive predictive value, and 99.5% negative predictive value and was similar to that of IgM (11.1% sensitivity, 93.2% specificity, 0.9% positive predictive value, and 92.7% negative predictive value). Conclusions: Maternal screening using CMV IgG and AI can identify pregnancies with CCI from primary infection, but overlooks a number of those from nonprimary infection.
2017年10月30日, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 65 (10), 1652 - 1658, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
[査読有り][招待有り]
Background: Surgical meshes are widely used in incisional hernia repair. However, there are no reports of pregnancies complicated by infection of surgical meshes used for hernia repair. This is the first case report of a pregnant woman who experienced surgical site infection associated with surgical mesh used for repair of an abdominal wall incisional hernia. Case presentation: We report a case of a 41-year-old pregnant Japanese woman with surgical site infection after mesh repair of an abdominal wall incisional hernia. She was diagnosed with an abdominal wall incisional hernia at 3 months after her third cesarean section, and she underwent an operation of hernia repair with use of monofilament polypropylene mesh 7 months after the third cesarean section. However, a surgical site infection associated with surgical mesh occurred. During antibiotic treatment, she was found to be pregnant. She was referred to our hospital at 13 weeks and 2 days of gestation. The surgeons removed the infected mesh at 16 weeks and 3 days of gestation. Neither the hernia nor infection at the surgical site recurred throughout pregnancy. We planned a cesarean section using a transverse uterine fundal incision method with an upper abdominal incision. The patient delivered a 2478-g healthy female infant. Conclusions: The present report shows that removal of mesh can safely control surgical site infection during pregnancy.
BioMed Central Ltd., 2017年03月11日, Journal of Medical Case Reports, 11 (1), 66, 英語[査読有り]
研究論文(学術雑誌)
Background. This prospective study aimed to determine maternal clinical, laboratory, and ultrasound findings that effectively predict the occurrence of congenital cytomegalovirus (CMV) infection (CCI) in high-risk pregnant women. Methods. Three hundred CMV immunoglobulin (Ig) M-positive pregnant women were enrolled. The maternal clinical and laboratory findings, including serum CMV IgM and IgG; IgG avidity index (AI); antigenemia assay (C7-HRP); polymerase chain reaction (PCR) for the detection of CMV-DNA in the maternal serum, urine, and uterine cervical secretion; and prenatal ultrasound findings, were evaluated. To determine predictive factors for the occurrence of CCI, logistic regression analyses were performed. Results. In 22 of the 300 women, CCI was confirmed using PCR for CMV-DNA in newborn urine. Univariate analyses demonstrated that the presence of maternal flu-like symptoms, presence of ultrasound fetal abnormalities, serum titers of CMV IgM, positive results for C7-HRP, CMV IgG AI <40%, and positive PCR results in the uterine cervical secretion were statistically associated with the occurrence of CCI. Multivariable analysis revealed that the presence of ultrasound fetal abnormalities (odds ratio [OR], 31.9; 95% confidence interval [CI], 8.5-120.3; P<.001) and positive PCR results in the uterine cervical secretion (OR, 16.4; 95% CI, 5.0-54.1; P<.001) were independent predictive factors of CCI in CMV IgM-positive women. Conclusions. This is the first prospective cohort study to suggest that the presence of CMV-DNA in the maternal uterine cervical secretion and ultrasound fetal abnormalities are predictive of the occurrence of congenital CMV infection in high-risk pregnant women.
OXFORD UNIV PRESS INC, 2017年01月, CLINICAL INFECTIOUS DISEASES, 64 (2), 159 - 165, 英語[査読有り]
研究論文(学術雑誌)
研究論文(その他学術会議資料等)
[査読有り]
研究論文(その他学術会議資料等)
[査読有り]
研究論文(その他学術会議資料等)
研究論文(その他学術会議資料等)
[査読有り]
研究論文(その他学術会議資料等)
[査読有り]
研究論文(その他学術会議資料等)
研究論文(その他学術会議資料等)
Purpose: To evaluate the interobserver variability and diagnostic performance of a developed magnetic resonance imaging (MRI)-based scoring system for invasive placenta previa. Materials and Methods: Prenatal MR images of 70 women were retrospectively evaluated, 18 of whom were diagnosed with invasive placenta. The six MR features (dark band on T2-weighted images, intraplacental abnormal vascularity, placental bulge, heterogeneous placenta, myometrial thinning, and placental protrusion sign) were scored on 5-point Likert scale separately, and the cumulative radiological score (CRS) was defined as the sum of each score. Two more experienced radiologists (readers A and B) and two less experienced residents (readers C and D) calculated the CRS. Interobserver variability was assessed by measuring the intraclass correlation coefficient. Diagnostic performance was evaluated by means of receiver operating characteristic (ROC) analysis. Results: Interobserver variability for CRS was excellent for the more experienced radiologists (0.85), and good for all readers (0.72) and the less experienced residents (0.66). The area under the ROC curve (Az) and accuracy (Acc) for CRS were significantly higher or equivalent to those of other MR features for all readers (Az and Acc for reader A CRS, 0.92, 91.4% intraplacental T2 dark band, 0.83, P = 0.009, 81.4%, P = 0.03 intraplacental abnormal vascularity, 0.9, P = 0.3, 90.0%, P = 1.00 placental bulge, 0.81, P = 0.0008, 80.0%, P = 0.02 heterogeneous placenta, 0.85, P = 0.11, 74.3%, P = 0.002 myometrial thinning, 0.84, P = 0.06, 60.0%, P < 0.0001 placental protrusion sign, 0.81, P = 0.01, 81.4%, P = 0.26). Conclusion: This developed MRI-based scoring system demonstrated excellent or good interobserver variability, and good diagnostic performance for invasive placenta previa. J. Magn. Reson. Imaging 2016 44:573–583.
John Wiley and Sons Inc., 2016年09月01日, Journal of Magnetic Resonance Imaging, 44 (3), 573 - 583, 英語[査読有り]
研究論文(学術雑誌)
[査読有り][招待有り]
研究論文(研究会,シンポジウム資料等)
研究論文(その他学術会議資料等)
研究論文(その他学術会議資料等)
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
Background: Newborn screening for urinary cytomegalovirus (CMV) and early introduction of antiviral treatment are expected to improve neurological outcomes in symptomatic congenital CMV-infected infants. This cohort study prospectively evaluated neurological outcomes in symptomatic congenital CMV-infected infants following the introduction of hospital-based newborn urinary CMV screening and antiviral treatment. Subjects/methods: Following institutional review board approval and written informed consent from their parents, newborns were prospectively screened from 2009 to 2014 for urinary CMV-DNA by PCR within 1 week after birth at Kobe University Hospital and affiliated hospitals. CMV-positive newborns were further examined at Kobe University Hospital, and those diagnosed as symptomatic were treated with valganciclovir for 6 weeks plus immunoglobulin. Clinical neurological outcomes were evaluated at age 12 months and categorized by the presence and severity of neurologic sequelae. Results: Urine samples of 6348 newborns were screened, with 32 (0.50%) positive for CMV. Of these, 16 were diagnosed with symptomatic infection and 12 received antiviral treatment. Four infants developed severe impairment (33%), three developed mild impairment (25%), and five developed normally (42%). Conclusions: This is the first Japanese report of neurological assessments in infants with symptomatic congenital CMV infection who received early diagnosis and antiviral treatment. Urinary screening, resulting in early diagnosis and treatment, may yield better neurological outcomes in symptomatic congenital CMV-infected infants. (C) 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
ELSEVIER SCIENCE BV, 2016年02月, BRAIN & DEVELOPMENT, 38 (2), 209 - 216, 英語[査読有り]
研究論文(学術雑誌)
Background: Few studies have targeted psychomotor development and associated perinatal risk factors in Japanese very low birth weight (VLBW) infants who are severely small for gestational age (SGA). Design/subjects: A single-center study was conducted in 104 Japanese VLBW infants who were born preterm, due to maternal, umbilical cord, or placental abnormalities, between 2000 and 2007. Psychomotor development as a developmental quotient (DQ) was assessed using the Kyoto Scale of Psychological Development at 3 years corrected age. Severely SGA was defined as birth weight or length below -2 standard deviation values of the mean values at the same gestation. VLBW infants were divided into 2 subgroups based on gestational age at birth: >= 28 weeks (n = 64) and <28 weeks (n = 40). DQs of infants with severe SGA were compared with those of infants who were appropriate for gestational age (AGA). Factors associated with developmental disabilities in VLBW infants with severe SGA (n = 23) were determined. Results: In the group born at >= 28 weeks gestation, infants with severe SGA had normal DQ values and did not significantly differ from those with AGA. However, in the group born at <28 weeks gestation, severe SGA infants had significantly lower postural motor DQ values than AGA infants. Gestational age <28 weeks was an independent factor for low postural motor DQ, regardless of the cause of severe SGA or pregnancy termination. Conclusions: Extremely preterm newborns with severe SGA are at risk of motor developmental disability at age 3 years. (C) 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
ELSEVIER SCIENCE BV, 2016年02月, BRAIN & DEVELOPMENT, 38 (2), 188 - 195, 英語[査読有り]
研究論文(学術雑誌)
研究論文(その他学術会議資料等)
[査読有り][招待有り]
研究論文(学術雑誌)
This prospective study aimed to evaluate pregnancy outcome and complications in women with recurrent pregnancy loss (RPL) and protein S (PS) deficiency, who received low dose aspirin (LDA) or LDA plus heparin (LDA/H) therapies. Clinical characteristics, pregnancy outcome and complications of 38 women with two or more RPL and <60% of plasma free PS antigen were compared among three groups: antiphospholipid antibody (aPL)-negative women who received LDA (group A), aPL-negative women who received LDA/H (group B) and aPL-positive women who received LDA/H (group C). Gestational weeks (GW) at delivery in group C (median 32 GW) were earlier than 40 GW in group A and 38.5 GW in group B (p < 0.05). The birth weight in group C (median 1794 g) was less than 2855 g in group B (p < 0.05). The incidences of fetal growth restriction (37.5%), pregnancy-induced hypertension (37.5%), and preterm delivery (62.5%) in group C were higher than those (4.5%, 0%, and 4.5%, respectively) in group B (p<0.05). Women with RPL, PS deficiency, and positive aPL had high risks for adverse pregnancy outcome and complications, even when they received LDA/H therapy. Among women with RPL, PS, and negative aPL, there was no difference in these risks between LDA alone and LDA/H therapies.
TAYLOR & FRANCIS LTD, 2016年, GYNECOLOGICAL ENDOCRINOLOGY, 32 (8), 672 - 674, 英語[査読有り]
研究論文(学術雑誌)
Objectives: To determine the risk factors for glucose intolerance (GI) during the postpartum period in women with gestational diabetes mellitus (GDM). Methods: This prospective cohort study included 72 Japanese women with GDM who underwent 75 g oral glucose tolerance tests (OGTT) at 12 weeks after delivery. These women were divided into the GI group and the normal group based on postpartum OGTT. Risk factors for GI, including levels of blood glucose (BG), area under the curve (AUC) of glucose, AUC insulin, HbA1c, homeostasis model assessment-insulin resistance (HOMA-IR), HOMA-beta, insulinogenic index (II) and the oral disposition index (DI) in antepartum OGTT, were analyzed by logistic regression analyses. Results: Of the 72 women, 60 (83.3%) were normal and 12 (16.7%) had GI. By univariate logistic regression analyses, fasting BG, AUC glucose, HOMA-beta, II and oral DI were selected as risk factors for GI. Multivariate logistic regression analysis revealed that the level of II in antepartum OGTT was a significant factor that predicted GI after delivery (odds ratio, 0.008; 95% CI, 0.0001-0.9; p < 0.05). Conclusions: II measured by OGTT during pregnancy might be a useful predictor of GI within the early postpartum period in women with GDM.
TAYLOR & FRANCIS LTD, 2016年, GYNECOLOGICAL ENDOCRINOLOGY, 32 (10), 803 - 806, 英語[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
Epithelial-mesenchymal transition is a key process influencing cancer progression and metastasis. The purpose of this study was to investigate the expression of epithelial-mesenchymal transition-related factors in chorionic villi and decidual cells in adherent placenta. The current study included 19 patients diagnosed with adherent placenta after hysterectomy. The expression of E-cadherin, Vimentin, Snail, and transforming growth factor- in placental tissues was analyzed by immunohistochemical staining. Immunostaining intensity was semiquantitatively evaluated using the HSCORE algorithm. In the chorionic villi of the invasive part (placenta with invasion into myometrium), E-cadherin expression was significantly lower than that in the noninvasive part (placenta with no invasion). In the decidual cells of the invasive part, expression of transforming growth factor- and Snail significantly increased. These results suggest that epithelial-mesenchymal transition may contribute to excessive trophoblast invasion into the myometrium in adherent placenta.
LIPPINCOTT WILLIAMS & WILKINS, 2015年11月, INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY, 34 (6), 584 - 589, 英語[査読有り]
研究論文(学術雑誌)
Primary Toxoplasma gondii (T. gondii) infection during pregnancy may lead to congenital toxoplasmosis. Maternal screening using T. gondii IgG avidity measurement and multiplex nested PCR was performed. The aim of this prospective cohort study was to determine a cut-off value of IgG avidity index (AI) for the prediction of the presence of T. gondii DNA in the amniotic fluid. One hundred thirty-nine women with positive or equivocal tests for IgM underwent both serum IgG avidity measurement and PCR analysis for the amniotic fluid. Nine had positive PCR results, and three of them were diagnosed as having congenital infection. A cut-off value of IgG AI was determined using receiver operating characteristic analysis. IgG AI (mean 13%) in women with positive PCR results was significantly lower than that (39%) in women with negative results. A cut-off value of <25% IgG AI yields the best results with 77.8% sensitivity and 81.5% specificity for the presence of T. gondii DNA in the amniotic fluid. None of women with IgG AI of >= 30% had a positive PCR result or congenital infection. This study firstly demonstrated that a cut-off value of 25 -30% IgG AI might be useful for the prediction of the presence of T. gondii DNA in the amniotic fluid and congenital infection. (C) 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
ELSEVIER SCIENCE BV, 2015年09月, JOURNAL OF INFECTION AND CHEMOTHERAPY, 21 (9), 668 - 671, 英語[査読有り]
研究論文(学術雑誌)
This study aimed to evaluate changes in natural killer (NK) cell activity and the percentage of monocytes in women with recurrent miscarriage who received medium-dose intravenous immunoglobulin (IVIg) therapy. Fourteen women with a history of six or more recurrent miscarriages of unexplained etiology received 60-g IVIg therapy (20 g daily, for three days) during early gestation. NK cell activity in the peripheral blood decreased to 12% one week after therapy compared with before therapy (median, 22%, P < 0.001) and the percentage of monocytes increased from 5.2% to 7.5% (P < 0.005). Four pregnancies ended in live births of healthy neonates, whereas the other ten pregnancies ended in miscarriages. Excluding one miscarriage with a chromosomal abnormality, the live birth rate was 30.8% (4/13). The rate of reduction of NK cell activity in the success group (-58.8%) tended to be greater than that in the failure group (-14.8%, P = 0.057).
2015年06月, Journal of reproductive immunology, 109, 48 - 51, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Background: Human Cytomegalovirus (CMV) is the virus most frequently responsible for severe diseases of the fetus and newborn. The reported intrauterine transmission rate of CMV following primary maternal infection is approximately 40%. Invasive techniques are needed for the prenatal diagnosis of congenital CMV infection. Objectives: The aim of this study was to evaluate whether the rapidity of change in the CMV IgG avidity index (AI) is associated with the presence of congenital CMV infection among mothers with suspected primary CMV infection. Study design: The serum CMV IgG AI was repeatedly measured in 17 pregnant women with positive or borderline test results for CMV IgM together with an initial IgG AI value of <40%. Their neonates underwent polymerase chain reaction analyses for the presence of CMV DNA in the urine. The rapidity of change in the IgG AI per 4 weeks was defined as the Delta AI (%). The Delta AI of women with congenital CMV infection was compared with that of women with no infection. Results: The Delta AI of nine mothers with congenital CMV infection (median, 15.7%; range, 7.8-42.8%) was significantly higher than that of eight mothers with no infection (median, 6.5%, range, 2.0-8.8%; p < 0.001). The incidences of congenital CMV infection were 100.0%, 16.7%, and 0.0% among mothers with a Delta AI of >10, 5-10, and <5%, respectively. Conclusions: Measurement of the Delta AI in pregnant women might be useful for estimating the risk of mother-to-neonate CMV transmission. (C) 2015 Elsevier B.V. All rights reserved.
ELSEVIER SCIENCE BV, 2015年05月, JOURNAL OF CLINICAL VIROLOGY, 66, 44 - 47, 英語[査読有り]
研究論文(学術雑誌)
OBJECTIVE: Adherent placenta is a life-threatening condition in pregnancy, and is often complicated by placenta previa. The aim of this prospective study was to determine prenatal imaging findings that predict the presence of adherent placenta in pregnancies with placenta previa. STUDY DESIGN: The study included 58 consecutive pregnant women with placenta previa who underwent both ultrasonography and magnetic resonance imaging prenatally. Ultrasonographic findings of anterior placental location, grade 2 or higher placental lacunae (PL≥G2), loss of retroplacental hypoechoic clear zone (LCZ) and the presence of turbulent blood flow in the arteries were evaluated, in addition to MRI findings. Forty-three women underwent cesarean section alone; 15 women with adherent placenta underwent cesarean section followed by hysterectomy with pathological examination. To determine imaging findings that predict adherent placenta, univariate and multivariate logistic regression analyses were performed. RESULTS: Univariate logistic regression analyses demonstrated that anterior placental location, PL≥G2, LCZ, and MRI were associated with the presence of adherent placenta. Multivariate analyses revealed that LCZ (p<0.01, odds ratio 15.6, 95%CI 2.1-114.6) was a single significant predictor of adherent placenta in women with placenta previa. CONCLUSION: This prospective study demonstrated for the first time that US findings, especially LCZ, might be useful for identifying patients at high risk for adherent placenta among pregnant women with placenta previa.
2015年04月, European journal of obstetrics, gynecology, and reproductive biology, 187, 41 - 4, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Objectives: The aim of this survey study was to evaluate a state of mother-to-child infections in Japan. Methods: A nationwide survey on 2714 obstetric facilities where regular maternity checkups were carried out was conducted. A primary questionnaire assessed numbers of pregnancies including induced abortion, spontaneous abortion, still-birth as well as live-birth, which were affected by congenital infections of 6 pathogens during a year of 2011. The secondary questionnaire assessed clinical information, diagnostic modality, and the outcome for each case. The clinical features and diagnostic problems were evaluated. Results: The high reply rates for the primary (73.7%) and the secondary questionnaire (100%) were achieved. The presence of congenital infections for 34 cases with cytomegalovirus (CMV), 1 with Toxoplasma gondii, 4 with rubella virus, 5 with Treponema pallidum, 8 with herpes simplex virus, and 69 with parvovirus B19 was confirmed after questionnaire assessment. The incidence of fetal demise among pregnancies with congenital parvovirus B19 infection was up to 71.0%. Eleven mothers with hydrops fetalis received prenatal fetal therapies involving fetal blood transfusion and immunoglobulin administration, whereas only three pregnancies (27.3%) ended in live-births. Conclusions: This survey study for the first time revealed the annual frequency of pregnancies with mother-to-child infections of 6 pathogens in Japan. The results involve important information and are helpful for clinical practitioners. The majority of neonates with congenital infection of CMV or T. gondii might be undiagnosed in obstetric facilities. (C) 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
SPRINGER JAPAN KK, 2015年03月, JOURNAL OF INFECTION AND CHEMOTHERAPY, 21 (3-4), 161 - 164, 英語[査読有り]
研究論文(学術雑誌)
Aims: Neurological outcomes differ considerably between symptomatic and asymptomatic infants with congenital cytomegalovirus (CMV) infection. Our objective was to characterize laboratory markers in symptomatic newborns in comparison with asymptomatic newborns with congenital CMV infection. Methods: Ten newborns with symptomatic and 13 newborns with asymptomatic congenital CMV infection were included in this 3-year prospective cohort study. Total immunoglobulin M (IgM), CMV-IgM, CMV antigenemia, and CMV-DNA in blood and urine were measured and their positive rates and quantitative values compared between the symptomatic and asymptomatic groups. Results: Fifty percent of newborns in the symptomatic group were positive based on total IgM; this was significantly lower than in the asymptomatic group (100%). Quantitative total IgM values were significantly lower, and there were significantly more copies of CMV-DNA in the blood of symptomatic newborns than in -asymptomatic newborns (median values for total IgM: 14 vs. 43 mg/dL and blood CMV-DNA: 3.2 x 10(2) vs. 3.5 x 10(1) copies/10(6) white blood cells). CMV-IgM, CMV antigenemia, and urine CMV-DNA did not differ significantly between groups. Conclusion: Low total IgM values and high blood CMV loads were associated with the presence of symptoms in newborns with congenital CMV infection.
WALTER DE GRUYTER GMBH, 2015年03月, JOURNAL OF PERINATAL MEDICINE, 43 (2), 239 - 243, 英語[査読有り]
研究論文(学術雑誌)
Two independent guidelines on appropriate weight gain for Japanese pregnant women have been established in 1997 and 2006. This study aimed to evaluate changes in the amount of gestational weight gain in pregnant women, the birth weight of their neonates, and the incidence of complications of pregnancy and neonatal outcome in women who delivered at Hyogo Prefectural Kaibara Hospital. Between 1988 and 2014, 6367 women delivered live singleton neonates at full term. The study period was divided into period I (1988–1996), period II (1997–2005), and period III (2006–2014). Changes in weight gain and birth weight were assessed. Complications of pregnancy and neonatal outcome were compared among the periods. Weight gain had been decreased in periods I and II, and weight gain was increased in period III. There was no difference in birth weights between the periods. The incidences of pregnancy-induced hypertension in periods II and III were higher than that in period I (p< 0.01). The incidences of vacuum extraction in periods II and III were less than that in period I (p< 0.01). The incidence of macrosomia in periods II was less than that in period I (p< 0.01). There were no significant differences in the incidence of cesarean section, light-for-date, heavy-for-date, or low birth weight among the three periods. The establishment of guidelines for weight gain and maternity education based on the two guidelines significantly affected complications of pregnancy and neonatal outcome. Prevention of pregnancy-induced hypertension might be difficult when only reducing weight gain in pregnant women.
Kobe University School of Medicine, 2015年, Kobe Journal of Medical Sciences, 61 (3), E86 - E92, 英語[査読有り]
研究論文(学術雑誌)
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and/or pregnancy complications. b2-glycoprotein I (b2GPI) complexed with phospholipid is recognized as a major target for autoantibodies in APS however, less than half the patients with clinical manifestations of APS possess autoantibodies against the complexes. Therefore, the range of autoantigens involved in APS remains unclear. Recently, we found that human leukocyte antigen (HLA) class II molecules transport misfolded cellular proteins to the cell surface via association with their peptide-binding grooves. Furthermore, immunoglobulin G heavy chain/HLA class II complexes were specific targets for autoantibodies in rheumatoid arthritis. Here, we demonstrate that intact b2GPI, not peptide, forms a complex with HLA class II molecules. Strikingly, 100 (83.3%) of the 120 APS patients analyzed, including those whose antiphospholipid antibody titers were within normal range, possessed autoantibodies that recognize b2GPI/HLA class II complexes in the absence of phospholipids. In situ association between b2GPI and HLA class II was observed in placental tissues of APS patients but not in healthy controls. Furthermore, autoantibodies against b2GPI/HLA class II complexes mediated complement-dependent cytotoxicity against cells expressing the complexes. These data suggest that b2GPI/HLA class II complexes are a target in APS that might be involved in the pathogenesis. (Blood. 2015 125(18):2835-2844)
American Society of Hematology, 2015年, Blood, 125 (18), 2835 - 2844, 英語[査読有り]
研究論文(学術雑誌)
研究論文(学術雑誌)
BACKGROUND: Cytomegalovirus (CMV) causes congenital infection with high mortality and morbidity rates in affected neonates. OBJECTIVES: To evaluate the maternal IgG avidity value for the prediction of congenital CMV infection. STUDY DESIGN: The serum IgG avidity in all mothers was measured, and the urine of their neonates was assessed for CMV DNA in a prospective cohort study. RESULTS: Of 759 women with a positive test for CMV IgG, 14 had congenital CMV infection. CMV IgG avidity indices in the congenital infection group (median 35.1%) were significantly lower than those in the non-congenital infection group (70.4%). A cutoff value of <40% IgG avidity index with 96.1% specificity and 64.3% sensitivity for congenital infection was determined by receiver operating characteristic curve analyses. The highest sensitivity (88.9%), 96.2% specificity, 27.6% positive predictive value, 99.8% negative predictive value, and 96.1% accuracy were found when IgG avidity was measured in <28 weeks of gestation. CONCLUSION: The IgG avidity measurement with a cutoff value of <40% IgG avidity index might be helpful in predicting congenital CMV infection, especially in <28 weeks of gestation.
2014年11月, Journal of perinatal medicine, 42 (6), 755 - 9, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
The aim of this trial study was to assess the preventive efficacy of immunoglobulin with a high titer of anti-CMV antibody for mother-to-fetus cytomegalovirus (CMV) transmission among pregnant women with primary/acute CMV infection. The primary CMV infection in mothers was diagnosed by a positive test for CMV IgM and/or low IgG avidity. Intact type immunoglobulin with a high titer of anti-CMV antibody was injected intravenously at a dosage of 2.5-5.0 g/day for consecutive 3 days to mothers with primary CMV infection. Four pregnant women were enrolled. One pregnancy ended in no congenital infection, while two pregnancies ended in congenital CMV infection. The other one pregnancy was terminated. The mother-to-fetus CMV transmission rate was found to be high as 66.7% (2/3). This preliminary result suggests that intravenous immunoglobulin injections are not effective for the prevention of mother-to-fetus CMV transmission in the present protocol.
2014年07月11日, The Kobe journal of medical sciences, 60 (2), E25-9 - 9, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
Mother-to-child infections cause congenital infection with disease and sequelae. To evaluate a state of maternal blood screening for mother-to-child infections in Japan, we for the first time conducted a nationwide survey on obstetric facilities where regular maternity checkups were carried out. A questionnaire assessment involved an annual number of deliveries, scale of facilities and a state of maternal blood screening for eight pathogens. A high rate (73.7%) of reply to the questionnaire was achieved from 1990 facilities, covering 75.1% of annual number of delivery in 2011. The performance rates of blood screening were more than 99% for rubella virus, Treponema pallidum, human immunodeficiency virus (HIV), human T cell leukemia virus type 1 (HTLV-1), hepatitis B virus, and hepatitis C virus, while the rate was found to be only 4.5% for cytomegalovirus (CMV), and 48.5% for Toxoplasma gondii with large differences in regions. Most of the facilities performed blood tests for rubella virus, Treponema pallidum, HIV, hepatitis B virus and hepatitis C virus once in early pregnancy, while approximately 28% of the facilities performed blood tests for HTLV-1 once during the 2nd or 3rd trimester. Most of the facilities used HA tests for Toxoplasma gondii, whereas there was a wide variation in antibody measurement methods for CMV. Generally, the obstetric facilities in Japan have performed maternal blood screening properly according to the current recommendations. The results of this survey involve important information and are helpful for clinical practitioners.
WILEY-BLACKWELL, 2014年05月, CONGENITAL ANOMALIES, 54 (2), 100 - 103, 英語[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
To review established magnetic resonance (MR) criteria and describe a new MR finding for the diagnosis of invasive placenta praevia. A retrospective review of prenatal MRI examinations of 65 patients (median age: 35 years) who underwent MR for the screening of invasive placenta praevia. All MRIs were performed on a 1.5-T unit, including axial, coronal and sagittal T2-weighted half-Fourier single-shot turbo spin echo imaging. Fifteen patients were diagnosed with invasive placenta praevia. Two experienced radiologists reviewed the MR images and evaluated a total of six MRI features of the placenta, including our novel finding of the placental protrusion into the internal os (placental protrusion sign). Inter-rater reliability was assessed by using kappa statistics. Features with a kappa statistic > 0.40 were evaluated using Fisher's two-sided exact test for comparison of their capabilities for placental invasion assessment. Interobserver reliability was moderate or better for the intraplacental T2 dark band, intraplacental abnormal vascularity, uterine bulging, heterogeneous placenta and placental protrusion sign. Fisher's two-sided exact test results showed all these features were significantly associated with invasive placenta praevia. The novel MRI finding of a placental protrusion sign is a useful addition to the established MRI findings for the diagnosis of invasive placenta praevia. aEuro cent Prenatal diagnosis for an invasive placenta is essential for perinatal planning. aEuro cent Magnetic resonance imaging provides useful information for the diagnosis of invasive placenta. aEuro cent The placental protrusion sign is a useful novel MRI finding for predicting invasive placenta.
SPRINGER, 2014年04月, EUROPEAN RADIOLOGY, 24 (4), 881 - 888, 英語[査読有り]
研究論文(学術雑誌)
Specific HLA class II alleles are strongly associated with susceptibility to rheumatoid arthritis (RA); however, how HLA class II regulates susceptibility to RA has remained unclear. Recently, we found a unique function of HLA class II molecules: their ability to aberrantly transport cellular misfolded proteins to the cell surface without processing to peptides. Rheumatoid factor (RF) is an autoantibody that binds to denatured IgG or Fc fragments of IgG and is detected in 70-80% of RA patients but also in patients with other diseases. Here, we report that intact IgG heavy chain (IgGH) is transported to the cell surface by HLA class II via association with the peptide-binding groove and that IgGH/HLA class II complexes are specifically recognized by autoantibodies in RF-positive sera from RA patients. In contrast, autoantibodies in RF-positive sera from non-RA individuals did not bind to IgGH/HLA class II complexes. Of note, a strong correlation between autoantibody binding to IgG complexed with certain HLA-DR alleles and the odds ratio for that allele's association with RA was observed (r = 0.81; P = 4.6 × 10(-5)). Our findings suggest that IgGH complexed with certain HLA class II alleles is a target for autoantibodies in RA, which might explain why these HLA class II alleles confer susceptibility to RA.
2014年03月11日, Proceedings of the National Academy of Sciences of the United States of America, 111 (10), 3787 - 92, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
To reduce the incidence of infants with congenital infections, women should be aware of and know prevention measures against maternal infection with mother-to-child infections during pregnancy. Our objective was to assess the awareness of and knowledge about mother-to-child infections in Japanese pregnant women. A survey of 343 Japanese pregnant women was completed. Awareness of 13 pathogens capable of mother-to-child transmission was surveyed. Knowledge about the transmission route, the most susceptible time of infection that may cause severe fetal disease during pregnancy, and methods to prevent maternal infection were investigated for four major pathogens (cytomegalovirus, rubella virus, Toxoplasma gondii, and parvovirus B19) and results were compared between these pathogens. The proportion of women aware of pathogens concerning TORCH syndrome was the following: rubella virus 76%, Treponema pallidum 69%, Toxoplasma gondii 58%, parvovirus B19 28%, herpes simplex virus 27%, and cytomegalovirus 18%. Only 8% knew how cytomegalovirus is transmitted, and only 12% knew how parvovirus B19 is transmitted; both were significantly lower than those who knew transmission routes for rubella virus or Toxoplasma gondii. The proportion of women who knew the most susceptible time for severe fetal infection by maternal acquisition of cytomegalovirus, Toxoplasma gondii, or parvovirus B19 was significantly lower than that for rubella virus. The vast majority of surveyed women were not aware of methods to prevent maternal infection with cytomegalovirus or parvovirus B19. In conclusion, current awareness of and knowledge about cytomegalovirus and parvovirus B19 infection are low in Japanese pregnant women.
WILEY, 2014年02月, CONGENITAL ANOMALIES, 54 (1), 35 - 40, 英語[査読有り]
研究論文(学術雑誌)
Objective To determine the factors related to adverse pregnancy outcomes and neonatal thyroid dysfunction in pregnancies complicated by Graves' disease. Study design Thirty-five pregnancies complicated by Graves' disease were divided into two groups: adverse pregnancy outcome (n = 15) and no adverse pregnancy outcome (n = 20). Adverse pregnancy outcomes included spontaneous abortion, stillbirth, premature delivery, fetal growth restriction, and pregnancy-induced hypertension. The 31 pregnancies resulting in live births were also divided into two groups: neonatal thyroid dysfunction (n = 9) and normal neonatal thyroid function (n = 22). Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), TSH-receptor antibody (TRAb), the duration of hyperthyroidism in pregnancy, doses of antithyroid medication, and the duration of maternal antithyroid medication throughout pregnancy were compared. Results There were no significant differences in these factors between pregnancies with an adverse pregnancy outcome and those with no adverse pregnancy outcome. However, serum levels of FT4, TRAb, the duration of hyperthyroidism in pregnancy, the maximum daily dose of antithyroid medication, and the total dose of antithyroid medication were significantly different between pregnancies with neonatal thyroid dysfunction and those with normal neonatal thyroid function. Multivariate logistic regression analysis showed that the FT4 level in mothers was a significant factor related to the development of neonatal thyroid dysfunction (odds ratio 28.84, 95% confidence interval 1.65-503.62, p < 0.05). Conclusion Graves' disease activity in women of childbearing age should be well controlled prior to conception. © 2014 Elsevier Ireland Ltd.
Elsevier Ireland Ltd, 2014年, European Journal of Obstetrics Gynecology and Reproductive Biology, 177, 89 - 93, 英語[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
研究論文(その他学術会議資料等)
研究論文(その他学術会議資料等)
We report a monochorionic diamniotic twin pair born at 29 weeks of gestation in which both twins developed severe retinopathy of prematurity (ROP) with retinal detachment. The pregnancy was terminated due to reversal of donor-recipient phenotypes in possible TTTS. Both twins had unstable cardiopulmonary status during the first week, and developed chronic lung disease. The larger twin, born at 1372 g, developed stage 4a ROP in both eyes, and the smaller twin, born at 1168 g, developed stage 4a ROP in the left eye. Genetic analysis of NDP, FZD4, LRP5, TSPAN12 genes revealed no mutations; however, VEGF gene polymorphism analysis showed heterozygous carrier state of the VEGF 936T allele in both twins, which is a risk factor for threshold ROP in Japanese newborn infants. We speculate the synergistic effects of unstable perinatal cardiopulmonary status and genetic predisposition due to VEGF 936C>T polymorphism caused the development of severe ROP with retinal detachment.
2013年06月, Pediatrics international : official journal of the Japan Pediatric Society, 55 (3), 366 - 8, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
A 31-year-old woman contracted acute varicella at 13 weeks of gestation. Severe hydrops fetalis, hepatomegaly, and intrauterine fetal death were detected at 16 weeks of gestation by ultrasound examinations. An examination at autopsy, histopathology, and polymerase chain reaction (PCR) provided evidence of varicella-zoster virus (VZV) infection of the fetus. Second trimester intrauterine fetal death caused by mother to fetus infection of VZV is extremely rare. J. Med. Virol. 85:935938, 2013. (c) 2013 Wiley Periodicals, Inc.
WILEY-BLACKWELL, 2013年05月, JOURNAL OF MEDICAL VIROLOGY, 85 (5), 935 - 938, 英語[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
Cytomegalovirus (CMV) causes congenital infection with high mortality and morbidity rates in affected neonates. The aim of this study was to assess whether prenatal clinical or laboratory findings in pregnant women who had high risks for primary CMV infection predicted the presence of congenital infection. Fifty pregnant women who had serum CMV IgG and positive or borderline tests for serum CMV IgM were included in this prospective study. Serum IgG avidity was measured, and PCR was conducted for CMV DNA in maternal serum, urine, and uterine cervical secretion. All neonates underwent PCR testing for CMV DNA in the urine for the presence of congenital infection. Risk factors were compared between congenital infection group and group without congenital infection. As a result, nine neonates (18%) were diagnosed as having congenital infection. The frequencies of ultrasound fetal abnormality and positive test for CMV DNA in cervical secretion, CMV IgM titer and IgM/IgG ratio in the congenital infection group were significantly higher than those in the group without congenital infection. Conversely, IgG avidity index in the congenital infection group was significantly lower than that in the group without congenital infection. By multivariate logistic regression analyses, IgG avidity index (Odds ratio 0.91, 95% CI: 0.830.99) and ultrasound fetal abnormality (291.22, 2.7231125.05), were selected independently as significant signs predictive of congenital CMV infection. Among pregnant women with positive or borderline tests for CMV IgM, when they have findings of low serum CMV IgG avidity or ultrasound fetal abnormality, the probability of congenital CMV infection may increase. J. Med. Virol. 84:19281933, 2012. (c) 2012 Wiley Periodicals, Inc.
WILEY-BLACKWELL, 2012年12月, JOURNAL OF MEDICAL VIROLOGY, 84 (12), 1928 - 1933, 英語[査読有り]
研究論文(学術雑誌)
No medical intervention guideline for prenatally diagnosed symptomatic congenital cytomegalovirus infection (CCMVI) is currently available. The aim of the study was to assess the efficacy of immunoglobulin fetal therapy for symptomatic CCMVI. With informed consent, hyper-immunoglobulin was injected into the peritoneal cavity of affected fetuses or into the maternal blood in 12 women who had symptomatic CCMVI. After immunoglobulin therapy, ultrasound examinations demonstrated the following changes: Ascites disappearance 57.1% (4/7) and a decrease in ascites volume 14.3% (1/7); improvement in intrauterine growth restriction 54.5% (6/11); disappearance of mild ventriculomegaly 40% (2/5); and in one case hepatomegaly and hydronephrosis disappeared. The survival rate of affected infants was found to be 83.3% (10/12). Concerning morbidity, 25.0% (3/12) of the infants developed normally. An additional two cases had only unilateral hearing difficulty without other sequelae. Therefore, 41.7% (5/12) of symptomatic CCMVI infants whose mothers received prenatal immunoglobulin therapies had no or only minimal sequelae (unilateral hearing difficulty). No direct adverse effects were observed. Immunoglobulin therapy may be effective for symptomatic CCMVI, reducing the incidence and severity of sequelae. To confirm the efficacy, a randomized study should be further performed. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
ELSEVIER IRELAND LTD, 2012年09月, JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 95 (1-2), 73 - 79, 英語[査読有り]
研究論文(学術雑誌)
1999〜2006年に出生し、母体および胎盤・臍帯要因で早産となった極低出生体重児(VLBW)のうち、修正3歳時に新版K式発達検査を施行した104症例を対象に、精神運動発達予後を検討した。在胎28週以上のVLBWは64例で、appropriate for gestational age(AGA) 36例、small-for-gestational age(SGA) 13例、severe small-for-gestational age(severe SGA) 15例に分類できた。在胎週数はAGAに比べSGA、severe SGAで有意に長く、severe SGAは男児の割合が有意に多かった。AGAに比べ、SGAは出生時体重が有意に少なく、severe SGAは出生時体重・身長・頭囲が有意に小さかった。3歳児の発達指数(DQ値)に有意差はなかった。在胎28週未満のVLBWは40例で、AGA 30例、SGA 2例、severe SGA 8例であった。AGAに比べ、severe SGAは出生時体重・身長・頭囲が有意に小さかった。DQ値では、姿勢・運動領域がAGAより有意に低値であった。Severe SGAの原因の約60%が妊娠高血圧症候群・高血圧合併症妊娠であった。妊娠中断の理由の約60%が胎児機能不全であった。severe SGAの3歳時の運動発達不良を予測するための因子を検討した結果、妊娠中断理由からは有意な因子は抽出されなかったが、在胎週が独立した予測因子として抽出された。
(一社)日本周産期・新生児医学会, 2012年09月, 周産期学シンポジウム, (30), 53 - 59, 日本語[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
A 33-year-old woman developed deep venous thrombosis at 7 gestational weeks (GW). Heparin-induced thrombocytopenia was evident at 9 GW during unfractionated heparin infusion. Immediately, anticoagulation therapies together with antithrombin (AT) infusion were commenced with the use of argatroban from 9 GW, and fondaparinux was substituted for argatroban after 24 GW. The patient had hereditary AT deficiency type I determined by laboratory findings and results of genomic DNA analysis. The pregnancy ended in full-term vaginal delivery of a healthy male without adverse effects of the anticoagulation therapies. This was the first report of a pregnant woman who developed heparin-induced thrombocytopenia caused by heparin therapy for deep venous thrombosis due to AT deficiency.
WILEY-BLACKWELL, 2012年04月, JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH, 38 (4), 749 - 752, 英語[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
研究論文(研究会,シンポジウム資料等)
[査読有り]
研究論文(学術雑誌)
【目的】高血圧合併妊娠における児の転帰と患者背景との関わりを明らかにしようとした.
【方法】2006年1月から2010年12月までに当院で分娩した高血圧合併妊娠42症例を,血圧が軽症域であったMHT群22例,重症高血圧となったSHT群9例,そして加重型妊娠高血圧腎症を発症したSP群11例に分類し,臨床事象や母体背景を後方視的に群間で比較した.なお,子宮内胎児死亡,新生児死亡,出生体重1500g未満,出生児体重-2.0SD以下,重症新生児仮死(5分後Apgar値3点以下)のいずれかを児転帰不良とした.【成績】児転帰不良であったのはMHT,SHT,SP群それぞれ1例(4.5%),5例(55.6%),2例(18.2%)であり,3群間に有意差を認めた(p=0.005).なお,児転帰不良症例のうち子宮内胎児死亡の2例はいずれもSHT群に,新生児死亡の1例はSP群であった.帝王切開率はMHT群:6/22(27.2%),SHT群:4/7(57.1%)(IUFDの2例は除く),SP群:9/11(81.8%)(p=0.007)であった.分娩週数の中央値はMHT群:38週0日,SHT群:35週5日,SP群:35週0日(p=0.007)であった.出生児体重の中央値はMHT群:2917g,SHT群:1980g,SP群:2074g(p=0.009)であった.その他母体年齢,非妊娠時・分娩時BMI,妊娠初期の降圧薬使用頻度については有意差を認めなかった.ただし,児転帰不良例と良好例間では妊娠20週未満の降圧薬療法開始例の頻度に有意差があった(8例中7例(88%)対34例中11例(32%),p=0.015).【結論】高血圧合併妊娠においては,高血圧のみの重症化も妊娠高血圧腎症の発症と同様周産期予後を悪化させる因子である.また妊娠20週以前の降圧薬療法適応症例は児予後のハイリスクであると考えられる.〔産婦の進歩64(1):17-22,2012(平成24年2月)〕
[査読有り][招待有り]
論文集(書籍)内論文
[査読有り]
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
Caffeine is known to modulate placental and fetal umbilical circulation. It is demonstrated that apoptosis of human umbilical vein endothelial cells (HUVECs) is associated with placental umbilical vascular diseases. The present study was conducted to investigate the effects of caffeine on apoptosis of HUVECs. Isolated HUVECs were cultured under serum-free conditions for 24 h, and then treated with graded concentrations of caffeine (30, 100 and 300 μM) for additional 24 h and 48 h. The number of viable HUVECs was determined by cell counting. Apoptotic HUVECs were assessed by Hoechst33342 dye staining. The expression of caspase-9, caspase-8, caspase-3 and poly(ADP-ribose) polymerase (PARP) was assessed by Western blot analysis. Caffeine induced a dose- and time-dependent decrease in the number of viable HUVECs. Caffeine at concentrations higher than 100 μM significantly increased the percentage of apoptotic HUVECs. Caffeine at concentrations higher than 100 μM significantly increased cleaved caspase-9, caspase-3 and PARP expression in HUVECs at 24-h treatment compared with untreated cultures, whereas 30 μM caffeine significantly increased only caspase-3 expression at 24 h. Caffeine did not affect cleaved caspase-8 expression at 48 h. These results suggest that high concentrations of caffeine inhibit cell growth of HUVECs and induce apoptosis through the caspase-9 pathway. © 2006 Taylor & Francis.
2006年01月, Gynecological Endocrinology, 22 (1), 48 - 53, 英語[査読有り]
研究論文(学術雑誌)
Objective: Betacellulin (BTC), purified and cloned from mouse beta cell tumor (BTC-JC10), is regarded as a new member of the epidermal growth factor family. The present study was conducted to clarify the expression of BTC and its receptors, ErbB-1 and ErbB-4, in the trophoblasts in the human placenta over the course of pregnancy. Design and Methods: Human placental tissues were obtained from 4 pregnant women at the 4th to 5th week of pregnancy (very early placentas), 10 women at the 6th to 12th week (early placentas), 5 women at the 18th to 21st week (mid placentas) and 8 women at the 38th and 40th week (term placentas). The mRNA expressions of BTC, erbB-1 and erbB-4 were evaluated by quantitative RT-PCR with Southern blotting and the expression of the soluble form of BTC was determined by western immunoblot with a specific antibody to BTC protein. Immunohistochemical staining of BTC, ErbB-1 and ErbB-4 was also performed. Results: The levels of BTC mRNA expression in early and mid placentas were significantly higher than those in term placentas. The soluble form of BTC protein with an estimated molecular mass of 9.5 kDa was expressed in early and mid placentas, whereas the soluble form was not detected in term placentas. BTC from very early placentas until mid placentas was immunolocalized in syncytiotrophoblasts (S-cells), and was most abundant in early placentas. In contrast, BTC was immunolocalized in extravillous trophoblasts (EVTs), but not in villous trophoblasts in term placentas. The levels of erbB-1 mRNA in the early and mid placentas were significantly higher than those in term placentas, whereas the levels of erbB-4 mRNA in early placentas were significantly lower than those in mid and term placentas. ErbB-1 was immunolocalized in cytotrophoblasts in very early placentas, whereas it was immunolocalized in S-cells from early until term placentas. ErbB-4 from very early placentas until mid placentas was immunolocalized in S-cells, whereas ErbB-4 in the term placentas was detected in EVTs, but not in villous trophoblasts. Conclusions: These findings provide evidence for changes in expression and cytological localization of BTC and its receptors in the trophoblasts in human placenta over the course of pregnancy. BTC may play a pivotal role as a local growth factor in promoting the differentiated villous trophoblastic function via ErbB-1 in early placentas and in contributing to placental growth through the maintenance of EVT cell function via ErbB-4 in term placentas. © 2004 Society of the European Journal of Endocrinology.
2004年07月, European Journal of Endocrinology, 151 (1), 93 - 101, 英語[査読有り]
研究論文(学術雑誌)
研究発表ペーパー・要旨(国際会議)
AIM: To evaluate pregnancy outcome and complications in subsequent pregnancies after severe post-partum hemorrhage (PPH) between women with and without a history of uterine artery embolization (UAE). METHODS: Women who had a history of severe PPH, and delivered newborns at ≥22 gestational weeks in subsequent pregnancies were enrolled. Severe PPH was defined as blood loss volume of more than 2000 mL. RESULTS: The blood loss volume (median 1581 mL) in women with UAE (n = 14) was significantly more than that in women without UAE (median 1021 mL, n = 32, P < 0.01), and the recurrence rate of severe PPH in women with UAE (n = 5, 35.7%) was significantly higher than that in women without UAE (n = 3, 9.4%, P < 0.05). There were no significant differences in frequencies of premature delivery, hypertensive disorders of pregnancy, fetal growth restriction, or placenta previa/low lying placenta. Of 14 women with UAE, 7 (50.0%) had abnormally invasive placenta, whereas of 32 women without UAE, none had abnormally invasive placenta. CONCLUSION: Subsequent pregnancies after UAE for severe PPH had high risks for recurrence of severe PPH.
2020年01月, The journal of obstetrics and gynaecology research, 46 (1), 119 - 123, 英語, 国際誌[査読有り]
<Key Points>(1)最近では、先天性CMV感染児の症候性/無症候性の割合や後遺症リスクは、母体の妊娠中のCMV初感染/非初感染の別にかかわらず同程度とされる。(2)全妊婦を対象とした抗体スクリーニングでは、半数以上を占める母体CMV非初感染(非活性化ないし再感染)による先天性感染児を見逃す。(3)妊婦ターゲットスクリーニングとして、リスク因子の症状や所見を認めた場合、母体血CMV IgGとIgMを測定する。IgG陽性であれば、保険適用で新生児尿CMV核酸検査を行う。(4)新生児聴覚スクリーニングでリファー(要再検)の新生児には、保険適用で新生児尿CMV核酸検査を生後3週以内にその分娩施設で行う。(5)トキソプラズマIgM陽性妊婦からの出生児は、症状や所見がなくても生後12ヵ月までフォローアップし、血液検査を行う。(6)出生前羊水でトキソプラズマDNA陰性であっても、分娩時羊水や新生児血液でDNA陽性となって先天性感染と診断されることがある。(著者抄録)
(株)東京医学社, 2020年01月, 小児内科, 52 (1), 23 - 29, 日本語Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2018 there were nine themed workshops, five of which are summarised in this report. These workshops discussed new perspectives and knowledge in the following areas of research: 1) preeclampsia; 2) abnormally invasive placenta; 3) placental infection; 4) gestational trophoblastic disease; 4) drug delivery to treat placental dysfunction.
2019年09月01日, Placenta, 84, 9 - 13, 英語, 国際誌研究発表ペーパー・要旨(国際会議)
妊娠中に維持透析療法を要した慢性腎不全(CRF)合併妊娠3症例の臨床経過を調べ、周産期管理の問題点を検討した。症例1(43歳、G3P2)は腎血管性高血圧によるCRF患者で、妊娠26週に透析導入したが、高血圧が持続するため、Dry Weight(DW)を漸減したところ、羊水過少傾向を示し、胎児発育不全(FGR)となった。症例2(40歳、G1P0)は、IgA腎症によるCRFにて38歳時に透析導入となり、妊娠中期からDWを漸増したところ、羊水過多症を合併した。症例3(37歳、G1P0)は、膀胱尿管逆流症によるCRFにて18歳時に透析導入となり、血圧コントロールの目的でDWを漸減したところ、羊水過少傾向となったが、重篤なFGRは認めなかった。3例とも早産で、2例が極低出生体重児であった。維持透析を要する妊婦の管理には産科、新生児科、腎臓内科の綿密な連携が必須であることが示唆された。
「産婦人科の進歩」編集室, 2019年05月, 産婦人科の進歩, 71 (2), 103 - 108, 日本語[査読有り]
Human cytomegalovirus (CMV) is a common cause of congenital infection that may lead to severe long-term sequelae. Because there are no established vaccines, fetal interventions or neonatal treatments, neither maternal nor neonatal screening is recommended. However, recent studies have indicated that early antiviral treatment may improve neurological outcomes in symptomatic infants with congenital infection. Therefore, prenatal detection may be important in newborns at high risk of such infection. Polymerase chain reaction for CMV DNA in the amniotic fluid is considered the gold standard for diagnosis of intrauterine infection, but its use is limited because amniocentesis is an invasive procedure. In a prospective cohort study, we have reported that the presence of CMV DNA in secretions of the maternal uterine cervix were predictive of congenital infection in groups at high risk. However, we also recently demonstrated that maternal serological screening for primary CMV infection using specific immunoglobulin G, the immunoglobulin G avidity index or specific immunoglobulin M can overlook many cases. Previous research has indicated that the combination of early detection by universal neonatal screening of urinary CMV DNA combined with early antiviral therapy can improve outcomes in infants with symptomatic congenital infection. In this article, we review the current state of maternal and neonatal screening for congenital CMV infection.
2019年03月, J Obstet Gynaecol Res, 45 (3), 514 - 521, 英語, 国際誌[査読有り]
[招待有り]
記事・総説・解説・論説等(学術雑誌)
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
Early diagnosis and treatment of infants with symptomatic congenital cytomegalovirus (CMV) infection may improve neurological outcomes. For this reason, prenatal detection of newborns at high risk for congenital CMV infection is important. A polymerase chain reaction (PCR) assay for CMV DNA in the amniotic fluid is the gold standard for the diagnosis of intrauterine CMV infection; however, amniocentesis is an invasive procedure. Recently, we have found that the presence of CMV DNA in the maternal uterine cervical secretion is predictive of the occurrence of congenital CMV infection in CMV immunoglobulin M (IgM)-positive pregnant women. In contrast, we have suggested that maternal serological screening for primary CMV infection using CMV-specific immunoglobulin G (IgG), the IgG avidity index, or CMV-specific IgM overlooks a number of newborns with congenital CMV infection. We will review current knowledge of the potential biomarkers for predicting congenital CMV infection.
2018年11月, Int J Mol Sci, 19 (12), 英語, 国際誌[査読有り]
研究発表ペーパー・要旨(国際会議)
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
[招待有り]
記事・総説・解説・論説等(学術雑誌)
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
記事・総説・解説・論説等(学術雑誌)
記事・総説・解説・論説等(学術雑誌)
[査読有り]
記事・総説・解説・論説等(学術雑誌)
研究発表ペーパー・要旨(国際会議)
研究発表ペーパー・要旨(国際会議)
研究発表ペーパー・要旨(国際会議)
研究発表ペーパー・要旨(国際会議)
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
記事・総説・解説・論説等(学術雑誌)
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
その他
会議報告等
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
[査読有り]
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
研究発表ペーパー・要旨(国際会議)
研究発表ペーパー・要旨(国際会議)
研究発表ペーパー・要旨(国際会議)
研究発表ペーパー・要旨(国際会議)
研究発表ペーパー・要旨(国際会議)
研究発表ペーパー・要旨(国際会議)
研究発表ペーパー・要旨(国際会議)
[招待有り]
会議報告等
研究発表ペーパー・要旨(国際会議)
研究発表ペーパー・要旨(国際会議)
[査読有り]
会議報告等
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
[査読有り]
会議報告等
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
[査読有り]
[査読有り]
研究発表ペーパー・要旨(国際会議)
研究発表ペーパー・要旨(国際会議)
研究発表ペーパー・要旨(国際会議)
研究発表ペーパー・要旨(国際会議)
記事・総説・解説・論説等(学術雑誌)
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
会議報告等
研究発表ペーパー・要旨(国際会議)
会議報告等
会議報告等
会議報告等
会議報告等
会議報告等
会議報告等
記事・総説・解説・論説等(学術雑誌)
会議報告等
The aim of this trial study was to assess the preventive efficacy of immunoglobulin with a high titer of anti-CMV antibody for mother-to-fetus cytomegalovirus (CMV) transmission among pregnant women with primary/acute CMV infection. The primary CMV infection in mothers was diagnosed by a positive test for CMV IgM and/or low IgG avidity. Intact type immunoglobulin with a high titer of anti-CMV antibody was injected intravenously at a dosage of 2.5-5.0 g/day for consecutive 3 days to mothers with primary CMV infection. Four pregnant women were enrolled. One pregnancy ended in no congenital infection, while two pregnancies ended in congenital CMV infection. The other one pregnancy was terminated. The mother-to-fetus CMV transmission rate was found to be high as 66.7% (2/3). This preliminary result suggests that intravenous immunoglobulin injections are not effective for the prevention of mother-to-fetus CMV transmission in the present protocol.
2014年07月11日, The Kobe journal of medical sciences, 60 (2), E25-9, 英語, 国内誌会議報告等
会議報告等
会議報告等
会議報告等
会議報告等
会議報告等
会議報告等
会議報告等
会議報告等
会議報告等
[招待有り]
記事・総説・解説・論説等(学術雑誌)
[査読有り][招待有り]
その他
[査読有り][招待有り]
記事・総説・解説・論説等(学術雑誌)
[査読有り]
[査読有り]
[査読有り]
[査読有り]
[招待有り]
記事・総説・解説・論説等(学術雑誌)
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
会議報告等
会議報告等
会議報告等
会議報告等
会議報告等
会議報告等
会議報告等
会議報告等
会議報告等
会議報告等
会議報告等
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
[査読有り]
[査読有り]
記事・総説・解説・論説等(学術雑誌)
[査読有り]
[査読有り]
[査読有り]
[査読有り]
[査読有り]
[招待有り]
記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)
一般書・啓蒙書
学術書
学術書
学術書
学術書
学術書
学術書
学術書
学術書
学術書
学術書
学術書
学術書
学術書
[招待有り]
シンポジウム・ワークショップパネル(指名)
[招待有り]
シンポジウム・ワークショップパネル(指名)
口頭発表(一般)
[招待有り]
シンポジウム・ワークショップパネル(指名)
[招待有り]
シンポジウム・ワークショップパネル(指名)
ポスター発表
口頭発表(一般)
口頭発表(一般)
[招待有り]
シンポジウム・ワークショップパネル(指名)
口頭発表(一般)
ポスター発表
その他
シンポジウム・ワークショップパネル(指名)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
口頭発表(一般)
ポスター発表
ポスター発表
シンポジウム・ワークショップパネル(指名)
ポスター発表
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
その他
口頭発表(一般)
ポスター発表
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
その他
ポスター発表
ポスター発表
ポスター発表
口頭発表(一般)
シンポジウム・ワークショップパネル(公募)
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
[招待有り]
シンポジウム・ワークショップパネル(指名)
口頭発表(一般)
ポスター発表
ポスター発表
口頭発表(一般)
ポスター発表
ポスター発表
ポスター発表
口頭発表(一般)
口頭発表(一般)
ポスター発表
ポスター発表
[招待有り]
シンポジウム・ワークショップパネル(指名)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
ポスター発表
ポスター発表
ポスター発表
シンポジウム・ワークショップパネル(公募)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
ポスター発表
口頭発表(一般)
ポスター発表
ポスター発表
ポスター発表
口頭発表(一般)
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
公開講演,セミナー,チュートリアル,講習,講義等
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
[招待有り]
シンポジウム・ワークショップパネル(指名)
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
ポスター発表
ポスター発表
口頭発表(一般)
ポスター発表
シンポジウム・ワークショップパネル(公募)
口頭発表(一般)
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
その他
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
ポスター発表
口頭発表(一般)
口頭発表(一般)
シンポジウム・ワークショップパネル(公募)
[招待有り]
シンポジウム・ワークショップパネル(指名)
口頭発表(一般)
口頭発表(一般)
ポスター発表
ポスター発表
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
口頭発表(一般)
ポスター発表
口頭発表(一般)
ポスター発表
ポスター発表
ポスター発表
ポスター発表
口頭発表(一般)
ポスター発表
ポスター発表
口頭発表(一般)
ポスター発表
口頭発表(一般)
シンポジウム・ワークショップパネル(公募)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
[招待有り]
口頭発表(招待・特別)
口頭発表(招待・特別)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
ポスター発表
口頭発表(一般)
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
口頭発表(一般)
その他
口頭発表(一般)
その他
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
その他
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
その他
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
本研究では、aβ2GPI/HLA class Ⅱ測定法の不育症の原因検索や重症度診断における有用性を明らかする。また、HLA class Ⅱの新しい機能を応用し、不育症を引き起こす未知の抗原を探索する。ミスフォールド蛋白/HLA class Ⅱ複合体に対する自己抗体の新検出法が、抗リン脂質抗体症候群(APS)の診断や不育症の原因精査に有用かを調べる。この複合体抗体に起因する不育症の新たな治療法を開発し確立することを目的とする。また、検査法の標準化と汎用化のために、ELISAプレートやビーズを用いた測定法を新たに開発する。 今年度の研究実績を下に記す。 目的:不育症患者のaβ2GPI/HLA-DR7複合体(ネオ・セルフ)抗体と不育症との関係を明らかにすることを目的とした。対象と方法:2回以上の流産ないし1回以上の死産の既往がある不育症女性227人を対象とした。流死産歴無し、生産歴あり、抗リン脂質抗体(aPL)陰性、自己免疫疾患無しの女性208人をコントロールとした。コントロール女性の血清の99%ile を基準値として、対象でaβ2GPI/HLA-DR7抗体価を測定した。結果:52.6 U/mlが基準値となった。不育症女性227人中、52人(22.9%)が、aβ2GPI/HLA-DR7抗体陽性であった。不育症の原因/リスク因子が不明の121人中24人(19.8%)で、またAPS症状があるが基準aPLが陰性の114人中22人(19.3%)において、aβ2GPI/HLA-DR7抗体が陽性であることが初めて明らかになった。結論:これまで原因/リスク因子不明とされていた不育症女性の19.8%で陽性になったことから、aβ2GPI/HLA-DR7複合体抗体は、新たな不育症の原因である可能性が示された。前向きコホート研究や介入研究の臨床試験によって、因果関係の決定が今後期待される。Arthritis & Rheumatologyに投稿、リバイス中である。
不育症患者のaB2GPI/HLA-DR7(ネオセルフ)抗体と不育症との関係を明らかにすることを目的とした。不育症女性108人を対象とした。流死産歴無し生産歴ありのコントロール女性100人の99%ile(52.6 U/ml)を基準値として、対象で抗体を測定した。結果、不育症女性108人中、23人(21 %)が、ネオセルフ抗体陽性であった。陽性であった不育症女性23人中、17人 は他の aPL も陰性であった。原因不明の不育症69人中12人(17 %)でネオセルフ抗体が陽性であることを初めて明らかにした。ネオセルフ抗体は、新たな不育症の原因である可能性が示された。